Manual annotation and analysis of the defensin gene cluster in the C57BL/6J mouse reference genome

Amid, Clara, Rehaume, Linda M., Brown, Kelly L., Gilbert, James G. R., Dougan, Gordon, Hancock, Robert E. W. and Harrow, Jennifer L. (2009) Manual annotation and analysis of the defensin gene cluster in the C57BL/6J mouse reference genome. BMC Genomics, 10 606.1-606.13. doi:10.1186/1471-2164-10-606


Author Amid, Clara
Rehaume, Linda M.
Brown, Kelly L.
Gilbert, James G. R.
Dougan, Gordon
Hancock, Robert E. W.
Harrow, Jennifer L.
Title Manual annotation and analysis of the defensin gene cluster in the C57BL/6J mouse reference genome
Journal name BMC Genomics   Check publisher's open access policy
ISSN 1471-2164
Publication date 2009-12-15
Sub-type Article (original research)
DOI 10.1186/1471-2164-10-606
Open Access Status DOI
Volume 10
Start page 606.1
End page 606.13
Total pages 13
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Background: Host defense peptides are a critical component of the innate immune system. Human alpha- and beta-defensin genes are subject to copy number variation (CNV) and historically the organization of mouse alpha-defensin genes has been poorly defined. Here we present the first full manual genomic annotation of the mouse defensin region on Chromosome 8 of the reference strain C57BL/6J, and the analysis of the orthologous regions of the human and rat genomes. Problems were identified with the reference assemblies of all three genomes. Defensins have been studied for over two decades and their naming has become a critical issue due to incorrect identification of defensin genes derived from different mouse strains and the duplicated nature of this region.

Results: The defensin gene cluster region on mouse Chromosome 8 A2 contains 98 gene loci: 53 are likely active defensin genes and 22 defensin pseudogenes. Several TATA box motifs were found for human and mouse defensin genes that likely impact gene expression. Three novel defensin genes belonging to the Cryptdin Related Sequences (CRS) family were identified. All additional mouse defensin loci on Chromosomes 1, 2 and 14 were annotated and unusual splice variants identified. Comparison of the mouse alpha-defensins in the three main mouse reference gene sets Ensembl, Mouse Genome Informatics (MGI), and NCBI RefSeq reveals significant inconsistencies in annotation and nomenclature. We are collaborating with the Mouse Genome Nomenclature Committee (MGNC) to establish a standardized naming scheme for alpha-defensins.

Conclusions: Prior to this analysis, there was no reliable reference gene set available for the mouse strain C57BL/6J defensin genes, demonstrating that manual intervention is still critical for the annotation of complex gene families and heavily duplicated regions. Accurate gene annotation is facilitated by the annotation of pseudogenes and regulatory elements. Manually curated gene models will be incorporated into the Ensembl and Consensus Coding Sequence (CCDS) reference sets. Elucidation of the genomic structure of this complex gene cluster on the mouse reference sequence, and adoption of a clear and unambiguous naming scheme, will provide a valuable tool to support studies on the evolution, regulatory mechanisms and biological functions of defensins in vivo. 
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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