GiM lecture 4 and 5 Flashcards Preview

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Flashcards in GiM lecture 4 and 5 Deck (31):
1

Does Multifactoral disease have a genetic component

Twin Studies
- monozygotic twins had higher concordance than Dizygotic twins

2

What are problems with Twin Studies

Assumes MZ twin have same environment
DZ twins can share more that half of their genes

3

What causes phenotypes

many genes at different Loci
genes are additive
gaussian distribution curve
influenced by environment too

4

what disordes show multifactoral inheritance

Congenital Malformations - cleft lip, hip dislocation, heart defects, neural tube defects,

Acquired diseases
asthma, autism, cancer, epilepsy, crohns, MS, parkinson,

5

What is a genome wide association study

relate variation in human DNA with disease or trait

estimates population attributable risk

controls match cases and be representative of population

6

What are Single Nucleotide Polymorphisms

common mutations

7

What is linkage disequilibrium

most disease bearing chromosomes come from an ancestral chromosome

8

What are the genetics of alzhrimers

sequence variants at polymorphic locus have affect on age of onset

- APOE gene - app-lipoprotein - also linked heart disease
3 types of APOE
APOE*E2/3/4

9

How does APOE gene affect alzheimers

APOE*E4 - increase susceptibility
APOE*E2 - protective effect

E4/E4 homozygotes - very early onset

10

What is age related macular degeneration

irreversible central visual dysfunction - degeneration of macula

early deposition of drusen = hall mark risk for AMD

11

What are the genetic effectors of AMD

What are the environmental factors that increase AMD risk

CFH (1q) ARMS2(10q)

Smoking x70 increase

12

Define Penetrance

% with gene who get condition
- modified by genetic variation
- modified by environmental factors

13

What Gatekeepers

Monitor and control cell division, death preventing accumulation of mutations

14

What are caretakers

improve genomic stability (repair mutations)

15

What are landscapers

control surrounding stromal environment

16

A sporadic Defect causes what> and what chance of colorectal cancer?

adenomatous polyp
5% risk

17

A Gate keeper Defect causes what> and what chance of colorectal cancer?

Multiple adenomatous polyps
>95% risk
FAP

18

A Caretaker Defect causes what> and what chance of colorectal cancer?

andenomatous polyp
70% risk
HNPCC

19

a landscaper defect causes what and what chance of colorectal cancer

Hamartomatous polyps
10-20% cancer

20

What are tumor suppressor genes

protect cells from becoming cancerous
loss = inc risk cancer
APC, BRACA1/2, TP53, Rb

21

What are oncogenes

Regluate cell growth and differentiation
gain of function = cancer risk inc
growth and signal transduction factors, RET gene

22

what rule do most cancers obey

Knudson's two hit hypothesis
Recessive at celluar level
Autosomal dominant inheritance

23

examples of cancers that follow an autosomal recessive inheritance pattern

MYH associated polyposis, Fanconi anaemia,
Ataxia telangiectasia

24

name mutation types

splice site mutations
Deletions, duplications
translocation

25

Signs of Sporadic Cancer

Onset older age
one cancer in individual
unaffected family members
cancer type rarely genetic - lung, cervix etc

26

Signs of familial cancer

onset younger age
multiple primaries in individual
family members affected
same type/genetically related cancers

27

Explain Retinoblastoma

childhood ocular cancer
1/15,000-30,000
classic knudson 2hit
retinoblastoma Rb1 gene

Bilateral cases = usually germline fault
15% "sporadic" actually germ line = new mutation rate is high

increases risk of other cancers

28

FAP Familial Adenomatour Polyposis

1% of all bowel cancers
high risk of bowel cancer if untreated
HUNDREDS of bowel polyps
CHRPE, desmoid tumors, osteomas,

fault in APC tumor supresson genes
autosomal dominant inheritance

colonoscopies and cholectomy

29

HNPCC Hereditart Non polposis colorectal cancer

2-3% of bowel cancers
polyps common
60-80% risk of bowel cancer
risk of other cancers - endometrial, ovarian, stomach

Error in Mismatch repair genes
MLH1 50%, MSH2 (40%) MSH6 10%
Autosomal dominant inheritance

Amsterdam Criteria
- 1 member diagnosed colorectal cancer b4 50yo
- 2 affected generations
- 3 affected relatives
- FAP excluded
- tumours verified by pathology

30

BRCA1/2 genes

involved in DNA repair
autosomal dominant inheritance
80% risk breast cancer
BRCA1 40% BRCA2 - 20%

31

Li Fraumeni syndrome

P53 mutations (RARE)
autosomal dominant
50% risk cancer by 40yo
100% lifetime
avoid radiotherapy - inc cancer risk
poor prognosis