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T Mohandas

Publications and source records attributed to T Mohandas.

At least 19 recordsLinked to original sources
PubMed1996

Generation of sequence-tagged sites from Xp22.3 by isolating common Alu-PCR products of radiation hybrids retaining overlapping human X chromosome fragments.

Several human diseases have been mapped to Xp22.3 on the distal short arm of the human X chromosome, and many genes in this area have been found to be expressed from the inactive X chromosome. To facilitate physical mapping and characterization of this interesting region, we have constructed a battery of radiation hybrids containing human X chromosomal fragments, and isolated two hybrid clones A with overlapping fragments of Xp22.3. Alu-PCR on these hybrids and identification of sequences common to both hybrids allowed the isolation of six sequences-tagged sites (STSs) from Xp22.3. Five of the STSs were mapped+ to individual YACs comprising a recently constructed contig of this region. These novel STSs are useful markers for further physical characterization of this part of the genome.

Animals↗
PubMed1994

Assignment of the zeta-crystallin gene (CRYZ) to human chromosome 1p22-p31 and identification of restriction fragment length polymorphisms.

zeta-Crystallin is a lens protein that has been associated with autosomal dominant congenital cataracts in guinea pigs and thus is a candidate for human congenital cataracts. We have assigned the zeta-crystallin gene (CRYZ) to human chromosome 1 using a Southern panel of 17 human-mouse somatic cell hybrids and regionally localized it to 1p22-p31 by fluorescence in situ hybridization. Five restriction fragment length polymorphisms were identified by analyzing the DNA from 10 unrelated, unaffected individuals. Our results will permit evaluation of its role in human cataractogenesis.

Alleles↗
PubMed1994

Isolation and characterization of XE169, a novel human gene that escapes X-inactivation.

Overlapping cDNA clones for a novel human X-linked gene, XE169, have been isolated and characterized. The composite cDNA sequence comprises 5910 bp (or 5901 bp) plus a poly(A) tail, with a 531 bp 5' and 696 bp 3' untranslated regions. The sequence represents a full-length or near full-length cDNA for the gene since Northern blot analysis reveals only a single prominent band approximately 6 kb in size. Alternative splicing generates two distinct transcripts either containing or missing a stretch of nine nucleotides in the XE169 single large open reading frame, which in turn predict two XE169 protein isoforms composed of 1557 and 1560 amino acids, respectively. Southern hybridization analysis of a panel of human-mouse somatic cell hybrids containing various portions of translocated human X chromosomes has assigned XE169 to the proximal half of the X short arm between Xp21.1 and the centromere. XE169 is expressed in multiple human tissues tested and homologous sequences exist on the human Y chromosome and in the genomes of five other eutherian mammals examined. RT-PCR analysis of somatic cell hybrids containing either an active or an inactive human X chromosome on a rodent background demonstrated that XE169 escapes X-inactivation.

Alternative Splicing↗
PubMed1993

Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia.

We describe a novel cytoplasmic tyrosine kinase, termed BPK (B cell progenitor kinase), which is expressed in all stages of the B lineage and in myeloid cells. BPK has classic SH1, SH2, and SH3 domains, but lacks myristylation signals and a regulatory phosphorylation site corresponding to tyrosine 527 of c-src. BPK has a long, basic amino-terminal region upstream of the SH3 domain. BPK was evaluated as a candidate for human X-linked agammaglobulinemia (XLA), an inherited immunodeficiency characterized by a severe deficit of B and plasma cells and profound hypogammaglobulinemia. BPK mapped to within 100 kb of a probe defining the polymorphism most closely linked to XLA at DXS178. Reduction in or the absence of BPK mRNA, protein expression, and kinase activity was observed in XLA pre-B and B cell lines. BPK is likely the XLA gene and functions in pathways critical to B cell expansion.

Agammaglobulinemia↗
PubMed1993

Mapping of aldose reductase gene sequences to human chromosomes 1, 3, 7, 9, 11, and 13.

Aldose reductase (alditol:NAD(P)+ 1-oxidoreductase; EC 1.1.1.21) (AR) catalyzes the reduction of several aldehydes, including that of glucose, to the corresponding sugar alcohol. Using a complementary DNA clone encoding human AR, we mapped the gene sequences to human chromosomes 1, 3, 7, 9, 11, 13, 14, and 18 by somatic cell hybridization. By in situ hybridization analysis, sequences were localized to human chromosomes 1q32-q42, 3p12, 7q31-q35, 9q22, 11p14-p15, and 13q14-q21. As a putative functional AR gene has been mapped to chromosome 7 and a putative pseudogene to chromosome 3, the sequences on the other seven chromosomes may represent other active genes, non-aldose reductase homologous sequences, or pseudogenes.

Aldehyde Reductase↗
PubMed1993

The Ah receptor nuclear translocator gene (ARNT) is located on q21 of human chromosome 1 and on mouse chromosome 3 near Cf-3.

We have mapped the Ah receptor nuclear translocator (ARNT) gene to a conserved linkage group located on mouse chromosome 3 and human chromosome 1. EcoRI-digested DNA from a panel of 17 human x mouse somatic cell hybrids was probed with a cDNA fragment of the human ARNT gene. Six of the 17 independent mouse x human hybrids were positive for human bands. Human chromosome 1 showed complete cosegregation with the gene, whereas discordant segregation was observed for all other human chromosomes. The human gene was localized to 1q21 by using DNA from mouse x human hybrid clones that retain translocations involving human chromosome 1, by segregation analysis in nine informative CEPH families, and by in situ hybridization. The mouse homologue was mapped to mouse chromosome 3 using a panel of 16 hamster x mouse somatic cell hybrids. Six of 16 mouse x hamster hybrids were positive for mouse bands, showing complete concordance with mouse chromosome 3. The mouse Arnt gene was regionally mapped on chromosome 3, using linkage analysis in an interspecific backcross. The results indicate that the mouse gene resides about 40 cM from the centromere and about 10 cM proximal to Cf-3, the gene for tissue factor.

Animals↗
PubMed1993

Chromosomal organization of mammalian POU domain factors.

We present the chromosomal locations in mouse of eight new members of the mammalian POU domain family of transcriptional regulators. Chromosomal assignments were made for Brn-1 (Chr 1), Brn-2 (Chr 4), Brn-4 (Chr X), Brn-3.0 (Chr 14), Brn-3.1 (Chr 18), Brn-5.0 (Chr 15), Skn-1a/i (Chr 9), and Sprm-1 (Chr 13) in addition to the previously reported Pit-1 (Chr 16), Tst-1 (Chr 4), Oct-3/4 (Chr 17), Oct-1 (Chr 1), and Oct-2 (Chr 7) genes. Several conclusions have emerged from this analysis. First, among the most highly related family members (Brn-1, Brn-2, Brn-4, and Tst-1; Brn-3.0 and Brn-3.1; Oct-1, Oct-2, and Skn-1a/i) no chromosomal linkage is noted. Second, no clusters of genes are observed, irrespective of homology. Finally, no obvious linkages to genes for known additional regulatory factors with a specific origin of cell type are apparent. Thus, members of this large gene family, presumably arising as duplication events from common ancestral genes, apparently function in distinct chromosomal milieu under independent regulation. Some of these newly localized genes map in close proximity to existing mouse mutations.

Animals↗
PubMed1993

Mapping of multiple mouse loci related to the farnesyl pyrophosphate synthetase gene.

The prenyltransferases are a class of enzymes involved in the synthesis of sterol and nonsterol isoprene compounds. We report here the chromosomal mapping of nine loci in the mouse 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 nonsterol branches of the isoprene biosynthetic pathway. Mapping was performed with genomic DNA from a mouse-hamster somatic cell hybrid panel, and by linkage analysis with recombinant inbred strains and the progeny of an interspecific backcross. The mapped loci have been designated farnesyl pyrophosphate synthetase-like-1 (Fpsl-1) on mouse Chromosome (Chr) 3; Fpsl-2 on Chr 4; Fpsl-3, Fpsl-4, and Fpsl-5, dispersed on Chr 10; Fpsl-6 on Chr 12; Fpsl-7 on Chr 13; Fpsl-8 on Chr 17; and Fpsl-9 on Chr X. It is presently unclear which of these loci encode active prenyltransferases and which may correspond to pseudogenes. The strongly hybridizing loci provide convenient genetic markers for seven mouse chromosomes.

Animals↗
PubMed1993

Assignment of tear lipocalin gene to human chromosome 9q34-9qter.

We assigned the gene for tear lipocalin to the long arm of human chromosome 9. Polyadenylated RNA was extracted from lacrimal gland. The coding region for tear lipocalin was amplified, sequenced and used to probe a panel of somatic cell hybrid DNA by Southern blot analysis. Regional mapping was accomplished by probing a panel of subfragments of the indicated chromosome. Restriction of genomic DNA with EcoRI failed to reveal any bands corresponding to the human tear lipocalin gene in mouse-human hybrids all of which lack chromosome 9. Southern blot analysis of human-hamster hybrids demonstrated a human 5.6 kb TaqI restriction fragment that segregated to the q34-qter region of chromosome 9 and assigned the gene for tear lipocalin to this region. Structurally homologous proteins of the lipocalin family, human placental protein 14, human alpha 1 microglobulin, and human brain prostaglandin synthase, have been mapped to this region. We suggest that the gene for tear lipocalin is part of an important lipocalin superfamily gene cluster on chromosome 9 within band q34.

Animals↗
PubMed1992

Sequence analysis of a partial deletion of the human steroid sulfatase gene reveals 3 bp of homology at deletion breakpoints.

The majority of patients with steroid sulfatase deficiency have a deletion of the entire STS gene located on the distal short arm of the human X chromosome; however, two patients with partial gene deletions have been identified. We now report the sequences at the breakpoints of a deletion of the 3' end of the STS gene. The deletion starts within intron 7 of the gene and extends over 150 kb downstream toward the centromere. Analysis of sequences flanking the deletion breakpoints revealed 3 bp of homology. The 3' flanking sequence provides a new probe for isolation of YAC clones and for studying patients with deletions in this region of the X chromosome.

Arylsulfatases↗
PubMed1992

Assignment of the beta-subunit of rod photoreceptor cGMP phosphodiesterase gene PDEB (homolog of the mouse rd gene) to human chromosome 4p16.

The gene encoding the beta-subunit of rod photoreceptor cGMP phosphodiesterase (gene symbol PDEB, homolog of the mouse rd gene) is mapped to human chromosome 4 using somatic cell hybrids and further localized to the chromosome band 4p16 using in situ hybridization. A mutation in the mouse gene underlies the recessive trait of retinal degeneration in the rd mouse. Thus, the human homolog is a candidate for lesions causing retinal degeneration.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1992

Isolation of a new gene from the distal short arm of the human X chromosome that escapes X-inactivation.

A gene, designated GS1, was identified by its association with a CpG island approximately 100 kb telomeric to the steroid sulfatase (STS) locus on the distal short arm of the human X chromosome. Both cDNA and genomic clones of the GS1 gene have been isolated and characterized. The cDNA clone detects a 2.3 kb transcript in human placenta and fibroblasts, and may encode a protein of 214 amino acid residues. Although sequences homologous to GS1 cDNA are present on chromosomes 1, 20, X, and Y, the functional GS1 gene is on the X chromosome. The GS1 gene appears to be non-essential, as there are no obvious clinical differences between STS deficient patients with point mutations in the STS gene, and patients with a deletion of the STS and GS1 genes. The GS1 gene is expressed from mouse-human cell hybrids containing active or inactive human X chromosomes, indicating that it escapes X inactivation. Characterization of GS1 genomic clones revealed that the gene consists of 4 exons spanning over 105 kb, with its transcriptional direction opposite to that of the STS gene. The isolation and characterization of a new gene which escapes X inactivation from distal Xp is of interest as it adds to our understanding of the structural organization of the human X chromosome and may help in providing clues regarding the mechanism of X-inactivation.

Amino Acid Sequence↗
PubMed1991

The human Hb (mu) class glutathione S-transferases are encoded by a dispersed gene family.

The human glutathione S-transferases are products of a gene superfamily which consists of at least four gene families. The various glutathione S-transferase genes are located on different human chromosomes, and new gene(s) are still being added to the gene superfamily. We have characterized a cDNA in pGTH4 encoding human glutathione S-transferase subunit 4 (GST mu) and mapped its gene (or a homologous family member) on chromosome 1 at p31 by in situ hybridization. Genomic Southern analysis with the 3' noncoding region of the cDNA revealed at least four human DNA fragments with highly homologous sequences. Using a panel of DNAs from mouse-human somatic cell hybrids in genomic DNA hybridization we show that the Hb (or B) genes of human glutathione S-transferases are on three separate chromosomes: 1, 6, and 13. Therefore, the glutathione S-transferase B gene family, which encodes the Hb (mu) class subunits, is a dispersed gene family. The GST mu (psi) gene, whose expression is polymorphic in the human population, is probably located on chromosome 13. We propose that the GST mu (psi) gene was created by a transposition or recombination event during evolution. The null phenotype may have resulted from a lack of DNA transposition just as much as from the deletion of an inserted gene.

Animals↗
PubMed1991

Assignment of the gene for cyclic AMP-response element binding protein 2 (CREB2) to human chromosome 2q24.1-q32.

The regulatory element TGACGTCA is found upstream of a number of viral and cellular genes. This element has been demonstrated to mediate cyclic AMP induction of cellular genes and activation of viral genes. A group of closely related cellular genes known as cyclic AMP-response element binding proteins (CREB) or activating transcription factor (ATF) have been found to bind to this motif and mediate activation by cyclic AMP and the adenovirus E1A protein. One of these genes, CREB1, was previously mapped to human chromosome 2q32.3-q34. Southern blot analysis of genomic DNA from a panel of mouse-human somatic cell hybrids indicated that the CREB2 gene, another member of this family, also resides on human chromosome 2. In situ hybridization further regionalized this gene to 2q24.1-q32. Thus, the genes for CREB1 and CREB2 that have only limited DNA sequence homology map to a similar region of the long arm of chromosome 2, though whether they are part of a gene cluster is unclear.

Activating Transcription Factor 2↗