A novel imprinted gene, HYMAI, is located within an imprinted domain on human chromosome 6 containing ZAC

Transient neonatal diabetes mellitus (TNDM) is a rare disease characterized by intrauterine growth retardation, dehydration, and failure to thrive due to a lack of normal insulin secretion. This disease is associated with paternal uniparental disomy or paternal duplication of chromosome 6, suggesting that the causative gene(s) for TNDM is imprinted. Recently, Gardner et al. (1999, J. Med. Genet. 36: 192-196) proposed that a candidate gene for TNDM lies within chromosome 6q24.1-q24.3. To find human imprinted genes, we performed a database search for EST sequences that mapped to this region, followed by RT-PCR analysis using monochromosomal hybrid cells with a human chromosome 6 of defined parental origin. Here we report the identification of a novel imprinted gene, HYMAI. This gene exhibits differential DNA methylation between the two parental alleles at an adjacent CpG island and is expressed only from the paternal chromosome. A previously characterized imprinted gene, ZAC/LOT1, is located 70 kb downstream of HYMAI and is also expressed only from the paternal allele. In the pancreas, both genes are moderately expressed. HYMAI and ZAC/LOT1 are therefore candidate genes involved in TNDM. Furthermore, the human chromosome 6q24 region is syntenic to mouse chromosome 10 and represents a novel imprinted domain.     

The gene cluster for human U2 RNA is located on chromosome 17q21

The gene cluster for human U2 RNA has been mapped to chromosome 17q21 by in situ hybridization and hybridization analysis of DNA from mouse/human somatic cell hybrids.     

The terminal deoxynucleotidyltransferase gene is located on human chromosome 10 (10q23----q24) and on mouse chromosome 19

Terminal deoxynucleotidyltransferase (TdT) is a DNA polymerase expressed in immature lymphocytes of the thymus and bone marrow, as well as certain leukemic cells. Chromosomal assignment of the gene coding for human TdT was accomplished by in situ hybridization of a 3H-labeled cDNA probe to human chromosome preparations and by Southern blot analysis of somatic cell hybrid DNAs. The human TdT gene was mapped to the region q23----q24 of chromosome 10. Breaks at this site have been reported in different translocations in human leukemias. The mouse TdT gene was assigned to chromosome 19 by Southern blot analysis of mouse X Chinese hamster somatic cell hybrids. This result adds a fourth locus to the conserved syntenic group on mouse chromosome 19 and human chromosome 10.     

Induction of a human carbonyl reductase gene located on chromosome 21

Carbonyl reductase (EC 1.1.1.184) belongs to the group of enzymes called aldo-keto reductases. It is a NADPH-dependent cytosolic protein with specificity for many carbonyl compounds including the antitumor anthracycline antibiotics, daunorubicin and doxorubicin. Human carbonyl reductase was cloned from a breast cancer cell line (MCF-7). The cDNA clone contained 1219 base paires with an open reading frame corresponding to 277 amino acids encoding a protein of Mr 30,375. Southern analysis of genomic DNA digested with several restriction enzymes and analyzed by hybridization with a labeled cDNA probe indicated that carbonyl reductase is probably coded by a single gene and does not belong to a family of structurally similar enzymes. Southern analysis of 17 mouse/human somatic cell hybrids showed that carbonyl reductase is located on chromosome 21. Carbonyl reductase mRNA could be induced 3-4-fold in 24 h with 10 microM 2,(3)-t-butyl-4-hydroxyanisole (BHA), beta-naphthoflavone or Sudan 1.     

The structural gene for human coagulation factor X is located on chromosome 13q34

The gene coding for coagulation factor X was studied in a family segregating chromosomal abnormalities involving chromosomes 13 and 6. An individual monosomic for 13q34 was deficient in levels of clotting factors VII and X, while her brother, who is trisomic for 13q34, had elevated levels. DNA dosage studies with a cloned human factor X gene demonstrated that the low levels of factor X expression in the individual with the chromosome 13q34 deletion were due to the absence of one copy of the factor X structural gene. This confirms the assignment of the human gene coding for factor X to 13q34.     

The human mineralocorticoid receptor gene (MLR) is located on chromosome 4 at q31.2

The gene for the human mineralocorticoid receptor (MLR) was previously localized to chromosome 4. Here, we have localized this gene to 4q31.2 by in situ hybridization. This precise mapping of MLR will assist in the linkage analysis and genetic characterization of pseudohypoaldosteronism, an autosomal recessive disorder which likely results from a defect in the MLR gene.     

PHF2, a novel PHD finger gene located on human Chromosome 9q22

We have isolated and characterized a novel PHD finger gene, PHF2, which maps to human Chromosome (Chr) 9q22 close to D9S196. Its mouse homolog was also characterized and mapped to the syntenic region on mouse Chr 13. The predicted human and mouse proteins are 98% identical and contain a PHD finger domain, eight possible nuclear localization signals, two potential PEST sequences, and a novel conserved hydrophobic domain. Northern analysis shows widespread expression of PHF2 in adult tissues, while in situ hybridization on mouse embryos reveals staining in the neural tube and dorsal root ganglia significantly above a ubiquitous low level expression signal. From its expression pattern and its chromosomal localization, PHF2 is a candidate gene for hereditary sensory neuropathy type I, HSN1. Received: 9 July 1998 / Accepted: 16 October 1998     

The mouse immune interferon receptor gene is located on chromosome 10

When mouse L cells are incubated with 32P-labeled recombinant murine immune interferon ( [32P]Mu-IFN-gamma) and subsequently cross-linked with disuccinimidyl suberate, a major complex with an apparent molecular mass of 95,000-125,000 daltons can be visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The complex was not formed when the binding was performed in the presence of excess unlabeled Mu-IFN-gamma or when Chinese hamster ovary cells were used. This complex therefore represents the Mu-IFN-gamma receptor (or its interferon-binding subunit). The chromosomal location of the Mu-IFN-gamma receptor (or the binding subunit of the receptor) gene, termed Ifgr, was identified by performing the binding and cross-linking reactions on a series of mouse-hamster somatic cell hybrids with different subsets of mouse chromosomes. The presence of mouse chromosome 10 was shown to be necessary and sufficient for the formation of the cross-linked complex. Thus, the gene coding for the binding subunit of the Mu-IFN-gamma receptor was localized to mouse chromosome 10. The presence of this chromosome in the hybrid cells was not sufficient, however, to confer antiviral resistance to the hybrids when they were treated with Mu-IFN-gamma and challenged with encephalomyocarditis virus.     

The gene encoding human vimentin is located on the short arm of chromosome 10.

The gene for vimentin, an intermediate-filament protein, is growth regulated. We used Southern blot analysis and in situ chromosome hybridization to determine the location of the human vimentin gene. Our results show that there is only one copy of the vimentin gene and that it is located on the short arm of chromosome 10 (10pter-10q23) close to the interleukin-2 receptor gene, which is also growth regulated. In situ hybridization studies suggest that the most likely location of the vimentin gene is 10p13. Sequence similarities and homologies of human vimentin to other genes are presented.     

The primary erythermalgia-susceptibility gene is located on chromosome 2q31-32

Primary erythermalgia is a rare disorder characterized by recurrent attacks of red, warm, and painful hands and/or feet. The symptoms are generally refractory to treatment and persist throughout life. Five kindreds with multiple cases of primary erythermalgia were identified, and the largest was subjected to a genomewide search. We detected strong evidence for linkage of the primary erythermalgia locus to markers from chromosome 2q. The highest LOD score (Z) was obtained with D2S2330 (Z(max) = 6.51). Analysis of recombination events identified D2S2370 and D2S1776 as flanking markers, on chromosome 2q31-32. This defines a critical interval of 7.94 cM that harbors the primary erythermalgia gene. Affected members within the additional families also shared a common haplotype on chromosome 2q31-32, supporting our linkage results. Identification of the primary erythermalgia gene will allow a better clinical classification of this pleomorphic group of disorders.     

The human lactase-phlorizin hydrolase gene is located on chromosome 2

The lactase-phlorizin hydrolase gene was assigned to chromosome 2 by analysis of Southern blots of DNA from a panel of human-rodent cell hybrids containing characteristic sets of human chromosomes. The hybridization probe used was a recently isolated cDNA clone of the human lactase-phlorizin hydrolase gene.     

The human gene encoding acetylcholinesterase is located on the long arm of chromosome 7.

Acetylcholinesterase (AChE) is a secreted enzyme essential for regulating cholinergic neurotransmission at neuronal and neuromuscular synapses. In view of the altered expression of AChE in some central neurological and neuromuscular disorders with a probable genetic basis, we have identified the chromosomal location of the gene encoding AChE. Chromosomal in situ suppression hybridization analysis revealed a single gene to be at 7q22, a result which was confirmed by PCR analysis of genomic DNA from a human/hamster somatic cell hybrid containing a single human chromosome 7. The AChE gene thus maps to the same region in which frequent nonrandom chromosome 7 deletions occur in leukemias of myeloid cell precursors known to express the enzyme during normal differentiation.     

The human apolipoprotein A-II gene is located on chromosome 1

Apolipoprotein (apo) A-II is a major constituent of high density lipoproteins (HDL). The gene for apoA-II has been localized to the p21----qter region of chromosome 1 in man by Southern blot hybridization analysis of DNA from human-mouse cell hybrids using a cloned human apoA-II cDNA probe. The regional assignment was established using two hybrids carrying a reciprocal translocation involving chromosomes 1 and 2. Comparison with previously established gene loci on chromosomes 1 suggests that apoA-II may reside in a conserved linkage group with renin and peptidase C. On the other hand, apoA-II is not linked to the apoA-I gene, which has been localized previously to chromosome 11.     

A gene that regulates DNA replication in response to DNA damage is located on human chromosome 4q.

Inhibition of replicative DNA synthesis following gamma-irradiation is observed in eukaryotic cells but is defective in cells derived from patients with the cancer-prone inherited disorder ataxia-telangiectasia (A-T) and in A-T-like Chinese hamster cell mutants. Chinese hamster cells show a less pronounced inhibition of DNA synthesis after gamma-irradiation when compared to irradiated human HeLa or mouse A9 cells. Therefore, to identify new human genes involved in the regulation of DNA replication in response to ionizing radiation in mammalian cells, single human chromosomes were introduced into Chinese hamster cells by microcell-mediated chromosome transfer. It is found that a new gene on human chromosome 4q inhibits DNA synthesis following gamma- and UV irradiation in hamster cells. However, this delay of DNA replication did not improve cell survival or the level of chromosomal aberrations induced by X-rays, indicating that the lack of the inhibition of DNA synthesis after X-irradiation is not a prerequisite for the X-ray sensitivity and chromosomal instability, which is observed in A-T and A-T-like hamster cells.     

The mouse Cebp gene encoding a DNA-binding protein is polymorphic and is located on chromosome 7

The mouse gene Cebp, encoding the DNA-binding protein C/EBP, has been localized to the proximal region of chromosome 7 by determining the strain distribution patterns of a restriction fragment length polymorphism among the BXD and AKXL recombinant inbred mouse lines.