? Many traits relevant to the National Heart, Lung and Blood Institute (NHLBI) are under multigenic control. The completed human genome sequence, the mouse and rat draft sequences, and the 20 or so more mammalian genomes to be sequenced promise to increase our understanding of the genetic basis of disease. The PhysGen PGA provides a powerful approach to dissect multigenic traits through the development of panels of chromosomal substitution strains of rats (consomic rat panels). In a complete panel of consomic rats, each chromosome is replaced one at a time (strain A to strain B), so that the contribution of genes on each chromosome can be assessed by phenotyping the consomic strain for the traits of interest on an inbred background. The contribution of genes on each chromosome can then be assessed by genetic mapping simply by phenotyping the consomic rats for the traits of interest without additional genotyping. QTLs with weak effects can be identified in fewer rats ? than are required with segregating crosses and many other mapping methods. Consomic strains overcome the confounding effects of heterogeneous genomic backgrounds in which the phenotypic noise may make the detection of weak QTLs difficult. This is an important issue in studies utilizing segregating crosses, recombinant inbred strains, and recombinant congenic strains. Consomics provide a renewable source of animals and a platform upon which subsequent genetic studies and/or physiological studies can be used to study a QTL on the chromosome. We propose the following to ensure this important HLB resource is not lost:
Specific Aim 1 : To clean-up the MCW consomic colonies and to establish foundation and limited production colonies for rat distribution. Unfortunately, MCW's consomic rats carry pinworm, which effectively prevents the distribution of the rats from MCW. We will be caesarian re-deriving the strains at the VA hospital in Milwaukee, enabling us build a foundation and small production colony for each strain. Without this supplement, consomic rats will not be available (unless people can import dirty animals) to the public after December 31, 2004 KEY reasons to support this supplement: 1) The BN, FHH and SS are dominant strains with bacterial artificial chromosomes (BACs), largest number QTLs mapped is in these strains. 2) Initial genetic mapping completed. 3) Increased rate of gene discovery for QTLs. 4) Built in controls for physiological studies. 5) Public database of all phenotyping data. 6) The cost to support these animals is a marginal cost over the investment already made in these animals and the genetic and genomic resources that have been built to support their use. (End of Abstract) ? ?
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