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

In the present study we use the same approach as our previous characterization of IGH to analyze complete haploid reconstructions of the IGK and IGL loci, which to date, compared to IGH, remain less well investigated. The IGL region has only been fully sequenced and analyzed once in its entirety 13 , using multiple cosmid and BAC library resources. The region spans approximately 0.9 MB, and includes 69 IGLV, seven IGLJ, and seven IGLC functional/open reading frame (ORF) genes and pseudogenes. Additional V, J, and C genes not present in this haplotype are known to occur as insertion variants in the human population 2, [14] [15] [16] . Similarly, the initial sequence of the IGK locus was generated from a composite assembly of cosmid, bacteriophage, and BAC clone libraries 17 . A unique feature of the IGK locus is that it includes two large inverted segmental duplications (SDs) that comprise distinct V-gene containing regions (termed proximal and distal); these regions remain separated by a large, currently unsequenced, assembly gap. The proximal region spans 0.54 MB and includes 69 IGKV functional/ORF genes and pseudogenes, whereas the distal region spans 0.43 MB and includes 62 V genes and pseudogenes (distal V genes are denoted by a "D"; e.g., IGKV1D-13), five functional IGKJ genes, and a single functional IGKC gene also reside downstream of the proximal V gene cluster.