13. Multifactorial Disorders

incomplete penetrance

Not all individuals with a mutant genotype show the mutant phenotype

dyskeratosis congenita

genetic disease that leads to dysfunction in shelterin + telomerase complexes

osteogenesis imperfecta

brittle bone disease resulting from disease of collagen

severe combined immunodeficiency disease (SCID)

multiple genes lead to impaired T cell function

retinitis pigmentosa

digenic disorder (homozygous dz ROM1 + perpherin locus) leading to issues with retina/vision

digenic inheritance

additive effect of two genes

polygenic inheritance

additive effect of many genes at different loci

monogenic trait

only a few (usually 2) phenotypes d/t few alleles/spot

polygenic trait

lots of genes involved, numerous potential phenotypes

continuous traits

polygenic traits that lead to a distribution of phenotypes

discontinuous traits

traits with only a few possible phenotypes

qualitative trait

-phenotypes with discrete/easy to measure values-Mendelian inheritance-molecular marks

quantitative traits

-cannot easily be placed into phenotypic groups-complex mode of inheritance-environmental effect-distribution falls into Bell curve

threshold trait

a polygenic trait in which phenotypes are expressed in categories

multifactorial trait

-inherited trait that involves two or more genes and environmental component -can occur in isolation-no clear Mendelian pattern-environmental +/- risk-more frequently in one gender-1st degree relatives w/ higher risk

deep vein thrombosis

-missense mutation in clotting factor V + in prothrombin-environmental factors(trauma, sx, prolonged immobility, OCS)-double heterozygotes 20x risk

Hirschsprung disease

-intestinal nerve cells do not form correctly -- decreased colonic peristalsis leading to megacolon + severe constipation->8 loci involved-no specific environmental factors known, but it's believed triggered during pregnancy

MZ twins

-single fertilized zygote splits-share 100% alleles

DZ twins

-2 eggs fertilized by two sperm-share ~50% alleles


probability pair of individuals will have a certain characteristic if one person has the characteristic


-fraction of total phenotypic variance of quantitative trait d/t allelic variation-how much genetic vs. environmental


0 on heritability equation


1 on heritability equation

familial aggregation

family on the right side of the bell curve of polygenic traits will be more likely to develop diseases

relative risk ratio

prevalence of disease in relatives of pt/prevalence of general population disease-bigger proportion = more likely develop disease

limitations of heritability + RRR

- ascertainment bias (research study participation skewed)-different pops might have different heritability estimates-potential genetic drift/epigenetic differences-environmental exposures might be different even with twins

quantitative trait loci

-regions of the genome where variation is associated w/ quant. trait-identified by stat. assn. btwn genetic markers + phenotypes-ex. height, weight, blood pressure

QTL mapping

finding a linkage between phenotype and "signpost" in genome

association mapping

looks for markers that appear more frequently in individuals with the trait (phenotype) than the general population

genome-wide association studies

large-scale analysis of the genomes of many people having a certain phenotype or disease, with the aim of finding genetic markers that correlate with that phenotype or disease.

LOD score

log10 of likelihood disease genotype/likelihood normal genotype->3 marker is close to gene contributing to disease