16/ human genetics 3

Question 1

3 features of complex diseases

Answer 1

• multifactorial: polygenic and environmental
• identified risk alleles suggest susceptibility - not deterministic
• are familial

Question 2

examples of complex diseases - general, psychiatric, congenital

Answer 2

• obesity, rheumatoid arthritis, diabetes (both), ms, epilepsy, hyperthyroidism, some cancers
• alzheimers, bipolar, depression, tourettes
• cleft lip, neural tube defects, pyloric stenosis

Question 3

single nucleotide polymorphisms - snps. how many, where are they found

Answer 3

• 11-15 mil common variants
• coding and non coding regions

Question 4

what is minor allele frequency maf

Answer 4

• second most common allele in a population
• common snps maf >5%
• rare maf <5%

Question 5

2 methods to find risk alleles for complex diseases

Answer 5

• family based linkage analysis. mapping occurrence of disease in families. limited by small numbers
• genome wide association studies GWAS. search for alleles in a pop that occur more frequently in disease cases than matched controls. more powerful at identifying rare risk alleles and those that only contribute small risk

Question 6

phenotypic variation def

Answer 6

sum of genetic and environmental variation

Question 7

heritability def

Answer 7

degree of variation in a pop due to genetic variation

Question 8

equation for phenotypic variance

Answer 8

phenotypic variance = genetic variance + environmental variance

Question 9

heritability equation

Answer 9

• heritability = genetic variance / phenotypic variance
• higher heritability = higher genetic contribution

Question 10

how are twin studies used to determine heritability

Answer 10

• monozygotic twins share 100% of genes and share environemnt
• dizygotic twins share 50% of alleles and share environment
• can see the effect of that other 50% of alleles
• greater the difference in concordance between mono and di = greater heritability of trait

Question 11

twin studies ACE model

Answer 11

• A - genetic variance/heritability (constant in mono not di)
• C - common environmental variance (common between twins)
• E - specific environmental variance (variables between twin types)

Question 12

complex diseases and type of phenotype, when does disease occur

Answer 12

• continuous phenotype can arise
• many loci contribute to variation so broad range of phenotypic variation
• environmental factors affect phenotype
• threshold

Question 13

evidence of threshold hypothesis - pyloric stenosis

Answer 13

• narrowing of opening between stomach and small intestine
• 5 times more common in males than females - females have higher liability threshold than males
• females carry more risk alleles, so relatives of females at greater risk

Question 14

3 possible genetic architectures of complex diseases

Answer 14

• small number of dominant alleles confer large increase in risk - parkinsons
• common disease common variant model - many alleles confer small increase in risk - type II diabetes
• intermediate - one major allele exerts large effect, numerous lower risk alleles - breast cancer