title: Identification of a doublet missense substitution in the bovine LRP4 gene as a candidate causal mutation for syndactyly in Holstein cattle.
abstract: Syndactyly in Holstein cattle is an autosomal recessive abnormality characterized by the fusion of the functional digits. This disorder has been previously mapped to the telomeric part of bovine chromosome 15. Here, we describe the fine-mapping of syndactyly in Holstein cattle to a 3.5-Mb critical interval using a comparative mapping approach and an extended pedigree generated by embryo transfer. We report genetic evidence for the exclusion of two genes previously suggested as candidates (EXT2 and ALX4) and describe the identification of a doublet mutation in complete linkage disequilibrium with syndactyly in one gene of the critical interval: LRP4. Finally, based on recent discoveries concerning the mouse mutants dan and mdig and a mouse knockout for Lrp4, we present solid evidence that the subsequent substitution in LRP4 exon 33 is a strong candidate causal mutation for syndactyly in Holstein cattle.
authors.affiliation: Laboratoire de Génétique Biochimique et de Cytogénétique, Département de Génétique Animale, INRA-CRJ, 78350 Jouy-en-Josas, France.
authors.forename: A
authors.initials: A
authors.lastname: Duchesne
authors.forename: M
authors.initials: M
authors.lastname: Gautier
authors.forename: S
authors.initials: S
authors.lastname: Chadi
authors.forename: C
authors.initials: C
authors.lastname: Grohs
authors.forename: S
authors.initials: S
authors.lastname: Floriot
authors.forename: Y
authors.initials: Y
authors.lastname: Gallard
authors.forename: G
authors.initials: G
authors.lastname: Caste
authors.forename: A
authors.initials: A
authors.lastname: Ducos
authors.forename: A
authors.initials: A
authors.lastname: Eggen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002418:Cattle Diseases / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005121:Extremities / Q000196:embryology / Q000254:growth & development; D005260:Female; D005808:Genes, Recessive; D023281:Genomics; D015810:Linkage Disequilibrium; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy; D011973:Receptors, LDL / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D013576:Syndactyly / Q000235:genetics / Q000473:pathology / Q000662:veterinary*
chemical_list: D017931:DNA Primers; D011973:Receptors, LDL; D004247:DNA