학술논문

Discovery of Five Conserved β-Defensin Gene Clusters Using a Computational Search Strategy
Document Type
research-article
Source
Proceedings of the National Academy of Sciences of the United States of America, 2002 Feb . 99(4), 2129-2133.
Subject
Genetics
Genes
Genomics
Exons
Blasts
Amino acids
Chromosomes
Multigene family
Genomes
Nucleotide sequences
Search strategies
Language
English
ISSN
00278424
Abstract
The innate immune system includes antimicrobial peptides that protect multicellular organisms from a diverse spectrum of microorganisms. β-Defensins comprise one important family of mammalian antimicrobial peptides. The annotation of the human genome fails to reveal the expected diversity, and a recent query of the draft sequence with the Blast search engine found only one new β-defensin gene (DEFB3). To define better the β-defensin gene family, we adopted a genomics approach that uses Hmmer, a computational search tool based on hidden Markov models, in combination with Blast. This strategy identified 28 new human and 43 new mouse β-defensin genes in five syntenic chromosomal regions. Within each syntenic cluster, the gene sequences and organization were similar, suggesting each cluster pair arose from a common ancestor and was retained because of conserved functions. Preliminary analysis indicates that at least 26 of the predicted genes are transcribed. These results demonstrate the value of a genomewide search strategy to identify genes with conserved structural motifs. Discovery of these genes represents a new starting point for exploring the role of β-defensins in innate immunity.