Melanie Pritchard; Week 4 MED1011; Biochemistry
Multifactorial disorders are often polygenic (several pairs of genes at different loci with additive effects); but are also affected by the environment. Fingerprint ridge is polygenic; height and skin colour are multifactorial. Multifactorial disorders have familial clustering but no Mendelian inheritance.
A continuous multifactorial trait does not have a discreet phenotype, eg height. A discontinuous has a discreet phenotype such as asthma or autism. Environmental continous factors can be height, IQ, BP, skin colour. Multifactorial inheritance accounts for most congenital abnormalities. The recurrence risk of multifactorial disorders is higher if more than one family member is affected, the affected individual is of the less commonly affected sex (heart disease), the severity is more severe in affected individual.
- Recurrence of first degree relatives is the square root of the incidence rate in the population.
Familial aggregation does not prove a genetic susceptibility as families share the same environment generally. Frequency of the disease in spouses is used as a control.
Monozygotic twins are identical, dizygotic are fraternal. If both twins share a trait they are concordant. Discordant is where they do not share a trait. Autism, pyloric stenosis, IDDM have high concordance so high genetic factors, CAD has some concordance but not much stressing the importance of environmental factors. If a male develops CAD before 55 brothers have 5x relative risk, sisters 2.5x. If female develops it before 65 siblings have a 7x relative risk.
Epistasis is where one allele is influenced by a completely separate gene, or several separate genes. Interaction can be synergistic or antagonistic. Lack of penetrance (dominant gene fails to be expressed) usually due to epistasis. Expressivity is where genes are expressed to a different degree, such as polydactyly.
Life (9th) 250-253, 330