Structural analysis of the chicken BRCA2 gene facilitates identification of functional domains and disease causing mutations

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...

Full description

Saved in:
Bibliographic Details
Published in:Human molecular genetics 2002-04, Vol.11 (7), p.841-851
Main Authors: Warren, Madhuri, Smith, Amanda, Partridge, Natalie, Masabanda, Julio, Griffin, Darren, Ashworth, Alan
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Avian Proteins
Biological and medical sciences
BRCA2 gene
BRCA2 Protein - genetics
Chickens
chromosome 1
chromosome 13
Chromosome Mapping
Fundamental and applied biological sciences. Psychology
Gallus gallus
Genes. Genome
In Situ Hybridization, Fluorescence
Molecular and cellular biology
Molecular genetics
Molecular Sequence Data
Mutation
Phylogeny
Protein Structure, Tertiary
Sequence Alignment
Sequence Analysis, DNA
Sequence Analysis, Protein
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0964-6906
1460-2083
1460-2083
DOI:10.1093/hmg/11.7.841