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Biomedical subjects

S Povey

Publications and source records attributed to S Povey.

At least 73 records · Page 4Linked to original sources
PubMed1993

Irradiation hybrids for human chromosome 11: characterization and use for generating region-specific markers in 11q14-q23.

High-dose irradiation hybrids containing fragments of chromosome 11 have been generated, with a view to isolating new region-specific markers. Forty-seven lines were scored for 34 markers: average retention was 6%. Fourteen lines contain markers from 11q14 to 11q23. One of these, Jo12, has 11q markers extending from tyrosinase (q14-q21) to PBGD (q23.3) plus one marker (TYRL, p11.2) from 11p. In situ hybridization using Alu PCR products from Jo12 as probe confirmed that the human DNA is derived from two regions, one in proximal 11p and a second, larger region in 11q23. Plasmid libraries of Alu PCR products from this and three other hybrids have been made. Six of eight recombinants identified as having single-copy inserts were mapped back to the regions of 11q22-q23 detected in the originating hybrid; only one mapped to a region not originally detected, and one was of hamster origin. These six clones provide new markers in 11q22-q23 that can be used directly for polymorphism studies. This series of hybrids is therefore a valuable resource for the rapid generation of markers from specific, defined regions of chromosome 11.

Animals↗
PubMed1993

Localization of genes encoding three distinct flavin-containing monooxygenases to human chromosome 1q.

We have used the polymerase chain reaction to map the gene encoding human flavin-containing monooxygenase (FMO) form II (N. Lomri, Q. Gu, and J. R. Cashman, 1992, Proc. Natl. Acad. Sci. USA 89: 1685-1689) to chromosome 1. We propose the designation FMO3 for this gene as it is the third FMO gene to be mapped. The two other human FMO genes identified to date, FMO1 and FMO2, are also located on chromosome 1 (C. Dolphin, E. A. Shephard, S. Povey, C. N. A. Palmer, D. M. Ziegler, R. Ayesh, R. L. Smith, and I. R. Phillips, 1991, J. Biol. Chem. 266: 12379-12385; C. Dolphin, E. A. Shephard, S. F. Povey, R. L. Smith, and I. R. Phillips, 1992, Biochem. J. 286: 261-267). The localization of FMO1, FMO2, and FMO3 has been refined to the long arm of chromosome 1. Analysis of human metaphase chromosomes by in situ hybridization confirmed the mapping of FMO1 and localized this gene more precisely to 1q23-q25.

Base Sequence↗
PubMed1993

Cloning of the human dopamine D5 receptor gene and identification of a highly polymorphic microsatellite for the DRD5 locus that shows tight linkage to the chromosome 4p reference marker RAF1P1.

We identified a cosmid clone with exact sequence homology to part of the human dopamine D5 receptor gene (DRD5) after screening a cosmid library with the human DRD1 gene. The dopamine D5 receptor was mapped to chromosome 4p15.1-p15.3 by in situ hybridization and using a somatic cell hybrid panel. We report here the further localization of the DRD5 gene following identification of a highly polymorphic dinucleotide repeat sequence in the cosmid clone. The microsatellite (D5(CT/GT/GA)n) had 12 alleles with a polymorphic information content value of 0.77. Linkage analysis in 39 CEPH pedigrees demonstrated tight linkage to the chromosome 4p reference marker RAF1P1 (Zmaxf 20.66 at theta f 0.05 and ZmaxM 16.57 at theta m 0.07).

Base Sequence↗
PubMed1993

Mapping of the human homologs of the murine paired-box-containing genes.

Mutations in paired-box-containing (Pax) genes have recently been found to be the primary lesions underlying human genetic disorders such as Waardenburg's Syndrome type 1 and mouse developmental mutants such as undulated (un), splotch (Sp), and small eye (Sey). In addition, PAX-6 is a strong candidate gene for aniridia in man. Eight independent Pax genes have been isolated in the mouse. All eight map to distinct regions of the mouse genome; they do not appear to be clustered in the same way as some groups of homeobox-containing genes. We have now mapped the human homologs of all eight of these genes; PAX genes are found on human Chromosomes (Chr) 1, 2, 7, 9, 10, 11, and 20.

Animals↗
PubMed1993

HNF4 and HNF1 as well as a panel of hepatic functions are extinguished and reexpressed in parallel in chromosomally reduced rat hepatoma-human fibroblast hybrids.

Rat hepatoma-human fibroblast hybrids of two independent lineages containing only 8-11 human chromosomes show pleiotropic extinction of thirteen out of fifteen hepatic functions examined. Reexpression of the entire group of functions most often occurs in a block, and except for one discordant subclone, correlates with loss of human chromosome 2. The extinguished cells and their reexpressing derivatives have been examined for the expression of seven liver-enriched transcription factors. C/EBP, LAP, DBP, HNF3, and vHNF1 expression are not systematically extinguished in parallel with the hepatic functions. However, HNF1 and HNF4 show a perfect correlation with phenotype: these factors are expressed only in the cells showing pleiotropic reexpression. Since recent evidence indicates that HNF4 controls HNF1 expression, it can be proposed that the HNF4 gene is the primary target of the pleiotropic extinguisher.

Albumins↗
PubMed1993

Description of a dinucleotide repeat polymorphism in the human elastin gene and its use to confirm assignment of the gene to chromosome 7.

Informative polymorphisms have been very difficult to detect in the elastin gene, and this has hampered the analysis of heritable connective tissue disorders, notably the Marfan syndrome. We have recently detected a dinucleotide repeat polymorphism in intron 17 of the human elastin gene consisting of 8 alleles with sizes between 161 and 175 bp. Analysis of 540 chromosomes from unrelated Caucasian individuals revealed a bimodal frequency distribution typical of (dC-dA)n.(dG-dT)n repeat polymorphisms, with allele frequencies ranging from 0.004 (161 bp) to 0.574 (163 bp). As the elastin gene was originally assigned to chromosome 2q31-ter and because more recent data have suggested an assignment to 7q11.1-21.1, we have genotyped a sub-set of the CEPH pedigrees and carried out pairwise linkage analysis with markers on chromosomes 7 and 2. Lod-scores of between +3.70 and +13.69 were obtained with markers spanning 7p13-q22.1, whilst negative lod-scores were observed with the chromosome 2 markers. Analysis of type II human ovarian teratomas placed the elastin gene within 11 cM of the centromere on chromosome 7. Additionally, we detected the dinucleotide repeat in human-rodent cell hybrids containing chromosome 7, but not those containing chromosome 2. These data confirm the assignment of elastin to chromosome 7 and provide a new, highly informative marker for the analysis of heritable disorders of connective tissue for which elastin is a candidate gene.

Animals↗
PubMed1993

Localization of the Tamm-Horsfall glycoprotein (uromodulin) gene to chromosome 16p12.3-16p13.11.

Mapping studies using a panel of 22 rodent-human somatic cell hybrids have helped to localize the Tamm-Horsfall glycoprotein (uromodulin) gene (UMOD), which has previously been reported to map to 16p13.11, to the region 16p12.3-qter. The combined results indicate that UMOD is located distal to D16S295 and proximal to D16S287 and in the region 16p12.3-16p13.11. Uromodulin is known to affect the formation of calcium-containing kidney stones, and this localization of UMOD will help in studies of families with autosomal forms of nephrolithiasis.

Animals↗
PubMed1993

Regional localization of the lactase-phlorizin hydrolase gene, LCT, to chromosome 2q21.

The gene LCT which codes for the intestinal disaccharidase lactase-phlorizin hydrolase has previously been mapped, using somatic cell hybrids and linkage analysis, using the CEPH families, to chromosome 2. We describe here the regional localization of LCT to chromosome 2q21 by polymerase chain reaction (PCR) analysis of somatic cell hybrids and in situ hybridization. LCT is closely linked to D2S44, with a lod score of 30.6 at theta = 0.10.

Animals↗
PubMed1993

Regional localization of the gene coding for the GM2 activator protein (GM2A) to chromosome 5q32-33 and confirmation of the assignment of GM2AP to chromosome 3.

The gene coding for the GM2 activator protein (GM2A) was previously mapped by us to chromosome 5 by an ELISA-based technique. Here we confirm this assignment using a PCR analysis of somatic cell hybrids and describe a regional localization to chromosome 5q32-33 by in situ hybridization. We also confirm the assignment of a pseudogene GM2AP to chromosome 3.

Animals↗
PubMed1993

Localization of the retinoid X receptor alpha gene (RXRA) to chromosome 9q34.

The retinoid X receptor alpha is one of a number of retinoic acid receptors which are members of the steroid/thyroid hormone superfamily. Localization of RXRA was achieved using the polymerase chain reaction on a panel of somatic cell hybrids. A cosmid clone was isolated using the RXRA PCR product, and this was used to further localize the gene by fluorescence in situ hybridization to chromosome 9q34 distal to the dopamine beta hydroxylase gene (DBH). This mapping position was confirmed by PCR on a panel of translocation hybrids.

Animals↗
PubMed1993

Mapping of RXRB to human chromosome 6p21.3.

Retinoid X Receptor beta (RXRB) is a member of the retinoid X receptor (RXR) family of nuclear receptors which are involved in mediating the effects of retinoic acid (RA). We have confirmed the localization of RXRB to chromosome 6 and we have mapped the gene to chromosome 6p21.3-p21.1 by PCR amplification of 5' untranslated sequence in panels of rodent-human somatic cell hybrids and to 6p21.3 by fluorescent in situ hybridization.

Animals↗
PubMed1993

ABO genotyping of complete hydatidiform moles.

It has been suggested that the ABO blood group of a patient and her partner influence the clinical outcome for patients having a pregnancy with a complete hydatidiform mole (CHM). Since CHM lack red blood cells, it has not previously been possible to type CHM serologically and investigate the relationship between the blood group of the CHM and that of the patient. In the present study we have demonstrated the feasibility of using molecular genotyping to determine the ABO genotype of CHM, the ABO genotype being consistent with the androgenetic origin of CHM in all cases. In the series of 48 cases of CHM, the requirement for chemotherapy was not significantly different in those patients with a CHM of like blood group compared with those with a CHM of unlike blood group.

ABO Blood-Group System↗
PubMed1993

An index marker map of chromosome 9 provides strong evidence for positive interference.

An index marker map of chromosome 9 has been constructed using the Centre d'Etude du Polymorphisme Humain reference pedigrees. The map comprises 26 markers, with a maximum intermarker interval of 13.1 cM and only two intervals > 10 cM. Placement of all but one marker into the map was achieved with > 10,000:1 odds. The sex-equal length is 151 cM, with male length of 121 cM and female length of 185 cM. The map extends to within 2%-3% of physical length at the telomeres, and its coverage therefore is expected to be within 20-30 cM of full map length. The markers are all of the GT/CA repeat type and have average heterozygosity .77, with a range of .60-.89. The map shows both marked contraction of genetic distance relative to physical distance in the pericentromeric region and expansion in the telomeric regions. Genotypic data were carefully examined for errors by using the crossover routine of the program DATAMAN. Five new mutations were observed among 17,316 meiotic events examined. There were two double-crossover events occurring within an interval of 0-10 cM, and another eight were observed within an interval of 10-20 cM. Many of these could be due to additional mutational events in which one parental allele converted to the other by either gene conversion or random strand slippage. When there was no correction for these possible mutational events, the number of crossovers displayed by the maternal and paternal chromosomes was significantly different (P < .001) from that predicted by the Poisson distribution, which would be expected in the absence of interference. In addition, the observed crossover distribution for paternally derived chromosomes was similar to that predicted from cytogenetic chiasma frequency observations. In all, the data strongly support the occurrence of strong positive interference on human chromosome 9 and suggest that flanking markers at an interval of < or = 20 cM are generally sufficient for disease gene inheritance predictions in presymptomatic genetic counseling by linkage analysis.

Base Sequence↗
PubMed1992

Cloning, primary sequence and chromosomal localization of human FMO2, a new member of the flavin-containing mono-oxygenase family.

We have previously reported the cloning of cDNAs for a flavin-containing mono-oxygenase (FMO) of man, designated FMO1 [Dolphin, Shephard, Povey, Palmer, Ziegler, Ayesh, Smith & Phillips (1991) J. Biol. Chem. 266, 12379-12385], that is the orthologue of pig and rabbit hepatic FMOs. We now describe the isolation and characterization of cDNA clones for a second human FMO, which we have designated FMO2. The polypeptide encoded by the cDNAs is 558 amino acid residues long, has a calculated M(r) of 63337, and contains putative FAD- and NADP-binding sites that align exactly with those described in other mammalian FMOs. Human FMO2 has 51-53% primary sequence identity with human FMO1, rabbit pulmonary FMO and rabbit liver FMO form 2, and thus represents a fourth, distinct, member of the mammalian FMO family. The corresponding mRNA is present in low abundance in adult human liver. Southern blot hybridization with single-exon probes demonstrated that human FMO2 and FMO1 are the products of single genes. The gene encoding FMO2 (designated FMO2) was mapped, by the polymerase chain reaction, to human chromosome 1, the same chromosome on which FMO1 is located.

Amino Acid Sequence↗