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

As a means to improve existing genomic resources in the IG loci, we have sequenced the IGK and IGL gene clusters from the CHORI-17 BAC library (CH17, BACPAC resources), previously constructed from a haploid hydatidiform mole cell line (CHM1htert). Together with data produced previously for the IGH locus from the CH17 library 7 , these sequences represent the first complete human haplotypes of all three IG loci from a single individual. Using these data, we have conducted the first comparison of genetic diversity between the three IG regions in the same haploid genome. Our analyses have facilitated the identification of novel single nucleotide polymorphisms (SNPs) within IGL and IGK gene coding regions and regulatory elements, and also revealed a novel large sequence conversion event between the IGKV proximal and distal regions. In addition, our unbiased tri-locus comparison shows a striking enrichment of structural and nucleotide diversity in the IGH locus, confirming previous suggestions that germline variation within the light chain gene loci is lower than that observed in IGH 15, 22, 23 .