Apr 10, 2020

Revealing heritability missed by single locus analyses by examining epistasis in mouse chromosome substitution strains

BioRxiv : the Preprint Server for Biology
Anna K MillerD. A. Buchner

Abstract

The genetic contribution of additive versus non-additive (epistasis) effects in the regulation of hematologic and other complex traits is unclear. While genome-wide association studies typically ignore gene-gene interactions, in part because of the lack of statistical power for detecting them, mouse chromosome substitution strains (CSSs) represent an alternate and powerful model for detecting epistasis given their limited allelic variation. Therefore, we utilized CSSs to identify and map both additive and epistatic loci that regulate a range of hematologic- and metabolism-related traits, as well as hepatic gene expression. Quantitative trait loci (QTLs) were identified using a modified backcross strategy involving the segregation of variants on the A/J-derived substituted chromosomes 4 and 6 on an otherwise C57BL/6J genetic background. By analyzing the transcriptomes of offspring from this cross, we identified and mapped additive QTLs regulating the expression of 768 genes, and epistatic QTL pairs for 519 genes. Similarly, we identified additive QTLs for fat pad weight, platelets, and the percentage of granulocytes in blood, as well as epistatic QTL pairs controlling the percentage of lymphocytes in blood and red cell distribut...Continue Reading

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Mentioned in this Paper

Biochemical Pathway
Antiporter
Impacted Tooth
Phosphate Measurement
Biomedical Engineering Field
Complement Bb Measurement
Glucosephosphate Dehydrogenase
Structure
Simulation
Analysis

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