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KARIM, Latifa; TAKEDA, Haruko; HARRIS, Bevin L; KEEHAN, Mike D; LITTLEJOHN, Mathew D; SPELMAN, Richard J; GEORGES, Michel; COPPIETERS, Wouter; LI LIN; DRUET, Tom; ARIAS, Juan A. C; BAURAIN, Denis; CAMBISANO, Nadine; DAVIS, Stephen R; FARNIR, Frederic; GRISART, Bernard
Nature genetics, 05/2011, Volume: 43, Issue: 5Journal Article, Web Resource
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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