ANHB1102 Lecture Notes - Lecture 29: Quantitative Trait Locus, Coronary Artery Disease, Sickle-Cell Disease
25 May 2018
School
Course
Professor
Complex Traits Notes:
Genetic Variation and Complex Traits:
-Most phenotypic variation not due to single gene differences
-Tendency for relatives to resemble one another
Complex vs Simple Traits:
Simple Traits:
Example: Sickle Cell Disease: Monogenic:
Haemoglobin Variation:
Monogenic
Polygenic
Synonyms:
Mendelian
Simple
Complex
Quantitative
Multifactorial
Number of Loci:
One
Several
Usual Environmental Effect:
Small
Small or Large
Nature of Trait:
Discrete (Discontinuous)
Continuous or Discrete
Haemochromatosis: Monogenic:
Incomplete Penetration:
Complex Traits:
Stature:
-Continuous complex trait
-Known to be influenced by genetics (~80-90%)
-1st known genetic variation to affect height found in 2007
-Single nucleotide change in HMGA2 gene
-Homozygote = 1cm taller (<1% variation at population level)
-2008: genome wide association analysis identifies 20 loci that influence adult height (~3%
variation ~ 5cm)
Coronary Artery Disease (CAD) - Polygenic
-Discrete complex trait
-Single largest killer in males and females (Western countries)
-Multiple genetic and environmental influences and interactions
-Some risk factors have a significant heritability
-Cholesterol
-Hypertension
-Obesity
-All of which have many genes involves
Key Questions:
-For a particular trait, is the observed variation influenced by genetic variation or simple by
environmental factors?
-How important is genetic variation as a source of total phenotypic variation (heritability:
measure of how much phenotypic variation is due to genetic variation)
-0 = environmental
-1 = genetic
-How many genes are involved and where in the genome are they distributed? (Polygenic
inheritance, linkage and association studies)
-If there is genetic variation, what is the phenotype of the various genotypes in different
environments? (How environment influences expression of phenotype)
Polygenic Model of Inheritance:
-1 Locus Model:
-A = +6cm
-Environmental influence (e.g food):
-2 Locus Model:
-Multiple genotypes can give rise to the same height (not much environmental influence)
-3 Locus Model:
Document Summary
Most phenotypic variation not due to single gene differences. Tendency for relatives to resemble one another. Known to be in uenced by genetics (~80-90%) 1st known genetic variation to affect height found in 2007. Homozygote = 1cm taller (<1% variation at population level) 2008: genome wide association analysis identi es 20 loci that in uence adult height (~3% variation ~ 5cm) Single largest killer in males and females (western countries) Multiple genetic and environmental in uences and interactions. Some risk factors have a signi cant heritability. All of which have many genes involves. How important is genetic variation as a source of total phenotypic variation (heritability: measure of how much phenotypic variation is due to genetic variation) How many genes are involved and where in the genome are they distributed? (polygenic inheritance, linkage and association studies) If there is genetic variation, what is the phenotype of the various genotypes in different environments? (how environment in uences expression of phenotype)
