Exam 3 Main Points Flashcards

1
Q

First successful GWA study

A

Age-related macular degeneration

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2
Q

Other successful GWA study

A

Chron’s disease

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3
Q

GWA and inflammatory bowel diseases

A

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

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4
Q

SLCO1B1

A

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

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5
Q

Problems with GWAs

A

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

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6
Q

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

A

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

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7
Q

CDRV

A

GWAs will not identify rare variants in most cases.

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8
Q

T1D and HLA - what form is the highest risk

A

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

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9
Q

T1D and VNTR (INS)

A

Short (26 - 63 repeats) predispose to T1D

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

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10
Q

Concordance of T1D

A

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

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11
Q

T2D and concordance

A

70%

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12
Q

Best predictor for T2D

A

Insulin resistance

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13
Q

TCF7L2

A

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

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14
Q

T allele of rs7903146

A

Enhances expression of TCF7L2 -> impairs insulin secretion.

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15
Q

SLC30A8 (zinc transporter)

A

Confers T2D risk in addition to TCF7L2 gene.

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16
Q

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

A

Beta cell dysfunction than insulin resistance.

17
Q

T2D: 80-90% SNPs are

A

Intergenic/intrionic

18
Q

T2D: common variants contribute more than

A

Rare variants

19
Q

Features of MODY

A
Early onset
No autoimmune disorder/antibodies
No insulin resistance
Low insulin
Absence of obesity
20
Q

Major classes of cancer genes

A
Oncogenes
Tumor suppressor (TS) genes
21
Q

Tumor suppressor (TS) genes

A

Gatekeepers

Caretakers

22
Q

Number of mutations needed in TS genes to show phenotype

A

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

23
Q

Function of TS cells

A

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

24
Q

RB1 (cancer)

A

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

25
Hyper phosphorylated RB1 (cancer)
Inhibits transition from G1 to S. Increased phosphorylation -> E2F released -> cell can go into S phase.
26
In the absence of RB1
E2F not repressed -> cells undergo more cell divisions
27
Caretaker TS genes encode
Proteins to detect and repair DNA Proteins involved in normal chromosome disjunction Programmed cell death machinery
28
Examples of caretaker TS genes
BRCA1 & 2 - involved in cellular response to dsDNA breaks.
29
Tp53 gatekeeper
"Guardian of the genome" Activates DNA repair proteins Holds cell at G1/S cell cycle checkpoint Can initiate apoptosis
30
Mutation of Tp53 gatekeeper genes
DNA not repaired, cell cycle not arrested.
31
EAOD inheritance
Autosomal dominant.
32
WES and EOAD
Sorting protein related receptor gene SORL1.
33
Number of genes associated with LOAD
20 genes, including TREM2
34
APOE4
Strongest genetic risk factor for AD; also decreases age of onset.
35
APOE4 amino acids
Arginine, arginine
36
APOE3 amino acids
Cysteine, arginine
37
APOE4 is not sufficient to
Predict disease status. Not all APOE4 homogzygotes develop AD.