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

Eight BAC clones were analyzed in the IGK locus, forming two independent contigs, one in the proximal region totalling 644 Kbp, and a second in the distal region of the locus totalling Table 2 ). We observed ten allelic differences at IGKV gene loci, and one allelic variant at IGKJ2; ten of these allelic variants, including IGKJ2*04, involved non-synonymous changes. We characterized nine novel alleles that were not represented in IMGT, including three that were observed in the Kawasaki haplotype. In two instances, we observed the presence of alleles that had been previously classified as either "distal" or "proximal" alleles residing at loci in the alternate location. For example, we found an allele that matched with 100% sequence identity to IGKV1-13*02 at the IGKV1D-13 locus in the CH17 haplotype, for which there had previously been only one allele described, IGKV1D-13*01. IGKV1D-13*01, which differs from IGKV1-13*02 by only a single nucleotide, was initially classified as an ORF due to an abnormal V-heptamer sequence, but was later identified in a productive rearrangement, indicating that it is likely functional 27 .