Assignment of the human gene for cholesteryl ester transfer protein to chromosome 16q12-16q21

We have used a cDNA probe for human cholesteryl ester transfer protein (CETP) to determine the chromosomal location for the human gene. Southern blot analysis of DNA from 17 independent mouse-human somatic cell hybrids demonstrated the presence of the gene for human CETP on chromosome 16. Regional mapping of the gene by in situ hybridization was consistent with these results and indicated that the gene resides in the 16q12-21 region of the chromosome. These findings provide an additional polymorphic marker for chromosome 16, as several relatively common restriction fragment length polymorphisms of the gene have previously been reported, and they have significance for studies directed at the identification of genetic factors affecting plasma lipoprotein metabolism and atherosclerosis.     

The poliovirus sensitivity (PVS) gene is on chromosome 19q12----q13.2

Sensitivity to nonmodified poliovirus infection is an autosomal dominant trait, specific to primates. The gene for poliovirus sensitivity (PVS) is encoded on human chromosome 19. In order to sublocalize the PVS gene, we infected rodent-human hybrid cell lines that divide human chromosome 19 into four regions with poliovirus 1 and/or 3. When infected, these hybrid cell lines showed the typical cytopathic effect of poliovirus infection only if they contained 19q12----q13.2 as the smallest region of overlap. Appropriate negative and positive controls were used. PVS may be of relevance to myotonic dystrophy (DM) and the inherited motor neuron diseases: to DM because it localizes to the same region of chromosome 19 and to the inherited motor neuron diseases because it encodes a cell-surface receptor expressed on motor neurons.     

The cell surface antigen locus, MIC2X, escapes X-inactivation

Recently, it was shown that the cell surface antigen defined by the monoclonal antibody 12E7 is expressed by both the human X and Y chromosomes; the gene loci on the X and Y chromosomes are referred to as MIC2X and MIC2Y, respectively. It was also shown that MIC2X is located in the region Xp22.3----Xpter and MIC2Y is in the region Ypter-Yq1.1. Here, we show that MIC2X escapes X-inactivation on structurally normal and abnormal inactive human X chromosomes.     

Human pepsinogen C (progastricsin). Isolation of cDNA clones, localization to chromosome 6, and sequence homology with pepsinogen A

The entire pepsinogen C (PGC) coding sequence was determined by analysis of a series of five overlapping cDNA clones identified in a library constructed from human gastric mucosa poly(A+) RNA. A partial cDNA clone was initially identified using a 256-fold degenerate oligonucleotide probe for amino acid residues 4-12 of pepsin C, and subsequently 4 additional clones were identified upon rescreening with a probe complementary to the 5' region of the original cDNA clone. Northern analysis of gastric mucosa poly(A+) RNA with a PGC cDNA probe revealed an mRNA 1.5-kilobase species that was indistinguishable from that detected with a human pepsinogen A (PGA) cDNA probe. In contrast, the PGC and PGA cDNA probes detected distinct genomic restriction fragments indicating there was no detectable cross-hybridization under high stringency conditions. The PGC gene was localized to human chromosome 6 by analysis of a panel of human x mouse somatic cell hybrids. The regions containing the active site aspartyl groups of PGC are conserved in relationship to several other aspartic proteinases. We propose that the absence of detectable immunologic cross-reactivity between the two groups of human pepsinogens, A and C, results from divergent evolution of sequences located on the surface of the zymogens in contrast to the strongly conserved active site regions located within the binding cleft of the enzymes that are inaccessible for antigenic recognition.     

Human monoamine oxidase A and B genes map to xp11.23 and are deleted in a patient with norrie disease

Monoamine oxidase A and B (MAO A and B) are the central enzymes that catalyze oxidative deamination of biogenic amines throughout the body. The regional locations of genes encoding MAO A and B on the X chromosome were determined by using full-length cDNA clones for human MAO A and B, respectively. Using somatic cell hybrids, in situ hybridization, and field-inversion gel electrophoresis as well as deletion mapping in a patient with Norrie disease, we concluded that these two genes are close to each other and to the DXS7 locus (Xp11.3).     

The apolipoprotein(a) gene resides on human chromosome 6q26–27, in close proximity to the homologous gene for plasminogen

Summary Apolipoprotein(a) [apo(a)], the glycoprotein associated with the lipoprotein(a) [Lp(a)] subfraction of plasma lipoproteins, has been shown to exhibit heritable molecular weight isoforms ranging from 400–700 kDa. Increased serum concentrations of Lp(a) correlate positively with the risk of atherosclerosis. Variations in Lp(a) plasma levels among individuals are inherited as a codominant quantitative trait. As part of an effect to define the basis of these variations and further clarify the expression of the protein, we have determined the chromosomal location of the human apo(a) gene. Blot hybridization analysis of DNA from a panel of mouse-human somatic cell hybrids with an apo(a) cDNA probe revealed a complex pattern of bands, all of which segregated with chromosome 6. In situ hybridization yielded a single peak of grain density located on chromosome 6q26–27. Apo(a) cDNA sequences exhibit striking homology to those of the plasma protease plasminogen, and, therefore, we have reexamined the chromosome assignment of the plasminogen gene. We conclude that both the apo(a) and plasminogen genes reside on human chromosome 6q22–27, consistent with a gene duplication mechanism for their evolutionary origin. The results are of significance for the genetic control of apo(a) expression and genetic influences predisposing to atherosclerosis.     

Dispersed family of human genes with sequence similarity to farnesyl pyrophosphate synthetase

Prenyltransferases are a group of enzymes involved in the biosynthesis of both sterol and nonsterol isoprene compounds. Somatic cell hybrid studies and in situ hybridization show that the human genome contains five distinct loci that hybridize to the cDNA for the enzyme farnesyl pyrophosphate synthetase (FPS), a prenyltransferase that catalyzes the synthesis of an intermediate common to both the sterol and the nonsterol branches of the isoprene biosynthetic pathway. The loci identified in this report may correspond to unique prenyltransferase genes related to FPS or to pseudogenes. The loci mapped have been identified as farnesyl pyrophosphate synthetase-"like"-1 (FPSL-1) on chromosome 1q24-31, FPSL-2 on chromosome 7, FPSL-3 on chromosome 14, FPSL-4 on chromosome 15q14-q21, and FPSL-5 on chromosome Xq21-22. Multiple copies of sequences similar to those of FPS are also present in both the mouse and the rat.