Genes - Lecture 21, Complex traits

Question 1

What are the differences between mendelian and complex traits?

Answer 1

M = Monogenic C = Polygenic
M = Predictable inheritance C = Familial clustering but not predictable
M = Simple relationship between geno and pheno C = Complex relationship between geno and pheno
C= Influenced by environment

Question 2

How is type 2 diabetes affected by both genes and environment?

Answer 2

Genetic impacts:
One affected parent = 15%
Two = 75%

Environment:
BMI over 30 = 20%

Question 3

What is meant by discontinuous traits?

Answer 3

Complex traits can be discontinuous or discrete
This is whether the trait is present or not

Question 4

What formula is used to identify the influence of both genetics and environment?

Answer 4

Vp = Vg + Ve
Vp = total phenotypic variance

Question 5

What is the equation to identify heritability?

Answer 5

H2 = Vg/Vp

Question 6

What are the two types of genetic variant and human disease hypotheses?

Answer 6

Common disease - Rare variant
Common disease - Common variant

Question 7

Why should disease associated alleles be common?

Answer 7

Late onset diseases dont have much effect on fitness
Alleles that used to be advantageous or neutral may now make people more susceptible to disease
Disease causing alleles can be maintained by balancing selection

Question 8

What are Genome wide association studies GWAS?

Answer 8

A population level approach to gene mapping

Question 9

What is meant by the odds ratio?

Answer 9

For the C allele:
Odds of disease with C / Odds of disease with T
[A/B]/[C/D]
Used to calculate the probability of association between each SNP and the disease

Question 10

What does it imply if the odds ratio is under or over one?

Answer 10

Over 1 = Allele gives higher risk of disease
Under 1 = Allele is protective

Question 11

What are haplotypes?

Answer 11

Closely linked SNPs on the same chromosome
Often inherited together in haplotype blocks, which are regions without crossing over

Question 12

What is linkage disequilibrium?

Answer 12

The co-inheritance of SNPs in a haplotype block

Question 13

What has GWAS taught us about the genetics of human disease?

Answer 13

The majority disease associated variants confer a small increased risk of disease
Over 90% of variants are in non-coding DNA, it can be difficult to identify the causal variant
It generates new biological hypotheses about causes of disease
Studies of rare SNPs are needed to understand complex traits more