Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Somatic variant”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 649 records · Page 36Linked to original sources
PubMed2004

An intronic variant of the TGFBR1 gene is associated with carcinomas of the kidney and bladder.

TGF-beta signaling is frequently perturbed in many human cancers, including renal cell carcinomas (RCCs) and transitional cell carcinomas (TCCs) of the bladder. Genetic alterations of the TGF-beta type 1 receptor (TGFBR1) may contribute to these perturbations. We therefore examined variations in the TGFBR1 gene by PCR, SSCP and RFLP in carcinomas of the urinary system and in tissues from noncancer, age-matched controls. A G-->A variant 24 bp downstream of the exon/intron 7 boundary of the TGFBR1 gene (Int7G24A) was evident in patients with RCC (46.5%, n = 86) and bladder and upper urinary tract TCC (49.2%, n = 65) significantly more frequently than in age-matched controls (28.3%, n = 113, p < 0.002 by chi2 test). Moreover, 8 homozygous variant carriers were found in the cancer groups, whereas not a single homozygous variant carrier was found in the control group. The Int7G24A allele (both heterozygous G/A and homozygous A/A carriers) was associated with increased RCC incidence (OR = 2.20, 95% CI 1.22-3.96) and TCC incidence (OR = 2.45, 95% CI 1.89-3.16). One somatic mutation of serine to phenylalanine at codon 57 of the TGFBR1 gene was confirmed in an upper urinary tract TCC. In conclusion, the Int7G24A variant in the TGFBR1 gene is significantly more frequent in patients with RCC and TCC than normal age-matched controls, suggesting that it may represent a risk factor for the development of kidney and bladder carcinomas.

Activin Receptors, Type I↗
PubMed2002

Minisatellite instability at the Adh locus reveals somatic polymorphism in amphioxus.

Amphioxus (subphylum Cephalochordata) is the closest living relative to vertebrates and widely used for phylogenetic analyses of vertebrate gene evolution. Amphioxus genes are highly polymorphic, but the origin and nature of this variability is unknown. We have analyzed the alcohol dehydrogenase locus (Adh3) in two amphioxus species (Branchiostoma lanceolatum and Branchiostoma floridae) and found that genetic variation is related to repetitive DNA sequences, mainly minisatellites. Small pool-PCR assays indicated that allelic variants are generated by minisatellite instability. We conclude that the generation of new forms was not preferentially linked to germline processes but rather to somatic events leading to mosaic adult animals. Furthermore, most Adh minisatellites belong to a novel class, which we have named mirages. Their distinctive feature is that the repeat subunit spans the exon-intron boundaries and generates potential duplications of the splice sites. However, splicing may not be compromised as no aberrant mRNA variants were detected.

Alcohol Dehydrogenase↗
PubMed1992

Analysis of the promoter for the gene encoding the testis-specific histone H1t in a somatic cell line: evidence for cell-cycle regulation and modulation by distant upstream sequences.

Gene H1t encodes a testis-specific variant of the H1 histone family expressed in pachytene spermatocytes during the meiotic phase of spermatogenesis. Fusions between various upstream fragments of the H1t gene and the chloramphenicol acetyltransferase-encoding reporter gene were analyzed in mouse L cells by both transient and permanent transfection. Expression of the minimal promoter [174 nucleotides (nt) upstream from the transcription start point] was enhanced by sequences extending to nt -693, but was reduced in constructs with kb of upstream sequence. Using synchronized cells, expression was at least twofold higher in growing than in inhibited cells. Thus, the H1t promoter is modulated both positively and negatively by distant upstream sequences, and it displays some of the S-phase-dependent character of a replication-dependent histone.

Animals↗
PubMed1987

[Genetic transformation of somatic cells. XIII. Limited replication of DNA containing a fragment of human satellite DNA III in mouse cells].

The plasmids containing the variant sequence of human satellite III "rescued" after replication in Chinese hamster cells were transfected into Chinese hamster, mouse and human cells by DEAE-dextran method. Several days after transfection extrachromosomal fractions were isolated, treated with DpnI, transformed into E. coli. In mouse cells, transformed with oncogene v-myc, after transient transfection of HS3-containing plasmids the appearance of rearranged and non-rearranged DpnI-resistant plasmids has been found. At the same time MboI-sensitive plasmids were not found in this material. The data suggest a limited replication (1 round) of HS3-containing plasmids in mouse cells transformed with oncogene v-myc.

Animals↗
PubMed2002

Involvement of ATM missense variants and mutations in a series of unselected breast cancer cases.

It has been proposed that women carrying heterozygous mutations of the ATM gene could be at increased risk of developing breast cancer. However, data in the literature are contrasting and no firm conclusion has been reached. Our aim was to verify whether ATM inactivation could play a role in breast tumor development. Following the classical tumor suppressor inactivation scheme, tumors showing loss of heterozygosity (LOH) at the ATM locus should present an increased proportion of mutated ATM forms. We screened a cohort of 173 nonselected primary breast tumors for LOH in a 4 cM region at 11q23 spanning the ATM gene. We analyzed 25 tumors presenting LOH within the ATM locus for mutations in the ATM coding sequence using an RT-PCR-SSCP approach. Five patients were found to bear a coding missense variant, out of which four corresponded to a frequent polymorphism in exon 39. One patient presented a previously unreported variant in exon 19 (2614C>T) resulting in a nonconservative change (Pro>Ser) at aa 872. This variant was not found in any of the other 172 patients nor in 63 healthy controls tested, indicating that it is a rare ATM variant. LOH involved the ATM wild-type allele in the tumor presenting variant 2614. However, because the ATM gene presents a relatively large number of rare coding polymorphism it is difficult, in the absence of familial data, to be conclusive on the significance of this variant. Searching for further variants in exons 19 and 39 in the whole set of 173 breast tumors, we found one tumor showing an acquired deletion of four bases in the ATM gene. Somatic mutations affecting the ATM gene thus seem rare in breast cancer. In our cohort of breast cancer patients, tumors presenting LOH at the ATM locus did not show an increased frequency of sequence variants. Furthermore, allelic imbalance profiles in a 4-cM region of chromosome arm 11q spanning the ATM locus revealed that hot spots of LOH were more likely to correspond to a region localized telomeric to the gene. Therefore, these data suggest that other target genes for genetic inactivation exist in the 11q23 region.

Alleles↗
PubMed1999

Somatization in Family Practice: Comparing 5 Methods of Classification.

BACKGROUND: It has been suggested that patients with somatoform disorders are high utilizers of medical care, yet interpretation of studies has been difficult because of variant methods of diagnosis. The goal of this study was to compare 5 different methods of classification on the same group of subjects and to examine prevalence rates of somatoform disorders and medical utilization. METHOD: Subjects completed a demographic questionnaire in the physician's office and the somatization section of the Diagnostic Interview Schedule (DIS) by telephone. Subsequently, their medical charts were examined. Using the 5 methods of diagnosis, somatizers were compared with nonsomatizers for level of utilization of medical services. The setting was a medical school-based family practice residency training center. Participants were 119 patients waiting to see their family doctors. The main outcome measures were prevalence of somatization symptoms and chart information (utilization, number of health problems). RESULTS: One subject met the Diagnostic and Statistical Manual (DSM-IV)-based DIS criteria for somatization disorder. With the Bucholz modification for scoring the DIS, 10 subjects were diagnosed with somatization disorder. With the abridged Escobar criteria of 6 symptoms, 7 subjects met diagnostic criteria, while 28 met the criteria for multisomatoform disorder of 3 symptoms, as suggested by Kroenke. The diagnosis of undifferentiated somatoform disorder, requiring only 1 unexplained symptom, was obtained by 94 of the subjects. CONCLUSION: Findings from this study revealed widely divergent prevalence rates of somatoform disorders, depending on methods of diagnosis used. Correlation with rates of medical utilization is suggested as an external criterion for validating diagnostic methods.

Journal Article↗
PubMed2026

Discordant neoplasms in monozygotic twins with a germline RECQL5 variant.

RECQL5 is a member of the RecQ helicase family involved in DNA replication, homologous recombination, and maintenance of genomic stability. While germline pathogenic variants in other RecQ helicases cause established cancer predisposition syndromes, the role of RECQL5 in human cancer susceptibility remains uncertain. We report monozygotic adolescent twins with distinct tumors: dysembryoplastic neuroepithelial tumor in one twin and Burkitt lymphoma in the other. Clinical genome sequencing was initially nondiagnostic, but reanalysis identified a rare heterozygous nonsense variant in RECQL5 (NM_004259.7:c.2698C>T, p.(Gln900Ter)), present in both twins and their unaffected mother. The variant is predicted to undergo nonsense-mediated mRNA decay or produce a truncated protein lacking the C-terminal SRI (Set2-Rpb1 interacting) domain, which mediates interaction with RNA polymerase II. However, tumor sequencing data were not available to evaluate loss of heterozygosity or second somatic events. Given the unaffected carrier parent, lack of tumor molecular confirmation, and the biological heterogeneity of the tumors, a causal relationship for this variant cannot be established. This case highlights the challenges of interpreting rare germline variants in genes with emerging but incompletely characterized disease associations. Although the available evidence is insufficient to establish a definitive causal relationship, the identification of a shared loss-of-function RECQL5 variant in monozygotic twins with distinct tumors is noteworthy and adds to the limited clinical evidence suggesting a potential role for RECQL5 in cancer susceptibility. Additional functional studies, tumor-based analyses and the accumulation of well-characterized clinical cases will be essential to determine whether RECQL5 contributes to hereditary cancer predisposition.

Adolescent↗
PubMedDate not supplied

Somatic inactivation of genes on chromosome 13 is a common event in retinoblastoma.

Through family studies and analysis of patients with congenital chromosome abnormalities, the germ-line mutation responsible for the hereditary form of the eye tumour, retinoblastoma, has been assigned to the q14 region on chromosome 13 and closely linked to an enzyme called esterase D (ESD). Knudson has proposed that as few as one somatic event in addition to the germ-line mutation is required to induce tumours in patients with the hereditary form of retinoblastoma; the non-hereditary form requires two somatic events to occur in the same cell. The somatic event(s) may involve either mutation of the remaining normal gene at 13q14 or mutation of a gene at another site in the genome. Here we have examined six retinoblastoma patients who are heterozygous for electrophoretic variants of ESD. Although the normal cells of all six patients expressed both variants, the tumour cells of four patients expressed enzyme from only one of the two ESD alleles. We tentatively conclude that induction of a retinoblastoma tumour requires the somatic inactivation of genes near the ESD locus including the remaining normal gene at the retinoblastoma (RB) locus.

Cell Line↗
PubMed1999

In vitro poly(ADP-ribosyl)ated histones H1a and H1t modulate rat testis chromatin condensation differently.

Rat testis H1 proteins were poly(ADP-ribosyl)ated in vitro. The modifying product, poly(ADP-ribose), was found covalently bound to each histone variant at various extents and exhibited distinct structural features (linear and short, rather than branched and long chains). Interest was focused on the somatic H1a, particularly abundant in the testis, as compared with other tissues, and the testis-specific H1t, which appears only at the pachytene spermatocyte stage of germ cell development. These H1s were modified with poly(ADP-ribose) by means of two in vitro experimental approaches. In the first system, each variant was incubated with purified rat testis poly(ADP-ribose)polymerase in the presence of [(32)P] NAD. In parallel, poly(ADP-ribosyl)ated H1s were also prepared following incubation of intact rat testis nuclei with [(32)P] NAD. In both experiments, the poly(ADP-ribosyl)ated proteins were purified from the native forms by means of phenyl boronic agarose chromatography. The results from both analyses were in agreement and showed qualitative differences with regard to the poly(ADP-ribose) covalently associated with H1a and H1t. Comparison of the bound polymers clearly indicated that the oligomers associated with H1a were within 10-12 units long, whereas longer chains (</=20 ADP-R units) were linked to H1t. Individual poly(ADP-ribosyl)ated H1s were complexed with homologous H1-depleted oligonucleosomes (0.5-2.5 kbp) in order to measure their ability to condensate chromatin, in comparison with the native ones. Circular dichroism showed that the negative charges of the oligomeric polyanion, although present in limited numbers, highly influenced the DNA-binding properties of the analyzed H1s. In particular, the poly(ADP-ribosyl)ated H1a and H1t had opposite effects on the condensation of H1-depleted oligonucleosomes.

Animals↗
PubMed1996

A unique variant of a homeobox gene related to Drosophila cut is expressed in mouse testis.

Mammalian homologues of the Drosophila cut homeobox gene encode transcriptional repressors that are involved in tissue-specific and developmental gene regulation. We examined the expression of a murine cut homologue (Cux-1) in the adult mouse. In many somatic tissues, Cux-1 was expressed as a 13-kb transcript. However, the highest expression of Cux-1 was in the testis, where a unique 2.4-kb splice variant was identified. Less abundant transcripts of 5 kb, 6.5 kb, and 8.5 kb were also detected only in the testis. The nucleotide sequence of the 2.4-kb Cux-1 transcript was identical to the 13-kb transcript in the region of overlap, but the testis-specific transcript encoded a truncated protein that contained only one Cut repeat in addition to the Cut-related homeodomain. Studies of mice homozygous for the atrichosis (at/at) mutation suggested that the 2.4-kb transcript was expressed in germ cells in the testis. In situ hybridization verified that Cux-1 was transiently expressed in post-meiotic germ cells at the round spermatid stage. Immunoblot analysis of nuclear extracts showed that the testis-specific Cux-1 transcripts encoded a 55-kDa protein. These results demonstrate that multiple products of a cut-related homeobox gene are expressed in the testis. The highly restricted pattern of expression of Cux-1 in the testis suggests that it may be involved in regulation of postmeiotic gene expression.

Amino Acid Sequence↗
PubMed1998

Restricted use of VH4 germline segments in an acute multiple sclerosis brain.

Multiple sclerosis (MS) cerebrospinal fluid and brain contain increased IgG and oligoclonal bands. Whether this oligoclonal and polyclonal IgG is directed against a disease-relevant antigen remains unknown. To distinguish between random activation versus a targeted B-cell response, we analyzed the IgG heavy chain variable region (VH) repertoire expressed in different lesions of an acute MS brain. To obtain a representative sample of the VH repertoire, we constructed directional complementary DNA libraries from plaque-periplaque messenger RNA and amplified VH regions from the library by nested polymerase chain reaction. When MS VH sequences were aligned to germline segments, about 60% of different VH sequences in the acute MS brain were VH4 germline segments, significantly greater than the known approximately 20% VH4 germline prevalence. Specific VH sequences were overrepresented and expressed at multiple plaque sites. Within some overexpressed populations, there were distinct sequence differences (clonal variants) indicative of clonal expansion. Alignment of VH sequences to their closest germline counterparts revealed extensive somatic mutation and the preferential accumulation of amino acid replacement mutations in complementarity determining regions. These observations suggest the limited B-cell response found in this acute MS brain was antigen driven.

Amino Acid Sequence↗
PubMed1979

Glucocorticoid induction of tyrosine aminotransferase in cultured cells.

For over a decade, tyrosine aminotransferase induction in tissue culture cells has been a useful model system in which to study glucocorticosteroid action. In the 1960s, the establishment in culture of rat hepatomas expressing the inducible enzyme, already known to be induced in liver in vivo, provoked a wide-ranging series of experiments. The data from these experiments have provided considerable information regarding the mechanism of action of steroids. These include the fundamental facts that the steroids act directly on the induced cell in unmetablized form, that removal of steroid results in deinduction, that induction does not require DNA synthesis or massive changes in RNA synthesis, and that cytoplasmic receptor occupancy by active steroids correlates closely with the steroids' ability to affect inductions. Studies in tissue culture cells have led to the analysis of transcriptional and posttranscriptional models attempting to explain enzyme induction. The effects on enzyme induction of nonsteroid hormones and other factors have been studied through the use of tissue culture cells. Finally, cells and clones of cell variants are being used to study enzyme induction, through biochemical analysis and cell genetic approaches, including somatic cell hybridization.

Animals↗
PubMed2002

Cytochrome P450 1B1, a new keystone in gene-environment interactions related to human head and neck cancer?

Alcohol consumption and tobacco smoking are major causes of head and neck cancers, and regional differences point to the importance of research into gene-environment interactions. Much interest has been focused on polymorphisms of CYP1A1 and of GSTM1 and GSTT1, but a number of studies have not demonstrated significant effects. This has mostly been ascribed to small sample sizes. In general, the impact of polymorphisms of metabolic enzymes appears inconsistent, with some reports of weak-to-moderate associations, and with others of no elevation of risks. The classical cytochrome P450 isoenzyme considered for metabolic activation of polycyclic aromatic hydrocarbons (PAH) is CYP1A1. A new member of the CYP1 family, CYP1B1, was cloned in 1994, currently representing the only member of the CYP1B subfamily. A number of single nucleotide polymorphisms of the CYP1B1 gene have been reported. The amino acid substitutions Val432Leu ( CYP1B1*3) and Asn453Ser ( CYP1B1*4), located in the heme binding domain of CYP1B1, appear as likely candidates to be linked with biological effects. CYP1B1 activates a wide range of PAH, aromatic and heterocyclic amines. Very recently, the CYP1B1 codon 432 polymorphism ( CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squamous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has pointed to interactive effects. This provides new molecular evidence that tobacco smoke-specific compounds relevant to head and neck carcinogenesis are metabolically activated through CYP1B1 and is consistent with a major pathogenetic relevance of PAH as ingredients of tobacco smoke.

Amino Acid Substitution↗
PubMed1987

Molecular organization and haplotype analysis of centromeric DNA from human chromosome 17: implications for linkage in neurofibromatosis.

The alpha satellite DNA subset located at the centromere of human chromosome 17 has been shown to be tightly linked genetically to the gene for von Recklinghausen neurofibromatosis (NF1). The centromeric DNA polymorphisms used for linkage analyses in NF1 are complex and involve a "locus" (D17Z1) that spans over one million base pairs of satellite DNA. To understand more completely the basis for these polymorphisms and how they might be best scored and used in the analysis of NF1, we have examined the molecular composition of the alpha satellite array on individual copies of chromosome 17 by two complementary approaches. First, we have analyzed segregation of chromosome 17 alpha satellite haplotypes in large, three-generation families that provide information on the different types of alpha satellite segregating in a block fashion. Second, we have analyzed directly the extent of variation in different D17Z1 arrays by genomic blotting analysis of haploid copies of chromosome 17 isolated in rodent/human somatic cell hybrids. The data indicate the existence of a wide range of different alpha satellite variants on individual copies of chromosome 17, each haplotype differing in the size, restriction map, and relative proportion of particular polymorphic repeat forms. Despite this complexity, the D17Z1 markers provide a potentially useful and genetically close starting point for the molecular and clinical analysis of NF1.

Animals↗
PubMed2006

Mitochondrial DNA G10398A polymorphism imparts maternal Haplogroup N a risk for breast and esophageal cancer.

Mitochondria are the major source of Reactive Oxygen Species (ROS) and mtDNA G10398A (Ala-->Thr) polymorphism, proposed to be involved in increased ROS production, has been shown in association with invasive breast cancer in African-American (AA) women [J.A. Canter, A.R. Kallianpur, F.F. Parl, R.C. Millikan, Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women, Cancer Res. 65 (2005) 8028-8033] and prostate cancer in AA men [M.P. Mims, T.G. Hayes, S. Zheng, S.M. Leal, A. Frolov, M.M. Ittmann, et al., Mitochondrial DNA G10398A polymorphism and invasive breast cancer in African-American women, Cancer Res. 66 (2006) 1880; author reply 1880-1881]. The role of mitochondria, however, in cancer development has been in question recently [A. Salas, Y.G. Yao, V. Macaulay, A. Vega, A. Carracedo, H.J. Bandelt, A critical reassessment of the role of mitochondria in tumorigenesis, PLoS Med. 2 (2005) e296], which has made it pertinent to analyze the data and test the hypotheses by conducting fresh case-control studies. This study, therefore, makes an attempt to validate the exclusive presence of mtG10398A (Ala-->Thr) polymorphism in a haplotype constituting mtDNA haplogroup N and its sublineages, imparting this group a higher risk for breast cancer, based on the re-analyses of approximately 1000 complete human mtDNA sequences worldwide and collated information on 2334 individuals belonging to 18 regions in India. The conclusion drawn of mt10398A allele providing a risk towards cancer is confirmed in a case-control comparison study of 124 sporadic breast cancer patients and 273 controls; and 55 squamous cell carcinoma of esophagus, ESCC, and 163 controls, matched for age, ethnicity and sex from north India. It is further apparent from the study that such a mtDNA polymorphism background provides a higher risk for the cancers of the tissues which could be affected by environmental insults directly as in the ESCC, observed with a high acquired (somatic) rate of mutation in p53 when compared to the breast cancer, suggesting that the mtDNA variants that arose as energetic adaptations, influence our health differentially under different environment conditions and a given genetic background of the mt genome.

Adolescent↗
PubMed2005

[Epigenetics: Paramecium as a model system].

Since the middle of the last century, Paramecium has appeared as an intriguing genetic model, displaying a variety of heritable characters which do not follow the Mendel laws but are cytoplasmically inherited. The analysis of the hereditary mechanisms at play in this eukaryotic unicellular organism has provided new insight into epigenetics mechanisms. Interestingly, the revealing phenomena concern two pecularities of Paramecium, its highly elaborate surface structure (with thousands of ciliary basal bodies as cytoskeleton organizers), and its nuclear dualism (coexistence of a diploid "germline" micronucleus and a highly polyploid somatic macronucleus devoted to transcription, which contains a rearranged version of the germline genome). Analysis of variant cortical organization has led to the concept of structural inheritance, implying that assembly of new organelles and supramolecular protein complexes is guided by pre-existing organization. Analysis of other cytoplasmically inherited characters revealed that the developing macronucleus is epigenetically programmed by the maternal macronucleus through RNA-mediated, homology-dependent effects, suggesting the transcriptome should be recognized as a third actor in cellular inheritance, along with the "structurome" and the genome.

Animals↗
PubMed2003

Markers of genetic susceptibility in human environmental hygiene and toxicology: the role of selected CYP, NAT and GST genes.

Inherited genetic traits co-determine the susceptibility of an individual to a toxic chemical. Special emphasis has been put on individual responses to environmental and industrial carcinogens, but other chronic diseases are of increasing interest. Polymorphisms of relevant xenobiotic metabolising enzymes may be used as toxicological susceptibility markers. A growing number of genes encoding enzymes involved in biotransformation of toxicants and in cellular defence against toxicant-induced damage to the cells has been identified and cloned, leading to increased knowledge of allelic variants of genes and genetic defects that may result in a differential susceptibility toward environmental toxicants. "Low penetrating" polymorphisms in metabolism genes tend to be much more common in the population than allelic variants of "high penetrating" cancer genes, and are therefore of considerable importance from a public health point of view. Positive associations between cancer and CYP1A1 alleles, in particular the *2C I462V allele, were found for tissues following the aerodigestive tract. Again, in most cases, the effect of the variant CYP1A1 allele becomes apparent or clearer in connection with the GSTM1 null allele. The CYP1B1 codon 432 polymorphism (CYP1B1*3) has been identified as a susceptibility factor in smoking-related head-and-neck squameous cell cancer. The impact of this polymorphic variant of CYP1B1 on cancer risk was also reflected by an association with the frequency of somatic mutations of the p53 gene. Combined genotype analysis of CYP1B1 and the glutathione transferases GSTM1 or GSTT1 has also pointed to interactive effects. Of particular interest for the industrial and environmental field is the isozyme CYP2E1. Several genotypes of this isozyme have been characterised which seem to be associated with different levels of expression of enzyme activity. The acetylator status for NAT2 can be determined by genotyping or by phenotyping. In the pathogenesis of human bladder cancer due to occupational exposure to "classical" aromatic amines (benzidine, 4-aminodiphenyl, 1-naphthylamine) acetylation by NAT2 is regarded as a detoxication step. Interestingly, the underlying European findings of a higher susceptibility of slow acetylators towards aromatic amines are in contrast to findings in Chinese workers occupationally exposed to aromatic amines which points to different mechanisms of susceptibility between European and Chinese populations. Regarding human bladder cancer, the hypothesis has been put forward that genetic polymorphism of GSTM1 might be linked with the occurrence of this tumour type. This supports the hypothesis that exposure to PAH might causally be involved in urothelial cancers. The human polymorphic GST catalysing conjugation of halomethanes, dihalomethanes, ethylene oxide and a number of other industrial compounds could be characterised as a class theta enzyme (GSTT1) by means of molecular biology. "Conjugator" and "non-conjugator" phenotypes are coincident with the presence and absence of the GSTT1 gene. There are wide variations in the frequencies of GSTT1 deletion (GSTT1*0/0) among different ethnicities. Human phenotyping is facilitated by the GST activity towards methyl bromide or ethylene oxide in erythrocytes which is representative of the metabolic GSTT1 competence of the entire organism. Inter-individual variations in xenobiotic metabolism capacities may be due to polymorphisms of the genes coding for the enzymes themselves or of the genes coding for the receptors or transcription factors which regulate the expression of the enzymes. Also, polymorphisms in several regions of genes may cause altered ligand affinity, transactivation activity or expression levels of the receptor subsequently influencing the expression of the downstream target genes. Studies of individual susceptibility to toxicants and gene-environment interaction are now emerging as an important component of molecular epidemiology.

Arylamine N-Acetyltransferase↗
PubMed1982

Chromatin diminution in Ascaris suum: nucleotide sequence of the eliminated satellite DNA.

We have determined the prototype sequence of the DNA which is eliminated in the course of chromatin diminution in Ascaris suum. This DNA which is virtually absent from somatic cells but retained in the germ line consists predominantly of highly repetitive sequences which are variants of an AT rich 123 base pair repeat unit. Both major and minor variants have been sequenced. The overall structure of this germ line limited DNA corresponds to the segmental organization characteristic of satellite DNAs. Possible correlations between the mechanism of chromatin diminution and some properties of the satellite sequence are discussed.

Animals↗