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The chromosome 17q21.31 inversion is a 900-kb common structural polymorphism found primarily in European population. Although the genetic flux within inversion region was assumed to be considerable suppressed, it is still unclear about the details of genetic exchange between the H1 (non-inverted sequence) and H2 (inverted sequence) haplotypes of this inversion. Here we describe a refined map of genetic exchanges between pairs of gene arrangements within the 17q21.31 region. Using HapMap phase II data of 1,546 single nucleotide polymorphisms, we successfully deduced 96 H1 and 24 H2 haplotypes in European samples by neighbor-joining tree reconstruction. Furthermore, we identified 15 and 26 candidate tracts with reciprocal and non-reciprocal genetic exchanges, respectively. In all 15 regions harboring reciprocal exchange, haplotypes reconstructed by clone sequencing did not support these exchange events, suggesting that such signals of exchange between two sister chromosomes in certain heterozygous individual were caused by phasing error regions. On the other hand, the finished clone sequencing across 4 of 26 tracts with non-reciprocal genetic flux confirmed that this kind of genetic exchange was caused by gene conversion. In summary, as crossover between pairs of gene arrangements had been considerably suppressed, gene conversion might be the most important mechanism for genetic exchange at 17q21.31.

HLA is the most polymorphic gene family in human genome, which is imperative for human to face numerous heterogeneous bio-molecules. Previous studies on the formation of HLA polymorphism have been focused on gene crossover. Here, we investigated the contribution of gene conversion, which is an important mechanism to generate polymorphism at shaping different patterns of HLA-DRB genes. Analysis of all known HLA-DRB haplotypes and alleles demonstrated that this was a highly polymorphic gene family. Using Ester Betran's algorithm, 32 gene conversion regions were identified. The minimal conversion tract was as short as 2 bp, and the maximum interval between two furthest SNPs was 204 bp. Moreover, gene conversion occurred more frequently in certain regions (71-75, 18-221) of various alleles, suggesting that these segments were conversion hotspots. Further analysis showed that the conversion regions of 71-75 and 205-217 appeared to correlate with populations of Oriental and Caucasian, respectively, indicating that conversion hotspots might be population specific.