Genes Lecture 8- Complex Traits

Question 1

complex traits (quantitative traits )

Answer 1

more than one gene that contributes to phenotype and is influenced by environmental factors

Question 2

mendelian traits are also known as

Answer 2

multifactoral traits

Question 3

Mendelian vs complex traits

Answer 3

Mendelian traits
single gene (monogenic) with high penetrance
predictable mode of inheritance
simple relationship between genotype and phenotype
e.g. cystic fibrosis

Complex traits
multiple genes (polygenic) with low penetrance
familial clustering but inheritance not predictable
complex relationship between genotype and phenotype
often strongly influenced by environment

Question 4

examples of complex traits in humans

Answer 4

-Alzheimer’s disease
-Crohn’s disease
-Neural tube defects
-Asthma
-Cleft Lip
-Coronary heart disease
-Type 1 and Type 2 Diabetes’s

Question 5

prevalence of complex diseases

Answer 5

600/1000

Question 6

% of pop with type 2 diabetes

Answer 6

6-8%

Question 7

discontinuous traits

Answer 7

the trait or disease is either present or not
For example: gender, blood group, eye colour

Question 8

continuous traits

Answer 8

quantitative or continuous traits e.g. height, blood pressure, serum cholesterol, body mass index (BMI), crop yield

Question 9

what graph is usually used for discrete/ discontinuous traits

Answer 9

bar

Question 10

what graph is used for continuous traits

Answer 10

normal distribution: bell or Gaussian curve

Question 11

total phenotypic variance formula

Answer 11

VP (or VT) = VG + VE
total phenotypic variance= genetic variance + environmental variance

Question 12

heritability

Answer 12

H2 = VG/ VP
heritability= genetic variance /total phenotypic variance
-statistical measure of how much genetic variance is present within a phenotypic trait

Question 13

high heritability

Answer 13

genetic differences in the population explain a high proportion of the phenotypic variation
-it’s easier to identify genetic variants associated with the trait than for a trait with low heritability

Question 14

relatedness of MZ twins

Answer 14

r=1

Question 15

relatedness of DZ twins

Answer 15

r=0.5

Question 16

concordance

Answer 16

the probability that if one twin is affected, the other twin is also affected by a trait

concordance = 1.0: if one twin is affected the other twin is always affected
concordance = 0.6: if one twin is affected the chance of the second twin being affected is 0.6 (60%)

Question 17

what is differences in concordance used to measure

Answer 17

heritability

Question 18

heritability formula in terms of MZ and DZ twins

Answer 18

H^2 = 2(MZ-DZ)

Question 19

assumptions when using MZ and DZ twins for heritability

Answer 19

Random mating of parents
Equal environments on MZ and DZ twins

Question 20

Why should disease-associated alleles be common?

Answer 20

Alleles that were advantageous or neutral in the past may confer disease susceptibility in modern societies (‘thrifty gene’)

Disease causing alleles can be maintained at high frequency by balancing selection

Late onset diseases have little effect on fitness (weak purifying selection)

Question 21

purifying selection

Answer 21

removal of alleles that are deleterious

Question 22

Genome wide association studies (GWAS)

Answer 22

a population level approach to disease gene mapping

Question 23

Odds ratio

Answer 23

used to calculate the probability of association between SNP and the disease

Question 24

OR > 1.0

Answer 24

allele gives higher risk of disease

Question 25

OR < 1.0

Answer 25

allele is protective

Question 26

Manhattan Plot

Answer 26

graphical representation of P-values for genetic variants across the genome
x-axis: Variants are arranged according to their position on chromosomes.
y-axis: The -log10(P-value) is plotted showing the probability of association

Question 27

skyscrapers in the Manhattan plot

Answer 27

Variants with highly significant associations with the trait

Question 28

haplotypes

Answer 28

Closely linked SNPs on the same chromosomeh

Question 29

haplotype blocks

Answer 29

Closely linked SNPs on the same are often inherited together
-regions without crossing over

Question 30

how are haplotype blocks defined

Answer 30

by a small number of tag SNPs: ~1 million tag SNPs represent all 10 million common SNPs