Download - Genetics and internal medicine (1)
Genetics Course:Mastering Medical Genetics
Dr. Ahmed Elshebiny , MDDr. Ahmed Elshebiny , MDLecturer of Internal MedicineLecturer of Internal Medicine
Faculty of Medicine, Menoufyia UniversityFaculty of Medicine, Menoufyia University
Former Clinical Research FellowFormer Clinical Research Fellow,,Joslin Diabetes Center, Harvard UniversityJoslin Diabetes Center, Harvard University
Course includes1. Basic Principles of Medical Genetics 2. Genetic basis of disease: How diseases could be
inherited? 3. Medical Genetics in Clinical Practice : What is the
impact of genetics on the present and future of Medicine?
Let us start with this introductory video about genes
Medical Genetics Any application of genetic principles
to medical practice. “Genetics – study of individual genes
and their effects”
Outline
The Genetics course
Basics Diseases ApplicationsStructure & Facts
Functions
Inherited disorders
Gene Therapy
Cloning
Stem Cell
Genetic Testing
1. The Human Genome 2. DNA structure and packaging3. Mitochondrial DNA4. Chromosomal Morphology
5. Chromosome Replication6. Gene Expression7. Meiosis , Mitosis and Gametogenesis8. Epigenetics
9. Population Genetics10. Consanguinity11. Family medical History12. Inherited disorders13. Mendelian inheritance14. Non Mendelian inheritance15. Cytogenetic abnormalities
Structure & Facts of the Human Genome
Functions& Physiology
Clinical Genetics
2 -Genetic basis of disease1. Chromosomal abnormalities
2. Genetics of Metabolism
3. Genetics of Hemoglobinopathies
4. Genetics of Bleeding disorders
5. Genetics of Development
6. Cancer Genetics
3-Medical Genetics in Clinical Practice
Genetic testing Genetic screening Molecular diagnostics Genetic engineering Gene Therapy Stem cell therapy Cloning
Genetics Course (1):Mastering Medical Genetics
The Human Nuclear Genome Genome = all of the DNA in an organism or
cell Size of human genome: 3.4 billion base pairs Number of human genes: ~30,000 Genes vary in length and can cover thousands of
bases average size: ~3,000 bp Only about 2% of the human genome contains
coding genes Action of much of the genome is unknown
DNA Structure
DNA Structure
Epigenetics Epigenetics is the study of heritable changes
in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence, hence the name epi- (Greek: επί- over, above) -genetics.
These changes may remain through cell divisions for the remainder of the cell's life and may also last for multiple generations.
Chromosome Facts # of chromosomes per somatic cell: 22 pairs + 1 pair
sex-determining chromosomes = 46 # of chromosomes per gamete (egg/sperm): 23 One chromosome of each pair donated from each
parent’s egg or sperm Sex chromosomes: XY for males; XX for females Largest chromosome #1 = ~263 million base pairs
(bp) Smallest chromosome Y = ~59 million bp
Chromosomal morphology methods Chromosomal staning FISH
Chromosomal Banding
Chromosomes
Mitochondrial DNA
Circular Several copies No histones
Function of DNA
The Human genome functions
Gene Expression Transcription Translation
Meiosis , Mitosis and Gametogenesis Mitosis is the process by which a cell
separates its duplicated genome into two identical halves
Meiosis is the process that transforms one diploid into four haploid cells.
Where do your genes come from?
Genomic imprinting Most genes expressed equally from both alleles Small number of genes show differential expression
dependent on parent of origin (mainly on chromosomes 6,7,11,14,15)
‘Imprint’ is mediated by methylation transcriptional inactivation
Imprint persists through cell divisions in embryo Imprint removed at gametogenesis and then re-
established according to sex of transmitting parent
Population Genetics Is the study of distributions of genes in
populations Disease frequency Genotype frequencies from generation to
generation Genetic Polymorphisms
SNPs
Polymorphism Occurrence of 2 or more alleles at aspecific
genetic locus in frequencies greater than can be explained by mutations alone
Single nucleotide polymorphisms Restriction fragment length polymorphism
(RFLP) Variable number tandem repeat
polymorphism (VNTR)
Clinical genetics
Clinical genetics is the practice of clinical medicine with particular attention to hereditary disorders.
Inherited disorders Cytogenetic Single gene Polygenic Multifactorial
Clinical Genetics Genotype: An individual’s genetic makeup - forms of a
particular gene at a given locus
Phenotype: The observable expression of a genotype
Homozygous: Identical forms of a particular gene
Heterozygous: Different forms of a gene– CARRIER if one normal and one abnormal
Dominant: Condition phenotypically expressed in someone carrying one copy of a mutant gene
Recessive: Condition phenotypic ally expressed only in someone with two copies of the mutant gene
Autosomal dominance Vertical transmission
On average, 50% of offspring of affected parent will be affected
Unaffected individuals do not transmit trait
Males and females equally affected
Autosomal Dominant Conditions Marfan Syndrome Achondroplasia Familial (early-onset) Alzheimer
Disease Huntington Disease Familial Hypercholesterolemia Familial Breast Cancer (BRCA1 or
BRCA2 mutations)
Autosomal Recessive Inheritance Horizontal transmission; disease in siblings but usually not in earlier
generations (unaffected, carrier parents)
On average, 25% recurrence risk
Males and females equally affected
Increased consanguinity (relatedness) seen
Autosomal Recessive Conditions Sickle cell disease Cystic fibrosis Tay-Sachs disease Hemochromatosis Phenylketonuria Thalassemias
X-linked recessive inheritance Incidence of trait is much higher in males than
females No father-to-son transmission 100% of daughters of affected males are
(unaffected) carriers 50% of sons of carrier females are affected and
50% of daughters are carriers Trait may be transmitted through series of
carrier females
X-linked recessive conditions Haemophilia Duchenne and Becker muscular dystrophy Androgen insensitivity syndrome Hunter syndrome Glucose-6-phosphate-dehydrogenase
deficiency Bruton agammaglobulinaemia
Xplinked dominant Males and females affected, females usually less
severely affected than males 1 in 2 risk to children of affected female (M+F) All daughters of affected male affected but no male
to male transmission
X-linked dominant inheritance Males and females affected
Vitamin D resistant ricketsOTCDFragile X syndrome
Lethal in malesIncontinentia pigmentiRett syndromeXL chondrodysplasia
punctataGoltz syndrome
Mitochondrial inheritance Mitochondria are
exclusively maternally inherited
Males and females affected but only females will transmit to offspring
Risks to offspring of affected or carrier females are difficult to determine 0-100%
Family Medical Historyfamily medical history represents a “genomic
tool” that can capture the interactions of genetic susceptibility, shared environment and common behaviors in relation to disease risk.
References Merck manual : online textbook
E-medicine , online textbook , specialties,.
BRS series : Genetics 2010 Lecture notes : Genetics (2006) Kumar & Klark : Clinical Medicine 2009 Other Web Resources & books
Genetics Course (2):Mastering Medical Genetics