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

Flint and Mott 2008; Nature 456: 724

Behavioural traits Non-behavioural traits

Genetic architecture:Additive and dominance effects

http://en.wikipedia.org/wiki/Mendelian_genetics

Red is dominant over white 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 co-

localize?

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?