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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
trait
higher correlation for
The Normal distribution
SD = standard deviation
Degrees of relationship
Relationship
Average % shared genes
1st degree
MZ twins
100
DZ twins, sibs, parents/offspring
50
2nd degree
Uncles/aunts/nephews/nieces
25
Grandparents/grandchildren
25
3rd degree
1st cousins
12.5
Great-grandparents/great-grandchildren
12.5
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 you’ve got it
or you haven’t
• 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 patient’s relatives
• In diseases with a genetic component, patient’s
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 1st, 2nd or
3rd 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
Gene A
Gene B
Allele:
With trait Without
With trait Without
1
97
100
80
100
2
103
100
120
100
• Example: diabetes and insulin gene