Transcript APgenetics0708

TEACHING ABOUT HUMAN GENETIC
DISEASES 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 17
10 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 commentary
200-500 CE
CIRCUMCISION RULES
“It once happened with four sisters at Sepphoris that when
the first had circumcised her child he died [of exsanguination], when the second died similarly, and the third also
died. The fourth sister came before [the rabbi] who told
her, ‘you must not circumcise the child’”
CIRCUMCISION RULES
“If a woman had her first child circumcised and he
died as a result of the circumcision…and similarly her
second child –whether the latter child was from her
first husband or second husband – the third son may
not be circumcised”
HUMAN CHROMOSOMES
SEX CHROMOSOME INHERITANCE
SEX LINKAGE OF HEMOPHILIA
TREATMENT OF HEMOPHILIA
Antihemophilic Factor
(Recombinant)
Recombinate
CASE 2: PHENYLKETONURIA
A MEDICAL MYSTERY
Ferric chloride
Glucose
Control
Patients
Asbjorn Folling
1934
A MEDICAL MYSTERY SOLVED
MEDICAL GENETICS
GENETIC DISEASE
NEWBORN SCREENING FOR PKU
Vol. 72 No. 3 September 1983, pp. 390-398
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
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
Volume 307
July 1,
1982
A sensitive new prenatal test for sickle-cell anemia
J. C. Chang and Y. W. Kan
TESTING FOR GENETIC
DIFFERENCES IN DNA
TESTING FOR SICKLE CELL
ANEMIA BY DNA ANALYSIS
CASE 4: CANCER AS A
GENETIC DISEASE:
DIAGNOSIS
CANCER CHARACTERISTICS
Inappropriate cell reproduction
CANCER CHARACTERISTICS
Loss of cell specialization
SCLC and normal
lung cells
CANCER CHARACTERISTICS
Metastasis
CANCER CHARACTERISTICS
Angiogenesis
CANCER MOLECULAR BIOLOGY
Tumor DNA changes determine the properties of tumor cells
CANCER DNA EXPRESSION
Growth factors to
stimulate cell
reproduction
is expressed in
cancer cells as
proteins such as..
DNA….
Enzymes to produce
harmful substances
Scaffolds to change
cell 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 APC
gene: Polyp
Mutation in DCC
gene: Adenoma
Mutation in p53
gene: Carcinoma
Mutation in ras
gene: Precancerous
lesion
Mutation in antimetastasis genes:
Metastatic tumor
BREAST CANCER
181,000 new cases, 41,000 deaths, USA, 2007
Letters to Nature
Nature 415, 530-536 (31 January 2002) |
Gene expression profiling predicts clinical
outcome of breast cancer
Laura J. van 't Veer and others
GENE EXPRESSION SIGNATURE
GENE EXPRESSION SIGNATURE
FOR BREAST CANCER
Green:
Good Prognosis
Red:
Poor prognosis
CASE 5: CANCER AS A
GENETIC DISEASE:
TREATMENT
LEUKEMIA
CANCER CHEMOTHERAPY
SHUFFLING THE GENETIC DECK IN
CANCER
9
9
(q+)
Ph
22
(22q-)
bcr
bcr-abl
abl
FUSION PROTEIN
WITH TYROSINE
KINASE ACTIVITY
TARGETING THE NEW
PROTEIN IN LEUKEMIA
April 5, 2001
Efficacy and Safety of a Specific Inhibitor of the BCRABL 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 GENETIC
DISEASES FOR AP SUCCESS
Hemophilia
Phenylketonuria
Sickle-cell disease
Cancer diagnosis
Cancer treatment