GEN: complex diseases

Question 1

what are complex diseases?

Answer 1

diseases involving multiple loci and environmental effects

Question 2

what are the features of complex diseases?

Answer 2

• raised familial risk (can be slight in comparison to pop. risk)
• no clear inheritance mode
• multiple genes are contributors
• environmental effects contribute
• gene-gene and gene-environment interactions

Question 3

what are some examples of complex diseases?

Answer 3

inflammatory bowel disease, depression, schizophrenia, multiple sclerosis, asthma, rheumatoid arthritis, diabetes and heart disease

Question 4

what kind of disease is huntingtons

Answer 4

mendelian

Question 5

what kind of disease is cycstic fibrosis

Answer 5

mendelian

Question 6

what is heritability?

Answer 6

the proportion of population varied of a trait explained by genetics compared by both explained by genetics and environment

Question 7

what are some Mendelian rare variants?

Answer 7

Huntington’s disease, cystic fibrosis, SMA

Question 8

what are some common variants?

Answer 8

CVD, rheumatoid arthritis, schizophrenia, depression

Question 9

what are some mix of common and rare variants?

Answer 9

autism, epilepsy, ALS, Alzheimer’s, breast cancer (BRCA1/2)

Question 10

what are the two major breast cancer genes?

Answer 10

BRCA1 and BRCA2

Question 11

what are the three rare high risk Alzheimer’s genes?

Answer 11

APP
PSENI
PSEN2

Question 12

what can Alzheimers Disease risk be increased by 2 things/ what are the 2 moderate risk genes?

Answer 12

APOE allele e4
variants of TREM2

Question 13

what are some low risk variants identified through association studies in Alzheimers Disease?

Answer 13

SNPS in genes:

CLU
CRU
PICALM

Question 14

how many factors are involved in mendelian disease vs complex

Answer 14

mendelian = one factor (gene) involved

comple = multiple factors (both genetic and environment) involved

Question 15

whats the difference in predictability in mendelian disease vs complex

Answer 15

mendelian = knowledge of the factor (genotype) is high predictive

complex = not very predictive

Question 16

whats the difference in segregation patterns in mendelian disease vs complex

Answer 16

mendelian = clear segregation pattern, either dominant or recessive

complex = no clear segregation but can ‘run in families’

Question 17

what does the genome wide association study GWAS do?

Answer 17

tests whether an allele of a specific genetic variant (SNPs) alters disease risk

Question 18

how are GWAS tests done?

Answer 18

• case control studies with clear clinical criteria and random samples - both have similar genetic backgrounds
• SNP tests of two alleles - genotype frequencies or alleles
• statistical analysis: chi-square test
• chip tech used
• regression methods using covariants to account for confounding
• Manhattan plot: genomic position at x axis

Question 19

what types of risk do we look at for Mendelian and polygenic diseases?

Answer 19

• Mendelian: absolute risk

penetrance → probability of developing disease

• Polygenic: relative risk

odds ratio (or relative risk) comparing disease risk for different genotypes

Question 20

how many SNPs were found to be associated with coronary artery disease?

Answer 20

58 - each SNP increases risk slightly

Question 21

what SNP was found to be significantly associated with CAD?

Answer 21

rs17087335 on chromosome 4

Question 22

what are polygenic risk scores?

Answer 22

outcome measured using an individual’s genotype to construct a risk score focussed on associated risks

Question 23

are genetic and environmental risk factors predicitive enough for an individual’s risk?

Answer 23

NO - these risk are not predictive enough for an individuals risk - but gives useful population level information

Question 24

what are the 3 allelles of APO-E and risk relation to AD

Answer 24

e4 allele: increases risk of AD

e3 allele: baseline risk

e2 allele: protective against AD