Module coordinators:
Prof. dr. D.J.M. Peters
Human Genetics
Ph: 071 526 69490
From patient DNA
to personalized
medicine
Prof. dr. A.M.J.M. van den Maagdenberg
Human Genetics
Ph: 071 52 69460
M O D U L E B O O K
Bachelor Medicine, third year
Course year 2014-2015
Dr. W.M.C. van Roon-Mom
Human Genetics
Ph: 071 526 9435
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Table of Contents
Module committee and teachers ............................................................................................................ 1
Overview involved teachers .................................................................................................................... 3
Overview programme ............................................................................................................................. 4
Preface ..................................................................................................................................................... 5
Introduction and general information .................................................................................................... 6
Study goals of the module ....................................................................................................................... 7
Competency lines .................................................................................................................................... 8
Assessment matrix .................................................................................................................................. 9
Assessment information ........................................................................................................................ 10
Theme 1: Monogenetic disorders: genetic testing & disease mechanisms ...................................... 13
Overview Programme Module Theme 1 ............................................................................................... 15
Theme 2: New Genome Analysis –Ethics ............................................................................................ 23
Overview Programme Module Theme 2 ............................................................................................... 25
Theme 3: Gene(s) & environment ....................................................................................................... 26
Overview Programme Module Theme 3 ............................................................................................... 35
Theme 4: Personal genomics: pharmacogenomics & genetic therapies ........................................... 44
Overview Programme Module Theme 4 ............................................................................................... 46
Theme 5: Literature assignment: Writing report & Mini-symposium ............................................... 52
Overview Programme Module Theme 5 ............................................................................................... 53
1
Modulecommitteeandteachers
Module coordinators
Prof. dr. D.J.M. Peters
Human Genetics
Prof. dr. A.M.J.M. van den Maagdenberg
Human Genetics
Dr. W.M.C. van Roon-
Mom
Human Genetics
Logistical support
Module committee
Dr. A.M. Aartsma-Rus
Human Genetics
Prof. dr. P. Devilee
Hukan Genetics
Prof. dr. H.J. Guchelaar
Clinical Pharmacology
Drs. A. van Haeringen
Clinical Genetics
Dr. P.A.C. ’t Hoen
Human Genetics
Prof. dr. P. de Knijff
Human Genetics
Dr. M. Kriek
Clinical Genetics
Dr. P.E.M. Taschner
Human Genetics
Prof. dr. ir. J.A.P. Willems van Dijk
Human Genetics
2
Secretariat
Mw. A.W. Remmelzwaal
Human Genetics
Involved disciplines:
Human Genetics (HG), Clinical Genetics (CG), Laboratory for Diagnostic Genome Analysis (LDGA), Cardiology (Car), Obstetrics (Obs), Neurology (Neur), Nephrology (Neph), Internal Medicine (IM), Gastroenterology (Gast), Medical Ethics (MedEth), Molecular Epidemiology (ME), Pathology (Path), Anatomy (Ana), Clinical Pharmacology (CP), Clinical Oncology (CO), Molecular Cell Biology (MCB), Medical Statistics (MedStat), Toxicogenetics (Tox), Endocrinology (Endo)
3
Overviewinvolvedteachers
Dr. M. Kriek (CG), Prof.dr. P. Devilee (HG), Drs. A. van Haeringen (CG),
Dr. R. Bökenkamp-Gramann (KJG), Prof.dr. M.H. Breuning (CG), Drs. S.
ten Broeke (CG), Dr. H.B. Ginjaar (LDGA), Prof.dr. M.J.T.H. Goumans
(MCB), Dr. N. Gruis (Huid), Dr. K.B.M. Hansson (LDGA), Dr. C. Harteveld
(LDGA), Drs. Y. Hilhorst-Hofstee (CG), Dr. N.S. den Hollander (CG), Dr.
M.R.M. Jongbloed (Ana) , Dr. S.G. Kant (CG), Dr. S.A.M.J. Lesnik
Oberstein (CG), Prof.dr. A.M.J.M. van den Maagdenberg (HG), Prof.dr. J.
Morreau (Path), Drs. M. Nielsen (CG), Prof.dr. D.J.M. Peters (HG), Dr.
W.M.C. van Roon-Mom (HG), Drs. D. Soonawala (Neph), Dr. C. Tops
(LDGA), Prof.dr. H.F.A. Vasen (Gast), Dr J.S. Verbeek (HG), Prof.dr.
J.J.G.M. Verschuuren (Neur)
Prof.dr. D.J.M. Peters (HG), Prof.dr. A.M.J.M. van den
Maagdenberg (HG), Dr. W.M.C. van Roon-Mom (HG),
Prof.dr. T. Hankemeier (UvL/LACDR), Prof.dr. S.M. van der
Maarel (HG), Prof.dr. G.J.B. van Ommen (HG)
Prof.dr. P. de Knijff (HG) and Dr. P.E.M. Taschner (HG),
Prof.dr. M.H. Breuning (CG), Dr. H.P.J. Buermans (HG),
Drs. J.N.G.M. van Dartel (MedEth), Prof.dr. J.T. den Dunnen (HG),
Mr. dr. R.E. van Hellemondt (MedEth), Dr. P.A.C. 't Hoen (HG),
Dr. M. Kriek (CG)Dr. G.W.E. Santen (CG), Dr. H. Sminia (HG),
Prof.dr. A. Tibben (CG)
Prof.dr. ir. J.A.P. Willems van Dijk (HG) and Dr. P.A.C. 't Hoen
(HG), Prof.dr. C.J. van Asperen (CG), Prof.dr. R. Fodde (Erasmus
MC), Dr. V.J.A. van Harmelen (HG), Dr. K.M. Hettne (HG), Prof.dr
J.J. van Hilten (Neuro), Prof.dr. A.M.J.M. van den Maagdenberg
(HG), Dr. E.C. Robanus Maandag (HG), Dr. M. Kriek (CG), Prof.dr.
H. Pijl (Endo), Dr. M. Roos (HG), Prof. dr. P. Slagboom (Epi), Dr.
G.M. Terwindt (Neuro), Dr. E.A. Tolner (HG), Dr. M.P.G.
Vreeswijk (HG), Dr. H. Vrieling (Tox), Dr. B. de Vries (HG)
Prof.dr. H.J. Guchelaar (CP) and Dr. A.M. Aartsma-Rus (HG), Dr. P. Bank (CP), Prof.dr. M.H. Breuning (CG), Prof.dr. A.J.
Gelderblom (CO), Dr. P.C. Giordano (CG), Dr. C.L. Harteveld (CG),
Dr. J. den Hartigh (CP), Dr. K. Janssen (CG), Prof.dr. J.-L. Kerkhof
(EUR), Dr. M. Lolkema (CO, UMCU), Dr. M. Phylipsen (CG), Dr. J.
Rens (Prosensa Therap.), Dr. J.J. Swen (CP), E. Vroom (DMD
Patient Association)
Week 1
Week 2
Monogenetic
disorders – genetic
testing in clinical
routine
New genome
analysis-
Ethics
Gene(s) and
environment
Personal genomics:
Pharmacogenetics
and genetic
therapies
Literature
assignment:
Writing report and
mini-symposium
Week 3
Week 4
Week 5
Week 6
Week 7
Week 8
Week 9
Week 10
4
Overviewprogramme
The students will write a research proposal and give an oral presentation. A
mini-symposium with keynote speakers will highlight the future of genetics
in the clinic.
Provide the students with a basic understanding of genetics in clinical
routine and learn how to establish a genetic diagnosis
Learning and discussing about the background and new opportunities
of next generation sequencing technologies, along with its ethical
implications
Identifying the opportunities and challenges of several genetic
therapies and the different perspectives of patients, clinicians and
industry on clinical trials. Through several case studies the influence of
the genome on response to drug treatment and the opportunity for
therapy development will be investigated.
Understanding the principles of complex diseases and the influence of
the environment. What is ‘risk prediction’ for complex diseases. A
clinical introduction of several diseases and functional studies in cell
and animal models of the respective diseases will be given.
Monogenetic
disorders – genetic
testing in clinical
routine
New genome
analysis-
Ethics
Gene(s) and
environment
Personal genomics:
Pharmacogenetics
and genetic
therapies
Literature
assignment:
Writing report and
mini-symposium
5
Preface
Today, we stand at the threshold of a new era in healthcare. Within the foreseeable future analysis
of a complete patient’s genome (e.g. full genome analysis) will play a prominent role in the
consulting rooms of almost every medical specialist. In other words, healthcare will become more
and more DNA-based.
Sequencing of the human genome was completed in 2001, providing a map of all genes at the base-
pair level. Above all, the complete sequence of the human genome has accelerated developments in
genetic testing technologies. Presently, all protein coding parts of the human genome can be
sequenced in just a few days at affordable costs. Genetic testing is therefore expected to change the
clinical routine for a broad range of diseases, beyond those with a clear familial background or
Mendelian inheritance pattern.
This Genomics revolution will have a fundamental impact on our healthcare system and this requires
different levels of basic knowledge of our genome for every healthcare professional. It is expected to
improve and accelerate the diagnosis, improve healthcare and facilitate a more personalized health
management, and raises the opportunity for the application of (new) targeted therapies. It is also
expected to create more detailed insight into the mechanisms of disease at the molecular, cellular
and organismal level. A possible downside would be e.g. ethical implications for patients and their
families
In this course, the student will learn how genetic testing will impact disease diagnosis, prognosis, and
treatment with examples from a broad range of medical disciplines. The student will get an
understanding of the basics of genetic testing in clinical routine and will learn how to establish a
genetic diagnosis. The student will be introduced into the concepts of Next Generation Sequencing
and the ethical concerns. It is important to understand the possibilities, but also the limitations of
large amounts of genomic data for clinical practice. Finally, the student will get a better
understanding of the implications for treatments, i.e. novel and cutting edge ideas for the
development of genetic therapies but also the influence of genetic variation on drug response so-
called Pharmacogenomics.
6
Introductionandgeneralinformation
7
Studygoalsofthemodule
Test form
Knowledge test/
Anamnesis
Knowledge test/ Grant proposal/Oral
presentation
Grant proposal/Oral
presentation
Knowledge test/
Gene to disease task
Knowledge test/ Grant proposal/Oral
presentation
Gene to disease task
Grant proposal/Oral
presentation
Learning objectives
The student can
take a family anamnesis and draw the patient pedigree
describe and explain the impact of the Next Generation
Sequencing (NGS) technologies in health care, as well as the
ethical consequences;
discuss how different clinical treatment strategies for different
clinical disciplines will be affected by implementation of NGS
will have a basic understanding of, and will be able to translate
the results of a genetic test into the clinic
understand and explain how the risk of patients for certain
diseases and/or their response to certain (pharmacological)
treatments can be affected by their genetic background
is able to describe the medical relevance of genomic variants
communicate acquired knowledge on genetics in the clinic in a
written report and oral presentation in a concise and structured
way
8
Competencylines
• Medical expert
• Scholar
• Collaborator and Manager
• Health advocate
Prerequisites
-Van Mens tot Cel (vakcode: 301117000Y);
-Van Cel tot Molecuul (vakcode: 301118000Y);
-Academische en Wetenschappelijke vorming (blok en lijn) (vakcode: 301119000Y).
Place in the curriculum
Year 3 (10 weeks; Level 300; points 15)
9
Assessmentmatrix
Assignment Gene to disease
task Anamnesis Knowledge
test Grant proposal Oral
Presentation
Type of exam
Computer assignment
Written exam Written exam
Report of 1000 words + 2 illustrations
(end assignment)
Oral Presentation (end assignment)
Area Knowledge, academic skills
Knowledge, professional skills
Knowledge, academic skills, global health
Academic skills, knowledge, global health, communication, collaboration
Academic skills, communication, collaboration
Time Week 5 Week 5 Week 9
Week 9-10 Week 9-10
Lenght
1 hour 1 hour 1 hour 30 hour preparation
10 hour preparation
Weight
(% of end mark)
10% 10 % 25 %
40 %
15 %
Collaboration Individual basis Individual basis Individual basis
In pairs In pairs
Assessed by
Minor teachers
Medical Specialists involved in the half minor
Minor teachers
Minor teachers Assigned tutor plus minor teachers
Number of questions
4 8 20 Not applicable Not applicable
10
Assessmentinformation
Week 5:
Gene to disease task:
Computer assignment. The knowledge obtained in computer tasks in week 1-6 will be tested. The
exam exists of 4 open questions
Rating: 1-10
Assessed by: 2 minor teachers
Assessment: Application of bioinformatics skills to a clinical problem.
Feedback: By course coordinators in week 8
Week 6:
Anamnesis
The knowledge to establish a genetic anamnesis obtained in weeks 1-5 will be tested in a multiple
choice test.
Rating: 1-10
Assessed by: 2 minor teachers (clinical background)
Assessment: Application of clinical skills to reach a clinical genetic diagnosis
Feedback: By the assessment minor teachers
Week 9:
Knowledge test
Final multiple choice exam testing the students’ knowledge on genetic technologies, monogenetic
disorders, genetic testing in a clinical routine, genes and environment, pharmacogenetics, genetic
therapies and ethics.
Rating: 1-10
Assessed by: Course coordinators
Assessment: Application of genetics knowledge to genetic technologies, monogenetic disorders,
genetic testing in a clinical routine, genes and environment, pharmacogenetics, genetic therapies and
ethics.
Week 10
Grant proposal
Write a project proposal of 1500-2000 words in groups of two students.
Rating: 1-10
Assessed by: course coordinators expert researcher that supervised the students during their
assignment
Assessment: The written report will be graded with respect to scientific accuracy, quality of the
experimental part of the proposal, and how well it reflects the combination of knowledge on several
criteria that will be explained to the student when the proposal tasks are handed out (October 27
9.00 – 10.00). The individual contribution of each student to the preparation of the written proposal
will be assessed by the minor teachers involved in the specific subject of the proposal and by the
course coordinators. The three course organizers will compare the reviews of the expert researchers
11
and give final marks for the written assignment. Each student will get an individual mark. Students
will receive their final mark within 3 weeks after the end of the course.
Feedback: Students will get a short written feedback by the expert researcher through email.
Week 10:
Oral presentation of topic related to the project proposal:
Give a power point presentation on a particular subject in groups of two students.
Rating: 1-10
Assessed by: course coordinators and expert researchers
Assessment: Each student will get an individual mark. Students will receive their final mark within 3
weeks after the end of the course. Together with the expert researchers that supervised the student
group in the final two weeks, the course organisers will judge whether students will be graded either
half a point higher or lower than the group average for the oral presentation or whether the student
will get the mark of the group presentation. This allows for a differentiation in the evaluation in case
the students performed differently well during the group assignment.
Feedback: Students will get feedback during the presentations.
Study books
Emery’s Elements of Medical Genetics, by P. Turnpenny, S. Ellard
Relevant websites
http://www.ncbi.nlm.nih.gov/omim
http://www.lgtc.nl/
http://genome.ucsc.edu/
http://www.ncbi.nlm.nih.gov/SNP/
12
13
Theme1:
Monogeneticdisorders:genetictesting&diseasemechanisms
Clinical and Scientific
coordinators: Dr. M. Kriek (CG) and Prof.dr. P. Devilee (HG), Drs. A. van Haeringen (CG)
Other teachers involved: Dr. R. Bökenkamp-Gramann (KJG), Prof.dr. M.H. Breuning (CG), Drs. S.
ten Broeke (CG), Dr. H.B. Ginjaar (LDGA), Prof.dr. M.J.T.H. Goumans
(MCB), Dr. N. Gruis (Huid), Dr. K.B.M. Hansson (LDGA), Dr. C. Harteveld
(LDGA), Drs. Y. Hilhorst-Hofstee (CG), Dr. N.S. den Hollander (CG), Dr.
M.R.M. Jongbloed (Ana) , Dr. S.G. Kant (CG), Dr. S.A.M.J. Lesnik
Oberstein (CG), Prof.dr. A.M.J.M. van den Maagdenberg (HG), Prof.dr. J.
Morreau (Path), Drs. M. Nielsen (CG), Prof.dr. D.J.M. Peters (HG), Dr.
W.M.C. van Roon-Mom (HG), Drs. D. Soonawala (Neph), Dr. C. Tops
(LDGA), Prof.dr. H.F.A. Vasen (Gast), Dr J.S. Verbeek (HG), Prof.dr.
J.J.G.M. Verschuuren (Neur)
In the first two weeks of this course, we will discuss the present-day clinical routine for a number of
medical disciplines, including Neurology, Cardiology, Oncology, Nephrology, and Gastroenterology.
What is the anamnesis of an ‘average patient’ seen in these clinics, and how often is a genetic
diagnosis warranted? How is this differential diagnosis established and which diagnostic information
is essential to arrive at the right diagnosis? This will be exemplified by patient demonstrations. In
addition, this part of the course will refresh basic genetic principles, such as inheritance patterns,
chromosomal disorders, and diagnostic approaches.
Learning objectives:
The student
• will be able to establish if and when a genetic diagnosis in the clinical arena is warranted for
optimal treatment of the patient.
• can take a family anamnesis and draw the patient pedigree.
• will be able to draw diagnostic conclusions on the most likely genetic cause of a patient’s
disease on the basis of his/her personal anamnesis and family history.
• can discuss the genetic, disease-related and anamnestic complexities of a variety of disorders
for which heritability forms an important part of their etiology.
• can explain the differences between various inheritance patterns, including monogenic
versus polygenic inheritance.
• will acquire and apply knowledge on chromosomes, genes, and variation in DNA sequences.
• will have a basic understanding of, and will be able to translate the results of a genetic test
into the clinic.
• will be able to describe the clinical implications of a genetic diagnosis to counselees for
several clinical disciplines.
This part of the course will include:
- Genetic diseases in daily practice: lectures and patient demonstrations for different disorders,
i.e. colon cancer, developmental, neuromuscular, cardiac and renal disorders
- Lectures and practical skills in genetic counselling
- Lectures, working group and quiz on monogenetic inheritance patterns and conventional
genome analysis
- An interactive lecture and debate on prenatal screening
- From mice to man: animal models to study monogenetic diseases
14
- In depth approach of a clinical problem: critical evaluation of literature to answer a question
from clinical practice – Self-study, working group and presentations
Contact hours 22: e.g. lectures, patient demonstrations
Interaction hours 15: e.g. practicals, contact hours, quiz
Self-study hours 14
Evaluation:
-10 minute student presentation
- Multiple choice exam
- Quiz
Knowledge that the Student should have prior to entering the Minor:
Chapters 2-5, 7, 16-22 Emery’s Elements of Medical Genetics, by P. Turnpenny, S. Ellard
15
OverviewProgrammeModuleTheme1
Topic Type of activity Name
Week 1 Monday September 1
Tuesday September 2 Conventional genome analysis
9.00-9.30 Introduction - 1/2 Minor Lecture Prof.dr. A. van den Maagdenberg, Prof.dr. D.H.M. Peters and Dr. W.M.C. van Roon-Mom
9.30-9.45 Introduction first two weeks Lecture Prof.dr. P. Devilee and Dr. M. Kriek
10.00-10.45 Genetic Counseling Lecture Prof.dr. M.H. Breuning
11.00-11.45 Chromosomes/DNA/genes- the complexity of the genome Lecture Dr. M. Kriek
13.00-13.45 Monogenic inheritance- different types, case-based explanation Quiz Dr. M. Kriek
14.00-14.45 Genetic Linkage Lecture Dr. N. Gruis
15.00-15.45 Patient demonstration- Malformation -Myotonic dystrophia Patient demonstration Drs. A. van Haeringen
Wednesday September 3
9.00-9.45 Patient demonstration developmental delay - Williams syndrome Patient demonstration Drs. A. van Haeringen
10.00-10.45 Prenatal diagnostics in daily clinical genetic practice Lecture Dr. N.S. den Hollander
11.00-11.45 NIPT heelprick discussion Lecture Prof.dr. M.H. Breuning
13.00-13.45 Background of in depth approach of a clinical problem Contact Drs. A. van Haeringen and Dr. M. Kriek
14.00-14.45 Assignment Question/answer approach Contact Drs. A. van Haeringen and Dr. M. Kriek
15.00-16.45 Assignment Question/answer approach Self study
Thursday September 4 Developmental aberrations
9.00-9.45 Chromosome analysis Lecture Dr. K.B.M. Hansson and Dr. C. Harteveld
10.00-10.45 SNP array analysis Lecture Dr. K.B.M. Hansson and Dr. C. Harteveld
11.00-11.45 Mutation scanning Lecture Dr. K.B.M. Hansson and Dr. C. Harteveld
13.00-14.45 Interpretation of sequence data using Alamut Practical Dr. C. Tops
15.00-16.45 Interpretation of sequence data using Alamut Practical Dr. C. Tops
Friday September 5
9.00-10.15 Discussion of outcome of assignment. Contact Drs. A. van Haeringen and Dr. M. Kriek
10.30-11.15 neurology in daily practice Lecture Prof. dr. J.J.G.M. Verschuuren
11.30-12.15 CADASIL Lecture Dr. S.A.M.J. Lesnik Oberstein
Topic Type of activity Name
Week 2 Monday September 8 Lecture
9.00-9.45 Cardiology/ Daily practice Lecture Dr. R. Bökenkamp-Gramann
9.45-10.30 Link between Clinical Genetics and cardiology Lecture Dr. Y. Hilhorst
10.30-11.00 pauze
11.00-11.45 Morphogenesis and anatomy of congenital heart disease Lecture Dr. M.R.M. Jongbloed
11.45-12.30 Stem cell therepy in cardiac disease: from cells to patient therapy Lecture Prof. dr. M.J.T.H. Goumans
14.00-16.45 In depth approach of a clinical problem self study
Tuesday September 9
9.00-9.45 Gastro-intestinal hepatologist: patients in daily practice Lecture Prof.Dr. H.F.A. Vasen
10.00-10.45 Heriditary forms of Colon cancer: clinical genetics Monogenetic Lecture Dr. M. Nielsen
11.00-12.15 Microscopy of heriditary colon cancer samples Practical Prof. dr. J. Morreau
13.00-13.30 Scientific research in colon cancer Lecture Drs. S. ten Broeke
13.30-14.30 In depth approach of a clinical problem, contact with senior contact/self study Drs A. van Haeringen, dr. M. Kriek and Prof.dr. Devilee
14.30-16.00 In depth approach of a clinical problem self study
Wednesday September 10
9.00-9.45 Mouse models to study genetic diseases Lecture Dr. J.S. Verbeek
10.00-10.45 Nephrologist:patients in daily practice patient demonstration Drs. D. Soonawala
11.00-12.00 Polycystic Kidney Disease: from mice to patients Lecture Prof. dr. D.J.M. Peters
13.00-13.45 Limb Girdle Muscular Dystrophy: genotype-phenotype Lecture Dr. H.B. Ginjaar
14.00-16.45 In depth approach of a clinical problem self study
Thursday September 11
9.00-9.45 Counseling session by students, of students about a disorder practical Drs van Haeringen and Dr. M. Kriek
10.00-10.45 Pedigree drawing/ physical examination /ordering DNA test etc by students practical Drs van Haeringen and Dr. M. Kriek
11.00-11.45 Patient demonstration: kleingroei (Acromesomele dysplasie) practical/patient demonstration Dr. S.G. Kant
13.00-16.45 In depth approach of a clinical problem self study
Friday September 12
9.00-12.30 In depth approach of a clinical problem - presentation by students Assessment Drs A. van Haeringen, dr. M. Kriek and Prof.dr. Devilee
16
Tuesday September 2
Lecture 9.00 – 09.30
Title Introduction to this half minor
Instructors: Prof.dr. A. van den Maagdenberg, Prof.dr. D.H.M. Peters and Dr. W.M.C. van Roon-
Mom
Goal Introductory remarks
Lecture 9.30 - 9.45
Title Introduction first two weeks
Instructors Prof.dr. P. Devilee and Dr. M. Kriek
Goal Explaining the specific goals and learning targets for the first two weeks of the
course.
Lecture 10.00-10.45
Title Genetic Counselling
Instructor Prof.dr. M.H. Breuning
Goal To understand the process of genetic counselling and its clinical ramifications.
Genetic counselling is the process by which patients or relatives at risk of an
inherited disorder are advised of the consequences and nature of the disorder, the
probability of developing or transmitting it, and the options open to them in
management and family planning. This complex process can be separated into
diagnostic (the actual estimation of risk) and supportive aspects. An important part
of the counselling’s process are the relevant anamnestic questions to ask. In this
lecture, and in others, these relevant questions will continue to be discussed.
Lecture 11.00-11.45
Title Chromosomes/DNA/genes - the complexity of the genome
Instructor Dr. M. Kriek
Goal To understand the basis of how genes and genetic materials are organized in
humans. In modern molecular biology and genetics, the genome is the genetic
material of an organism. It is encoded either in DNA or, for many types of viruses, in
RNA. The genome includes both the genes and the non-coding sequences of the
DNA/RNA.
Quiz 13.00-13.45
Title Monogenic inheritance- different types, case-based explanation
Instructor Dr. M. Kriek
Goal To refresh knowledge – in a question-and-answer-session – on monogenetic
Mendelian inheritance, i.e., autosomal or sex-linked inheritance, dominant or
recessive inheritance.
Lecture 14.00-14.45
Title Genetic Linkage
Instructor Dr. N. Gruis
Goal To understand the basic principles underlying Mendelian inheritance, and genetic
linkage. Genetic linkage is the tendency of genes that are located proximal to each
other on a chromosome to be inherited together during meiosis. Genes whose loci
are nearer to each other are less likely to be separated onto different chromatids
during chromosomal crossover, and are therefore said to be genetically linked.
Patient demonstration 15.00-15.45
17
Title Malformation -Myotonic dystrophia
Instructor Drs. A. van Haeringen
Goal Gain experience with different aspects of a genetic counselling and learn what the
implication are of a DNA verified diagnosis for the patient and his/her family. In this
patient demonstration the emphasis will be on how one patient can lead to an
extensive family with multiple affected family members. Again, relevant anamnestic
questions will show to be very important in this process.
Wednesday September 3 -
Patient Demonstration 9.00-9.45
Title Patient demonstration developmental delay – Williams Syndrome –
Instructor Drs A. van Haeringen
Goal Gain experience with different aspects of a genetic counselling and learn what the
implications are of a DNA verified diagnosis for the patient and his/her family. In this
patient demonstration the emphasis will be on the impact of getting a genetic
diagnosis in a child, and what the impact is on daily life at home and at school.
Lecture 10.00-10.45
Title Prenatal diagnostics in daily clinical genetic practice
Instructor Dr. N.S. den Hollander
Goal To understand which prenatal questions are addressed in clinical genetic practice.
Some pregnancies have an increased chance of genetic disorder / chromosome
alteration. Examples of these situations are:
• Previous child with a genetic disorder/syndrome
• Fetus with an increased nuchal translucency
• Fetus with structural abnormalities observed during the 20 weeks ultrasound
During this lecture the students will get an inside of the different prenatal issues that
are discussed with the pregnant women and their partners.
Interactive Lecture 11.00-11.45
Title NIPT Heel prick discussion
Instructor Prof.dr. M.H. Breuning
Goal Introduction of the heel prick and its related social discussions. The neonatal heel
prick or Guthrie test is a screening test done on newborns. Currently the newborn is
screened for the genetic predisposition of ~25 disorders. These disorders are
medically actionable in the sense that there is an opportunity to prevent a problems
by direct clinical intervention. The question is whether it is appropriate to expand the
application of the heel prick by also including disorder that are not medically
actionable for the newborn, but could have direct consequences for the family
involved.
Contact 13.00-13.45
Title Background of in-depth approach of a clinical problem
Instructors Drs. A. van Haeringen and Dr. M. Kriek
Goal During this session students are taught how to access an in-depth approach of a
clinical problem by discussing an already completed approach.
Contact 14.00-14.45
Title Assignment Question/answer approach
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Instructors Drs. A. van Haeringen and Dr. M. Kriek
Goal Gain experience with the in-depth approach by studying a rather simple clinical
problem. This problem will initially be similar for all students so that possible
obstacles can be identified plenary.
Self-study 15.00-16.45
Goal Gain experience with the in-depth approach by self-study.
Thursday September 4
Lecture 9.00-9.45
Title Chromosome analysis
Instructors Dr. K.B.M. Hansson and Dr. C. Harteveld
Goal To learn about different applications of chromosome analysis or karyotyping.
Karyotyping is a test that evaluates the number and structure of a person's
chromosomes in order to detect abnormalities. Chromosomes are thread-like
structures within each cell nucleus and contain the body's genetic blueprint. Each
chromosome contains hundreds of genes in specific locations. These genes are
responsible for a person’s inherited physical characteristics and they have a profound
impact on growth, development, and function.
Lecture 10.00-10.45
Title SNP array analysis
Instructors Dr. K.B.M. Hansson and Dr. C. Harteveld
Goal To understand why Single nucleotide polymorphism (SNP) array has a significant
added value compared to karyotyping in a diagnostic setting. SNP array can be used
to measure both DNA polymorphism and dosage changes. Our laboratory has applied
SNP microarray analysis to uncover sub-microscopic genomic copy number gains and
losses in different cancers. This session will focus on the range of applications of SNP
microarray analysis.
Lecture 11.00-11.45
Title Mutation scanning
Instructors Dr. K.B.M. Hansson and Dr. C. Harteveld
Goal To learn about different applications of mutation scanning, a process by which a
segment of DNA is screened via one of a variety of methods to identify variant gene
region(s). Variant regions are further analyzed (usually by sequence analysis or
mutation analysis) to identify the sequence alteration.
Practical 13.00-14.45 & 15.00 – 16:45
Title Interpretation of sequence data using Alamut
Instructor Dr. C. Tops
Goal Gain experience with software that is used in a diagnostic setting to support the
decision making process. Alamut Visual integrates genetic and genomic information
from different sources into one consistent and convenient environment to describe
variants using HGVS nomenclature and help interpret their pathogenic status.
Dedicated to mutation diagnostics, Alamut Visual is used by clinical and molecular
research laboratories worldwide.
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Friday September 5
Contact 9.00-10.15
Title Discussion of outcome of assignment
Instructors Drs. A. van Haeringen and Dr. M. Kriek
Goal Feedback of the first assignment and identification of possible obstacles that should
be addressed prior to the start of a real in-depth approach of a clinical problem.
Lecture 10.30-11.15
Title (Child) neurologist; neurology in daily practice
Instructor Prof. Dr. J.J.G.M. Verschuuren
Goal To learn about the variety of clinical issues addressed in daily practice of a
neurologist (specialized in neuromuscular disorders). Disorders discussed will be
Duchenne and Becker muscular dystrophy, Facio- Humeral- Scapulo Dystrophy
(FSHD) en Limb Girdle Muscular Dystrophy (LGMD).
Lecture 11.30-12.15
Title CADASIL
Instructor Dr. S.A.M.J. Lesnik Oberstein
Goal To understand the clinical and genetic issues related to CADASIL (Cerebral autosomal
dominant arteriopathy with subcortical infarcts and leukencephalopathy). The
students will gain insight into the importance of a multidisciplinary approach of the
(pre-symptomatic) counselling process.
Monday September 8
Lecture 9.00-9.45
Title Cardiology – Daily practice
Instructor Dr. R. Bökenkamp-Gramann
Goal To learn about the variety of clinical issues addressed in daily practice of a
cardiologist. Cardiology includes medical diagnosis and treatment of congenital heart
defects, coronary artery disease, heart failure, valvular heart disease and
electrophysiology.
Lecture 9.45-10.30
Title Link between Clinical Genetics and cardiology
Instructor Dr. Y. Hilhorst-Hofstee
Goal: Gain insight into the proportion of cardiac problems that are part of a genetic disorder /
syndrome; how are the patients identified, what is the expertise of the clinical geneticist.
Lecture 11.00-11.45
Title Morphogenesis and anatomy of congenital heart disease
Instructor Dr. M.R.M. Jongbloed
Goal To understand how structural heart abnormalities are diagnosed in a clinical setting.
Lecture 11.45-12.30
Title Stem cell therapy in cardiac disease – from cells to patient therapy
Instructor Prof.dr. M.J.T.H. Goumans
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Goal To understand different levels of scientific research related to cardiac disease.
Self-study 14.00-16.45
Title In-depth approach of a clinical problem
Goal Formulating an answer to a clinical problem by an in-depth literature study
approach.
Tuesday September 9
Lecture 9.00-9.45;
Title Gastro-intestinal hepatologist: patients in daily practice
Instructors Prof.dr. H.F.A. Vasen
Goal To learn about the variety of clinical issues addressed in daily practice of a
gastroenterologist. Gastroenterology and Hepatology specialists provide
comprehensive clinical services related to the digestive tract, liver and pancreas.
They diagnose and manage complex and chronic gastrointestinal and liver disorders.
Lecture 10.00-10.45
Title Hereditary forms of Colon cancer – clinical genetics Monogenetic
Instructor Dr. M. Nielsen
Goal Gain insight of the proportion of intestinal problems that are part of a genetic
disorder / syndrome; how are the patients identified, what is the expertise of the
clinical geneticist.
Practical 11.00-12.15
Title Microscopy of hereditary colon cancer samples
Instructor Prof.dr. J. Morreau
Goal To understand the process of diagnostic process related to hereditary colon cancer
on a histological level.
Lecture 13.00-13.30
Title Scientific research in colon cancer
Instructor Drs. S. ten Broeke
Goal To understand how scientific research is set up. Drs. ten Broeke will discuss data
assembly, analysis of families with hereditary colon cancer related disorder and
estimated penetrance of the different disorders.
Contact/ Self-study 13.30-14.30
Title In-depth approach of a clinical problem, contact with senior
Instructor Drs A. van Haeringen, dr. M. Kriek and Prof.dr. Devilee
Goal To address questions related to the in-depth approach
Self-study 14.30-16.00;
Title In-depth approach of a clinical problem
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Goal Formulating an answer to a clinical problem by an in-depth literature study approach
Wednesday September 10
Lecture 9.00-9.45
Title Mouse models to study genetic diseases
Instructor Dr J.S. Verbeek
Goal To understand the possibilities of the application of animal model to study a genetic
disorder. An animal model is a living, non-human animal used during the research
and investigation of human disease, for the purpose of better understanding the
disease process without the added risk of harming an actual human. The animal
chosen will usually meet a determined taxonomic equivalency to humans, so as to
react to disease or its treatment in a way that resembles human physiology as
needed. Many drugs, treatments and cures for human diseases have been developed
with the use of animal models. Predictive models are similar to a particular human
disease in only a couple of aspects. However, these are useful in isolating and making
predictions about mechanisms of a set of disease features.
Practical 10.00-10.45;
Title Nephrologist – patients in daily practice
Instructors Drs. D. Soonawala
Goal To learn about the variety of clinical issues addressed in daily practice of a
Nephrologist. Nephrology concerns itself with the study of normal kidney function,
kidney problems, the treatment of kidney problems and renal replacement therapy
(dialysis and kidney transplantation).
A patient with Polycystic kidney disease(PKD) will be interviewed. PKD is one of the
most common life-threatening genetic diseases, affecting an estimated 12.5 million
people worldwide. It is a cystic genetic disorder and is characterized by the presence
of multiple cysts (hence, "polycystic") typically in both kidneys. The two major forms
of polycystic kidney disease are distinguished by their patterns of inheritance.
Lecture 11.00-12.00
Title Polycystic Kidney Disease – from mice to patients
Instructor Prof.dr. D.J.M. Peters
Goal To understand different levels of scientific research related to Polycystic kidney
disease, with focus on model systems.
Lecture 13.00-13.45
Title Limb Girdle Muscular Dystrophy – from genotype to phenotype
Instructor Dr. H.B. Ginjaar
Goal To understand the diagnostic approaches for molecular verification (or exclusion) of
a clinical muscular diagnosis. Limb-girdle muscular dystrophy is an autosomal class of
muscular dystrophy that is similar but distinct from Duchenne muscular dystrophy
and Becker's muscular dystrophy. Limb-girdle muscular dystrophy encompasses a
large number of rare disorders.
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Self-study 14.00-16.45;
Title In-depth approach of a clinical problem
Goal Formulating an answer to a clinical problem by an in-depth literature study approach
Thursday September 11
Practical 09.00-09.45;
Title Counseling session by students, of students about a disorder
Instructors Drs van Haeringen and Dr. M. Kriek
Goal Gain experience with counseling. Which questions should be asked to identify a
possible genetic cause of a certain phenotype.
Practical 10.00-10.45
Title Pedigree drawing/ physical examination /ordering DNA test etc by students
Instructor Dr. M. Kriek
Goal Gain experience with pedigree drawing, physical examination and sequent ordering
different DNA tests.
Patient demonstration 11.00 – 11.45;
Title Kleingroei (Acromesomele dysplasie)
Instructor Dr. S.G. Kant
Goal Gain experience with different aspects of a genetic counselling and learn what the
implications are of a DNA verified diagnosis for the patient and his/her family.
Self-study 13.00-16.45
Title In-depth approach of a clinical problem
Goal Formulating an answer to a clinical problem by an in-depth literature study approach
Friday September 12
Contact 09.00 – 12.30; presentations, discussion, assessment
Title In-depth approach of a clinical problem – presentation by students
Instructors Drs A. van Haeringen, dr. M. Kriek and Prof.dr. Devilee
Goal During this session, the students will give a presentation in which they answer the
clinical problem that was addressed during the last days by applying an in-depth
literature study.
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Theme2:NewGenomeAnalysis–Ethics
Clinical and Scientific
coordinators: Prof.dr. P. de Knijff (HG) and Dr. P.E.M. Taschner (HG)
Other teachers involved: Prof.dr. M.H. Breuning (CG), Dr. H.P.J. Buermans (HG), Drs. J.N.G.M. van
Dartel (MedEth), Prof.dr. J.T. den Dunnen (HG), Mr. dr. R.E. van
Hellemondt (MedEth), Dr. P.A.C. 't Hoen (HG), Dr. M. Kriek (CG)Dr.
G.W.E. Santen (CG), Dr. H. Sminia (HG), Prof.dr. A. Tibben (CG)
In recent years, the application of "Next generation sequencing” ( NGS ) really has taken off in
medical research and diagnostics . The major difference to conventional method is that millions of
reactions can be analyzed in parallel, in contrast to only one fragment in conventional sequencing.
This has major advantages but also raises ethical questions related to unexpected information
concerning possible diseases.
In week 3 and 4 the principle of NGS and its applications will be discussed as well as ethical
questions. NGS, and especially exome sequencing has identified many causative genes for hereditary
and congenital disorders in recent years. Using examples, it is illustrated why NGS is suitable for this
purpose and some of the problems that are encountered. The application of NGS as a diagnostic tool
will also be discussed. The impact on health in a broader sense is also prominent. It is very likely that
genome-wide analysis will play a prominent role in many doctor's offices and throughout all levels of
health care in the near future. Here, it is important to know what information the
student can, and cannot (yet) get out of the genome. It is currently impossible, for example, to
generate a reliable genetic risk profile. There is also a risk of chance findings. This means that a
genetic modification is identified that has no relation with the condition of the patient, but could
have clinical consequence. Patients should be informed well in advance of this possibility.
Learning objectives:
The student
• will be able to describe next-generation sequencing in terms of technology, different
types of data analysis, and applications
• can assess the potential consequences of a DNA variant
• can discriminate between genetic and non-genetic phenotypes
• can describe the complexity of the content of a personal genome
• can discuss the various ethical, philosophical and legal aspects and implications of the
rapid changes in medical research.
• will be able to systematically analyse the moral implications of clinical counselling
• can discuss the moral and legal conditions of a genetic population survey
• can name the different responsibilities and organizations important in the field of
genetic screening and population surveys.
This part of the course will include:
- Implications of genomic medicine based on the concept of everyday medical practice. Current
transformation of medicine: from cure to improvement. Developments in the future: from
enhancement to trans-humanism?
- Clinical genetics: which ethical and legal questions arise in clinical (counseling) practice? Related
Topics: secrecy and privacy; shifting family relationships
- Genetic screening and screening. Related topics: government role, role provider. Protection,
autonomy and self-management support. Equitable access.
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- Direct-to-consumer genetic testing. Related topics: government role, role provider. Protection,
autonomy and self-management support. Equitable access.
Contact hours 24: including lectures and patient demonstrations
Interaction hours 14: including practicals, quiz, presentations
Self-study hours 12
Evaluation:
- Presentation of a clinical problem
Knowledge that the Student should have prior to entering the Minor:
Chapters 4, 17, 20, 24 Emery’s Elements of Medical Genetics, by P. Turnpenny, S. Ellard
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OverviewProgrammeModuleTheme2
Topic Type of activity Name
Week 3 Monday September 15
9.00-9.15 Introduction Contact Coordinators
9.15-10.00 NGS technology: history and current Lecture Prof.dr. J.T. den Dunnen
10.15-11.00 NGS technology: current and future Lecture Prof.dr. J.T. den Dunnen
11.15-12.15 Task data analysis (exome based) Practical Dr. H. Sminia
12.15-12.30 Saliva sampling for DNA analysis Practical Dr. H.P.J. Buermans
13.00-16.30 Self study assignment: Knowledge from fictitious genome Self study
16.30-17.30 Reading review and preparing questions Self study
Tuesday September 16
9.00-9.45 NGS data analysis: Types of variants Lecture Dr. P.E.M. Taschner
10.00-10.45 NGS data analysis: Potential consequences of a variant Lecture Dr. P.E.M. Taschner
11.00-11.45 WES/WGS and data analysis Lecture Dr. G.W.E. Santen
12.00-12.30 Databases and Genome browsing Practical Dr. P.E.M. Taschner
13.00-17.00 Prepare presentation September 24 - Knowledge from genome Self study
Wednesday September 17
9.00-11.00 Is this heritable or not Q&A voting Prof. dr. P. de Knijff
I have a genome, what do I know Q&A > task for studentsProf. dr. P. de Knijff
11.15-12.30 Databases and Genome browsing Practical Dr. H. Sminia
13.00-17.00 Prepare presentation September 24 - Knowledge from genome Self study
Thursday September 18
9.00-9.45 Ethics and law: Implications of Genome based Medicine Lecture Dr. J.N.G.M. van Dartel and Mr. dr. R.E. van Hellemondt
10.00-12.30 Transhumanism and other images of the future Working group Dr. J.N.G.M. van Dartel and Mr. dr. R.E. van Hellemondt
13.00-17.00 Ethics self-study and tasks Self study
Friday September 19
9.00-9.45 Practical and emotional implications of a severe genetic diseasePatient demonstration Prof.dr. A. Tibben
9.45-12.30 Family Dynamics Lectures Prof.dr. A. Tibben, Dr. J.N.G.M. van Dartel, Mr. dr. R.E. van Hellemondt
13.00-17.00 Ethics selfstudy and tasks Self study
Topic Type of activity Name
Week 4 Monday September 22
9.00-10.00 DNA isolation Practical Dr. H.P.J. Buermans
10.00-11.00 LGTC/Sequencing facility tour Dr. H.P.J. Buermans
11.00-12.00 DNA quantification Practical Dr. H.P.J. Buermans
13.00-14.00 Prepare for practicals and presentation Self study
14.00-15.00 PCR setup for DNA profile & SNV test Practical Dr. H.P.J. Buermans
Tuesday September 23
9.00-9.45 Transcriptomics, proteomics, metabolomics Lectures Dr. P.A.C. 't Hoen
10.00-10.45 The future hospital, personal monitoring Lectures Prof.dr. M.H. Breuning
11.00-11.45 My genome sequence Q&A what do I know Dr. M. Kriek
13.00-16.00 DNA profile & SNV test Practical Dr. H.P.J. Buermans
Wednesday September 24
13.30-17.00 Presentations knowledge from your genome 10 min students presentationsProf. dr. P. de Knijff, Dr. H. Sminia
Thursday September 25
9.00-12.15 Ethics and Law: Incidental findings Lectures Dr. M. Kriek, Mr. dr. R.E. van Hellemondt and Dr. J.N.G.M. van Dartel
13.00-17.00 Ethics and Law: The future of neonatal screening Practical Dr. M. Kriek, Mr. dr. R.E. van Hellemondt and Dr. J.N.G.M. van Dartel
Friday September 26
9.00-16.00 Ethics and law: Commercial screening Lectures Dr. M. Kriek, Mr. dr. R.E. van Hellemondt and Dr. J.N.G.M. van Dartel
16.00-17.00 Evaluation with students Contact Dr. M. Kriek and Dr. J.N.G.M. van Dartel
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Theme week 3 & 4: New Genome Analysis – Ethics
Monday September 15
Contact 9.00 – 9.15
Title Evaluation with students
Instructors Coordinators
Goal Evaluation.
Lectures 9.15 – 10.00; 10.15 – 11.00
Title NGS technology: 1) history and current; 2) current and future
Instructor Prof. Dr. J.T. den Dunnen (Head Leiden Genome Technology Center (LGTC); Human
Genetics department, LUMC)
Goal Next Generation Sequencing technology has great impact on research and DNA
diagnostics. Students will receive a short introduction on NGS technology.
Practical 11.15 – 12.15
Title Task data analysis (exome based)
Instructor Dr. H. Sminia (Human Genetics department, LUMC)
Goal Students get their fictitious genome. This genome is a random selection of variants
from the 1000 genomes project. This genome is stored in a gene variant database
and has been enriched with variants that will be used during this minor to
demonstrate the relation between gene variants and phenotype. The students will
learn how to look for information in their genome in order to fulfil their assignments.
Practical 12.15 – 12.30
Title Saliva sampling for DNA analysis
Instructor Dr. H.P.J. Buermans (LGTC, Human Genetics department, LUMC)
Goal Students will provide saliva samples to isolate their own DNA for use in later
practicals.
Self-study 13.00 – 16.30
Title Knowledge from fictitious genome
Goal Students will read background information to prepare for their data analysis tasks.
The assignment is to search their genomes for variants linked to severe genetic
disorders and other variants that are associated with interesting phenotypes or
traits. Students will use their results to prepare their presentations for Wednesday
September 24 - Knowledge from genome according to the following guidelines:
1. Prepare a presentation of 10-15 min and include appropriate images
2. Explain the application of genome analysis
3. Explain the principle of genome analysis
4. Show a typical result from genome analysis
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5. Explain how these results should be interpreted
Self-study 16.30 – 17.30
Title Reading review and preparing questions for lecture Tuesday September 16 Dr.
G.W.E. Santen (11.00 – 11.45)
Goal Each student has to prepare a question for the lecture based on the article below
Literature de Ligt et al. Diagnostic Exome Sequencing in Persons with Severe Intellectual
Disability. N Engl J Med 2012;367:1921-9.
Tuesday September 16
Lectures 9.00 – 9.45; 10.00 – 10.45
Title 1) NGS data analysis, types of variants; 2) Potential consequences of a variant
Instructor Dr. P.E.M. Taschner (Human Genetics department, LUMC)
Goal Students will learn which types of variants can be detected and what their potential
consequences on gene function can be.
Lecture 11.00 – 11.45
Title WES/WGS and data analysis
Instructor Dr. G.W.E. Santen (Clinical Genetics department, LUMC)
Goal Whole exome (WES) and genome (WGS) sequencing techniques are rapidly being
introduced in clinical diagnostics. With WES and especially WGS many variants are
identified, and finding the causative variant(s) in a patient is not always
straightforward. The relative merits of WES and WGS will be discussed, and the
difficulties in the analysis of this type of large datasets will be illustrated using
several examples.
Practical 12.00 – 12.30
Title Databases and Genome browsing
Instructor Dr. P.E.M. Taschner (Human Genetics department, LUMC)
Goal Students will learn to find information needed to fulfil their exome-based data
analysis tasks and prepare their presentations.
Self-study 13.00 – 17.00
Title Knowledge from genome
Students continue to prepare their presentations for Wednesday September 24 -
Knowledge from genome.
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Wednesday September 17
Q&A voting 9.00 – 11.00
Title 1) Is this heritable or not? 2) I have a genome, what do I know?
Instructor Prof. dr. P. de Knijff (FLDO, Human Genetics department, LUMC)
Goal During this mix of lecturing and Q&A, students will be familiarized with the
consequences of knowing genome variation based health predictions using
aconcrete and detailed case example.
Practical 11.15 – 12.30
Title Databases and Genome browsing
Instructor Dr. H. Sminia (Human Genetics department, LUMC)
Goal Students will learn to find information needed to fulfil their exome-based data
analysis tasks and prepare their presentations.
Self-study 13.00 – 17.00
Title Knowledge from genome
Students continue to prepare their presentations for Wednesday September 24 -
Knowledge from genome.
Thursday September 18
Lecture 9.00 – 9.45
Title Ethics and law: Implications of Genome based Medicine
Instructor Dr. J.N.G.M. van Dartel and Mr. dr. R.E. van Hellemondt (Medical Ethics and Law
department, LUMC)
Goal Student receive an introduction on the ethical implications of Genome based
Medicine
Working group 10.00 – 12.30
Title Transhumanism and other images of the future.
Instructor Dr. J.N.G.M. van Dartel and Mr. dr. R.E. van Hellemondt (Medical Ethics and Law
department, LUMC)
Goal The student can explain how Genome Based Medicine is related with philosophical
views of humankind and its future. The student can explain what the impact is of
these technological images of medicine on the patient-physician relationship.
Self-study 13.00 – 17.00
Title Genetics and Genomics: Impact on Medicine and Society.
Goal The student can describe the changes in orientation in modern medicine and
critically reflect on the pros and cons of this development. The students have to
write a short paper (350 words) about the pros and the cons regarding the
developments in medicine.
Literature - Norgren A, Responsible Genetics. The Moral Responsibility of Geneticists for the
Consequences of Human Genetics Research, blz 218 – 223.
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- McKenny GP, The ethics of Regenerative Medicine: Beyond Humanism and
Posthumanism, in: Ip KT, (editor) The Bioethics of Regenerative Medicine, blz.155-
169.
Friday September 19
Patient Demonstration 9.00 – 9.45
Instructor Prof.dr. A. Tibben (Clinical Genetics department, LUMC).
Title Practical and emotional implications of a severe genetic disease
Goal In this patient demonstration the student learns the practical and emotional
implications of being confronted with a severe genetic disease.
Working group 10.00 – 12.30
Title Family Dynamics.
Instructor Prof. dr. A. Tibben (Clinical Genetics department, LUMC), Dr. J.N.G.M. van Dartel
and mr. dr. R.E. van Hellemondt (Medical Ethics department, LUMC)
Goal The student takes part in a role-play game that demonstrates the impact of
Huntington Disease on a family.
Self-study 13.00 – 17.00
Ethics and tasks.
Title Incidental findings.
Goal The student can explain the values and norms concerning incidental findings in
counselling and medical practice and reflects on his own position in this matter, for
instance regarding giving feedback to tested patients and expecting parents.
The students have to answer some questions in order to prepare for working group
‘incidental findings’ on Thursday 25 September.
Literature - Bredenoord AL, Onland Moret NI, Van Delden J, Feedback of individual
genetic results to research patients: in favour of a qualified disclosure policy, in:
Human Mutation 32(2010): 861-867.
- Search for relevant literature in Pudmed
- American Academy of Pediatrics, Committee on Bioethics, Committee on Genetics,
and American College of Medical Genetics and Genomics Social Ethical and Legal
Issues Committee. 2013.
Policy statement: Ethical and policy issues in genetic testing and screening of
children. Pediatrics 131(3): 620–622.
Monday September 22
Practical 9.00 – 10.00
Title DNA isolation
Instructor Dr. H.P.J. Buermans (LGTC, Human Genetics department, LUMC)
Goal Students will isolate their own DNA from the saliva samples taken previously
Tour 10.00 – 11.00
30
Title LGTC/Sequencing facility tour
Instructor Dr. H.P.J. Buermans (LGTC, Human Genetics department, LUMC)
Goal Students will visit LGTC/Sequencing facility while their DNA is dissolving
Practical 11.00 – 12.00
Title DNA quantification
Instructor Dr. H.P.J. Buermans (LGTC, Human Genetics department, LUMC)
Goal Students will quantify their DNA.
Self-study 13.00 – 14.00
Title Knowledge from genome
Students continue to prepare their presentations for Wednesday September 24 -
Knowledge from genome.
Practical 14.00 – 15.00
Title PCR setup for DNA profile & SNV test
Instructor Dr. H.P.J. Buermans (LGTC, Human Genetics department, LUMC)
Goal Students will set up PCR reactions for the DNA profile & SNV tests.
Tuesday September 23
Lecture 9.00 – 9.45
Title Transcriptomics, proteomics, metabolomics
Instructor Dr. P.A.C. 't Hoen (Human Genetics department, LUMC)
Goal Biomarkers are measurable molecular entities that serve as indicators of normal
biological or pathological processes. New –omics technologies are increasingly used
to identify RNA, protein or metabolite biomarkers in body fluids such serum or urine.
These biomarkers may be used in differential and early diagnosis, and in monitoring
of disease progression or therapeutic response. In this lecture, the technologies for
biomarker identification will be discussed. Moreover, with Duchenne Muscular
Dystrophy as an exemplar disease, it will be shown how molecular biomarkers can
support clinical measures in clinical trials for new drugs.
Lecture 10.00 – 10.45
Title The future hospital, personal monitoring
Instructor Prof. dr. M.H. Breuning (Clinical Genetics department, LUMC)
Goal Personalized medicine is expected to benefit from combining genomic information
with regular monitoring of physiological states by multiple high-throughput methods.
An integrative personal omics profile (iPOP), an analysis that combines genomic,
transcriptomic, proteomic, metabolomic, and autoantibody profiles from a single
individual can be used to interpret healthy and diseased states by connecting
genomic information with additional dynamic omics activity. It is expected that this
form of monitoring will revolutionize health care in the near future.
Contact 11.00 – 11.45
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Title My genome sequence
Instructor Dr. M. Kriek (Clinical Genetics department, LUMC)
Goal Q & A session on genome sequence topic
Preparation (paper placed on Blackboard)
Practical 13.00 – 16.00
Title DNA profile & SNV test
Instructor Dr. H.P.J. Buermans (LGTC, Human Genetics department, LUMC)
Goal Students will analyze PCR products for the DNA profile & SNV tests. The DNA profile
will be analysed using the Qiaxcel system; the SNV test using High Resolution Melting
Curve Analysis.
Wednesday September 24
Assessment 13.30 – 17.00
Title Oral presentations of students
Instructors Prof. dr. P. de Knijff (FLDO, Human Genetics department, LUMC), Dr. H. Sminia
(Human Genetics department, LUMC)
Goal Each student will give an oral presentation on Knowledge from genome that has
been prepared in weeks 3 & 4.
Thursday September 25
Lectures 9.00 – 12.15
Title Ethics and Law: Incidental findings
Instructor Dr. M. Kriek (department of Clinical Genetics, LUMC), mr. dr. R.E. van Hellemondt
and Dr. J.N.G.M. van Dartel (Medical Ethics department, LUMC)
Goal Students receive an introduction on ethical and legal aspects of incidental findings
identified by whole exome and whole genome sequencing.
Students receive information on how to handle incidental findings in a diagnostic -
and in a scientific setting
Practical 13.00 – 17.00
Title Ethics and Law: The future of neonatal screening
Instructor Dr. M. Kriek (Clinical Genetics department, LUMC), mr. dr. R.E. van Hellemondt
and dr. J.N.G.M. van Dartel (Medical Ethics and Law department, LUMC)
Goal The students will be invited to discuss some ethical and legal issues of neonatal
screening. The students will summarise the outcome of the discussion in a short
report. In this report, the students will describe both the pros and the cons of
extending neonatal screening by including untreatable (non-actionable disorders)
diseases . Finally they will ‘advice the health council” about the future of neonatal
screening.
Friday September 26
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Lectures 9.00 – 16.00 with a break (1 hour)
Title Ethics and law: Commercial screening
Instructor Dr. M. Kriek (Clinical Genetics department, LUMC), mr. dr. R.E. van Hellemondt en
Dr. J.N.G.M. van Dartel (Medical Ethics and Law department, LUMC)
Goal Student receive an introduction on ethical and legal aspects of genetic screening,
population surveys and direct-to-consumer testing.
Students will learn to write a reader’s letter on an actual screening issue.
Contact 16.00 – 17.00
Title Evaluation with students
Instructors Dr. J.N.G.M. van Dartel (Medical Ethics department, LUMC), Dr. M. Kriek (Clinical
Genetics department, LUMC)
Goal Evaluation of ethics and legal tasks.
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Theme3:Gene(s)&environment
Clinical and Scientific
coordinators: Prof.dr. ir. J.A.P. Willems van Dijk (HG) and Dr. P.A.C. 't Hoen (HG)
Other teachers involved: Prof.dr. C.J. van Asperen (CG), Prof.dr. R. Fodde (Erasmus MC), Dr. V.J.A.
van Harmelen (HG), Dr. K.M. Hettne (HG), Prof.dr J.J. van Hilten (Neuro),
Prof.dr. A.M.J.M. van den Maagdenberg (HG), Dr. E.C. Robanus Maandag
(HG), Dr. M. Kriek (CG), Prof.dr. H. Pijl (Endo), Dr. M. Roos (HG), Prof. dr.
P. Slagboom (Epi), Dr. G.M. Terwindt (Neuro), Dr. E.A. Tolner (HG), Dr.
M.P.G. Vreeswijk (HG), Dr. H. Vrieling (Tox), Dr. B. de Vries (HG)
Complex diseases, such as type 2 diabetes, migraine and Parkinson’s disease, are also called
polygenic diseases since they are usually not caused by mutations in a single gene but a result of a
set of genetic predispositions and their interplay with environmental factors. This poses significant
challenges that will be addressed in weeks 5 & 6.
We will discuss strategies how to identify genetic contributors to disease. Since any of the individual
factors usually contributes only a small risk, epidemiological studies in large populations are
required. Disease risk is modified by genetic and environmental factors such as microbiota and more
classical risk factors such as obesity, hypertension and smoking. As in complex diseases, the different
contributors to disease seldom act independently but usually form pathways or networks, much of
the focus of week 5 will be devoted on how to identify and study disease-specific pathways, including
approaches to visualize these pathways. Reliable biomarkers, for example proteins that can be
measured in the serum or plasma, can aid physicians in diagnosing their patients. Biomarkers can
also be instrumental to predict disease progression and response to therapy. In the biomarker show
case, the student will take up one the role of one of the important stakeholders, the doctor, the
patient, the researcher, the start-up company founder, or a member of registration board at the
qualification agency.
Based on genetic and molecular information, cellular and animal models can be designed to study
the pathophysiology of complex diseases and strategies to do this type of research will be discussed.
Also the impact of genetic understanding of complex diseases on the clinical counselling and clinical
care will a main focus. This will be illustrated based on four different complex diseases, metabolic
syndrome, migraine, breast and colon cancer. Much attention will be paid to both the clinical and
molecular aspects of these diseases and their prospects for personalized medicine.
Learning objectives and competences:
The student
• Can explain the main principles and pitfalls of genome-wide association studies
• Can use genetic risk prediction in the context of complex disease
• Is able to describe how environmental factors contribute to complex disease
• Is able to perform pathway analyses based on genetic findings
• Can play the role of different stakeholders in bringing biomarker assays to the market
• Can translate genetic knowledge to meaning full cellular and animal disease models
• Can use genetic knowledge of gene-function in cellular assays for breast cancer
This part of the course will include:
- Lectures on complex genetics and genome wide associations, i.e. migraine, breast cancer.
- Discussion on 23&me profile - what can we derive from a risk profile for complex diseases –
Alzheimer as example.
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- Lectures and working groups on the role of genes and environment in disease, i.e. cardio
vascular disease, migraine, metabolic syndrome, colon cancer.
- The design of a questionaire on familial risk assessment.
- A ‘role play’ to learn the points of view of different parties involved in the discovery and
qualification of biomarkers for polygenic diseases.
- Working groups on pathway analysis and functional studies for assigning functions to genetic
variants in complex disease.
Contact hours (27 hours over 10 days): e.g. designing a questionnaire, patient demonstrations
Interaction hours (15 hours over 10 days): e.g. risk profiling, panel discussion, workgroup
Self-study hours (10 hours): e.g. risk prediction assignment, preparation for migraine lecture,
Evaluation:
-risk prediction assignment (group feedback; ‘responsie college’)
-Gene to Disease test: variant annotation [INDIVIDUAL OFFICIAL EVALUATION]
- Anamnesis test [INDIVIDUAL OFFICIAL EVALUATION]
-Role play in biomarker show case assignment (group feedback)
-Migraine workgroup (group feedback)
-Design questionnaire for familial risk assessment (group feedback)
Knowledge that the Student should have prior to entering the Minor:
Chapters 8-10, 11, 12, 15, 20, 21, 23 Emery’s Elements of Medical Genetics, by P. Turnpenny, S. Ellard
35
OverviewProgrammeModuleTheme3
Topic Type of activity Name
Week 5 Monday September 29
9.00-10.00 Introduction: genetics of complex disease (family risk) Lecture Prof. K. Willems van Dijk
10.15-11.00 GWAS studies (principles plus platforms (array and NGS) explained) Lecture Dr. P-B. 't Hoen
13.00-14.00 Introduction Parkinson Lecture Dr. H. Marinus
14.00-16.00 23&me profile - what can we derive from a risk profile for complex diseases - Parkinson Practical Dr. P-B. 't Hoen
Tuesday September 30
9.00-10.00 Introduction gene - environment interactions (microbiotica) Lecture Prof. K. Willems van Dijk
10.15-11.15 Risk prediction: Cardiovascular disease Lecture Dr. M. Beekman
13.00-16.00 Self study - reading of review + answering questions Self study Prof. K. Willems van Dijk
16.00-17.00 Reflection on selfstudy Contact Prof. K. Willems van Dijk
Wednesday October 1
9.00-10.00 Introduction pathway / network analysis Lecture Dr. K. Hettne
10.15-11.15 GWAS and pathway analysis - migraine as example Lecture Dr. B. de Vries
13.00-15.30 Pathway visualization / network analysis Practical Drs. M. Roos & K. Hettne
15.30-16.30 Gene to disease task + anamnesis Assessment Dr. P-B. 't Hoen and Dr. M. Kriek
Thursday October 2
9.00 -10.00 Introduction show cases: discovery and qualification of biomarkers for polygenic diseases Lecture Dr. P-B. 't Hoen
10.00-15.00 Self study / preparation Role play Dr. P-B. 't Hoen
15.00-17.00 Presentations by groups: assessment of arguments by the group and by the instructors Contact Dr. P-B. 't Hoen
Friday October 3 “Leidens ontzet” no course today
Topic Type of activity Name
Week 6 Monday October 6
9.00-10.00 Genetic Susceptibility to Breast Cancer Lecture Dr. M. Vreeswijk
10.15-11.15 Breast cancer in the family: clinical genetic aspects Lecture Prof. C. van Asperen
11.15- 12.15 Testing genetic variants of unknown significance in functional cellular assays Lecture Dr. H. Vrieling
13.00-16.00 DNA sequence analysis in breast cancer families; how to determine clinical significance Practical Dr. H. Vrieling and Dr. M. Vreeswijk
Tuesday October 7
9.00-10.00 Clinical introduction metabolic syndrome Lecture Prof. H. Pijl
10.15-11.15 Inflammation in Metabolic Syndrome Lecture Dr. V. van Harmelen
13.00-16.00 Self study: papers migraine Self study Prof. A. van den Maagdenberg
17.00 Deadline questions for lecture on the following day Self study Prof. A. van den Maagdenberg
Wednesday October 8
9.00-10.00 Clinical introduction migraine Lecture Dr. G.Terwindt
10.15-11.15 Functional studies in mouse models Lecture Prof. A. van den Maagdenberg
13.00-17.00 Working group migraine functional & genetics Working group Drs. E. Tolner / B. de Vries
Thursday October 9
9.00 -10.00 Mouse models for colon cancer Lecture Prof. dr. R. Fodde
10.15-11.15 Microbiome as an environmental risk modifier of colon cancer Lecture Dr. E. Robanus-Maandag
13.00-16.00 Self study
16.00-17.00 Discussion of review by students Working group Dr. E. Robanus-Maandag
Friday October 10
9.00 -10.00 Introduction show case: unravelling the heriditary components of complex disorders Lecture Prof. C. van Asperen
10.15 -17.00 Show case: Design a questionaire on familial risk assessment Working group Prof. C. van Asperen
36
Monday September 29
Lecture 9.00 – 10.00
Title Introduction: genetics of complex disease (family risk)
Instructor Prof.dr. K. Willems van Dijk
Goal Both type 2 diabetes and cardiovascular disease are highly heritable as evidenced by
the dramatically increased risk for subjects with young affected relatives in the first
degree. A small proportion of this family risk is explained by monogenic inheritance.
However, the inheritance pattern of the risk in the majority of families is not
monogenic but complex. In this lecture, examples of genetic complex disease and
their interaction with environmental factors will be discussed.
Lecture 10.15 – 11.00
Title GWAS studies (principles plus platforms (array and NGS) explained)
Instructor Dr. P.A.C. 't Hoen
Goal Genome-wide association studies (GWAS) are powerful methods to identify genes
that explain the heritability of complex diseases. The identified genes frequently
provided new insights in the aetiology of the disease. In this lecture the principles of
GWAS, the molecular technology and the analysis methods will be explained. The
novel biological insights in diabetes, obtained through GWAS, will be discussed.
Lecture 13.00 – 14.00
Title Introduction Parkinson
Instructor Prof.dr. J. J. van Hilten
Goal Parkinson is a disease where GWAS has provided important insights in the molecular
pathways involved in the disease. The different clinical manifestations, genetic basis
and molecular pathways involved will be discussed. An overview of the clinical
research on Parkinson’s performed at LUMC will be given.
Practical 14.00 – 16.00
Title 23andMe profile - what can we derive from a risk profile for complex diseases -
Parkinson
Instructor Dr. P.A.C. 't Hoen
Goal 23andMe provides a molecular genetic tests to regular consumers without
intervention of a clinician. The report provided to the customer contains a risk
prediction for the development of complex diseases like Parkinson. Here we learn
how these risk scores are calculated, how they should be interpreted, and what the
potential impact of these tests on customers and their treating clinicians could be.
Tuesday September 30
Lecture 9.00 – 10.00
Title Introduction gene - environment interactions (microbiota)
Instructor Prof.dr. K. Willems van Dijk
Goal The microbiome, encoded by all microorganisms in and on our body, has also been
termed our second genome. For example, there are 10 times more bacteria in our
gut than we have cells. These bacteria are not just bystanders, but function in the
37
harvest of energy from our food and play a role in the development and
maintenance of the immune system. Gut microbiota have been associated with
metabolic and immune disorders and could function as targets for intervention. In
this lecture, recent insight into the role of gut microbiota in metabolic and
cardiovascular disease will be discussed.
Lecture 10.15 – 11.15
Title Risk prediction: Cardiovascular disease
Instructor Prof.dr. P. Slagboom (Dept. of Molecular Epidemiology)
Goal This lecture will explain the principles behind the calculations used in risk
predictions. More and more, the genetic make-up of an individual is used to
calculate disease risk. As an example, the burden test is used to combine the relative
risks from individual genetic loci into an aggregate genetic risk score. This, and the
relative merits and complementarity of classical (such as body mass index), genetic
and metabolic risk scores will be discussed in the context of the mortality from
cardiovascular disease.
Selfstudy 13.00 – 16.00
Title Reading review and answering questions
Literature Sommer F & Bäckhed F. The gut microbiota--masters of host development and
physiology. Nat Rev Microbiol. 2013;11(4):227-38
Contact 16.00 – 17.00
Title Reflection on selfstudy
Instructor Prof.dr. K. Willems van Dijk (Dept. Human Genetics)
Goal Discussion of selfstudy Sommer F & Bäckhed F paper.
Wednesday October 1
Lecture 9.00 – 10.00
Title Introduction pathway / network analysis
Instructor Dr. K. Hettne (Dept. Human Genetics)
Goal The interplay between an array of molecular factors lies at the basis of complex
diseases. Previously, genes were studied mostly in their isolation. More recently,
pathway and molecular network analysis methods have been developed that study
the concerted action of sets of genes, proteins and metabolites. This has two
important advantages: joint analyses are more powerful and joint analyses make
results better interpretable. An overview of molecular pathway and network-based
approaches to reveal the genetic basis of complex diseases will be given.
Lecture 10.15 – 11.15
Title GWAS and pathway analysis - migraine as example
Instructor Dr. B. de Vries (Dept. Human Genetics)
38
Goal Overview of the use of GWAS to identify migraine genes. The lecture will highlight
which genes have been identified in which patient groups and how knowledge on
mechanisms involved in the pathophysiology of migraine is achieved.
Practical 13.00 – 15.30
Title Pathway visualization / network analysis
Instructors Dr. M. Roos and Dr. K. Hettne (Dept. Human Genetics)
Goal In this computer practical the student will get to know bioinformatics tools that help
to visualize molecular pathways and networks underlying complex diseases.
Projection of results from large molecular datasets onto these pathways or networks
will facilitate the interpretation of these datasets and help to identify critical proteins
in these pathways and potential druggable targets.
Assessment 15.30 – 16.30
Title Gene to disease task + anamnesis
Instructors Dr. P.A.C. 't Hoen and Dr. M. Kriek
Goals In the gene to disease task, the student will receive a set of genetic variants and
evaluate their potential involvement in disease.
Preparation The student should review which characteristics discriminate genetic variants with
functional impact (such as their involvement in monogenic or complex disease) from
‘neutral’ genetic variation.
Thursday October 2
Lecture 9.00 – 10.00
Title Introduction show cases: discovery and qualification of biomarkers for polygenic
diseases
Instructor Dr. P.A.C. 't Hoen
Goals Biomarkers are molecular characteristics that can be used to determine disease
susceptibility, disease progression or response to therapy. Determination of
biomarker levels may help to individualize clinical care. An introduction on molecular
biomarkers will be given, followed by the introduction of the case study. The case
study will reflect the optimization of strategies for biomarker discovery and the route
towards authorization of biomarkers in clinical practice.
Role play 10.00 – 15.00
Title Self-study / preparation
Goal Students will be divided in groups with different roles: researcher, doctor, business
developer, patient, qualification agency (FDA / EMA). From these different
perspectives, the students will research the potential and added value of a given
biomarker for the current clinical practice and prepare a presentation for the whole
group where they argue for or against its introduction in clinical practice.
39
Contact 15.00 – 17.00
Title Presentations by groups: assessment of arguments by the group and by the
instructors
Instructors Dr. P.A.C. ’t Hoen & Prof. dr. K. Willems van Dijk
Goal Students will present what they have prepared for the assessment.
Friday October 3
“Leidens ontzet” so no course today
Monday October 6
Lecture 9.00 – 10.00
Title Genetic Susceptibility to Breast Cancer
Instructor Dr. M. Vreeswijk
Goal Since the discovery of BRCA1 and BRCA2 the search for additional breast cancer
susceptibility genes is ongoing. Depending on the associated breast cancer risk,
different methodologies are used for the identification of these genes. The function
of the genes will be discussed as well as the opportunities for personalized
healthcare.
Lecture 10.15 – 11.15
Title Breast cancer in the family: clinical genetic aspects
Instructor Prof.dr. C. van Asperen
Goal Overview of hereditary aspects of breast cancer: which genes are involved and how
is this knowledge applied into clinical practice (genetic counselling, screening high
risk groups, preventive surgery)
Lecture 11.15 – 12.15
Title Testing genetic variants of unknown significance in functional cellular assays
Instructor Dr. H. Vrieling
Goal High-throughput sequence analysis in patients with hereditary forms of cancer is
yielding a rapidly increasing number of genetic variants in cancer-predisposing genes
for which the clinical significance in terms of cancer risk is unknown. Functional
cellular assays have been developed to determine the impact of these variants on
gene function.
Practical 13.00 – 16.00
Title DNA sequence analysis in breast cancer families; how to determine the clinical
significance
Instructors Dr. M. Vreeswijk and Dr. H. Vrieling
Goal Many DNA alterations are identified during DNA sequencing in breast cancer
families. Students will learn how to use and interpret web-based tools to predict
whether certain DNA variants will affect protein function. Based on pedigree
information they have to decide which additional research should be commenced in
the family and which screening guidelines should be advised.
40
Tuesday October 7
Lecture 9.00 – 10.00
Title Clinical introduction metabolic syndrome
Instructor Prof.dr. H. Pijl
Goal Modern humans are severely mismatched with their nutritional environment, which
has resulted in a worldwide epidemic of obesity. Obesity is the driving force of the
metabolic syndrome, which is characterize by the co-occurrence of several metabolic
and vascular risk factors, associated with an increased risk for type 2 diabetes and
cardiovascular disease. In this lecture, the obesity epidemic will be discussed by
considering nutrition in the context of human evolution.
Lecture 10.15 – 11.15
Title Inflammation in Metabolic Syndrome
Instructor Dr. V. van Harmelen
Goal Obesity is closely associated with insulin resistance, type-2 diabetes (T2DM),
dyslipidemia, hypertension and cardiovascular disease. Expanding white adipose
tissue plays an important role in the patho-physiology of obesity associated disorders
as it responds to the energy overload with stress signals which in turn can elicit local
immune responses and inflammation. In my lecture I will describe the underlying
mechanisms for inflammation in white adipose tissue.
Selfstudy 13.00 – 15.00
Title Reading papers migraine & preparing questions for the lecture of Prof Dr. A.M.J.M.
van den Maagdenberg on Wednesday October 8
Goal After detailed reading each student prepares at least one relevant question that will
be addressed in the lecture of Prof Dr. A.M.J.M. van den Maagdenberg on
Wednesday October 8
Preparation De Vries B et al. “Molecular genetics of migraine” Hum Genet 2009;126:115-32.
van den Maagdenberg AM et al. “Migraine: gene mutations and functional
consequences” Curr Opin Neurol. 2007; 20(3):299-305.
Selfstudy 15.00 – 16.00
Title Reading papers migraine & preparing questions for Working group migraine
functional and genetics on Wednesday October 8
Goal Students are prepared for the Working group Migraine
Preparation Eising E et al. “Pearls and pitfalls in genetic studies of migraine” Cephalalgia 2013;
33(8):614-25; Charles A. Migraine: a brain state. Curr Opin Neurol. 2013
Jun;26(3):235-9
Contact 17.00
Title Deadline for sending in question lecture () on the following day
Instructor Prof.dr. A.M.J.M. van den Maagdenberg
41
Goal Each student sends at least one relevant question Prof Dr. A.M.J.M. van den
Maagdenberg by email ([email protected])
Wednesday October 8
Lecture 9.00 – 10.00
Title Clinical introduction migraine
Instructor Dr. G. M. Terwindt
Goal Migraine is a chronic, paroxysmal, neurologic disorder, characterized by severe
unilateral pulsating headache. Two types of migraine are distinguished: migraine
with and without aura. In migraine with aura, headache attacks are preceded or
accompanied by visual disturbances. In this lecture we will discuss the classification
and diagnosis of different forms of migraine.
Lecture 10.15 – 11.15
Title Functional studies in mouse models
Instructor Prof.dr. A.M.J.M. van den Maagdenberg
Goal Familial forms of severe migraine have led to the discovery of genes that play a role
in the etiology of a migraine attack. These genes have modified in mouse models and
these models provide novel insight into the underlying triggers for and mechanisms
of migraine. Migraine mouse models and functional studies to gain insight into
migraine will be discussed.
Workgroup 13.00 – 17.00
Title Working group migraine functional and genetics
Instructors Dr. E.A. Tolner and Dr. B. de Vries
Goals After a 15 min introduction about the working groups (13:00 – 13:15), the students
will be split into 2 groups of max 8 students. One working group will cover the
genetics of migraine and the other working group the functional mechanisms
involved in migraine, after 1,5 hour the students will switch groups.
The genetic working group will cover the identification of genetic factors for common
migraine. Genome-wide association studies (GWAS) are a typical approach to
identify these factors and have been very successful for migraine. An example for
migraine without aura (MO) will be discussed, and students will learn about the
clinical and methodological challenges involved in these studies (e.g. the difference
between clinic-based and population-based diagnoses) and the relevance of the
GWAS results for migraine patients.
The functional working group will cover underlying mechanisms of migraine, with
focus on changes in neuronal excitability and migraine susceptibility caused by
human pathogenic mutations. Migraine-relevant readouts will be discussed that
including the phenomenon of cortical spreading depression (CSD), the
neurobiological mechanism underlying the migraine aura. Students will learn to
recognize the effect of altered neuronal excitability, gender and a common migraine
trigger stress on the migraine-relevant readout CSD.
Preparation See self-study instructions for Tuesday October 7 2014
42
Thursday October 9
Lecture 9.00 – 10.00
Title Mouse models for colon cancer
Instructor Prof.dr. R. Fodde
Goal Familial forms of colon cancer have led to the discovery of genes that play a role in
the etiology of colon cancer. These genes have modified in mouse models and these
models provide novel insight into the underlying triggers for and mechanisms of
colon cancer. Colon cancer mouse models and functional studies to gain insight into
colon cancer will be discussed.
Lecture 10.15 – 11.15
Title Microbiome as an environmental risk modifier of colon cancer
Instructor Dr. E. Robanus Maandag
Goal Intestinal microbes protect against enteropathogens, extract nutrients and energy
from diets, and contribute to normal immune function. Disruptions to the normal
balance between the intestinal microbiota and the host can contribute to
susceptibility for diseases such as obesity, fatty liver disease, type 1 and 2 diabetes
and kidney disease. In this lecture, the role of microbiota in the development of
colon cancer will be discussed.
Selfstudy 13.00 – 16.00
Preparation Sears and Garrett. “Microbes, microbiota, and colon cancer”. Cell host & Microbe
2014; 15:317-328. Walsh et al. “Beneficial modulation of the gut microbiota”. FEBS
Lett. 2014; doi: 10.1016/j.febslet.2014.03.035.
Goal After detailed reading each group of 2 students can explain to the other students the
essentials of any paragraph of both papers.
Workgroup 16.00 – 17.00
Title Discussion of review by students
Instructor Dr. E. Robanus Maandag
Goal Each student knows the recent insights into the contributions of gut microbiota to
colon cancer and into beneficial modulation of these microbiota.
Friday October 10
Lecture 9.00 – 10.00
Title Introduction show case: unravelling the hereditary components of complex disorders
Instructor Prof.dr. C. van Asperen
Goal Pedigrees are a starting point for making a diagnosis hereditary cancer. Cases will be
discussed in order to decide if further investigations will be recommended.
Workgroup 10.15 – 15.00
Title Show case: Design a questionnaire on familial risk assessment
43
Goal Students will form groups and write a short introduction on family risk as
information for patients for different diseases: colon cancer, breast cancer, diabetes,
cardiovascular disease etc. (1 disease per group). In addition the questionnaire is
designed in a patient friendly manner.
Contact 15.00 - 17.00
Title Show case: Design a questionnaire on familial risk assessment
Instructors Prof.dr. C. van Asperen and Prof.dr. K. Willems van Dijk
Goal Students will present the short introduction on family risk as information for patients
and the questionnaires.
44
Theme4:
Personalgenomics:pharmacogenomics&genetictherapies
Clinical and Scientific
coordinators: Prof.dr. H.J. Guchelaar (CP) and Dr. A.M. Aartsma-Rus (HG)
Other teachers involved: Dr. P. Bank (CP), Prof.dr. M.H. Breuning (CG), Prof.dr. A.J. Gelderblom
(CO), Dr. P.C. Giordano (CG), Dr. C.L. Harteveld (CG), Dr. J. den Hartigh
(CP), Dr. K. Janssen (CG), Prof.dr. J.-L. Kerkhof (EUR), Dr. M. Lolkema (CO,
UMCU), Dr. M. Phylipsen (CG), Dr. J. Rens (Prosensa Therap.), Dr. J.J.
Swen (CP), E. Vroom (DMD Patient Association)
In this part of the course the topics of pharmacogenomics (week 7), health prevention screening
(week 7 & 8) and genetic therapies (week 8), which together form the core of Personalized medicine,
are covered.
Individual genetic variation and mutations cause genetic diseases and increase the risk for
developing complex diseases. Pharmacogenomics studies how genetic variation may also result in an
altered individual drug response, which can have serious implications for treating patients. The
potential problem is serious as genetic variation accounts for no less than 20-95% of the variability in
drug response. Drug response is complex with significant inter-patient variability with poor drug
efficacy as a main outcome. Even more dramatic, if pharmacogenomics is not taken into account,
patients may suffer from serious adverse events of using drugs that can directly affect the health of
patients, but could have been prevented. Needless to say that treating physicians should be made
well aware of the principles of pharmacogenomics and how genetic variation can affect treating their
patients. Fortunately, pharmacogenomic information is accumulating rapidly for an increasing
number of drugs and this will certainly impact clinical care more and more over the next few years.
Several consortia have published guidelines to aid physicians and pharmacists with the interpretation
of pharmacogenetic test results and multiple medical centers have initiated prospective genotyping
programs for “pharmaco-genes”.
DNA technology also has an impact on health prevention, for instance by neonatal screening of
newborns for a number of serious congenital diseases and/or diseases that can be treated if the
physician and parents are aware of the disease risk in the child. Hemoglobinopathies are good
examples of related monogenic diseases in blood for which health prevention screening is being
applied. Not unimportant, current therapeutic options for hemoglobinopathies have shortcomings
that are addressed in the course. Disease burden in patients and their families as well as the
economic burden due to expensive treatment has led to the implementation of prevention programs
in many countries where hemoglobinopathies are endemic. Also in The Netherlands
hemoglobinopathies is an increasing health problem. In our multi-ethnic population counselling and
primary prevention is an important strategy to tackle this problem. From 2007, Sickle Cell Disease
has been added to the list of diseases checked for in the heel-prick screening. It is one of the few
genetic diseases that can easily be screened by relatively simple and cheap biochemical methods
instead of the more expensive DNA screening. Benefits and pitfalls of offering screening for a genetic
disease, such as hemoglobinopathies, to the public will be discussed.
Molecular knowledge has the potential to lead to targeted therapies to treat disease, so-called
genetic therapies. Different personalized medicine approaches are in development, including gene
therapy, cell therapy, exon skipping, stop codon read-through and up-regulation of homologous
genes. Notably, the exon skipping approach can be exploited in different ways for different genetic
conditions, including Duchenne muscular dystrophy. Performing clinical trials for personalized
45
medicine approaches is challenging, especially when trials are performed in children. The main
technologies of genetic therapies, the perspectives of the researcher, the patient, and industry are
discussed in this part of the course, as well as the ethical considerations that link to dealing with sick
patients in drug testing.
Learning objectives:
The student
• Can identify the opportunities and challenges of different gene therapy approaches.
• Is able to critically review different gene therapy approaches.
• Can reproduce how exon skipping can be exploited for different diseases.
• Is able to discuss the key aspects of clinical trials from various stakeholder perspectives.
• Can give an example of how screening for a common monogenic disease can be offered
to the public.
• Can discuss various therapies and their limitations to prevent hemoglobinopathies.
• Is able to define the reasons and benefits for genetic population screening.
This part of the course will include various specific topics:
- Various introductory lectures on, a) pharmacogenomics and pharmacogenetics that are
important to understand how genetic variation can alter drug response (i.e. drug efficacy and
adverse events), b) health prevention screening (taking hemoglobinopathies as the example),
and c) genetic therapies (e.g. exon skipping as a promising molecular approach to design
therapy).
- Specific disease-targeted lectures and practical lectures that discuss how therapeutic drug
monitoring and drug intervention is performed in clinical practice
- Several hands-on topics, including preparing CYP2D6 student-specific drug passports, generating
a Wikipedia page, and a exon skip[ping workshop.
- A student debate on ethical aspects of therapy development.
Contact hours (8 hours), divided over 8 days: e.g. feedback on Wikipedia page, student debate
Interaction hours (28 hours), divided over 8 days: e,g. practicals, exon skipping workshop
Self-study hours (17 hours): e.g. preparing Wikipedia page, preparing for student debate
Evaluation:
- Wikipedia page assignment (feedback per student group). Pass/ no-pass
- CYP2D6 drug passport assignment (feedback per student group). Pass/ no-pass
- Student debate on ethical aspects of therapy development (group feedback)
Knowledge that the Student should have prior to entering the Minor:
Chapters 8, 10, 12, 20, 23 Emery’s Elements of Medical Genetics, by P. Turnpenny, S. Ellard
46
OverviewProgrammeModuleTheme4
Topic Type of activity Name
Week 7 Monday October 13
9.00-10.00 Introduction - Individualized Medicine "One size fits all" Lecture Prof. H.-J. Guchelaar
10.15-11.00 Basic pharmacokinetics and dynamics - a refresher Lecture Dr. J. Swen
11.15-12.00 Therapeutic drug monitoring in clinical practice Lecture Dr. J. den Hartig
12.00-13.00 Pharmacogenetics - Examples from clinical practice Lecture Prof. H.-J. Guchelaar
13.00-16.00 Planning: generating a Wikipedia page - hand out assignments Self study Dr. J. Swen
Tuesday October 14
10.15-11.15 Clinical application of pharmacogenetics Lecture Dr. J. Swen
11.30-12.30 Oncology pharmacogenetics in the LUMC Lecture/Patient contact Prof. H. Gelderblom
13.30 -14.30 CPCT - Center for Personilized Cancer Treatment Lecture Dr. M. Lolkema, UMCU
14.30-15.30 Self study: Wikipedia page Self study -
Wednesday October 15
9.00-12.00 Practical CYP2D6 genotyping Practical Dr. P. Bank
13.00-16.00 Self study: Wikipedia page Self study -
16.00 Self study: handing in draft version of Wikipedia page Contact Dr. J. Swen
Thursday October 16
9.00-12.00 Results from own genome test on CYP2D6 & preparation CYP2D6 drug passport Practical Dr. J. Swen
15.00-17.00 Discussion on personalized CYP2D6 drug passports Lecture/Patient contact Prof. H.-J .Guchelaar/Dr. J. Swen
Friday October 17
9.00-10.00 Population genetics screening-health prevention Lecture Prof. M. Breuning
10.15-11.15 The clinical example: hemoglobinopathies Lecture Dr. K. Harteveld
13.00-14.00 Clinical & health problem of hemoglobinopathies Lecture Prof. J.L. Kerkhoff, EUR
14.00-17.00 Practical: Hemoglobinopathy diagnostics & counseling Practical Dr. M. Phylipsen
Topic Type of activity Name
Week 8 Monday October 20
9.00-10.00 Sickle cell disease: a growing problem in The Netherlands Lecture Dr. K. Harteveld
10.15-11.15 Prevention strategies of hemoglobinopathies Lecture Dr. P. Giordano
13.00-16.00 Feedback to students on draft Wikipedia page + continuing optimisation Contact/Self study Dr. J. Swen
TuesdayOctober 21
9.00-10.00 Introduction on genetic therapies Lecture Dr. A. Aartsma-Rus
10.15-11.15 Assignment on genetic therapies Workgroup Dr. A. Aartsma-Rus
13.00-16.00 Literature assignment therapies Self study -
16.00-17.00 Discussion on genetic therapies for Duchenne muscular dystrophy Contact Dr. A. Aartsma-Rus
Wednesday October 22
9.00-9.30 Introduction on exon skipping Lecture Dr. A. Aartsma-Rus
9.45-12.00 Workshop exon skipping Workshop Dr. A. Aartsma-Rus
13.00-16.00 Ethical aspects of therapy development (based on Youtube movies) Self study -
Thursday October 23
9.30 -16.45 Attend the European Society of Gene and Cell Therapy Conference Conference
Friday October 24
9.00 -10.00 Launching student Wikepedia pages Lecture Dr. J. Swen
10.00 -12.00 Write short report on European Society of Gene and Cell Therapy Conference Workgroup Dr. A. Aartsma-Rus
14.00-15.00 Panel discussion on gene therapy Panel discussion Drs. A. Aartsma-Rus/Harteveld
47
Monday October 13
Lecture 9.00 – 10.00
Title Introduction - Individualized Medicine "One size fits one"
Instructor Prof.dr. H.-J. Guchelaar (Dept. of Clinical Pharmacy and Toxicology)
Goal Introduce the concept of pharmacogenetics and how this may affect
pharmacotherapy.
Lecture 10.15 – 11.00
Title Basic pharmacokinetics and dynamics - a refresher
Instructor Dr. J.J. Swen (Dept. of Clinical Pharmacy and Toxicology)
Goal To update basic knowledge on drug pharmacokinetics and dynamics.
Lecture 11.15 – 12.00
Title Therapeutic drug monitoring in clinical practice
Instructor Dr. J. den Hartigh (Dept. of Clinical Pharmacy and Toxicology)
Goal To explain how currently individualized drug dosing is achieved by therapeutic drug
dosing for several drug classes i.e. antibiotics, anticonvulsive and
immunosuppressive drugs.
Lecture 12.00 – 13.00
Title Principles of Pharmacogenetics
Instructor Prof.dr. H.-J. Guchelaar (Dept. of Clinical Pharmacy and Toxicology)
Goal To explain the background and principles of pharmacogenomics. How can genetic
variation influence drug response?
Contact 13.00 – 16.00
Title Planning: generating a Wikipedia page - hand out assignments
Instructor Dr. J.J. Swen (Dept. of Clinical Pharmacy and Toxicology)
Goal Students will be asked to prepare a Wikipedia page on a pharmacogenomics topic.
To this end they will perform a literature search, analyse and interpret collected
information and explain the pharmacogenomics topic in text that is understandable
to the interested lay public
Tuesday October 14
Lecture 10.15 – 11.15
Title Clinical application of pharmacogenetics
Instructor Dr. J.J. Swen (Dept. of Clinical Pharmacy and Toxicology)
Goal The student will gain insight in the current implementation of pharmacogenetics in
the LUMC. Available guidelines and online resources for pharmacogenomic
information will be discussed.
Lecture 11.30 – 12.30
Title Oncology pharmacogenetics in the LUMC
Instructor Prof.dr. H.J. Gelderblom (Dept. of Clinical Oncology)
Goal The application pharmacogenomics will be discussed from an oncology point of view.
How may germline and somatic variations in DNA be combined to optimize
treatment?
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Lecture 13.30 – 14.30
Title CPCT - Center for Personilized Cancer Treatment
Instructor Dr. M. Lolkema (Dept. of Clinical Oncology, UMCU)
Goal The mission and work of the Center for Personalized Cancer Treatment to
individualize cancer treatment will be presented.
Selfstudy 14.30 – 15.30
Title Wikipedia page
Goal To work on the Wikipedia assignment.
Wednesday October 15
Contact 9.00 – 12.00
Title Practical CYP2D6 genotyping
Instructor Drs. P. Bank (Dept. of Clinical Pharmacy and Toxicology)
Goal The student will determine his own CYP2D6 genotype.
Selfstudy 13.00 – 16.00
Title Wikipedia page
Goal To work on the Wikipedia assignment.
Contact 16.00
Title Handing in draft version of Wikipedia page
Instructor Dr. J.J. Swen (Dept. of Clinical Pharmacy and Toxicology)
Goal Handing in draft version of the Wikipedia page.
Thursday October 16
Contact 9.00 – 12.00
Title Results from own genome test on CYP2D6 & preparation CYP2D6 drug passport
Instructor Dr. J.J. Swen (Dept. of Clinical Pharmacy and Toxicology)
Goal Based on the available guidelines and his own CYP2D6 genotype the student will
prepare a written report, referred to as CYP2D6 passport.
Contact 15.00 – 17.00
Title Discussion on personalized CYP2D6 drug passports
Instructors Prof.dr. H.-J. Guchelaar & Dr. J.J. Swen (Dept. of Clinical Pharmacy and Toxicology)
Goal Plenary discussion of the CYP2D6 drug passport.
Friday October 17
Lecture 9.00 – 10.00
Title Population genetics screening-health prevention
Instructor Prof.dr. M. Breuning (Dept. of Clinical Genetics)
Goal The presenter will provide the students with the perspective of health prevention
through screening the population for genetic diseases.
Lecture 10.15 – 11.15
Title The clinical example: hemoglobinopathies
Instructor Dr. C.L. Harteveld (Dept. of Clinical Genetics)
49
Goal Providing the students with the necessary background of hemoglobinopathies as an
example of a complex monogenic trait in which prevention benefits from carrier
diagnostics.
Lecture 13.00 – 14.00
Title Clinical/health problem of hemoglobinopathies
Instructor Dr. J.-L. Kerkhoff (Hematologist, HAGA hospital, The Hague)
Goal The presenter will provide the students with background of pathology and current
treatment and curative options for Sickle Cell Disease and beta-thalassemia major.
Contact 14.00-17.00
Title Practical: Hemoglobinopathy diagnostics and counseling
Coordinator Dr. M.Phylipsen (Dept of Clinical Genetics)
Goal The student will learn to interpret lab results and act as a counsellor in performing
risk assessment for HbP-carriers in presumed couples at risk.
Monday October 20 Lecture 9.00 – 10.00
Title Sickle cell disease: a growing problem in The Netherlands
Instructor Dr. C.L. Harteveld (Dept. of Clinical Genetics)
Goal The presenter will explain how immigration can introduce a previously rare genetic
disease into a non-endemic country and change health policies.
Lecture 10.15 – 11.15
Title Prevention strategies of hemoglobinopathies
Instructor Dr. P.C. Giordano (Dept. of Clinical Genetics)
Goal The presenter will introduce the concept of prevention strategies to offer prevention
for severe genetic diseases to society using hemoglobinopathies as an example.
Contact 13.00 – 16.00
Title Feedback to students on draft Wikipedia page + continuing optimisation
Instructor Dr. J.J. Swen (Dept. of Clinical Pharmacy and Toxicology)
Goal Groups of students will receive feedback on the draft Wikipedia page.
Tuesday October 21
Lecture 9.00 – 10.00
Title Introduction on genetic therapies
Instructor Dr. A. Aartsma-Rus (Dept. of Human Genetics)
Goal Introduce different concepts of personalized medicine through genetic therapies to
the students.
Contact 10.15 – 11.15
Title Assignment on genetic therapies
Instructor Dr. A. Aartsma-Rus (Dept. of Human Genetics)
Goal Introduce Duchenne muscular dystrophy and outline the assignment to the students.
For the assignment, students will form groups of 3-4 and will receive 1-2 papers on
different genetic therapy approaches currently in development for DMD. Based on
the paper and literature research the students will have to outline the rationale of
the approach, the most important challenges and opportunities for each approach
50
and have to list for which other diseases the approach could apply as well in a 5-10
minute presentation. Each presentation is followed by a 5 minute discussion. Each
group will have to assign 1 presenter, 1 chair and 1-2 people asking questions to
other groups.
Selfstudy 13.00-16.00
Title Literature assignment therapies
Goal Students have time to read the provided paper and prepare their presentations
Contact 16.00-17.00
Title Discussion on genetic therapies for Duchenne muscular dystrophy
Instructor Dr. A. Aartsma-Rus (Dept. of Human Genetics)
Goal Each group will present their genetic approach as outlined above (1 presenter). The
previous group chairs the presentation and leads the discussion, the following group
has to ask questions (although everyone may ask questions).
Wednesday October 22
Lecture 9.00 – 9.30
Title Introduction on exon skipping
Instructor Dr. A. Aartsma-Rus (Dept. of Human Genetics)
Goal The exon skipping approach is explained to the students
Workshop 9.45-12.00
Title Exon skipping
Coordinator Dr. A. Aartsma-Rus
Goal The students form groups of ~4 students each and have to discuss their assignment,
which involves specific questions on exon skipping for a specific disease. In the last
hour the questions will be discussed by the entire group.
Selfstudy 13.00-16.00
Title Ethical aspects of therapy development
[De kans bestaat dat de studenten op 23 oktober naar de European Society of Gene and Cell Therapy mogen
alwaar een symposium zal plaatsvinden over ethical issues of trial development for rare diseases/children with
rare diseases. Het is op dit moment nog niet duidelijk of dit doorgang zal vinden. Zo ja, dan komt het
programma voor 23 oktober te vervallen, maar blijft het goed dat de studenten zich voorbereiden met deze
zelfstudie.]
Goal The students will be split in 2 equal groups and will have a debate on ethical issues in
involving children in clinical trials, with a focus on DMD (make sure there is at least
one student speaking Dutch in each group as some information is only available in
Dutch, so one student will need to brief the non-Dutch speakers). During the debate
each group will give an oral introduction (5 minutes) highlighting either arguments
against or in favour of performing trials in children, using what happened for DMD as
a showcase.
Things to consider are:
- Burden of participating in a trial for the child
- Informed consent
- Necessity of involving children in trials
- Trials to test safety vs trials to test efficacy of a drug
- Risk/benefit
- Need for multicenter trials for rare diseases
51
In preparation students can watch youtube movies on the impact of Duchenne
muscular dystrophy on daily living
(https://www.youtube.com/watch?v=BoLYm35FKtQ (in Dutch),
http://www.duchenne.nl/nieuws/in-de-media/date/2012 (in English)) and read the
following papers on ethical issues on performing clinical trials in children
(http://issuu.com/betapublishers/docs/medicines_06_2013/23?e=1264402/5910482
(in Dutch) and (http://nieuwsuur.nl/onderwerp/547650-kinderen-als-medisch-
proefpersoon.html) and
http://www.fda.gov/forconsumers/consumerupdates/ucm048699.htm. and this
newspaper article in Dutch on DMD trials that were not allowed in the Netherlands:
http://www.volkskrant.nl/vk/nl/2686/Binnenland/archief/article/detail/330148/200
9/05/09/Kinderen-van-de-rekening.dhtml
These links are a starting point – there is much more information out there.
Thursday October 23
Conference 9.00 – 16.45
Title Attend Conference on Gene and Cell Therapy in The Hague
Instructor Dr. A. Aartsma-Rus (Dept. of Human Genetics)
Goal Attending the European Society of Gene and Cell Therapy will provide the students
the opportunity to attend and international research conference.
Friday October 24
Contact 9.00 – 10.00
Title Launching student Wikipedia pages
Instructors Dr. J.J. Swen (Dept. of Clinical Pharmacy and Toxicology)
Goal Launch and completion of the Wikipedia assignement.
Selfstudy 10.00 – 12.00
Title Write a short report Conference on the Gene and Cell Therapy Conference in The
Hague
Goal The students will write a short report of two lectures they have attended at the Gene
and Cell Therapy Conference in The Hague. The report for each lecture should not be
more than 200 words.
Contact 14.00 – 15.00
Instructor Dr. A. Aartsma-Rus (Dept. of Human Genetics)
Title Panel discussion on gene therapy
Goal Students discuss with the instructor and with each other the possibilities (with pros
and cons) as well as the ethical implication of gene therapy.
52
Theme5:
Literatureassignment:Writingreport&Mini-symposium
Clinical and Scientific
coordinators: Prof.dr. D.J.M. Peters (HG), Prof.dr. A.M.J.M. van den Maagdenberg
(HG), Dr. W.M.C. van Roon-Mom (HG)
Other teachers involved: Prof.dr. T. Hankemeier (UvL/LACDR), Prof.dr. S.M. van der Maarel (HG),
Prof.dr. G.J.B. van Ommen (HG)
In the two final weeks (weeks 9 & 10) of the course students will apply their knowledge from the
previous weeks and will write a scientific paper/research proposal under the expert guidance of a
senior researcher. Three experts in the field of genetics will give a mini-symposium highlighting the
important role genetics will play in the clinic in the near future. Students will give an oral
presentation on their scientific research proposal in the closing student symposium.
Learning objectives:
The student
• Can communicate the acquired knowledge in a written report (“grant proposal”) and oral
presentation in a concise and structured way.
• Can critically assess the content of oral presentations of other student groups.
• Can critically assess the opportunities and limitations of knowing a patient’s full genome.
• Is able to discuss the broad implications of genetics in the future.
This part of the course will include various specific topics:
- Student take part in student group assignments to write a scientific research proposal. Students
closely interact in small groups with an expert researcher to define a relevant clinical problem
and tackle this with a research proposal that uses knowledge acquired in the course.
- Students prepare a written report and an oral presentation on the research topic.
- Several lectures of experts in the field of genetics will shine light on the future landscape of
genetics and how genetics will further add clinicians in treating patients.
Contact hours (6.5 hours over 10 days): e.g. contact expert research on progress of assignments
Interaction hours (15 hours over 10 days): e.g. lectures on future developments in genetics
Self-study hours (~40 hours over 10 days): preparation of written report and oral presentation
Evaluation:
-Written report
-Oral presentation
53
OverviewProgrammeModuleTheme5
Topic Type of activity Name
Week 9 Monday October 27
9.00-10.00 Introduction of Topics and senior scientists Contact Peters/Maagdenb/vRoon-M
10.15-11.15 Contact with senior Contact Diverse experts based on disease topic
11.30-17.00 Selfstudy Selfstudy
Tuesday October 28
9.00-10.00 Contact with expert senior scientist Contact Diverse experts based on disease topic
10.00-17.00 selfstudy Selfstudy
Wednesday October 29
9.00-15.00 selfstudy Selfstudy
Thursday October 30
9.00-10.30 Knowledge Test Assessment Peters/Maagdenb/vRoon-M
10.00-11.00 Contact with expert senior scientist Contact Diverse experts based on disease topic
Friday October 31
9.00-15.00 selfstudy Selfstudy
Topic Type of activity Name
Week 10 Monday November 3
9.00-10.00 Contact with expert senior scientist Contact Diverse experts based on disease topic
10.00-17.00 Selfstudy Self study
Tuesday November 4
9.00-15.00 selfstudy Selfstudy
Wednesday November 5 Mini symposium: Genetics of the future
9.00-10.00 Epigenetics and disease Lecture Prof.Dr. S.M. van der Maarel
10.00-11.00 Systems biology and genetic disease Lecture Prof.Dr. T. Hankemeier
11.00-12.00 The future of Genetics Lecture Prof.Dr. G.J.B. van Ommen
13.30-14.30 Contact with expert senior scientist Contact Diverse experts based on disease topic
Thursday November 6
9.00 -17.00 Self study Self study
-24.00 Deadline for handing in grant proposal Asessment Expert on disease topic
Friday November 7 Symposium with oral presentations
9,00-9,30 Half minor wrap-it-all-up: what have we learnt? Minor coordinators
9.00 -12.30 Presentations Assessment Diverse experts based on disease topic
12.30 - 13.00 Half minor evaluation with students Minor coordinators
54
Monday October 27
Contact 9.00 – 10.00
Title Introduction of Topics and senior scientists
Instructors Prof.dr. A.M.J.M. van den Maagdenberg, PhD; Prof.dr. D.M. Peters, PhD and Dr. W.
van Roon (half minor coordinators)
Goal Explanation about the student task to write a grant proposal and prepare an oral
presentation for the Student Symposium on November 7. Students will receive a
short introduction on the various disease topics and expert senior scientists.
Students will choose one fellow student for the student task and one of the disease
topic. In weeks 9 & 10 the students will work in pairs on the specific disease topic.
Self-study 10.00 – 17.00
Student pairs will have time to prepare the student task (grant proposal and oral
presentation).
Tuesday October 28
Contact 9.00 – 10.00
Title Contact with expert senior scientist
Instructor Expert on specific disease topic of the student pair
Goal Student pairs will meet with the senior scientist to discuss progress of the student
task (grant proposal and oral presentation)
Self-study 10.00 – 17.00
Student pairs will have time to prepare the student task (grant proposal and oral
presentation).
Wednesday October 29
Self-study 9.00 – 15.00
Student pairs will have time to prepare the student task (grant proposal and oral
presentation).
Thursday October 30
Assessment 9.00 – 10.00
Title Knowledge test
Instructors Prof.dr. A.M.J.M. van den Maagdenberg, PhD; Prof.dr. D.M. Peters, PhD and Dr. W.
van Roon (half minor coordinators)
Goals The students will make a written exam with 20 questions that will test the students’
knowledge on genetic technologies, monogenetic disorders, genetic testing in a
clinical routine, genes and environment, pharmacogenetics, genetic therapies and
ethics. The questions link to learning objectives of the course (i.e. both the general
objectives (Knowledge, academic skills, global health, collaboration) and course-
specific objectives).
Preparation Students have studied the course information that is placed on Blackboard
Contact 10.00 – 11.00
Title Contact with expert senior scientist
Instructor Expert on specific disease topic of the student pair
Goal Student pairs will meet with the senior scientist to discuss progress of the student
task (grant proposal and oral presentation)
55
Friday October 31
Self-study 9.00 – 15.00
Student pairs will have time to prepare the student task (grant proposal and oral
presentation).
Monday November 3
Contact 9.00 – 10.00
Title Contact with expert senior scientist
Instructor Expert on specific disease topic of the student pair
Goal Student pairs will meet with the senior scientist to discuss progress of the student
task (grant proposal and oral presentation)
Self-study 10.00 – 15.30
Student pairs will have time to prepare the student task (grant proposal and oral
presentation).
Self-study 15.30 – 17.00
Student pairs will have time to prepare the student task (grant proposal and oral
presentation).
Title Reading review and preparing questions for lecture Wednesday November 5
Prof.dr. S.M. van der Maarel (9.00 – 10.00)
Goal Each student has to prepare a question for the lecture based on the article below
Literature van der Maarel SM. Epigenetic mechanisms in health and disease. Ann Rheum Dis.
2008;67 Suppl 3:97-100. de Greef JC, Frants RR, van der Maarel SM. Epigenetic
mechanisms of facioscapulohumeral muscular dystrophy. Mutat Res. 2008;647(1-
2):94-102.
Tuesday November 4
Self-study 9.00 – 15.00
Student pairs will have time to prepare the student task (grant proposal and oral
presentation).
Wednesday November 5
Mini symposium: Genetics of the future
Lecture 9.00 -10.00
Title Epigenetics and disease
Instructor Prof.dr. S.M. van der Maarel (head Human Genetics department, LUMC)
Goal In “Epigenetics” heritable changes in gene activity are studied that are not caused by
changes in the DNA sequence. It can also be used to describe the study of stable,
long-term alterations in the transcriptional potential of a cell that are not necessarily
heritable. It becomes more and more clear that epigenetic changes of DNA can cause
human disease. In this lecture a few key diseases, some of which are highly relevant
to clinical care in the LUMC, will be discussed. The students will learn how epigenetic
changes can modify disease mechanisms and provide possible targets for drug
intervention.
Preparation Epigenetic review paper placed on Blackboard
56
Lecture 10.00 – 11.00
Title Systems Biology and genetic disease
Instructor Prof.dr. T. Hankemeier (director Netherlands Metabolomics Center, Leiden
University)
Goal Most biological systems are very complex and involve many proteins, peptides and
metabolites that are tightly regulated. Systems biology is a biology-based inter-
disciplinary field of study that focuses on complex interactions within biological
systems, using a holistic approach (holism instead of the more traditional
reductionism) to biological and biomedical research. A systems biology approach will
aid to better understand disease pathology and goes beyond the dysfunction of a
single gene product. In this lecture it will be made clear what are the main challenges
to measure molecules of various classes and how to study their interaction in
biological systems. Key examples will be presented that will illustrate the need and
power of systems biology in modern genetic research. The students will learn about
the opportunities of systems biology and how it can be used to understand disease
mechanisms and help identifying possible targets for drug intervention.
Preparation Systems biology review paper placed on Blackboard
Lecture 11.00 – 12.00
Title Future of Genetics
Instructor Prof.dr. GJ van Ommen (director of BBMRI, former head department Human
Genetics LUMC)
Goal There are many technical developments in modern genetic research that will cause a
revolution in how patients will be treated by physicians in a few years from now.
Genetic research itself also is developing rapidly with large consortia in which
researchers work together to advance knowledge on a specific disease. The
development of biobanks with large patient samples collected in an organised
manner has turned out a very productive way to perform such research. Physicians
will notice in their day-to-day practice that these new developments will change the
way they diagnose and perhaps even treat their patients. This lecture will paint the
future landscape of genetic research. The students will learn about new
opportunities from genetic developments for taking care of their patients that most
likely have been implemented when they start treating patients themselves.
Contact 13.30 – 14.30
Title Contact with expert senior scientist
Instructor Expert on specific disease topic of the student pair
Goal Student pairs will meet with the senior scientist to discuss progress of the student
task (grant proposal and oral presentation)
Tuesday November 6
Self-study 9.00 – 17.00
Student pairs will have time to prepare the student task (grant proposal and oral
presentation).
Assessment <24.00
Title Deadline for handing in grant proposal
Instructor Expert on specific disease topic of the student pair
Goal Each student pair needs to complete their grant proposal and send it by email to the
expert senior scientist that has guided them in weeks 9 & 10.
Preparation Grant proposal text: Report of max. 2500 words and 2 illustrations
57
Friday November 7
Student symposium
Lecture 9.00 – 9.30
Title Half minor wrap-it-all-up: what have we learnt?
Instructor Prof.dr. A.M.J.M. van den Maagdenberg (Dept. Human Genetics & Neurology,
LUMC)
Goal Short overview of the course topics in relation to the learning objectives. The
students will see how the different topics of the half minor are interconnected.
Assessment 9.30 – 13.00
Title Oral presentations of student pairs
Instructors Prof.dr. A.M.J.M. van den Maagdenberg, PhD; Prof.dr. D.M. Peters, PhD and Dr. W.
van Roon (half minor coordinators)
Goal Each student pair will give an oral presentation on the specific disease topic that
have studied in weeks 9 & 10.
Contact 13.00 – 13.30
Title Half minor evaluation with students
Instructors Prof.dr. A.M.J.M. van den Maagdenberg, PhD; Prof.dr. D.M. Peters, PhD and Dr. W.
van Roon (half minor coordinators)
Goal There will be a discussion between students and half minor coordinators to evaluate
the components of the half minor.