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 Red is dominant over whiteNo 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:

Why care about genetic architecture? Evolution – speciation, e.g., Hawthorne and Via 2001, Nature 412:

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: ) Other?