We report mapping of a quantitative trait locus (QTL) with a major effect on bovine stature to a ∼780-kb interval using a Hidden Markov Model–based approach that simultaneously exploits linkage and linkage disequilibrium. We re-sequenced the interval in six sires with known QTL genotype and identified 13 clustered candidate quantitative trait nucleotides (QTNs) out of >9,572 discovered variants. We eliminated five candidate QTNs by studying the phenotypic effect of a recombinant haplotype identified in a breed diversity panel. We show that the QTL influences fetal expression of seven of the nine genes mapping to the ∼780-kb interval. We further show that two of the eight candidate QTNs, mapping to the PLAG1-CHCHD7 intergenic region, influence bidirectional promoter strength and affect binding of nuclear factors. By performing expression QTL analyses, we identified a splice site variant in CHCHD7 and exploited this naturally occurring null allele to exclude CHCHD7 as single causative gene.
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This work was funded by Livestock Improvement Corporation (LIC; Hamilton, New Zealand) and by grants from the Unit of Animal Genomics, the University of Liège, the Communauté Française de Belgique (ARC Biomod) and the Belgian Science Policy Organisation (SSTC Genefunc PAI). T.D. is Research Associate of the Fond National de Recherche Scientifique. We are grateful for the support of the GIGA-R sequencing core facility.
The authors declare no competing financial interests.
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Karim, L., Takeda, H., Lin, L. et al. Variants modulating the expression of a chromosome domain encompassing PLAG1 influence bovine stature. Nat Genet 43, 405–413 (2011) doi:10.1038/ng.814
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