Inter-population variability of DEFA3 gene absence: correlation with haplotype structure and population variability

BMC Genomics. 2007 Jan 10;8:14. doi: 10.1186/1471-2164-8-14.


Background: Copy number variants (CNVs) account for a significant proportion of normal phenotypic variation and may have an important role in human pathological variation. The alpha-defensin cluster on human chromosome 8p23.1 is one of the better-characterized CNVs, in which high copy number variability affecting the DEFA1 and DEFA3 genes has been reported. Moreover, the DEFA3 gene has been found to be absent in a significant proportion of control population subjects. CNVs involving immune genes, such as alpha-defensins, are possibly contributing to innate immunity differences observed between individuals and influence predisposition and susceptibility to disease.

Results: We have tested the DEFA3 absence in 697 samples from different human populations. The proportion of subjects lacking DEFA3 has been found to vary from 10% to 37%, depending on the population tested, suggesting differences in innate immune function between populations. Absence of DEFA3 was correlated with the region's haplotype block structure. African samples showed a higher intra-populational variability together with the highest proportion of subjects without DEFA3 (37%). Association analysis of DEFA3 absence with 136 SNPs from a 100-kb region identified a conserved haplotype in the Caucasian population, extending for the whole region.

Conclusion: Complexity and variability are essential genomic features of the alpha-defensin cluster at the 8p23.1 region. The identification of population differences in subjects lacking the DEFA3 gene may be suggestive of population-specific selective pressures with potential impact on human health.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Continental Ancestry Group / genetics
  • Asian Continental Ancestry Group / genetics
  • Chromosomes, Human, Pair 8 / genetics
  • Computational Biology
  • European Continental Ancestry Group / genetics
  • Genetics, Population
  • Haplotypes*
  • Humans
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide
  • alpha-Defensins / genetics*


  • alpha-Defensins
  • human neutrophil peptide 3