RT Journal Article
SR Electronic
T1 Sequencing of the human IG light chain loci from a hydatidiform mole BAC library reveals locus-specific signatures of genetic diversity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 006866
DO 10.1101/006866
A1 Corey T. Watson
A1 Karyn Meltz Steinberg
A1 Tina A. Graves
A1 Rene L. Warren
A1 Maika Malig
A1 Jacqueline Schein
A1 Richard K. Wilson
A1 Robert A. Holt
A1 Evan E. Eichler
A1 Felix Breden
YR 2014
UL http://biorxiv.org/content/early/2014/07/03/006866.abstract
AB Germline variation at immunoglobulin gene (IG) loci is critical for pathogen-mediated immunity, but establishing complete reference sequences in these regions is problematic because of segmental duplications and somatically rearranged source DNA. We sequenced BAC clones from the essentially haploid hydatidiform mole, CHM1, across the light chain IG loci, kappa (IGK) and lambda (IGL), creating single haplotype representations of these regions. The IGL haplotype is 1.25Mb of contiguous sequence with four novel V gene and one novel C gene alleles and an 11.9kbp insertion. The IGK haplotype consists of two 644kbp proximal and 466kbp distal contigs separated by a gap also present in the reference genome sequence. Our effort added an additional 49kbp of unique sequence extending into this gap. The IGK haplotype contains six novel V gene and one novel J gene alleles and a 16.7kbp region with increased sequence identity between the two IGK contigs, exhibiting signatures of interlocus gene conversion. Our data facilitated the first comparison of nucleotide diversity between the light and IG heavy (IGH) chain haplotypes within a single genome, revealing a three to six fold enrichment in the IGH locus, supporting the theory that the heavy chain may be more important in determining antigenic specificity.