Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 99, Issue 4, Pages 2129-2133Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.042692699
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Funding
- NCI NIH HHS [CA-85188] Funding Source: Medline
- NHLBI NIH HHS [HL-61234, P50 HL061234] Funding Source: Medline
- NICHD NIH HHS [K12 HD027748, P30-HD27748] Funding Source: Medline
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The innate immune system includes antimicrobial peptides that protect multicellular organisms from a diverse spectrum of microorganisms. beta-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 beta-defensin gene (DEF83). To define better the G-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 beta-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 beta-defensins in innate immunity.
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