Things to Remember

Question 1

Chromosomes with C bands (hotspots for human specific evolutionary change)

Answer 1

1, 9, 16, and Y

Question 2

2 factors that influence nondisjunction

Answer 2

1. Nondisjunction events are related to the positioning of chiasmata; crossover events that occur too near or too far from the centromere increase chromosome nondisjunction.
2. Nondisjunction events are also related to the frequency of crossover events. The reduction or absence of recombination events increases the likelihood of nondisjunction.

Question 3

t(9;22)

Answer 3

diagnostic for chronic lymphocytic leukemias (CML), which can be treated with a specific tyrosine kinase inhibitor, Imatinib mesylate, also known as Gleevec

Question 4

t(15;17)

Answer 4

diagnostic for a specific acute myeloid leukemia (AML), which can be treated with retinoic acid and arsenic trioxide

Question 5

3 types of FISH probes

Answer 5

1. centromere (cen)
2. Locus Specific Identifier (LSI)
3. Fusion (F)

Question 6

Centromere FISH probe is used for:

Answer 6

Enumeration

ALL, Cen 8,21

Question 7

LSI FISH probe is used for:

Answer 7

Deletion/Duplication

p53; N-myc;Her2/neu

Question 8

F FISh probe is used for:

Answer 8

Translocations
(BCR;ABL t(9;22)
PML;RARA t(15;17))

Question 9

CMA can detect ____ and ____ but not ____

Answer 9

deletions, duplications

NOT translocations

Question 10

Frequent location of a Robertsonian translocation

Answer 10

chr.14 - chr. 21 fusion. Notice this often results in trisomy 21 (gamete has the copy of chr. 14 with 21 stuck onto it as well as the normal copy of 21).

Question 11

Two types of chromosomal deletions

Answer 11

1. Terminal deletion

2. Interstitial Deletion

Question 12

Contiguous gene syndrome

Answer 12

Disorder due to overexpression or deletion of multiple gene loci that are adjacent to one another.

Ex: Velocardiofacial syndrome (del 22q11) and DiGeorge syndrome (del 22q11)

Question 13

DNA Methylation as the Epigenetic Mark

Answer 13

1. The modification must be established in the gametes, the point in time when the maternal and paternal alleles are in separate compartments and can be differentially modified.
2. The allelic modification must be stably maintained after fertilization.
3. The modification must be capable of being erased and reset during the production of the germ cells such that the appropriate sex-specific imprint is transmitted to the progeny

Question 14

In somatic cells, methylation is maintained by which enzyme?

Answer 14

maintenance methyltransferase

Question 15

Mechanism of methylation in germ line

Answer 15

whole scale erasure of all of the methylation marks leads to demethylation of chromosomes, x chromosome reactivation and biallelic expression. Then, remethylation occurs through denovo methyltransferases happens in a sex specific manner. Occurs prior to initiation of meiosis in primordial germ cells.

Question 16

Testing for Down Syndrome

Answer 16

amniocentesis at 16 weeks

chorionic villus sampling at 11-12 weeks

Question 17

Physical features of a patient with Down Syndrome

Answer 17

Normal growth parameters, brachycephaly, mid face hypoplasia, up-slanting palpebral fissures, epicanthal folds, Brushfield spots, dysplastic small pinnae, heart murmur may be present, genitalia may be abnormal, especially in males (undescended testicles, small phallus, hypospadias), incurving 5th finger, small digits, increased space b/w 1st and 2nd toes, increased joint range of motion, diffuse hypotonia

Question 18

Medical conditions and prevalence of these conditions in patients with DS

Answer 18

• Congenital heart disease (1/3-1/2 of babies). Endocardial cushion defect, which is also called atrioventricular canal (AVC).
• GI tract defects: 10-15% of babies with DS. Esophageal or duodenal atresias, which leads to polyhydramnios during pregnancy.
• Both require surgical repair.
• Others: Small tear ducts, small eustachion tubes, small airway, eye problems (stabismus, nysatmus, cataracts, myopia), ear problems (infections, hearing loss), thyroid problems, celiac disease, diabetes, feeding issues, GERD, constipation, intellectual disabilities, autism, depression, Alzheimers.

Question 19

Understand why many biochemical variants are not deleterious.

Answer 19

1. Degeneracy of genetic code
2. “Like” amino acid replacement is often unnoticed
3. Amino acid replacement in the “non-business” portion of protein may not markedly influence function
4. Most importantly, Man is diploid for autosomal genes and thus has multiple
   alleles for most proteins.

Question 20

Gene rich chromosome

Answer 20

19

Question 21

Gene poor chromosomes

Answer 21

13, 18, 21

Question 22

Unstable region of Chr 5q13 is associated with

Answer 22

Spinal muscular atrophy (SMA)

Question 23

unstable region of Chr 22q is associated with

Answer 23

DiGeorge Syndrome

Question 24

Alu family

Answer 24

SINEs
300 bp related members
500,00 copies in genome

Question 25

L1 family

Answer 25

LINEs
6 kb related members
100,000 copies in genome

Question 26

Estimated number of genes

Answer 26

25,000-30,000

Question 27

Two ways that drigs are metabolized through biotransformations

Answer 27

Phase I- attach a polar group onto the compound to make it more soluble; usually
a hydroxylation step
Phase II- attach a sugar/acetyl group to detoxify the drug and make it easier to
excrete

Question 28

Six genes that are involved in metabolism of about 90% commonly used medications

Answer 28

CYP1A1
CYP1A2
CYP2C9
CYP2C19
CYP2D6
CYP3A4

Question 29

CYP3A substrates

Answer 29

Felodopine, Cyclosporin

Question 30

CYP3A inhibitors

Answer 30

Ketoconazole, grapefruit juice

Question 31

CYP3A Inducers

Answer 31

Rifampinn

Question 32

CYP2D6 substrates

Answer 32

Tricyclic antidepressants, codeine (activates to morphine)

Question 33

CYP2D6 Inhibitors

Answer 33

Quinidine, fluoxetine, Paroxetine

Question 34

CYP2C9 substrates

Answer 34

Warfarin

Question 35

NAT substrates

Answer 35

Isoniazid for tuberculosis

Question 36

TMPT substrates

Answer 36

6-mercaptopurine

6-thioguanine

Question 37

TMPT absent activity

Answer 37

Absent activity (~1:300-400) ! if you give these children with ALL (leukemia)
standard doses you will KILL the child due to immunosuppression

Question 38

G6PD substrates

Answer 38

sulfonamide, dapsone

Question 39

G6PD mechanism

Answer 39

X-linked enzyme

Question 40

G6PD deficient individuals are susceptible to ______

Answer 40

hemolytic anemia after drug exposure

Question 41

VKORC substrate

Answer 41

warfarin