Lecture 42 Prof Duncan Shaw

Genetic variation & normal traits Normal traits include height, IQ, blood pressure These are influenced by many genes (called polygenes) and the environment In a large population, they are distributed according to normal distribution Genetic influence is apparent when trait is correlated in related individuals –Higher degree of relationship higher correlation for trait

The Normal distribution SD = standard deviation

Degrees of relationship

Genetic variation & disease Many diseases are familial and have a genetic component - increased incidence in relatives of affected individuals Suggests involvement of polygenes Unlike normal traits, disease is a discontinuous trait - either youve got it or you havent Described by the liability threshold model

Some diseases with genetic influence Congenital malformations –Cleft lip/palate, neural tube defects –Heart defects, hip dislocation Adult onset –Diabetes –Epilepsy, migraine –Cancer (many types) –Manic depression, schizophrenia

Consequences for patients relatives In diseases with a genetic component, patients relatives are at greater risk than general population For cleft lip/palate: –Population risk 0.1% –Risk to 1st degree relatives 4% –Risk to 2nd degree relatives 1% –Risk to 3rd degree relatives 0.5% Risk is greater if patient is more severely affected Risk is greater if >1 affected relative in family

Heritability The proportion of the trait (or disease) that is due to genetic factors Estimated by comparing degree to which 1 st, 2 nd or 3 rd degree relatives of patient are affected Also estimated by comparing concordance rates in MZ and DZ twins About 80% for schizophrenia, asthma; 65% for coronary artery disease; 35% for congenital heart disease

Which genes are important? Test candidate genes to see if they are genetically associated with the trait Example: diabetes and insulin gene