Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “nucleotide polymorphism patterns”

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 1,477 records · Page 82Linked to original sources
PubMed1996

High frequencies of identical T cell clonotypes in synovial tissues of rheumatoid arthritis patients suggest the occurrence of common antigen-driven immune responses.

OBJECTIVE: To investigate T cell antigen receptor (TCR) clonotypes in rheumatoid arthritis (RA) lesions. METHODS: Reverse transcriptase-polymerase chain reaction with TCR V beta family-specific primers and subsequent single-strand conformation polymorphism (SSCP) analysis were performed. Direct nucleotide sequencing was also conducted. RESULTS: A distinct clonal expansion of T cells was observed in the synovium. Furthermore, identical bands in samples of different areas of the same lesion were obtained by SSCP analysis. Nucleotide sequencing revealed that T cell clonotypes of identical mobility on SSCP analysis had the same nucleotide sequence and thus were identical clones. In 6 RA patients, 60-100% of the expanded T cell clonotypes had identical migration patterns in 2 different samples, indicating that this percentage represents commonly existing T cell clonotypes in the affected joint. Furthermore, the J beta 2.1 gene segment was used predominantly by the TCR V beta clonotypes that commonly expanded in the different portions of the same joint. CONCLUSION: These results suggest that the immune response in RA is not random, but rather is driven by common stimuli.

Adult↗
PubMed1997

Allelic variants of the human MHC class I chain-related B gene (MICB).

The human major histocompatibility complex (MHC) is located within a 4 megabase segment on chromosome 6p21.3. Recently, a highly divergent MHC class I chain-related gene family, MIC was identified within the class I region. The MICA and MICB genes in this family have unique patterns of tissue expression. The MICA gene is highly polymorphic, with more than 20 alleles identified to date. To elucidate the extent of MICB allelic variations, we sequenced exons 2 (alpha 1), 3 (alpha 2), 4 (alpha 3), and 5 (transmembrane) as well as introns 2 and 4 of this gene in 46 HLA homozygous B-cell lines. We report the identification of eleven alleles based on seven non-synonymous, two synonymous, and four intronic nucleotide variations. Interestingly, one allele has a nonsense mutation resulting in a premature termination codon in the alpha 2 domain. Thus, MICB appears to have fewer alleles than MICA, not unlike the allelic ratio between the HLA-C and -B loci. A preliminary linkage analysis of the MICB alleles with those of the closely located MICA and HLA-B genes revealed no conspicuous linkage disequilibrium between them, implying the presence of a potential recombination hotspot between the MICB and MICA genes.

Alleles↗
PubMed2002

Genetic variation and population differentiation of Michelia formosana (Magnoliaceae) based on cpDNA variation and RAPD fingerprints: relevance to post-Pleistocene recolonization.

We used sequence variation of the atpB- rbcL intergenic spacer of cpDNA and nested clade analysis to assess the phylogeographic pattern of Michelia formosana, a species restricted to Taiwan and the Ryukyus. In total, 31 haplotypes were identified and clustered into four major chlorotypes. Genetic composition of nearly all populations was heterogeneous and paraphyletic phylogenetically. Although the apportionment of cpDNA variation hardly revealed a geographic pattern due to the coancestry of dominant sequences, some chlorotypes were restrictedly distributed. According to the patterns of clade dispersion and displacement, a reconstructed minimum spanning network revealed that historical events of past fragmentation and range expansion, associated with glaciation, may have shaped the phylogeographic patterns of M. formosana. Four possible refugia were identified: the Iriomote and Ishigaki Islands (the southern Ryukyus), Wulai (northern Taiwan), and Nanjen (southern Taiwan), on the basis of the interior positions of their haplotypes in the network and the high level of nucleotide diversity. Given insufficient time for coalescence at the cpDNA locus since the late Pleistocene recolonization, lineage sorting led to low levels of genetic differentiation among populations. In contrast, hierarchical examination of the random amplified polymorphic DNA (RAPD) data scored from six populations across three geographical regions, using an analysis of molecular variance (AMOVA), indicated high genetic differentiation both among populations (Phi(ST) = 0.471) and among regions (Phi(CT) = 0.368). An unweighted pair group method with arithmetic mean (UPGMA) tree of the RAPD fingerprints revealed that populations of two offshore islands of eastern Taiwan ( M. formosana var. kotoensis) were clustered with geographically remote populations of the Ryukyus instead of those in southern Taiwan, suggesting some historical division due to geographic barriers of the central mountain range. In contrast to the paraphyly of the nearly neutral cpDNA alleles, differentiated RAPDs may have experienced diversifying selection.

Journal Article↗
PubMed2002

PCR-RFLP identification of endemic Chilean species of Rhagoletis (Diptera: Tephritidae) attacking Solanaceae.

Four species of the genus Rhagoletis are native to Chile: R. nova (Schiner), R. conversa, (Brèthes), R. penela Foote and R. tomatis Foote. Currently, identification of these species is based on morphological criteria, but their strong similarity makes precise recognition difficult. To clarify species separation for quarantine purposes, a reliable method based on a PCR-RFLP procedure is reported. A DNA region containing mitochondrial NADH dehydrogenase genes was selected as a target sequence for the analysis. The amplification products (c. 1 kb) were digested with either SspI or DdeI, yielding specific patterns that differentiated each of the endemic species. Complete nucleotide sequences were determined, confirming empirical restriction maps. This report updates information on the geographical distribution of Rhagoletis species in Chile.

Animals↗
PubMed1998

Expression of cellular adhesion regulatory molecule in hepatocellular carcinoma.

Cellular adhesion regulatory molecule (CMAR) enhances the adhesiveness of cells to collagen and laminin and is considered to be a candidate anti-oncogene. The purpose of the present study was to investigate the relationship between the expression of CMAR and clinical features of hepatocellular carcinoma (HCC). Small amounts of liver tissue were obtained from HCC and non-cancerous portions of the liver in 29 patients and from normal liver in seven patients with metastatic liver tumour by biopsy under ultrasound guidance. RNA was extracted with acid guanidinium thiocyanate-phenol-chloroform. Expression of CMAR was assessed by quantitative PCR using beta-actin as an internal standard. A 4 b.p. insertion polymorphism at nucleotide 241 of the CMAR coding region was then investigated using extracted RNA to assess the relationship between the expression of variant mRNA of CMAR and HCC carcinogenesis. The relative expression of CMAR was significantly reduced in HCC compared with non-cancerous and normal livers and had a relationship with certain clinical background factors. The reduced expression of CMAR was thought to be closely associated with the progression of HCC. However, the 4 b.p. insertion polymorphism pattern of CMAR was the same between HCC and non-cancerous liver in all cases in which it was found. These results suggest that progression of HCC may be predicted based on the relative expression of CMAR.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1999

Expression of aberrantly spliced oncogenic ikaros isoforms in childhood acute lymphoblastic leukemia.

PURPOSE: We sought to determine if molecular abnormalities involving the Ikaros gene could contribute to the development of acute lymphoblastic leukemia (ALL) in children. PATIENTS AND METHODS: We studied Ikaros gene expression in normal human bone marrow, normal thymocytes, normal fetal liver-derived immature lymphocyte precursor cell lines, eight different ALL cell lines, and leukemic cells from 69 children with ALL (T-lineage ALL, n = 18; B-lineage ALL, n = 51). Expression of Ikaros protein and its subcellular localization were examined by immunoblotting and confocal laser-scanning microscopy, respectively. Polymerase chain reaction (PCR) and nucleotide sequencing were used to identify the specific Ikaros isoforms expressed in these cells. Genomic sequencing of splice junction regions of the Ikaros gene was performed in search for mutations. RESULTS: In each of the ALL cases, we found high-level expression of a non-DNA-binding or aberrant DNA-binding isoform of Ikaros with abnormal subcellular compartmentalization patterns. In contrast, only wild-type Ik-1 and Ik-2 isoforms with normal subcellular localization were found in normal bone marrow cells and thymus-derived or fetal liver-derived normal lymphocyte precursors. In leukemic cells expressing the aberrant Ikaros coding sequences with the 30-base-pair deletion, genomic sequence analysis of the intron-exon junctions between exons 6 and 7 yielded the wild-type sequence. We identified a single nucleotide polymorphism (SNP) affecting the third base of the triplet codon for a proline (CCC or CCA) in the highly conserved bipartite activation region (viz, A or C at position 1002 numbering from the translation start site of Ik-1) within our Ikaros clones. Bi-allelic expression of truncated and/or non-DNA-binding isoforms along with wild-type isoforms was observed in leukemic cells, which implicates trans-acting factor(s) affecting splice site recognition. CONCLUSION: Our findings link specific molecular defects involving the Ikaros gene to childhood ALL. Posttranscriptional regulation of alternative splicing of Ikaros RNA seems to be defective in leukemic lymphocyte precursors from most children with ALL. Consequently, leukemic cells from ALL patients, in contrast to normal lymphocyte precursors, express high levels of non-DNA-binding Ikaros isoforms that are reminiscent of the non-DNA-binding Ikaros isoforms that lead to lymphoblastic leukemia in mice.

Adolescent↗
PubMed2000

A unique and common restriction fragment pattern of the nucleotide sequences homologous to the genome of vf33, a filamentous bacteriophage, in pandemic strains of Vibrio parahaemolyticus O3:K6 O4:K68, and O1:K untypeable.

Vf33 is a filamentous bacteriophage isolated from Vibrio parahaemolyticus. We performed Southern blot hybridization analysis to examine the distribution of Vf33-related genetic elements in the pandemic strains (O3:K6 strains isolated between 1995 and 1997, O4:K68 and O1:K untypeable strains isolated between 1997 and 1999) of V. parahaemolyticus. Nucleotide sequences homologous to the Vf33 DNA were detected in all 57 test strains including pandemic and non-pandemic strains. However, the profiles of hybridization, including the restriction fragment length polymorphism, with nine Vf33-derived DNA probes exhibited by the pandemic strains were identical and were different from those by the non-pandemic strains. The results support the hypothesis that the pandemic strains are clonal, and suggest a possibility that they have acquired (a) new gene(s) via a Vf33-like filamentous phage.

Bacteriophages↗
PubMed2006

Systematic screening for polymorphisms in the CYP3A4 gene in the Chinese population.

OBJECTIVES: Cytochrome P450 3A4 (CYP3A4) is a major CYP enzyme in the liver and intestine. It is involved in the metabolism of over 50% of all drugs currently in use. The present study was designed to determine the genetic basis of CYP3A4 variability. METHODS: Single nucleotide polymorphism (SNP) analysis of the CYP3A4 gene was performed on 60 healthy Chinese subjects consisting of 20 Han, 30 She and ten Dong subjects, using direct sequencing. Linkage disequilibrium, haplotype inference and Hardy-Weinberg equilibrium were also determined for these samples. RESULTS: A total of 20 SNPs were found in the CYP3A4 gene, including 11 known SNPs and nine novel SNPs. The known SNPs detected in our study were CYP3A4*1B, CYP3A4*1G, CYP3A4*10, CYP3A4*13, CYP3A4*14, CYP3A4*15, CYP3A4*17, CYP3A4*18, rs3091339, rs3091430 and rs28371761, and the novel SNPs were -658 A-->C, G27A (E10K), T48A, G14284A (G167D), A15623G (N191D), C15635A (L196I), T15656C (F203L), G14199A (intron 5) and C15566T (intron 6). The allelic frequencies found in our sample varied from 1-37%. The novel SNPs detected in the CYP3A4 gene suggest that the Chinese population has different patterns of allele frequency compared with other populations. CONCLUSION: Several SNPs were detected in the CYP3A4 gene. The study of genetic variants in CYP3A4 may have an important significance for the understanding of genotype and phenotype relationships.

Adult↗
PubMed1997

Reduced expression and normal nucleotide sequence of androgen receptor gene coding and promoter regions in a family with partial androgen insensitivity syndrome.

BACKGROUND AND OBJECTIVES: Androgen insensitivity syndrome (AIS) is an X-linked disorder of XY males characterized by varying degrees of impaired masculinization. In many AIS cases, mutations have been identified in the coding sequence of the human androgen receptor (AR) gene which impair receptor function. Cases have also been reported in which reduced AR mRNA expression may contribute to AIS in association with AR gene mutations. The purpose of this study was to define the molecular basis of AIS in members of a family with clinical and laboratory features of partial androgen insensitivity (PAIS). DESIGN: Genital skin fibroblast (GSF) cultures were established from foreskin tissue for androgen receptor binding analysis. Genomic DNA was obtained from blood leucocytes for AR gene nucleotide sequence analysis. AR mRNA levels were determined in total RNA extracted from GSF cultures. PATIENTS: Three related subjects with perineo-scrotal hypospadias, bifid scrotum and microphallus were studied. The family pedigree of these subjects suggested an X-linked pattern of inheritance. Hormone assay results were consistent with AIS. MEASUREMENTS: AR binding capacity and affinity were determined in three subjects and compared with unaffected male controls. The coding sequence and 1.4 kb of promoter region of the AR gene were amplified in overlapping fragments by polymerase chain reaction from genomic DNA and sequenced. GSF AR mRNA was measured by a competitive PCR technique. RESULTS: In the PAIS subjects, AR affinity in cultured GSF was normal (Kd = 0.24, 0.30, 0.48 vs 0.27 +/- 0.07 (SD) nmol/l) but binding capacity was reduced (Bmax = 0.31, 0.36, 0.27 vs 1.26 +/- 0.37 (SD) fmol/microgram DNA). Sequence analysis of the CAG repeat polymorphism within exon 1 of the AR gene showed that both mothers were heterozygous at this locus, and that the three subjects had inherited the same allele. GSF AR mRNA levels were reduced in all three patients compared with controls (0.25, 0.74 and 0.74 vs 3.8 +/- 0.9 (SEM), range 1.8-7.3 amol/microgram total RNA). The nucleotide sequences of the entire AR coding region and of a 1.4 kb segment containing the promoter region were normal. CONCLUSION: Members of this family with clinical and biochemical evidence of X-linked partial androgen insensitivity syndrome demonstrated normal androgen receptor binding affinity and androgen receptor gene nucleotide sequence but reduced androgen receptor binding capacity and reduced androgen receptor mRNA. These results suggest that partial androgen insensitivity syndrome in this family may be caused by reduced expression of a normal androgen receptor gene.

Cells, Cultured↗
PubMed2026

Genetic Association Between Sleep Traits and Vertigo Risk: A Two-sample Bidirectional Mendelian Randomization Study.

BACKGROUND: Observational studies suggest the potential association between sleep traits and vertigo; however, causal evidence remains limited. OBJECTIVE: This study aimed to explore the relationship between genetically predicted sleep traits and vertigo with the Mendelian randomization (MR) method. METHODS: Instrumental variables for sleep traits (snoring, sleep duration, insomnia, daytime sleepiness, daytime napping, and chronotype) were adopted from genomewide association studies (GWAS) data of European ancestry from UK Biobank. The summary-level datasets of vertigo were retrieved from the GWAS of FinnGen. Inversevariance weighted (IVW) method was adopted as the main analysis. RESULTS: IVW analysis revealed a significant association between genetically predicted daytime napping (OR = 1.51, 95% CI =1.08-2.12, P = 0.016) and chronotype (OR = 1.13, 95% CI =1.01-1.26, P = 0.033), both of which were associated with an increased risk of vertigo. However, we did not find evidence for a causal effect of snoring, overall sleep duration, long sleep duration, short sleep duration, insomnia, and excessive daytime sleepiness on vertigo. No reverse causality was detected. CONCLUSION: Our findings suggest that abnormal sleep patterns may serve as risk factors for vertigo disorders and offer opportunities for the prevention and management of vertigo disorders.

Humans↗
PubMed1992

DNA fingerprinting in horses using a simple (TG)n probe and its application to population comparisons.

A synthetic polynucleotide (TG)n was hybridized to equine DNA digested with HinfI and hypervariable hybridization patterns were obtained. Mendelian inheritance of these DNA fingerprinting patterns was confirmed by pedigree analysis. Estimates of the probabilities of identical band patterns in unrelated individuals of different breeds (Swedish Trotters, North Swedish Trotters, Thoroughbreds and Arabians) were in the range 1 x 10(-4) - 7 x 10(-6). The variability derived with the (TG)n probe in horses was higher than what we obtained with several other commonly used probes for DNA fingerprinting. Individuals within breeds tended to be more similar to each other with regard to DNA fingerprint pattern than to individuals of other breeds. Moreover, a parsimony analysis made on the basis of the hybridization patterns gave clustering of individuals within breeds. The possibility of using hypervariable probes for the identification of breed-specific characters is discussed.

Animals↗
PubMed1998

The GnRH receptor gene is preferentially expressed in functioning gonadotroph adenomas and displays a Mae III polymorphism site.

OBJECTIVE: Given the central role of the GnRH receptor (GnRHR) in the regulation of the gonadotrophin secretion, it might be implicated directly or indirectly in the pathogenesis of gonadotroph tumours. DESIGN: We determined if GnRHR mRNA was expressed in gonadotroph tumours using RT-PCR and analysed the GnRHR gene for the presence of mutations in its coding region, using direct sequencing of PCR products. Results were analysed according to the pattern of expression of alpha, beta-FSH and beta-LH subunit (SU) genes. SUBJECTS: RNA was extracted from 20 gonadotroph tumours identified by immunohistochemistry (> 10% of stained cells): 9 adenomas were functioning (high serum gonadotrophin levels), 3 were associated with high alpha-SU levels and 8 were nonfunctioning. Genomic DNA was extracted from 64 normal subjects. RESULTS: We found GnRHR mRNA in 12 tumours (60%): 8/9 functioning (88%), 1/3 alpha-secreting (33%) and 3/8 nonfunctioning (37.5%) gonadotroph adenomas. There was a significant association between GnRHR expression and immunostaining for beta-FSH (P = 0.014). The nucleotide sequence of the amplified products was identical to that of human pituitary except for the presence, in 3 functioning adenomas, of a silent C to T transition at nucleotide 453 encoding for the serine residue situated in the second intracellular loop at position 151. Heterozygosity provided evidence that both alleles were transcribed in these tumours. This substitution creates a Mae III restriction site. Genomic DNA from normal subjects were then tested for the presence of this new polymorphism. The frequency of the heterozygosity (18.7%) was not significantly different from that found in gonadotroph tumours (25%) and this new Mae III polymorphism site cannot be used as a tumoural marker. CONCLUSION: The GnRHR gene is preferentially expressed in functioning rather than in nonfunctioning gonadotroph adenomas, but no mutations altering the coding region of the gene were found to further substantiate its role in the pathogenesis of gonadotroph tumours.

Adenoma↗
PubMed2005

Genetic evidence for the existence of sibling species within Contracaecum rudolphii (Hartwich, 1964) and the validity of Contracaecum septentrionale (Kreis, 1955) (Nematoda: Anisakidae).

Specimens of Contracaecum rudolphii sensu lato (s.l.) (Nematoda: Anisakidae) from Phalacrocorax carbo sinensis from northeastern and central Italy were characterised genetically and compared with those from Phalacrocorax aristotelis from Galician coasts, Spain (identified as C. rudolphii A by multilocus enzyme electrophoresis) and with specimens of C. septentrionale from Alca torda from the Galician coasts, Spain. The first (ITS-1) and second (ITS-2) internal transcribed spacers (ITS) of ribosomal DNA (rDNA) were amplified by polymerase chain reaction (PCR) from individual nematodes and the amplicons subjected to single-strand conformation polymorphism (SSCP) analysis and/or sequencing. For each ITS region, C. septentrionale specimens were distinct from those of C. rudolphii (s.l.) and C. rudolphii A based on SSCP profiles and ITS sequences. Some specimens of C. rudolphii (s.l.) had the same SSCP profiles and ITS sequences as C. rudolphii A, whereas the others had distinct SSCP profiles and ITS sequences and were suggested to represent C. rudolphii B based on host and geographical origins and genetic similarity to C. rudolphii A. While no length or nucleotide variation in the ITS-1 and ITS-2 sequences was detected within each taxon, nucleotide differences of 1.8-5.5% (ITS-1) and 5.1-12.2% (ITS-2) were detected among them. The results support the hypothesis that C. rudolphii represents a complex of at least two sibling species and provide support for the validity of C. septentrionale as a separate species. The definition of genetic markers in the ITS rDNA provides opportunities for investigating the life cycles, transmission patterns and ecology of the anisakid nematodes studied herein.

Animals↗
PubMed2004

CTLA-4 polymorphisms in allergy and asthma and the TH1/ TH2 paradigm.

BACKGROUND: Several genomic regions are reported to be associated with the development of asthma and allergy, including chromosome 2q33. This region harbors the candidate gene cytotoxic T-lymphocyte antigen 4 (CTLA-4), an important regulator of T-cell activation and differentiation. OBJECTIVE: We sought to explore possible associations between CTLA-4 polymorphisms and allergy and asthma. METHODS: Seven single nucleotide polymorphisms (SNPs; MH30, -1147CT, +49AG, CT60, JO31, JO30, JO27_1) in CTLA-4 were analyzed for associations with total serum IgE, allergic sensitization (positive skin prick test to common allergens), bronchial hyperresponsiveness (BHR) to methacholine, asthma, and lung function (FEV1 % of predicted) in 364 asthmatic families from 3 European countries. RESULTS: Transmission disequilibrium test analysis showed that several SNPs were significantly associated with serum IgE levels, allergy, asthma, and FEV1 % predicted below 80%, but not with BHR, and CTLA-4 polymorphisms of potentially direct pathogenic significance in atopic disorders were identified. CONCLUSION: We identified associations between 4 newly discovered SNPs in the CTLA-4 gene and serum IgE levels, allergy, asthma, and reduced lung function, but not BHR, suggesting an important role for CTLA-4 in atopy and reduced lung function in asthmatic subjects rather than asthma per se. The particular SNP alleles found positively associated with our phenotypes were recently shown to be associated negatively with autoimmune disorders. Although a skewing toward a TH1 reactivity pattern is believed to characterize autoimmune diseases, atopic diseases are considered TH2-mediated. Hence, our data suggest a role for CTLA-4 polymorphisms in determining the TH1/TH2 balance and identify CTLA-4 signaling as a potential therapeutic target in atopic disease.

Adolescent↗
PubMed1998

Use of a reverse transcriptase-polymerase chain reaction assay to analyze allele-specific expression in individual hippocampal neurons.

We report here a single-cell RT-PCR assay for allele-specific gene expression that can be used to probe for somatic variability within the CNS. Such variability, arising from epigenetic (nonmutational) events or somatic mutation early in development, may give clues as to clonal origin and may also affect the inheritance pattern of some CNS disorders. As a model system, we used reciprocal F1 hybrids of the cross Mus musculus C57BL/6J x Mus musculus castaneus. RNA was isolated from individual dissociated pyramidal neurons from hippocampi of F1 pups. For each gene of interest, single base polymorphisms were identified between the two parental strains by automated sequencing of RT-PCR products. Allele-specific expression was then analyzed by means of the previously described quantitative RT-PCR single nucleotide primer extension (SNuPE) assay (Singer-Sam et al., PCR Methods Appl. 1:160-163, 1992). Individual neurons showed monoallelic expression of the two control genes, X-linked Rps4, and the imprinted gene Snrpn; in contrast expression of Ncam and F3cam, coding for neural cell adhesion molecules, was found to be biallelic.

Alleles↗
PubMed2004

New genomic region for Wegener's granulomatosis as revealed by an extended association screen with 202 apoptosis-related genes.

Wegener's granulomatosis (WG) is a systemic disease with complex genetic background. It is characterized by necrotizing granulomatous inflammation of the upper and lower respiratory tract, glomerulonephritis, vasculitis and the presence of antineutrophil cytoplasmatic autoantibodies (C-ANCAs) in sera of patients. Here, we report on an extended association screen (EAS) with 202 microsatellite markers, representing apoptosis-related genes and further genes down-regulated in apoptotic neutrophils, using pooled DNA of 150 Northern German patients suffering from WG and 100 healthy Northern German controls. Six microsatellite allele patterns were found significantly associated with WG, three of which could be confirmed by individual genotyping. One marker remained significantly associated after multiple corrections. This marker representing the retinoid X receptor beta gene (RXRB, P=7.60x10(-6), distance to gene: approximately 5.3 kb) is localised in the major histocompatibility complex (MHC) region between the HLA-DPB1 and DAXX genes. HLA-DPB1 typing and fine mapping of the region with additional microsatellites and single-nucleotide polymorphisms (SNPs) revealed a strong association of WG with the significantly over-represented DPB1*0401 ( P=1.51x10(-10), OR=3.91) allele compared with the control cohort. In addition, an extended haplotype DPB1*0401/RXRB03 was identified showing an even stronger association with WG ( P=7.13x10(-17), OR=6.41). These results represent the strongest association of a genomic region with WG, suggesting a major genetic contribution in the aetiology of the disease. Thus, our data demonstrate that EAS may be a valuable alternative approach for determining genetic predisposition factors in multifactorial diseases.

Apoptosis↗
PubMed2003

Global patterns in peatmoss biodiversity.

DNA sequence data from the nuclear ribosomal internal transcribed spacers (ITS) and the trnL-trnF chloroplast DNA regions were used to quantify geographical partitioning of global biodiversity in peatmosses (Sphagnum), and to compare patterns of molecular diversity with patterns of species richness. Molecular diversity was estimated for boreal, tropical, Neotropical, nonboreal (tropical plus Southern Hemisphere), Old World and New World partitions, based on a total of 436 accessions. Diversity was partitioned among geographical regions in terms of combined nuclear and chloroplast sequence data and separately for the ITS and trnL-trnF data sets. Levels of variation were estimated using phylogenetic diversity (PD), which incorporates branch lengths from a phylogenetic tree, and the number of polymorphic nucleotide sites. Estimates of species richness suggest that peatmoss diversity is higher in New World than Old World regions, and that the Neotropics constitute a "hotspot" of diversity. Molecular estimates, in contrast, indicate that peatmoss biodiversity is almost evenly divided between New and Old World regions, and that the Neotropics account for only 20-35% of global peatmoss diversity. In general, levels of tropical and boreal peatmoss molecular diversity were comparable. Two species, S. sericeum from the Old World tropics and S. lapazense from Bolivia, are remarkably divergent in nucleotide sequences from all other Sphagna and together account for almost 20% of all peatmoss diversity, although they are represented by only three of the 436 accessions (0.7%). These species clearly demonstrate the nonequivalence of species biodiversity value.

Base Sequence↗
PubMed1997

Characterization of the rat neurofibromatosis 2 gene and its involvement in asbestos-induced mesothelioma.

The neurofibromatosis 2 (NF2) tumor suppressor gene was recently implicated in the genesis of human mesothelioma. To investigate the role of this tumor suppressor gene in rat asbestos-induced mesothelioma, a commonly used model for the human disease, we characterized the rat homologue of NF2 and examined rat chrysotile-induced primary mesotheliomas and cell lines derived from chrysotile- and crocidolite-induced mesotheliomas for alterations in this gene. The coding sequence obtained for the rat NF2 gene had 90% nucleotide homology with the human NF2 gene. The rat NF2 gene was ubiquitously expressed as a 4.4-kb transcript in normal rat tissues as well as in rat mesothelioma cell lines. Reverse transcription-polymerase chain reaction analysis to examine splicing of NF2 exons in mesothelioma cells indicated that the exon splicing pattern was similar in normal and neoplastic cells. To determine if mutations had occurred in the NF2 coding region in rat mesotheliomas, single-strand conformation polymorphism analysis and direct sequencing were used to screen 10 primary tumors and six tumor cell lines. No DNA sequence alterations were observed in any of the rat mesothelioma samples examined. These findings contrast with data reported previously for human mesotheliomas, in which the NF2 gene was found to be mutated in 40% of cases. Taken together, these data suggest that the role of NF2 in the development of rodent asbestos-induced mesothelioma may differ significantly from the role in the human disease.

Animals↗