Exam 3 Main Points

Question 1

First successful GWA study

Answer 1

Age-related macular degeneration

Question 2

Other successful GWA study

Answer 2

Chron’s disease

Question 3

GWA and inflammatory bowel diseases

Answer 3

GWA only showed a small part of genetic variance in inflammatory bowel disease.

Question 4

SLCO1B1

Answer 4

A variant of a chromosome associated with statin-induced myopathy.

Question 5

Problems with GWAs

Answer 5

Etiology of genes questionable
Difficulty of finding relevant gene
Low penetrate
Identified region far away from actual gene.

Question 6

Changes in _ rather than changes in _ underlie most GWA associations.

Answer 6

Changes in gene regulation rather than changes in proteins underlie most GWA associations.

Question 7

CDRV

Answer 7

GWAs will not identify rare variants in most cases.

Question 8

T1D and HLA - what form is the highest risk

Answer 8

D3/DR4. At least 1 allele present in 95% of patients with TD

Question 9

T1D and VNTR (INS)

Answer 9

Short (26 - 63 repeats) predispose to T1D

Long (140 - 210 repeats) are protective of B cells.

Question 10

Concordance of T1D

Answer 10

Concordance of 50% of monozygotic twins, environmental factors are important.

Question 11

T2D and concordance

Answer 11

70%

Question 12

Best predictor for T2D

Answer 12

Insulin resistance

Question 13

TCF7L2

Answer 13

First important gene identified in T2D. Associated with impaired beta cell function, but not with insulin resistance.

Question 14

T allele of rs7903146

Answer 14

Enhances expression of TCF7L2 -> impairs insulin secretion.

Question 15

SLC30A8 (zinc transporter)

Answer 15

Confers T2D risk in addition to TCF7L2 gene.

Question 16

T2D: most of the genes identified by GWAs apppear to be involved in

Answer 16

Beta cell dysfunction than insulin resistance.

Question 17

T2D: 80-90% SNPs are

Answer 17

Intergenic/intrionic

Question 18

T2D: common variants contribute more than

Answer 18

Rare variants

Question 19

Features of MODY

Answer 19

Early onset
No autoimmune disorder/antibodies
No insulin resistance
Low insulin
Absence of obesity

Question 20

Major classes of cancer genes

Answer 20

Oncogenes
Tumor suppressor (TS) genes

Question 21

Tumor suppressor (TS) genes

Answer 21

Gatekeepers

Caretakers

Question 22

Number of mutations needed in TS genes to show phenotype

Answer 22

Mutations are recessive; function of both alleles must be lost to be cancerous.

Question 23

Function of TS cells

Answer 23

Block uncontrolled cell growth
Cell adhesion molecules
Negative regulators of cell cycle
Repair of mutations in DNA

Question 24

RB1 (cancer)

Answer 24

Controls cell proliferation and binds E2F (required for cell cycle progression).

Question 25

Hyper phosphorylated RB1 (cancer)

Answer 25

Inhibits transition from G1 to S. Increased phosphorylation -> E2F released -> cell can go into S phase.

Question 26

In the absence of RB1

Answer 26

E2F not repressed -> cells undergo more cell divisions

Question 27

Caretaker TS genes encode

Answer 27

Proteins to detect and repair DNA
Proteins involved in normal chromosome disjunction
Programmed cell death machinery

Question 28

Examples of caretaker TS genes

Answer 28

BRCA1 & 2 - involved in cellular response to dsDNA breaks.

Question 29

Tp53 gatekeeper

Answer 29

“Guardian of the genome”
Activates DNA repair proteins
Holds cell at G1/S cell cycle checkpoint
Can initiate apoptosis

Question 30

Mutation of Tp53 gatekeeper genes

Answer 30

DNA not repaired, cell cycle not arrested.

Question 31

EAOD inheritance

Answer 31

Autosomal dominant.

Question 32

WES and EOAD

Answer 32

Sorting protein related receptor gene SORL1.

Question 33

Number of genes associated with LOAD

Answer 33

20 genes, including TREM2

Question 34

APOE4

Answer 34

Strongest genetic risk factor for AD; also decreases age of onset.

Question 35

APOE4 amino acids

Answer 35

Arginine, arginine

Question 36

APOE3 amino acids

Answer 36

Cysteine, arginine

Question 37

APOE4 is not sufficient to

Answer 37

Predict disease status. Not all APOE4 homogzygotes develop AD.