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Chunk #0 — Results — Phenomes

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Joint mouse-human phenome-wide association to test gene function and disease risk.
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Phenome data were generated using a large cohort of recombinant inbred strains—the BXD family—that was derived by crossing two fully inbred parents—C57BL/6J (B6) and DBA/2J (D2). Members of the BXD family collectively segregate for all sequence variants that distinguish the two parents—and in this cross these are by definition common variants. There are also interesting rare but still undefined alleles unique to each family member. The level of both genetic and phenotypic variation between parents and among the strains is high (Fig. 1a). This BXD phenome includes ∼4,500 quantitative metabolic, physiological, pharmacological, toxicological, morphometric and behavioural phenotypes (Fig. 1b). These traits are almost all quantitative and have been systematically grouped into 15 major phenotype categories (Supplementary Data 1). We have also generated and assembled a large molecular phenome that includes expression phenotypes from ∼90 large open-access eQTL studies generated over the past decade (Fig. 1b and Supplementary Data 2). On average 1.5 × 106 mRNA, 1.7 × 104 proteomic and 6.8 × 103 metabolomic assays are available per strain (Fig. 1b). Most phenotypes vary markedly across strains within the family.