TEACHING ABOUT HUMAN GENETICDISEASES FOR AP SUCCESS

DAVID SADAVA, PH.D.Lung Cancer Specialist

The Claremont Colleges

CASE 1: AN ANCIENT RITUAL

CIRCUMCISION: AN ANCIENT RITUAL

CIRCUMCISION RULES

Genesis 1710 This is my covenant with you and your descendants after you, the covenant you are to keep: Every male among you shall be circumcised. 11 You are to undergo circumcision, and it will be the sign of the covenant between me and you. 12 For the generations to come every male among you who is eight days old must be circumcised,

Luke 2:21  21On the eighth day, when it was time to circumcise him, he was named Jesus, the name the angel had given him before he had been conceived.

CIRCUMCISION RULES

Talmud:Biblical commentary200-500 CE

CIRCUMCISION RULES

“It once happened with four sisters at Sepphoris that whenthe first had circumcised her child he died [of exsanguin-ation], when the second died similarly, and the third also died. The fourth sister came before [the rabbi] who toldher, ‘you must not circumcise the child’”

CIRCUMCISION RULES

“If a woman had her first child circumcised and hedied as a result of the circumcision…and similarly hersecond child –whether the latter child was from herfirst husband or second husband – the third son maynot be circumcised”

HUMAN CHROMOSOMES

SEX CHROMOSOME INHERITANCE

SEX LINKAGE OF HEMOPHILIA

TREATMENT OF HEMOPHILIA

Antihemophilic Factor(Recombinant)Recombinate

CASE 2: PHENYLKETONURIA

A MEDICAL MYSTERY

Asbjorn Folling1934

Ferric chloride

Glucose

Control

Patients

A MEDICAL MYSTERY SOLVED

MEDICAL GENETICS

GENETIC DISEASE

NEWBORN SCREENING FOR PKU

Newborn Screening for Phenylketonuria: Predictive Validity

as a Function of Age

Edward R. B. McCabe MD, PhD, Linda McCabe PhD, Gayle A. Mosher MS, Richard J. Allen MD, and Julian L. Berman MD

Vol. 72 No. 3 September 1983, pp. 390-398

Hospital loses $70 million lawsuit

REDWOOD CITY -- Cara Cook says no amount of money can take back the amount of pain her young son has suffered in nine years.

But the mother of four said a San Francisco jury's decision to award her family more than $70 million in their suit against Stanford Hospital and Palo Alto Medical Clinic will provide resources to her son Michael, who was diagnosed with a rare metabolic disorder at age 5.

"I'd give it all back to have a healthy child, every penny so Michael can have a normal life," Cook said.

Michael, 9, suffered irreversible brain damage and is developmentally disabled because of delayed diagnosis and treatment of his disorder, known as phenylketonuria, or PKU. Those with PKU cannot metabolize a certain amino acid that is found in meats and dairy products.

The Redwood City family sued the two medical facilities after learning that the Stanford Hospital medical staff administered a standard blood screening test for metabolic disorders when their son was just 4 hours old.

Cara Cook said administering the test so soon after birth can often lead to a failure in detecting the disorder, as happened in Michael's case. Cook said in order for such a screening test to be accurate, it shouldn't be done at least until after a newborn has digested some food, or after 24 hours.

MEDICAL TREATMENT

CASE 3: SICKLE CELL DISEASE

SICKLE-CELL DISEASE

SICKLE CELL DISEASE AND MALARIA

Malaria Sickle-cell disease

SICKLE-CELL DISEASE AND HEMOGLOBIN

SICKLE CELL ANEMIA:MOLECULAR DIAGNOSIS

A sensitive new prenatal test for sickle-cell anemia

J. C. Chang and Y. W. Kan

Volume 307

 

 

July 1, 1982

TESTING FOR GENETICDIFFERENCES IN DNA

TESTING FOR SICKLE CELLANEMIA BY DNA ANALYSIS

CASE 4: CANCER AS A GENETIC DISEASE:

DIAGNOSIS

CANCER CHARACTERISTICS

Inappropriate cell reproduction

CANCER CHARACTERISTICS

Loss of cell specialization

SCLC and normallung cells

CANCER CHARACTERISTICS

Metastasis

CANCER CHARACTERISTICS

Angiogenesis

CANCER MOLECULAR BIOLOGY

Tumor DNA changes determine the properties of tumor cells

                              

CANCER DNA EXPRESSION

DNA….

is expressed in cancer cells as proteins such as..

Growth factors to stimulate cell reproduction

Enzymes to produceharmful substances

Scaffolds to changecell structures

THE DNA GENES CHANGED IN CANCER

ONCOGENES: “Gas pedals” to stimulate cell

reproduction

TUMOR SUPPRESSOR GENES:“Brakes” cut off so reproduction

is allowed to occur

ONCOGENES

TUMOR SUPPRESSOR GENES

COLON CANCER

112,000 new cases, 52,000 deaths, USA, 2007

THE PATH TO COLON CANCER

THE PATH TO COLON CANCER

Mutation in APCgene: Polyp

Mutation in rasgene: Precancerouslesion

Mutation in DCC gene: Adenoma

Mutation in p53gene: Carcinoma

Mutation in anti-metastasis genes:Metastatic tumor

BREAST CANCER

181,000 new cases, 41,000 deaths, USA, 2007

Gene expression profiling predicts clinical outcome of breast cancer

Laura J. van 't Veer and others

Letters to Nature

Nature 415, 530-536 (31 January 2002) |

GENE EXPRESSION SIGNATURE

Green:Good Prognosis

Red:Poor prognosis

GENE EXPRESSION SIGNATURE FOR BREAST CANCER

CASE 5: CANCER AS A GENETIC DISEASE:

TREATMENT

LEUKEMIA

CANCER CHEMOTHERAPY

SHUFFLING THE GENETIC DECK IN CANCER

FUSION PROTEINWITH TYROSINEKINASE ACTIVITY

22

bcr

abl

Ph

(22q-)

bcr-abl

9 9

(q+)

TARGETING THE NEW PROTEIN IN LEUKEMIA

April 5, 2001

Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia

Brian J. Druker, M.D., Moshe Talpaz, M.D., Debra J. Resta, R.N., Bin Peng, Ph.D., Elisabeth Buchdunger, Ph.D., John M. Ford, M.D., Nicholas B. Lydon, Ph.D., Hagop Kantarjian, M.D., Renaud Capdeville, M.D., Sayuri Ohno-Jones, B.S., and Charles L. Sawyers, M.D.

GLEEVEC -- THE PROTOTYPE DRUG FOR MOLECULAR MEDICINE

• Rob wrote:Just received my 9 month results from Portland. Of the 200 cells examined by FISH, there is no evidence of the Philadelphia Chromosome. I am very thankful to everyone involved with Gleevec, and pray that everyone else on the drug, or soon to be on the drug, has the same extraordinary results! Stay well, Rob dx 11/98 Gleevec 1/00 A Big Fat Zero 9/00

TEACHING ABOUT HUMAN GENETICDISEASES FOR AP SUCCESS

Hemophilia

Phenylketonuria

Sickle-cell disease

Cancer diagnosis

Cancer treatment