PHYSICAL LOCATION OF THE HUMAN-IMMUNOGLOBULIN LAMBDA-LIKE GENES, 14.1, 16.1, AND 16.2

The human immunoglobulin lambda-like (IGLL) genes, which are homologous to the human immunoglobulin lambda (IGL) light chain genes, are expressed only in pre-B cells and are involved in B cell development. Three IGLL genes, 14.1, 16.1, and 16.2 are present in humans as opposed to one, lambda5 (Igll), found in the mouse. To precisely map the location of the human IGLL genes in relation to each other and to the human IGL gene locus, at 22q11.1-2, a somatic cell hybrid panel and pulsed field gel electrophoresis (PFGE) were used. Hybridization with a lambda-like gene-specific DNA probe to somatic cell hybrids revealed that these genes reside on 22q11.2 between the breakpoint cluster region (BCR) and the Ewing sarcoma breakpoint at 22q12 and that gene 161 was located distal to genes 14.1 and 16.2. Gene 14.1 was found by PFGE to be proximal to 16.2 by at least 30 kilobases (kb). A 210 kb Not I fragment containing genes 14.1 and 16.2 is adjacent to a 400 kb Not I fragment containing the BCR locus, which is just distal to the IGL-C (IGL constant region) genes. We have determined that the IGLL genes 14.1 and 16.2 are approximately 670 kb and 690 to 830 kb distal, respectively, to the 3'-most IGL-C gene in the IGL gene locus, IGL-C7. We thus show the first physical linkage of the IGL and the IGLL genes, 14.1 and 16.2. We discuss the relevance of methylation patterns and CpG islands to expression, and the evolutionary significance of the IGLL gene duplications. Consistent with the GenBank nomenclature, these human IGLL genes will be referred to as IGLL1 (14.1), IGLL2 (16.2), and IGLL3 (16.1), reflecting their position on chromosome 22, as established by this report.