Linkage analyses of murine immunoglobulin heavy chain and serum prealbumin genes establish their location on chromosome 12 proximal to the T (5;12) 31H breakpoint in band 12F1.

Abstract

Analysis of backcross mice carrying the Harwell translocation T(5;12)31H has led to the definitive localization of the immunoglobulin heavy chain gene cluster. BothIgh-1 and Pre-] loci were found to segregate in tight linkage with the chromonomal markers S and 125, which define the balanced translocation T(5^12)31H. Additional data establish the location of these genes at the telbmeric end of chromosome 12. That both lci are proximal to the chromosomal breakpoint in band 12F1 is shown by the phenotypes of segregants aneuploid for the presence or absence ofthe small marker 512. The order of loci inferred from a single recovered recombinant is:centromere-Ijgh-1 -Pre-1-7(5; 12)31H.The genes coding for the immundolobulin polypeptides present unique features with respect to their organization, structure, and expression (1). Interest in their chromosomal location has been rekindled by the evidence that the codon sequences of each light chain, K and X, are constructed during differentiation of plasma cell precursors by the joining of DNA segments that were previously far apart (2-4). Aside from other general implications, information on the map position of the immunoglobulin genes may allow direct investigation on the nature of the relationship between somatic gene rearrangement and allelic exclusion (3). Particularly with regard to the heavy chain genes, knowledge of their location can be used to explore other phenomena, such as switching of heavy chain gene expression (5) and somatic crossovers between variable and constant region determinants (6). Nevertheless, none of the three unlinked clusters of the K, A, and heavy chain immunoglobulin genes has been unequivocally mapped in any species (7,8).In the mouse, the chromosomal segment comprising the heavy chain variable and constant regions, Igh-V and Igh-C, respectively, (9), extends for at least 7-11 units (10) and is linked, probably at its Igh-C end, with the serum prealbumin locus Pre-1 at a distance of about 11 units (11). Although more than 80% of the mouse genetic map has been examined, linkage analyses have failed to position either locus (12). Recently, conflicting reports have been published on the assignment of the Igh genes. The results obtained by renaturing specific cDNA transcripts with chromosomal DNA preparations from human fibrosarcoma-mouse macrophage cell hybrids led Valbuena et al. (13) to conclude that the most probable location of the Igh-C genes was on mouse chromosome 15. In contrast, Hengartner et al. (14), analyzing the immunoglobulin production of intraspecific cell hybrids, have tentatively assigned the Igh-V and Igh-C group to mouse chromosome 12, which was clearly excluded in the former study. Interestingly, both assignments failed to match with the probable locations inferred from negative linkage data. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18], whereas the sex chromosome and chromosome 19 remain structurally unmarked. The inbred strains C57BL/6J, LP/J, and BALB/cJ were purchased from the Jackson Labora...

Hypermutation at the immunoglobulin heavy chain locus in a pre-B-cell line.

“…The L chain loci are usually in the embryonic configuration; that is, their gene segments have not been joined to form functional L chain genes (4). The line is diploid for chromosome 12 (3), which carries the H chain locus (5,6). In both homologous chromosomes, the V, D, and J gene segments have been correctly joined to form H chain genes (7).…”

Provisional chromosome assignment of the rat major histocompatibility complex.

“…Our data fulfil this prediction and further substantiate the current notion that the chromosome banding similarity reflects the conservation of the homologous gene in different species, as have been shown by comparative gene mapping (Human Gene Mapping 5, 1979;Garver et al 1980). In this context, a recent report of Schroder et al (1980) may merit special attention, who suggested the immunoglobulin heavy chain (Igh) locus of the rat on chromosome 14, in spite of the fact that Igh locus of the mouse have been assigned to chromosome 12 but not to chromosome 17 coding for H-2 complex (Hengartner et al 1978;Meo et al 1980). Wiener et al (1982), however, are of opinion that the rat Igh is located on chromosome 6, which is similar to mouse chromosome 12.…”

H-40, an antigen controlled by an Igh linked gene and recognized by cytotoxic T lymphocytes. I. Genetic analysis of H-40 and distribution of its product on B cell tumors.

“…The lgh complex is on the murine 12th chromosome and contains the genes (Igh-C) that encode the constant (C) portion of/~, 6, 3', a, and e immunoglobulin (Ig) heavy chains together with J, D, and V region genes that encode their corresponding variable (V) regions (1)(2)(3). In addition to these Igh genes, there are several other linked genes, some of which may play a role in immune reactivity.…”