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S Povey

Publications and source records attributed to S Povey.

At least 163 records · Page 9Linked to original sources
PubMed1987

Evidence that the gene for tuberous sclerosis is on chromosome 9.

Linkage analysis was undertaken in nineteen families with tuberous sclerosis by use of 26 polymorphic markers. All affected members fulfilled strict diagnostic criteria and unaffected members were rigorously investigated to confirm their status. Maximum lod scores were 1.20 for adenylate kinase 1 (AK1) at zero recombination and 3.85 for the ABO blood group at zero recombination (confidence limits 0-0.10). These findings support the assignment of the gene for tuberous sclerosis to the distal long arm of chromosome 9.

Adenylate Kinase↗
PubMed1987

Locus determining the human sperm-specific lactate dehydrogenase, LDHC, is syntenic with LDHA.

From the data presented in this report, the human LDHC gene locus is assigned to chromosome 11. Three genes determine lactate dehydrogenase (LDH) in man. LDHA and LDHB are expressed in most somatic tissues, while expression of LDHC is confined to the germinal epithelium of the testes. A human LDHC cDNA clone was used as a probe to analyze genomic DNA from rodent/human somatic cell hybrids. The pattern of bands with LDHC hybridization is easily distinguished from the pattern detected by LDHA hybridization, and the LDHC probe is specific for testis mRNA. The structural gene LDHA has been previously assigned to human chromosome 11, while LDHB maps to chromosome 12. Studies of pigeon LDH have shown tight linkage between LDHB and LDHC leading to the expectation that these genes would be syntenic in man. However, the data presented in this paper show conclusively that LDHC is syntenic with LDHA on human chromosome 11. The terminology for LDH genes LDHA, LDHB, and LDHC is equivalent to Ldh1, Ldh2, and Ldh3, respectively.

Animals↗
PubMed1987

Loss of heterozygosity in hypotriploid cell cultures from testicular tumours.

We have established cell lines with a hypotriploid chromosome number from four testicular tumours. Each line had at least one Y chromosome and most of the informative centrosome and enzyme markers were heterozygous implying that the tumours originated from germ cells before the first meiotic division. The small metacentric marker chromosome (i12p), specific for testicular tumours, was present in all tumour cell lines and up to three copies were found in some lines. Rearrangements of chromosome 1 and 11 were each found in three out of four tumours. The rearrangements of chromosome 1 all resulted in duplication of 1q and deletion of short-arm material from the same chromosome giving loss of heterozygosity for enzyme markers on 1p. Loss of satellite material from chromosome 13 and the centromere region of chromosome 9 were found in single cases. This study shows that even where the chromosome number of tumour cells is near triploid, regions of the genome can be deleted. The chromosomes most frequently involved in rearrangements, 1, 11, and 12 all contain sites of ras oncogenes and it is suggested that loss of normal alleles could result in homozygosity for mutant oncogenes which may play a part in tumour progression.

Cell Line↗
PubMed1987

Isolation of a cDNA probe for a human jejunal brush-border hydrolase, sucrase-isomaltase, and assignment of the gene locus to chromosome 3.

We report the nucleotide sequence and derived amino acid sequence of a cDNA clone encoding most of the N-terminal, isomaltase region of human sucrase-isomaltase (SI). A plasmid containing this cDNA, pS12, identifies a 6-kb mRNA found in human jejunum and the human colon carcinoma cell line Caco-2. This human SI cDNA shows extensive overall homology with recently published rabbit SI cDNA. Using pS12 to probe DNA from a panel of somatic cell hybrids, we have assigned the gene encoding human SI to chromosome 3.

Amino Acid Sequence↗
PubMed1987

Species- and tissue-specific expression of human alpha 1-antitrypsin in transgenic mice.

alpha 1-Antitrypsin (alpha 1AT) is an abundant serum protein whose major site of synthesis is in the hepatocyte. alpha 1AT transcripts are also present, albeit at a lower level, in a variety of other human tissues. This pattern of expression is partly related to initiation of transcription at sites with distinct tissue specificities. The mouse alpha 1AT gene, in contrast, is more strictly liver specific in its expression. To explore the regulation of the alpha 1AT gene we have microinjected a cosmid insert carrying the human gene into fertilized mouse eggs. In three lines obtained from transgenic mice, inheritance of copies of the human gene is accompanied by a high serum concentration of the human protein. Human alpha 1AT RNA accumulates to the highest level in liver of transgenic animals. The presence of transcripts in other tissues indicates that the human pattern of expression is maintained, whereas the temporal activity of the introduced gene parallels that of the endogenous one during mouse embryogenesis.

Animals↗
PubMed1987

The gene for human alpha-lactalbumin is assigned to chromosome 12q13.

A cDNA clone complementary to the mRNA encoding human alpha-lactalbumin (ALA) has been used as a probe in the analysis of DNA from panels of rodent/human somatic cell hybrids. The presence of the ALA gene correlates with the presence of chromosome 12. In situ hybridization localizes the ALA gene to 12q13.

Animals↗
PubMed1987

Localization of PEPD to the long arm of chromosome 19.

A panel of human-rodent somatic cell hybrids containing different regions of chromosome 19 has been used to obtain a regional localization for peptidase D. The results assign PEPD to the long arm of chromosome 19, in the region cen-q13.2

Animals↗
PubMed1987

Characterization of a panel of highly variable minisatellites cloned from human DNA.

Five of the most variable loci detected in human DNA by hybridization with DNA fingerprint probes have been cloned and characterized. Each locus consists of a tandem-repetitive minisatellite, with repeat units ranging in length from 9 to 45 base pairs depending on the locus. All of these cloned minisatellites act as locus-specific hybridization probes, and detect extremely variable Mendelian loci with heterozygosities ranging from 90 to 99%. These five hypervariable loci, together with a previously-isolated minisatellite designated p lambda g3, are dispersed over four autosomes (chromosomes 1, 5, 7 and 12). Syntenic pairs on chromosomes 1 and 7 show no detectable pair-wise linkage, and thus these hypervariable loci show no evidence of clustering within the genome and should provide valuable markers for mapping inherited disease. The locus-specific minisatellites act as very sensitive hybridization probes, and can be pooled to detect several hypervariable loci simultaneously. The applications of these probes in individual identification, paternity testing and analysis of cell chimaerism are discussed, and are illustrated by an analysis of forensic specimens from two victims who had been sexually assaulted and murdered.

Chromosomes↗
PubMed1987

The hypervariable gene locus PUM, which codes for the tumour associated epithelial mucins, is located on chromosome 1, within the region 1q21-24.

A single hypervariable autosomal gene locus, PUM, codes for a family of mucin-type glycoproteins present in human urine, and in several other normal and malignant tissues of epithelial origin. These mucins can be detected after electrophoresis using a series of monoclonal antibodies that show a pronounced tumour specificity on immunohistochemistry. Using a recently cloned cDNA, pMUC10, coding for the core protein of the PUM coded mucins, to probe DNA isolated from a series of human-rodent somatic cell hybrids, we have assigned the PUM locus to chromosome 1. This assignment was confirmed by in situ hybridization of pMUC10 to lymphocyte metaphase chromosomes and the gene was shown to be located within the region 1q21-24.

Animals↗
PubMed1987

The human chorionic gonadotrophin alpha subunit gene in gestational trophoblastic disease. 1. Restriction fragment length polymorphisms in hydatidiform moles.

The distribution of EcoR1 and HindIII restriction fragment length polymorphisms in the region of the gene coding for the alpha subunit of human chorionic gonadotrophin have been examined in 71 normal controls, six families, and 65 cases of hydatidiform mole, all of European origin. In control samples the genotypes generated by the presence or absence of the restriction sites, fitted a Hardy Weinberg distribution while in family studies the two polymorphisms showed Mendelian inheritance. The distribution of the genotypes in hydatidiform moles differed from that in control samples. However, the frequency of the alternative alleles R+, R- and H+, H- was not significantly different in the two populations and differences in the distribution of genotypes could be explained in terms of the unique origin of hydatidiform moles. The frequency of the rare homozygous genotype R-R-,H+H+, which has previously been suggested to be associated with the development of choriocarcinoma, was similar in those complete moles which resolved spontaneously (35 per cent) and those which progressed to trophoblastic tumours (27 per cent). No association was found between the genotype of the hydatidiform mole and the subsequent clinical outcome of the patient. Thus the pattern of restriction fragment length polymorphisms associated with the human chorionic gonadotrophin alpha subunit gene would not appear to be an appropriate marker of clinical outcome in patients with hydatidiform moles.

Female↗
PubMed1986

Assignment of the gene determining human carbonic anhydrase, CAI, to chromosome 8.

A cDNA clone complementary to the mRNA encoding the rabbit erythrocyte specific carbonic anhydrase, CAI, has been used as probe for human CAI sequences in the analysis of DNA from panels of rodent/human somatic cell hybrids. The presence of the human CAI gene in all hybrids correlates with the presence of chromosome 8. Together with published mapping data, this assignment indicates that three CA loci are situated on chromosome 8.

Animals↗
PubMed1986

Assignment of the human gene for beta-glycerol phosphatase to chromosome 8.

The segregation of the human gene for beta-glycerol phosphatase (GPB) was examined in human-Syrian hamster and human-Chinese hamster somatic cell hybrids. Electrophoretic analysis of the GPB in hybrids suggested that the enzyme is a dimer. Human GPB cosegregated with chromosome 8 in the twenty-five hybrids examined.

Animals↗
PubMed1986

Assignment of the human gene for uridine 5'-monophosphate phosphohydrolase (UMPH2) to the long arm of chromosome 17.

Two distinct isozymes of uridine 5'-monophosphate phosphohydrolase (UMPH) have been identified in mammalian cells. Both of these isozymes hydrolyse other pyrimidine nucleotides. One of the isozymes, UMPH2, is more active against deoxy-nucleotides than non-deoxy-nucleotides and has a wider substrate specificity. We examined the segregation of the human gene for UMPH2 in human-mouse somatic cell hybrids. Electrophoretic analysis of UMPH2 in hybrids suggested that the enzyme is a dimer. Human UMPH2 cosegregated with the long arm of chromosome 17 in the nineteen hybrids examined. The ease of separation of the rodent and human isozymes of UMPH2 and the relative simplicity of the enzyme assay suggest that UMPH2 may be a more useful marker gene for chromosome 17 than galactokinase.

5'-Nucleotidase↗
PubMed1986

The gene for human muscle specific carbonic anhydrase (CAIII) is assigned to chromosome 8.

A cDNA clone complementary to the mRNA encoding the human muscle specific carbonic anhydrase CAIII has been used as probe in the analysis of DNA from panels of rodent/human somatic cell hybrids. The presence of the CA III gene in all hybrids correlates with the presence of chromosome 8. This is the first assignment of the CAIII gene in any species and, together with published mapping data, indicates that all of the human CA loci are situated on chromosome 8.

Animals↗
PubMed1986

Chromosome 1 in relation to human disease.

Chromosome 1 is thought to represent about 6% of the total human genome and the 85 loci so far identified may constitute about 1% of the genes present on this chromosome. The existence of at least 22 loci sufficiently polymorphic in Europeans to be useful as genetic markers has allowed the construction of an elementary genetic map. This permits comparisons with physical and chiasma maps and has demonstrated striking homologies between different regions of chromosome 1 and mouse chromosomes 1, 3, and 4. The existence of a map should be of great help in developing a more systematic approach to further mapping studies. A wide range of disease can be attributed to allelic variation on chromosome 1 and the homologies with the mouse may be useful in predicting the position of other genes involved in human disease. Rearrangements of this chromosome are a common finding in many different types of malignancy. Loss of material from the short arm and activation of one or more of the four oncogenes in this region may play an important role in the later stages of tumour development. Polymorphic markers of all kinds will be useful in the future for investigating the somatic events which have occurred during the malignant process.

Animals↗
PubMed1986

Duchenne muscular dystrophy in one of monozygotic twin girls.

Monozygotic twin girls are reported, one of whom has the typical clinical features of Duchenne muscular dystrophy despite a normal female karyotype. Although certain features of the biopsy were atypical, the clinical diagnosis was supported by persistent markedly raised blood creatine kinase levels and findings typical of DMD on electromyography and magnetic resonance spectroscopy. Analysis of an X linked DNA polymorphism in 16 independent somatic cell hybrids made between cells derived from each girl and a mouse line suggest that in one twin only the maternal X chromosome is active, whereas in the other the active X was paternally derived. More data are needed to exclude sampling error. These preliminary experimental results support the hypothesis that both girls are heterozygous for Duchenne muscular dystrophy. X inactivation, by chance, resulted in two contrasting cell masses with different active X chromosomes. This segregation was followed by, and may even have resulted in, twinning into a female pair, one normal and one with the full clinical features of the disease.

Biopsy↗
PubMed1986

Tissue culture model of transitional cell carcinoma: characterization of twenty-two human urothelial cell lines.

Twenty-two continuous cell lines derived from normal and neoplastic urothelium, maintained under identical culture conditions, were characterized in terms of isozyme phenotype, tumorigenicity, and xenograft morphology following xenotransplantation to nude mice, cytological appearance, in vitro growth rate, labelling index, and colony-forming efficiency, in parallel with separate studies of in vitro drug sensitivities and monoclonal antibody reactivities. Three groups were identified: (a) distinct lines with differing isozyme patterns, a broad spectrum of growth characteristics, and xenograft morphologies similar to the histopathology of the parent tumors after periods of up to 17 yr following establishment in vitro; (b) cross-contaminated sublines (maintained separately in different laboratories for periods of up to 10 yr), with identical isozyme patterns and similar growth characteristics, but differing markedly in tumorigenicity and xenograft morphology; and (c) lines derived from normal urothelium which were nontumorigenic and had an isozyme pattern usually only encountered in untransformed cells. These data indicate that cell lines representative of human transitional cell carcinomas can be selected on the basis of xenograft morphology and isozyme patterns, and that a panel of lines derived from normal and neoplastic urothelium could provide a model system to study the biology and treatment of this disease.

Carcinoma, Transitional Cell↗