Many genes contribute to the phenotype, creating a range of outcomes
Multifactorial trait
Estimation of risk stratified by gender, age, or other factor
Threshold of liability
Estimate based on genetics, environment, and familial relations.
Ex: risk to siblings and offspring is the square root of the population risk. Pop=.01 and Sibling=.10
Recurrence risk
Qualitative measure
Twin study where a trait is shared by both twins or not
Concordant/discordant trait
Proportion of variance of a trait that is determined by genes.
Heritability
Criteria for recurrence risk that indicate that a trait shows multifactorial inheritance
Higher risk for: More than one family member affected Proband is more severely affected Proband is of less affected sex Risk to siblings = sqrt of population risk
Factors that appear to be due to defects in a gene, but are really due to other factors
Ex: Phocomelia and Thalidomide
Phenocopies
Factors that add together
EX: Framingham score for genes
QTL’s (Quant trait loci)
Two affected siblings who share the gene of interest
Affected sib-pair method
Familial hypercholesterolemia is a defect in what receptor
LDL receptor gene
The mutation in the LDL receptor gene causes 5 manifestations
I. No receptor found II. Receptor cannot leave ER III. Receptor cannot bind LDL IV. Receptor cannot migrate to coated pits V. Receptor cannot dissociate from LDL
Coronary heart disease gene
Related to LDL receptor gene
Long QT syndrome gene
Genes regulating sodium and potassium channels
DM type 1
associated with defective HLA genes
DM type 2
associated with Calpain-10 and PPAR-gamma
MODY gene
mutation in HNF (Hepatocyte Nuclear factor
