Tandem Repeats (tandem + repeat)

Distribution by Scientific Domains
Distribution within Life Sciences

Kinds of Tandem Repeats

  • autosomal short tandem repeat
  • number tandem repeat
  • short tandem repeat
  • variable number tandem repeat

  • Terms modified by Tandem Repeats

  • tandem repeat analysis
  • tandem repeat locus
  • tandem repeat polymorphism

  • Selected Abstracts

    Hierarchical modeling of genome-wide Short Tandem Repeat (STR) markers infers native American prehistory

    Cecil M. Lewis Jr.
    Abstract This study examines a genome-wide dataset of 678 Short Tandem Repeat loci characterized in 444 individuals representing 29 Native American populations as well as the Tundra Netsi and Yakut populations from Siberia. Using these data, the study tests four current hypotheses regarding the hierarchical distribution of neutral genetic variation in native South American populations: (1) the western region of South America harbors more variation than the eastern region of South America, (2) Central American and western South American populations cluster exclusively, (3) populations speaking the Chibchan-Paezan and Equatorial-Tucanoan language stock emerge as a group within an otherwise South American clade, (4) Chibchan-Paezan populations in Central America emerge together at the tips of the Chibchan-Paezan cluster. This study finds that hierarchical models with the best fit place Central American populations, and populations speaking the Chibchan-Paezan language stock, at a basal position or separated from the South American group, which is more consistent with a serial founder effect into South America than that previously described. Western (Andean) South America is found to harbor similar levels of variation as eastern (Equatorial-Tucanoan and Ge-Pano-Carib) South America, which is inconsistent with an initial west coast migration into South America. Moreover, in all relevant models, the estimates of genetic diversity within geographic regions suggest a major bottleneck or founder effect occurring within the North American subcontinent, before the peopling of Central and South America. Am J Phys Anthropol 2010. © 2009 Wiley-Liss, Inc. [source]

    Genetic diversity of Y-specific STRs in chimpanzees (Pan troglodytes)

    L. Gusmão
    Abstract Using the primers described for humans, sequences for 11 Y-specific microsatellites (DYS434, DYS435, DYS436, DYS437, DYS438, DYS439, GATA A10, A7.1, A7.2, C4, and H4 [Gusmão et al., in press]), previously described in 10 male chimpanzees (Pan troglodytes), were confirmed in nine additional male chimpanzees. Sequences for nine additional microsatellites (DYS19, DYS385I and II, DYS389I and II, DYS390, DYS391, DYS392, and DYS393) were determined in all 19 male chimpanzees; homology to human Y-Short Tandem Repeat (STRs) was confirmed by sequencing. Good amplification results were not obtained for DYS19 and DYS385I/II. Two amplicons were obtained for DYS389I/II, but in contrast to humans, the larger fragment was not Y-specific. Moreover, no polymorphism was observed for DYS434, DYS435, or GATA A10. Consequently, these eight STRs were eliminated from further analyses, and haplotype and allele frequencies were estimated for the remaining 12 STRs. A high haplotype diversity value was found (1.000 ± 0.017), demonstrating the usefulness and informative power of these Y-STRs for future studies on chimpanzee population genetics.Am. J. Primatol. 57:21,29, 2002. © 2002 Wiley-Liss, Inc. [source]

    Interleukin-1 receptor antagonist and tumour necrosis factor-alpha gene polymorphisms in Turkish patients with allergic contact dermatitis

    CONTACT DERMATITIS, Issue 2 2009
    Ilgen Ertam
    Background: It has been shown that the family of interleukin-1 receptor antagonist (IL-1 RA) and tumour necrosis factor-alpha (TNF,) genes are polymorphic and related to some inflammatory diseases. Allergic contact dermatitis is the classic presentation of delayed-type hypersensitivity responses to exogenous agents. A number of genes playing role in inflammatory response may be associated with allergic contact dermatitis. Objectives: To investigate whether there is an association between IL-1RA and TNF, gene polymorphisms and allergic contact dermatitis in Turkish patients with allergic contact dermatitis. Methods: This study was performed by the collaboration of Departments of Dermatology and Medical Genetics, Ege University, Faculty of Medicine. A total of 50 patients (31 females and 19 males) with allergic contact dermatitis, and 100 age- and sex-matched controls (58 females and 42 males) were included in the study. IL-1RA Variable Number of Tandem Repeats (VNTR) polymorphism in intron 2 and TNF,-308G-A polymorphism were genotyped by using polymerase chain reaction and agarose gel electrophoresis. Results: The frequency of IL-1RA 1/2 (48%) genotype was significantly higher (P = 0.002) in patient group than that is found in control group (22%). The frequency of TNF, (TNF G-308A) G/G genotype was significantly higher in patient group (68%) than that is found in control group (31%) (P = 0.008). Conclusions: Our findings suggest that TNF, (G/G) gene polymorphism may play role in susceptibility to allergic contact dermatitis in Turkish patients. [source]

    Allele Frequency Data for 19 Short Tandem Repeats (PowerPlex® 16 and FFFl) in a Belgian Population Sample

    Ronny Decorte Ph.D
    POPULATION: Belgian Caucasians (Dutch speaking; n=198). [source]

    Analysis of Short Tandem Repeats by Using SERS Monitoring and Electrochemical Melting,

    ANGEWANDTE CHEMIE, Issue 34 2010
    Zum Mitnehmen: Elektrochemisches Schmelzen mit SERS-Detektion an nanostrukturierten Elektroden wurde genutzt, um DNA-Sequenzen mit unterschiedlicher Zahl an kurzen GATA-Tandemwiederholungen zu differenzieren (siehe Diagramm). Die Technik bietet sich für die Konstruktion von transportablen DNA-Analysegeräten an. [source]

    Nucleotide sequence diversity of the 5S rDNA spacer in the simple blade kelp genera Laminaria, Cymathaere and Kjellmaniella (Laminariales, Phaeophyceae) from northern Japan

    Norishige Yotsukura
    SUMMARY Tandem repeats of the 5S ribosomal RNA gene (rDNA) were confirmed for almost all laminarian, cymathaerean and kjellmaniellan species distributed in northern Japan. The nucleotide sequence of the spacer region between tandemly repeated 5S rDNA was investigated for 79 samples from 31 sites. Phylogenetic analysis of the 29 different sequences detected revealed two lineages: (1) Laminaria coriacea group, including Laminaria coriacea Miyabe, Laminaria cichorioides Miyabe, Laminaria sachalinensis (Miyabe) Miyabe, Laminaria yendoana Miyabe, Cymathaere japonica Miyabe et Nagai, Kjellmaniella gyrata (Kjellman) Miyabe and Kjellmaniella crassifolia Miyabe; (2) Laminaria japonica group including Laminaria japonica Areschoug, Laminaria religiosa Miyabe, Laminaria ochotensis Miyabe, Laminaria diabolica Miyabe, Laminaria longipedalis Okamura, Laminaria angustata Kjellman and Laminaria longissima Miyabe. In addition, the latter group was divided into two: subgroup (2a) including L. angustata and L. longissima and subgroup (2b) including L. japonica, L. religiosa, L. ochotensis, L. diabolica and L. longipedalis. Members of the three groups differ from each other in the appearance of ornaments (bullation, gyration and folds) on the surface of the blade. These are absent in group (2a), only present in the early stages of the lifespan of group (2b), and present for the duration of the lifespan in group (1). Genetic distances among samples were extremely small within group (2a). Together with previous crossing studies and data on ocean currents and distribution, these findings suggest that gene flow occurs within group (2b). [source]

    Dopamine transporter gene (DAT1) VNTR polymorphism in major psychiatric disorders: family-based association study in the Bulgarian population

    L. Georgieva
    Objective:,A 40-bp variable number tandem repeat in the 3,-UTR of dopamine transporter gene (DAT1) has been examined for association with major psychiatric disorders in several case,control studies. No significant results have been found. We used a new collection of parent,offspring trios to test for association with schizophrenia (SZ), bipolar 1 disorder (BPI) and schizoaffective (SA) disorder. Method:,We genotyped trios from Bulgarian origin where the proband had SZ (178 trios), BPI (77 trios) and SA (29 trios). Alleles ranging from 5 to 11 repeats were observed. The results were analysed with the extended TDT (ETDT). Results:,No preferential transmission of alleles was observed for any diagnostic group. The presence of allele DAT*10 was associated with the severity and frequency of auditory hallucinations, however, this result is not significant if corrected for multiple testing. Conclusion:,Our results are in agreement with previous reports of a lack of association between this polymorphism and major psychiatric disorders. [source]

    A systematic approach to molecular quantitative determination of mixed chimaerism following allogeneic bone marrow transplantation: an analysis of its applicability in a group of patients with severe aplastic anaemia

    Rocío Hassan
    Abstract:, Mixed chimaerism (MC) following allogeneic bone marrow transplantation (allo-BMT) is defined as the persistent cohabitation of haematopoietic cells from recipients and donors. Its kinetics, clinical implications and more efficient laboratory approaches for MC detection are the object of ongoing research in view of the possibility of developing useful markers. Here we describe a sequential analysis of chimaerism using variable number of tandem repeat (VNTR) polymerase chain reaction (PCR) followed by quantitative, fluorescent labelled, short tandem repeat (STR) PCR. A set of four, highly discriminative VNTR and four STR markers was used to assess chimaerism. Sensitivity and regression analysis indicated that this approach was reliable for routine application in a single BMT centre. We studied 12 patients with severe aplastic anaemia (SAA) who had received allo-BMT, and had been conditioned with cyclosphosphamide (Cy) with or without anti-thymocyte globulin (ATG). We found a 50% prevalence of MC in the whole group, with levels between 4% and 37% of recipient cells. A sustained stable MC pattern after BMT was characteristic of the Cy-only conditioned patients but was also recorded in one patient treated with the Cy + ATG regime who showed a sustained MC pattern over a period of 24 months post-BMT. In none of our patients, MC was associated with an increased risk of graft rejection in a median follow-up of 39.5 months. [source]

    Alternative splicing generates a family of putative secreted and membrane-associated MUC4 mucins

    FEBS JOURNAL, Issue 14 2000
    Nicolas Moniaux
    The MUC4 mucin gene encodes a putative membrane-anchored mucin with predicted size of 930 kDa, for its 26.5-kb allele. It is composed of two regions, the 850-kDa mucin-type subunit MUC4, and the 80-kDa membrane-associated subunit MUC4,. In this study, we cloned and characterized unique MUC4 cDNA sequences that differ from the originally published sequence. Eight alternative splice events located downstream of the central large tandem repeat array generated eight new, distinct cDNAs. The deduced sequences of these MUC4 cDNAs (sv1- MUC4 to sv8- MUC4, the full length cDNA being called sv0- MUC4) provided seven distinct variants, five secreted forms and two membrane-associated forms. Furthermore, two other alternative splicing events located on both sides of the tandem repeat array created two variants, MUC4/Y and MUC4/X, both lacking the central tandem repeat. Therefore, MUC4 can be expressed in three distinct forms, one membrane-bound, one secreted, and one lacking the hallmark feature of mucin, the tandem repeat array. Although no specific function has yet been discovered for the family of proteins putatively produced from the unique MUC4 gene, we suspect that the MUC4 proteins may be implicated in the integrity and renewal of the epithelium. [source]

    The central domain of bovine submaxillary mucin consists of over 50 tandem repeats of 329 amino acids

    FEBS JOURNAL, Issue 8 2000
    Chromosomal localization of the BSM1 gene, porcine counterparts, relations to ovine
    We previously elucidated five distinct protein domains (I,V) for bovine submaxillary mucin, which is encoded by two genes, BSM1 and BSM2. Using Southern blot analysis, genomic cloning and sequencing of the BSM1 gene, we now show that the central domain (V) consists of ,,55 tandem repeats of 329 amino acids and that domains III,V are encoded by a 58.4-kb exon, the largest exon known for all genes to date. The BSM1 gene was mapped by fluorescence in situ hybridization to the proximal half of chromosome 5 at bands q2.2,q2.3. The amino-acid sequence of six tandem repeats (two full and four partial) were found to have only 92,94% identities. We propose that the variability in the amino-acid sequences of the mucin tandem repeat is important for generating the combinatorial library of saccharides that are necessary for the protective function of mucins. The deduced peptide sequences of the central domain match those determined from the purified bovine submaxillary mucin and also show 68,94% identity to published peptide sequences of ovine submaxillary mucin. This indicates that the core protein of ovine submaxillary mucin is closely related to that of bovine submaxillary mucin and contains similar tandem repeats in the central domain. In contrast, the central domain of porcine submaxillary mucin is reported to consist of 81-amino-acid tandem repeats. However, both bovine submaxillary mucin and porcine submaxillary mucin contain similar N-terminal and C-terminal domains and the corresponding genes are in the conserved linkage regions of the respective genomes. [source]

    Additive effect of BDNF and REST polymorphisms is associated with improved general cognitive ability

    F. Miyajima
    Brain-derived neurotrophic factor (BDNF) is a pleiotropic protein involved in neuronal proliferation, differentiation, synaptic plasticity and survival. Independent studies investigating association between the functional BDNF Val66Met polymorphism and cognitive abilities have reported some conflicting findings, which may reflect inadequate sample size, variation in testing methods, population stratification or the confounding effects of other genes. To test the latter hypothesis, we screened and genotyped polymorphisms in the RE1-silencing transcription factor (REST) gene whose function includes the downregulation of BDNF expression. We identified an exon 4 hexadecapeptide variable number tandem repeat (VNTR) with either four or five copies that was located within a proline-rich domain and investigated a further five single nucleotide polymorphisms (SNPs). Using a cohort of 746 community-dwelling older volunteers, we analysed REST genotype data both independently and in combination with the BDNF Val66Met polymorphism. A haplotype within the REST gene containing the four copy VNTR and a non-synonymous SNP showed a weak but significant association with a higher score of general intelligence (P = 0.05). Analysis of this haplotype and the BDNF Val66Met polymorphism in combination showed a significant interaction (global P -value = 0.0003) with an additive increase in cognitive performance for those possessing the BDNF Val66 allele and the REST haplotype containing the four copy repeat (P = 0.004). The REST haplotypes in combination with the BDNF Met66 polymorphism did not reduce cognitive performance more than the independent influence of the Met66 allele. Our results suggest that investigation of a common REST polymorphism may be necessary to help reduce contrasting reports based around BDNF Val66Met and cognition. [source]

    MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and to glioblastoma outcome

    Ulrika Andersson
    Abstract The human telomerase reverse transcriptase (hTERT) gene is upregulated in a majority of malignant tumours. A variable tandem repeat, MNS16A, has been reported to be of functional significance for hTERT expression. Published data on the clinical relevance of MNS16A variants in brain tumours have been contradictory. The present population-based study in the Nordic countries and the United Kingdom evaluated brain-tumour risk and survival in relation to MNS16A minisatellite variants in 648 glioma cases, 473 meningioma cases and 1,359 age, sex and geographically matched controls. By PCR-based genotyping all study subjects with fragments of 240 or 271 bp were judged as having short (S) alleles and subjects with 299 or 331 bp fragments as having long (L) alleles. Relative risk of glioma or meningioma was estimated with logistic regression adjusting for age, sex and country. Overall survival was analysed using Kaplan,Meier estimates and equality of survival distributions using the log-rank test and Cox proportional hazard ratios. The MNS16A genotype was not associated with risk of occurrence of glioma, glioblastoma (GBM) or meningioma. For GBM there were median survivals of 15.3, 11.0 and 10.7 months for the LL, LS and SS genotypes, respectively; the hazard ratio for having the LS genotype compared with the LL was significantly increased HR 2.44 (1.56,3.82) and having the SS genotype versus the LL was nonsignificantly increased HR 1.46 (0.81,2.61). When comparing the LL versus having one of the potentially functional variants LS and SS, the HR was 2.10 (1.41,3.1). However, functionality was not supported as there was no trend towards increasing HR with number of S alleles. Collected data from our and previous studies regarding both risk and survival for the MNS16A genotypes are contradictory and warrant further investigations. © 2009 UICC [source]

    An intron 4 VNTR polymorphism of the endothelial nitric oxide synthase gene is associated with early-onset colorectal cancer

    Chih-Ching Yeh
    Abstract Endothelial-derived nitric oxide, which is produced by endothelial nitric oxide synthase (eNOS), may play an important role in colorectal carcinogenesis. However, the putative contribution of common eNOS genetic polymorphisms to colorectal cancer risk remains unknown. We genotyped 3 polymorphisms of eNOS (T-786C, G894T, and intron4b/a) in 727 colorectal adenocarcinoma cases and 736 age- and sex-matched healthy controls in Taiwan. Genotypes of the T-786C and G894T polymorphisms were determined by fluorescence polarization assays and the 27-bp variable number of tandem repeat (VNTR) polymorphism in intron 4 (intron4b/a) was analyzed by PCR. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Among younger participants (,60 yrs), the intron4a variant genotype was associated with a significantly increased risk of colorectal cancer, compared with the intron4bb genotype (OR = 1.60, 95% CI = 1.04,2.46). In addition, those young individuals bearing a greater number of high-risk genotypes (OR > 1, i.e., CT+TT for T-786C, ba+aa for intron4b/a, and GG for G894T) of eNOS had a higher colorectal cancer risk (ptrend = 0.039). Compared with younger individuals without any putative high-risk genotypes, those with 3 high-risk genotypes had a significantly greater cancer risk (OR = 1.89, 95% CI = 1.04,3.43). Our results suggest that the eNOS intron4b/a polymorphism may contribute to early-onset colorectal cancer risk in the Taiwanese population. © 2008 Wiley-Liss, Inc. [source]

    The MUC1 oncoprotein as a functional target: Immunotoxin binding to ,/, junction mediates cell killing

    Daniel B. Rubinstein
    Abstract MUC1, a heavily glycosylated mucin, has generated considerable interest as a target for tumor killing because of its overexpression in malignancies. Full-length MUC1 (MUC1/TM) is proteolytically cleaved after synthesis generating , and , subunits, which specifically bind in a noncovalent interaction. Although the , chain remains on the cell surface, the , chain binds in an on-and-off interaction. Most anti-MUC1 antibodies (Abs) described to date recognize epitopes within the highly immunogenic ,-chain tandem repeat. Because the ,-chain is shed, such Abs are sequestered and fail to reach MUC1-expressing cells. Immunizing with cDNA encoding MUC1/TM and the spliced MUC1/X isoform from which the tandem repeat has been deleted yielded antibodies to the MUC1 ,/, junction. Pseudomonas toxin PE38 linked to polyclonal anti-MUC1 ,/, junction Abs both bound and killed MUC1-positive malignant cells. Monoclonal DMC209 binds the MUC1 ,/, junction in both MUC1/X and MUC1/TM. When injected into SCID mice xenotransplanted with human breast cancer MDA-MB-231, monoclonal DMC209 showed significant in vivo tumor-suppressive activity. The MUC1/X ,/, junction presents a biologically-significant target in MUC1-expressing malignancies because (i) antibodies directed against cell-bound ,/, junction epitopes reach the intended cellular target, (ii) antibodies to junction epitope are internalized into cells, (iii) anti ,/, junction antibodies can effectively kill high MUC1-expressing cancer cells as antibody-toxin conjugates and (iv) antibodies targeting the MUC1 cell-bound ,/, junction results in tumor suppression in vivo. Our results indicate that cell-bound MUC1 ,/, junction, unlike shed alpha chain, represents a highly effective moiety for targeting and killing MUC1-expressing malignancies. © 2008 Wiley-Liss, Inc. [source]

    Identification of a novel single nucleotide polymorphism in the first tandem repeat sequence of the thymidylate synthase 2R allele

    Lisa F. Lincz
    Abstract Thymidylate synthase (TS) activity is an important determinant of response to chemotherapy with fluoropyrimidine prodrugs and its expression is largely determined by the number of functional upstream stimulatory factor (USF) E-box consensus elements present in the 5,regulatory region of the TYMS gene. Two known polymorphisms in this area, a variable number of tandem repeat (VNTR) consisting of 2 or 3 repeats (2R/3R) of a 28-bp sequence and a further G > C single nucleotide substitution within the second repeat of the 3R, result in genotypes with between 2 and 4 functional repeats in most humans. Here, we identify a further G > C SNP in the first repeat of the TYMS 2R allele, which effectively abolishes the only functional USF protein binding site in this promoter. The frequency of the new allele was found to be 4.2% (95% CI = 1.4,9.6%), accounting for 8.8% (95% CI = 2.9,19.3%) of all 2R alleles in our patient cohort. Thus, we observed that the lowest number of inherited functional binding sites is 1 instead of 2 as previously thought, and could potentially be 0 in a homozygous individual. This would severely decrease TS expression and may have implications for predicting efficacy and toxicity of therapy with commonly used fluorouracil-based therapy regimes. © 2007 Wiley-Liss, Inc. [source]

    The thymidylate synthase tandem repeat promoter polymorphism: A predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancer

    Katja Ott
    Abstract We evaluated DNA polymorphisms in the thymidylate synthase (TS) and 5,10- methylene-tetrahydrofolate reductase (MTHFR) genes for an association with response and survival in locally advanced gastric cancer treated with 5-FU based preoperative chemotherapy (CTx). DNA of 238 patients (CTx-group: total n = 135, completely resected (R0) n = 102; without CTx: R0 n = 103) was isolated from blood or from nontumorous tissues. In the CTx-group, genotyping of the tandem repeat and the G/C polymorphism in the triple repeat in the promoter region of the TS gene and of the C677T polymorphism of the MTHFR gene was performed. None of the TS or MTHFR genotypes were associated with histopathological response and only the TS tandem repeat polymorphism was significantly related to survival (all patients n = 135, p = 0.002; R0 resected patients n = 102, p = 0.007; log-rank test). Multivariate analysis revealed ypN (p < 0.001) and the TS tandem repeat polymorphism as independent prognostic factors in the CTx-R0-group (p = 0.003). Analyzing the prognostic significance of the TS polymorphisms in the R0-group without CTx, TS genotypes were not significantly associated with survival. Comparing survival between R0 patients with and without CTx in the respective TS genotype groups of the tandem repeat polymorphism, a significant survival benefit for the patients with CTx was found for the 2rpt/2rpt (n = 49; p = 0.002) and 2rpt/3rpt genotypes (n = 99; p = 0.004), but not for the 3rpt/3rpt genotype (n = 57; p = 0.93). Patients' survival after CTx was associated with the TS tandem repeat polymorphism. CTx did not improve survival of patients with the 3rpt/3rpt genotype. Thus, a different therapy might be more appropriate for these patients. © 2006 Wiley-Liss, Inc. [source]

    Association of serotonin transporter gene-linked polymorphic region and variable number of tandem repeat polymorphism of the serotonin transporter gene in lichen simplex chronicus patients with psychiatric status

    Necmettin Kirtak MD
    Background, The serotonin (5-hydroxytryptamine; 5-HT) is a key neurotransmitter in the central nervous system and a responsible mediator for the itch. Dysregulation of serotonergic pathways has been implicated in the pathogenesis of many complex neuropsychiatric diseases. Objectives, The purpose of this study was to evaluate the relationship between lichen simplex chronicus and dysfunction and serotonin transporter (5-HTT) gene polymorphism. Methods, Thirty-nine patients with lichen simplex chronicus and 61 healthy control subjects were examined. Results, The results for the patients and control subjects were not significantly different (P > 0.05) in long/long (L/L) and long/short (L/S) genotypes of 5-HTT gene-linked polymorphic region (HTTLPR) polymorphism, but short/short S/S genotype was lower in lichen simplex chronicus patients (17.9%) than in controls (42.6%). This difference was statistically significant (P = 0.028). The results for the patients and control subjects were not significantly different in 12/12, 10/12 and 10/10 genotypes of variable number of tandem repeat (VNTR) polymorphism (P > 0.05). Beck depression inventory (BDI) scores and symptom checklist-90-revised (SCL-90) psychotic subscale were overrepresented significantly in the 12/12 genotypes than 10/12 genotypes. State and Trait Anxiety Inventory tests (STAI-I and -II) point averages were not statistically significant (P > 0.05) Conclusion, S/S genotypes of HTTLPR polymorphism in the 5-HTT gene may be related to lichen simplex chronicus and that patients who have 12/12 genotypes of VNTR polymorphism may be affected psychiatrically. [source]

    IL-1 receptor antagonist gene polymorphism in idiopathic recurrent spontaneous abortion in a Chinese Han population

    M. Z. Dai
    Summary Interleukin-1 receptor antagonist (IL-1Ra) has been supposed to play important roles in pregnancy. The purpose of this study was to evaluate the association between the polymorphisms of IL-1Ra gene (IL1RN) variable number tandem repeat (VNTR) in intron 2 with idiopathic recurrent spontaneous abortion (RSA). Ninety-two RSA patients and hundred normal women with at least one live birth and no history of miscarriage were included in the study. Frequencies of the IL1RN alleles and genotypes were determined. Data revealed that the prevalence of IL1RN allele and genotype was not significant between the RSA and control group (all P > 0.05). Our finding indicated that the polymorphism VNTR of IL1RN gene in intron 2 may not be a risk factor for RSA in the Chinese Han population. [source]

    Study on VNTR polymorphism of gene IL-1RA in 19 Chinese populations

    J. Jiang
    Summary Earlier studies suggested that a variable number tandem repeat (VNTR) polymorphism in intron 2 of the interleukin-1 receptor antagonist (IL-1RA) gene might be associated with some chronic inflammatory diseases, autoimmune diseases and solid tumours. To study the distribution of this polymorphism in China, 1352 samples were collected from 19 widely distributed Chinese populations. PCR was used to genotype the VNTR. The overall frequencies of allele 1 and allele 2 were 0.913 and 0.064 respectively. The frequency of the allele 2 was significantly different between the northeastern and the northwestern populations. Moreover, the allele frequencies at this locus in three Chinese Han populations were different from that in minority populations. When compared with other populations worldwide, the frequencies of the two alleles in China were not significantly different from those in the Asian and Pacific Islands. However, the prevalence of allele 1 in China was significantly higher, and the prevalence of allele 2 was significantly lower, than those in American and European Caucasians, and the pairwise Fst values reinforced this observation. The differences of the allele frequencies between different regions and within the same region showed that geography and race have important roles in the population differentiation for the IL-1RA gene. In summary, our results provide a valuable reference for population genetic information and future disease association studies in Chinese populations. [source]

    The genetic differences with whole genome linkage disequilibrium mapping between responder and non-responder in interferon-, and ribavirin combined therapy for chronic hepatitis C patients

    P.-J. Chen
    Summary Interferon-, and ribavirin combined therapy has been a mainstream treatment for hepatitis C infection. The efficacy of this combined treatment is around 30% to 60%, and the factors affecting the responsiveness are still poorly defined. Our study is intended to investigate the genetic differences between responder and non-responder patients. The genome-wide linkage disequilibrium screening for loci associated with genetic difference between two patient groups was conducted by using 382 autosomal short tandem repeat (STR) markers involving 92 patients. We have identified 19 STR markers displaying different allele frequencies between the two patient groups. In addition, based on their genomic location and biological function, we selected the CD81 and IL15 genes to perform single nucleotide polymorphism genotyping. In conclusion, this study may provide a new approach for identifying the associated polymorphisms and the susceptible loci for interferon-, and ribavirin combined therapy in patients with chronic hepatitis C. [source]

    MICA-STR, HLA-B haplotypic diversity and linkage disequilibrium in the Hunan Han population of southern China

    W. Tian
    Summary Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located 46 kb centromeric to HLA-B and encodes a stress-inducible protein. MICA allelic variation is thought to be associated with disease susceptibility and immune response to transplants. This study was aimed to investigate the haplotypic diversity and linkage disequilibrium between human leukocyte antigen (HLA)-B and (GCT)n short tandem repeat in exon 5 of MICA gene (MICA-STR) in a southern Chinese Han population. Fifty-eight randomly selected nuclear families with 183 members including 85 unrelated parental samples were collected in Hunan province, southern China. HLA-B generic typing was performed by polymerase chain reaction,sequence-specific priming (PCR,SSP), and samples showing novel HLA-B-MICA-STR linkage were further typed for HLA-B allelic variation by high-resolution PCR,SSP. MICA-STR allelic variation and MICA gene deletion (MICA*Del) were detected by fluorescent PCR,size sequencing and PCR,SSP. Haplotype was determined through family segregation analysis. Statistical analysis was applied to the data of the 85 unrelated parental samples. Nineteen HLA-B specificities and seven MICA-STR allelic variants were observed in 85 unrelated parental samples, the most predominant of which were HLA-B*46, -B60, -B*13, and -B*15, and MICA*A5, MICA*A5.1 and MICA*A4, respectively. Genotype distributions of HLA-B, MICA-STR loci were consistent with Hardy,Weinberg proportions. The HLA-B-MICA-STR haplotypic phases of all 85 unrelated parental samples were unambiguously assigned, which contained 30 kinds of HLA-B, MICA-STR haplotypic combinations, nine of them have not been reported in the literature. Significant positive linkage disequilibria between certain HLA-B and MICA-STR alleles, including HLA-B*13 and MICA*A4, HLA-B*38 and MICA*A9, HLA-B*58 and MICA*A9, HLA-B*46 and MICA*A5, HLA-B*51 and MICA*A6, HLA-B*52 and MICA*A6, and HLA-B60 and MICA*A5.1, were observed. HLA-B*48 was linked to MICA*A5, MICA*A5.1 and MICA*Del. HLA-B*5801-MICA*A10 linkage was found in a family. Our data indicated a high degree of haplotypic diversity and strong linkage disequilibrium between MICA-STR and HLA-B in a southern Chinese Han population, the data will inform future studies on anthropology, donor,recipient HLA matching in clinical transplantation and HLA-linked disease association. [source]

    C-reactive protein levels and common polymorphisms of the interleukin-1 gene cluster and interleukin-6 gene in patients with coronary heart disease

    G. Latkovskis
    Summary C-reactive protein (CRP) is an inflammatory marker associated with increased cardiovascular risk. Production of CRP is regulated by interleukin (IL)-1,, IL-1 receptor antagonist and IL-6. In 160 patients with coronary heart disease (CHD) confirmed by angiography, we examined the relationship between CRP level and five polymorphisms in genes coding for these cytokines: IL-1B(,511), IL-1B(+3954), a variable number tandem repeat (VNTR) polymorphism in intron 2 of IL-1RN [IL-1RN(VNTR)], IL-6(,174) and IL-6(,572). CRP values were logarithmically normalized (log-CRP) for statistical calculations. In univariate analysis, carrier status for the IL-1B(+3954)T allele and IL-1RN(VNTR) allele 2 [IL-1RN(VNTR)*2] correlated with higher (P < 0.01) and lower (P < 0.05) log-CRP values, respectively. Among the potential confounding factors analysed, smoking, body mass index, total cholesterol (P < 0.05 for all) and diabetes (P = 0.056) were positively correlated with CRP level. After adjustment for non-genetic covariates, CRP levels remained significantly (P < 0.01) higher in carriers of IL-1B(+3954)T than in non-carriers: mean log-CRP (with 95% confidence interval) was 0.443 (0.311,0.574) for CT or TT genotypes compared with 0.240 (0.107,0.373) for the CC genotype, which corresponded to back-transformed CRP levels of 2.77 and 1.74 mg l,1, respectively. Adjusted association was also significant for IL-1RN(VNTR)*2 (P < 0.01), with lower CRP levels in the presence of allele 2: the mean log-CRP value was 0.252 (0.115,0.388) for carriers and 0.421 (0.290,0.552) for non-carriers (CRP 1.79 and 2.64 mg l,1, respectively). When alleles of both polymorphisms were entered into the model simultaneously, the association remained significant for IL-1B(+3954)T (P < 0.05), but not for IL-1RN(VNTR)*2. We conclude that IL-1B(+3954)T is associated with higher CRP levels in patients with CHD, and we found that this association was significant after adjustment for major risk factors. Our data also suggest a possible relationship of IL-1RN(VNTR)*2 with lower CRP levels in the same patients. [source]

    Association of the OGG1 Ser326Cys polymorphism with tooth loss

    Yoshinori Hasui
    Abstract Although tooth loss is a serious health problem for elderly people, little is known about the genetic basis for susceptibility to it. In the present study we aimed to find a single nucleotide polymorphism (SNP) associated with tooth loss. DNA samples from 119 outpatients (mean age=78.8 years) were genotyped on seven polymorphisms (tumor necrosis factor-, ,1031T/C, interleukin-1, ,511C/T, interleukin-6 ,634C/G, macrophage migration inhibitory factor ,173G/C, interleukin-1 receptor antagonist variable number of tandem repeat in intron 2, matrix metalloproteinase-1 ,16071G/2G, and oxoguanine glycosylase 1 (OGG1) Ser326Cys (1245C/G)), and the results were statistically evaluated. Of the seven polymorphisms tested, only OGG1 Ser326Cys was revealed to associate with tooth loss at a statistically significant level (P=0.0086). In addition, a multivariate logistic regression analysis in which age, gender, body mass index (BMI), and ischemic heart disease were included as independent variables indicated that Ser326Cys could be an independent factor affecting tooth loss (OR, 3.191; 95%CI, 1.174,8.672). The data suggest that the OGG1 Ser326Cys polymorphism may be associated with tooth loss. J. Clin. Lab. Anal. 20:47,51, 2006. © 2006 Wiley-Liss, Inc. [source]

    Association of interleukin-1 receptor antagonist gene polymorphisms with early onset periodontitis in Japanese

    Hideaki Tai
    Abstract Background/Aims: Early onset periodontitis (EOP), newly ,aggressive periodontitis', is considered to have genetic basis, which have not been clearly defined. The interleukin-1 (IL-1) gene cluster polymorphism as one of genetic factors may influence the expression of several chronic inflammatory diseases. The aim of this study is to investigate the frequency of single nucleotide polymorphisms (SNPs) in the genes encoding IL-1,, IL-1, and a variable number of tandem repeat (VNTR) polymorphisms in the IL-1 receptor antagonist gene (IL-1RN) in 47 generalized EOP (G-EOP) patients and 97 periodontally healthy controls. Material and methods: All subjects were of Japanese descent and systemically healthy. They were identified according to established clinical criteria. SNPs in the IL-1, (+ 4845) and IL-1, (, 511, + 3954) genes were analyzed by amplifying the polymorphic region using polymerase chain reaction (PCR), followed by restriction-enzyme digestion and agarose gel electrophoresis. IL-1RN (VNTR) polymorphisms were then detected by PCR amplification and fragment size analysis. Results: There was no significant difference in the IL-, (+ 4845) and IL-1, (, 511, +,3954) genotypes and allele frequencies between G-EOP patients and healthy controls. However, the frequency of IL-1RN (VNTR) polymorphic alleles was found to be significantly increased in G-EOP patients (,2 test, P = 0.007; odds ratio = 3.40). Additionally, the carriage rate of IL-1RN (VNTR) polymorphisms was significantly higher in G-EOP patients than in healthy controls (,2 test, P = 0.005; odds ratio = 3.81). Conclusion: These findings suggest that IL-1RN (VNTR) polymorphisms are associated with G-EOP in Japanese. [source]

    Direct STR Amplification from Whole Blood and Blood- or Saliva-Spotted FTA® without DNA Purification,

    Su Jeong Park Ph.D.
    Abstract:, The DNA purification step has been thought to be essential for typing of STR DNA. However, this process is time-consuming, and there is a risk of unexpected cross-contamination during purification. We report a new method for direct short tandem repeat (STR) amplification using a newly developed direct PCR buffer, AnyDirectÔ, which can amplify STR loci from whole blood and blood- or saliva-spotted FTA® cards without DNA purification. The autosomal and Y chromosomal STR loci were analyzed for whole blood and blood or saliva spots of random individuals, followed by comparison of the results with those of corresponding purified DNA. The results from whole blood and blood spots showed perfect concordance with those from purified DNA without allele or locus drop-out. However, in the case of saliva spots, no amplification or locus drop-out was observed in some of the samples, which offers a topic for further study. Additionally, some commercial hot-start DNA polymerases other than AmpliTaq Gold® DNA polymerase were also found to be compatible with this buffer system. Therefore, this direct PCR buffer was demonstrated to be useful for fast forensic DNA analysis or criminal DNA databases for which there is no need to store DNA samples. [source]

    The Application of Miniplex Primer Sets in the Analysis of Degraded DNA from Human Skeletal Remains§

    Kerry L. Opel M.A.
    ABSTRACT: A new set of multiplexed PCR primers has been applied to the analysis of human skeletal remains to determine their efficacy in analyzing degraded DNA. These primer sets, known as Miniplexes, produce shorter amplicons (50,280 base pairs (bp)) than standard short tandem repeat (STR) kits, but still utilize the 13 CODIS STR loci, providing results that are searchable on national DNA databases. In this study, a set of 31 different human remains were exposed to a variety of environmental conditions, extracted, and amplified with commercial and Miniplex DNA typing kits. The amplification efficiency of the Miniplex sets was then compared with the Promega PowerPlex® 16 system. Sixty-four percent of the samples generated full profiles when amplified with the Miniplexes, while only 16% of the samples generated full profiles with the Powerplex® 16 kit. Complete profiles were obtained for 11 of the 12 Miniplex loci with amplicon sizes less than 200 bp. These data suggest smaller PCR amplicons may provide a useful alternative to mitochondrial DNA for anthropological and forensic analysis of degraded DNA from human skeletal remains. [source]

    MAOA Interacts With the ALDH2 Gene in Anxiety,Depression Alcohol Dependence

    ALCOHOLISM, Issue 7 2010
    Sheng-Yu Lee
    Background:, Alcohol dependence is usually comorbid with anxiety disorder, depressive disorder, or both; this comorbidity may increase drinking behavior. We previously hypothesized that anxiety,depressive alcohol dependence (ANX/DEP ALC) was a genetically specific subtype of alcohol dependence. ANX/DEP ALC may be related to dopamine and serotonin, which are catalyzed by monoamine oxidase A (MAOA) and acetaldehyde dehydrogenase 2 (ALDH2). The aim of this study was to determine whether the interaction between the MAOA and the ALDH2 genes is associated with ANX/DEP ALC. Methods:, We recruited 383 Han Chinese men in Taiwan: 143 ANX/DEP ALC and 240 healthy controls. The diagnosis of ANX/DEP ALC (alcohol dependence with a past or current history of anxiety, depressive disorder, or both) was made using DSM-IV criteria. Genotypes of ALDH2 and MAOA-uVNTR (variable number of tandem repeat located upstream) were determined using PCR-RFLP. Results:, The ALDH2, but not the MAOA-uVNTR, polymorphism was associated with ANX/DEP ALC. After stratifying the MAOA-uVNTR polymorphism, we found a stronger association between the ALDH2*1/*2 and *2/*2 genotypes and the controls in the MAOA-uVNTR 4-repeat subgroup. Logistic regression significantly associated the interaction between ALDH2 and MAOA variants with ANX/DEP ALC. Conclusion:, We conclude that the MAOA and ALDH2 genes interact in ANX/DEP ALC. Although the MAOA gene alone is not associated with ANX/DEP ALC, we hypothesize that different variants of MAOA-uVNTR polymorphisms modify the protective effects of the ALDH2*2 allele on ANX/DEP ALC in Han Chinese in Taiwan. [source]

    MAOA-uVNTR Polymorphism May Modify the Protective Effect of ALDH2 Gene Against Alcohol Dependence in Antisocial Personality Disorder

    ALCOHOLISM, Issue 6 2009
    Sheng-Yu Lee
    Background:, Antisocial alcoholism is related to dopamine and serotonin which are catalyzed by monoamine oxidase A (MAOA) and acetaldehyde dehydrogenase 2 (ALDH2). The objective of this study is to determine whether the interaction between the MAOA and the ALDH2 genes is associated with subjects with antisocial personality disorder (ASPD) having alcoholism. Methods:, A total of 294 Han Chinese men in Taiwan including 132 ASPD with alcoholism (Antisocial ALC) and 162 without alcoholism (Antisocial Non-ALC) were recruited in this study. Alcohol dependence and ASPD were diagnosed according to DSM-IV criteria. Genotypes of ALDH2 and MAOA-uVNTR were determined using PCR-RFLP. Results:, A significant difference of ALDH2 polymorphisms (p = 3.39E-05), but not of MAOA, was found among the 2 study groups. However, only after the stratification of the MAOA-uVNTR (variable number of tandem repeat located upstream) 3-repeat, a significant association between Antisocial Non-ALC and ALDH2*1/*2 or *2/*2 genotypes was shown (p = 1.46E,05; odds ratio = 3.913); whereas stratification of MAOA-uVNTR 4-repeat revealed no association. Multiple logistic regression analysis further revealed significant interaction of MAOA and ALDH2 gene in antisocial ALC (odds ratio = 2.927; p = 0.032). Conclusion:, The possible interaction of MAOA and ALDH2 gene is associated with Antisocial ALC in Han Chinese males in Taiwan. However, the protective effects of the ALDH2*2 allele against alcoholism might disappear in subjects with ASPD and carrying MAOA-uVNTR 4-repeat allele in the Han Chinese male population. [source]

    The 3, Part of the Dopamine Transporter Gene DAT1/SLC6A3 Is Associated With Withdrawal Seizures in Patients With Alcohol Dependence

    ALCOHOLISM, Issue 1 2008
    Yann Le Strat
    Background: Some studies have reported that the A9 allele of the variable nucleotide tandem repeat (VNTR) of the gene which encodes the dopamine transporter (DAT1/SLC6A3) is associated with alcoholism withdrawal symptoms such as alcohol withdrawal seizures (WSs), whereas others did not. We investigated whether polymorphisms within the DAT1 gene are associated with WS taking into account some of the confounding factors such as the severity of alcohol dependence. Methods: To further assess the role of this gene in WS, we genotyped the VNTR and 7 single nucleotide polymorphisms (SNPs) encompassing the DAT1 gene in a sample of 250 alcohol-dependent subjects (175 men and 75 women), of whom 24% exhibited WSs, taking into account the severity of alcohol dependence. Results: The VNTR is associated with an increased risk of WSs (odd ratio = 3.5; p = 0.019), even when controlling for confounding factors (p = 0.031). As 2 SNPs, in roughly the same location of the gene (namely rs27072 and rs27048), are also associated with WSs, it is possible that the initial association of the VNTR polymorphism was tagging a specific haplotype of this gene. Indeed, in our sample of alcohol-dependent patients, 2 haplotypes were associated with a significantly different risk of WSs. Conclusions: The present study adds evidence for a significant role of the 3, part of the DAT1 gene in WS of alcohol-dependent patients, not only because it is in accordance with previous work, but also because of larger statistical power (as relying on a sample over sampled with the studied phenotype), as it gives a more precise analysis of different SNPs within the DAT1 gene, and as it confirms the association when major potentially confounding factors are taken into account in a logistical regression analysis. [source]

    Age-related change in the association between a polymorphism in the PER3 gene and preferred timing of sleep and waking activities

    Summary The objective of this study was to investigate the effect of age on the association between preferred timing of sleep and waking activities and a coding-region variable number tandem repeat (VNTR) polymorphism in the clock gene PER3. We have previously reported this polymorphism to associate with diurnal preference and delayed sleep phase syndrome (DSPS). Participants (n = 1590; 707 males and 883 females) completed the Horne,Östberg (HÖ) questionnaire for diurnal preference and provided a DNA sample. Overall HÖ scores were plotted against age. The 5% extremes and intermediates were selected for genotyping. Frequencies of the PER3 4- and 5-repeat alleles were examined in separate age groups (18,29, 30,39, 40,49 and 50+ years of age). The 4-repeat allele was significantly more frequent in evening types, and the 5-repeat allele more frequent in morning types (Fisher's exact test, P = 0.016). Analysis in the four age groupings revealed that the strength of this association attenuated with age and was significant only in the youngest group (18,29 years). These results extend our previous finding of an association between the PER3 VNTR and diurnal preference. They also demonstrate that diurnal preference in young people is more closely associated with this polymorphism than it is in other age groups. [source]