Genetic Basis of Multi-factorial Inheritance

Question 1

Single-gene diseases

Answer 1

Abnormal function of a single gene is sufficient to cause disease

Follows Mendelian inheritance

Question 2

Multi-factorial traits/diseases

Answer 2

Requires contribution from multiple genes as well as environmental factors

Generally occurs among relatives of affected individuals more frequently than in the general population

Question 3

What two categories can multi-factorial diseases be classified as?

Answer 3

Qualitative: either present or absent (Ex. lung cancer)

Quantitative: measurable physiological or biochemical quantity (Ex. blood pressure)

Question 4

What are the two models of multi-factorial inheritance?

Answer 4

Polygenic model

Threshold model

Question 5

Polygenic model

Answer 5

Two or more loci have additive effects to determine the value of a trait or manifestation of a phenotype

Easy to conceptualize with quantitative traits

Question 6

Threshold model

Answer 6

Total risk factors (genetic variants and environmental exposures) for a disease falls on a spectrum

Phenotype manifests beyond a threshold point; higher threshold means less risk of disease but higher risk of recurrence within family of those with the phenotype

May include differences for each gender

Easy to conceptualize with qualitative traits

Question 7

Monozygotic twins

Answer 7

Nearly identical genotypes at every locus

Question 8

Dizygotic twins

Answer 8

On average share 50% of the alleles at all loci

Question 9

Concordant/concordance

Answer 9

When twins have the same disease

When <100% –> Evidence that non-genetic factors contribute to the disease

The greater concordance in monozygotic twins vs dizygotic twins –> Evidence of genetic component of the disease

Question 10

Discordant/discordance

Answer 10

When one twin is affected and the other is not

Question 11

Linkage analysis

Answer 11

Uses family pedigree to follow inheritance of a disease

Question 12

Association analysis

Answer 12

Uses entire history of a population to look for increased or decreased frequency of a particular allele in affected individuals compared with unaffected controls

Question 13

Direct gene sequencing

Answer 13

Sequencing the entire genome of affected individuals and their parents compared to reference genome to find candidate genes

Question 14

Homologous recombination

Answer 14

Homologus chromosomes exchange material during meiosis 1

Question 15

Haplotype

Answer 15

A group of genes within an organism that was inherited together from a single parent

Question 16

Linkage equillibrium

Answer 16

Haplotype frequencies are as expected from allele frequencies. (Ex. Frequency of allele E = 0.5, frequency of allele A = 0.9, and haplotype EA = 0.45)

Question 17

Linkage disequillibrium

Answer 17

Haplotype frequencies diverge from what is expected from allele frequencies (Ex. Frequency of allele B = 0.5, frequency of allele D = 0.1, and haplotype B-D = 0.1; thus there is linkage)

The closer two alleles are to one another on a chromosome the more linked they are