Exam II

Question 1

What three trisomys are compatible w/ life?

Answer 1

13, 18, 21

Question 2

Which is the short arm of a choromosone…p or q?

Answer 2

p

Question 3

Symptoms of Trisomy 18

Answer 3

Edwards syndrome

• small size, small head
• congenital heart defects
• overlapping fingers
• only 5% survive beyond 1 year

Question 4

Frequency of trisomys

Answer 4

+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)

Question 5

Symptoms of Trisomy 21

Answer 5

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

Question 6

Symptoms of Trisomy 13

Answer 6

Patau syndrome: most rare.

scalp defects, 
small head
cleft lip/palate
multiple fingers
renal abnormalities
only 5% survive 6 months

Question 7

Klinefelter Syndrome

Answer 7

• tall stature,
• learning differences
• small testicles
• infertility
• man boobs (gynecomastia)

Question 8

Turner Syndrome

Answer 8

• lymphedema in infancy
• heart problems
• short
• 45X
• infertility
• low hairline, short neck

Question 9

47XXX

Answer 9

1/1000
-speech delay, IQ 10-15 below siblings
-increased risk for infertility
Most offspring are chromosomally normal

Question 10

47 XYY

Answer 10

1/1000

• lower IQ
• may be at risk for behavioral problems, impulsivity
• most offspring are chromosomally normal

Question 11

When does heterodisomy occur?

Answer 11

In M1 block (H comes before I)

Question 12

When does isodisomy occur?

Answer 12

If Meiosis II was blocked

Question 13

Trisomic Rescue

Answer 13

When there are 3 chromosomes and one disappears

Question 14

What percent of SAB’s have a normal karyotype?

Answer 14

60%

Question 15

What is the most frequent trisomy seen in abortions?

Answer 15

Trisomy 16

Question 16

What percent of X genes escape X inactivation?

Answer 16

About 15%

Question 17

steps involved in x-inactivation

Answer 17

1. counting
2. choice
   - abnormal X inactivated if it has XIST
   - translocation between X and autosome, normal X inactivated
3. cis inactivation

Question 18

Example of microdeletion

Answer 18

williams syndrome (deletion on chromosome 7 on elastin gene)

Question 19

example of insertion

Answer 19

chrones disease

Question 20

example of duplications

Answer 20

duplication of PMP22 on chromosome 17; Charcot-Marie-Tooth disease (neuropathy)

Question 21

examples of frameshift mutatioons

Answer 21

1. neurofibromatosis type 1
2. breast and colon cancer
3. hemophilia

Question 22

Promotor mutation example

Answer 22

dyskeratosis congenita: premature aging and bone marrow disease

Question 23

Classical recessive inheritance

Answer 23

ex: PKU. when 2 abnormal copies of gene are necessary to see disease

Question 24

Haploinsufficiency

Answer 24

AD. When 1 copy is mild, 2 copies is severe. Also called incomplete dominance. Ex: familial hypercholesterolemia

Question 25

Dominant Negative

Answer 25

AD. when the mutant copy interferes with the other normal copy. Example: OI

Question 26

How are SNPs inherited?

Answer 26

in sets called haplotypes

Question 27

What percent of human genome varies from person to person

Answer 27

12%

Question 28

How was kabuki syndrome discovered?

Answer 28

Whole exome sequencing.

Question 29

What percent of cancers are germline?

Answer 29

5-10%

Question 30

What are indications of hereditary cancer?

Answer 30

young age <50, bilateral tumors, rare tumors

Question 31

What are examples of hereditary cancers?

Answer 31

retinablastoma in both eyes, whilms tumor

Question 32

How many gene copies in an oncogene need to be mutated to get cancer?

Answer 32

1

Question 33

What are examples of oncogene mutation cancers

Answer 33

RET (multiple endocrine neoplasia, BCR (leukemia) and HRAS=costello

Question 34

What are examples of tumor suppressor genes?

Answer 34

Rb, NF1, p53, APC

Question 35

What is an example of a mismatch repair cancer?

Answer 35

lynch syndrome/HNPCC (need 2 copies mutated)

Question 36

What combinations of cancers in a family history are indicative of hereditary cancer?

Answer 36

Breast, pancreatic, ovarian (BRCA) | Breast, sarcomas, leukemia, brain (p53)

Question 37

red flags for BRCA

Answer 37

early onset, male breast cancer, ovarian cancer, bilateral, ashkenazi jewish descent (1/40 carrier rate)

Question 38

What things ameliorate BRCA risk?

Answer 38

1. breast feeding >12 months 2. oral contraceptive use 3. Masectomy reduced cancer by 95% 4. Oophorectomy reduced risk by age 40 More children increased risk for BRCA 1 but not 2

Question 39

What is an example for a variable penetrance inherited cancer?

Answer 39

Colorectal cancer. | Familial adenomatous polyposis coli

Question 40

Which diagnostic test can be performed 1st semester?

Answer 40

CVS; amniocentesis is second semester

Question 41

When can a nuchal translucency test be performed and what is the measurment that indicates risk for aneuploidy?

Answer 41

11-13 weeks, >3 mm

Question 42

What percent of aneuploidy does nuchal translucency detect?

Answer 42

60%

Question 43

What is an echogenic intracardiac foci?

Answer 43

a soft marker that has an increased risk of T21 seen on an ultrasound

Question 44

What gets tested in a maternal serum marker?

Answer 44

11-13 weeks: free B-HcG, PAPPA | 2nd tri: quad screen, AFP, uE3, HcG, inhibin A

Question 45

When is NIPT not useful?

Answer 45

not valid in twins, not enough data

Question 46

When is CVS used?

Answer 46

10-13 weeks. 1-300 chance of miscarriage | 1% chance of confined mosaicism

Question 47

What is pre implantation genetic screening?

Answer 47

use a microarray to test for aneuploidy; not diagnostic due to mosaicism

Question 48

What is a pre implantation genetic diagnosis?

Answer 48

looks for 1 family gene mutation; not actually diagnostic