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R S Sparkes

Publications and source records attributed to R S Sparkes.

At least 55 records · Page 3Linked to original sources
PubMed1993

Chromosomal localization of the human vesicular amine transporter genes.

The physiologic and behavioral effects of pharmacologic agents that interfere with the transport of monoamine neurotransmitters into vesicles suggest that vesicular amine transport may contribute to human neuropsychiatric disease. To determine whether an alteration in the genes that encode vesicular amine transport contributes to the inherited component of these disorders, we have isolated a human cDNA for the brain transporter and localized the human vesicular amine transporter genes. The human brain synaptic vesicle amine transporter (SVAT) shows unexpected conservation with rat SVAT in the regions that diverge extensively between rat SVAT and the rat adrenal chromaffin granule amine transporter (CGAT). Using the cloned sequences with a panel of mouse-human hybrids and in situ hybridization for regional localization, the adrenal CGAT gene (or VAT1) maps to human chromosome 8p21.3 and the brain SVAT gene (or VAT2) maps to chromosome 10q25. Both of these sites occur very close to if not within previously described deletions that produce severe but viable phenotypes.

Adrenal Glands↗
PubMed1993

Localization of the transcription factor SP1 gene to human chromosome 12q12-->q13.2.

The cellular transcription factor SP1 binds to critical regulatory elements in a variety of cellular and viral promoters. The gene encoding the approximately 100-kDa SP1 protein contains zinc finger DNA-binding domains and glutamine-activation domains. Since SP1 is involved in the regulation of a variety of cellular genes, we wished to determine its chromosomal localization. Southern blot analysis of genomic DNA from a panel of mouse x human somatic cell hybrids indicated that SP1 was localized to chromosome 12. In situ hybridization allowed the localization of the gene encoding SP1 to human chromosome 12q12-->q13.2, with 12q13.1 being the most probable location.

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↗
PubMed1993

Linkage analysis of Norrie disease with an X-chromosomal ornithine aminotransferase locus.

Norrie disease is a rare disease of newborn males caused by prenatal or perinatal retinal detachment, which may be associated with mental retardation, psychosis, and/or hearing loss. DXS7 (L1.28) and MAO A and B loci have been linked to the ND locus on the short arm of the X chromosome. Sequences homologous to OAT also have been mapped to the short arm of the X chromosome. We performed linkage analyses between the ND locus and one of the OAT-like clusters of sequences on the X chromosome (OATL1), using a ScaI RFLP in a ND family, and increased the previously calculated lod score (z) to over 3 (3.38; theta = 0.05). Similarly, we calculated a lod score of 4.06 (theta = 0.01) between the OATL1 and DXS7 loci. Alone, the OATL1 ScaI RFLP system is expected to be informative in 48% of females. If this system were used in combination with the DXS7 TaqI polymorphism, 71% of females would be informative for at least one of the markers and 21% would be informative for both. Because the OATL1 ScaI RFLP is a relatively common polymorphism, this system should be useful for the identification of ND carriers and affected male fetuses and newborns.

DNA↗
PubMed1992

Cloning and chromosomal mapping of a human immunodeficiency virus 1 "TATA" element modulatory factor.

A critical regulatory element in many promoters transcribed by RNA polymerase II is the "TATA" box, which is located 25-30 nucleotides upstream of the transcription initiation site. TFIID is a biochemically defined HeLa cell nuclear fraction containing a transcription factor activity that binds specifically to the TATA box and is critical in determining both basal and regulated promoter activity. Recently, the gene for a TATA-binding protein was cloned and found to bind to various TATA elements and to substitute for TFIID in stimulating basal gene expression in in vitro transcription systems. However, it is possible that additional cellular factors can bind to the TATA element and influence the level of gene expression. By using lambda gt11 expression cloning with oligonucleotides corresponding to the human immunodeficiency virus 1 TATA element, we report the identification of a cellular protein with a calculated molecular mass of 123 kDa that we designate TATA element modulatory factor (TMF). TMF binds to the human immunodeficiency virus 1 TATA element in gel-retardation assays and inhibits activation of the viral long terminal repeat by the TATA-binding protein in in vitro transcription assays. TMF contains leucine-zipper amino acid motifs and exhibits homology in its DNA binding domain with the phage-encoded DNA binding protein Ner. Chromosomal mapping localizes the TMF gene to human chromosome 3p12-p21, which is a site of frequent rearrangements in lung and renal carcinomas. Thus, TMF is a transcription factor that likely regulates the expression of both viral and cellular genes.

Amino Acid Sequence↗
PubMed1992

Startle disease, or hyperekplexia: response to clonazepam and assignment of the gene (STHE) to chromosome 5q by linkage analysis.

Familial startle disease (also known as hyperekplexia and congenital "stiff-man" syndrome) is an autosomal dominant disorder characterized by an exaggerated startle reaction of sudden, unexpected auditory or tactile stimuli; affected neonates also have severe and occasionally fatal hypertonia. We recently encountered a large, five-generation family with startle disease, and treated 16 patients (including 1 neonate) with clonazepam; all experienced dramatic and sustained improvement. We performed systematic linkage analysis in this family, and found tight linkage between the disease locus and a polymorphic genetic marker locus (colony-stimulating factor receptor, or CSF1R) that has been physically mapped to chromosome 5q33-q35. The maximum odds ratio favoring linkage over nonlinkage is greater than 10,000,000:1 (lod score, 7.10) at 3% recombination. Several genes encoding neurotransmitter receptor components have been physically mapped to the subtelomeric region of chromosome 5q, and are thus candidates for the startle disease gene. The availability of additional large pedigrees with startle disease should facilitate identification and characterization of the gene for this disorder.

Adult↗
PubMed1992

Localisation of the gene for Norrie disease to between DXS7 and DXS426 on Xp.

A highly informative microsatellite marker, DXS426, which maps proximal to DXS7 in the interval Xp11.4-Xp11.23, has been used to refine further the localisation of the gene for Norrie disease (NDP). The results from a multiply informative crossover localize the NDP gene proximal to DXS7. In conjunction with information from 2 NDP patients who have a deletion for DXS7 but not for DSX426, our data indicate that the NDP gene lies between DXS7 and DXS426 on proximal Xp.

Base Sequence↗
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

Mapping of the gene for the cardiac sarcolemmal Na(+)-Ca2+ exchanger to human chromosome 2p21-p23.

The cardiac sarcolemmal Na(+)-Ca2+ exchanger is the primary mechanism for extrusion of calcium from the cardiac myocyte and therefore is important in regulating cardiac contractility. As part of an effort to determine whether the exchanger is associated with any genetic disorders of the heart or blood pressure, we have assigned the exchanger gene (designated NCX1) to human chromosome 2p21-p23 by analysis of a panel of mouse-human somatic cell hybrids and by in situ hybridization.

Animals↗
PubMed1992

The L-isoaspartyl/D-aspartyl protein methyltransferase gene (PCMT1) maps to human chromosome 6q22.3-6q24 and the syntenic region of mouse chromosome 10.

We have mapped the genes for the human and mouse L-isoaspartyl/D-aspartyl protein carboxyl methyltransferase (EC 2.1.1.77) using cDNA probes. We determined that the human gene is present in chromosome 6 by Southern blot analysis of DNA from a panel of mouse-human somatic cell hybrids. In situ hybridization studies allowed us to confirm this identification and further localize the human gene (PCMT1) to the 6q22.3-6q24 region. By analyzing the presence of an EcoRI polymorphism in DNA from backcrosses of C57BL/6J and Mus spretus strains of mice, we localized the mouse gene (Pcmt-1) to chromosome 10, at a position 8.2 +/- 3.5 cM proximal to the Myb locus. This region of the mouse chromosome is homologous to the human 6q24 region.

Animals↗
PubMed1992

Cloning of the human cholesterol 7 alpha-hydroxylase gene (CYP7) and localization to chromosome 8q11-q12.

Cholesterol 7 alpha-hydroxylase (7 alpha-hydroxylase) is a microsomal cytochrome P450 that catalyzes the first step in bile acid synthesis. In this paper, we describe the cloning, characterization, and chromosomal mapping of the human 7 alpha-hydroxylase gene (CYP7). The gene spans 10 kb and contains six exons and five introns. The exon-intron boundaries are completely conserved between the human and rat genes. Sequencing of the 5' flanking region revealed consensus recognition sequences for a number of liver-specific transcription factors. The human CYP7 gene was mapped to chromosome 8q11-q12 using both mouse-human somatic cell hybrids and in situ chromosomal hybridization studies. A total of four single-stranded conformation-dependent DNA polymorphisms and an Alu sequence-related polymorphism were identified. Of the individuals analyzed, 80% were heterozygous for at least one of these five polymorphisms. The localization and characterization of the human 7 alpha-hydroxylase gene, as well as the identification of polymorphisms, provide the molecular tools necessary to investigate the role of this gene in disorders of cholesterol and bile acid metabolism.

Amino Acid Sequence↗
PubMed1992

Genetic marker associations with proliferative retinopathy in persons diagnosed with diabetes before 30 yr of age.

It has been suggested that HLA-DR4 is a marker of genetic predisposition to proliferative retinopathy. To investigate this relationship and potential associations between other polymorphic genes and proliferative retinopathy, a sample (n = 428) of participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy was selected for typing for HLA-A, -B, -C, and -DR and a panel of other polymorphic genes. The presence of proliferative retinopathy was determined from grading of stereoscopic color fundus photographs taken at 2 examinations, 4 yr apart. In logistic regression models with repeated measures, persons with HLA-DR4 who were negative for DR3 were five times more likely to have proliferative retinopathy than those negative for both antigens after adjusting for other potential risk factors (Odds ratio = 5.43, 95% Confidence Interval (Cl) = 1.04, 28.30). HLA-C2, AK-2, and MNSs-S also were associated positively with proliferative retinopathy, and HLA-DR8 was associated inversely with this complication of diabetes in each case before adjusting for the number of comparisons. These data suggest that the genetically determined immunopathic mechanisms leading to diabetes, and in linkage disequilibrium with DR4, may independently contribute to the development of proliferative retinopathy.

Adolescent↗
PubMed1991

Monozygotic twins of discordant sex both with 45,X/46,X,idic(Y) mosaicism.

A female twin with short stature, unusual facial appearance, widely spaced nipples, and coarctation of the aorta was found to have a peripheral blood lymphocyte karyotype of 45,X(43%)/46,X,idic(Y)(p11). Her twin brother, also short with similar facial appearance, had the same mosaicism (40% 45,X). Cultured skin fibroblast studies showed discrepant karyotypes of 45,X (100%) in the girl and 45,X (78%)/46,X,idic(Y)(p11) in the boy. The mother and the father had normal chromosomes. Comparison of 27 biochemical markers yielded a likelihood of monozygosity of 0.9977. This report documents the occurrence of discordant phenotypic sex in monozygotic twins, involving gonadal dysgenesis with an abnormal dicentric Y, which presumably occurred de novo, followed by anaphase lag probably before the occurrence of twinning. Unequal distribution of the two resultant cell lines in various tissues of each twin could account for the development of the very different phenotypes, apparently normal boy and Ullrich-Turner girl.

Dermatoglyphics↗
PubMed1991

The cytogenetics of ataxia telangiectasia.

Ataxia-telangiectasia (AT) is a heterogeneous autosomal recessive disorder marked by cerebellar ataxia, oculocutaneous telangiectases, hypersensitivity to ionizing radiation, immunodeficiency, and cancer susceptibility. AT is also a spontaneous chromosomal breakage syndrome, notable for tissue-specific cytogenetic changes and telomeric fusions. Molecular characterization of rearrangements specific to T-lymphocytes suggests that a DNA repair/processing defect is potentially responsible for the diverse array of chromosomal abnormalities observed in a variety of AT cell types.

Ataxia Telangiectasia↗
PubMed1991

A U6 snRNA gene with an internal promoter is juxtaposed to an snRNP protein sequence within an intron of a human G protein gene.

A complex locus on human chromosome 1 brings together sequences homologous to a G protein and two components of the RNA processing machinery of eukaryotic cells. Specifically, the seventh intron of the human Gi3 alpha gene contains a fusion of a partial snRNP E protein pseudogene to a variant U6 snRNA gene. The novel U6 sequence contains nine point mutations and a one nucleotide deletion relative to the major U6 genes from humans. Unlike all other vertebrate U6 genes characterized to date, the variant U6 gene is efficiently transcribed by RNA polymerase III even in the absence of all natural flanking sequences. The union of elements from the signal transduction pathway and the RNA processing machinery suggests the possibility of functional interplay.

Amino Acid Sequence↗