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A Quantitative Overview to Gene Expression Profiling in Animal Genetics Final Remarks Genetical Genomics & Systems Biology Armidale Animal Breeding Summer Course, UNE, Feb. 2006 A Quantitative Overview to Gene Expression Profiling in Animal Genetics Genetical Genomics Use arrays to identify genes that are DE in relevant tissues of individuals sorted by QTL genotype. If those DE genes map the chromosome region of interest, they would become very strong candidates for QTL. Source: Jansen and Nap, 2001 Armidale Animal Breeding Summer Course, UNE, Feb. 2006 A Quantitative Overview to Gene Expression Profiling in Animal Genetics Genetical Genomics Use arrays to identify genes that are DE in relevant tissues of individuals sorted by QTL genotype. If those DE genes map the chromosome region of interest, they would become very strong candidates for QTL. Never enough! …not greed but algebra: Vq 2 pq 2 …………particularly useful for: a d q p 1. Speed up and enhance power to finding New QTL 2. Developing “Diagnostic Kits” 3. Deciphering the genetics of Complex Traits Ability to score individuals rapidly (and cheaply) at a very large number of loci. A trait that is affected by many, often interacting, environmental and genetic factors such that no factor is completely sufficient nor are all factors necessary. (Andersson and Georges, 2004) Armidale Animal Breeding Summer Course, UNE, Feb. 2006 A Quantitative Overview to Gene Expression Profiling in Animal Genetics Genetical Genomics Where does this leave Quantitative Geneticists? Where does this leave Phenotypes (the need to measure)? Very well, ………I’m afraid (can’t retire yet ) Quantitative Geneticists: Never enough QTL Association studies Study of variation The individual needs to exists in order to be genotyped. With BLUP a predictions of a non-existent individual can be given Phenotypes: Mutation is continuously generating new variation Selective breeding on genotypes reduces effective population size Systems Biology: Integration of all types of data Armidale Animal Breeding Summer Course, UNE, Feb. 2006 A Quantitative Overview to Gene Expression Profiling in Animal Genetics Final Remarks Systems Biology PNAS, Nov 2005, 102:17296 My Own Interpretation Systems Biology is about integrating data from different sources to provide a more comprehensive answer to a given biological question Armidale Animal Breeding Summer Course, UNE, Feb. 2006 A Quantitative Overview to Gene Expression Profiling in Animal Genetics Systems Biology Predict Future Performance 3 Types of Data Phenotype + Pedigree Phenotype + Marker Gene (protein/metabolite) Expression How to integrate them? Armidale Animal Breeding Summer Course, UNE, Feb. 2006 A Quantitative Overview to Gene Expression Profiling in Animal Genetics Systems Biology Predict Future Performance Mixed-Inheritance Model y Xβ Z1u Z 2q e Wang, Fernando & Grossman, 1998 Many authors and species NB: Segregation Variance Issues Infinitesimal Model y Xβ Z1u e Var(u) A u2 ANOVA Model Phenotype + Pedigree Henderson, 1975 Phenotype + Marker Systems Biology ˆ ˆΛ W K 1 T 2 X Cov( X) KΛΛ Henshall et al, ’01, ’03, ‘05 Gene (protein/metabolite) Expression T Chiaromonte & Matinelli, 2002 (leukemia, humans) Many authors and species Segregation Analysis IBD Probabilities Dimension Reduction y Xβ Wα e y Xβ Z2q e ANOVA Model y Xβ Z3g e Genetical Genomics y Xβ Z 2q e Jansen and Nap, 2001 (arabidopsis) Brem et al, 2002 (yeast) Schadt et al., 2003 (mice) Cui and Churchill, 2003; Reverter et al., 2004, 2005 Armidale Animal Breeding Summer Course, UNE, Feb. 2006 A Quantitative Overview to Gene Expression Profiling in Animal Genetics Armidale Animal Breeding Summer Course, UNE, Feb. 2006