MULTIFACTORIAL TRAITS
© 2005-2008 James Bier
Objectives
1. Define polygenic and multifactorial traits.
2. Describe how QTLs work.
3. Define empirical risk and describe how it is determined.
4. Define heritability and recognize its influence on determining the genetic basis of traits.
5. Describe how adoption, twins, and SNPs are used to distinguish environmental effects and
multifactorial genes.
Outline
A. Polygenic Traits
B. Multifactorial Traits
1. Identifying Multifactorial Traits
2. Heritability (H)
3. “Experimental Techniques”
a. Adoption
b. Twin Studies
c. Association Studies
A. Polygenic Traits
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Trait affected by multiple genes
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Quantitative Trait Loci (QTL)
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Sort independently (Mendelian)
Alleles usually have additive effect
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Each contribute some to phenotype
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Contributions not all equal
Creates continuous varying trait
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e.g., height, eye color, skin color
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B. Multifactorial Traits
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Trait influenced by both genes and environment
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e.g., cardiovascular disease, obesity
1. Identifying Multifactorial Traits
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Empirical Risk
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Statistical observation
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Incidence within a population
3
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Affected by:
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Relation to affected individuals
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Proportion of relatives affected
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Severity of phenotype
1. Heritability (H)
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Proportion of variation due to inheritance
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Genetic component of a trait
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Measured between 0 and 1
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1=completely genetic
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0=completely environmental
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Narrow Sense Heritability
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Additive effects of many recessive alleles
Broad Sense Heritability
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Also includes:
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Dominant alleles
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Epistatic effects
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2. “Experimental Techniques”
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Coefficient of Relatedness
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Relative proportion of shared genes
a. Adoption
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Separates genetics from environment
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biological family = genetics
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adoptive family = environment
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e.g., mortality due to infection
• 5x more likely if biological parent died same way
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e.g., mortality from cardiovascular disease
• 3x more likely if adopted parent died same way
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b. Twin Studies
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monozygotic v. dizygotic twins
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if genetic, then trait more common in both MZ than both DZ twins
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Concordance
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Correlation of trait between twins
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if completely genetic and penetrant
• monozygotic – 100%
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dizygotic dominant – 50%
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dizygotic recessive – 25%
Can combine twins and adoption
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Further separates familial bias in environment
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c. Association Studies
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Compare groups with/without trait
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Correlate between markers and trait
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Due to linkage disequilibrium
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SNP - Single Nucleotide Polymorphism
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Variation in single nucleotide
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Used as markers for genes
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Found in >1% of population
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12-16 million in human genome
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