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

Compared to the number of allelic variants observed between the IGHV CH17 haplotype and the reference genome (19 allelic variants/40 V gene loci 31 ), V gene allelic variation described in this study for IGL (6 allelic variants/37 V gene loci) and IGK (10 allelic variants/44 V gene loci) was noticeably lower. This prompted us to also compare other genomic characteristics between the three loci. Excluding regions of structural variation between haplotypes, we first generated SNP calls (not including gaps and single bp indels) between the CH17 and reference haplotypes for all three loci; 491, 1046, and 2897 SNPs were identified for IGKV, IGLV, and IGHV, respectively (Table 2; Figure 4 , left panel). After cross referencing these SNPs with dbSNP135 and 1KG datasets, 74, 110, and 407 SNPs in the IGKV, IGLV, and IGHV gene regions were determined to be novel variants, not represented in either dataset. Not surprisingly, given the number of SNPs in the 1KG datasets, fewer SNPs at each locus were represented in dbSNP ( Figure 4 ). We examined these sites in publicly available Illumina data generated from . CC-BY-NC 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/006866 doi: bioRxiv preprint the CHM1 genomic DNA to determine if the novel SNPs were supported by an orthogonal platform. We identified 73/74, 103/110, and 406/407 sites in IGKV, IGLV, and IGHV, respectively, that are supported by the Illumina data. The discrepancies may represent sequencing errors. The novel SNPs for each region reported in GRCh37 coordinates are in Supplementary Table 3 .