[en] Alleles ; Animals ; Base Sequence ; Cattle/anatomy & histology/genetics ; Chromosome Mapping ; Crosses, Genetic ; DNA Primers/genetics ; Female ; Genetic Variation ; Genome-Wide Association Study ; Haplotypes ; Linkage Disequilibrium ; Open Reading Frames ; Male ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Quantitative Trait Loci ; RNA Splice Sites ; Regulon ; Sequence Homology, Nucleic Acid
[en] We report mapping of a quantitative trait locus (QTL) with a major effect on bovine stature to a approximately 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 approximately 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.