Exam II Flashcards
What three trisomys are compatible w/ life?
13, 18, 21
Which is the short arm of a choromosone…p or q?
p
Symptoms of Trisomy 18
Edwards syndrome
- small size, small head
- congenital heart defects
- overlapping fingers
- only 5% survive beyond 1 year
Frequency of trisomys
+21 (down) 1 in 700
+18 (Edwards) 1-2 in 6000
+13 (Patau) 1-2 in 10,000 (biggest chromosome/lots of genes hard to live with)
Symptoms of Trisomy 21
Flat facial profile upslanted palpebral fissures abnormal ears nuchal skin fold single palmar crease clinodactyly intellectual disability congenital heart disease leukemia, thyroid abnormalities hypotonia (decreased muscle) hyperflexibility
Symptoms of Trisomy 13
Patau syndrome: most rare.
scalp defects, small head cleft lip/palate multiple fingers renal abnormalities only 5% survive 6 months
Klinefelter Syndrome
- tall stature,
- learning differences
- small testicles
- infertility
- man boobs (gynecomastia)
Turner Syndrome
- lymphedema in infancy
- heart problems
- short
- 45X
- infertility
- low hairline, short neck
47XXX
1/1000
-speech delay, IQ 10-15 below siblings
-increased risk for infertility
Most offspring are chromosomally normal
47 XYY
1/1000
- lower IQ
- may be at risk for behavioral problems, impulsivity
- most offspring are chromosomally normal
When does heterodisomy occur?
In M1 block (H comes before I)
When does isodisomy occur?
If Meiosis II was blocked
Trisomic Rescue
When there are 3 chromosomes and one disappears
What percent of SAB’s have a normal karyotype?
60%
What is the most frequent trisomy seen in abortions?
Trisomy 16
What percent of X genes escape X inactivation?
About 15%
steps involved in x-inactivation
- counting
- choice
- abnormal X inactivated if it has XIST
- translocation between X and autosome, normal X inactivated - cis inactivation
Example of microdeletion
williams syndrome (deletion on chromosome 7 on elastin gene)
example of insertion
chrones disease
example of duplications
duplication of PMP22 on chromosome 17; Charcot-Marie-Tooth disease (neuropathy)
examples of frameshift mutatioons
- neurofibromatosis type 1
- breast and colon cancer
- hemophilia
Promotor mutation example
dyskeratosis congenita: premature aging and bone marrow disease
Classical recessive inheritance
ex: PKU. when 2 abnormal copies of gene are necessary to see disease
Haploinsufficiency
AD. When 1 copy is mild, 2 copies is severe. Also called incomplete dominance. Ex: familial hypercholesterolemia
Dominant Negative
AD. when the mutant copy interferes with the other normal copy. Example: OI
How are SNPs inherited?
in sets called haplotypes
What percent of human genome varies from person to person
12%
How was kabuki syndrome discovered?
Whole exome sequencing.
What percent of cancers are germline?
5-10%
What are indications of hereditary cancer?
young age <50, bilateral tumors, rare tumors
What are examples of hereditary cancers?
retinablastoma in both eyes, whilms tumor
How many gene copies in an oncogene need to be mutated to get cancer?
1
What are examples of oncogene mutation cancers
RET (multiple endocrine neoplasia, BCR (leukemia) and HRAS=costello
What are examples of tumor suppressor genes?
Rb, NF1, p53, APC
What is an example of a mismatch repair cancer?
lynch syndrome/HNPCC (need 2 copies mutated)
What combinations of cancers in a family history are indicative of hereditary cancer?
Breast, pancreatic, ovarian (BRCA)
Breast, sarcomas, leukemia, brain (p53)
red flags for BRCA
early onset, male breast cancer, ovarian cancer, bilateral, ashkenazi jewish descent (1/40 carrier rate)
What things ameliorate BRCA risk?
- breast feeding >12 months
- oral contraceptive use
- Masectomy reduced cancer by 95%
- Oophorectomy reduced risk by age 40
More children increased risk for BRCA 1 but not 2
What is an example for a variable penetrance inherited cancer?
Colorectal cancer.
Familial adenomatous polyposis coli
Which diagnostic test can be performed 1st semester?
CVS; amniocentesis is second semester
When can a nuchal translucency test be performed and what is the measurment that indicates risk for aneuploidy?
11-13 weeks, >3 mm
What percent of aneuploidy does nuchal translucency detect?
60%
What is an echogenic intracardiac foci?
a soft marker that has an increased risk of T21 seen on an ultrasound
What gets tested in a maternal serum marker?
11-13 weeks: free B-HcG, PAPPA
2nd tri: quad screen, AFP, uE3, HcG, inhibin A
When is NIPT not useful?
not valid in twins, not enough data
When is CVS used?
10-13 weeks. 1-300 chance of miscarriage
1% chance of confined mosaicism
What is pre implantation genetic screening?
use a microarray to test for aneuploidy; not diagnostic due to mosaicism
What is a pre implantation genetic diagnosis?
looks for 1 family gene mutation; not actually diagnostic
