International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

D25 The Structure of Distal CHR 12 Including IGH and Environs

Roy Riblet, America Mauhar, Brendan Brinkman, and Christophe Chevillard. Torrey Pines Institute, 3550 General Atomics Court, San Diego, California 92121 USA

One of our goals is the complete molecular definition of the mouse immunoglobulin heavy chain (Igh) locus and the identification and sequencing of all variable region (Vh) genes. To determine the structure of this complex locus in the C57BL/6 strain we have identified a deeply redundant yeast artificial chromosome (YAC) contig of over 40 clones that contains all Igh elements. In the B6 (Ighb) haplotype we found that the Igh locus covers more than three megabases and contains at least 134 Vh genes classified in 15 partially interspersed families.

To clone a different haplotype of Igh for evolutionary and functional comparisons we have assembled a partial contig of 129/Sv BAC clones. This contig covers the Igh-C, -J and -D regions and contains the proximal Igh-V gene families. In addition we extended the BAC contig 3' of the Igh locus to contain both the large and highly repetitive 3' Igh enhancer and locus control region, and the origin of replication that is located approximately 80 kb 3' of Igh. We have identified the nearest neighboring genes, including Serrate and Crip, and are investigating the evolutionary and regulatory properties of this flanking region.

In man the IGH locus on distal CHR 14 extends to the telomere, and in all mammalian species where Igh has been mapped it is telomeric, suggesting a possible relationship between the variability of telomeric regions and the extreme polymorphism of Igh. In mouse, however, several non-Ig genes have been roughly mapped distal to Igh. We have used YAC and BAC physical mapping, Radiation Hybrid analysis, and FISH to clarify the structure of distal Chr 12.


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