Assignment of a gene for human quinoid-dihydropteridine reductase (QDPR,EC 1.6.5.1) to chromosome 4

Summary An acrylamide gel electrophoretic procedure is described which allows the separation of human quinoid-dihydropteridine reductase (QDPR), EC 1.6.5.1) from the homologous enzyme expressed in established rodent cell lines. The human enzyme marker segregates exclusively with chromosome 4 in a series of well characterized man-mouse somatic cell hybrid clones from our clone bank. This observation supports the assignment of a structural gene for QDPR to human chromosome 4.     

Assignment of the gene (RLBP1) for cellular retinaldehyde-binding protein (CRALBP) to human chromosome 15q26 and mouse chromosome 7.

Cellular retinaldehyde-binding protein (CRALBP) has properties that suggest that it is involved in the visual process and, therefore, potentially with retinal diseases. A human cDNA probe has been used to map this gene to human chromosome 15q26 (somatic cell hybrids and in situ hybridization) and to mouse chromosome 7 by somatic cell hybrids.     

Assignment of the gene for acid beta-glucosidase to human chromosome 1.

The structural gene for human acid beta-glucosidase (GBA) has been assigned to chromosome 1 using somatic cell hybridization techniques for gene mapping. The human enzyme was detected in mouse RAG cell-human fibroblast cell hybrids by a sensitive double antibody immunoprecipitation assay using a mouse antihuman GBA antibody. No cross-reactivity between mouse beta-glucosidase and human GBA or neutral beta-glucosidase (GBN) was observed. Fifty-two primary, secondary, and tertiary manmouse hybrid lines, derived from three separate fusion experiments, were analyzed for human GBA and enzyme markers for the human chromosomes. Without exception, the presence of human GBA in these hybrid clones was correlated with the presence of human chromosome 1 or its enzymatic markers, phosphoglucomutase 1 (PGM1), and fumarate hydratase (FH). All other human chromosomes were eliminated by the independent segregation of GBA and their respective enzyme markers and/or chromosomes. Using a RAG X human fibroblast line with a mouse-human rearrangement of human chromosome 1, the locus for GBA was limited to the region 1p11 to 1qter.     

Assignment of the human 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible cytochrome P1-450 gene to chromosome 15.

The human 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible cytochrome P1-450 full-length cDNA has been recently isolated and sequenced [Jaiswal, A.K., Gonzalez, F.J. and Nebert, D.W. (1985) Science, in press]. A 1521-bp 5' DNA fragment representing almost all of the translating region was used to probe DNA from human, mouse, hamster, 53 human X mouse somatic cell hybrids, and 36 human X hamster somatic cell hybrids. These data indicate that the P1-450 gene resides on human chromosome 15. Knowledge of the chromosomal assignment of this gene should help in our understanding of its regulation and role in development and disease.     

Assignment of the human 3 beta-hydroxysteroid dehydrogenase gene (HSDB3) to the p13 band of chromosome 1

Three-beta-hydroxysteroid dehydrogenase (HSDB3) is the enzyme which catalyses the oxidative conversion of delta 5-3 beta-hydroxy steroids to the delta 4-3-keto configuration and is therefore involved in the biosynthesis of all classes of hormonal steroids, namely progesterone, glucocorticoids, mineralocorticoids, androgens, and estrogens. Deficiency of the enzyme is associated with congenital adrenal hyperplasia and is usually lethal in early life. Despite its crucial role, chromosome assignment of the gene for this enzyme has not been reported. Using in situ hybridization, we report that hybridization with labeled human HSDB3-specific cDNA yielded 27% of silver grains associated with chromosome 1 with a maximal concentration in the p13 band.     

Assignment of a gene (NEM1) for autosomal dominant nemaline myopathy to chromosome 1

Nemaline myopathy (NEM) is a neuromuscular disorder characterized by the presence, in skeletal muscle, of nemaline rods composed at least in part of alpha-actinin. A candidate gene and linkage approach was used to localize the gene (NEM1) for an autosomal dominant form (MIM 161800) in one large kindred with 10 living affected family members. Markers on chromosome 19 that were linked to the central core disease gene, a marker at the complement 3 locus, and a marker on chromosome 1 at the alpha-actinin locus exclude these three candidate genes. The family was fully informative for APOA2, which is localized to 1q21-q23. NEM1 was assigned to chromosome 1 by close linkage for APOA2, which is localized to 1q21-q23. NEM1 was assigned to chromosome 1 by close linkage to APOA2, with a lod score of 3.8 at a recombination fraction of 0. Recombinants with NGFB (1p13) and AT3 (1q23-25.1) indicate that NEM1 lies between 1p13 and 1q25.1. In total, 47 loci were investigated on chromosomes 1, 2, 4, 5, 7-11, 14, 16, 17, and 19, with no indications of significant linkage other than to markers on chromosome 1.     

Assignment of the human aminopeptidase N (peptidase E) gene to chromosome 15q13-qter

The gene for aminopeptidase N (EC 3.4.11.2) has been located on the human chromosome 15q13-qter using HindIII-cleaved DNA from a panel of hybrids between rodent and human cells. The Southern blots were probed by the 5'-EcoRI fragment of the recently cloned human aminopeptidase N cDNA.     

Assignment of a human serum glycoprotein SP-40,40 gene (CLI) to chromosome 8.

SP-40,40 is a serum glycoprotein consisting of two different subunits (alpha and beta) assembled into a dimer by disulfide bonds. Northern blot hybridization, using total RNA from several cell lines, showed that SP-40,40 is expressed in glioblastoma and testicular tumor cells, as well as hepatoma cells. Spot blot hybridization of flow-sorted human chromosomes, using a SP-40,40 cDNA fragment as a probe, localized the gene for SP-40,40 to human chromosome 8. This gene has been given the designation CLI, for complement lysis inhibitor, by the Human Gene Nomenclature Committee.     

Assignment of the gene for human spasmolytic protein (hSP/SML1) to chromosome 21

Summary A human cDNA corresponding to the porcine pancreatic spasmolytic protein (PSP) was isolated, and the recombinant clone was originally termed hSP for human spasmolytic protein. Later, the term SML1 for spasmolysin was suggested for the human gene. This protein shows a remarkable sequence homology to pS2, a protein coded by an estrogen-induced gene isolated from the breast carcinoma cell line MCF-7. Although, at the DNA level, the gene sequences pS2 and hSP/SML1 display insufficient homology for cross-hybridization, their expression in tumor cells occurs with remarkable coordination. The human pS2 gene sequence has been assigned to chromosome 21, and we have therefore attempted to map the hSP/SMLl gene by using cDNA and Southern blotting of genomic DNAs from a panel of human-rodent somatic cell hybrids carrying different complements of human chromosomes. Interestingly, the hSP/SMLl gene is also localized on chromosome 21.     

The structural gene for the mitochondrial aldehyde dehydrogenase maps to human chromosome 12

Summary A cloned 850 bp cDNA fragment corresponding to the 3-coding part of human ALDHI-mRNA was used as a probe for the chromosomal assignment of the ALDHI gene. Southern blot analysis of human-rodent somatic cell hybrids indicates that the human ALDHI gene resides on chromosome 12.Dedicated to Prof. Dr. H. Holzer on the occasion of his 65. birthday     

Assignment of a structural gene for beta-glucuronidase to human chromosome C7.

An electrophoretic technique was developed which allows the separation of human beta-glucuronidase (GUS EC 3.2.1.3.1) from the enzyme present in cultured murine. Chinese and Syrian hamster cells in one buffer system on Cellogel. Using this technique a number of independent human-mouse somatic cell hybrids have been analyzed for the segregation of GUS, other enzyme markers, and all human chromosomes. The results indicate that a structural gene for human beta-glucuronidase is located on chromosome C7.     

Assignment of human pepsinogen C (PGC) gene to chromosome 6

cDNA of rat pepsinogen C (PGC) hybridizes to, among others, a 3.2-kb band in Southern blot analysis of BamHI-cleaved human genomic DNA. This property was employed to localize the human PGC gene. Use of flow-sorted human chromosomes and 12 human x mouse somatic cell hybrid lines demonstrated that the gene is located on chromosome 6.