Subsets Of Human Chromosomes Research Articles

The dynamic nature and evolutionary history of subtelomeric and pericentromeric regions

The organization and evolution of the subtelomeric and pericentromeric regions of human chromosomes exhibit unique characteristics compared to other regions of the genome. As shown in Fig. 1 the functional elements of the centromere and telomere are comprised of highly repetitive DNA sequences, which are responsible for carrying out the main mechanistic duties of these two regions: chromosome segregation and end replication, respectively. The nature of the repeats in these two regions and their function have been reviewed separately and, therefore, will not be discussed in more detail here (Sullivan et al., 1996, 2001; McEachern et al., 2000; Henikoff et al., 2001). Adjacent to these functional element regions, the centromere and telomere regions share an interesting architecture as depicted in Fig. 1. For both pericentromeric and subtelomeric regions, blocks of recent genomic duplications form a zone of shared sequence homologies between certain subsets of human chromosomes. The dynamic nature and evolutionary history of these regions and the unique DNA sequence adjacent to them will be the focus of this review.

The gene for human complement C9 is on chromosome 5

By hybridizing a cloned cDNA coding for human complement factor C9 to hybrid cells containing subsets of human chromosomes on a rodent background, we have determined that the human gene for C9 is localized on chromosome 5.

The gene for the human putative apoE receptor is on chromosome 12 in the segment q13–14

We have previously described the cDNA coding for a new lipoprotein receptor that contains domains closely related to the ligand-binding domain of the LDL receptor. We have now investigated the localization of the gene for this new receptor by hybridization of the cDNA to panels of rodent cells containing subsets of human chromosomes and by in situ hybridization of the cDNA to chromosomes. The gene maps to 12q13–14, a known hot spot for chromosomal rearrangements in human neoplasia. Of particular interest is the frequent involvement of the 12q13–14 segment in clonal abnormalities in lipomas and myxoid liposarcomas, and it is possible that LRP may play a role in the pathogenesis of such tumors.

Localisation on human chromosome 19 of three genes for cell surface antigens defined by monoclonal antibodies

Expression of three distinct human cell surface antigens defined by monoclonal antibodies (mAbs) was examined in a series of rodent-human somatic cell hybrids retaining different subsets of human chromosomes. Cell surface reactivity with mAbs F8 and G253, detecting a 95 kilodalton (kD) glycoprotein (gp95); with mAbs F10 and A103, detecting a 50 kD glycoprotein (gp50); and with mAb S7 was found to cosegregate with human chromosome 19. However, differential antigen expression was observed with hybrids containing fragments of the 19 and hybrids constructed with different human cell types. Comparison of results from the serological typing with the presence of a number of chromosome 19 DNA markers in hybrid cells and cytogenetic analysis suggests that MSK20, the gene coding for the F10/A103 antigen gp50, is located in chromosome region 19pter----19p13.2. The genes coding for the F8/G253 antigen, gp95 (gene symbol MSK19) and the S7 antigen (MSK37) are located in region 19p13.2----19q13.2. Thus, the cell surface antigens described in this study may be used as selectable markers for specific portions of human chromosome 19.

Interferon-beta-related DNA on human chromosome 4.

A DNA subclone (pPE-4000) derived from the lambda B4 interferon-beta-related human genomic DNA clone was used as a probe in blot-hybridization experiments of DNA from a panel of human-rodent somatic cell hybrids containing overlapping subsets of human chromosomes. The DNA hybridization experiments showed that the lambda B4 IFN-beta locus is localized to human chromosome 4. A provisional regional assignment to 4q12-qter was also obtained. Thus available hybridization data implicate human chromosomes 2, 4, and 9 in the human IFN-beta system while the available biological data also implicated human chromosome 5.

Endothelial cell hybrids and the suspension of factor VIII related antigen expression.

Hybrid somatic cell clones have been generated by fusing human vascular endothelial cells in primary culture to cells of four rodent lines. Factor VIII related antigen (VIIIR:Ag) was clearly demonstrable in the cultured endothelial cells, even when they had been co-cultured with rodent cells. But in none of 14 hybrid clones was VIIIR:Ag detectable. Isozyme analyses for human chromosome markers show that all the assayed human chromosomes were represented among the hybrids, and that various subsets of human chromosomes have been deleted from individual hybrid clones. It may be concluded, therefore, either that VIIIR:Ag production depends on a particular combination of human chromosomes not represented in any of the hybrids, or that the rodent cells contribute some agent which intracellularly blocks VIIIR:Ag expression.