title: Inter-population variability of DEFA3 gene absence: correlation with haplotype structure and population variability.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Genes and Disease Program, Center for Genomic Regulation (CRG), Barcelona, Catalonia, Spain. ester.ballana@crg.es <ester.ballana@crg.es>
authors.forename: Ester
authors.initials: E
authors.lastname: Ballana
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: González
authors.forename: Nina
authors.initials: N
authors.lastname: Bosch
authors.forename: Xavier
authors.initials: X
authors.lastname: Estivill
mesh_terms: D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D019295:Computational Biology; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics; D023084:alpha-Defensins / Q000235:genetics*
chemical_list: D023084:alpha-Defensins; C406427:human neutrophil peptide 3