title: Variants modulating the expression of a chromosome domain encompassing PLAG1 influence bovine stature.
abstract: 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.
authors.affiliation: Unit of Animal Genomics, Interdisciplinary Institute of Applied Genomics (GIGA-R) and Faculty of Veterinary Medicine, University of Liège (B34), Liège, Belgium.
authors.forename: Latifa
authors.initials: L
authors.lastname: Karim
authors.forename: Haruko
authors.initials: H
authors.lastname: Takeda
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Tom
authors.initials: T
authors.lastname: Druet
authors.forename: Juan A C
authors.initials: JA
authors.lastname: Arias
authors.forename: Denis
authors.initials: D
authors.lastname: Baurain
authors.forename: Nadine
authors.initials: N
authors.lastname: Cambisano
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Davis
authors.forename: Frédéric
authors.initials: F
authors.lastname: Farnir
authors.forename: Bernard
authors.initials: B
authors.lastname: Grisart
authors.forename: Bevin L
authors.initials: BL
authors.lastname: Harris
authors.forename: Mike D
authors.initials: MD
authors.lastname: Keehan
authors.forename: Mathew D
authors.initials: MD
authors.lastname: Littlejohn
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Spelman
authors.forename: Michel
authors.initials: M
authors.lastname: Georges
authors.forename: Wouter
authors.initials: W
authors.lastname: Coppieters
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002417:Cattle / Q000033:anatomy & histology* / Q000235:genetics*; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D017931:DNA Primers / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006239:Haplotypes; D015810:Linkage Disequilibrium; D008297:Male; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D040641:Quantitative Trait Loci; D022821:RNA Splice Sites; D018085:Regulon; D012689:Sequence Homology, Nucleic Acid
chemical_list: D017931:DNA Primers; D022821:RNA Splice Sites