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What is a QTL?

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?.

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What is a QTL?

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  1. 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

  2. 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

  3. Why would you want to map QTL? • Identify genes responsible for variation • Understand genetic architecture

  4. What is genetic architecture? • Number of loci that contribute to a trait • Distribution of effect sizes • “Mode of action” of loci

  5. 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

  6. Genetic architecture: Distribution of effect sizes Non-behavioural traits Behavioural traits Flint and Mott 2008; Nature 456: 724

  7. Genetic architecture:Additive and dominance effects Red is dominant over white No dominance http://en.wikipedia.org/wiki/Mendelian_genetics

  8. 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

  9. Why care about genetic architecture? • Evolution – adaptation, e.g., Peichel et al 2001, Nature 414: 901-905

  10. Why care about genetic architecture? • Evolution – speciation, e.g., Hawthorne and Via 2001, Nature 412: 905-907

  11. Why care about genetic architecture? • Evolution – do QTL from different studies co-localize?

  12. Marker assisted selection (MAS) in agriculture • Advantages/disadvantages

  13. QTL mapping vs. other strategies • What is the question? • Which genes contribute to variation? • Which genes contribute to trait?

  14. 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?

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