title: Canine TCOF1; cloning, chromosome assignment and genetic analysis in dogs with different head types.
abstract: We describe the construction of a dog embryonic head/neck cDNA library and the isolation of the dog homolog of the Treacher Collins Syndrome gene, TCOF1. The protein shows a similar three-domain structure to that described for human TCOF1, but the dog gene lacks exon 10 and contains two exons not present in the human sequence. In addition, exon 19 is differentially spliced in the dog. How these structural differences relate to TCOF1 phosphorylation is discussed. Isolation of a genomic clone allowed the exon/intron boundaries to be characterized and the dog TCOF1 gene to be mapped to CF Chr 4q31, a region syntenic to human Chr 5. Genetic analysis of DNA of dogs from 13 different breeds identified nine DNA sequence variants, three of which gave rise to amino acid substitutions. Grouping dogs according to head type showed that a C396T variant, leading to a Pro117Ser substitution, is associated with skull/face shape in our dog panel. The numbers are small, but the association between the T allele and brachycephaly, broad skull/short face, was highly significant (p = 0.000024). The short period of time during which the domestic dog breeds have been established suggests that this mutation has arisen only once in the history of dog domestication.
authors.affiliation: MRC Human Biochemical Genetics Unit, University College London, Wolfson House, 4 Stephenson Way, London NW1 2HE, UK.
authors.forename: K E
authors.initials: KE
authors.lastname: Haworth
authors.forename: I
authors.initials: I
authors.lastname: Islam
authors.forename: M
authors.initials: M
authors.lastname: Breen
authors.forename: W
authors.initials: W
authors.lastname: Putt
authors.forename: E
authors.initials: E
authors.lastname: Makrinou
authors.forename: M
authors.initials: M
authors.lastname: Binns
authors.forename: D
authors.initials: D
authors.lastname: Hopkinson
authors.forename: Y
authors.initials: Y
authors.lastname: Edwards
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000829:Animals, Domestic; D001947:Breeding; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D004285:Dogs / Q000033:anatomy & histology* / Q000145:classification / Q000235:genetics*; D005091:Exons / Q000235:genetics; D015723:Gene Library; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007438:Introns / Q000235:genetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics*; D010641:Phenotype; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D016415:Sequence Alignment
chemical_list: D018076:DNA, Complementary; D009687:Nuclear Proteins; D010750:Phosphoproteins; C105442:TCOF1 protein, human