title: Structural analysis of the chicken BRCA2 gene facilitates identification of functional domains and disease causing mutations.
abstract: Carriers of mutations in the BRCA2 gene have a high risk of developing breast and other cancers. The BRCA2 gene, which is located on human chromosome 13, encodes a very large protein of only poorly understood function. To define regions of sequence conservation and highlight potentially functionally important domains, we have cloned and characterized the chicken BRCA2 gene, the first non-mammalian BRCA2 gene to be described. The gene is organized similarly to the human BRCA2 gene, but is more compact and is localized to the subtelomeric region of chicken chromosome 1q, within a region that contains other genes from human chromosome 13. The chicken BRCA2 gene encodes a protein of 3399 amino acids, which is poorly conserved with mammalian BRCA2 proteins, having only 37% amino acid identity overall with human BRCA2. However, certain domains are much more highly conserved, indicating functional significance. We describe genes with some of these conserved domains in organisms as diverse as intracellular parasites, mosquitoes and plants. The evolutionarily divergent chicken BRCA2 sequence may also be useful in assigning the large number of sequence variants that have been described in the human BRCA2 gene which are of unknown significance in disease causation.
authors.affiliation: CRC Gene Function and Regulation Group, The Breakthrough Toby Robins Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
authors.forename: Madhuri
authors.initials: M
authors.lastname: Warren
authors.forename: Amanda
authors.initials: A
authors.lastname: Smith
authors.forename: Natalie
authors.initials: N
authors.lastname: Partridge
authors.forename: Julio
authors.initials: J
authors.lastname: Masabanda
authors.forename: Darren
authors.initials: D
authors.lastname: Griffin
authors.forename: Alan
authors.initials: A
authors.lastname: Ashworth
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D024682:BRCA2 Protein / Q000235:genetics*; D002645:Chickens; D002874:Chromosome Mapping; D017404:In Situ Hybridization, Fluorescence; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D020539:Sequence Analysis, Protein
chemical_list: D030161:Avian Proteins; D024682:BRCA2 Protein; C447900:BRCA2 protein, chicken