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Genomics‐based approaches to gene discovery in innate immunity
Author(s) -
Scheetz Todd,
Bartlett Jennifer A.,
Walters Jesse D.,
Schutte Brian C.,
Casavant Thomas L.,
B. McCray Paul
Publication year - 2002
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1034/j.1600-065x.2002.19010.x
Subject(s) - synteny , biology , genome , comparative genomics , genetics , gene , computational biology , defensin , gene prediction , genomics , gene family , gene cluster , human genome
Summary: The completion of draft sequences of the human and mouse genomes offers many opportunities for gene discovery in the field of immunology through the application of the methods of computational genomics. One arm of the innate immune system includes the antimicrobial peptides that protect multicellular organisms from a diverse spectrum of microorganisms. The β‐defensins comprise an important family of mammalian antimicrobial peptides. To better define the β‐defensin gene family, we developed an approach to search genomic databases for conserved motifs present in the β‐defensin family using HMMER, a computational search tool based on hidden Markov models (HMMs), in combination with the basic local alignment search tool. The approach was first used to identify candidate second‐exon coding regions, and later applied to finding associated first exons. This strategy discovered 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 that each cluster pair arose from a common ancestor and was retained because of conserved functions. These findings demonstrate an important proof‐of‐principle for a genome‐wide search strategy to identify genes with conserved structural motifs. Such an approach may be readily adopted to address other questions of relevance to immunology.