IntegrationofQTL,GeneExpressionandSequence…整合基因，基因表达序列….pptVIP

Integration of QTL, Gene Expression and Sequence Analyses: A Pathway to the Detection of Quantitative Trait Nucleotides. Robert Hitzemann, Ph.D. Department of Behavioral Neuroscience Oregon Health and Science University Multiple Cross Mapping (MCM) Built from the observation that for open-field/basal activity, three different diallele crosses (B6xC, B6xA and B6xD2) appeared to generate similar QTLs, most notably on distal chromosome1 (Hitzemann et al. 2000). We interpreted these data to indicate that the C, A and D2 strains have common allele(s) in the region of interest. The more general interpretation was that polymorphic and non-polymorphic alleles are not randomly distributed and thus, provide a source of information. MCM could be used to “mine” this information (haplotype structure) to reduce the QTL interval (Hitzemann et al. 2002, 2003). MCM provides a mechanism to interrogate the data obtained from gene and protein array analysis. Leverages the most successful aspect of QTL analysis – namely QTL detection. * LOD 0 1 2 3 4 5 6 Free Dominant Recessive Additive D2MIT80 D2MIT464 D2MIT521 D2MIT241 D2MIT458 D2MIT94 D2MIT420 D2MIT102 D2MIT491 D2MIT493 D2MIT412 D2MIT282 D2MIT229 . . . . . . . . . . . . . 10 cM I Alcp1q Scn1a Gad1 Plcb2 Adra2b Snap25 Lorr2 Ntsr Kcna1-rs2 N = 600 Phenotype = Ethanol-Induced Locomotor Activation Chromosome 2 LPxB6 F2 The Problem. “All genetic studies begin with variation because perturbations in biological processes reveal functionally important elements in the life history of an organism. Naturally occurring variation still drives many studies because complex genetic traits remain important in humans, model organisms and agriculturally important animal and plant species. The existing challenge in complex trait analysis is to distinguish the mutations responsible for trait variability from closely linked, selectively neutral polymorphisms.” Nadeau and Dunn (1998) Multiple Cross Mapping C57BL6/J (B6