title: Sequencing of the human IG light chain loci from a hydatidiform mole BAC library reveals locus-specific signatures of genetic diversity.
abstract: Germline variation at immunoglobulin (IG) loci is critical for pathogen-mediated immunity, but establishing complete haplotype sequences in these regions has been problematic because of complex sequence architecture and diploid source DNA. We sequenced BAC clones from the effectively haploid human hydatidiform mole cell line, CHM1htert, across the light chain IG loci, kappa (IGK) and lambda (IGL), creating single haplotype representations of these regions. The IGL haplotype generated here is 1.25 Mb of contiguous sequence, including four novel IGLV alleles, one novel IGLC allele, and an 11.9-kb insertion. The CH17 IGK haplotype consists of two 644 kb proximal and 466 kb distal contigs separated by a large gap of unknown size; these assemblies added 49 kb of unique sequence extending into this gap. Our analysis also resulted in the characterization of seven novel IGKV alleles and a 16.7-kb region exhibiting signatures of interlocus sequence exchange between distal and proximal IGKV gene clusters. Genetic diversity in IGK/IGL was compared with that of the IG heavy chain (IGH) locus within the same haploid genome, revealing threefold (IGK) and sixfold (IGL) higher diversity in the IGH locus, potentially associated with increased levels of segmental duplication and the telomeric location of IGH.
authors.affiliation: Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada.|Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Corey T
authors.initials: CT
authors.lastname: Watson
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.|The Genome Institute, Washington University, St. Louis, MO 63108, USA.
authors.forename: Karyn Meltz
authors.initials: KM
authors.lastname: Steinberg
authors.affiliation: The Genome Institute, Washington University, St. Louis, MO 63108, USA.
authors.forename: Tina A
authors.initials: TA
authors.lastname: Graves
authors.affiliation: Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, V5Z 4S6, Canada.
authors.forename: Rene L
authors.initials: RL
authors.lastname: Warren
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Maika
authors.initials: M
authors.lastname: Malig
authors.affiliation: Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, V5Z 4S6, Canada.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Schein
authors.affiliation: The Genome Institute, Washington University, St. Louis, MO 63108, USA.
authors.forename: Richard K
authors.initials: RK
authors.lastname: Wilson
authors.affiliation: Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia, V5Z 4S6, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Holt
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.|Howard Hughes Medical Institute, Seattle, WA 98195, USA.
authors.forename: Evan E
authors.initials: EE
authors.lastname: Eichler
authors.affiliation: Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada.
authors.forename: Felix
authors.initials: F
authors.lastname: Breden
mesh_terms: D045744:Cell Line, Tumor; D022202:Chromosomes, Artificial, Bacterial; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain; D050439:Genes, Immunoglobulin Light Chain; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy