Sequencing of the human IG light chain loci from a hydatidiform mole BAC library reveals locus-specific signatures of genetic diversity

Corey T Watson; Karyn Meltz Steinberg; Tina A Graves-Lindsay; Rene L Warren; Maika Malig; Jacqueline E Schein; Richard K Wilson; Rob Holt; Evan Eichler; Felix Breden

The distinct clustering and genomic partitioning of V gene families within the IGL locus, and the observation that, compared to IGH and IGK, there are fewer IGL orphans present in other regions of the genome, has prompted the suggestion that IGL genes have undergone less "evolutionary shuffling" 22 , which may be linked to lower levels of diversity in the locus 15 and would be consistent with the results presented here. In comparison to the other two loci, we found IGKV to have the lowest locus-wide SNP density, nearly 6-fold lower than that observed in IGHV. Due to the large inverted duplication of the proximal and distal regions, over 80% of the IGKV locus consists of SDs with >95% sequence identity. This suggests that, unlike in IGHV, SDs may be responsible for sequence homogenization rather than an increase in SNP diversity.