Genomics‐based approaches to gene discovery in innate immunity

Abstract

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 beta-defensins comprise an important family of mammalian antimicrobial peptides. To better define the beta-defensin gene family, we developed an approach to search genomic databases for conserved motifs present in the beta-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 beta-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.

Antimicrobial peptides and pregnancy

“…In contrast, the human b-defensins (HBDs) are predominantly epithelial products. HBD1-4 are the best characterized, although many additional defensin genes have been identified (Scheetz et al 2002, Yamaguchi et al 2002. HBD1-3 are widely expressed at epithelial surfaces, whereas HBD4 has more restricted expression, found in testis, stomach, uterus, neutrophils, thyroid, and kidney (Garcia et al 2001b).…”

Aspartyl Aminopeptidase, Encoded by an Evolutionarily Conserved Syntenic Gene, Is Colocalized with Its Cluster in Secretory Granules of Pancreatic Islet Cells

“…Many homologous genes are clustered in genomes and evolutionarily conserved in syntenic segments cross-species, 1,2) including immunoglobulin genes 3) and chemosensory receptor genes. 4) As more genomes are sequenced, more syntenic clustered genes will be identified through comparative genomics, which will dramatically enhance understanding of the significance of functional genomes in the physiology and pathophysiology of life.…”

Peptidomimetics and their Applications in Antifungal Drug Design

“…It has been shown recently that -amino acid residues bearing side chains branched at the first carbon have a strong 3 14 helix propensity [155,156]. The helix stability can be significantly enhanced by acylating the free amino terminus of oligoureas [157]. Although the amide bond is undoubtedly a consensual motif for the elaboration of peptidomimetics folding oligomers ("foldamers"), it was shown that the urea moiety, by its capacity to form auto-complementarities and bidirectional hydrogen bonds can be substituted for the amide linkage to generate oligomeric strands with strong propensity for helix formation [158,159].…”

“…Recently researchers attempted to model antimicrobial peptide by QSAR and other in silico methods. For example a HMM (Hidden Markov Model) based method has been developed for searching conserved motifs of -defensin family in genome databases [157]. Combinatorial chemistry, high-throughput screening, and analogous techniques have become powerful tools to promote drug discovery in peptidomimetics research.…”