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Transcript
What is a QTL?
• Quantitative trait locus (loci)
• Region of chromosome that contributes to
variation in a quantitative trait
• Generally used to study “complex traits”, i.e.,
controlled by many genes and environmental
factors
Why would you want to map QTL?
• Identify genes responsible for variation, e.g.,
• Medicine – disease susceptibility, reaction to
drugs
• Agriculture – crop/livestock improvement
• Evolution
Why would you want to map QTL?
• Identify genes responsible for variation
• Understand genetic architecture
What is genetic architecture?
• Number of loci that contribute to a trait
• Distribution of effect sizes
• “Mode of action” of loci
Genetic architecture: Number of loci
• Number of loci contributing to differences in a trait
between two lines/ strains
• Historically, estimated in various ways, especially the
Castle-Wright index/ estimator
• Castle-Wright index assumes
– Two homozygous parents are crossed, one only has
increasing alleles and the other only has decreasing alleles
for the trait
– All loci affect the trait equally
– Loci affecting the trait are unlinked
– No dominance or epistasis
• More modern methods avoid some of these
assumptions
Genetic architecture:
Distribution of effect sizes
Behavioural traits
Non-behavioural traits
Flint and Mott 2008; Nature 456: 724
Genetic architecture:
Additive and dominance effects
Red is dominant over white
http://en.wikipedia.org/wiki/Mendelian_genetics
No dominance
Why care about genetic architecture?
Can the identification of QTL useful if
you do not identify the underlying
genes?
• How big are the largest effect sizes? Is a QTL
worth pursuing?
• Why are traits correlated? Do they share QTL
(pleiotropy)? E.g.,
• Medicine – QTL for reading disability and
ADHD
Why care about genetic architecture?
• Evolution – adaptation, e.g., Peichel et al
2001, Nature 414: 901-905
Why care about genetic architecture?
• Evolution – speciation, e.g., Hawthorne and
Via 2001, Nature 412: 905-907
Why care about genetic architecture?
• Evolution – do QTL from different studies colocalize?
Marker assisted selection (MAS) in
agriculture
• Advantages/disadvantages
QTL mapping vs. other strategies
• What is the question?
– Which genes contribute to variation?
– Which genes contribute to trait?
QTL mapping vs. other strategies
•
•
•
•
QTL mapping
Candidate gene studies
Mutagenesis
Microarray, serial analysis of gene expression
(SAGE) – gene vs. network focus (Flint and
Mott 2008, Nature 456: 724-727)
• Other?