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Sample records for vntr allele vntr

  1. Molecular strain typing of Brucella abortus isolates from Italy by two VNTR allele sizing technologies.

    Science.gov (United States)

    De Santis, Riccardo; Ancora, Massimo; De Massis, Fabrizio; Ciammaruconi, Andrea; Zilli, Katiuscia; Di Giannatale, Elisabetta; Pittiglio, Valentina; Fillo, Silvia; Lista, Florigio

    2013-10-01

    Brucellosis, one of the most important re-emerging zoonoses in many countries, is caused by bacteria belonging to the genus Brucella. Furthermore these bacteria represent potential biological warfare agents and the identification of species and biovars of field strains may be crucial for tracing back source of infection, allowing to discriminate naturally occurring outbreaks instead of bioterrorist events. In the last years, multiple-locus variable-number tandem repeat analysis (MLVA) has been proposed as complement of the classical biotyping methods and it has been applied for genotyping large collections of Brucella spp. At present, the MLVA band profiles may be resolved by automated or manual procedures. The Lab on a chip technology represents a valid alternative to standard genotyping techniques (as agarose gel electrophoresis) and it has been previously used for Brucella genotyping. Recently, a new high-throughput genotyping analysis system based on capillary gel electrophoresis, the QIAxcel, has been described. The aim of the study was to evaluate the ability of two DNA sizing equipments, the QIAxcel System and the Lab chip GX, to correctly call alleles at the sixteen loci including one frequently used MLVA assay for Brucella genotyping. The results confirmed that these technologies represent a meaningful advancement in high-throughput Brucella genotyping. Considering the accuracy required to confidently resolve loci discrimination, QIAxcel shows a better ability to measure VNTR allele sizes compared to LabChip GX.

  2. Allele distribution and genetic diversity of VNTR loci in Salmonella enterica serotype Enteritidis isolates from different sources

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    Bartkus Joanne M

    2008-09-01

    Full Text Available Abstract Background Salmonella enterica serotype Enteritidis (S. Enteritidis is a zoonotic pathogen, which can be found in many sources including animals and the environment. However, little is known about the molecular relatedness among S. Enteritidis isolates from different sources. We have applied multiple-locus variable number tandem repeat analysis (MLVA to study the genetic diversity of S. Enteritidis isolates from human and non-human sources. Results We identified 38 unique MLVA types using nine VNTR loci markers for discrimination between 145 S. Enteritidis isolates from different sources including humans (n = 41, chickens (n = 45, and eggs (n = 40. There were 20 distinct MLVA types identified from human isolates, 17 distinct MLVA types from chicken isolates, and 5 from egg isolates. We compared allele distribution and frequency for each VNTR marker and measured allelic polymorphism within each VNTR locus of S. Enteritidis isolates from the sources using Nei's diversity index (D. Differences in allele distribution and frequency were detected in most loci of study isolates. Different genetic diversity for certain loci was identified in isolates from different sources. The average of genetic diversity (D was lower in egg isolates (0.16 compared to human (0.41 and chicken (0.30. However, for loci SE3, SE7, and SE9, human isolates showed significantly higher diversity than both chicken and egg isolates. Whereas for loci SE5 and SE10, chicken isolates had significantly higher diversity than both human and egg isolates. Minimum-spanning tree (MST comprised one major cluster, a minor cluster, and four clonal expansions. MLVA application enabled a cluster analysis by the MST of the S. Enteritidis isolates by sources, which allows a great insight into the genetic relatedness and the possible flow of these organisms between different reservoirs and humans. Conclusion Differences in allele distribution and genetic diversity of VNTR loci in S

  3. Variation of DAT1 VNTR alleles and genotypes among old ethnic groups in Mesopotamia to the Oxus region.

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    Banoei, Mohammad Mehdi; Chaleshtori, Morteza Hashemzadeh; Sanati, Mohammad Hossein; Shariati, Parvin; Houshmand, Massoud; Majidizadeh, Tayebeh; Soltani, Niloofar Jahangir; Golalipour, Massoud

    2008-02-01

    Variation of a VNTR in the DAT1 gene in seven ethnic groups of the Middle East was used to infer the history and affinities of these groups. The populations consisted of Assyrian, Jewish, Zoroastrian, Armenian, Turkmen, and Arab peoples of Iran, Iraq, and Kuwait. Three hundred forty subjects from these seven ethnic groups were screened for DAT1. DAT1 VNTR genotyping showed 3, 6, 7, 8, 9, 10, 11, and 12 alleles in the samples. Analysis of these data revealed differentiation and relationship among the populations. In this region, which covers an area of 2-2.5 million km2, the influence of geography and especially of linguistic characteristics has had potentially major effects on differentiation. Religion also has played a major role in imposing restrictions on some ethnic groups, who as a consequence have maintained their community. Overall, these ethnic groups showed greater heterogeneity compared to other populations.

  4. Novel alleles of 31-bp VNTR polymorphism in the human cystathionine -synthase (CBS) gene were detected in healthy Asians

    Indian Academy of Sciences (India)

    Yik-Yuen Gan; Chuan-Fei Chen

    2010-12-01

    A 31-bp variable number of tandem repeats (VNTR) polymorphism of the cystathionine -synthase (CBS) gene was earlier reported in Caucasians of predominantly European descent and Indo–Caucasoid populations.We report here for the first time, the detection of allele 20, which was absent in Caucasian and Indo–Caucasoid populations, as a common allele present in Singaporean Chinese (6.25%), Indians (11.7%), and Malays (11.5%). Hence, allele 20 might be a specific allele for Asian populations. A relatively common allele 19 found in the Caucasian and Indo–Caucasoid populations (10.4%–10.6%) was absent in the Asian samples of this study. Therefore, allele 19 might be a specific allele for the Caucasian populations. A novel and rare allele 13, which was not reported before in the Caucasian and Indo–Caucasoid populations, was found in 0.5% of Singaporean Chinese as genotype 13/17 heterozygotes. The presence of alleles 13 and 20 were verified by DNA sequencing. There were five new genotypes (13/17, 16/20, 17/20, 18/20 and 20/20) not reported before in the Caucasian and Indo–Caucasoid populations, detected in this study. Nine genotypes (15/18, 16/18, 16/21, 17/19, 18/19, 18/21, 19/19, 19/21 and 21/21) which were present in the Caucasian and/or Indo–Caucasoid populations were absent in this study. Our results showed that CBS 31-bp VNTR polymorphism has a distinct genetic difference in allele and genotype frequencies between the European Caucasians, Indo–Caucasoid and Asian populations.

  5. [Evaluation of variable number of tandem repeats (VNTR) isolates of Mycobacterium bovis in Algeria].

    Science.gov (United States)

    Sahraoui, Naima; Muller, Borna; Djamel, Yala; Fadéla, Boulahbal; Rachid, Ouzrout; Jakob, Zinsstag; Djamel, Guetarni

    2010-01-01

    The discriminatory potency of variable number of tandem repeats (VNTR), based on 7 loci (MIRU 26, 27 and 5 ETRs A, B, C, D, E) was assayed on Mycobacterium bovis strains obtained from samples due to tuberculosis in two slaughterhouses in Algeria. The technique of MIRU-VNTR has been evaluated on 88 strains of M. bovis and one strain of M. caprea and shows 41 different profiles. Results showed that the VNTR were highly discriminatory with an allelic diversity of 0.930 when four loci (ETR A, B, C and MIRU 27) were highly discriminatory (h>0.25) and three loci (ETR D and E MIRU 26) moderately discriminatory (0.11VNTR loci were highly discriminatory be adequate for the first proper differentiation of strains of M. bovis in Algeria. The VNTR technique has proved a valuable tool for further development and application of epidemiological research for the of tuberculosis transmission in Algeria.

  6. Mutations in the VNTR of the carboxyl-ester lipase gene (CEL) are a rare cause of monogenic diabetes

    DEFF Research Database (Denmark)

    Torsvik, Janniche; Johansson, Stefan; Johansen, Anders;

    2009-01-01

    of the VNTR, and determined the VNTR-length of each allele. When blindly testing 56 members of the two families with known single-base deletions in the CEL VNTR, the method correctly assessed the mutation carriers. Screening of 241 probands from suspected maturity-onset diabetes of the young (MODY) families...... negative for mutations in known MODY genes (95 individuals from Denmark and 146 individuals from UK) revealed no deletions in the proximal repeats of the CEL VNTR. However, we found one Danish patient with a short, novel CEL allele containing only three VNTR repeats (normal range 7-23 in healthy controls......). This allele co-segregated with diabetes or impaired glucose tolerance in the patient's family as six of seven mutation carriers were affected. We also identified individuals who had three copies of a complete CEL VNTR. In conclusion, the CEL gene is highly polymorphic, but mutations in CEL are likely...

  7. Brain morphometric correlates of MAOA-uVNTR polymorphism in violent behavior

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    C. Romero-Rebollar

    2015-01-01

    Discussion: This findings suggests that grey matter integrity in superior temporal pole could be a neurobiological correlate of the allelic association between MAOA-uVNTR polymorphism and violent behavior due to its implication in socio-emotional processing.

  8. Polymorphism Identification of VNTR30 and VNTR36 Loci in Pathogenic Leptospira Serovares in Iran

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    Sama Reza Soltani

    2014-01-01

    Full Text Available Abstract Background and objective: Leptospirosis, is the zoonotic disease which is characterized as an emerging infectious disease with large documented outbreaks. Epidemiological investigations are needed to distinguish outbreak situations or to trace reservoirs of the organisms. Today MLVA technique is used for segregating and identifying of Leptospira serovares. The method has potential application in furthering the understanding of Leptospiral molecular epidemiology. The propose of this study is rapid identification of pathogenic Leptospira serovares in Iran. Materials and methods: A total 12 pathogenic Leptospiral serovares and 1 saprophytic serovar that maintained from microbial bank of Razi Vaccine and Serum Research Institute, Karaj, Iran. The Genomic DNA of Leptospira was extracted .PCR was performed with primers for loci VNTR30, VNTR36. The amplified fragments were analyzed by gel electrophoresis . The sizes of the amplified products were estimated by comparison with a 100 -bp ladder. Results: All loci successfully amplified in all pathogenic leptospira serovars. The saprophytic serovar showed no amplified fragments. The results show VNTR30 has a wide range of polymorphism between Atumnalis, Hardjo St.Hardjo bovis, Pomona St. UT364, Icterohaemorrhagia St. RGA and VNTR36 shows variation between Canicola St. Hondutrecht IV , Hardjo St.Hardjo bovis, Pomona St. UT364 Conclusion: Most of the VNTR patterns were similar in different serovares while showed significant differences with same serovares of South America and Europe. On the other our serovares resemble Southeast Asia serovares because of the same geographical area. Among serovares Canicola St. Hondutrecht IV and Canicola St. Fiocruz LV133 identified by MLVA, PFGE was unable to differentiate them. In conclusion MLVA technique with wide range of polymorphism is known as good marker for identification serovares.

  9. A panel of VNTR markers in pigs.

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    Signer, E N; Gu, F; Jeffreys, A J

    1996-06-01

    By cloning tandemly repeated sequences from the pig genome by use of non-porcine minisatellite probes for library screening, five novel polymorphic VNTR loci were isolated: three minisatellites and two satellite-like loci. Four of them could be mapped onto chromosomes by linkage analysis and/or in situ hybridization. They were assigned to Chromosomes (Chrs) 5, 6, 14, and 16. Physical mapping on both presumed satellites and on one of the minisatellites revealed that the former resided near or at the centromere and the latter towards the chromosome ends. The location of the minisatellite is of particular interest since, together with data on three other minisatellites previously isolated, it supports the idea that, as in humans, minisatellites may preferentially be subtelomeric also in pigs.

  10. FREQUENCY DISTRIBUTION OF INTRONIC POLYMORPHISMS OF IL1-raVNTR AND IL-4VNTR IN RHEUMATIC MITRAL VALVE DISEASE IN CAUCASIAN POPULATION OF SIBERIA

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    A. V. Ponasenko

    2015-01-01

    Full Text Available A search for associations between allelic variations of immune response genes, and mitral stenosis associated with rheumatic heart disease, represents an important task when studying the pathogenesis of cardiovascular disorders among inhabitants of large industrial regions in Western Siberia. Among multiple polymorphisms of interleukin-encoding genes, a particular attention should be paid to association studies of some intronic polymorphisms with variable numbers of tandem repeats (VNTR. In this respect, genotyping of interleukin 1 receptor antagonist genes (IL-1ra86bp VNTR and interleukin 4 (IL-470bp VNTR has shown positive associations between the intron 2 IL-1ra*3R/3R microsatellite polymorphism, intron 3 IL-4*2R/2R variant, and the risk of mitral stenosis development in patients with rheumatic heart disease (OR = 12.71; p = 0.0001.  

  11. Associations between mutations and a VNTR in the human phenylalanine hydroxylase gene

    Energy Technology Data Exchange (ETDEWEB)

    Goltsov, A.A.; Eisensmith, R.C.; Woo, S.L.C. (Baylor College of Medicine, Houston, TX (United States)); Konecki, D.S.; Lichter-Konecki, U.

    1992-09-01

    The HindIII RFLP in the human phenylalanine hydroxylase (PAH) gene is caused by the presence of an AT-rich (70%) minisatellite region. This region contains various multiples of 30-bp tandem repeats and is located 3 kb downstream of the final exon of the gene. PCR-mediated amplification of this region from haplotyped PAH chromosomes indicates that the previously reported 4.0-kb HindIII allele contains three of these repeats, while the 4.4-kb HindIII allele contains 12 of these repeats. The 4.2-kb HindIII fragment can contain six, seven, eight, or nine copies of this repeat. These variations permit more detailed analysis of mutant haplotypes 1, 5, 6, and, possibly, others. Kindred analysis in phenylketonuria families demonstrates Mendelian segregation of these VNTR alleles, as well as associations between theses alleles and certain PAH mutations. The R261Q mutation, associated with haplotype 1, is associated almost exclusively with an allele containing eight repeats; the R408W mutation, when occurring on a haplotype 1 background, may also be associated with the eight-repeat VNTR allele. Other PAH mutations associated with haplotype 1, R252W and P281L, do not appear to segregate with specific VNTR alleles. The IVS-10 mutation, when associated with haplotype 6, is associated exclusively with an allele containing seven repeats. The combined use of this VNTR system and the existing RFLP haplotype system will increase the performance of prenatal diagnostic tests based on haplotype analysis. In addition, this VNTR may prove useful in studies concerning the origins and distributions of PAH mutations in different human populations. 32 refs., 3 figs., 3 tabs.

  12. Association of the NOS3 intron-4 VNTR polymorphism with aneurysmal subarachnoid hemorrhage

    DEFF Research Database (Denmark)

    Staalsø, Jonatan Myrup; Edsen, Troels; Kotinis, Alexandros;

    2014-01-01

    OBJECT: The nitric oxide system has been linked to the pathogenesis of aneurysmal subarachnoid hemorrhage (SAH). The authors performed a case-control study to investigate the association between SAH and common genetic variants within the endothelial nitric oxide synthase gene (NOS3). METHODS: Three......-VNTR. Haplotype analysis revealed that no single haplotype containing the b-allele was responsible for the observed genotype effect. CONCLUSIONS: The authors' results suggest that the NOS3 27-bp-VNTR b/b genotype independent of other risk factors act in concert with male sex to substantially increase risk of SAH....... This effect is not mediated by any single NOS3 haplotype....

  13. Identification of GATA2 and AP-1 activator elements within the enhancer VNTR occurring in intron 5 of the human SIRT3 gene

    Science.gov (United States)

    Human SIRT3 gene contains an intronic VNTR enhancer. A T > C transition occurring in the second repeat of each VNTR allele implies the presence/absence of a putative GATA binding motif. A partially overlapping AP-1 site, not affected by the transition, was also identified. Aims of the present study ...

  14. Lack of Association Between IL-1 Receptor Antagonist Gene 86bp VNTR Polymorphism and Leiomyoma

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    Mohammadoo Khorasani

    2014-04-01

    Full Text Available Background Uterine leiomyoma (ULs is the most common gynecological tumor and a significant health concern for many women .The interleukin-1 receptor antagonist (IL-1Ra is a naturally occurring cytokine inhibiting interleukin- 1 (IL-1 activity by binding to the IL-1 receptors without signal transduction. Objectives The aim of this study was to investigate the association between interleukin-1 receptor antagonist gene variable number of tandem repeat (VNTR polymorphism and ULs in women of the South- East of Iran. Patients and Methods A total number of 99 patients with leiomyoma and 102 controls were studied. Genotyping of IL-1Ra (VNTR polymorphism was determined by gel electrophoresis after PCR amplification. Frequency of alleles and genotypes in patients and control group was statistically analyzed using χ2 test or fisher exact test. Results The frequency of alleles 1, 2 and 3 of IL-1Ra VNTR polymorphism were %71, %27 and %22 in control group and %74, %20 and %6 in the ULs patients, respectively and there were no significant differences between these two groups. No statistically significant differences were observed between the frequency of IL-1Ra genotypes in the study and control groups. Conclusions This study showed that 86bp VNTR polymorphism of IL-1Ra gene is not associated with leiomyoma in the studied population.

  15. Genotyping of Chlamydophila abortus strains by multilocus VNTR analysis.

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    Laroucau, Karine; Vorimore, Fabien; Bertin, Claire; Mohamad, Khalil Yousef; Thierry, Simon; Hermann, Willems; Maingourd, Cyril; Pourcel, Christine; Longbottom, David; Magnino, Simone; Sachse, Konrad; Vretou, Evangelia; Rodolakis, Annie

    2009-06-12

    Chlamydophila (C.) abortus is the causative agent of ovine enzootic abortion with zoonotic potential whose epidemiology has been held back because of the obligate intracellular habitat of the bacterium. In the present study, we report on a molecular typing method termed multiple loci variable number of tandem repeats (VNTR) Analysis (MLVA) for exploring the diversity of C. abortus. An initial analysis performed with 34 selected genetic loci on 34 ruminant strains including the variant Greek strains LLG and POS resulted in the identification of five polymorphic loci, confirming the widely held notion that C. abortus is a very homogeneous species. Analysis of additional 111 samples with the selected five loci resulted in the classification of all strains into six genotypes with distinct molecular patterns termed genotypes [1] through [6]. Interestingly, the classification of the isolates in the six genotypes was partly related to their geographical origin. Direct examination of clinical samples proved the MLVA to be suitable for direct typing. Analysis of the genomic sequences in six C. abortus prototypes of amplicons generated with each of the five selected VNTR primers revealed that variation between genotypes was caused by the presence or absence of coding tandem repeats in three loci. Amplification of Chlamydophila psittaci reference strains with the five selected VNTR primers and of the six C. abortus prototype strains with the eight VNTR primers established for the typing of C. psittaci [Laroucau, K., Thierry, S., Vorimore, F., Blanco, K., Kaleta, E., Hoop, R., Magnino, S., Vanrompay, D., Sachse, K., Myers, G.S., Bavoil, P.M., Vergnaud, G., Pourcel, C., 2008. High resolution typing of Chlamydophila psittaci by multilocus VNTR analysis (MLVA). Infect. Genet. Evol. 8(2), 171-181] showed that both MLVA typing systems were species-specific when all respective VNTR primer sets were used. In conclusion, the newly developed MLVA system provides a highly sensitive

  16. Linkage of the VNTR/insulin-gene and type I diabetes mellitus: Increased gene sharing in affected sibling pairs

    Energy Technology Data Exchange (ETDEWEB)

    Owerbach, D.; Gabbay, K.H. (Baylor College of Medicine, Houston, TX (United States))

    1994-05-01

    Ninety-six multiplex type I diabetic families were typed at the 5' flanking region of the insulin gene by using a PCR assay that better resolves the VNTR into multiple alleles. Affected sibling pairs shared 2, 1, and 0 VNTR alleles - identical by descent - at a frequency of .47, .45, and .08, respectively, a ratio that deviated from the expected 1:2:1 ratio (P<.001). These results confirm linkage of the chromosome 11p15.5 region with type I diabetes mellitus susceptibility. 20 refs., 2 tabs.

  17. IL-1RN VNTR Polymorphism in Adult Dermatomyositis and Systemic Lupus Erythematosus

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    Zornitsa Kamenarska

    2014-01-01

    Full Text Available Polymorphisms in the cytokine genes and their natural antagonists are thought to influence the predisposition to dermatomyositis (DM and systemic lupus erythematosus (SLE. A variable number tandem repeat (VNTR polymorphism of 86 bp in intron 2 of the interleukin-1 receptor antagonist (IL-1RN gene leads to the existence of five different alleles which cause differences in the production of both IL-1RA (interleukin-1 receptor antagonist and IL-1β. The aim of this case-control study was to investigate the association between the IL-1RN VNTR polymorphism and the susceptibility to DM and SLE in Bulgarian patients. Altogether 91 patients, 55 with SLE and 36 with DM, as well as 112 unrelated healthy controls, were included in this study. Only three alleles were identified in both patients and controls ((1 four repeats, (2 two repeats, and (3 five repeats. The IL-1RN*2 allele (P=0.02, OR 2.5, and 95% CI 1.2–5.4 and the 1/2+2/2 genotypes were found prevalent among the SLE patients (P=0.05, OR 2.6, and 95% CI 1–6.3. No association was found between this polymorphism and the ACR criteria for SLE as well as with the susceptibility to DM. Our results indicate that the IL-1RN VNTR polymorphism might play a role in the susceptibility of SLE but not DM.

  18. VNTR analysis reveals unexpected genetic diversity within Mycoplasma agalactiae, the main causative agent of contagious agalactia

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    Ayling Roger D

    2008-11-01

    Full Text Available Abstract Background Mycoplasma agalactiae is the main cause of contagious agalactia, a serious disease of sheep and goats, which has major clinical and economic impacts. Previous studies of M. agalactiae have shown it to be unusually homogeneous and there are currently no available epidemiological techniques which enable a high degree of strain differentiation. Results We have developed variable number tandem repeat (VNTR analysis using the sequenced genome of the M. agalactiae type strain PG2. The PG2 genome was found to be replete with tandem repeat sequences and 4 were chosen for further analysis. VNTR 5 was located within the hypothetical protein MAG6170 a predicted lipoprotein. VNTR 14 was intergenic between the hypothetical protein MAG3350 and the hypothetical protein MAG3340. VNTR 17 was intergenic between the hypothetical protein MAG4060 and the hypothetical protein MAG4070 and VNTR 19 spanned the 5' end of the pseudogene for a lipoprotein MAG4310 and the 3' end of the hypothetical lipoprotein MAG4320. We have investigated the genetic diversity of 88 M. agalactiae isolates of wide geographic origin using VNTR analysis and compared it with pulsed field gel electrophoresis (PFGE and random amplified polymorphic DNA (RAPD analysis. Simpson's index of diversity was calculated to be 0.324 for PFGE and 0.574 for VNTR analysis. VNTR analysis revealed unexpected diversity within M. agalactiae with 9 different VNTR types discovered. Some correlation was found between geographical origin and the VNTR type of the isolates. Conclusion VNTR analysis represents a useful, rapid first-line test for use in molecular epidemiological analysis of M. agalactiae for outbreak tracing and control.

  19. Association of VNTR polymorphisms in DRD4, 5-HTT and DAT1 genes with obesity.

    Science.gov (United States)

    Uzun, Mustafa; Saglar, Emel; Kucukyildirim, Sibel; Erdem, Beril; Unlu, Hande; Mergen, Hatice

    2015-05-01

    To investigate the association between VNTR polymorphisms of DRD4, DAT1 and 5-HTT genes and obesity. Peripheral blood samples of 234 obese (BMI ≥ 30) and 148 healthy individuals (BMI ≤ 25) were objected to PCR to detect the VNTR of the 2nd intron of 5-HTT, 3rd exon of DRD4 and 3'UTR of DAT1 genes. The association between obesity and genotype distributions of 5-HTT, DAT1 and DRD4 genes and between obesity and distributions of allele frequencies were tested by Chi Square (χ(2)) test and were not found statistically significant. BMI values for genotype of obese and morbidly obese (BMI > 40) individuals were analyzed by Kruskal-Wallis and not found statistically significant differences between BMI values for the most frequent genotypes of 5-HTT, DAT1 and DRD4 genes. As a conclusion, there was no association between 5-HTT, DAT1 and DRD4 genes VNTR polymorphisms and obesity.

  20. No association of the insulin gene VNTR polymorphism with polycystic ovary syndrome in a Han Chinese population

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    Gao Guihua

    2009-12-01

    Full Text Available Abstract Background Polycystic ovary syndrome (PCOS is a common endocrine disorder associated with an increased risk of type II diabetes mellitus. The results of previous research about the association of the VNTR polymorphism in 5-prime flanking region of the insulin (INS gene with PCOS have been inconsistent. The present study was to investigate the association of the INS-VNTR polymorphism with PCOS in a Han Chinese population. Methods The -23/HphI polymorphism as a surrogate marker of the INS-VNTR length polymorphism was genotyped by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP in 216 PCOS patients and 192 non-PCOS women as a control group. Allelic and genotypic frequencies were compared between patients and controls, and these results were analyzed in respect to clinical test data. Results No significant differences were observed between the cases and controls groups either in allele (P = 0.996 or genotype (P = 0.802 frequencies of INS-VNTR polymorphism; Regarding anthropometric data and hormone levels, there were no significant differences between INS-VNTR genotypes in the PCOS group, as well as in the non-PCOS group. Conclusion The present study demonstrated for the first time that the INS-VNTR polymorphism is not a key risk factor for sporadic PCOS in the Han Chinese women. Further studies are needed to give a global view of this polymorphism in pathogenesis of PCOS in a large-scale sample, family-based association design or well-defined subgroups of PCOS.

  1. Association of the NOS3 intron-4 VNTR polymorphism with aneurysmal subarachnoid hemorrhage.

    Science.gov (United States)

    Staalsø, Jonatan Myrup; Edsen, Troels; Kotinis, Alexandros; Romner, Bertil; Springborg, Jacob Bertram; Olsen, Niels Vidiendal

    2014-09-01

    The nitric oxide system has been linked to the pathogenesis of aneurysmal subarachnoid hemorrhage (SAH). The authors performed a case-control study to investigate the association between SAH and common genetic variants within the endothelial nitric oxide synthase gene (NOS3). Three hundred thirty-three Caucasian SAH patients and 498 controls were genotyped for the -922A > G (rs 1800779), -786T > C (rs2070744), and 894G > T (rs1799983) single nucleotide polymorphisms and the intron-4 27-bp variable number of tandem repeats polymorphism (27-bp-VNTR). The b/b (5 repeats) genotype of the 27-bp-VNTR was overrepresented in cases (77%) versus controls (69%) (p = 0.02). In male patients the b/b genotype was found in 85% compared with 67% in male controls, whereas in women, the frequencies were 73% and 72%, respectively. This corresponds to an odds ratio of 2.8 (95% CI 1.5-5.6, p = 0.0005) for SAH in men with the b/b genotype versus men with a/b or a/a. In women, no such association was found (OR 1.1, 95% CI 0.7-1.6, p = 0.76). Stepwise logistic regression including arterial hypertension, smoking, sex, and age with interactions yielded similar effect estimates of the 27-bp-VNTR. Haplotype analysis revealed that no single haplotype containing the b-allele was responsible for the observed genotype effect. The authors' results suggest that the NOS3 27-bp-VNTR b/b genotype independent of other risk factors act in concert with male sex to substantially increase risk of SAH. This effect is not mediated by any single NOS3 haplotype.

  2. VNTR-DAT1 and COMTVal158Met Genotypes Modulate Mental Flexibility and Adaptive Behavior Skills in Down Syndrome

    Science.gov (United States)

    del Hoyo, Laura; Xicota, Laura; Langohr, Klaus; Sánchez-Benavides, Gonzalo; de Sola, Susana; Cuenca-Royo, Aida; Rodriguez, Joan; Rodríguez-Morató, Jose; Farré, Magí; Dierssen, Mara; de la Torre, Rafael; Cuenca-Royo, Aida

    2016-01-01

    Down syndrome (DS) is an aneuploidy syndrome that is caused by trisomy for human chromosome 21 resulting in a characteristic cognitive and behavioral phenotype, which includes executive functioning and adaptive behavior difficulties possibly due to prefrontal cortex (PFC) deficits. DS also present a high risk for early onset of Alzheimer Disease-like dementia. The dopamine (DA) system plays a neuromodulatory role in the activity of the PFC. Several studies have implicated trait differences in DA signaling on executive functioning based on genetic polymorphisms in the genes encoding for the catechol-O-methyltransferase (COMTVal158Met) and the dopamine transporter (VNTR-DAT1). Since it is known that the phenotypic consequences of genetic variants are modulated by the genetic background in which they occur, we here explore whether these polymorphisms variants interact with the trisomic genetic background to influence gene expression, and how this in turn mediates DS phenotype variability regarding PFC cognition. We genotyped 69 young adults of both genders with DS, and found that VNTR-DAT1 was in Hardy-Weinberg equilibrium but COMTVal158Met had a reduced frequency of Met allele homozygotes. In our population, genotypes conferring higher DA availability, such as Met allele carriers and VNTR-DAT1 10-repeat allele homozygotes, resulted in improved performance in executive function tasks that require mental flexibility. Met allele carriers showed worse adaptive social skills and self-direction, and increased scores in the social subscale of the Dementia Questionnaire for People with Intellectual Disabilities than Val allele homozygotes. The VNTR-DAT1 was not involved in adaptive behavior or early dementia symptoms. Our results suggest that genetic variants of COMTVal158Met and VNTR-DAT1 may contribute to PFC-dependent cognition, while only COMTVal158Met is involved in behavioral phenotypes of DS, similar to euploid population. PMID:27799900

  3. VNTR-DAT1 and COMTVal158Met genotypes modulate mental flexibility and adaptive behavior skills in Down syndrome

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    Laura Del Hoyo

    2016-10-01

    Full Text Available Down syndrome (DS is an aneuploidy syndrome that is caused by trisomy for human chromosome 21 resulting in a characteristic cognitive and behavioral phenotype, which includes executive functioning and adaptive behavior difficulties possibly due to prefrontal cortex (PFC deficits. DS also present a high risk for early onset of Alzheimer Disease (AD-like dementia. The dopamine (DA system plays a neuromodulatory role in the activity of the PFC. Several studies have implicated trait differences in DA signaling on executive functioning based on genetic polymorphisms in the genes encoding for the catechol-O-methyltransferase (COMTVal158Met and the dopamine transporter (VNTR-DAT1. Since it is known that the phenotypic consequences of genetic variants are modulated by the genetic background in which they occur, we here explore whether these polymorphisms variants interact with the trisomic genetic background to influence gene expression, and how this in turn mediates DS phenotype variability regarding PFC cognition. We genotyped 69 young adults of both genders with DS, and found that VNTR-DAT1 was in Hardy-Weinberg equilibrium but COMTVal158Met had a reduced frequency of Met allele homozygotes. In our population, genotypes conferring higher DA availability, such as Met allele carriers and VNTR-DAT1 10-repeat allele homozygotes, resulted in improved performance in executive function tasks that require mental flexibility. Met allele carriers showed worse adaptive social skills and self-direction, and increased scores in the social subscale of the Dementia Questionnaire for People with Intellectual Disabilities than Val allele homozygotes. The VNTR-DAT1 was not involved in adaptive behavior or early dementia symptoms. Our results suggest that genetic variants of COMTVal158Met and VNTR-DAT1 may contribute to PFC-dependent cognition, while only COMTVal158Met is involved in behavioral phenotypes of DS, similar to euploid population.

  4. Dopamine transporter (DAT1) VNTR polymorphism and alcoholism in two culturally different populations of south India.

    Science.gov (United States)

    Bhaskar, Lakkakula V K S; Thangaraj, Kumarasamy; Wasnik, Samiksha; Singh, Lalji; Raghavendra Rao, Vadlamudi

    2012-01-01

    It is well established that the central dopaminergic reward pathway is likely involved in alcohol intake and the progression of alcohol dependence. Dopamine transporter (DAT1) mediates the active re-uptake of DA from the synapse and is a principal regulator of dopaminergic neurotransmission. The gene for the human DAT1 displays several polymorphisms, including a 40-bp variable number of tandem repeats (VNTR) ranging from 3 to 16 copies in the 3'-untranslated region (UTR) of the gene. To assess the role of this gene in alcoholism, we genotyped the VNTR of DAT1 gene in a sample of 206 subjects from the Kota population (111 alcohol dependence cases and 95 controls) and 142 subjects from Badaga population (81 alcohol dependence cases and 61 controls). Both populations inhabit a similar environmental zone, but have different ethnic histories. Phenotype was defined based on the DSM-IV criteria. Genotyping was performed using PCR and electrophoresis. The association of DAT1 with alcoholism was tested by using the Clump v1.9 program which uses the Monte Carlo method. In both Kota and Badaga populations, the allele A10 was the most frequent allele followed by allele A9. The genotypic distribution is in Hardy-Weinberg equilibrium in both cases and control groups of Kota and Badaga populations. The DAT1 VNTR was significantly associated with alcoholism in Badaga population but not in Kota population. Our results suggest that the A9 allele of the DAT gene is involved in vulnerability to alcoholism, but that these associations are population specific.

  5. Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder

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    Tzeng Dong-Sheng

    2011-05-01

    Full Text Available Abstract Background The MAOA uVNTR polymorphism has been documented to affect the MAOA gene at the transcriptional level and is associated with aggressive impulsive behaviors, depression associated with suicide (depressed suicide, and major depressive disorder (MDD. We hypothesized that the uVNTR polymorphism confers vulnerability to MDD, suicide or both. The aim of this study was to explore the association between the MAOA uVNTR and depressed suicide, using multiple controls. Methods Four different groups were included: 432 community controls, 385 patients with MDD who had not attempted suicide, 96 community subjects without mental disorders who had attempted suicide, and 109 patients with MDD who had attempted suicide. The MAOA uVNTR polymorphism was genotyped by a PCR technique. The symptom profiles and personal characteristics in each group were also compared. Results The MAOA 4R allele was more frequent in males with MDD than in male community controls (χ2 = 4.182, p = 0.041. Logistic regression analysis showed that, among the depressed subjects, those younger in age, more neurotic or who smoked had an increased risk of suicide (β = -0.04, p = 0.002; β = 0.15, p = 0.017; β = 0.79, p = 0.031, respectively. Moreover, among those who had attempted suicide, those younger in age, with more paternal overprotection, and more somatic symptoms were more likely to be in the MDD group than in the community group (β = -0.11, p Conclusion The MAOA 4R allele is associated with enhanced vulnerability to suicide in depressed males, but not in community subjects. The MAOA 4R allele affects vulnerability to suicide through the mediating factor of depressive symptoms. Further large-scale studies are needed to verify the psychopathology of the relationships among MAOA uVNTR polymorphism, symptom profiles, and suicidal behavior.

  6. Enterococcus faecium strains characterization through polymorphism study of VNTR loci

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    Belteghi, C.,

    2008-12-01

    Full Text Available Enterococci are commensally bacteria of the gastrointestinal and female genital tract in humans and some mammals and birds, and one of the significant causes of hospital-acquired infections, especially in immuno-compromised patients. Genetic fingerprinting (DNA fingerprinting is a tool for identifying, marking and prevention of infectious agents dissemination. SSR (short sequence repeat are known to suffer frequent variations in the number of repetitive units.MLVA (multiple locus variable number tandem repeats analysis is a variant of genetic fingerprinting, in epidemiological studies on the pathogenetic Enterococcus faecium. Our study included laboratory Enterococcus faecium strains or isolated from clinical cases or from the environment (2003-2008. All analyzed strains of Enterococcus faecium were sensitive to vancomycin, except BM4147, and resistant to oxacilin. Strains isolated from the birds’ samples have shown a smaller resistance profile than those of human origin. 33 Enterococus faecium strains were analyzed by PCR amplification. 27 MT (VNTR profiles were obtained: six in the case of the strains isolated from birds, 15 in the case of the strains isolated form humans, 4 in the case of the collection strains and 2 in the case of the strains isolated from water samples. Among the strains isolated from humans and those isolated from animals, identical profiles were not recorded. Within the strains isolated from clinical cases, and those isolated from birds, circulating genotypes were noted, which can be considered as epidemical. The strains used as probiotics proved to be different from those circulating in birds. All MLVA profiles codes compared with those published on line in the UMC Utrecht database proved to be different. Results obtained in this study support the usefulness of the polymorphic VNTR analysis, as genetic marker, inepidemiological investigations.

  7. Lab on a chip genotyping for Brucella spp. based on 15-loci multi locus VNTR analysis

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    Marianelli Cinzia

    2009-04-01

    Full Text Available Abstract Background Brucellosis is an important zoonosis caused by the genus Brucella. In addition Brucella represents potential biological warfare agents due to the high contagious rates for humans and animals. Therefore, the strain typing epidemiological tool may be crucial for tracing back source of infection in outbreaks and discriminating naturally occurring outbreaks versus bioterroristic event. A Multiple Locus Variable-number tandem repeats (VNTR Analysis (MLVA assay based on 15 polymorphic markers was previously described. The obtained MLVA band profiles may be resolved by techniques ranging from low cost manual agarose gels to the more expensive capillary electrophoresis sequencing. In this paper a rapid, accurate and reproducible system, based on the Lab on a chip technology was set up for Brucella spp. genotyping. Results Seventeen DNA samples of Brucella strains isolated in Sicily, previously genotyped, and twelve DNA samples, provided by MLVA Brucella VNTR ring trial, were analyzed by MLVA-15 on Agilent 2100. The DNA fragment sizes produced by Agilent, compared with those expected, showed discrepancies; therefore, in order to assign the correct alleles to the Agilent DNA fragment sizes, a conversion table was produced. In order to validate the system twelve unknown DNA samples were analyzed by this method obtaining a full concordance with the VNTR ring trial results. Conclusion In this paper we described a rapid and specific detection method for the characterization of Brucella isolates. The comparison of the MLVA typing data produced by Agilent system with the data obtained by standard sequencing or ethidium bromide slab gel electrophoresis showed a general concordance of the results. Therefore this platform represents a fair compromise among costs, speed and specificity compared to any conventional molecular typing technique.

  8. Functional Domains of Autoimmune Regulator (AIRE) Modulate INS-VNTR Transcription in Human Thymic Epithelial Cells*

    Science.gov (United States)

    Sparks, Avis E.; Chen, Chiachen; Breslin, Mary B.; Lan, Michael S.

    2016-01-01

    INS-VNTR (insulin-variable number of tandem repeats) and AIRE (autoimmune regulator) have been associated with the modulation of insulin gene expression in thymus, which is essential to induce either insulin tolerance or the development of insulin autoimmunity and type 1 diabetes. We sought to analyze whether each functional domain of AIRE is critical for the activation of INS-VNTR in human thymic epithelial cells. Twelve missense or nonsense mutations in AIRE and two chimeric AIRE constructs were generated. A luciferase reporter assay and a pulldown assay using biotinylated INS-class I VNTR probe were performed to examine the transactivation and binding activities of WT, mutant, and chimeric AIREs on the INS-VNTR promoter. Confocal microscopy analysis was performed for WT or mutant AIRE cellular localization. We found that all of the AIRE mutations resulted in loss of transcriptional activation of INS-VNTR except mutant P252L. Using WT/mutant AIRE heterozygous forms to modulate the INS-VNTR target revealed five mutations (R257X, G228W, C311fsX376, L397fsX478, and R433fsX502) that functioned in a dominant negative fashion. The LXXLL-3 motif is identified for the first time to be essential for DNA binding to INS-VNTR, whereas the intact PHD1, PHD2, LXXLL-3, and LXXLL-4 motifs were important for successful transcriptional activation. AIRE nuclear localization in the human thymic epithelial cell line was disrupted by mutations in the homogenously staining region domain and the R257X mutation in the PHD1 domain. This study supports the notion that AIRE mutation could specifically affect human insulin gene expression in thymic epithelial cells through INS-VNTR and subsequently induce either insulin tolerance or autoimmunity. PMID:27048654

  9. Functional Domains of Autoimmune Regulator (AIRE) Modulate INS-VNTR Transcription in Human Thymic Epithelial Cells.

    Science.gov (United States)

    Sparks, Avis E; Chen, Chiachen; Breslin, Mary B; Lan, Michael S

    2016-05-20

    INS-VNTR (insulin-variable number of tandem repeats) and AIRE (autoimmune regulator) have been associated with the modulation of insulin gene expression in thymus, which is essential to induce either insulin tolerance or the development of insulin autoimmunity and type 1 diabetes. We sought to analyze whether each functional domain of AIRE is critical for the activation of INS-VNTR in human thymic epithelial cells. Twelve missense or nonsense mutations in AIRE and two chimeric AIRE constructs were generated. A luciferase reporter assay and a pulldown assay using biotinylated INS-class I VNTR probe were performed to examine the transactivation and binding activities of WT, mutant, and chimeric AIREs on the INS-VNTR promoter. Confocal microscopy analysis was performed for WT or mutant AIRE cellular localization. We found that all of the AIRE mutations resulted in loss of transcriptional activation of INS-VNTR except mutant P252L. Using WT/mutant AIRE heterozygous forms to modulate the INS-VNTR target revealed five mutations (R257X, G228W, C311fsX376, L397fsX478, and R433fsX502) that functioned in a dominant negative fashion. The LXXLL-3 motif is identified for the first time to be essential for DNA binding to INS-VNTR, whereas the intact PHD1, PHD2, LXXLL-3, and LXXLL-4 motifs were important for successful transcriptional activation. AIRE nuclear localization in the human thymic epithelial cell line was disrupted by mutations in the homogenously staining region domain and the R257X mutation in the PHD1 domain. This study supports the notion that AIRE mutation could specifically affect human insulin gene expression in thymic epithelial cells through INS-VNTR and subsequently induce either insulin tolerance or autoimmunity.

  10. Genetic diversity of the Mycobacterium tuberculosis Beijing family based on SNP and VNTR typing profiles in Asian countries.

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    Yih-Yuan Chen

    Full Text Available The Mycobacterium tuberculosis (MTB Beijing strain is highly virulent, drug resistant, and endemic over Asia. To explore the genetic diversity of this family in several different regions of eastern Asia, 338 Beijing strains collected in Taiwan (Republic of China were analyzed by mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR typing and compared with published MIRU-VNTR profiles and by the Hunter-Gaston diversity index (HGDI of Beijing strains from Japan and South Korea. The results revealed that VNTR2163b (HGDI>0.6 and five other loci (VNTR424, VNTR4052, VNTR1955, VNTR4156 and VNTR 2996; HGDI>0.3 could be used to discriminate the Beijing strains in a given geographic region. Analysis based on the number of VNTR repeats showed three VNTRs (VNTR424, 3192, and 1955 to be phylogenetically informative loci. In addition, to determine the geographic variation of sequence types in MTB populations, we also compared sequence type (ST data of our strains with published ST profiles of Beijing strains from Japan and Thailand. ST10, ST22, and ST19 were found to be prevalent in Taiwan (82% and Thailand (92%. Furthermore, classification of Beijing sublineages as ancient or modern in Taiwan was found to depend on the repeat number of VNTR424. Finally, phylogenetic relationships of MTB isolates in Taiwan, South Korea, and Japan were revealed by a minimum spanning tree based on MIRU-VNTR genotyping. In this topology, the MIRU-VNTR genotypes of the respective clusters were tightly correlated to other genotypic characters. These results are consistent with the hypothesis that clonal evolution of these MTB lineages has occurred.

  11. Identification of Variable-Number Tandem-Repeat (VNTR) Sequences in Acinetobacter baumannii and Interlaboratory Validation of an Optimized Multiple-Locus VNTR Analysis Typing Scheme▿†

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    Pourcel, Christine; Minandri, Fabrizia; Hauck, Yolande; D'Arezzo, Silvia; Imperi, Francesco; Vergnaud, Gilles; Visca, Paolo

    2011-01-01

    Acinetobacter baumannii is an important opportunistic pathogen responsible for nosocomial outbreaks, mostly occurring in intensive care units. Due to the multiplicity of infection sources, reliable molecular fingerprinting techniques are needed to establish epidemiological correlations among A. baumannii isolates. Multiple-locus variable-number tandem-repeat analysis (MLVA) has proven to be a fast, reliable, and cost-effective typing method for several bacterial species. In this study, an MLVA assay compatible with simple PCR- and agarose gel-based electrophoresis steps as well as with high-throughput automated methods was developed for A. baumannii typing. Preliminarily, 10 potential polymorphic variable-number tandem repeats (VNTRs) were identified upon bioinformatic screening of six annotated genome sequences of A. baumannii. A collection of 7 reference strains plus 18 well-characterized isolates, including unique types and representatives of the three international A. baumannii lineages, was then evaluated in a two-center study aimed at validating the MLVA assay and comparing it with other genotyping assays, namely, macrorestriction analysis with pulsed-field gel electrophoresis (PFGE) and PCR-based sequence group (SG) profiling. The results showed that MLVA can discriminate between isolates with identical PFGE types and SG profiles. A panel of eight VNTR markers was selected, all showing the ability to be amplified and good amounts of polymorphism in the majority of strains. Independently generated MLVA profiles, composed of an ordered string of allele numbers corresponding to the number of repeats at each VNTR locus, were concordant between centers. Typeability, reproducibility, stability, discriminatory power, and epidemiological concordance were excellent. A database containing information and MLVA profiles for several A. baumannii strains is available from http://mlva.u-psud.fr/. PMID:21147956

  12. Association between INS-VNTR polymorphism and polycystic ovary syndrome in a Korean population.

    Science.gov (United States)

    Yun, Ji-Hyun; Gu, Bon-Hee; Kang, Yu-Bin; Choi, Bum-Chae; Song, Sangjin; Baek, Kwang-Hyun

    2012-07-01

    Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive ages. But its etiology is not fully understood yet. Variability in the number of tandem repeats of the insulin gene (INS-VNTR) is known to associate with PCOS, and it is associated with an increased risk of diabetes mellitus and other cardiovascular diseases. The aim of our study was to analyze an association between the INS-VNTR polymorphism and PCOS in a Korean population. The -23/Hph I polymorphism was used as a surrogate marker for INS-VNTR polymorphism and a total of 218 PCOS patient and 141 control DNAs were analyzed by restriction fragment length polymorphism method. Statistical analysis of genotyping results were performed using HapAnalyzer. χ² test and logistic regression were used to analyze the association between two groups. A p value In conclusion, there was no association between PCOS and INS-VNTR polymorphism (p = 0.0544, odds ratio = 1.69). Our present data demonstrate that INS-VNTR polymorphism is not related with PCOS in Korean women. Thus, it is suggested that INS-VNTR polymorphism is not a key factor in the etiology and the pathogenesis of PCOS in a Korean population.

  13. Frequencies of VNTR and RFLP polymorphisms associated with factor VIII gene in Singapore

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    Fong, I.; Lai, P.S.; Ouah, T.C. [National Univ. of Singapore (Malaysia)] [and others

    1994-09-01

    The allelic frequency of any polymorphism within a population determines its usefulness for genetic counselling. This is important in populations of non-Caucasian origin as RFLPs may significantly differ among ethnic groups. We report a study of five intragenic polymorphisms in factor VIII gene carried out in Singapore. The three PCR-based RFLP markers studied were Intron 18/Bcl I, Intron 19/Hind III and Intron 22/Xba I. In an analysis of 148 unrelated normal X chromosomes, the allele frequencies were found to be A1 = 0.18, A2 = 0.82 (Bcl I RFLP), A1 = 0.80, A2 = 0.20 (Hind III RFLP) and A1 = 0.58, and A2 = 0.42 (Xba I RFLP). The heterozygosity rates of 74 females analyzed separately were 31%, 32% and 84.2%, respectively. Linkage disequilibrium was also observed to some degree between Bcl I and Hind III polymorphism in our population. We have also analyzed a sequence polymorphism in Intron 7 using hybridization with radioactive-labelled {sup 32}P allele-specific oligonucleotide probes. This polymorphism was not very polymorphic in our population with only 2% of 117 individuals analyzed being informative. However, the use of a hypervariable dinucleotide repeat sequence (VNTR) in Intron 13 showed that 25 of our of 27 (93%) females were heterozygous. Allele frequencies ranged from 1 to 55 %. We conclude that a viable strategy for molecular analysis of Hemophilia A families in our population should include the use of Intron 18/Bcl I and Intron 22/Xba I RFLP markers and the Intron 13 VNTR marker.

  14. Variable Number Tandem Repeat (VNTR) analysis reveals genetic diversity within Mycoplasma mycoides mycoides small colony isolates from Nigeria.

    Science.gov (United States)

    Nwankpa, N D; Manso-silvan, L; Lorenzon, S; Yaya, A; Lombin, L H; Thiaucourt, F

    2010-12-15

    A Variable Number Tandem Repeat (VNTR) analysis was conducted on thirteen (13) M. mycoides mycoides Small Colony isolates from Nigeria using Tandem Repeat (TR) 34 which is a predicted lipoprotein located within the hypothetical protein MAG6170. The analysis revealed diversity within the M. mycoides mycoides Small Colony isolates with five different VNTR types indicated. Some correlation was determined between the VNTR types and their geographical origin. VNTR analysis may represent a useful, rapid first-line test for use in molecular epidemiological analysis of M. mycoides mycoides Small Colony for possible outbreak tracing and disease control.

  15. PCR-based VNTR core sequence analysis for inferring genetic diversity in the shrimp Litopenaeus vannamei

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    Freitas Patrícia Domingues de

    2002-01-01

    Full Text Available The genetic variation in two farmed strains (F3-Panama and F17-Venezuela of the shrimp Litopenaeus vannamei was examined based on DNA multiloci analyses. Eighteen adults of each strain were analyzed by PCR using a set of VNTR core sequence primers. Genetic similarity, mean allele frequency, mean heterozygosity and the frequency of polymorphic loci were determined for both strains. A dendrogram of genetic similarity was produced by UPGMA clustering. The results for three primers (INS, M13, YN73 revealed different levels of genetic variation within the strains. The higher genetic similarity seen within strain F17 was apparently related to inbreeding, although a bottleneck effect could not be discarded. The low level of genetic variability of this strain could account for the reduced adaptive advantage of these animals and their inability to adjust to breeding conditions in Brazil.

  16. Association of STin2 VNTR Polymorphism of Serotonin Transporter Gene with Lifelong Premature Ejaculation: A Case-Control Study in Han Chinese Subjects.

    Science.gov (United States)

    Huang, Yuanyuan; Zhang, Xiansheng; Gao, Jingjing; Tang, Dongdong; Gao, Pan; Peng, Dangwei; Liang, Chaozhao

    2016-10-07

    BACKGROUND The STin2 VNTR polymorphism has a variable number of tandem repeats in intron 2 of the serotonin transporter gene. We aimed to explore the relationship between STin2 VNTR polymorphism and lifelong premature ejaculation (LPE). MATERIAL AND METHODS We recruited a total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as LPE, and 101 controls without PE complaint. Allelic variations of STin2 VNTR were genotyped using PCR-based technology. We evaluated the associations between STin2 VNTR allelic and genotypic frequencies and LPE, as well as the intravaginal ejaculation latency time (IELT) of different STin2 VNTR genotypes among LPE patients. RESULTS The patients and controls did not differ significantly in terms of any characteristic except age. A significantly higher frequency of STin2.12/12 genotype was found among LPE patients versus controls (P=0.026). Frequency of patients carrying at least 1 copy of the 10-repeat allele was significantly lower compared to the control group (28.3% vs. 41.8%, OR=0.55; 95%CI=0.31-0.97, P=0.040). In the LPE group, the mean IELT showed significant difference in STin2.12/12 genotype when compared to those with STin2.12/10 and STin2.10/10 genotypes. The mean IELT in10-repeat allele carriers was 50% longer compared to homozygous carriers of the STin2.12 allele. CONCLUSIONS Our results indicate the presence of STin2.10 allele is a protective factor for LPE. Men carrying the higher expression genotype STin2. 12/12 have shorter IELT than 10-repeat allele carriers.

  17. Association of STin2 Variable Number of Tandem Repeat (VNTR) Polymorphism of Serotonin Transporter Gene with Lifelong Premature Ejaculation: A Case-Control Study in Han Chinese Subjects

    Science.gov (United States)

    Huang, Yuanyuan; Zhang, Xiansheng; Gao, Jingjing; Tang, Dongdong; Gao, Pan; Peng, Dangwei; Liang, Chaozhao

    2016-01-01

    Background The STin2 VNTR polymorphism has a variable number of tandem repeats in intron 2 of the serotonin transporter gene. We aimed to explore the relationship between STin2 VNTR polymorphism and lifelong premature ejaculation (LPE). Material/Methods We recruited a total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as LPE, and 101 controls without PE complaint. Allelic variations of STin2 VNTR were genotyped using PCR-based technology. We evaluated the associations between STin2 VNTR allelic and genotypic frequencies and LPE, as well as the intravaginal ejaculation latency time (IELT) of different STin2 VNTR genotypes among LPE patients. Results The patients and controls did not differ significantly in terms of any characteristic except age. A significantly higher frequency of STin2.12/12 genotype was found among LPE patients versus controls (P=0.026). Frequency of patients carrying at least 1 copy of the 10-repeat allele was significantly lower compared to the control group (28.3% vs. 41.8%, OR=0.55; 95%CI=0.31–0.97, P=0.040). In the LPE group, the mean IELT showed significant difference in STin2.12/12 genotype when compared to those with STin2.12/10 and STin2.10/10 genotypes. The mean IELT in10-repeat allele carriers was 50% longer compared to homozygous carriers of the STin2.12 allele. Conclusions Our results indicate the presence of STin2.10 allele is a protective factor for LPE. Men carrying the higher expression genotype STin2. 12/12 have shorter IELT than 10-repeat allele carriers. PMID:27713390

  18. First report of MIRU-VNTR genotyping of Mycobacterium avium subsp. paratuberculosis isolates from Egypt.

    Science.gov (United States)

    Fawzy, A; Fayed, A; Youssef, H; El-Sayed, A; Zschöck, M

    2016-01-01

    Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne's disease, an economically important disease in ruminants worldwide. It was first isolated in Egypt in 2005. Since then, the pathogen has been detected in different Egyptian provinces. In order to trace the source of infection, genotyping using simple methods of high discriminatory power such as mycobacterial interspersed repetitive unit-variable number tandem repeats (MIRU-VNTR) were carried out in different countries. Until now there is no published information about MIRU-VNTR genotyping of MAP isolates in Egypt. To address that point, 100 faecal samples were collected and cultivated from 3 different suspected dairy farms. Fourteen isolates belonging to one farm were identified as MAP and subjected to genotyping using 8 different MIRU-VNTR loci PCRs. Two different genotypes were recognized based on size polymorphism observed in one locus (VNTR-7) that was confirmed by sequencing. Our work provides a preliminary basis of constructing a MIRU-VNTR genotyping database of MAP in Egypt.

  19. Diabetes susceptibility at IDDM2 cannot be positively mapped to the VNTR locus of the insulin gene.

    Science.gov (United States)

    Doria, A; Lee, J; Warram, J H; Krolewski, A S

    1996-05-01

    An inconsistency has come to light between the conclusion of Lucassen et al. that IDDM2 (11p15.5) must lie within a 4.1 kilobase (kb) segment at the insulin (INS) locus and their own data showing statistically significant associations between insulin-dependent diabetes mellitus (IDDM) and markers beyond the boundaries of that segment. We present data from an independent study of 201 IDDM patients and 107 non-diabetic control subjects that also show significant association with a marker 5' of the INS locus. Patients and control subjects were genotyped at INS/+ 1140 A/C (a surrogate for the variable number tandem repeat (VNTR) polymorphism in the regulatory part of the INS gene) and a marker 5' of the tyrosine hydroxylase (TH) gene, TH/pINS500-RsaI, making it 10 kb 5' of the VNTR. Homozygotes for INS/ + 1140 allele '+' were significantly more frequent among IDDM patients than among control subjects (73 vs 45%, p < 0.001) giving an odds ratio of 3.3 (95% confidence interval (CI): 2.0-5.3). A very similar association was found for homozygotes for the TH/RsaI allele '+' (53 vs 31%, p < 0.001) giving an odds ratio of 2.6 (95%CI 1.6-4.2). By multilocus analysis, the TH/RsaI allele '+' identified a subset of INS/ + 1140 alleles '+' haplotypes that are more specifically associated with IDDM (odds ratio = 5.4, 95%CI 2.9-10.4) than allele + 1140 '+' as a whole. In conclusion, the segment of chromosome 11 that is associated with IDDM spans, at least, the INS and TH loci. No legitimate claim can be made that IDDM2 corresponds to the VNTR polymorphism at the INS locus until the correct boundaries for IDDM2 have been defined and other loci within them have been excluded as determinants of IDDM.

  20. VNTR molecular typing of salmonella enterica serovar typhi isolates in Kathmandu valley

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    B Acharya

    2012-03-01

    Full Text Available Background: Typhoid fever continues to be a worldwide health problem, especially in developing countries. Effective epidemiological surveillance is needed to monitor the presence and spread of disease. Materials and Methods: Variable number tandem repeats (VNTR was performed for Salmonella enterica serovar typhi by multiplex-PCR in 28 Nepalese isolates of sporadic typhoid fever. Results: From all 28 total isolates, we could identify 12 VNTR profiles among the isolates, signifying multiple variants in circulation within the region. Conclusion: The VNTR-based typing assay for serovar typhi isolates can be used during an outbreak of enteric fever. The typing could eventually form the basis of an effective epidemiological surveillance system for developing rational strategies to control typhoid fever. DOI: http://dx.doi.org/10.3126/jpn.v2i3.6026 JPN 2012; 2(3: 220-223

  1. DRD4-exonIII-VNTR moderates the effect of childhood adversities on emotional resilience in young-adults.

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    Debjani Das

    Full Text Available Most individuals successfully maintain psychological well-being even when exposed to trauma or adversity. Emotional resilience or the ability to thrive in the face of adversity is determined by complex interactions between genetic makeup, previous exposure to stress, personality, coping style, availability of social support, etc. Recent studies have demonstrated that childhood trauma diminishes resilience in adults and affects mental health. The Dopamine receptor D4 (DRD4 exon III variable number tandem repeat (VNTR polymorphism was reported to moderate the impact of adverse childhood environment on behaviour, mood and other health-related outcomes. In this study we investigated whether DRD4-exIII-VNTR genotype moderates the effect of childhood adversities (CA on resilience. In a representative population sample (n = 1148 aged 30-34 years, we observed an interactive effect of DRD4 genotype and CA (β = 0.132; p = 0.003 on resilience despite no main effect of the genotype when effects of age, gender and education were controlled for. The 7-repeat allele appears to protect against the adverse effect of CA since the decline in resilience associated with increased adversity was evident only in individuals without the 7-repeat allele. Resilience was also significantly associated with approach-/avoidance-related personality measures (behavioural inhibition/activation system; BIS/BAS measures and an interactive effect of DRD4-exIII-VNTR genotype and CA on BAS was observed. Hence it is possible that approach-related personality traits could be mediating the effect of the DRD4 gene and childhood environment interaction on resilience such that when stressors are present, the 7-repeat allele influences the development of personality in a way that provides protection against adverse outcomes.

  2. Rapid clonal analysis of recurrent tuberculosis by direct MIRU-VNTR typing on stored isolates

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    de Viedma Darío

    2007-07-01

    Full Text Available Abstract Background The application of molecular tools to the analysis of tuberculosis has revealed examples of clonal complexity, such as exogenous reinfection, coinfection, microevolution or compartmentalization. The detection of clonal heterogeneity by standard genotyping approaches is laborious and often requires expertise. This restricts the rapid availability of Mycobacterium tuberculosis (MTB genotypes for clinical or therapeutic decision-making. A new PCR-based technique, MIRU-VNTR, has made it possible to genotype MTB in a time frame close to real-time fingerprinting. Our purpose was to evaluate the capacity of this technique to provide clinicians with a rapid discrimination between reactivation and exogenous reinfection and whether MIRU-VNTR makes it possible to obtain data directly from stored MTB isolates from recurrent episodes. Results We detected differences, between the MIRUtypes of recurrent isolates in 38.5% (5/13 of the cases studied. These included cases of i exogenous reinfection, often with more resistant strains, ii likely examples of microevolution, leading to the appearance of new clonal variants and iii a combination of microevolution, coinfection and competition. Conclusion MIRU-VNTR rapidly obtained clinically useful genotyping data in a challenging situation, directly from stored MTB isolates without subculturing them or purifying their DNA. Our results also mean that MIRU-VNTR could be applied for easy, rapid and affordable massive screening of collections of stored MTB isolates, which could establish the real dimension of clonal heterogeneity in MTB infection.

  3. Lineage specific evolution of the VNTR composite retrotransposon central domain and its role in retrotransposition of gibbon LAVA elements.

    Science.gov (United States)

    Lupan, Iulia; Bulzu, Paul; Popescu, Octavian; Damert, Annette

    2015-05-16

    VNTR (Variable Number of Tandem Repeats) composite retrotransposons - SVA (SINE-R-VNTR-Alu), LAVA (LINE-1-Alu-VNTR-Alu), PVA (PTGR2-VNTR-Alu) and FVA (FRAM-VNTR-Alu) - are specific to hominoid primates. Their assembly, the evolution of their 5' and 3' domains, and the functional significance of the shared 5' Alu-like region are well understood. The central VNTR domain, by contrast, has long been assumed to represent a more or less random collection of 30-50 bp GC-rich repeats. It is only recently that it attracted attention in the context of regulation of SVA expression. Here we provide evidence that the organization of the VNTR is non-random, with conserved repeat unit (RU) arrays at both the 5' and 3' ends of the VNTRs of human, chimpanzee and orangutan SVA and gibbon LAVA. The younger SVA subfamilies harbour highly organized internal RU arrays. The composition of these arrays is specific to the human/chimpanzee and orangutan lineages, respectively. Tracing the development of the VNTR through evolution we show for the first time how tandem repeats evolve within the constraints set by a functional, non-autonomous non-LTR retrotransposon in two different families - LAVA and SVA - in different hominoid lineages. Our analysis revealed that a microhomology-driven mechanism mediates expansion/contraction of the VNTR domain at the DNA level. Elements of all four VNTR composite families have been shown to be mobilized by the autonomous LINE1 retrotransposon in trans. In case of SVA, key determinants of mobilization are found in the 5' hexameric repeat/Alu-like region. We now demonstrate that in LAVA, by contrast, the VNTR domain determines mobilization efficiency in the context of domain swaps between active and inactive elements. The central domain of VNTR composites evolves in a lineage-specific manner which gives rise to distinct structures in gibbon LAVA, orangutan SVA, and human/chimpanzee SVA. The differences observed between the families and lineages are likely to

  4. Genotypic characterization by spoligotyping and VNTR typing of Mycobacterium bovis and Mycobacterium caprae isolates from cattle of Tunisia.

    Science.gov (United States)

    Lamine-Khemiri, Hela; Martínez, Remigio; García-Jiménez, Waldo Luis; Benítez-Medina, Jose Manuel; Cortés, Maria; Hurtado, Inés; Abassi, Mohammed Salah; Khazri, Imed; Benzarti, Mohammed; Hermoso-de-Mendoza, Javier

    2014-02-01

    This work is an approach to the molecular epidemiology of Mycobacterium tuberculosis complex (MTBC) bovine infections in Tunisia. A total of 35 MTBC isolates from both lateral retropharyngeal lymph node samples of cattle slaughtered in different Tunisian regions were genotyped by spoligotyping and variable number tandem repeat typing (VNTR)-typing. Spoligotyping allowed to identify two profiles not previously registered, namely SB2024, a Mycobacterium caprae isolate from Nabeul Region (North East Tunisia), the first description of this species in the country, and SB2025 (Mycobacterium bovis) from Sfax Region (Southern Tunisia). A second M. caprae isolate with a spoligotyping profile previously described in Europe mainland, SB0418, was also isolated from a bovine of Sfax region. Both isolates suggest the possibility of a widespread distribution of this species in the country. The predominant spoligotype was SB0120, present in all Tunisian regions selected for the study but Nabeul. Molecular typing also allowed to describe a mixed infection caused by two different M. bovis isolates (SB0120 and SB0848) in the same animal. VNTR typing was highly discriminant by testing a panel of six loci. Loci QUB3232 and QUB11b were the most discriminant, whereas ETR-D and QUB11a had the lower diversity index. The value of allelic diversity can significantly vary among countries; thus, it is important to standardize a panel of loci for future inter-laboratory comparisons. Although VNTR typing proved to be useful for an efficient discrimination among MTBC isolates, especially in combination with spoligotyping, further studies are needed in order to assess the genetic diversity of the MTBC in Tunisia.

  5. Paternity testing with VNTR DNA systems. II. Evaluation of 271 cases of disputed paternity with the VNTR systems D2S44, D5S43, D7S21, D7S22, and D12S11

    DEFF Research Database (Denmark)

    Hansen, Hanna Elsebeth; Morling, N

    1993-01-01

    Paternity testing was carried out in 271 cases of disputed paternity using the 5 VNTR systems D2S44 (YNH24), D5S43 (MS8), D7S21 (MS31), D7S22 (g3), and D12S11 (MS43a), and 10-15 conventional marker systems including the HLA-A,B system. By means of the matching criteria for the VNTR systems...

  6. Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder

    National Research Council Canada - National Science Library

    Lung, For-Wey; Tzeng, Dong-Sheng; Huang, Mei-Feng; Lee, Ming-Been

    2011-01-01

    The MAOA uVNTR polymorphism has been documented to affect the MAOA gene at the transcriptional level and is associated with aggressive impulsive behaviors, depression associated with suicide (depressed suicide...

  7. Evolutionary history of the PER3 variable number of tandem repeats (VNTR: idiosyncratic aspect of primate molecular circadian clock.

    Directory of Open Access Journals (Sweden)

    Flávia Cal Sabino

    Full Text Available The PER3 gene is one of the clock genes, which function in the core mammalian molecular circadian system. A variable number of tandem repeats (VNTR locus in the 18th exon of this gene has been strongly associated to circadian rhythm phenotypes and sleep organization in humans, but it has not been identified in other mammals except primates. To better understand the evolution and the placement of the PER3 VNTR in a phylogenetical context, the present study enlarges the investigation about the presence and the structure of this variable region in a large sample of primate species and other mammals. The analysis of the results has revealed that the PER3 VNTR occurs exclusively in simiiforme primates and that the number of copies of the primitive unit ranges from 2 to 11 across different primate species. Two transposable elements surrounding the 18th exon of PER3 were found in primates with published genome sequences, including the tarsiiforme Tarsius syrichta, which lacks the VNTR. These results suggest that this VNTR may have evolved in a common ancestor of the simiiforme branch and that the evolutionary copy number differentiation of this VNTR may be associated with primate simiiformes sleep and circadian phenotype patterns.

  8. First report of MIRU-VNTR genotyping of Mycobacterium avium subsp. paratuberculosis isolates from Egypt

    OpenAIRE

    A. Fawzy; Fayed, A.; Youssef, H; El-Sayed, A.; Zschöck, M.

    2016-01-01

    Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne’s disease, an economically important disease in ruminants worldwide. It was first isolated in Egypt in 2005. Since then, the pathogen has been detected in different Egyptian provinces. In order to trace the source of infection, genotyping using simple methods of high discriminatory power such as mycobacterial interspersed repetitive unit-variable number tandem repeats (MIRU-VNTR) were carried out in different co...

  9. Meta-analysis argues for a female-specific role of MAOA-uVNTR in panic disorder in four European populations.

    Science.gov (United States)

    Reif, Andreas; Weber, Heike; Domschke, Katharina; Klauke, Benedikt; Baumann, Christian; Jacob, Christian P; Ströhle, Andreas; Gerlach, Alexander L; Alpers, Georg W; Pauli, Paul; Hamm, Alfons; Kircher, Tilo; Arolt, Volker; Wittchen, Hans-Ulrich; Binder, Elisabeth B; Erhardt, Angelika; Deckert, Jürgen

    2012-10-01

    Panic disorder (PD) is a common mental disorder, ranking highest among the anxiety disorders in terms of disease burden. The pathogenesis of PD is multifactorial with significant heritability, however only a few convincing risk genes have been reported thus far. One of the most promising candidates is the gene encoding monoamine oxidase A (MAOA), due to its key role in monoaminergic neurotransmission, established validity of animal models, and the efficacy of MAO inhibitors in the treatment of PD. A promoter repeat polymorphism in MAOA (MAOA-uVNTR) impacts on gene expression; high-expression alleles have been reported to increase the risk for PD. To further scrutinize the role of this polymorphism, we performed a formal meta-analysis on MAOA-uVNTR and PD using original data from four published European (Estonian, German, Italian, and Polish) samples and genotypes from three hitherto unpublished German PD samples, resulting in the largest (n = 1,115 patients and n = 1,260 controls) genetic study on PD reported to date. In the unpublished samples, evidence for association of MAOA-uVNTR with PD was obtained in one of the three samples. Results of the meta-analysis revealed a significant and female-specific association when calculating an allelic model (OR = 1.23, P = 0.006). This sex-specific effect might be explained by a gene-dose effect causing higher MAOA expression in females. Taken together, our meta-analysis therefore argues that high-expression MAOA-uVNTR alleles significantly increase the risk towards PD in women. However, epigenetic mechanisms might obfuscate the genetic association, calling for ascertainment in larger samples as well as assessment of the MAOA promoter methylation status therein.

  10. Effect of ATRX and G-Quadruplex Formation by the VNTR Sequence on α-Globin Gene Expression.

    Science.gov (United States)

    Li, Yue; Syed, Junetha; Suzuki, Yuki; Asamitsu, Sefan; Shioda, Norifumi; Wada, Takahito; Sugiyama, Hiroshi

    2016-05-17

    ATR-X (α-thalassemia/mental retardation X-linked) syndrome is caused by mutations in chromatin remodeler ATRX. ATRX can bind the variable number of tandem repeats (VNTR) sequence in the promoter region of the α-globin gene cluster. The VNTR sequence, which contains the potential G-quadruplex-forming sequence CGC(GGGGCGGGG)n , is involved in the downregulation of α-globin expression. We investigated G-quadruplex and i-motif formation in single-stranded DNA and long double-stranded DNA. The promoter region without the VNTR sequence showed approximately twofold higher luciferase activity than the promoter region harboring the VNTR sequence. G-quadruplex stabilizers hemin and TMPyP4 reduced the luciferase activity, whereas expression of ATRX led to a recovery in reporter activity. Our results demonstrate that stable G-quadruplex formation by the VNTR sequence downregulates the expression of α-globin genes and that ATRX might bind to and resolve the G-quadruplex.

  11. Paternity testing with VNTR DNA systems. I. Matching criteria and population frequencies of the VNTR systems D2S44, D5S43, D7S21, D7S22, and D12S11 in Danes

    DEFF Research Database (Denmark)

    Morling, N; Hansen, Hanna Elsebeth

    1993-01-01

    of the putative father as an exclusion in paternity testing. This matching criterion was used for the comparisons of 1,197 DNA fragment differences in 247 pairs of children and putative fathers who had not been excluded by conventional marker systems. In all of these cases, the migration differences between......Paternity testing using DNA polymorphism of variable numbers of tandem repeat (VNTR) regions with restriction fragment length polymorphism (RFLP) was implemented. HinfI-digested DNA was separated by electrophoresis in agarose gels and hybridized with radiolabelled probes detecting the VNTR...... testing were established. The frequency distribution of HinfI digested DNA fragments of the 5 VNTR systems in 650 unrelated Danes is presented and the raw data is available....

  12. MIRU-VNTR Genotyping of Mycobacterium tuberculosis Strains Using QIAxcel Technology: A Multicentre Evaluation Study.

    Directory of Open Access Journals (Sweden)

    Vladyslav Nikolayevskyy

    Full Text Available Molecular genotyping of M.tuberculosis is an important laboratory tool in the context of emerging drug resistant TB. The standard 24-loci MIRU-VNTR typing includes PCR amplification followed by the detection and sizing of PCR fragments using capillary electrophoresis on automated sequencers or using agarose gels. The QIAxcel Advanced system might offer a cost-effective medium-throughput alternative.Performance characteristics of the QIAxcel Advanced platform for the standard 24 VNTR loci panel was evaluated at two centres on a total of 140 DNA specimens using automated capillary electrophoresis as a reference method. Additionally 4 hypervariable MIRU-VNTR loci were evaluated on 53 crude DNA extracts. The sizing accuracy, interlaboratory reproducibility and overall instrument's performance were assessed during the study.An overall concordance with the reference method was high reaching 98.5% and 97.6% for diluted genomic and crude DNA extracts respectively. 91.4% of all discrepancies were observed in fragments longer than 700bp. The concordance for hypervariable loci was lower except for locus 4120 (96.2%. The interlaboratory reproducibility agreement rates were 98.9% and 91.3% for standard and hypervariable loci, respectively. Overall performance of the QIAxcel platform for M.tuberculosis genotyping using a panel of standard loci is comparable to that of established methods for PCR fragments up to 700bp. Inaccuracies in sizing of longer fragments could be resolved through using in-house size markers or introduction of offset values. To conclude, the QiaXcel system could be considered an effective alternative to existing methods in smaller reference and regional laboratories offering good performance and shorter turnaround times.

  13. Interaction between insulin (VNTR) and hepatic lipase (LIPC-514C>T) variants on the response to an oral glucose tolerance test in the EARSII group of young healthy men.

    Science.gov (United States)

    Waterworth, Dawn M; Jansen, Hans; Nicaud, Viviane; Humphries, Steve E; Talmud, Philippa J

    2005-06-10

    Insulin resistance is polygenic in origin, and can be observed at an early age. We have shown that variations in APOC3-482T>C and hepatic lipase (LIPC)-514C>T), individually (APOC3 alone) and interactively, modulate insulin and glucose levels after an OGTT in young healthy men participating in the European Atherosclerosis Research Study II (EARSII). Variation in the insulin gene (INS) variable number tandem repeat (VNTR) has been found to predispose to type 1 and type 2 diabetes. We have evaluated the HphI site 23 bp upstream of the INS gene (a surrogate marker for the VNTR) in EARSII (n=822), to determine if variation in INS contributes to insulin resistance. Carriers of the INS VNTR class III (HphI-) allele (frequency=0.29 (95%CI 0.27, 0.31)) had significantly higher 60-min insulin concentrations after the OGTT (P=0.014) and a marginally higher AUC insulin (P=0.07), compared to class I (HphI+) homozygotes. However, this effect on AUC insulin was modified by the level of physical activity, displaying significant gene:environment interaction (P=0.03). We tested for gene:gene interaction between the INS VNTR and both the LIPC-514C>T and APOC3-482T>C. While there was a significant interaction between INS VNTR and LIPC-514C>T on AUC glucose (P=0.013) and on AUC insulin (P=0.015), there was no interaction with APOC3-482T>C. Thus, despite a modest effect of the INS VNTR alone, the influence of this variant on insulin sensitivity was modified by gene:environment and gene:gene interactions, illustrating the biological complexity of insulin resistance.

  14. No Direct Association of Serotonin Transporter (STin2 VNTR and Receptor (HT 102T>C Gene Variants in Genetic Susceptibility to Migraine

    Directory of Open Access Journals (Sweden)

    Gunjan Joshi

    2010-01-01

    Full Text Available We aimed to find out if the serotonin receptor (HT102T>C and serotonin transporter (STin 2 polymorphisms play any role in genetic susceptibility of migraine. For the study, 217 migraine patients and 217 healthy controls (HC were recruited and genotyping was carried out using the Polymerase Chain Reaction and Restriction Fragment Length polymorphism (PCR-RFLP method. All results were Bonferroni corrected. We could not find any significant differences in the genotype or allele frequencies in case of HT 102 T>C polymorphism between migraine patients and healthy controls (P value=0.224. No significant association was seen at allele and carrier levels. Sub-grouping the patients on the basis of gender or on basis of migraine type i.e. with or without aura also did not show any association. Similarly, no difference in genotype (P value=0.236, allele (P value=0.550 or carrier frequency (P value=0.771 in STin 2 VNTR polymorphism was observed between migraine patients. However, HT 102 TC genotype was observed to interact significantly with the STin 2.10/10 genotype in enhancing risk of migraine, both with and without aura. In conclusion, the HT102 T>C receptor and the STin 2 VNTR transporter polymorphisms, did not individually confer any significant risk of migraine or its clinical subtypes but the two polymorphisms appear to synergistically influence susceptibility to migraine. Serotonin transporter (STin2 VNTR and receptor (HT 102T>C polymorphisms; Migraine with aura (MA; Migraine without aura (MO; Genetic susceptibility

  15. Lack of association of DRD4 exon 3 VNTR genotype with reactivity to dynamic smoking cues in movies

    NARCIS (Netherlands)

    Lochbühler, K.C.; Verhagen, M.; Munafo, M.R.; Engels, R.C.M.E.

    2013-01-01

    Background: The objective of the present study was first to examine whether dynamic smoking cues in movies trigger craving, and second to explore whether the DRD4 48 bp variable number of tandem repeat (VNTR) exon 3 genotype modifies this relationship. Using an experimental design, daily adult smoke

  16. Genotyping of Mycobacterium tuberculosis Isolates from Hormozgan Province of Iran Based on 15-Locus MIRU-VNTR and Spoligotyping

    Science.gov (United States)

    Zamani, Samin; Haeili, Mehri

    2016-01-01

    Background. Considering that Hormozgan province in Iran (southern part of Iran on the Persian Gulf) is among the areas with high prevalence of MDR-MTB and attracts so many sailors and tourists, genetic diversity of MTB isolates circulating in this part of Iran was evaluated. Pattern of TB transmission was also examined. Methods and Material. A total of 38 isolates of MTB were cultured from TB patients from Hormozgan province of Iran and standard MIRU-VNTR typing and spoligotyping were applied to genotype these isolates. Drug susceptibility testing was performed using proportion method. Results. There were 28 VNTR profiles comprising 5 clusters and 23 unique isolates compared to 21 spoligotyping profiles, which contained 9 clusters and 12 unique isolates. Latin American-Mediterranean (n = 9, 23.6%) was found to be the most predominant lineage. MIRU-VNTR analysis, with an HGDI of 0.975, was more discriminating than spoligotyping, which had an HGDI of 0.955. The estimated proportion of TB cases due to recent transmission was 26.3% and 44.7% by MIRU-VNTR and spoligotyping, respectively. The rates of monodrug resistance and MDR were 15.8% and 7.9%, respectively. Two of 3 MDR strains were found to be related to MIRU-VNTR and belonged to the same spoligotyping cluster characterized with T1/SIT53 genotype. Conclusions. The high genetic diversity among MTB isolates suggests that transmission occurred from different sources to this area. Reactivation of a priori, latent MTB infection was found to contribute mainly to TB cases in this geographic region. PMID:27819023

  17. [Molecular epidemiology of Mycobacterium tuberculosis and its prospect based on variable number of tandem repeat (VNTR) genotyping--a strategy in Osaka City, Japan].

    Science.gov (United States)

    Wada, Takayuki; Hase, Atsushi

    2010-12-01

    The methodological establishment of variable number of tandem repeat(s) (VNTR) genotyping of Mycobacterium tuberculosis has opened a new era of molecular epidemiology against tuberculosis (TB). The method can provide simple, rapid and accurate identification of clinical isolates from TB patients that makes it possible to compare the isolates among different laboratories. Such advantages of VNTR not only help us certify the identification of isolates in putative outbreaks easily but also promote the reasonable estimation of unidentified transmissions in surveillance studies. Recently, the Japan Anti-Tuberculosis Association (JATA) (12)-VNTR has become a standard genotyping method of M. tuberculosis, and its spread has been expected in Japan. In Osaka City, located in the western part of the country, JATA (12)-VNTR has been applied to molecular epidemiological study of TB. Moreover, the additional 12 VNTR loci have been analyzed for various purposes, such as to enhance the discriminatory power (public health needs) or to further analyze the population genetic structure (research needs). As the nationwide findings of VNTR genotyping of M. tuberculosis are accumulated, this technology will be increasingly useful for detecting transmission of any specific strain in large geographic areas that could not be recognized by conventional epidemiological methods. The needs for the VNTR genotyping of M. tuberculosis and its practical uses are expected to expand drastically in the future.

  18. Examining impulsivity as an endophenotype using a behavioral approach: a DRD2 TaqI A and DRD4 48-bp VNTR association study

    Directory of Open Access Journals (Sweden)

    Beauchemin Joshua

    2007-01-01

    Full Text Available Abstract Background Research on the genetic basis for impulsivity has revealed an array of ambiguous findings. This may be a result of limitations to self-report assessments of impulsivity. Behavioral measures that assess more narrowly defined aspects of impulsivity may clarify genetic influences. This study examined the relationship between possession of the DRD2 TaqI A and DRD4 48 bp VNTR genetic polymorphisms and performance on a behavioral measure of impulsivity, the delay discounting task (DDT, and three traditional self-report measures. Methods 195 individuals (42% male were recruited from a university campus and were assessed in small group sessions using personal computers. Genotyping was conducted using previously established protocols. For the DRD2 TaqI A locus, individuals were designated as possessing at least one copy of the A1 allele (A1+ or not (A1-, and for the DRD4 48-bp VNTR locus, individuals were designated as having at least one long allele (7 repeats or longer, L+ or not (L-. Principal analyses used multiple univariate factorial 2 (A1+/A1- × 2 (L+/L- analyses of variance. Results A significant main effect of A1+ status on DDT performance was evident (p = .006 as well as a significant interaction effect (p = .006 between both genes. No other significant effects were evident on the self-report measures, with the exception of a trend toward an interaction effect on the Sensation Seeking Scale. Exploratory analyses suggested that the significant effects were not a function of population stratification or gender. Discussion These data suggest that the DRD2 TaqI A and DRD4 VNTR polymorphisms influence impulsivity as measured with a delay discounting task. Specifically, these findings suggest that an interaction between the functional effects of the two unlinked genotypes results in significant difference in the balance of mesolimbic dopaminergic activation relative to frontal-parietal activation. However, these findings are also

  19. Multiple-Locus VNTR Analysis (MLVA) for Bacterial Strain Identification - Quarterly Progress Report for the period 7/1/00 to 10/30/00

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Paul Keim

    2000-11-07

    Multiple locus VNTR analysis (MLVA) systems are being developed for B. anthracis, Y. pestis and F. tularensis. These are high resolution DNA fingerprinting systems that will allow for molecular epidemiology and forensic analysis of these pathogens.

  20. Multiple-Locus VNTR Analysis (MLVA) for Bacterial Strain Identification - Quarterly Progress Report for the Period 4/1/00 to 6/30/00

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Paul Keim

    2000-11-07

    Multiple locus VNTR analysis (MLVA) systems are being developed for B. anthracis, Y. pestis and F. tularensis. These are high resolution DNA fingerprinting systems that will allow for molecular epidemiology and forensic analysis of these pathogens.

  1. Regional cortical thinning of the orbitofrontal cortex in medication-naïve female patients with major depressive disorder is not associated with MAOA-uVNTR polymorphism

    OpenAIRE

    Won, Eunsoo; Choi, Sunyoung; Kang, June; Lee, Min-Soo; Ham, Byung-Joo

    2016-01-01

    Background Orbitofrontal cortex alterations have been suggested to underlie the impaired mood regulation in depression. MAOA-uVNTR (monoamine oxidase A-upstream variable number of tandem repeats) polymorphism has been reported to be associated with major depressive disorder by various studies. The influence of MAOA-uVNTR genotype on function and structure of the orbitofrontal cortex has previously been reported. In this study, we investigated the difference in orbitofrontal cortex thickness b...

  2. A novel multiple locus variable number of tandem repeat (VNTR) analysis (MLVA) method for Propionibacterium acnes.

    Science.gov (United States)

    Hauck, Yolande; Soler, Charles; Gérôme, Patrick; Vong, Rithy; Macnab, Christine; Appere, Géraldine; Vergnaud, Gilles; Pourcel, Christine

    2015-07-01

    Propionibacterium acnes plays a central role in the pathogenesis of acne and is responsible for severe opportunistic infections. Numerous typing schemes have been developed that allow the identification of phylotypes, but they are often insufficient to differentiate subtypes. To better understand the genetic diversity of this species and to perform epidemiological analyses, high throughput discriminant genotyping techniques are needed. Here we describe the development of a multiple locus variable number of tandem repeats (VNTR) analysis (MLVA) method. Thirteen VNTRs were identified in the genome of P. acnes and were used to genotype a collection of clinical isolates. In addition, publically available sequencing data for 102 genomes were analyzed in silico, providing an MLVA genotype. The clustering of MLVA data was in perfect congruence with whole genome based clustering. Analysis of the clustered regularly interspaced short palindromic repeat (CRISPR) element uncovered new spacers, a supplementary source of genotypic information. The present MLVA13 scheme and associated internet database represents a first line genotyping assay to investigate large number of isolates. Particular strains may then be submitted to full genome sequencing in order to better analyze their pathogenic potential.

  3. Fieldable genotyping of Bacillus anthracis and Yersinia pestis based on 25-loci Multi Locus VNTR Analysis

    Directory of Open Access Journals (Sweden)

    Carattoli Alessandra

    2008-01-01

    Full Text Available Abstract Background Anthrax and plague are diseases caused by Bacillus anthracis and Yersinia pestis respectively. These bacteria are etiological agents for worldwide zoonotic diseases and are considered among the most feared potential bioterror agents. Strain differentiation is difficult for these microorganisms because of their high intraspecies genome homogeneity. Moreover, fast strain identification and comparison with known genotypes may be crucial for naturally occurring outbreaks versus bioterrorist events discrimination. Results Thirty-nine B. anthracis and ten Y. pestis strains, representative of the species genetic diversity, were genotyped by Agilent 2100 Bioanalyzer using previously described Multiple Locus VNTR Analysis assays (MLVA. Results were compared to previous data obtained by standard genotyping system (capillary electrophoresis on automatic sequencer and, when necessary, direct amplicon sequencing. A reference comparison table containing actual fragment sizes, sequencer sizes and Agilent sizes was produced. Conclusion In this report an automated DNA electrophoresis apparatus which provides a cheaper alternative compared to capillary electrophoresis approaches was applied for genotyping of B. anthracis and Y. pestis. This equipment, uses pre-cast gels and provides easy transportation, low maintenance and overall general logistic requirements and costs, is easy to set up and provides rapid analysis. This platform is a candidate for on-site MLVA genotyping of biothreat agents as well as other bacterial pathogens. It is an alternative to the more expensive and demanding capillary electrophoresis methods, and to the less expensive but more time-consuming classical gel electrophoresis approach.

  4. PCSK6 VNTR Polymorphism Is Associated with Degree of Handedness but Not Direction of Handedness.

    Directory of Open Access Journals (Sweden)

    Larissa Arning

    Full Text Available Although the left and right human cerebral hemispheres differ both functionally and anatomically, the mechanisms that underlie the establishment of these hemispheric specializations, as well as their physiological and behavioral implications, remain largely unknown. Since cerebral asymmetry is strongly correlated with handedness, and handedness is assumed to be influenced by a number of genetic and environmental factors, we performed an association study of LRRTM1 rs6733871 and a number of polymorphisms in PCSK6 and different aspects of handedness assessed with the Edinburgh handedness inventory in a sample of unrelated healthy adults (n = 1113. An intronic 33bp variable-number tandem repeat (VNTR polymorphism in PCSK6 (rs10523972 shows a significant association (significance threshold: p<0.0025, adjusted for multiple comparisons with a handedness category comparison (P = 0.0005 and degree of handedness (P = 0.001. These results provide further evidence for the role of PCSK6 as candidate for involvement in the biological mechanisms that underlie the establishment of normal brain lateralization and thus handedness and support the assumption that the degree of handedness, instead the direction, may be the more appropriate indicator of cerebral organization.

  5. Hardy–Weinberg equilibrium analysis of the 48 bp VNTR in the III exon of the DRD4 gene in a sample of parents of ADHD cases

    Science.gov (United States)

    Trejo, Salvador; Toscano-Flores, José J; Matute, Esmeralda; Ramírez-Dueñas, María de Lourdes

    2015-01-01

    The aim of this study was to obtain the genotype and gene frequency from parents of children with attention-deficit/hyperactivity disorder (ADHD) and then assess the Hardy–Weinberg equilibrium of genotype frequency of the variable number tandem repeat (VNTR) III exon of the dopamine receptor D4 (DRD4) gene. The genotypes of the III exon of 48 bp VNTR repeats of the DRD4 gene were determined by polymerase chain reaction in a sample of 30 parents of ADHD cases. In the 60 chromosomes analyzed, the following frequencies of DRD4 gene polymorphisms were observed: six chromosomes (c) with two repeat alleles (r) (10%); 1c with 3r (1.5%); 36c with 4r (60%); 1c with 5r (1.5%); and 16c with 7r (27%). The genotypic distribution of the 30 parents was two parents (p) with 2r/2r (6.67%); 1p with 2r/4r (3.33%); 1p with 2r/5r (3.33%); 1p with 3r/4r (3.33%); 15p with 4r/4r (50%); 4p with 4r/7r (13.33); and 6p with 7r/7r (20%). A Hardy–Weinberg disequilibrium (χ2=13.03, P<0.01) was found due to an over-representation of the 7r/7r genotype. These results suggest that the 7r polymorphism of the DRD4 gene is associated with the ADHD condition in a Mexican population. PMID:26082657

  6. Hardy–Weinberg equilibrium analysis of the 48 bp VNTR in the III exon of the DRD4 gene in a sample of parents of ADHD cases

    Directory of Open Access Journals (Sweden)

    Trejo S

    2015-06-01

    Full Text Available Salvador Trejo, José J Toscano-Flores, Esmeralda Matute, María de Lourdes Ramírez-Dueñas Laboratorio de Neuropsicología y Neurolingüística, Instituto de Neurociencias CUCBA, Guadalajara, Jalisco, Mexico Abstract: The aim of this study was to obtain the genotype and gene frequency from parents of children with attention-deficit/hyperactivity disorder (ADHD and then assess the Hardy–Weinberg equilibrium of genotype frequency of the variable number tandem repeat (VNTR III exon of the dopamine receptor D4 (DRD4 gene. The genotypes of the III exon of 48 bp VNTR repeats of the DRD4 gene were determined by polymerase chain reaction in a sample of 30 parents of ADHD cases. In the 60 chromosomes analyzed, the following frequencies of DRD4 gene polymorphisms were observed: six chromosomes (c with two repeat alleles (r (10%; 1c with 3r (1.5%; 36c with 4r (60%; 1c with 5r (1.5%; and 16c with 7r (27%. The genotypic distribution of the 30 parents was two parents (p with 2r/2r (6.67%; 1p with 2r/4r (3.33%; 1p with 2r/5r (3.33%; 1p with 3r/4r (3.33%; 15p with 4r/4r (50%; 4p with 4r/7r (13.33; and 6p with 7r/7r (20%. A Hardy–Weinberg disequilibrium (χ2=13.03, P<0.01 was found due to an over-representation of the 7r/7r genotype. These results suggest that the 7r polymorphism of the DRD4 gene is associated with the ADHD condition in a Mexican population. Keywords: ADHD, parents, DRD4, HWE

  7. O polimorfismo VNTR no gene codificador do antagonista do receptor da interleucina-1 está associado com a doença arterial coronariana Interleukin-1 receptor antagonist gene VNTR polymorphism is associated with coronary artery disease

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    Ahmet Arman

    2008-11-01

    .BACKGROUND: Coronary Artery Disease (CAD is the atherosclerosis of coronary arteries that carry blood to the heart muscle. Atherosclerosis is an inflammatory disease. Cytokine gene variations such as those associated with the IL1 family are involved in the pathogenesis of atherosclerosis. OBJECTIVE: The purpose of this study was to determine the relationship between IL1 family polymorphisms (IL1RN VNTR, IL1B positions -511 and +3953 and CAD in Turkish population. METHODS: 427 individuals were submitted to coronary angiography and were grouped as 170 control subjects and 257 CAD patients. The CAD subjects were divided into two subgroups: 91 Single Vessel Disease (SVD and 166 Multiple Vessel Disease (MVD subjects. The genotypes of IL1RN and of IL1B (-511, +3953 were determined by polymerase chain reaction (PCR followed by restriction digestion analysis. RESULTS: No significant difference was found in IL1RN and IL1B (-511 and +3953 genotype distributions between CAD and control subjects or MVD and control subjects. However, significant association was seen in IL1RN 2/2 genotype between SVD and control subjects (P= 0.016, x2: 10.289, OR: 2.94, 95% CI: 1.183-7.229. Similarly, no statistically significant difference was found in IL1RN and IL1B (-511 and +3953 allele frequencies between CAD and control subjects, MVD and control subjects or SVD and control subjects. CONCLUSION: No association was found in either allele frequency or genotype distribution of IL1RN and IL1B polymorphisms between CAD and the control groups. However; IL1RN 2/2 genotype may be a risk factor for SVD in the Turkish population.

  8. Lack of Association between a 3'UTR VNTR Polymorphism of Dopamine Transporter Gene (SLC6A3) and ADHD in a Brazilian Sample of Adult Patients

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    Aperecida da Silva, Maria; Cordeiro, Quirino; Louza, Mario; Vallada, Homero

    2011-01-01

    Objective: To investigate a possible association between a 3'UTR VNTR polymorphism of the dopamine transporter gene (SLC6A3) and ADHD in a Brazilian sample of adult patients. Method: Study Case-control with 102 ADHD adult outpatients ("DSM-IV" criteria) and 479 healthy controls. The primers' sequence used were: 3'UTR-Forward: 5' TGT GGT…

  9. Lack of Association between a 3'UTR VNTR Polymorphism of Dopamine Transporter Gene (SLC6A3) and ADHD in a Brazilian Sample of Adult Patients

    Science.gov (United States)

    Aperecida da Silva, Maria; Cordeiro, Quirino; Louza, Mario; Vallada, Homero

    2011-01-01

    Objective: To investigate a possible association between a 3'UTR VNTR polymorphism of the dopamine transporter gene (SLC6A3) and ADHD in a Brazilian sample of adult patients. Method: Study Case-control with 102 ADHD adult outpatients ("DSM-IV" criteria) and 479 healthy controls. The primers' sequence used were: 3'UTR-Forward: 5' TGT GGT GAT GGG…

  10. Polymorphisms of the dopamine D4 receptor gene (DRD4 VNTR) and cannabinoid CB1 receptor gene (CNR1) are not strongly related to cue-reactivity after alcohol exposure.

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    van den Wildenberg, Esther; Janssen, Rob G J H; Hutchison, Kent E; van Breukelen, Gerard J P; Wiers, Reinout W

    2007-06-01

    Polymorphisms in the D4 dopamine receptor gene (DRD4) and the CB1 cannabinoid receptor gene (CNR1) have been associated with a differential response to alcohol after consumption. The goal of the present study was to investigate whether heavy drinkers with these polymorphisms would respond with enhanced cue-reactivity after alcohol exposure. Eighty-eight male heavy drinkers were genotyped for the DRD4 variable number of tandem repeats (VNTR) [either DRD4 long (L) or short (S)] and the CNR1 rs2023239 polymorphism (either CT/CC or TT). Participants were exposed to water and beer in 3-minute trials. Dependent variables of main interest were subjective craving for alcohol, subjective arousal and salivary reactivity. Overall, no strong evidence was found for stronger cue-reactivity (= outcome difference between beer and water trial) in the DRD4 L and CNR1 C allele groups. The DRD4 VNTR polymorphism tended to moderate salivary reactivity such that DRD4 L participants showed a larger beverage effect than the DRD4 S participants. Unexpectedly, the DRD4 L participants reported, on average, less craving for alcohol and more subjective arousal during cue exposure, compared with the DRD4 S participants. As weekly alcohol consumption increased, the CNR1 C allele group tended to report more craving for alcohol during the alcohol exposure than the T allele group. The DRD4 and CNR1 polymorphisms do not appear to strongly moderate cue-reactivity after alcohol cue exposure, in male heavy drinkers.

  11. Lack of association between VNTR polymorphism of dopamine transporter gene (SLC6A3 and schizophrenia in a Brazilian sample Ausência de associação entre o polimorfismo VNTR do gene do transportador de dopamina (SLC6A3 e esquizofrenia em uma população brasileira

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    Quirino Cordeiro

    2004-12-01

    Full Text Available A role of dopaminergic dysfunction has been postulated in the aetiology of schizophrenia. We hypothesized that variations in the dopamine transporter gene (SLC6A3 may be associated with schizophrenia. We conducted case-control and family based analysis on the polymorphic SLC6A3 variable number tandem repeat (VNTR in a sample of 220 schizophrenic patients, 226 gender and ethnic matched controls, and 49 additional case-parent trios. No differences were found in allelic or genotypic distributions between cases and controls and no significant transmission distortions from heterozygous parents to schizophrenic offspring were detected. Thus, our results do not support an association of the SLC6A3 VNTR with schizophrenia in our sample.Genes do sistema dopaminérgico são de escolha para a pesquisa de susceptibilidade para a esquizofrenia. Desse modo, possível contribuição do polimorfismo do gene do transportador de dopamina (SLC6A3 no aumento da vulnerabilidade para a esquizofrenia foi investigada no presente estudo. Analisou-se a distribuição do sítio polimórfico do gene do transportador de dopamina (VNTR em uma população de 220 pacientes com esquizofrenia (critério diagnóstico: DSM-IV e comparou-se com a distribuição em uma população controle de 226 indivíduos pareados para sexo e etnia. Nenhuma diferença foi observada na distribuição dos alelos entre casos e controles. O mesmo polimorfismo também foi investigado em uma segunda amostra composta por 49 trios (pais e probando. O resultado também foi negativo. Tais dados não dão suporte para a participação do polimorfismo do gene do transportador de dopamina no aumento de susceptibilidade para esquizofrenia na amostra estudada.

  12. SLC6A4 STin2 VNTR genetic polymorphism is associated with tobacco use disorder, but not with successful smoking cessation or smoking characteristics: a case control study.

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    Pizzo de Castro, Márcia Regina; Maes, Michael; Guembarovski, Roberta Losi; Ariza, Carolina Batista; Reiche, Edna Maria Vissoci; Vargas, Heber Odebrecht; Vargas, Mateus Medonça; de Melo, Luiz Gustavo Piccoli; Dodd, Seetal; Berk, Michael; Watanabe, Maria Angelica Ehara; Nunes, Sandra Odebrecht Vargas

    2014-06-27

    The aim of this study was to determine if variable number of tandem repeats (VNTR) in the second intron (STin2) of the serotonin transporter (SLC6A4) gene was associated with tobacco use disorder, successful smoking cessation, or smoking characteristics. In this case-control study, patients with current tobacco use disorder, diagnosed according to DSM IV criteria (n = 185), and never-smokers, diagnosed according to CDC criteria (n = 175), were recruited and received 52 weeks of combined pharmacotherapy and cognitive therapy. Successful smoking cessation was defined as exhaled carbon monoxide smoking cessation, smoking characteristics and increased alcohol or sedative use risk. Our results suggest that the STin2.10/10 genotype and STin2.12 allele are associated with tobacco use disorder or nicotine dependence, but not with treatment response or severity of dependence. It is hypothesized that the ST2in.12 allele by modulating the metabolism of serotonin may participate in the pathophysiology of tobacco use disorder or nicotine dependence.

  13. Determining the Risk of Intra-Community Transmission of Tuberculosis in the Northwest of Iran Through 15 Loci Miru-Vntr Typing

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    Afaghi-Gharamaleki, Ali; Moaddab, Seyyedreza; Darbouy, Mojtaba; Ansarin, Khalil; Hanifian, Shahram

    2017-01-01

    This study was carried out in order to investigating the effect of travelling on the transmission of tuberculosis from high- to low-burden TB countries. Mycobacteria samples isolated from patients of distinct and relatively co-related countries (Azerbaijan Republic and Tabriz [located in the northwest of Iran]) were analyzed through 15 loci MIRU-VNTR typing method. PCR was done using special primers for each of the loci; then the number of allele repeats for all loci were determined by the size of their fragments. Finally, the created numeric patterns for each isolate were analyzed and clustered, using MIRU-VNTRplus.org website. All 119 isolates dispersing at 106 distinct patterns were composed of 10 clusters with 23 members and 96 unique patterns. Nine and five loci had high and moderate discriminatory power, respectively, but only one of them was poor in clustering. The study showed that 89.08% of TB cases involved resulted from the reactivation pattern and 10.92% were related to ongoing transmission. Although Azerbaijan Republic is a higher-burden TB region than Tabriz and Azerbaijan people make frequent tours to Tabriz to receive low or free medical services, the findings showed no TB transmission from the regions at least during the year of the study.

  14. VNTR diversity in Yersinia pestis isolates from an animal challenge study reveals the potential for in vitro mutations during laboratory cultivation

    Science.gov (United States)

    Vogler, Amy J.; Nottingham, Roxanne; Busch, Joseph D.; Sahl, Jason W.; Shuey, Megan M.; Foster, Jeffrey T.; Schupp, James M.; Smith, Susan; Rocke, Tonie E.; Klein, Paul; Wagner, David M.

    2016-01-01

    Underlying mutation rates and other evolutionary forces shape the population structure of bacteria in nature. Although easily overlooked, similar forces are at work in the laboratory and may influence observed mutations. Here, we investigated tissue samples and Yersinia pestis isolates from a rodent laboratory challenge with strain CO92 using whole genome sequencing and multi-locus variable-number tandem repeat (VNTR) analysis (MLVA). We identified six VNTR mutations that were found to have occurred in vitro during laboratory cultivation rather than in vivo during the rodent challenge. In contrast, no single nucleotide polymorphism (SNP) mutations were observed, either in vivo or in vitro. These results were consistent with previously published mutation rates and the calculated number of Y. pestis generations that occurred during the in vitro versus the in vivo portions of the experiment. When genotyping disease outbreaks, the potential for in vitro mutations should be considered, particularly when highly variable genetic markers such as VNTRs are used.

  15. MIRU-VNTR genotype diversity and indications of homoplasy in M. avium strains isolated from humans and slaughter pigs in Latvia.

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    Kalvisa, Adrija; Tsirogiannis, Constantinos; Silamikelis, Ivars; Skenders, Girts; Broka, Lonija; Zirnitis, Agris; Jansone, Inta; Ranka, Renate

    2016-09-01

    Diseases which are caused by non-tuberculous mycobacteria (NTM) are an increasing problem in the developed countries. In Latvia, one of the most clinically important members of NTM is Mycobacterium avium (M. avium), an opportunistic pathogen which has been isolated from several lung disease patients and tissue samples of slaughter pigs. This study was designed to characterize the genetic diversity of the M. avium isolates in Latvia and to compare the distribution of genotypic patterns among humans and pigs. Eleven (Hall and Salipante, 2010) clinical M. avium samples, isolated from patients of Center of Tuberculosis and Lung Diseases (years 2003-2010), and 32 isolates from pig necrotic mesenterial lymph nodes in different regions (years 2003-2007) were analyzed. The majority (42 of 43) of samples were identified as M. avium subsp. hominissuis; one porcine isolate belonged to M. avium subsp. avium. MIRU-VNTR genotyping revealed 13 distinct genotypes, among which nine genotype patterns, including M. avium subsp. avium isolate, were newly identified. IS1245 RFLP fingerprinting of 25 M. avium subsp. hominissuis samples yielded 17 different IS1245 RFLP patterns, allowing an efficient discrimination of isolates. Clusters of identical RFLP profiles were observed within host species, geographical locations and time frame of several years. Additional in silico analysis on simulated MIRU-VNTR genotype population datasets showed that the MIRU-VNTR pattern similarity could partly arise due to probabilistic increase of acquiring homoplasy among subpopulations, thus the similar MIRU-VNTR profiles of M. avium strains even in close geographical proximity should be interpreted with caution.

  16. Associação entre polimorfismo SLC6A3 3’UTR VNTR e a resposta ao tratamento da dependência de nicotina

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    Guilherme Rubino de Azevedo Focchi

    2011-01-01

    Full Text Available Objetivo: Avaliar a associação entre a resposta ao tratamento da dependência de nicotina com bupropiona e a presença do polimorfismo SLC6A3 3’UTR VNTR, localizado no gene que codifica o transportador dopaminérgico. Método: Foram acompanhados no Ambulatório de Tabagismo do Instituto de Psiquiatria da Faculdade de Medicina da USP 100 pacientes do sexo masculino com diagnóstico de dependência de nicotina, sem outras patologias. Todos receberam bupropiona até 300 mg ao dia por 12 semanas, associada à terapia cognitivo-comportamental em grupo. A Escala de Fagerström foi aplicada no início e no final do tratamento, e avaliou-se a parada do uso de cigarros na última semana de tratamento e um mês após. Os pacientes tiveram 10 ml de sangue colhidos e genotipados para a existência do polimorfismo SLC6A3 3’UTR VNTR. Resultados: Não foi encontrada associação entre cessação do uso de cigarro e presença do polimorfismo. Conclusão: São necessários mais estudos para avaliar se a presença do polimorfismo SLC6A3 3’UTR VNTR estaria relacionada à melhor resposta ao tratamento da dependência de nicotina.

  17. Suitability of IS6110-RFLP and MIRU-VNTR for Differentiating Spoligotyped Drug-Resistant Mycobacterium tuberculosis Clinical Isolates from Sichuan in China

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    Chao Zheng

    2014-01-01

    Full Text Available Genotypes of Mycobacterium tuberculosis complex (MTBC vary with the geographic origin of the patients and can affect tuberculosis (TB transmission. This study was aimed to further differentiate spoligotype-defined clusters of drug-resistant MTBC clinical isolates split in Beijing (n=190 versus non-Beijing isolates (n=84 from Sichuan region, the second high-burden province in China, by IS6110-restriction fragment length polymorphism (RFLP and 24-locus MIRU-VNTRs. Among 274 spoligotyped isolates, the clustering ratio of Beijing family was 5.3% by 24-locus MIRU-VNTRs versus 2.1% by IS6110-RFLP, while none of the non-Beijing isolates were clustered by 24-locus MIRU-VNTRs versus 9.5% by IS6110-RFLP. Hence, neither the 24-locus MIRU-VNTR was sufficient enough to fully discriminate the Beijing family, nor the IS6110-RFLP for the non-Beijing isolates. A region adjusted scheme combining 12 highly discriminatory VNTR loci with IS6110-RFLP was a better alternative for typing Beijing strains in Sichuan than 24-locus MIRU-VNTRs alone. IS6110-RFLP was for the first time introduced to systematically genotype MTBC in Sichuan and we conclude that the region-adjusted scheme of 12 highly discriminative VNTRs might be a suitable alternative to 24-locus MIRU-VNTR scheme for non-Beijing strains, while the clusters of the Beijing isolates should be further subtyped using IS6110-RFLP for optimal discrimination.

  18. 5-HTT VNTR多态性与偏头痛关系的系统评价%A systematic review with meta-analysis on the relationship of 5-HTT VNTR and migraine

    Institute of Scientific and Technical Information of China (English)

    王贤琦; 李光明; 柳华; 冯胜刚

    2011-01-01

    背景5羟色胺(5-HT)在偏头痛的发病机制中起着重要作用,但是研究5-HT转运体(5-HTT)基因多态性和偏头痛关系的单个遗传关联研究的结果却不一致.目的使用系统评价方法评价5-HTT可变数目串联重复序列(VNTR)多态性和偏头痛的关系.方法 广泛检索中英文数据库以发现合格研究,使用随机或固定效应模型计算合并比值比(OR值),使用Q检验评估研究之间异质性,Egger's(埃格)检验和漏斗图评估发表偏倚.以家族为基础的关联研究则进行描述性分析.结果 总共4个研究纳入meta分析,发现在所有人群中,5-HTT VNTR Stin2.12等位基因或12/12基因型增加了偏头痛的发病风险(Stin2.12等位基因:OR:1.34,95%CI:1.09~1.64,P=0.006; 12/12基因型:OR:1.55,95%CI:1.17~2.05,P=0.002).结论 现有证据表明,5-HTT VNTR多态性(主要是Stin2.12基因型)增加了偏头痛的发病风险,该结论需大样本研究进一步验证.%Objective Serotonin is known to play an important role in the pathogenesis of migraine, but individual genetic association studies that examine the relationship between polymorphisms of serotonin transporter (5-HTT) gene and migraine have yielded inconsistent results. This study aimed to evaluate the association between 5-HTT VNTR polymorphism and migraine using systematic review with meta-analysis. Methods Relevant studies were identified by searching English and Chinese databases extensively. Allele and genotype frequencies for each included study were extracted. The odds ratio (OR) was calculated using a random-effects or fixed-effects model. Q statistic was used to evaluate homogeneity, and Egger's test and Funnel plot were used to assess publication bias. For family-based association studies. A descriptive analysis was carried out) Results A total of 4 studies were identified for meta-analysis. It was found that the 5-HTT VNTR Stin2.12 allele or 12/12 genotype had an increased risk for migraine in the

  19. Association between MAOA-u VNTR polymorphism and its interaction with stressful life events and major depressive disorder in adolescents%MAOA-u VNTR多态性单独及和应激性生活事件交互作用与青少年重性抑郁障碍的关联分析

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    马静; 禹顺英; 梁珊; 丁军; 冯哲; 杨帆; 高维佳; 林佳妮; 黄春香

    2013-01-01

    目的 探讨单胺氧化酶A基因相关多态区域(MAOA-u VNTR)基因多态性与青少年重性抑郁障碍(major depressive disorder,MDD)有无关联,以及其与应激性生活事件(stressful life events,SLEs)之间的交互作用与MDD之间有无关联.方法 394名研究对象(MDD患者187人,正常对照207人)采用SNaP-shot系统进行基因分型,评估受试者近1年内的SLEs,采用统计学软件比较各配对组别MAOA-u VNTR基因型及等位基因的分布;建立基因×环境(GXE)交互作用的二分类logistic回归模型,分析MAOA-u VNTR基因型与SLEs交互作用与青少年MDD患病的关联性.结果 MAOA-u VNTR基因型及等位基因分布与青少年MDD是否发生、抑郁严重程度、是否共病焦虑、是否出现自杀观念/行为/企图均无直接相关性;男性及女性MAOA-u VNTR基因型与SLEs均不存在和青少年MDD患病相关的交互作用.结论 尚不能认为MAOA-u VNTR与青少年MDD相关;MAOA-u VNTR与SLEs间不存在与青少年MDD相关联的基因-环境交互作用.%Objective To investigate whether the genetic polymorphism,upstream variable number of tandem repeats (uVNTR),in the monoamine oxidase A (MAOA) gene,is associated with major depressive disorder (MDD) in adolescents and to test whether there is gene-environment interaction between MAOA-uVNTR polymorphism and stressful life events (SLEs).Methods A total of 394 Chinese Han subjects,including 187 adolescent patients with MDD and 207normal students as a control group,were included in the study.Genotyping was performed by SNaP-shot assay.SLEs in the previous 12 months were evaluated.The groups were compared in terms of the frequency distributions of MAOA-uVNTR genotypes and alleles using statistical software.The binary logistic regression model of gene-environment interaction was established to analyze the association of the gene-environment interaction between MAOA-u VNTR genotypes and SLEs with adolescent MDD.Results The distribution profiles

  20. Dopamine transporter 3'UTR VNTR genotype is a marker of performance on executive function tasks in children with ADHD

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    Polotskaia Anna

    2008-06-01

    Full Text Available Abstract Background Attention-Deficit/Hyperactivity Disorder (ADHD is a heterogeneous disorder from both clinical and pathogenic viewpoints. Executive function deficits are considered among the most important pathogenic pathways leading to ADHD and may index part of the heterogeneity in this disorder. Methods To investigate the relationship between the dopamine transporter gene (SLC6A3 3'-UTR VNTR genotypes and executive function in children with ADHD, 196 children diagnosed with ADHD were sequentially recruited, genotyped, and tested using a battery of three neuropsychological tests aimed at assessing the different aspects of executive functioning. Results Taking into account a correction for multiple comparisons, the main finding of this study is a significant genotype effect on performances on the Tower of London (F = 6.902, p = 0.009 and on the Wechsler Intelligence Scale for Children, Third Edition (WISC-III Freedom From Distractibility Index (F = 7.125, p = 0.008, as well as strong trends on Self Ordered Pointing Task error scores (F = 4,996 p = 0.026 and WISC-III Digit Span performance (F = 6.28, p = 0.023. Children with the 9/10 genotype exhibited, on average, a poorer performance on all four measures compared to children with the 10/10 genotype. No effect of genotype on Wisconsin Card Sorting Test measures of performance was detected. Conclusion Results are compatible with the view that SLC6A3 genotype may modulate components of executive function performance in children with ADHD.

  1. Molecular Typing of Mycobacterium Tuberculosis Complex by 24-Locus Based MIRU-VNTR Typing in Conjunction with Spoligotyping to Assess Genetic Diversity of Strains Circulating in Morocco.

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    Nada Bouklata

    Full Text Available Standard 24-locus Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeat (MIRU-VNTR typing allows to get an improved resolution power for tracing TB transmission and predicting different strain (sub lineages in a community.During 2010-2012, a total of 168 Mycobacterium tuberculosis Complex (MTBC isolates were collected by cluster sampling from 10 different Moroccan cities, and centralized by the National Reference Laboratory of Tuberculosis over the study period. All isolates were genotyped using spoligotyping, and a subset of 75 was genotyped using 24-locus based MIRU-VNTR typing, followed by first line drug susceptibility testing. Corresponding strain lineages were predicted using MIRU-VNTRplus database.Spoligotyping resulted in 137 isolates in 18 clusters (2-50 isolates per cluster: clustering rate of 81.54% corresponding to a SIT number in the SITVIT database, while 31(18.45% patterns were unique of which 10 were labelled as "unknown" according to the same database. The most prevalent spoligotype family was LAM; (n = 81 or 48.24% of isolates, dominated by SIT42, n = 49, followed by Haarlem (23.80%, T superfamily (15.47%, >Beijing (2.97%, > U clade (2.38% and S clade (1.19%. Subsequent 24-Locus MIRU-VNTR typing identified 64 unique types and 11 isolates in 5 clusters (2 to 3isolates per cluster, substantially reducing clusters defined by spoligotyping only. The single cluster of three isolates corresponded to two previously treated MDR-TB cases and one new MDR-TB case known to be contact a same index case and belonging to a same family, albeit residing in 3 different administrative regions. MIRU-VNTR loci 4052, 802, 2996, 2163b, 3690, 1955, 424, 2531, 2401 and 960 were highly discriminative in our setting (HGDI >0.6.24-locus MIRU-VNTR typing can substantially improve the resolution of large clusters initially defined by spoligotyping alone and predominating in Morocco, and could therefore be used to better study tuberculosis

  2. Association analysis between a VNTR intron 8 polymorphism of the dopamine transporter gene (SLC6A3 and obsessive- compulsive disorder in a Brazilian sample Análise de associação entre um polimorfismo VNTR no intron 8 do gene do transportador de dopamina (SLC6A3 e transtorno obsessivo-compulsivo em uma amostra brasileira

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    Karen Miguita

    2007-12-01

    Full Text Available Family, twin and segregation analysis have provided evidences that genetic factors are implicated in the susceptibility for obsessive-compulsive disorder (OCD. Several lines of research suggest that the dopaminergic system may be involved in the pathophysiology of OCD. Thus, the aim of the present study was to investigate a possible association between a polymorphism located in intron 8 of the dopamine transporter gene (SLC6A3 and OCD in a Brazilian sample composed by 208 patients and 865 healthy controls. No statistically differences were observed in allelic and genotype distributions between cases and controls. No association was also observed when the sample was divided according to specific phenotypic features such as gender, presence of tic disorders co-morbidity and age at onset of obsessive-compulsive symptoms (OCS. Our results suggest that the intron 8 VNTR of the SLC6A3 investigated in this study is not related to the susceptibility for OCD in our Brazilian sample.Estudos de família, gêmeos e de segregação têm demonstrado que fatores genéticos estão envolvidos na susceptibilidade para o desenvolvimento do transtorno obsessivo-compulsivo (TOC. Várias linhas de pesquisa sugerem que o sistema dopaminérgico possa estar envolvido na fisiopatologia do TOC. Assim, o objetivo do presente estudo foi investigar uma possível associação entre o polimorfismo localizado no intron 8 do gene do transportador da dopamina (SLC6A3 e o TOC em uma amostra brasileira composta por 208 pacientes e 865 controles sadios. Nenhuma diferença estatisticamente significante foi observada nas distribuições alélicas e genotípicas entre os grupos de pacientes e controles. Nenhuma associação também foi observada quando as amostras foram divididas de acordo com características fenotípicas específicas, tais como gênero, presença de co-morbidade com tiques e idade de início dos sintomas obsessivo-compulsivo (SOC. Nossos resultados sugerem que o VNTR

  3. Altered effect of dopamine transporter 3'UTR VNTR genotype on prefrontal and striatal function in schizophrenia.

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    Prata, Diana P; Mechelli, Andrea; Picchioni, Marco M; Fu, Cynthia H Y; Toulopoulou, Timothea; Bramon, Elvira; Walshe, Muriel; Murray, Robin M; Collier, David A; McGuire, Philip

    2009-11-01

    The dopamine transporter plays a key role in the regulation of central dopaminergic transmission, which modulates cognitive processing. Disrupted dopamine function and impaired executive processing are robust features of schizophrenia. To examine the effect of a polymorphism in the dopamine transporter gene (the variable number of tandem repeats in the 3' untranslated region) on brain function during executive processing in healthy volunteers and patients with schizophrenia. We hypothesized that this variation would have a different effect on prefrontal and striatal activation in schizophrenia, reflecting altered dopamine function. Case-control study. Psychiatric research center. Eighty-five subjects, comprising 44 healthy volunteers (18 who were 9-repeat carriers and 26 who were 10-repeat homozygotes) and 41 patients with DSM-IV schizophrenia (18 who were 9-repeat carriers and 23 who were 10-repeat homozygotes). Regional brain activation during word generation relative to repetition in an overt verbal fluency task measured by functional magnetic resonance imaging. Main effects of genotype and diagnosis on activation and their interaction were estimated with analysis of variance in SPM5. Irrespective of diagnosis, the 10-repeat allele was associated with greater activation than the 9-repeat allele in the left anterior insula and right caudate nucleus. Trends for the same effect in the right insula and for greater deactivation in the rostral anterior cingulate cortex were also detected. There were diagnosis x genotype interactions in the left middle frontal gyrus and left nucleus accumbens, where the 9-repeat allele was associated with greater activation than the 10-repeat allele in patients but not controls. Insular, cingulate, and striatal function during an executive task is normally modulated by variation in the dopamine transporter gene. Its effect on activation in the dorsolateral prefrontal cortex and ventral striatum is altered in patients with schizophrenia

  4. Effect of VNTR polymorphism of the Muc1 gene on litter size of pigs.

    Science.gov (United States)

    Xiao, Chen; Jinluan, Fu; Aiguo, Wang

    2012-05-01

    An investigation was undertaken to study the association between the variable number of tandem repeats polymorphism of the Muc1 gene and the litter size in pigs. Four different alleles were found in three breeds. The sequence analysis shows that the repetitive region of pig Muc1 gene is an array of 108-bp repeats. A total of 2,430 litter records from 897 sows genotyped at Muc1 gene were used to analyze the total number born (TNB) and number born alive (NBA). The study of the effects on litter size suggests that TNB and NBA of genotype AA are the highest in Large White, and the TNB and NBA of the third to ninth parities are 1.61 and 2.29 piglets per litter higher (P NBA of the genotype AA are 1.68 (P NBA of genotype AA are about 1.5 piglets per litter more than those of DD in the third to ninth parities, though not significantly. The research suggests that the smaller allele tends to have higher litter size. The results indicate that Muc1 gene is significantly associated with litter size in pigs.

  5. Genomic variability of Mycobacterium tuberculosis strains of the Euro-American lineage based on large sequence deletions and 15-locus MIRU-VNTR polymorphism.

    Directory of Open Access Journals (Sweden)

    Laura Rindi

    Full Text Available A sample of 260 Mycobacterium tuberculosis strains assigned to the Euro-American family was studied to identify phylogenetically informative genomic regions of difference (RD. Mutually exclusive deletions of regions RD115, RD122, RD174, RD182, RD183, RD193, RD219, RD726 and RD761 were found in 202 strains; the RD(Rio deletion was detected exclusively among the RD174-deleted strains. Although certain deletions were found more frequently in certain spoligotype families (i.e., deletion RD115 in T and LAM, RD174 in LAM, RD182 in Haarlem, RD219 in T and RD726 in the "Cameroon" family, the RD-defined sublineages did not specifically match with spoligotype-defined families, thus arguing against the use of spoligotyping for establishing exact phylogenetic relationships between strains. Notably, when tested for katG463/gyrA95 polymorphism, all the RD-defined sublineages belonged to Principal Genotypic Group (PGG 2, except sublineage RD219 exclusively belonging to PGG3; the 58 Euro-American strains with no deletion were of either PGG2 or 3. A representative sample of 197 isolates was then analyzed by standard 15-locus MIRU-VNTR typing, a suitable approach to independently assess genetic relationships among the strains. Analysis of the MIRU-VNTR typing results by using a minimum spanning tree (MST and a classical dendrogram showed groupings that were largely concordant with those obtained by RD-based analysis. Isolates of a given RD profile show, in addition to closely related MIRU-VNTR profiles, related spoligotype profiles that can serve as a basis for better spoligotype-based classification.

  6. Functional G894T (rs1799983) polymorphism and intron-4 VNTR variant of nitric oxide synthase (NOS3) gene are susceptibility biomarkers of obesity among Tunisians.

    Science.gov (United States)

    Nasr, Hela Ben; Dimassi, Saloua; M'hadhbi, Refka; Debbabi, Haithem; Kortas, Mondher; Tabka, Zouhair; Chahed, Karim

    2016-01-01

    The endothelial nitric oxide synthase (NOS3) has been shown to play a role in the modulation of lipolysis. The goal of this study was to examine the impact of the G894T (rs1799983) and a 27 bp variable number of tandem repeats (VNTR 4a/b) of NOS3 gene on obesity in a sample of the Tunisian population. The study included 211 normal weight subjects and 183 obese patients. NOS3 G894T and 4a/b variants were determined by PCR analysis and examined for association with obesity-related traits. The effect of obesity on forearm skin blood flow (FSBF) response to acetylcholine, an endothelium-dependent vasodilator was determined by laser Doppler iontophoresis. In case-control studies, both G894T and 4a/b variants were associated with obesity. A significantly increased risk of obesity was found with the NOS3(G894T) TT genotype (OR:2.62, P=0.04). This association remains significant after adjustments for age and gender (OR: 2.93, P=0.03). A higher risk was also observed for carriers of the G894T allele (OR: 1.72, P=0.001). Stratified analysis by gender revealed that obese men (but not women) had significantly higher frequency of TT genotypes compared to controls (9.9% vs. 2.9%, P=0.01). Carriers of the 4b allele presented a significantly higher risk of obesity than non-carriers even after adjustments for age and gender (OR (95%CI): 1.72 (1.16-2.56), P=0.004). Correlations with anthropometric parameters revealed that carriers of TT and bb genotypes had significantly higher body mass index compared to those homozygous for the G and a alleles (P=0.0004). This study provides the first evidence for the association of G894T and 4a/b variants with body mass index and the risk of obesity in Tunisians. These polymorphisms did not exhibit, however any significant association with both metabolic traits and vascular function. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  7. VNTR fingerprinting of Kluyveromyces marxianus strains WT, 7-1, and 8-1 by using different primer types to give best results in PCR and on electrophorese gel in order to find differentiation of the DNA of the yeast strains.

    Science.gov (United States)

    Using mutagenized Kluyveromyces marxianus strains (WT, 7-1, 8-1) we wish to find out the variable numbered tandem repeats (VNTR) of each of the DNA strains from the different mutagenized K. marxianus strains. To do this we used Phusion HF Buffer Pack to try and give a clear picture of the VNTR by u...

  8. Genotipificación por VNTR de aislados de Mycobacterium bovis de ganado sacrificado en Baja California, México

    Directory of Open Access Journals (Sweden)

    Carlos Martínez-Vidal

    2011-01-01

    Full Text Available En México, la tuberculosis bovina (TBB es uno de los principales problemas que enfrenta la ganadería nacional. Las diferentes técnicas de genotipificación pueden ayudar a establecer la relación que existe entre las diferentes cepas presentes en una región y determinar algunos factores que incidan posteriormente en los programas de control y erradicación de la enfermedad. En el presente trabajo se aplicó la técnica de número variable de repeticiones en secuencia (VNTR a 11 aislados provenientes de ganado sacrificado en un rastro de Mexicali BC, y a 10 aislados de ganado sacrificado en un rastro de Tijuana. Se utilizaron oligonucleótidos específicos para amplificar los loci ETR-A, ETR-B, QUB-11a, QUB-11b, QUB-1895, QUB-26, QUB-3232 y QUB-3336, determinándose el parentesco relativo entre las cepas aisladas, así como el poder discriminatorio para cada locus en particular y para todos los loci en su conjunto. Se obtuvieron 14 perfiles alélicos al utilizar los ocho loci con un poder discriminatorio de 0.90 siendo el locus QUB 3336 el que mostró el mayor poder discriminatorio (h=0.72 en tanto el locus ETR-B mostró un nulo poder discriminatorio (h=0.00. En un dendrograma, se observaron seis grupos genéticos, en los cuales se encuentran indistintamente aislados de Tijuana y Mexicali Baja California; sin embargo, se encontraron genotipos específicos para cada una de las dos regiones. Los resultados sugieren que aunque el movimiento de ganado y la compra-venta en la región han provocado la dispersión de cepas en estas dos áreas, se puede discernir el origen de la mayoría de los aislados.

  9. Distribution of α1 immunoglobulin gene VNTR polymorphisms in Chinese%我国汉族人群α1基因数目可变串联重复序列分布特征的研究

    Institute of Scientific and Technical Information of China (English)

    古宏标; 黄玮俊; 杜勇; 李彩霞; 李幼姬; 薛超; 陈素琴; 胡彬; 王一鸣

    2005-01-01

    目的:研究我国汉族人群免疫球蛋白α1基因中3个数目可变串联重复序列(VNTR)多态性分布特征,及其与已报道的高加索人群相比较的特点.方法:从现存数据库中寻找α1基因内的3个VNTR位点,即α1基因3'端的hs1,2增强子内的VNTR1、其上游6 Kb的VNTR2和位于α1基因第5外显子的E5VNTR.提取201例广东汉族人基因组DNA,PCR分别扩增含上述3个VNTR位点片段,2%-3%凝胶电泳分带鉴定基因型,并以测序证实.结果:与高加索人群比较我国汉族人群α1基因VNTR1多态性分布特征表现为:C(3次重复)等位基因频率明显升高(10.0% vs 1.0%),A(1次重复)等位基因频率偏低(30.3% vs 36.1%-39.4%),差异显著(x2=72.85,P<0.01).基因型BB占37.8%,AB占32.3%,AA占12%,BC占11.4%,AC占4.5%,CC占2.0%,BC、AC基因型分布频率显著高于高加索人群,而AB型分布频率显著低于高加索人群(x2=73.77,P<0.01).另外两个数据库中报道的VNTR位点(VNTR 2及E5VNTR)在我们所测人群中呈均一分布,PCR产物长度分别为136 bp(VNTR 2)和535bp(E5VNTR).结论:我国汉族人群α1基因VNTR多态性分布与基因组数据库中基于高加索人群的资料不尽相同,其中Iα1 hs1,2 VN-TR1多态性不同于高加索人群,突出表现为C等位基因频率及BC、AC基因型频率显著高于高加索人群.而VNTR2和E5VNTR在被检人群中未见多态性.本研究弥补了现存数据库中缺乏我国汉族人群相应数据的不足,同时为以α1基因为候选基因找寻疾病基因的研究提供了可靠的数据.

  10. Genotyping of French Bacillus anthracis strains based on 31-loci multi locus VNTR analysis: epidemiology, marker evaluation, and update of the internet genotype database.

    Directory of Open Access Journals (Sweden)

    Simon Thierry

    Full Text Available BACKGROUND: Bacillus anthracis is known to have low genetic variability. In spite of this lack of diversity, multiple-locus variable-number tandem repeat (VNTR analysis (MLVA and single nucleotide polymorphisms (SNPs including the canonical SNPs assay (canSNP have proved to be highly effective to differentiate strains. Five different MLVA schemes based on a collection of 31 VNTR loci (MLVA8, MLVA15, MLVA20, MLVA25 and MLVA31 with increased resolving power have been described. RESULTS: MLVA31 was applied to characterize the French National Reference Laboratory collection. The total collection of 130 strains is resolved in 35 genotypes. The 119 veterinary and environmental strains collection in France were resolved into 26 genotypes belonging to three canSNP lineages and four MLVA clonal complexes (CCs with particular geographical clustering. A subset of seven loci (MLVA7 is proposed to constitute a first line assay. The loci are compatible with moderate resolution equipment such as agarose gel electrophoresis and show a good congruence value with MLVA31. The associated MLVA and SNP data was imported together with published genotyping data by taking advantage of major enhancements to the MLVAbank software and web site. CONCLUSIONS: The present report provides a wide coverage of the genetic diversity of naturally occurring B. anthracis strains in France as can be revealed by MLVA. The data obtained suggests that once such coverage is achieved, it becomes possible to devise optimized first-line MLVA assays comprising a sufficiently low number of loci to be typed either in one multiplex PCR or on agarose gels. Such a selection of seven loci is proposed here, and future similar investigations in additional countries will indicate to which extend the same selection can be used worldwide as a common minimum set. It is hoped that this approach will contribute to an efficient and low-cost routine surveillance of important pathogens for biosecurity such as

  11. Genomic diversity of Mycobacterium tuberculosis Beijing strains isolated in Tuscany, Italy, based on large sequence deletions, SNPs in putative DNA repair genes and MIRU-VNTR polymorphisms.

    Science.gov (United States)

    Garzelli, Carlo; Lari, Nicoletta; Rindi, Laura

    2016-03-01

    The Beijing genotype of Mycobacterium tuberculosis is cause of global concern as it is rapidly spreading worldwide, is considered hypervirulent, and is most often associated to massive spread of MDR/XDR TB, although these epidemiological or pathological properties have not been confirmed for all strains and in all geographic settings. In this paper, to gain new insights into the biogeographical heterogeneity of the Beijing family, we investigated a global sample of Beijing strains (22% from Italian-born, 78% from foreign-born patients) by determining large sequence polymorphism of regions RD105, RD181, RD150 and RD142, single nucleotide polymorphism of putative DNA repair genes mutT4 and mutT2 and MIRU-VNTR profiles based on 11 discriminative loci. We found that, although our sample of Beijing strains showed a considerable genomic heterogeneity, yielding both ancient and recent phylogenetic strains, the prevalent successful Beijing subsets were characterized by deletions of RD105 and RD181 and by one nucleotide substitution in one or both mutT genes. MIRU-VNTR analysis revealed 47 unique patterns and 9 clusters including a total of 33 isolates (41% of total isolates); the relatively high proportion of Italian-born Beijing TB patients, often occurring in mixed clusters, supports the possibility of an ongoing cross-transmission of the Beijing genotype to autochthonous population. High rates of extra-pulmonary localization and drug-resistance, particularly MDR, frequently reported for Beijing strains in other settings, were not observed in our survey.

  12. Dopamine DRD2/ANKK1 Taq1A and DAT1 VNTR polymorphisms are associated with a cognitive flexibility profile in pathological gamblers.

    Science.gov (United States)

    Fagundo, Ana B; Fernández-Aranda, Fernando; de la Torre, Rafael; Verdejo-García, Antonio; Granero, Roser; Penelo, Eva; Gené, Manel; Barrot, Carme; Sánchez, Cristina; Alvarez-Moya, Eva; Ochoa, Cristian; Aymamí, Maria Neus; Gómez-Peña, Mónica; Menchón, Jose M; Jiménez-Murcia, Susana

    2014-12-01

    Like drug addiction, pathological gambling (PG) has been associated with impairments in executive functions and alterations in dopaminergic functioning; however, the role of dopamine (DA) in the executive profile of PG remains unclear. The aim of this study was to identify whether the DRD2/ANKK1 Taq1A-rs1800497 and the DAT1-40 bp VNTR polymorphisms are associated with cognitive flexibility (measured by Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT)) and inhibition response (measured by Stroop Color and Word Test (SCWT)), in a clinical sample of 69 PG patients. Our results showed an association between DA functioning and cognitive flexibility performance. The Taq1A A1+ (A1A2/A1A1) genotype was associated with poorer TMT performance (p<0.05), while DAT1 9-repeat homozygotes displayed better WCST performance (p<0.05) than either 10-repeat homozygotes or heterozygotes. We did not find any association between the DRD2 or DAT1 polymorphisms and the inhibition response. These results suggested that pathological gamblers with genetic predispositions toward lower availability of DA and D2 receptor density are at a higher risk of cognitive flexibility difficulties. Future studies should aim to shed more light on the genetic mechanisms underlying the executive profile in PG. © The Author(s) 2014.

  13. Genetic Diversity of Mycobacterium tuberculosis Isolates from Assam, India: Dominance of Beijing Family and Discovery of Two New Clades Related to CAS1_Delhi and EAI Family Based on Spoligotyping and MIRU-VNTR Typing.

    Science.gov (United States)

    Devi, Kangjam Rekha; Bhutia, Rinchenla; Bhowmick, Shovonlal; Mukherjee, Kaustab; Mahanta, Jagadish; Narain, Kanwar

    2015-01-01

    Tuberculosis (TB) is one of the major public health concerns in Assam, a remote state located in the northeastern (NE) region of India. The present study was undertaken to explore the circulating genotypes of Mycobacterium tuberculosis complex (MTBC) in this region. A total of 189 MTBC strains were collected from smear positive pulmonary tuberculosis cases from different designated microscopy centres (DMC) from various localities of Assam. All MTBC isolates were cultured on Lowenstein-Jensen (LJ) media and subsequently genotyped using spoligotyping and 24-loci mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) typing. Spoligotyping of MTBC isolates revealed 89 distinct spoligo patterns. The most dominant MTBC strain belonged to Beijing lineage and was represented by 35.45% (n = 67) of total isolates, followed by MTBC strains belonging to Central Asian-Delhi (CAS/Delhi) lineage and East African Indian (EAI5) lineage. In addition, in the present study 43 unknown spoligo patterns were detected. The discriminatory power of spoligotyping was found to be 0.8637 based on Hunter Gaston Discriminatory Index (HGDI). On the other hand, 24-loci MIRU-VNTR typing revealed that out of total 189 MTBC isolates from Assam 185 (97.9%) isolates had unique MIRU-VNTR profiles and 4 isolates grouped into 2 clusters. Phylogenetic analysis of 67 Beijing isolates based on 24-loci MIRU-VNTR typing revealed that Beijing isolates from Assam represent two major groups, each comprising of several subgroups. Neighbour-Joining (NJ) phylogenetic tree analysis based on combined spoligotyping and 24-loci MIRU-VNTR data of 78 Non-Beijing isolates was carried out for strain lineage identification as implemented by MIRU-VNTRplus database. The important lineages of MTBC identified were CAS/CAS1_Delhi (41.02%, n = 78) and East-African-Indian (EAI, 33.33%). Interestingly, phylogenetic analysis of orphan (23.28%) MTBC spoligotypes revealed that majority of these orphan

  14. Development of new VNTR markers for pike and assessment of variability at di- and tetranucleotide repeat microsatellite loci

    DEFF Research Database (Denmark)

    Hansen, Michael Møller; Taggart, J.B.; Meldrup, Dorte

    1999-01-01

    -0.57), though one highly variable microsatellite (13 alleles; expected heterozygosity 0.79) was identified. In combination with previously published microsatellites a set consisting of nine polymorphic loci appeared to be useful for discriminating populations, as determined by assignment tests. (C) 1999...

  15. Frequency of 3' VNTR Polymorphism in the Dopamine Transporter Gene SLC6A3 in Humans Predisposed to Antisocial Behavior.

    Science.gov (United States)

    Cherepkova, E V; Aftanas, L I; Maksimov, N; Menshanov, P N

    2016-11-01

    Predisposition to antisocial behavior can be related to the presence of certain polymorphic variants of genes encoding dopaminergic system proteins. We studied the frequencies of allele variants and genotypes of variable number tandem repeat polymorphism in 3' untranslated region (3' VTNR) of the dopaminergic transporter SLC6A3 gene in Caucasian men committed socially dangerous violent and non-violent crimes. Alleles with 9 and 10 repeats were most frequent in both the control group and group of men predisposed to antisocial behavior. At the same time, the 10/10 genotype was more frequently observed in the group of men prone to antisocial non-violent behavior. Hence, the presence of certain variants of 3' VTNR polymorphism of SLC6A3 gene in men is associated with predisposition to certain forms of antisocial behavior.

  16. Association of MAOA-VNTR with alcoholism: meta analysis%单胺氧化酶A串联重复序列多态性与酒精依赖行为关系的Meta分析研究

    Institute of Scientific and Technical Information of China (English)

    禚振华; 姚树桥

    2011-01-01

    目的 探讨酒精依赖行为与单胺氧化酶A串联重复序列多态性(MAOA-VNTR)的关系.方法 通过EMBASE、Sciencedirect、PubMed、Googlescholar、CNKI收集1990~2010年公开发表的关于酒精依赖行为与MAOA-VNTR相关性的病例对照研究,利用元分析软件(CMA)进行分析,通过计算合并优势比(OR值)进行比较.结果 通过筛选,共有10篇文献(共3831例受试,其中对照组2084例,酒精依赖组1747例)符合我们的纳入标准.结果 显示MAOA-VNTR多态性与酒精依赖行为之间关联不显著(OR=1.112,P=0.32),在亚组分析中MAOA-VNTR多态性与反社会酒精依赖亚型关联显著(OR=2.04,P<0.05).结论 MAOA-VNTR多态性可能是反社会酒精依赖亚型的危险因子,而非酒精依赖行为的危险因子.%Objective To explore the relationship between MAOA-VNTR and alcoholism. Methods We performed a meta-analysis of studies of the association between MAOA -VNTR and the alcoholism. The articles were identified from EMBASE , Sciencedirect, PubMed, Googlescholar and CNKI from 1990 to 2010. Results A random-effects model was used to combine results from ten case -control studies. The association is significant in antisocial alcoholics ( OR = 2.04,P <0. 05) ,not in alcoholics ( OR = 1. 112,P = 0. 32). Conclusions MAOA-VNTR might be a risk factor for antisocial alcoholics ,not for alcoholics.

  17. Genetic investigations in immigration cases and frequencies of DNA fragments of the VNTR systems D2S44, D5S43, D7S21, D7S22, and D12S11 in Turks

    DEFF Research Database (Denmark)

    Hansen, Hanna Elsebeth; Morling, N

    1993-01-01

    mainly Turks were investigated with DNA technique in parallel with investigations of 10-15 conventional systems. One man was excluded from paternity by both conventional and DNA investigations. Non-exclusion was observed with both conventional and DNA systems in 97 putative mother/child pairs and in 96...... putative father/child pairs. In a putative father/child combination with non-exclusion in 18 genetic systems, a single genetic inconsistency ('exclusion') in D7S21 (MS31) was observed. The frequency distributions of HinfI digested DNA fragments of the five VNTR systems in 105 Turks are presented....

  18. Suitability of the YNZ22 (D17S5) VNTR polymorphism for legal medicine investigations in the population of Catalonia (Spain).

    Science.gov (United States)

    Gené, M; Huguet, E; Sánchez-García, C; Moreno, P; Corbella, J; Mezquita, J

    1995-01-01

    Allele and phenotype frequencies for the YNZ22 locus were determined in a population sample from Catalonia (Spain) using the polymerase chain reaction (PCR). In 311 unrelated individuals, 14 alleles and 56 phenotypes were observed. No deviation from Hardy-Weinberg equilibrium was found. The observed heterozygosity was 81.35%. The YNZ22 polymorphism is useful for paternity testing with a CE value of 70% and an Essen-Möller value of 9.35 (log.).

  19. Study of the association of serotonin transporter triallelic 5-HTTLPR and STin2 VNTR polymorphisms with lithium prophylaxis response in bipolar disorder.

    Science.gov (United States)

    Tharoor, Hema; Kotambail, Ananthapadmanabha; Jain, Sanjeev; Sharma, Podila Satya Venkata Narasimha; Satyamoorthy, Kapaettu

    2013-04-01

    The 5-hydroxy tryptamine transporter (5-HTT) gene has been previously implicated in lithium response, but the roles of the triallelic 5-HTT linked promoter region (5-HTTLPR) and variable number tandem repeats in the second intron [serotonin transporter intron 2 (STin2)] have not been reported. We examined these polymorphisms in 122 patients with bipolar I disorder, among which 49 patients were classified as good responders, 49 as nonresponders, and 24 as partial responders to lithium prophylaxis. We observed significant variation in the genotype frequencies of STin2 polymorphism among the response groups (P=0.02). There was also a significant association of haplotype consisting of the S allele of 5-HTTLPR and 10 repeat allele of STin2 with lithium response (P=0.01) and no such relationship was found with 5-HTTLPR variants. Our data support preliminary information of a possible association of STin2 and its combined effect with 5-HTTLPR variants with lithium response and also suggest that lithium is likely to be more effective for patients carrying 5-HTT polymorphisms associated with reduced transcriptional activity.

  20. Individual identification of Chinese alligator Alligator sinensis with SSR and mtVNTR molecular markers%使用SSR和mtVNTR分子标记识别扬子鳄个体

    Institute of Scientific and Technical Information of China (English)

    黄磊; 王义权

    2005-01-01

    扬子鳄是中国特有的濒危物种,为有效避免种群衰退,最大限度地保持该物种现有的遗传多样性,有必要对种群的个体进行个体识别研究,以便重建遗传谱系,指导现有繁育工作.应用SSR (Simple sequence repeats) 与mtVNTR (Variable number tandem repeats on mitochondrial DNA) 两种分子标记对扬子鳄39个个体进行了个体识别分析,结果显示:8个SSR座位的累计个体识别率与累计父权排除率分别达0.9968、0.7697,mtVNTR的个体识别率为0.9146,联合SSR与mtVNTR两种分子标记的累计个体识别率理论值达0.9997,并在实际分析中将39个扬子鳄个体完全区分开,其区分能力较RAPD (Random amplified polymorphic DNA)、AFLP (Amplified fragment length polymorphism) 及mtDNA控制区5′端序列分析等分子标记要高.此外,SSR和mtVNTR还可对某些低频等位基因及其携带个体做有效的筛查,这对今后进行大量扬子鳄个体的分子标记识别和群体的遗传谱系建立等工作将具有一定实际意义[动物学报 51(3):501-506,2005].

  1. 儿童结核病101例临床分离结核分枝杆菌多位点串联重复序列分型%Genotyping of 101 Mycobacterium tuberculosis isolates from pediatrics tuberculosis in Chongqing by multiple locus VNTR analysis

    Institute of Scientific and Technical Information of China (English)

    王均; 黄延风; 张爱华; 许红梅

    2011-01-01

    Objective To study the distribution of the variable number tandem repeats (VNTR) in clinically isolated strains Mycobacterium tuberculosis (M. tuberculosis ) from pediatrics tuberculosis in Chongqing and explore the effective loci combination of them by multiple locus VNTR analysis (MLVA). Methods Twenty-four standardized MLVA loci was used to type the 101 clinically isolated M. tuberculosis strains, and the results were analyzed by BioNumerics 6.1 software, which including dendrogram and Hunter-Gaston index (HGI) of 24 loci. The HGI of different loci set (12 loci, 15 loci, and 24 loci) was evaluated. Results Twenty-four loci showed different polymorphism. All the 101 clinical isolates were typed into one group that displaying 83 genotypes, in which 69 strains (68.32%, 69/101 ) were typed 69 genotypes respectively, and 32 strains (31.68%) were typed 14 genotypes which showed cluster rate of 17.82%. The HGI of 24 loci was from 0. 168 to 0. 829, the number of VNTR loci with HGI higher than 0.5 was 16. Three loci set displayed different polymorphism. HGI of 12 loci, 15 loci, and 24 loci set were 0.995, 0.996, and 0.996 respectively. Conclusion The clinical strains of M. tuberculosis isolated from pediatrics tuberculosis in Chongqing show definite polymorphism and the standardization 15 loci VNTR set of MLVA can be used in the molecular epidemiological study of these strains in Chongqing.%目的 了解重庆地区儿童结核病中结核分枝杆菌临床分离株的数目可变串联重复序列(variable number tandem repeats,VNTR)的分布特征,寻找适合的VNTR位点组合.方法 采用多位点串联重复序列(multiple locus VNTR analysis,MLVA)分型方法,选择标化的24个VNTR位点,对101例结核分枝杆菌临床分离株DNA进行检测,结果采用BioNumerics 6.1数据库软件进行聚类分析和单位点Hunter-Gaston分辨率指数(Hunter-Gaston index,HGI)分析,并比较分析国际推荐的分组(12、15、24位点)的

  2. Association of low-activity MAOA allelic variants with violent crime in incarcerated offenders.

    Science.gov (United States)

    Stetler, Dean A; Davis, Chad; Leavitt, Kathryn; Schriger, Ilana; Benson, Katie; Bhakta, Samir; Wang, Lam Chee; Oben, Cynthia; Watters, Matthew; Haghnegahdar, Tara; Bortolato, Marco

    2014-11-01

    The main enzyme for serotonin degradation, monoamine oxidase (MAO) A, has recently emerged as a key biological factor in the predisposition to impulsive aggression. Male carriers of low-activity variants of the main functional polymorphism of the MAOA gene (MAOA-uVNTR) have been shown to exhibit a greater proclivity to engage in violent acts. Thus, we hypothesized that low-activity MAOA-uVNTR alleles may be associated with a higher risk for criminal violence among male offenders. To test this possibility, we analyzed the MAOA-uVNTR variants of violent (n = 49) and non-violent (n = 40) male Caucasian and African-American convicts in a correctional facility. All participants were also tested with the Childhood Trauma Questionnaire (CTQ), Barratt Impulsivity Scale (BIS-11) and Buss-Perry Aggression Questionnaire (BPAQ) to assess their levels of childhood trauma exposure, impulsivity and aggression, respectively. Our results revealed a robust (P crime. This association was replicated in the group of Caucasian violent offenders (P crime charges were not associated with CTQ, BIS-11 and BPAQ scores, carriers of low-activity alleles exhibited a mild, yet significant (P genetic determinant for criminal violence. Further studies are required to confirm these results in larger samples of inmates and evaluate potential interactions between MAOA alleles and environmental vulnerability factors.

  3. 抽动秽语综合征儿童的IL-1Ra基因多态性与执行功能%Relationship of IL-1Ra86bp VNTR and executive function in children with Gilles de la Tourette's syndrome

    Institute of Scientific and Technical Information of China (English)

    季卫东; 杨闯; 周家秀; 黄晓琪; 姚静; 郭田友; 郭兰婷; 刘协和

    2013-01-01

    目的:探讨白介素1受体拮抗剂第2内含子86bp可重复多态性(IL-1Ra86bp VNTR)与汉族抽动秽语综合征儿童(TS)及执行功能的关系.方法:选取符合美国精神疾病诊断统计手册第4版TS诊断标准的儿童112例,健康对照71例.采用聚合酶链反应(PCR)等位基因分型技术对所有对象的IL-1Ra86bp多态位点进行测定,分析该位点与TS疾病的关联,同时采用Stroop色词测验(Stroop test)测定研究对象的执行功能.结果:全部112例TS组和54例单纯TS组的IL-1 Ra86bp位点基因型频率(54.0%,56.0% vs.55.1%)和等位基因频率(77.0%,78.0% vs.77.0%)与对照组相比差异无统计学意义(均P>0.05).48例TS共病注意缺陷多动障碍(ADHD)组的IL-1Ra86bp长(L)位点基因型频率(79.0%vs.55.1%)和等位基因频率(90.0% vs.77.0%)明显高于对照组(均P<0.05).TS共病ADHD组L/L基因型的儿童C错误数多于对照组[(5.8±14.8)vs.(2.8±12.4),P <0.05].结论:IL-1Ra86bp基因多态性与共病ADHD的抽动秽语综合征可能存在关联,携带L/L基因型的抽动秽语综合征儿童执行功能可能较差.%Objective:To investigate the association between IL-1Ra gene polymorphism and Gilles de la Tourette's syndrome (TS).Methods:Totally 112 children who were diagnosed as Tourette's syndrome according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fourth Edition (DSM-Ⅳ) and 71 healthy children were selected.By using Amplification Refractory Mutation System (ARMS) Polymerase Chain Reaction (PCR) genotyping assay method,a polymorphism of IL-1 Ra gene was genotyped.The correlation between positive association of polymorphism of 1L-1Ra gene in TS and the executive function in patients with TS was also analyzed Results:Compared with control group,there was no significant difference in genotype frequency (54.0%,56.0% vs.55.1%) and allele frequency (77.0%,78.0% vs.77.0%) in 112 TS groups and 54 alone-TS groups

  4. Platelet glycoprotein gene Ia C807T, HPA-3, and Ibα VNTR polymorphisms are associated with increased ischemic stroke risk: Evidence from a comprehensive meta-analysis.

    Science.gov (United States)

    Liu, Hua; Wang, Yi; Zheng, Jian; Li, Guangming; Chen, Tao; Lei, Jianguo; Mao, Yiting; Wang, Jun; Liu, Wei; Zhao, Ge; Tacey, Mark; Yan, Bernard

    2017-01-01

    Background/aims Platelet glycoproteins play a crucial role in the initial stage of thrombus formation and may contribute to the pathophysiology of atherosclerosis. Polymorphisms in glycoprotein genes alter the function of the protein, possibly leading to increased risk of ischemic stroke. However, previous genetic association studies that examined the relationship between glycoprotein genes polymorphisms and ischemic stroke have yielded inconsistent results. This study aimed to evaluate the association between glycoprotein genes and ischemic stroke by the application of meta-analysis. Methods Relevant studies were identified by an extensive search through databases. The quality of included studies was assessed independently using the Newcastle-Ottawa Scale. Allele and genotype frequencies for each included study were extracted. The odds ratio (OR) with 95% confidence interval (95%CI) was calculated using a random-effects or fixed-effects model. Q statistic was used to evaluate homogeneity, and a meta-regression model was used to explore the study-level variables and to describe the heterogeneity in included studies. Egger's test and funnel plot were used to assess publication bias. Results A total of 60 studies (9 polymorphisms) were included and identified in the current meta-analysis. The Newcastle-Ottawa Scale scores ranged from 7 to 9 except for two studies with Newcastle-Ottawa Scale scores of 6. The T allele or TT genotype of the glycoprotein Ia C807T polymorphism were associated with an increased susceptibility to ischemic stroke in combined population (807T allele: OR, 95%CI: 1.24, 1.03-1.50, p = 0.02) or Asian populations (807T allele: OR, 95%CI: 1.31, 1.10-1.54, p = 0.002 and 807TT genotype: OR, 95%CI: 1.53, 1.13-2.08, p = 0.006, respectively), and the Ser allele of HPA-3 was associated with increased risk of ischemic stroke in combined population or in Asians (OR, 95%CI: 1.21, 1.04-1.40, p = 0.01 or 1.54, 1.18-2.01, p = 0.001). Of

  5. Short alleles revealed by PCR demonstrate no heterozygote deficiency at minisatellite loci D1S7, D7S21, and D12S11

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, S.; Castro, A.; Fernandez-Fernandez, I.; Pancorbo, M.M. de [Universidad del Pais Vasco, Vizcaya (Spain)

    1997-02-01

    Short VNTR alleles that go undetected after conventional Southern blot hybridization may constitute an alternative explanation for the heterozygosity deficiency observed at some minisatellite loci. To examine this hypothesis, we have employed a screening procedure based on PCR amplification of those individuals classified as homozygotes in our databases for the loci D1S7, D7S21, and D12S11. The results obtained indicate that the frequency of these short alleles is related to the heterozygosity deficiency observed. For the most polymorphic locus, D1S7, {approximately}60% of those individuals previously classified as homozygotes were in fact heterozygotes for a short allele. After the inclusion of these new alleles, the agreement between observed and expected heterozygosity, along with other statistical tests employed, provide additional evidence for lack of population substructuring. Comparisons of allele frequency distributions reveal greater differences between racial groups than between closely related populations. 45 refs., 3 figs., 6 tabs.

  6. Dopamine Receptor Gene DRD4 7-Repeat Allele X Maternal Sensitivity Interaction on Child Externalizing Behavior Problems: Independent Replication of Effects at 18 Months.

    Science.gov (United States)

    King, Anthony P; Muzik, Maria; Hamilton, Lindsay; Taylor, Alexander B; Rosenblum, Katherine L; Liberzon, Israel

    2016-01-01

    The DRD4 VNTR has been associated with child behavior problems in interaction with maternal insensitivity in European and American cohorts of preschoolers, with the 7-repeat (7R) allele associated with greater problems. We sought to replicate and expand these findings by examining effects on reports of child behavior problems at 18 months. A 63 family sample with data for observed maternal sensitivity ratings, DRD4 VNTR genotype, and maternal report of child behavior problems at 18-months was used in this preliminary analysis. Maternal sensitivity was measured at 6-months of age using laboratory observational measures (free-play and a teaching task). Maternal report of toddler behavior was obtained at 18-months via the standard Child Behavior Checklist, and infant genotype on the DRD4 VNTR was obtained using PCR. Infants carrying the DRD4 7R allele showed greater effects of maternal insensitivity than non-carriers for behavioral problems at 18-months. We replicated previous findings of association of infant DRD4 x maternal sensitivity interactions with child Externalizing problems in the European-ancestry sample (N = 42) in a median split of maternal sensitivity (p = .00011, eta2 = .329) and in regression analyses controlling for maternal age, maternal depression, and child gender in European ancestry (B = -3.4, SE 1.33, p = .01) and the total sample (B = -2.2, SE 1.02, p = .02). Exploratory analyses also found evidence of DRD4 x maternal sensitivity interaction with the CBCL ADHD scale. These findings replicate in an independent cohort DRD4 x maternal insensitivity interaction effect on child externalizing behavior problems at 18 months, further supporting the role of the DRD4 genotype in differential sensitivity to parenting.

  7. Persistence of the common Hartnup disease D173N allele in populations of European origin.

    Science.gov (United States)

    Azmanov, Dimitar N; Rodgers, Helen; Auray-Blais, Christiane; Giguère, Robert; Bailey, Charles; Bröer, Stefan; Rasko, John E J; Cavanaugh, Juleen A

    2007-11-01

    Hartnup disorder is an aminoaciduria that results from mutations in the recently described gene SLC6A19 on chromosome 5p15.33. The disease is inherited in a simple recessive manner and ten different mutations have been described to date. One mutation, the D173N allele, is present in 42% of Hartnup chromosomes from apparently unrelated families from both Australia and North America. We report an investigation of the origins of the D173N allele using a unique combination of variants including SNPs, microsatellites, and a VNTR across 211 Kb spanning the SLC6A19 locus. All individuals who carry the mutant allele share an identical core haplotype suggesting a single common ancestor, indicating that the elevated frequency of the D173N allele is not a result of recurrent mutation. Analyses of these data indicate that the allele is more than 1000 years old. We compare the reasons for survival of this allele with other major alleles in some other common autosomal recessive diseases occurring in European Caucasians. We postulate that survival of this allele may be a consequence of failure of the allele to completely inactivate the transport of neutral amino acids.

  8. Short mucin 6 alleles are associated with H pylori infection

    Institute of Scientific and Technical Information of China (English)

    Thai V Nguyen; Marcel JR Janssen; Paulien Gritters; René HM te Morsche; Joost PH Drenth; Henri van Asten; Robert JF Laheij; Jan BMJ Jansen

    2006-01-01

    AIM: To investigate the relationship between mucin 6(MUC6) VNTR length and H pylori infection.METHODS: Blood samples were collected from patients visiting the Can Tho General Hospital for upper gastrointestinal endoscopy. DNA was isolated from whole blood, the repeated section was cut out using a restriction enzyme (Pvu Ⅱ) and the length of the allele fragments was determined by Southern blotting. H pylori infection was diagnosed by 14C urea breath test. For analysis, MUC6 allele fragment length was dichotomized as being either long (> 13.5 kbp) or short (≤ 13.5 kbp)and patients were classified according to genotype [long-long (LL), long-short (LS), short-short (SS)].RESULTS: 160 patients were studied (mean age 43years, 36% were males, 58% H pylori positive). MUC6Pvu Ⅱ-restricted allele fragment lengths ranged from 7 to 19 kbp. Of the patients with the LL, LS, SS MUC6genotype, 43% (24/56), 57% (25/58) and 76% (11/46)were infected with H pylori, respectively (P = 0.003).CONCLUSION: Short MUC6 alleles are associated with H pylori infection.

  9. Clustering of Beijing genotype Mycobacterium tuberculosis isolates from the Mekong delta in Vietnam on the basis of variable number of tandem repeat versus restriction fragment length polymorphism typing

    Directory of Open Access Journals (Sweden)

    Huyen Mai NT

    2013-02-01

    Full Text Available Abstract Background In comparison to restriction fragment length polymorphism (RFLP typing, variable number of tandem repeat (VNTR typing is easier to perform, faster and yields results in a simple, numerical format. Therefore, this technique has gained recognition as the new international gold standard in typing of Mycobacterium tuberculosis. However, some reports indicated that VNTR typing may be less suitable for Beijing genotype isolates. We therefore compared the performance of internationally standardized RFLP and 24 loci VNTR typing to discriminate among 100 Beijing genotype isolates from the Southern Vietnam. Methods Hundred Beijing genotype strains defined by spoligotyping were randomly selected and typed by RFLP and VNTR typing. The discriminatory power of VNTR and RFLP typing was compared using the Bionumerics software. Results Among 95 Beijing strains available for analysis, 14 clusters were identified comprising 34 strains and 61 unique profiles in 24 loci VNTR typing ((Hunter Gaston Discrimination Index (HGDI = 0.994. 13 clusters containing 31 strains and 64 unique patterns in RFLP typing (HGDI = 0.994 were found. Nine RFLP clusters were subdivided by VNTR typing and 12 VNTR clusters were split by RFLP. Five isolates (5% revealing double alleles or no signal in two or more loci in VNTR typing could not be analyzed. Conclusions Overall, 24 loci VNTR typing and RFLP typing had similar high-level of discrimination among 95 Beijing strains from Southern Vietnam. However, loci VNTR 154, VNTR 2461 and VNTR 3171 had hardly added any value to the level of discrimination.

  10. Variable Number of Tandem Repeats (VNTR) analysis of Flavobacterium psychrophilum from salmonids in Chile and Norway

    DEFF Research Database (Denmark)

    Apablaza, Patricia; Brevik, Oyvind J.; Mjos, Svein

    2015-01-01

    isolates of this bacterium could play an important role in the development of good management strategies. The aim of this study was to identify genetic markers for discrimination between isolates. A selection of eight VNTRs from 53 F. psychrophilum isolates from Norway, Chile, Denmark and Scotland were...... compared to those from Norway, which suggests a more homogenous reservoir in Norway. Transgenerational transmission of F. psychrophilum from other countries, exporting salmon embryos to Chile, may explain the differences in diversity. The same transmission mechanisms could also explain the wide...

  11. RFLP analysis of forensic DNA samples with single-locus VNTR genetic markers.

    Science.gov (United States)

    Bing, D H; Bieber, F R

    2001-05-01

    This unit covers the many and varied methods for extracting DNA from such diverse specimens as blood, tissue, stamps and envelopes, and cigarette butts, among others. Modifications to the methods that allow the DNA to be used for either PCR or Southern blotbased analyses are also included.

  12. MAOA-uVNTR and Early Physical Discipline Interact to Influence Delinquent Behavior

    Science.gov (United States)

    Edwards, Alexis C.; Dodge, Kenneth A.; Latendresse, Shawn J.; Lansford, Jennifer E.; Bates, John E.; Pettit, Gregory S.; Budde, John P.; Goate, Alison M.; Dick, Danielle M.

    2010-01-01

    Background: A functional polymorphism in the promoter region of the monoamine oxidizing gene "monoamine oxidase A" ("MAOA") has been associated with behavioral sensitivity to adverse environmental conditions in multiple studies (e.g., Caspi et al. 2002; Kim-Cohen et al., 2006). The present study investigates the effects of genotype and early…

  13. The Dopaminergic Reward System and Leisure Time Exercise Behavior: A Candidate Allele Study

    Directory of Open Access Journals (Sweden)

    Charlotte Huppertz

    2014-01-01

    Full Text Available Purpose. Twin studies provide evidence that genetic influences contribute strongly to individual differences in exercise behavior. We hypothesize that part of this heritability is explained by genetic variation in the dopaminergic reward system. Eight single nucleotide polymorphisms (SNPs in DRD1: rs265981, DRD2: rs6275, rs1800497, DRD3: rs6280, DRD4: rs1800955, DBH: rs1611115, rs2519152, and in COMT: rs4680 and three variable number of tandem repeats (VNTRs in DRD4, upstream of DRD5, and in DAT1 were investigated for an association with regular leisure time exercise behavior. Materials and Methods. Data on exercise activities and at least one SNP/VNTR were available for 8,768 individuals aged 7 to 50 years old that were part of the Netherlands Twin Register. Exercise behavior was quantified as weekly metabolic equivalents of task (MET spent on exercise activities. Mixed models were fitted in SPSS with genetic relatedness as a random effect. Results. None of the genetic variants were associated with exercise behavior (P>.02, despite sufficient power to detect small effects. Discussion and Conclusions. We did not confirm that allelic variants involved in dopaminergic function play a role in creating individual differences in exercise behavior. A plea is made for large genome-wide association studies to unravel the genetic pathways that affect this health-enhancing behavior.

  14. Establishment of Multiple Locus Variable-number Tandem Repeat Analysis Assay for Genotyping of Borrelia burgdorferi sensu lato Detected in China

    Institute of Scientific and Technical Information of China (English)

    ZHOU Xin; HOU Xue Xia; GENG Zhen; ZHAO Rui; WAN Kang Lin; HAO Qin

    2014-01-01

    Objective Human Lyme Borreliosis (LB), which is caused by Borrelia burgdorferi sensu lato (B. burgdorferi), has been identified as a major arthropod-borne infectious disease in China. We aimed to develop a multiple locus variable-number tandem repeat (VNTR) analysis (MLVA) assay for the genotyping of Borrelia burgdorferi strains detected in China. Methods B. garinii PBi complete 904.246 kb chromosome and two plasmids (cp26 and lp54) were screened by using Tandem Repeats Finder program for getting potential VNTR loci, the potential VNTR loci were analyzed and identified with PCR and the VNTR loci data were analyzed and MLVA clustering tree were constrcted by using the categorical coefficient and the unweighted pair-group method with arithmetic means (UPGMA). Results We identified 5 new VNTR loci through analyzing 47 potential VNTR loci. We used the MLVA protocol to analyse 101 B. burgdorferi strains detected in China and finally identified 51 unique genotypes in 4 major clusters including B. burgdorferi sensu stricto (B.b.s.s), B. garinii, B. afzelii, and B. valaisiana, consistent with the current MLSA phylogeny studies. The allele numbers of VNTR-1, VNTR-2, VNTR-3, VNTR-4, and VNTR-5 were 7, 3, 9, 7, and 6. The Hunter-Gaston index (HGI) of five VNTR loci were 0.79, 0.22, 0.77, 0.71, and 0.67, respectively. The combined HGI of five VNTR loci was 0.96. Clustering of the strains of Xinjiang, Inner Mongolia and Heilongjiang was confirmed, and this situation was consistent with the close geographical distribution of those provinces. Conclusion The MLVA protocol esytablished in this study is easy and can show strains’ phylogenetic relationships to distinguish the strains of Borrelia species. It is useful for further phylogenetic and epidemiological analyses of Borrelia strains.

  15. Paternity testing with VNTR DNA systems. I. Matching criteria and population frequencies of the VNTR systems D2S44, D5S43, D7S21, D7S22, and D12S11 in Danes

    DEFF Research Database (Denmark)

    Morling, N; Hansen, Hanna Elsebeth

    1993-01-01

    -systems D2S44 (YNH24), D5S43 (MS8), D7S21 (MS31), D7S22 (g3), and D12S11 (MS43a). The intra gel variability of 970 duplicate investigations on the same gel of DNA from 122 individuals showed no differences exceeding 1.25 mm between the positions of the corresponding DNA fragments. The comparison of 1...

  16. Genomic Characterization of the Vaccinal Strain of Mycobacterium Avium Subspecies Paratuberculosis (MAP 316F by MIRU-VNTR

    Directory of Open Access Journals (Sweden)

    Zahra Ebrahim (MSc

    2015-10-01

    Full Text Available Background and Objective: Paratuberculosis is a chronic granulomatous enteritis of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP. this study aimed to characterize the genome of the MAP 316F strain. Methods: The MAP 316F strain was subjected to the PCR-F57 and PCR-IS900 experiments in order to ensure its identity as MAP. This was followed by application of the Thibault genotyping system consisting of eight loci including 292, x3, 25, 47, 3, 7, 10 and 32. Required genomic material for all experiments was prepared using the simple method of boiling. Gel electrophoresis findings related to the typing PCRs were backed by sequencing of amplification products. Results: In PCR amplification, eight products with the size of 300, 298, 350, 217, 208, 203, 803 and 649 bp were detected at 292, X3, 25, 47, 3, 7, 10 and 32 loci, holding 3, 2, 3, 3, 2, 2, 2 and 8 copies of TRs at these loci, respectively. Conclusion: This genomic pattern is matched with that of the MAP 316F vaccine strain from the French Merial company and also the MAP K10 fully-sequenced strain. Keywords: Mycobacterium avium subsp. paratuberculosis, Genomics, Genotyping techniques, Strain

  17. Sleep homeostatic pressure and PER3 VNTR gene polymorphism influence antidepressant response to sleep deprivation in bipolar depression.

    Science.gov (United States)

    Dallaspezia, Sara; Locatelli, Clara; Lorenzi, Cristina; Pirovano, Adele; Colombo, Cristina; Benedetti, Francesco

    2016-03-01

    Combined Total sleep deprivation (TSD) and light therapy (LT) cause a rapid improvement in bipolar depression which has been hypothesized to be paralleled by changes in sleep homeostasis. Recent studies showed that bipolar patients had lower changes of EEG theta power after sleep and responders to antidepressant TSD+LT slept less and showed a lower increase of EEG theta power then non-responders. A polymorphism in PER3 gene has been associated with diurnal preference, sleep structure and homeostatic response to sleep deprivation in healthy subjects. We hypothesized that the individual variability in the homeostatic response to TSD could be a correlate of antidepressant response and be influenced by genetic factors. We administered three TSD+LT cycles to bipolar depressed patients. Severity of depression was rated on Hamilton Depression Rating Scale. Actigraphic recordings were performed in a group of patients. PER3 polymorphism influenced changes in total sleep time (F=2.24; p=0.024): while PER3(4/4) and PER3(4/5) patients showed a reduction in it after treatment, PER3(5/5) subjects showed an increase of about 40min, suggesting a higher homeostatic pressure. The same polymorphism influenced the change of depressive symptomatology during treatment (F=3.72; p=0.028). Sleep information was recorded till the day after the end of treatment: a longer period of observation could give more information about the possible maintenance of allostatic adaptation. A higher sleep homeostatic pressure reduced the antidepressant response to TSD+LT, while an allostatic adaptation to sleep loss was associated with better response. This process seems to be under genetic control. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Assessment of Genetic Diversity of Zoonotic Brucella spp. Recovered from Livestock in Egypt Using Multiple Locus VNTR Analysis

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    Ahmed M. S. Menshawy

    2014-01-01

    Full Text Available Brucellosis is endemic in most parts of Egypt, where it is caused mainly by Brucella melitensis biovar 3, and affects cattle and small ruminants in spite of ongoing efforts devoted to its control. Knowledge of the predominant Brucella species/strains circulating in a region is a prerequisite of a brucellosis control strategy. For this reason a study aiming at the evaluation of the phenotypic and genetic heterogeneity of a panel of 17 Brucella spp. isolates recovered from domestic ruminants (cattle, buffalo, sheep, and goat from four governorates during a period of five years (2002–2007 was carried out using microbiological tests and molecular biology techniques (PCR, MLVA-15, and sequencing. Thirteen strains were identified as B. melitensis biovar 3 while all phenotypic and genetic techniques classified the remaining isolates as B. abortus (n=2 and B. suis biovar 1 (n=2. MLVA-15 yielded a high discriminatory power (h=0.801, indicating a high genetic diversity among the B. melitensis strains circulating among domestic ruminants in Egypt. This is the first report of the isolation of B. suis from cattle in Egypt which, coupled with the finding of B. abortus, suggests a potential role of livestock as reservoirs of several zoonotic Brucella species in the region.

  19. Assessment of genetic diversity of zoonotic Brucella spp. recovered from livestock in Egypt using multiple locus VNTR analysis.

    Science.gov (United States)

    Menshawy, Ahmed M S; Perez-Sancho, Marta; Garcia-Seco, Teresa; Hosein, Hosein I; García, Nerea; Martinez, Irene; Sayour, Ashraf E; Goyache, Joaquín; Azzam, Ragab A A; Dominguez, Lucas; Alvarez, Julio

    2014-01-01

    Brucellosis is endemic in most parts of Egypt, where it is caused mainly by Brucella melitensis biovar 3, and affects cattle and small ruminants in spite of ongoing efforts devoted to its control. Knowledge of the predominant Brucella species/strains circulating in a region is a prerequisite of a brucellosis control strategy. For this reason a study aiming at the evaluation of the phenotypic and genetic heterogeneity of a panel of 17 Brucella spp. isolates recovered from domestic ruminants (cattle, buffalo, sheep, and goat) from four governorates during a period of five years (2002-2007) was carried out using microbiological tests and molecular biology techniques (PCR, MLVA-15, and sequencing). Thirteen strains were identified as B. melitensis biovar 3 while all phenotypic and genetic techniques classified the remaining isolates as B. abortus (n = 2) and B. suis biovar 1 (n = 2). MLVA-15 yielded a high discriminatory power (h = 0.801), indicating a high genetic diversity among the B. melitensis strains circulating among domestic ruminants in Egypt. This is the first report of the isolation of B. suis from cattle in Egypt which, coupled with the finding of B. abortus, suggests a potential role of livestock as reservoirs of several zoonotic Brucella species in the region.

  20. Mucin variable number tandem repeat polymorphisms and severity of cystic fibrosis lung disease: significant association with MUC5AC.

    Directory of Open Access Journals (Sweden)

    Xueliang Guo

    Full Text Available Variability in cystic fibrosis (CF lung disease is partially due to non-CFTR genetic modifiers. Mucin genes are very polymorphic, and mucins play a key role in the pathogenesis of CF lung disease; therefore, mucin genes are strong candidates as genetic modifiers. DNA from CF patients recruited for extremes of lung phenotype was analyzed by Southern blot or PCR to define variable number tandem repeat (VNTR length polymorphisms for MUC1, MUC2, MUC5AC, and MUC7. VNTR length polymorphisms were tested for association with lung disease severity and for linkage disequilibrium (LD with flanking single nucleotide polymorphisms (SNPs. No strong associations were found for MUC1, MUC2, or MUC7. A significant association was found between the overall distribution of MUC5AC VNTR length and CF lung disease severity (p = 0.025; n = 468 patients; plus, there was robust association of the specific 6.4 kb HinfI VNTR fragment with severity of lung disease (p = 6.2×10(-4 after Bonferroni correction. There was strong LD between MUC5AC VNTR length modes and flanking SNPs. The severity-associated 6.4 kb VNTR allele of MUC5AC was confirmed to be genetically distinct from the 6.3 kb allele, as it showed significantly stronger association with nearby SNPs. These data provide detailed respiratory mucin gene VNTR allele distributions in CF patients. Our data also show a novel link between the MUC5AC 6.4 kb VNTR allele and severity of CF lung disease. The LD pattern with surrounding SNPs suggests that the 6.4 kb allele contains, or is linked to, important functional genetic variation.

  1. Stability of VNTR loci in Mycobacterium leprae during MDT%MDT治疗期间麻风菌VNTR位点的稳定性

    Institute of Scientific and Technical Information of China (English)

    温艳; 邢燕; 刘健; RAMA MURTHY SAKAMURI; VARALAKSHMI VISSA; 翁小满

    2010-01-01

    目的: 评价MDT化疗前和皮肤组织液中麻风菌VNTR位点的稳定性.方法: 分别从12例MB新发患者的皮损组织、皮肤切刮组织液中提取麻风菌DNA.4例患者的DNA标本采用多重PCR扩增17个VNTR位点,8例患者扩增5个VNTR位点,同时常规PCR扩增2个VNTR位点.经直接测序确定VNTR位点重复拷贝数,用Genemapper软件进行片段长度分析.结果: 4例患者的皮损和组织液DNA标本的17个VNTR位点,不仅在MDT治疗前,等位基因型,即拷贝数没有差异,而且治疗期间每2个月连续取材的DNA标本的17个位点也高度相似.另8例患者,4例患者的麻风菌在这5个VNTR位点上无等位基因的变化.结论: 药物治疗对VNTR位点的稳定性无大影响,可能由于MDT后大部分麻风菌停止繁殖,DNA终止复制.

  2. Experimental Evidence for Differential Susceptibility: Dopamine D4 Receptor Polymorphism (DRD4 VNTR) Moderates Intervention Effects on Toddlers' Externalizing Behavior in a Randomized Controlled Trial

    Science.gov (United States)

    Bakermans-Kranenburg, Marian J.; Van Ijzendoorn, Marinus H.; Pijlman, Femke T. A.; Mesman, Judi; Juffer, Femmie

    2008-01-01

    In a randomized controlled trial we tested the role of genetic differences in explaining variability in intervention effects on child externalizing behavior. One hundred fifty-seven families with 1- to 3-year-old children screened for their relatively high levels of externalizing behavior participated in a study implementing Video-feedback…

  3. Linkage mapping of the gene for Type III collagen (COL3A1) to human chromosome 2q using a VNTR polymorphism

    Energy Technology Data Exchange (ETDEWEB)

    Tiller, G.E.; Polumbo, P.A.; Summar, M.L. (Vanderbilt Univ. Medical Center, Nashville, TN (United States))

    1994-03-15

    The gene for the [alpha]1(III) chain of type III collagen, COL3A1, has been previously mapped to human chromosome 2q24.3-q31 by in situ hybridization. Physical mapping by pulsed-field gel electrophoresis has demonstrated that COL3A1 lies within 35 kb of COL5A2. The authors genotyped the CEPH families at the COL3A2 locus using a pentanucleotide repeat polymorphism within intron 25. They demonstrated significant linkage to 18 anonymous markers as well as the gene for carbamyl phosphate synthetase (CPSI), which had been previously mapped to this region. No recombination was seen between COL3A1 and COL5A2 (Z = 9.93 at [theta] = 0) or D2S24 (Z = 10.55 at [theta] = 0). The locus order is (D2S32-D2S138-D2S148)-(D2S24-COL5A2-COL3A1)-(D2S118-D2S161), with odds of 1:2300 for the next most likely order. These relationships are consistent with the physical mapping of COL3A1 to the distal portion of 2q and place it proximal to CPSI by means of multipoint analysis. These linkage relationships should prove useful in further studies of Ehlers-Danlos syndrome type IV and carbamyl phosphate synthetase I deficiency and provide an additional framework for localizing other genes in this region. 13 refs., 2 figs., 1 tab.

  4. Large-scale studies of the HphI insulin gene variable-number-of-tandem-repeats polymorphism in relation to Type 2 diabetes mellitus and insulin release

    DEFF Research Database (Denmark)

    Hansen, S K; Gjesing, A P; Rasmussen, S K

    2004-01-01

    The class III allele of the variable-number-of-tandem-repeats polymorphism located 5' of the insulin gene (INS-VNTR) has been associated with Type 2 diabetes and altered birthweight. It has also been suggested, although inconsistently, that the class III allele plays a role in glucose-induced ins......The class III allele of the variable-number-of-tandem-repeats polymorphism located 5' of the insulin gene (INS-VNTR) has been associated with Type 2 diabetes and altered birthweight. It has also been suggested, although inconsistently, that the class III allele plays a role in glucose...

  5. The origin and evolution of variable number tandem repeat of CLEC4M gene in the global human population.

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    Hui Li

    Full Text Available CLEC4M is a C-type lectin gene serving as cell adhesion receptor and pathogen recognition receptor. It recognizes several pathogens of important public health concern. In particular, a highly polymorphic variable number tandem repeat (VNTR at the neck-region of CLEC4M had been associated with genetic predisposition to some infectious diseases. To gain insight into the origin and evolution of this VNTR in CLEC4M, we studied 21 Africans, 20 Middle Easterns, 35 Europeans, 38 Asians, 13 Oceania, and 18 Americans (a total of 290 chromosomes from the (Human Genome Diversity Panel HGDP-CEPH panel; these samples covered most of alleles of this VNTR locus present in human populations. We identified a limited number of haplotypes among the basic repeat subunits that is 69 base pairs in length. Only 8 haplotypes were found. Their sequence identities were determined in the 290 chromosomes. VNTR alleles of different repeat length (from 4 to 9 repeats were analyzed for composition and orientation of these subunits. Our results showed that the subunit configuration of the same repeat number of VNTR locus from different populations were, in fact, virtually identical. It implies that most of the VNTR alleles existed before dispersion of modern humans outside Africa. Further analyses indicate that the present diversity profile of this locus in worldwide populations is generated from the effect of migration of different tribes and neutral evolution. Our findings do not support the hypothesis that the origin of the VNTR alleles were arisen by independent (separate mutation events and caused by differential allele advantage and natural selection as suggested by previous report based on SNP data.

  6. Replication studies in longevity

    DEFF Research Database (Denmark)

    Varcasia, O; Garasto, S; Rizza, T

    2001-01-01

    In Danes we replicated the 3'APOB-VNTR gene/longevity association study previously carried out in Italians, by which the Small alleles (less than 35 repeats) had been identified as frailty alleles for longevity. In Danes, neither genotype nor allele frequencies differed between centenarians and 20...

  7. [Evaluation of discriminatory power of molecular epidemiology techniques in Mycobacterium tuberculosis Venezuelan isolates].

    Science.gov (United States)

    Méndez, Marìa Victoria; León, Cristy; Escalona, Arnelly; Abadia, Edgar; Da Mata, Omaira; de Waard, Jacobus; Takiff, Howard Eugene

    2016-03-01

    The techniques of spoligotyping and mycobacterial interspersed repetitive unit and variable-number tandem repeat typing with 24 loci (MIRU-VNTR-24), have been used to study the molecular epidemiology of tuberculosis. The aim of this study was: to evaluate the discriminative power of MIRU-VNTR 24 loci alone and in association with spoligotyping in clinical isolates of M tuberculosis in Venezuela; the allelic diversity of the 24 loci; and the discriminative power for the combination of 24 and 15 loci, 12 traditional loci (12t), those with higher allelic diversity and a new combination named 12inv. We analyzed one set of 104 strains of different lineages and a second set of 431 strains belonging to the Latin-America and Mediterranean lineage (LAM) that is predominant in Venezuela. The determination of allelic diversity showed that 4052, 2163b, 424 y 2996 are highly discriminative. Clustering rates of MIRU-VNTR 24 loci, spoligotyping and MIRU-VNTR combined with spoligotyping for 104 isolates were 18.27%, 71.15% and 14.4%, respectively, whereas with the 431 LAM strains the values were 43.2 %, 95.8% and 37.4%. MIRU-VNTR combinations of 15, 12inv and 4 loci were more discriminatory than 12t. Clustering rates for MIRU-VNTR 15 and 12inv loci coupled with spoligotyping in the 104 isolated was 21% and 23%, while for LAM strains was 52% and 46% respectively. The number of different genetics patterns for 15 and 12inv loci were similar. In conclusion, we propose the use of a small number of informative loci MIRU-VNTR coupled to spoligotyping to investigate the transmission of tuberculosis in Venezuela.

  8. Repeat-based Sequence Typing of Carnobacterium maltaromaticum.

    Science.gov (United States)

    Rahman, Abdur; El Kheir, Sara M; Back, Alexandre; Mangavel, Cécile; Revol-Junelles, Anne-Marie; Borges, Frédéric

    2016-06-01

    Carnobacterium maltaromaticum is a Lactic Acid Bacterium (LAB) of technological interest for the food industry, especially the dairy as bioprotection and ripening flora. The industrial use of this LAB requires accurate and resolutive typing tools. A new typing method for C. maltaromaticum inspired from MLVA analysis and called Repeat-based Sequence Typing (RST) is described. Rather than electrophoresis analysis, our RST method is based on sequence analysis of multiple loci containing Variable-Number Tandem-Repeats (VNTRs). The method described here for C. maltaromaticum relies on the analysis of three VNTR loci, and was applied to a collection of 24 strains. For each strain, a PCR product corresponding to the amplification of each VNTR loci was sequenced. Sequence analysis allowed delineating 11, 11, and 12 alleles for loci VNTR-A, VNTR-B, and VNTR-C, respectively. Considering the allele combination exhibited by each strain allowed defining 15 genotypes, ending in a discriminatory index of 0.94. Comparison with MLST revealed that both methods were complementary for strain typing in C. maltaromaticum.

  9. A variable number of tandem repeats in the 3'-untranslated region of the dopamine transporter modulates striatal function during working memory updating across the adult age span.

    Science.gov (United States)

    Sambataro, Fabio; Podell, Jamie E; Murty, Vishnu P; Das, Saumitra; Kolachana, Bhaskar; Goldberg, Terry E; Weinberger, Daniel R; Mattay, Venkata S

    2015-08-01

    Dopamine modulation of striatal function is critical for executive functions such as working memory (WM) updating. The dopamine transporter (DAT) regulates striatal dopamine signaling via synaptic reuptake. A variable number of tandem repeats in the 3'-untranslated region of SLC6A3 (DAT1-3'-UTR-VNTR) is associated with DAT expression, such that 9-repeat allele carriers tend to express lower levels (associated with higher extracellular dopamine concentrations) than 10-repeat homozygotes. Aging is also associated with decline of the dopamine system. The goal of the present study was to investigate the effects of aging and DAT1-3'-UTR-VNTR on the neural activity and functional connectivity of the striatum during WM updating. Our results showed both an age-related decrease in striatal activity and an effect of DAT1-3'-UTR-VNTR. Ten-repeat homozygotes showed reduced striatal activity and increased striatal-hippocampal connectivity during WM updating relative to the 9-repeat carriers. There was no age by DAT1-3'-UTR-VNTR interaction. These results suggest that, whereas striatal function during WM updating is modulated by both age and genetically determined DAT levels, the rate of the age-related decline in striatal function is similar across both DAT1-3'-UTR-VNTR genotype groups. They further suggest that, because of the baseline difference in striatal function based on DAT1-3'-UTR-VNTR polymorphism, 10-repeat homozygotes, who have lower levels of striatal function throughout the adult life span, may reach a threshold of decreased striatal function and manifest impairments in cognitive processes mediated by the striatum earlier in life than the 9-repeat carriers. Our data suggest that age and DAT1-3'-UTR-VNTR polymorphism independently modulate striatal function. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

  10. Analysis of polymorphisms and haplotype structure of the human thymidylate synthase genetic region: a tool for pharmacogenetic studies.

    Directory of Open Access Journals (Sweden)

    Soma Ghosh

    Full Text Available 5-Fluorouracil (5FU, a widely used chemotherapeutic drug, inhibits the DNA replicative enzyme, thymidylate synthase (Tyms. Prior studies implicated a VNTR (variable numbers of tandem repeats polymorphism in the 5'-untranslated region (5'-UTR of the TYMS gene as a determinant of Tyms expression in tumors and normal tissues and proposed that these VNTR genotypes could help decide fluoropyrimidine dosing. Clinical associations between 5FU-related toxicity and the TYMS VNTR were reported, however, results were inconsistent, suggesting that additional genetic variation in the TYMS gene might influence Tyms expression. We thus conducted a detailed genetic analysis of this region, defining new polymorphisms in this gene including mononucleotide (poly A:T repeats and novel single nucleotide polymorphisms (SNPs flanking the VNTR in the TYMS genetic region. Our haplotype analysis of this region used data from both established and novel genetic variants and found nine SNP haplotypes accounting for more than 90% of the studied population. We observed non-exclusive relationships between the VNTR and adjacent SNP haplotypes, such that each type of VNTR commonly occurred on several haplotype backgrounds. Our results confirmed the expectation that the VNTR alleles exhibit homoplasy and lack the common ancestry required for a reliable marker of a linked adjacent locus that might govern toxicity. We propose that it may be necessary in a clinical trial to assay multiple types of genetic polymorphisms in the TYMS region to meaningfully model linkage of genetic markers to 5FU-related toxicity. The presence of multiple long (up to 26 nt, polymorphic monothymidine repeats in the promoter region of the sole human thymidylate synthetic enzyme is intriguing.

  11. Evolution of Variable Number Tandem Repeats and Its Relationship with Genomic Diversity in Salmonella Typhimurium

    Science.gov (United States)

    Fu, Songzhe; Octavia, Sophie; Wang, Qinning; Tanaka, Mark M.; Tay, Chin Yen; Sintchenko, Vitali; Lan, Ruiting

    2016-01-01

    Salmonella enterica serovar Typhimurium is the most common Salmonella serovar causing human infections in Australia and many other countries. A total of 12,112 S. Typhimurium isolates from New South Wales were analyzed by multi-locus variable number of tandem repeat (VNTR) analysis (MLVA) using five VNTRs from 2007 to 2014. We found that mid ranges of repeat units of 8–14 in VNTR locus STTR5, 6–13 in STTR6, and 9–12 in STTR10 were always predominant in the population (>50%). In vitro passaging experiments using MLVA type carrying extreme length alleles found that the majority of long length alleles mutated to short ones and short length alleles mutated to longer ones. Both data suggest directional mutability of VNTRs toward mid-range repeats. Sequencing of 28 isolates from a newly emerged MLVA type and its five single locus variants revealed that single nucleotide variation between isolates with up to two MLVA differences ranged from 0 to 12 single nucleotide polymorphisms (SNPs). However, there was no relationship between SNP and VNTR differences. A population genetic model of the joint distribution of VNTRs and SNPs variations was used to estimate the mutation rates of the two markers, yielding a ratio of 1 VNTR change to 6.9 SNP changes. When only one VNTR repeat difference was considered, the majority of pairwise SNP difference between isolates were 4 SNPs or fewer. Based on this observation and our previous findings of SNP differences of outbreak isolates, we suggest that investigation of S. Typhimurium community outbreaks should include cases of 1 repeat difference to increase sensitivity. This study offers new insights into the short-term VNTR evolution of S. Typhimurium and its application for epidemiological typing. PMID:28082952

  12. [The use of MLVA for Corynebacterium diphtheriae genotyping--preliminary studies].

    Science.gov (United States)

    Zasada, Aleksandra A; Jagielski, Marek; Rzeczkowska, Magdalena; Januszkiewicz, Aleksandra

    2011-01-01

    The complete genome sequence of strain NCTC 13129 C. diphtheriae were investigated in order to identify tandem repeats (VNTR). From 75 VNTR loci identified in the genome 14 were selected. Primers were designed and PCR conditions were optimized for amplification of the selected VNTR markers. Preliminary studies of usefulness of selected VNTR markers were conducted using a group of 28 C. diphtheriae strains. From 14 markers 8 were regarded as potentially useful. The diversity of individual markers ranged from 1 to 6 alleles (Simpson index from 0 to 0,746). No diversity were observed for 3 VNTR markers but it could be a results of too small group of strains analyzed in the tests. Simpson diversity index calculated for all the markers tested on 28 strains was 0,87. Results of the preliminary studies showed usefulness of MLVA for C. diphtheriae genotyping. Nevertheless, confirmation of reliability of the method should be done using a large group of strains. Moreover, the method should be compared with other genotyping methods.

  13. Study of a Functional Polymorphism in the PER3 Gene and Diurnal Preference in a Colombian Sample

    Science.gov (United States)

    Perea, Claudia S; Niño, Carmen L; López-León, Sandra; Gutiérrez, Rafael; Ojeda, Diego; Arboleda, Humberto; Camargo, Andrés; Adan, Ana; Forero, Diego A

    2014-01-01

    Polymorphisms in human clock genes have been evaluated as potential factors influencing circadian phenotypes in several populations. There are conflicting results for the association of a VNTR in the PER3 gene and diurnal preference in different studies. The objective of this study was to investigate the association between diurnal preference and daytime somnolence with the PER3 VNTR polymorphism (rs57875989) in healthy subjects from Colombia, a Latin American population.A total of 294 undergraduate university students from Bogotá, Colombia participated in this study. Two validated self-report questionnaires, the Composite Scale of Morningness (CSM) and the Epworth Sleep Scale (ESS) were used to assess diurnal preference and daytime somnolence, respectively. Individuals were genotyped for the PER3 VNTR using conventional PCR. Statistical comparisons were carried out with PLINK and SNPStats programs. The PER3 VNTR polymorphism was not associated with either diurnal preference or daytime somnolence in this population. No significant differences in mean scores for those scales were found between PER3 VNTR genotypes. In addition, there were no differences in allelic or genotypic frequencies between chronotype categories. This is consistent with several negative findings in other populations, indicating that the proposed influence of this polymorphism in diurnal preference, and related endophenotypes of neuropsychiatric importance, needs further clarification. This is the first report of molecular genetics of human circadian phenotypes in a Spanish-speaking population. PMID:24860629

  14. Importance of NOS3 genetic polymorphisms in the risk of development of ischemic stroke in the Turkish population.

    Science.gov (United States)

    Türkanoğlu Özçelik, Aysun; Can Demirdöğen, Birsen; Demirkaya, Şeref; Adalı, Orhan

    2014-12-01

    In the present study, we aimed to investigate the relationship between endothelial nitric oxide synthase 3 (NOS3) G894T, T-786C, and intron 4 variable number of tandem repeat (VNTR) variants, alone or in combination, and the risk of incidence of ischemic stroke in the Turkish population. The genotypes for all polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphism techniques on 245 ischemic stroke patients and 145 controls. In the case-control analysis, no significant difference was observed between stroke patients and controls with respect to NOS3 G894T, T-786C, and intron 4 VNTR polymorphisms genotype and allele frequency distribution. However, the copresence of G894T and intron 4 VNTR risk-elevating genotypes in the same individual increased the risk of stroke seven times (odds ratio=7.083, 95% confidence interval=0.866-57.963, p=0.029).

  15. Establishment of a Tumor-bearing Mouse Model Stably Expressing EGFP Labeled Human MUC1 VNTRs

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shu-zi; ZHANG Hai-hong; ZHANG Wa; SHI He-liang; YU Xiang-hui; KONG Wei; LI Wei

    2008-01-01

    Two eukaryotic vectors expressing 9 tandem repeats of human MUCI(VNTR),VRI012-VNTR,and pEGFP-VNTR,were constructed by cloning VNTR gene into VR1012 and pEGFP,respectively,VNTR stably expressing murine Lewis lung carcinoma(LLC) cell Iine(VNTR+ LLC) was established by Lipofectamine-mediated transfection of pEGFP-VNTR into LLC cells,The EGFP expression was observed under a fluorescent microscope and VNTR expression in VNTR+ LLC cells was confirmed by means of Western blotting,A syngenic graft tumor model was generated by subcutaneous injection of VNTR+ LLC cells into C57/BL6 mice and tumor size increased rapidly with time and in a cell number dependent manner,VNTR mRNA expression in the tumor formed was confirmed by RT-PCR.After the third immunization mice were challenged subcutaneously with 5x10 5 VNTR* LLC cells,a significant reduction of subcutaneous tumor growth was observed in the groups immunized with VNTR plasmid DNA compared with that in the groups immunized with the vector DNA alone,Thus,the suppression of subcutaneous tumor was antigen-specific,This model is useful for the development of tumor vaccines targeting MUCI VNTRs.

  16. Post-zygotic and inter-individual structural genetic variation in a presumptive enhancer element of the locus between the IL10Rβ and IFNAR1 genes.

    Directory of Open Access Journals (Sweden)

    Hamid Reza Razzaghian

    Full Text Available Although historically considered as junk-DNA, tandemly repeated sequence motifs can affect human phenotype. For example, variable number tandem repeats (VNTR with embedded enhancers have been shown to regulate gene transcription. The post-zygotic variation is the presence of genetically distinct populations of cells in an individual derived from a single zygote, and this is an understudied aspect of genome biology. We report somatically variable VNTR with sequence properties of an enhancer, located upstream of IFNAR1. Initially, SNP genotyping of 63 monozygotic twin pairs and multiple tissues from 21 breast cancer patients suggested a frequent post-zygotic mosaicism. The VNTR displayed a repeated 32 bp core motif in the center of the repeat, which was flanked by similar variable motifs. A total of 14 alleles were characterized based on combinations of segments, which showed post-zygotic and inter-individual variation, with up to 6 alleles in a single subject. Somatic variation occurred in ∼24% of cases. In this hypervariable region, we found a clustering of transcription factor binding sites with strongest sequence similarity to mouse Foxg1 transcription factor binding motif. This study describes a VNTR with sequence properties of an enhancer that displays post-zygotic and inter-individual genetic variation. This element is within a locus containing four related cytokine receptors: IFNAR2, IL10Rβ, IFNAR1 and IFNGR2, and we hypothesize that it might function in transcriptional regulation of several genes in this cluster. Our findings add another level of complexity to the variation among VNTR-based enhancers. Further work may unveil the normal function of this VNTR in transcriptional control and its possible involvement in diseases connected with these receptors, such as autoimmune conditions and cancer.

  17. Associations between period 3 gene polymorphisms and sleep- /chronotype-related variables in patients with late-life insomnia.

    Science.gov (United States)

    Mansour, Hader A; Wood, Joel; Chowdari, Kodavali V; Tumuluru, Divya; Bamne, Mikhil; Monk, Timothy H; Hall, Martica H; Buysse, Daniel J; Nimgaonkar, Vishwajit L

    2017-02-27

    A variable number tandem repeat polymorphism (VNTR) in the period 3 (PER3) gene has been associated with heritable sleep and circadian variables, including self-rated chronotypes, polysomnographic (PSG) variables, insomnia and circadian sleep-wake disorders. This report describes novel molecular and clinical analyses of PER3 VNTR polymorphisms to better define their functional consequences. As the PER3 VNTR is located in the exonic (protein coding) region of PER3, we initially investigated whether both alleles (variants) are transcribed into messenger RNA in human fibroblasts. The VNTR showed bi-allelic gene expression. We next investigated genetic associations in relation to clinical variables in 274 older adult Caucasian individuals. Independent variables included genotypes for the PER3 VNTR as well as a representative set of single nucleotide polymorphisms (SNPs) that tag common variants at the PER3 locus (linkage disequilibrium (LD) between genetic variants variables analyzed individually in prior analyses, dependent measures included PSG total sleep time and sleep latency, self-rated chronotype, estimated with the Composite Scale (CS), and lifestyle regularity, estimated using the social rhythm metric (SRM). Initially, genetic polymorphisms were individually analyzed in relation to each outcome variable using analysis of variance (ANOVA). Nominally significant associations were further tested using regression analyses that incorporated individual ANOVA-associated DNA variants as potential predictors and each of the selected sleep/circadian variables as outcomes. The covariates included age, gender, body mass index and an index of medical co-morbidity. Significant genetic associations with the VNTR were not detected with the sleep or circadian variables. Nominally significant associations were detected between SNP rs1012477 and CS scores (p = 0.003) and between rs10462021 and SRM (p = 0.047); rs11579477 and average delta power (p = 0.043) (analyses uncorrected

  18. Variable number of tandem repeat polymorphisms of DRD4: re-evaluation of selection hypothesis and analysis of association with schizophrenia

    Science.gov (United States)

    Hattori, Eiji; Nakajima, Mizuho; Yamada, Kazuo; Iwayama, Yoshimi; Toyota, Tomoko; Saitou, Naruya; Yoshikawa, Takeo

    2009-01-01

    Associations have been reported between the variable number of tandem repeat (VNTR) polymorphisms in the exon 3 of dopamine D4 receptor gene gene and multiple psychiatric illnesses/traits. We examined the distribution of VNTR alleles of different length in a Japanese cohort and found that, as reported earlier, the size of allele ‘7R' was much rarer (0.5%) in Japanese than in Caucasian populations (∼20%). This presents a challenge to an earlier proposed hypothesis that positive selection favoring the allele 7R has contributed to its high frequency. To further address the issue of selection, we carried out sequencing of the VNTR region not only from human but also from chimpanzee samples, and made inference on the ancestral repeat motif and haplotype by use of a phylogenetic analysis program. The most common 4R variant was considered to be the ancestral haplotype as earlier proposed. However, in a gene tree of VNTR constructed on the basis of this inferred ancestral haplotype, the allele 7R had five descendent haplotypes in relatively long lineage, where genetic drift can have major influence. We also tested this length polymorphism for association with schizophrenia, studying two Japanese sample sets (one with 570 cases and 570 controls, and the other with 124 pedigrees). No evidence of association between the allele 7R and schizophrenia was found in any of the two data sets. Collectively, this study suggests that the VNTR variation does not have an effect large enough to cause either selection or a detectable association with schizophrenia in a study of samples of moderate size. PMID:19092778

  19. [Clinical variations of chronic generalized periodontitis, genetic polymorphism and systemic production of inflammatory cytokines].

    Science.gov (United States)

    Grigorovich, E Sh; Pomorgailo, E G; Khomutova, E Yu; Stepanov, S S

    2015-01-01

    Carriage of polymorphic alleles of genes of cytokines-interleukines IL-1β, IL-1RN, TNFα, IL-4 can be a specific feature of chronic periodontitis patients. Genetic tests can be used to predict the course of the disease at its early manifestations. Objective: To establish the relationship of clinical manifestations of periodontal disease, inflammatory cytokines gene polymorphism and systemic levels of cytokine production. Periodontal tissue assessment and cone-beam computed tomography (CBCT) were performed in 150 periodontitis patients. A molecular--genetic testing for the presence of polymorphic alleles of genes IL-1β -511 C>T and +3953 C>T, IL-1RN (VNTR intron 2), IL-4 (VNTR intron 3), TNFα-308 G>A; content determined IL-1β, TNFα, IL-4 in peripheral blood was carried out in 150 patients with periodontitis and 150 healthy donors. Based on the analysis of the speed and nature of the supporting bone resorption and clinical manifestations patients are divided in "aggressive", "moderately progressive" and "slowly progressive" periodontits course groups. Disease severity was associated with distribution of genotypes and alleles of polymorphic genes cytokine IL-1RN (VNTR intron 2), TNFα-308 G>A and IL-4 (VNTR intron 3); haplotype IL-1β-511 TIL-1β +3953 T/IL-1RN 2R. There was no statistically significant difference in systemic level of IL-1β, TNFα and IL-4 between periodontitis groups but the donor level of cytokines was 2-4 times less.

  20. Laser mass spectrometry for DNA fingerprinting for forensic applications

    Science.gov (United States)

    Chen, C. H. Winston; Tang, Kai; Taranenko, N. I.; Allman, S. L.; Ch'ang, L. Y.

    1994-10-01

    The application of DNA fingerprinting has become very broad in forensic analysis, patient identification, diagnostic medicine, and wildlife poaching, since every individual's DNA structure is identical within all tissues oftheir body. DNA fingerprinting was initiated by the use of restriction fragment length polymorphisms (RFLP). In 1987, Nakamura et aL2 found that a variable number of tandem repeats (VNTR) often occurred in the alleles. The probability of different individuals having the same number of tandem repeats in several different alleles is very low. Thus, the identification of VNTR from genomic DNA became a very reliable method for identification of individuals. Take the Huntington gene as an example, there are CAG trinucleotide repeats. For normal people, the number of CAG repeats is usually between 10 and 40. Since people have chromosomes in pairs, the possibility oftwo individuals having the same VNTR in the Huntington gene is less than one percent, ifwe assume equal distribution for various repeats. When several allels containing VNTR are analyzed for the number of repeats, the possibility of two individuals being exactly identical becomes very unlikely. Thus, DNA fingerprinting is a reliable tool for forensic analysis. In DNA fingerprinting, knowledge of the sequence of tandem repeats and restriction endornuclease sites can provide the basis for identification.

  1. Spoligotyping and variable number tandem repeat analysis of Mycobacterium bovis isolates from cattle in Brazil

    Directory of Open Access Journals (Sweden)

    Patrícia Martins Parreiras

    2012-02-01

    Full Text Available We performed spoligotyping and 12-mycobacterial interspersed repetitive unit-variable number tandem repeats (MIRU-VNTRs typing to characterise Mycobacterium bovis isolates collected from tissue samples of bovines with lesions suggestive for tuberculosis during slaughter inspection procedures in abattoirs in Brazil. High-quality genotypes were obtained with both procedures for 61 isolates that were obtained from 185 bovine tissue samples and all of these isolates were identified as M. bovis by conventional identification procedures. On the basis of the spoligotyping, 53 isolates were grouped into nine clusters and the remaining eight isolates were unique types, resulting in 17 spoligotypes. The majority of the Brazilian M. bovis isolates displayed spoligotype patterns that have been previously observed in strains isolated from cattle in other countries. MIRU-VNTR typing produced 16 distinct genotypes, with 53 isolates forming eight of the groups, and individual isolates with unique VNTR profiles forming the remaining eight groups. The allelic diversity of each VNTR locus was calculated and only two of the 12-MIRU-VNTR loci presented scores with either a moderate (0.4, MIRU16 or high (0.6, MIRU26 discriminatory index (h. Both typing methods produced similar discriminatory indexes (spoligotyping h = 0.85; MIRU-VNTR h = 0.86 and the combination of the two methods increased the h value to 0.94, resulting in 29 distinct patterns. These results confirm that spoligotyping and VNTR analysis are valuable tools for studying the molecular epidemiology of M. bovis infections in Brazil.

  2. Validation study for using lab-on-chip technology for Coxiella burnetii multi-locus-VNTR-analysis (MLVA) typing: application for studying genotypic diversity of strains from domestic ruminants in France.

    Science.gov (United States)

    Prigent, Myriam; Rousset, Elodie; Yang, Elise; Thiéry, Richard; Sidi-Boumedine, Karim

    2015-01-01

    Coxiella burnetii, the etiologic bacterium of Q fever zoonosis, is still difficult to control. Ruminants are often carriers and involved in human epidemics. MLVA is a promising genotyping method for molecular epidemiology. Different techniques are used to resolve the MLVA band profiles such as electrophoresis on agarose gels, capillary electrophoresis or using the microfluidic Lab-on-Chip system. In this study, system based on microfluidics electrophoresis with Lab-on-Chip technology was assessed and applied on DNA field samples to investigate the genotypic diversity of C. burnetii strains circulating in France. The Lab-on-Chip technology was first compared to agarose gel electrophoresis. Subsequently, the set-up Lab-on-Chip technology was applied on 97 samples collected from ruminants in France using the 17 markers previously described. A discordance rate of 27% was observed between Lab-on-Chip and agarose gel electrophoresis. These discrepancies were checked and resolved by sequencing. The cluster analysis revealed classification based on host species and/or geographic origin criteria. Moreover, the circulation of different genotypic strains within the same farm was also observed. In this study, MLVA with Lab-on-Chip technology was shown to be more accurate, reproducible, user friendly and safer than gel electrophoresis. It also provides an extended data set from French ruminant C. burnetii circulating strains useful for epidemiological investigations. Finally, it raises some questions regarding the standardization and harmonization of C. burnetii MLVA genotyping.

  3. Prevalence of Chlamydia trachomatis Genotypes in Men Who Have Sex with Men and Men Who Have Sex with Women Using Multilocus VNTR Analysis-ompA Typing in Guangzhou, China.

    Directory of Open Access Journals (Sweden)

    Xiaolin Qin

    Full Text Available Chlamydia trachomatis is one of the most prevalent bacterial sexually transmitted infection in China. Although C. trachomatis genotypes can be discriminated by outer membrane protein gene (ompA sequencing, currently available methods have limited resolutions. This study used a high-resolution genotyping method, namely, multilocus variable number tandem-repeat analysis with ompA sequencing (MLVA-ompA, to investigate the local epidemiology of C. trachomatis infections among men who have sex with men (MSM and men who have sex with women (MSW attending a sexually transmitted diseases (STD clinic in Guangzhou, China.Rectal specimens from MSM and urethral specimens from MSW were collected between January 2013 and July 2014 at the Guangdong Provincial Center STD clinic. The specimens were sent to the laboratory for analyses. All specimens that were tested positive for C. trachomatis by the commercial nucleic acid amplification tests were genotyped by MLVA-ompA.Fifty-one rectal specimens from MSM and 96 urethral specimens from MSW were identified with C. trachomatis. One hundred and forty-four of the 147 specimens were fully genotyped by MLVA-ompA. Rectal specimens from MSM were divided into four ompA genotypes and urethral specimens from MSW into nine genotypes. No mixed infections were found among all specimens. The most frequent genotypes were D, G, J, E and F. All specimens were further divided into 46 types after ompA genotyping was combined with MLVA. Genotypes D-8.7.1 and G-3.4a.3 were the most frequent among MSM, whereas genotypes D-3.4a.4, E-8.5.1, F-8.5.1, and J-3.4a.2 were the most frequent subtypes among MSW. The discriminatory index D was 0.90 for MLVA, 0.85 for ompA, and 0.95 for MLVA-ompA.The most prevalent MLVA-ompA genotypes were significantly different between MSM and MSW from Guangzhou, China. Moreover, MLVA-ompA represented a more favorable degree of discrimination than ompA and could be a reliable complement for ompA for the routine subtypes of C. trachomatis.

  4. Multibeam collection for VNTR01WT: Multibeam data collected aboard Thomas Washington from 1989-08-28 to 1989-10-02, departing from San Diego, CA and returning to Manzanillo, Mexico

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set is part of a larger set of data called the Multibeam Bathymetry Database (MBBDB) where other similar data can be found at...

  5. Cytokine gene polymorphism [tumor necrosis factor-alpha (-308), IL-10 (-1082), IL-6 (-174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities.

    Science.gov (United States)

    Mokhtar, Galila M; El-Beblawy, Nagham M S; Adly, Amira A; Elbarbary, Nancy S; Kamal, Tarek M; Hasan, Esraa M

    2016-04-01

    To evaluate the association between development, progression, and response to therapy among patients with immune thrombocytopenia (ITP) and different cytokine gene polymorphisms known to be related to autoimmunity [tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, IL-6, IL-17, IL-1Ra]. A total of 50 pediatric patients with ITP (20 newly diagnosed, 30 chronic) and 50 healthy controls were investigated via PCR-restriction fragment length polymorphism analysis for cytokine gene polymorphism. Compared with controls, all patients showed a higher frequency of IL-6-174 CC [P = 0.0001, odds ratio (OR) = 7.048, 95% confidence interval (CI) = 2.18-22.7], higher GA genotype of TNF-α (-308) (P = 0.001, OR = 6.469, 95% CI = 2.0-20.9), higher CC genotype of IL-17F (P = 0.0001, OR = 55.545, 95% CI = 14.4-213.2), higher GG of IL-10-1082 (P = 0.029, OR = 3.6, 95% CI = 1.08-12.18), and A1A2 genotype of IL-1Ra (P = 0.039, OR = 2.374, 95% CI = 1.03-5.4). IL-10 GA and IL-1Ra A1A1 genotypes were higher among chronic patients (P = 0.042, P = 0.001 respectively) compared with newly diagnosed ones. Best platelet response to steroid treatment was found among GC genotype of IL-6 (-174) and GG genotype of IL-10 (-1082) in all patients with ITP. This suggests that previously mentioned cytokine gene polymorphisms possibly contribute to the susceptibility of acquisition of childhood ITP. Furthermore, GA genotype of IL-10 and A1A1 genotype of IL-1Ra polymorphisms are associated with increased risk of chronic ITP. IL-6 (-174) and IL-10 (-1082) genes might play a role in the effectiveness of steroid therapy among patients with ITP.

  6. The genotyping of Mycobacterium bovis isolated from Xinjiang region with MIRU-VNTR%新疆牛分枝杆菌MIRU-VNTR基因分型的初步研究

    Institute of Scientific and Technical Information of China (English)

    曹瑞; 胡桂学; 张喜悦; 孙照刚; 呼西旦; 田苗; 李妍; 胡文婷; 李传友; 范伟兴

    2010-01-01

    为了解牛分枝杆菌的基因型特点,初步建立适合新疆地区的MIRU-VNTR基因分型方法,本研究利用24个MIRU-VNTR位点,对30株牛分枝杆菌新疆分离株进行基因分型研究.结果显示,在24个MIRU-VNTR位点中,有9个位点(ETR-A、B、D、E;MIRU24;QUB11a、11b、1895、26)具有多态性,可将30株菌分为7个基因型,分型指数为0.611.而国际通用的5个ETRs位点(ETR-A~E)可将该30株菌分为4个基因型,分型指数为0.712.多态性位点中多态性指数较高的5个位点(ETR-B、ETR-D、MIRU24、QUB11a、QUB26)具有与9个位点相似的分型能力,分型指数为0.715.研究表明,新疆地区与其他地区或国家的牛分枝杆菌在基因分型方面存在差异.5个多态性较高的位点均具有良好的分型能力,表明MIRU-VNTR基因分型方法可以作为新疆地区牛分枝杆菌分子流行病学研究的辅助方法.

  7. Common polymorphic variation in the genetically diverse African insulin gene and its association with size at birth.

    Science.gov (United States)

    Petry, Clive J; Rayco-Solon, Pura; Fulford, Anthony J C; Stead, John D H; Wingate, Dianne L; Ong, Ken K; Sirugo, Giorgio; Prentice, Andrew M; Dunger, David B

    2009-09-01

    The insulin variable number of tandem repeats (INS VNTR) has been variably associated with size at birth in non-African populations. Small size at birth is a major determinant of neonatal mortality, so the INS VNTR may influence survival. We tested the hypothesis, therefore, that genetic variation around the INS VNTR in a rural Gambian population, who experience seasonal variation in nutrition and subsequently birth weight, may be associated with foetal and early growth. Six polymorphisms flanking the INS VNTR were genotyped in over 2,500 people. Significant associations were detected between the maternally inherited SNP 27 (rs689) allele and birth length [effect size 17.5 (5.2-29.8) mm; P = 0.004; n = 361]. Significant associations were also found between the maternally inherited African-specific SNP 28 (rs5506) allele and post-natal weight gain [effect size 0.19 (0.05-0.32) z score points/year; P = 0.005; n = 728). These results suggest that in the Gambian population studied there are associations between polymorphic variation in the genetically diverse INS gene and foetal and early growth characteristics, which contribute to overall polygenic associations with these traits.

  8. Nitric oxide synthase genotype modulation of impulsivity and ventral striatal activity in adult ADHD patients and healthy comparison subjects.

    Science.gov (United States)

    Hoogman, Martine; Aarts, Esther; Zwiers, Marcel; Slaats-Willemse, Dorine; Naber, Marlies; Onnink, Marten; Cools, Roshan; Kan, Cornelis; Buitelaar, Jan; Franke, Barbara

    2011-10-01

    Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder. The NOS1 gene encoding nitric oxide synthase is a candidate gene for ADHD and has been previously linked with impulsivity. In the present study, the authors investigated the effect of a functional variable number of tandem repeats (VNTR) polymorphism in NOS1 (NOS1 exon 1f-VNTR) on the processing of rewards, one of the cognitive deficits in ADHD. A sample of 136 participants, consisting of 87 adult ADHD patients and 49 healthy comparison subjects, completed a reward-related impulsivity task. A total of 104 participants also underwent functional magnetic resonance imaging during a reward anticipation task. The effect of the NOS1 exon 1f-VNTR genotype on reward-related impulsivity and reward-related ventral striatal activity was examined. ADHD patients had higher impulsivity scores and lower ventral striatal activity than healthy comparison subjects. The association between the short allele and increased impulsivity was confirmed. However, independent of disease status, homozygous carriers of the short allele of NOS1, the ADHD risk genotype, demonstrated higher ventral striatal activity than carriers of the other NOS1 VNTR genotypes. The authors suggest that the NOS1 genotype influences impulsivity and its relation with ADHD is mediated through effects on this behavioral trait. Increased ventral striatal activity related to NOS1 may be compensatory for effects in other brain regions.

  9. Dopamine D4 receptor and serotonin transporter gene effects on the longitudinal development of infant temperament.

    Science.gov (United States)

    Holmboe, K; Nemoda, Z; Fearon, R M P; Sasvari-Szekely, M; Johnson, M H

    2011-07-01

    Existing studies of the effect on infant temperament of the 48 base pair variable number of tandem repeats polymorphism in exon 3 of the dopamine D4 receptor gene, DRD4 VNTR, and the serotonin transporter-linked polymorphic region, 5-HTTLPR, have provided contradictory results, and age seems to be an important factor. The present study investigated the effect of these two polymorphisms on the stability of infant temperament between 4 and 9 months of age. Furthermore, the effect of a recently discovered single nucleotide polymorphism which modulates the 5-HTTLPR (rs25531) was investigated in relation to infant temperament. The study sample consisted of 90 infants, who were assessed by parental report at the two ages under consideration using the Revised Infant Behavior Questionnaire. It was found that infants carrying the 7-repeat allele of the DRD4 VNTR had higher levels of Negative Affect. Furthermore, there was an interaction between DRD4 VNTR and 5-HTTLPR genotype such that infants with the DRD4 VNTR 7-repeat allele and the highest expressing 5-HTTLPR genotype (L(A) L(A) ) had the highest level of Negative Affect. These effects were largely driven by scores on the Falling Reactivity scale. Genetic effects were stable across age. The results emphasize the need for developmental studies of genetic effects on temperament.

  10. [Discriminatory power of variable number on tandem repeats loci for genotyping Mycobacterium tuberculosis strains in China].

    Science.gov (United States)

    Chen, H X; Cai, C; Liu, J Y; Zhang, Z G; Yuan, M; Jia, J N; Sun, Z G; Huang, H R; Gao, J M; Li, W M

    2017-06-10

    Objective: Using the standard genotype method, variable number of tandem repeats (VNTR), we constructed a VNTR database to cover all provinces and proposed a set of optimized VNTR loci combinations for each province, in order to improve the preventive and control programs on tuberculosis, in China. Methods: A total of 15 loci VNTR was used to analyze 4 116 Mycobacterium tuberculosis strains, isolated from national survey of Drug Resistant Tuberculosis, in 2007. Hunter-Gaston Index (HGI) was also used to analyze the discriminatory power of each VNTR site. A set combination of 12-VNTR, 10-VNTR, 8-VNTR and 5-VNTR was respectively constructed for each province, based on 1) epidemic characteristics of M. tuberculosis lineages in China, with high discriminatory power and genetic stability. Results: Through the completed 15 loci VNTR patterns of 3 966 strains under 96.36% (3 966/4 116) coverage, we found seven high HGI loci (including QUB11b and MIRU26) as well as low stable loci (including QUB26, MIRU16, Mtub21 and QUB11b) in several areas. In all the 31 provinces, we found an optimization VNTR combination as 10-VNTR loci in Inner Mongolia, Chongqing and Heilongjiang, but with 8-VNTR combination shared in other provinces. Conclusions: It is necessary to not only use the VNTR database for tracing the source of infection and cluster of M. tuberculosis in the nation but also using the set of optimized VNTR combinations in monitoring those local epidemics and M. tuberculosis (genetics in local) population.

  11. Autism and serotonin transporter gene polymorphisms: a systematic review and meta-analysis.

    Science.gov (United States)

    Huang, Christine H; Santangelo, Susan L

    2008-09-05

    The serotonin transporter gene (5-HTT) plays a crucial role in serotonergic neurotransmission and has been found to be associated, with varying degrees of significance, with many diseases, including autism. Prior association studies of autism have yielded conflicting results regarding the association between two common 5-HTT polymorphisms, the promoter insertion/deletion (5-HTTLPR) and the intron 2 VNTR (STin2 VNTR). We conducted a systematic review and meta-analysis to test the following hypotheses: (i) there is an association between autism and either or both of the 5-HTTLPR and STin2 VNTR polymorphisms, and (ii) the S allele of 5-HTTLPR and/or the STin2.12 allele of the VNTR are the specific risk alleles for autism. All published family-based and population based studies were examined to determine the overall strength of association between 5-HTT polymorphisms and autism. After exclusion of studies with overlapping samples and studies whose data did not allow for calculation of an odds ratio, 16 studies were included for final analyses, all but two of which used a family-based design. The meta-analysis failed to find a significant overall association between either of the 5-HTT polymorphisms examined and autism. Further, no allelic transmission distortion was found when studies of simplex (11 studies) and multiplex (3 studies) family samples were analyzed separately. However, there was significant heterogeneity by ethnicity; family based studies of US mixed population samples showed preferential transmission of the S allele of 5-HTTLPR (S allele:L allele = 247:183), while there was no allelic distortion among the family-based studies of European and Asian samples.

  12. Genetic variations of the endothelial nitric oxide synthase gene are related to increased levels of C-reactive protein and macrophage-colony stimulating-factor in patients with coronary artery disease.

    Science.gov (United States)

    Lekakis, John P; Ikonomidis, Ignatios; Tsibida, Maria; Protogerou, Athanasios; Papada, Aggeliki; Papapanagiotou, Aggeliki; Revela, Ioanna; Papamichael, Christos M; Kalofoutis, Anastasios T; Kremastinos, Dimitrios T

    2006-10-01

    It was the objective of this study to investigate the relation between nitric oxide synthase (NOS3) gene polymorphisms, vascular inflammation, endothelial function, and atherosclerosis. We examined the effects of a variable nucleotide tandem repeats (VNTR) in intron 4, G894T in exon 7 and T-786C at the promoter region of NOS3 on i) C-reactive protein (CRP) and macrophage-colony stimulating-factor (MCSF), and ii) augmentation index (AI) measured by pulse-wave analysis , flow-mediated dilation (FMD) of the brachial artery, intima-media thickness (IMT) of the carotid and femoral artery using ultrasonography and ankle-brachial index (ABI) in 122 patients with chronic coronary artery disease (CAD) who underwent coronary angiography. MCSF and CRP were increased in patients withT-786C (77/122) or VNTR (40/122) allele compared to those without (F = 10.8, p = 0.002 and F = 3.8, p = 0.04 for T-786C and F = 3.65, p = 0.04 and F = 3.2 p = 0.049 forVNTR), even after adjustment for traditional risk factors and medication. Patients with combination of VNTR and T-786C (31/122) had higher MCSF or CRP than patients with one or none of these alleles (p 262 pg/ml or CRP>3.2 mg/l (n = 33/77) had a higher femoral and carotid IMT and number of plaques in the peripheral arteries than those with lower values of these inflammatory indices (p 262 pg/ml had also lower FMD and higher Gensini score than those with lower MCSF (p < 0.05). The intron 4-VNTR and T-786C mutation of NOS3 gene enhance the inflammatory process in patients with chronic CAD.

  13. Investigation of the population structure of Legionella pneumophila by analysis of tandem repeat copy number and internal sequence variation.

    Science.gov (United States)

    Visca, Paolo; D'Arezzo, Silvia; Ramisse, Françoise; Gelfand, Yevgeniy; Benson, Gary; Vergnaud, Gilles; Fry, Norman K; Pourcel, Christine

    2011-09-01

    The population structure of the species Legionella pneumophila was investigated by multilocus variable number of tandem repeats (VNTR) analysis (MLVA) and sequencing of three VNTRs (Lpms01, Lpms04 and Lpms13) in selected strains. Of 150 isolates of diverse origins, 136 (86 %) were distributed into eight large MLVA clonal complexes (VACCs) and the rest were either unique or formed small clusters of up to two MLVA genotypes. In spite of the lower degree of genome-wide linkage disequilibrium of the MLVA loci compared with sequence-based typing, the clustering achieved by the two methods was highly congruent. The detailed analysis of VNTR Lpms04 alleles showed a very complex organization, with five different repeat unit lengths and a high level of internal variation. Within each MLVA-defined VACC, Lpms04 was endowed with a common recognizable pattern with some interesting exceptions. Evidence of recombination events was suggested by analysis of internal repeat variations at the two additional VNTR loci, Lpms01 and Lpms13. Sequence analysis of L. pneumophila VNTR locus Lpms04 alone provides a first-line assay for allocation of a new isolate within the L. pneumophila population structure and for epidemiological studies.

  14. Study of a possible role of the monoamine oxidase A (MAOA) gene in paranoid schizophrenia among a Chinese population.

    Science.gov (United States)

    Sun, Yuhui; Zhang, Jiexu; Yuan, Yanbo; Yu, Xin; Shen, Yan; Xu, Qi

    2012-01-01

    Monoamine oxidase A (MAOA) is the enzyme responsible for degradation of several monoamines, such as dopamine and serotonin that are considered as being two of the most important neurotransmitters involved in the pathophysiology of schizophrenia. To study a possible role of the MAOA gene in conferring susceptibility to schizophrenia, the present study genotyped the variable number of tandem repeat (VNTR) polymorphism and 41 SNPs across this gene among 555 unrelated patients with paranoid schizophrenia and 567 unrelated healthy controls. Quantitative real-time PCR analysis was employed to quantify expression of MAOA mRNA in 73 drug-free patients. While none of these genotyped DNA markers showed allelic association with paranoid schizophrenia, haplotypic association was found for the VNTR-rs6323, VNTR-rs1137070, and VNTR-rs6323-rs1137070 haplotypes in female subjects. Nevertheless, no significant change of the expression of MAOA mRNA was detected in either female or male patients with paranoid schizophrenia. Our study suggests that the interaction between genetic variants within the MAOA gene may contribute to an increased risk of paranoid schizophrenia, but the precise mechanism needs further investigation.

  15. Gene-Gene-Environment Interactions of Serotonin Transporter, Monoamine Oxidase A and Childhood Maltreatment Predict Aggressive Behavior in Chinese Adolescents

    Science.gov (United States)

    Zhang, Yun; Ming, Qing-sen; Yi, Jin-yao; Wang, Xiang; Chai, Qiao-lian; Yao, Shu-qiao

    2017-01-01

    Gene-environment interactions that moderate aggressive behavior have been identified independently in the serotonin transporter (5-HTT) gene and monoamine oxidase A gene (MAOA). The aim of the present study was to investigate epistasis interactions between MAOA-variable number tandem repeat (VNTR), 5-HTTlinked polymorphism (LPR) and child abuse and the effects of these on aggressive tendencies in a group of otherwise healthy adolescents. A group of 546 Chinese male adolescents completed the Child Trauma Questionnaire and Youth self-report of the Child Behavior Checklist. Buccal cells were collected for DNA analysis. The effects of childhood abuse, MAOA-VNTR, 5-HTTLPR genotypes and their interactive gene-gene-environmental effects on aggressive behavior were analyzed using a linear regression model. The effect of child maltreatment was significant, and a three-way interaction among MAOA-VNTR, 5-HTTLPR and sexual abuse (SA) relating to aggressive behaviors was identified. Chinese male adolescents with high expression of the MAOA-VNTR allele and 5-HTTLPR “SS” genotype exhibited the highest aggression tendencies with an increase in SA during childhood. The findings reported support aggression being a complex behavior involving the synergistic effects of gene-gene-environment interactions. PMID:28203149

  16. Allele coding in genomic evaluation

    Directory of Open Access Journals (Sweden)

    Christensen Ole F

    2011-06-01

    Full Text Available Abstract Background Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call this centered allele coding. This study considered effects of different allele coding methods on inference. Both marker-based and equivalent models were considered, and restricted maximum likelihood and Bayesian methods were used in inference. Results Theoretical derivations showed that parameter estimates and estimated marker effects in marker-based models are the same irrespective of the allele coding, provided that the model has a fixed general mean. For the equivalent models, the same results hold, even though different allele coding methods lead to different genomic relationship matrices. Calculated genomic breeding values are independent of allele coding when the estimate of the general mean is included into the values. Reliabilities of estimated genomic breeding values calculated using elements of the inverse of the coefficient matrix depend on the allele coding because different allele coding methods imply different models. Finally, allele coding affects the mixing of Markov chain Monte Carlo algorithms, with the centered coding being

  17. Interleukin-1 gene cluster variants in hemodialysis patients with end stage renal disease: An association and meta-analysis.

    Science.gov (United States)

    Tripathi, G; Rangaswamy, D; Borkar, M; Prasad, N; Sharma, R K; Sankhwar, S N; Agrawal, S

    2015-01-01

    We evaluated whether polymorphisms in interleukin (IL-1) gene cluster (IL-1 alpha [IL-1A], IL-1 beta [IL-1B], and IL-1 receptor antagonist [IL-1RN]) are associated with end stage renal disease (ESRD). A total of 258 ESRD patients and 569 ethnicity matched controls were examined for IL-1 gene cluster. These were genotyped for five single-nucleotide gene polymorphisms in the IL-1A, IL-1B and IL-1RN genes and a variable number of tandem repeats (VNTR) in the IL-1RN. The IL-1B - 3953 and IL-1RN + 8006 polymorphism frequencies were significantly different between the two groups. At IL-1B, the T allele of - 3953C/T was increased among ESRD (P = 0.0001). A logistic regression model demonstrated that two repeat (240 base pair [bp]) of the IL-1Ra VNTR polymorphism was associated with ESRD (P = 0.0001). The C/C/C/C/C/1 haplotype was more prevalent in ESRD = 0.007). No linkage disequilibrium (LD) was observed between six loci of IL-1 gene. We further conducted a meta-analysis of existing studies and found that there is a strong association of IL-1 RN VNTR 86 bp repeat polymorphism with susceptibility to ESRD (odds ratio = 2.04, 95% confidence interval = 1.48-2.82; P = 0.000). IL-1B - 5887, +8006 and the IL-1RN VNTR polymorphisms have been implicated as potential risk factors for ESRD. The meta-analysis showed a strong association of IL-1RN 86 bp VNTR polymorphism with susceptibility to ESRD.

  18. Allele coding in genomic evaluation

    DEFF Research Database (Denmark)

    Standen, Ismo; Christensen, Ole Fredslund

    2011-01-01

    Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker...... effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous...... genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call...

  19. Association of serotonin transporter gene (5HTT) polymorphism and juvenile myoclonic epilepsy: a case-control study.

    Science.gov (United States)

    Esmail, Eman H; Labib, Dalia M; Rabie, Walaa A

    2015-09-01

    Serotonin levels might alter susceptibility to seizures. Serotonin transporter (5HTT) gene polymorphisms were found to be associated with some forms of epilepsy. Here, we attempted to examine an association between 5HTT VNTR allele variants in a serotonin transporter gene and epileptogenesis in juvenile myoclonic epilepsy (JME) cases. We conducted a case-control candidate gene study evaluating the frequencies of 5HTT VNTR allele variants using SYBR green real-time PCR with melting curve analysis in JME patients and healthy subjects. Forty patients with JME were selected from the Epilepsy Outpatient Clinic of Kasr Al Ainy Hospital, Cairo University, who had been classified according to the electroclinical classification of the ILAE. The control group consisted of 40 healthy Egyptian subjects. The less efficient transcriptional genotypes for 5-HTT polymorphisms were more frequent in JME patients (OR 9.33, CI 2.85-30.60; p value epileptogenesis in JME.

  20. Recurrence of the R408W Mutation in the Phenylalanine Hydroxylase Locus in Europeans

    OpenAIRE

    Eisensmith, Randy C.; Goltsov, Alexei A.; O'Neill, Charles; Tyfield, Linda A.; Schwartz, Eugene I.; Kuzmin, Alexei I.; Baranovskaya, Svetlana S.; Tsukerman, Gennady L.; Treacy, Eileen; Scriver, Charles R.; Güttler, Flemming; Guldberg, Per; Eiken, Hans G; Apold, Jaran; Svensson, Elisabeth

    1995-01-01

    The relative frequency of the common phenylalanine hydroxylase (PAH) mutation R408W and its associations with polymorphic RFLP, VNTR, and short-tandem-repeat (STR) sites in the PAH gene were examined in many European populations and one representative North American population of defined European descent. This mutation was found to cluster in two regions: in northwest Europe among Irish and Scottish peoples, and in eastern Europe, including the Commonwealth of Independent States. This allele ...

  1. Family-based association study of DRD4 gene in methylphenidate-responded Attention Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Leung, Patrick Wing-Leung; Chan, Janice Ka Yan; Chen, Lu Hua; Lee, Chi Chiu; Hung, Se Fong; Ho, Ting Pong; Tang, Chun Pan; Moyzis, Robert K; Swanson, James M

    2017-01-01

    The 48-basepair (48-bp) variable number tandem repeat (VNTR) polymorphism in exon 3 of the dopamine receptor D4 gene (DRD4) is implicated in the etiology of attention-deficit/ hyperactivity disorder (ADHD). In particular, ADHD in European-ancestry population is associated with an increased prevalence of the 7-repeat (7R) allele of the exon 3 VNTR. However, it is intriguing to note that the 7R allele has been found to be of very low prevalence in the Chinese general population. In a previous case-control study, our research team had found that the 7R allele was similarly absent in Chinese ADHD children in Hong Kong. Instead, there was an increased prevalence of the 2R allele in Chinese ADHD children. Interestingly, in Asian samples, the 2R allele had been found to be an evolutionary derivative of the 7R allele with equivalent biochemical functionality. So, the finding of an association between ADHD and 2R allele in Chinese population does not exactly contradict the original 7R allele finding in European-ancestry population. However, given the potential pitfall of population stratification in the previous case-control design, this current study tested the 2R allele and ADHD association using a methodologically more rigorous family-based approach on 33 Chinese ADHD probands who had favorable clinical responses to stimulant medication (methylphenidate). Haplotype Relative Risk (HRR) analysis and Transmission Disequilibrium Test (TDT) both showed a significant preferential transmission of the 2R allele from the biological parents to ADHD probands (pone-tailed = 0.038, OR = 2.04; pone-tailed = 0.048, OR = 2.29, respectively). A second hypothesis speculates that it is the deviation, including 7R and 2R alleles, from the conserved ancestral 4R allele which confers risk to ADHD. Thus, a preferential transmission of non-4R alleles, against the 4R allele, from biological parents to their ADHD probands is predicted. Both HRR analysis and TDT confirmed such prediction (pone

  2. 5-HTTLPR status moderates the effect of early adolescent substance use on risky sexual behavior.

    Science.gov (United States)

    Kogan, Steven M; Beach, Steven R H; Philibert, Robert A; Brody, Gene H; Chen, Yi-Fu; Lei, Man-Kit

    2010-09-01

    A longitudinal, prospective design was used to investigate a moderation effect in the association between early adolescent substance use and risky sexual behavior 2 years later. A genetic vulnerability factor, a variable nucleotide repeat polymorphism (VNTR) in the promoter region of the serotonin transporter gene SLC6A4, known as 5-HTTLPR, was hypothesized to moderate the link between substance use at age 14 and risky sexual behavior at age 16. This VNTR has been associated with risk-taking behavior. African American youths in rural Georgia (N = 185) provided 2 waves of data on their substance use and sexual behavior. Genetic data were obtained via saliva samples. Substance use and sexual risk behavior were assessed using youth self-report items developed for this investigation. Multiple regression analyses indicated that the presence of 1 or 2 copies of the short allele of the VNTR interacted with substance use to predict sexual behavior. Substance use had little effect on sexual behavior for youths without the short allele; this effect was greatly increased for youths with the short allele. Genetic vulnerability affected the implications of early onset substance use for later sexual behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  3. Choreography of Ig allelic exclusion.

    Science.gov (United States)

    Cedar, Howard; Bergman, Yehudit

    2008-06-01

    Allelic exclusion guarantees that each B or T cell only produces a single antigen receptor, and in this way contributes to immune diversity. This process is actually initiated in the early embryo when the immune receptor loci become asynchronously replicating in a stochastic manner with one early and one late allele in each cell. This distinct differential replication timing feature then serves an instructive mark that directs a series of allele-specific epigenetic events in the immune system, including programmed histone modification, nuclear localization and DNA demethylation that ultimately bring about preferred rearrangement on a single allele, and this decision is temporally stabilized by feedback mechanisms that inhibit recombination on the second allele. In principle, these same molecular components are also used for controlling monoallelic expression at other genomic loci, such as those carrying interleukins and olfactory receptor genes that require the choice of one gene out of a large array. Thus, allelic exclusion appears to represent a general epigenetic phenomenon that is modeled on the same basis as X chromosome inactivation.

  4. Detection of sequence variability of the collagen type IIalpha 1 3' variable number of tandem repeat.

    Science.gov (United States)

    van Meurs, J B; Arp, P P; Fang, Y; Slagboom, P E; Meulenbelt, I; van Leeuwen, J P; Pols, H A; Uitterlinden, A G

    2000-11-01

    The variable number of tandem repeat (VNTR) 3' of the collagen type II (COL2A1) gene has been shown to be highly variable with a complex molecular structure. In a previous pilot experiment we observed discordance between methods to genotype this informative marker. To further investigate the extent and molecular nature of this discordance, we genotyped a random sample of 207 Caucasian individuals with two genotyping methods and sequenced new alleles. We compared single-strand (SS) analysis, which is based on detection of size differences between the different alleles, and heteroduplex analysis (HA), which is sensitive to both size and sequence differences. Overall, 26% of discordance between the two methods was detected. Approximately two thirds of this discordance was caused by subdivision of SS-alleles 13R1 and 14R2 into HA-alleles 4A + 4B and 3B + 3C, respectively. Sequence analysis of the COL2A1 VNTR alleles 4B and 3C showed that these alleles differed in sequence, but not in size, from already described SS-alleles, which explains why they escape detection by SS. The 4B allele is a frequent allele in the population (14%) and is, therefore, important to distinguish in association studies. We conclude that HA is a reliable method when the described optimized electrophoretic conditions are used. HA is a sensitive genotyping method to document allelic diversity at this locus, which can distinguish more alleles compared to the SS method.

  5. Polymorphic haplotypes on R408BW PKU and normal PAH chromosomes in Quebec and European populations

    Energy Technology Data Exchange (ETDEWEB)

    Byck, S.; Morgan, K.; Scriver, C.R. [McGill Univ., Montreal (Canada)] [and others

    1994-09-01

    The R408W mutation in the phenylalanine hydroxylase gene (PAH) is associated with haplotype 2.3 (RFLP haplotype 2, VNTR 3 of the HindIII system) in most European populations. Another chromosome, first observed in Quebec and then in northwest Europe, carries R408W on haplotype 1.8. The occurrence of the R408W mutation on two different PKU chromosomes could be the result of intragenic recombination, recurrent mutation or gene conversion. In this study, we analyzed both normal and R408W chromosomes carrying 1.8 and 2.3 haplotypes in Quebec and European populations; we used the TCTA{sub (n)} short tandem repeat sequence (STR) at the 5{prime} end of the PAH gene and the HindIII VNTR system at the 3{prime} end of the PAH gene to characterize chromosomes. Fourteen of sixteen R408W chromosomes from {open_quotes}Celtic{close_quotes} families in Quebec and the United Kingdom (UK) harbor a 244 bp STR allele; the remaining two chromosomes, carry a 240 bp or 248bp STR allele. Normal chromosomes (n=18) carry the 240 bp STR allele. R408W chromosomes are different from mutant H1.8 chromosomes; mutant H2.3 carries the 240 bp STR allele (14 of 16 chromosomes) or the 236 allele (2 of 16 chromosomes). The HindIII VNTR comprises variable numbers of 30 bp repeats (cassettes); the repeats also vary in nucleotide sequence. Variation clusters toward the 3{prime} end of cassettes and VNTRs. VNTR 3 alleles on normal H2 (n=9) and mutant R408W H2 (n=19) chromosomes were identical. VNTR 8 alleles on normal H1 chromosomes (n=9) and on R408W H1 chromosomes (n=15) differ by 1 bp substitution near the 3{prime} end of the 6th cassette. In summary, the mutant H1.8 chromosome harboring the R408W mutation has unique features at both the 5{prime} and 3{prime} end of the gene that distinguish it from the mutant H2.3 and normal H1.8 and H2.3 counterparts. The explanation for the occurrence of R408W on two different PAH haplotypes is recurrent mutation affecting the CpG dinucleotide in PAH codon 408.

  6. Rs488087 single nucleotide polymorphism as predictive risk factor for pancreatic cancers.

    Science.gov (United States)

    Martinez, Emmanuelle; Silvy, Françoise; Fina, Fréderic; Bartoli, Marc; Krahn, Martin; Barlesi, Fabrice; Figarella-Branger, Dominique; Iovanna, Juan; Laugier, René; Ouaissi, Mehdi; Lombardo, Dominique; Mas, Eric

    2015-11-24

    Pancreatic cancer (PC) is a devastating disease progressing asymptomatically until death within months after diagnosis. Defining at-risk populations should promote its earlier diagnosis and hence also avoid its development. Considering the known involvement in pancreatic disease of exon 11 of the bile salt-dependent lipase (BSDL) gene that encodes variable number of tandem repeat (VNTR) sequences, we hypothesized upon the existence of a genetic link between predisposition to PC and mutations in VNTR loci. To test this, BSDL VNTR were amplified by touchdown-PCR performed on genomic DNA extracted from cancer tissue or blood samples from a French patient cohort and amplicons were Sanger sequenced. A robust method using probes for droplet digital (dd)-PCR was designed to discriminate the C/C major from C/T or T/T minor genotypes. We report that the c.1719C > T transition (SNP rs488087) present in BSDL VNTR may be a useful marker for defining a population at risk of developing PC (occurrence: 63.90% in the PC versus 27.30% in the control group). The odds ratio of 4.7 for the T allele was larger than those already determined for other SNPs suspected to be predictive of PC. Further studies on tumor pancreatic tissue suggested that a germline T allele may favor Kras G12R/G12D somatic mutations which represent negative prognostic factors associated with reduced survival. We propose that the detection of the T allele in rs488087 SNP should lead to an in-depth follow-up of patients in whom an association with other potential risk factors of pancreatic cancer may be present.

  7. Association Between Interleukin 4 Gene Seventy-Base-Pair Variable Number of Tandem Repeats Polymorphism and Uterine Leiomyoma

    Directory of Open Access Journals (Sweden)

    Salimi

    2014-06-01

    Full Text Available Background Uterine Leiomyoma (UL is the most common gynecological tumor and a public health problem. Higher serum interleukin 4 (IL-4 level, as an anti-inflammatory cytokine that regulates TH1/TH2 cells balance, has been observed in the uterine cavity. Objectives The aim of this study was to investigate the association between IL4 gene variable number of tandem repeats (VNTR polymorphism and the risk of UL in southeast of Iran. Patients and Methods We compared of 99 patients with UL with that of 102 healthy controls. The IL4 VNTR polymorphism was genotyped by gel electrophoresis after PCR amplification. Results There was no significant association between RP*1/RP*2 and RP*2/RP*2 genotypes and UL; however, a significant association between RP*2/RP*2 genotype and UL was found after adjustment for age (OR, 4; 95% CI, 1.3-12.4; and P = 0.015. The frequency of RP*2 allele was significantly higher in women with UL (OR, 1.9; 95% CI, 1.1-3.5; and P = 0.03. Conclusions The IL4 VNTR RP*2/RP*2 genotype could be an age-related risk factor for UL. Moreover, the frequency of RP*2 allele was significantly higher in women with UL.

  8. Associations between dopamine D4 receptor gene variation with both infidelity and sexual promiscuity.

    Directory of Open Access Journals (Sweden)

    Justin R Garcia

    Full Text Available BACKGROUND: Human sexual behavior is highly variable both within and between populations. While sex-related characteristics and sexual behavior are central to evolutionary theory (sexual selection, little is known about the genetic bases of individual variation in sexual behavior. The variable number tandem repeats (VNTR polymorphism in exon III of the human dopamine D4 receptor gene (DRD4 has been correlated with an array of behavioral phenotypes and may be predicatively responsible for variation in motivating some sexual behaviors, particularly promiscuity and infidelity. METHODOLOGY/PRINCIPAL FINDINGS: We administered an anonymous survey on personal history of sexual behavior and intimate relationships to 181 young adults. We also collected buccal wash samples and genotyped the DRD4 VNTR. Here we show that individuals with at least one 7-repeat allele (7R+ report a greater categorical rate of promiscuous sexual behavior (i.e., having ever had a "one-night stand" and report a more than 50% increase in instances of sexual infidelity. CONCLUSIONS/SIGNIFICANCE: DRD4 VNTR genotype varies considerably within and among populations and has been subject to relatively recent, local selective pressures. Individual differences in sexual behavior are likely partially mediated by individual genetic variation in genes coding for motivation and reward in the brain. Conceptualizing these findings in terms of r/K selection theory suggests a mechanism for selective pressure for and against the 7R+ genotype that may explain the considerable global allelic variation for this polymorphism.

  9. Association of a functional variant of the nitric oxide synthase 1 gene with personality, anxiety, and depressiveness.

    Science.gov (United States)

    Kurrikoff, Triin; Lesch, Klaus-Peter; Kiive, Evelyn; Konstabel, Kenn; Herterich, Sabine; Veidebaum, Toomas; Reif, Andreas; Harro, Jaanus

    2012-11-01

    A functional promoter polymorphism of the nitric oxide synthase 1 gene first exon 1f variable number tandem repeat (NOS1 ex1f-VNTR) is associated with impulsivity and related psychopathology. Facets of impulsivity are strongly associated with personality traits; maladaptive impulsivity with neuroticism; and adaptive impulsivity with extraversion. Both high neuroticism and low extraversion predict anxiety and depressive symptoms. The aim of the present study was to evaluate the effect of the NOS1 ex1f-VNTR genotype and possible interaction with environmental factors on personality, anxiety, and depressiveness in a population-representative sample. Short allele carriers had higher neuroticism and anxiety than individuals with the long/long (l/l) genotype. Male short/short homozygotes also had higher extraversion. In the face of environmental adversity, females with a short allele had higher scores of neuroticism, anxiety, and depressiveness compared to the l/l genotype. Males were more sensitive to environmental conditions when they had the l/l genotype and low extraversion. In conclusion, the NOS1 ex1f-VNTR influences personality and emotional regulation dependent on gender and environment. Together with previous findings on the effect of the NOS1 genotype on impulse control, these data suggest that NOS1 should be considered another plasticity gene, because its variants are associated with different coping strategies.

  10. Heme oxygenase-1 gene promoter microsatellite polymorphism is associated with progressive atherosclerosis and incident cardiovascular disease

    Science.gov (United States)

    Pechlaner, Raimund; Willeit, Peter; Summerer, Monika; Santer, Peter; Egger, Georg; Kronenberg, Florian; Demetz, Egon; Weiss, Günter; Tsimikas, Sotirios; Witztum, Joseph L.; Willeit, Karin; Iglseder, Bernhard; Paulweber, Bernhard; Kedenko, Lyudmyla; Haun, Margot; Meisinger, Christa; Gieger, Christian; Müller-Nurasyid, Martina; Peters, Annette; Willeit, Johann; Kiechl, Stefan

    2015-01-01

    Objective The enzyme heme oxygenase-1 (HO-1) exerts cytoprotective effects in response to various cellular stressors. A variable number tandem repeat (VNTR) polymorphism in the HO-1 gene promoter region has previously been linked to cardiovascular disease (CVD). We examined this association prospectively in the general population. Approach and Results Incidence of stroke, myocardial infarction, or vascular death was registered between 1995 and 2010 in 812 participants of the Bruneck Study aged 45 to 84 years (49.4% males). Carotid atherosclerosis progression was quantified by high-resolution ultrasound. HO-1 VNTR length was determined by polymerase chain reaction. Subjects with ≥32 tandem repeats on both HO-1 alleles compared to the rest of the population (recessive trait) featured substantially increased CVD risk (hazard ratio [95% confidence interval], 5.45 (2.39, 12.42); PSAPHIR, and KORA prospective studies (HR [95% CI], 3.26 [1.50, 7.33]; P=0.0043). Conclusions This study found a strong association between the HO-1 VNTR polymorphism and CVD risk confined to subjects with a high number of repeats on both HO-1 alleles, and provides evidence for accelerated atherogenesis and decreased anti-oxidant defence in this vascular high-risk group. PMID:25359861

  11. ALLELE FREQUENCIES IN MULTIGENE FAMILIES

    Directory of Open Access Journals (Sweden)

    S. Padmadisastra

    2010-11-01

    Full Text Available Results on allelle frequencies in three chromosomes, drawn at randomfrom a diploid population, evolving in equilibrium, at a particular generation, arepresented in this paper. The genes on each chromosome are subject to unbiased andreciprocal gene conversion and mutation. Using the coalescent approach we find theprobability distribution of the allelic configurations in the three chromosomes, andthe moments of the allelic numbers that exist in one of the three chromosomes orin a pair of chromosomes. We also consider the identity coefficients of two genesdrawn at random, one from each of two chromosomes, and the probability that allgenes in the three chromosomes are monomorphic. Numerical examples are alsogiven together with simulation results, and they agree well.

  12. Genetic variation in the dopamine D4 receptor (DRD4) gene and smoking cessation: follow-up of a randomised clinical trial of transdermal nicotine patch.

    Science.gov (United States)

    David, S P; Munafò, M R; Murphy, M F G; Proctor, M; Walton, R T; Johnstone, E C

    2008-04-01

    Smokers of European ancestry (n=720) who participated in a double-blind, randomised, placebo-controlled trial of transdermal nicotine replacement therapy, were genotyped for two functional polymorphisms (variable number of tandem repeats (VNTR) and a C to T transition at position -521 (C-521T)) in the dopamine D4 receptor gene (DRD4) gene. Logistic regression models of abstinence at 12- and 26-week follow-ups were carried out separately for each polymorphism. For the DRD4 VNTR models, the main effect of treatment was significant at both 12-week (P=0.001) and 26-week (P=0.006) follow-ups, indicating an increased likelihood of successful cessation on active nicotine replacement therapy transdermal patch relative to placebo. The main effect of DRD4 VNTR genotype was associated with abstinence at 12-week follow-up (P=0.034), with possession of one or more copies of the long allele associated with reduced likelihood of cessation (17 vs 23%), but this effect was not observed at 26-week follow-up. For the DRD4 C-521T models, no main effect or interaction terms involving genotype were retained in the models at either 12- or 26-week follow-up. These data are consistent with observations from studies of the DRD2 gene that genetic variants related to relatively decreased dopaminergic tone in the mesocorticolimbic system are associated with increased risk for relapse to smoking following a cessation attempt.

  13. Investigation of the population structure of Mycobacterium abscessus complex strains using 17-locus variable number tandem repeat typing and the further distinction of Mycobacterium massiliense hsp65 genotypes.

    Science.gov (United States)

    Yoshida, Shiomi; Arikawa, Kentaro; Tsuyuguchi, Kazunari; Kurashima, Atsuyuki; Harada, Toshiyuki; Nagai, Hideaki; Suzuki, Katsuhiro; Iwamoto, Tomotada; Hayashi, Seiji

    2015-03-01

    Mycobacterium abscessus complex is a significant pathogen in patients with non-cystic fibrosis (non-CF). Nevertheless, there is little description of the genetic diversity of this species. The aims of this study were to investigate the distribution of M. abscessus complex isolated from respiratory specimens by variable number tandem repeat (VNTR) typing. The results of 104 clinical isolates from 104 non-CF patients were compared using PFGE, hsp65 genotypes and clarithromycin susceptibility. The allelic diversity (Hunter-Gaston Discriminatory Index) of the 17 loci examined by VNTR typing was high (0.977). We determined that C28 sequevar erm(41) genotypes and clarithromycin-acquired resistance isolates were scattered in the minimum spanning tree. Intriguingly, VNTR typing and PFGE were highly congruent and revealed that there were clear examples of grouping of isolates from different individuals amongst both M. abscessus and M. massiliense, and showed five clusters of distinct identical isolates. Within these clusters, M. massiliense hsp65 type I formed three different clusters. Although the distribution of M. massiliense hsp65 type II-1 was low (9.3 %), M. massiliense hsp65 type II-1 isolates separated from clusters contained hsp65 type I isolates. Thus, M. massiliense hsp65 genotypes could be discriminated by analysing VNTRs with sufficient genetic distance for intra-species-level discrimination.

  14. The analysis of interleukin-1 receptor antagonist and interleukin-1beta gene polymorphisms in Turkish FMF patients: do they predispose to secondary amyloidosis?

    Science.gov (United States)

    Balci-Peynircioğlu, B; Taşkiran, Z E; Türel, B; Arici, M; Bakkaloğlu, A; Ozen, S; Yilmaz, E

    2008-01-01

    Amyloid development in familial Mediterranean fever (FMF) patients is associated with acute phase response and the acute phase reactant serum amyloid A which is induced by IL-1Beta. Its concentration can increase to more than 1000 fold during inflammation. In view of the inflammatory nature of FMF disease we have investigated whether IL-1Beta and IL-1 receptor antagonist gene polymorphisms may be involved in amyloid development in FMF patients. Ninety-nine FMF patients without amyloidosis; 54 FMF patients with amyloidosis and 60 healthy controls samples were genotyped for IL-1Beta-511 (C/T) and IL-1Beta+3953 (C/T) polymorphisms using PCR-RFLP and for IL-1Ra VNTR polymorphism using PCR. The allele and genotype frequencies of IL-1Beta-511 (C/T), IL-1Beta+3953 (C/T) and IL-1Ra VNTR polymorphisms in FMF patients with and without amyloidosis were all compared with those in controls. There were no significant differences between FMF patients with and without amyloidosis and healthy control samples for these polymorphisms (all P-values are >0.05). These polymorphisms were not associated with M694V mutation in FMF patients with and without amyloidosis. IL-1Beta-511 (C/T), IL-1Beta+3953 (C/T) and IL-1Ra VNTR polymorphisms are not associated with the development of amyloid in FMF patients.

  15. Functional polymorphism of genes inactivating biogenic amines and cognitive deficits in paranoid schizophrenia [Funkcjonalny polimorfizm genów enzymów inaktywujących aminy biogenne a deficyty procesów poznawczych w schizofrenii paranoidalnej

    Directory of Open Access Journals (Sweden)

    Tylec, Aneta

    2013-04-01

    Full Text Available Aim. The aim of the work was to assess relationship between gene polymorphism of enzymes influencing dopaminergic-, serotoninergic, and noradrenergic transfer and cognitive functioning of paranoid schizophrenic inpatients (ICD-10. Method. The following methods have been used in the study: The Test of Everyday Attention (TEA and The Visual Object and Space Perception Battery (VOSP , psychiatric scales (SAPS, SANS, BDI and techniques of genetic engineering (PCR reaction, RFLP and VNTR techniques. Subject groups included 100 schizophrenic patients (57 male and 50 healthy controls (20 male. Results. The results revealed positive correlation between polymorphism of Val158MetCOMT and cognitive deficits in schizophrenic patients. No statistically significant relationship was elicited between gene polymorphism of Val158Met COMT and VNTR MAO-A in promoter area and schizophrenia onset. Allelic polymorphism of Val158Met OMT and VNTR MAO-A in promoter area did not differ between the subject groups. The patients with genotype Val/Val of polymorphism Val 158MetCOMT showed major cognitive deficits.

  16. Spectrum of phylalanine hydroxylase gene mutations and genotype-phenotype correlation in the patients with phenylketonuria in Beijing area of China%北京地区苯丙酮尿症基因突变构成及基因型与表型相关分析

    Institute of Scientific and Technical Information of China (English)

    瞿宇晋; 宋昉; 金煜炜; 王红; 张玉敏; 秦金莉; 裘蕾

    2008-01-01

    Objective To identify the mutation spectrum and the distribution of minihaplotypes (STR/VNTR)of phenylalanine hydroxylase(PAH)gene and explore the C01Te]ations between genotype and phenotype of patients with phenylketonuria(PKU)in Beijing area of China.Method (1)Fifty cases with PKU were involved in this study.PKU was identified by the Neonatal Screening Center of Beijing.All 13 exons and their flanking intronic sequences of PAH gene of these patients were amplified and then subjected to SSCP analysis and direct sequencing.(2)The distribution of polymorphic locus of short tandem repeat (STR)and variable number tandem repeat(VNTR)was analyzed by PCR and denaturing gel electrophoresis.(3)The correlations between genotype and phenotype were studied by analysis of the matching rate between the expected and observed phenotypes.The predicted phenotype was determined on the basis of the sum of the assigned values of the two mutant alleles.Results (1)A total of 34 different mutations were detected with the relative frequency of 95% among 50 PKU patients.The prevalent mutations in this study were:R243Q(20%),EX6-96A>G(11%),Y356X(9%),and V399V(7%).The next common mutations were R111X(5%),R413P(5%),R252Q(3%)and A434D(3%).Thirty-four detected mutations were distributed throughout the whole PAH gene,except exon 1,8 and 13.Exon 7 and 11,with the mutant rate 34% and 19% respectively,seemed to be the hot mutant areas/regions of PAH gene.(2)The minihaplotypes(STR/VNTR)of 34 mutations were identified in this research.The STR and VNTR showed 8 and 3 alleles,respectively.Among them,244 bp(44%)and 240 bp(34%)were the prevalent STR alleles.Meanwhile,the VNTR3(83%)was the most common VNTR allele in PKU patients.(3)A better consistency(81.5%)between expected and observed phenotypes was revealed by analysis of correlation between genotype and phenotype.Especially in classic PKU,the consistency rate was up to 87.5%.Conclusion(1)The frequency distribution of common PAH gene mutations in

  17. A Novel Variable Number of Tandem Repeat of the Natriuretic Peptide Precursor B gene's 5'-Flanking Region is Associated with Essential Hypertension among Japanese Females

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    Kotoko Kosuge, Masayoshi Soma, Tomohiro Nakayama, Noriko Aoi, Mikano Sato, Yoichi Izumi, Koichi Matsumoto

    2007-01-01

    Full Text Available Background: Brain natriuretic peptide (BNP acts primarily as a cardiac hormone; it is produced by the ventricle and has both vasodilatory and natriuretic actions. Therefore, the BNP gene is thought to be a candidate gene for essential hypertension (EH. The present study identified variants in the 5'-flanking region of natriuretic peptide precursor B (NPPB gene and assessed the relationship between gene variants and EH. Methods: The polymerase chain reaction-single strand conformation polymorphism method and nucleotide sequencing were used to identify variants. Results: A novel variable number of tandem repeat (VNTR polymorphism in the 5'-flanking region (-1241 nucleotides from the major transcriptional initiation site was discovered. This VNTR polymorphism is a tandem repeat of the 4-nucleotide sequence TTTC. There were 8 alleles, ranging from 9-repeat to 19-repeat. An association study was done involving 317 EH patients and 262 age-matched normotensive (NT subjects. The 11-repeat allele was the most frequent (88.2%; the 16-repeat allele was the second most frequent (10.5% in the NT group. The observed and expected genotypes were in agreement with the predicted Hardy-Weinberg equilibrium values (P=0.972. Among females, the overall distribution of genotypes was significantly different between the EH and NT groups (p=0.039. The frequency of the 16-repeat allele was significantly lower in the female EH group (6.5% than in the female NT group (12.2%, p=0.046. Conclusions: The 16-repeat allele of the VNTR in the 5'-flanking region of NPPB appears to be a useful genetic marker of EH in females.

  18. Serotonin transporter evolution and impact of polymorphic transcriptional regulation

    DEFF Research Database (Denmark)

    Søeby, Karen; Larsen, Svend Ask; Olsen, Line

    2005-01-01

    in the VNTRs of all mammalian SERT genes. The number of these putative binding sites varies proportionally to the length of the VNTR. We propose that the intronic VNTR have been selectively targeted through mammalian evolution to finetune transcriptional regulation of the serotonin expression....

  19. Implementation of a Consensus Set of Hypervariable Mycobacterial Interspersed Repetitive-Unit-Variable-Number Tandem-Repeat Loci in Mycobacterium tuberculosis Molecular Epidemiology.

    Science.gov (United States)

    Trovato, Alberto; Tafaj, Silva; Battaglia, Simone; Alagna, Riccardo; Bardhi, Donika; Kapisyzi, Perlat; Bala, Silvana; Haldeda, Migena; Borroni, Emanuele; Hafizi, Hasan; Cirillo, Daniela Maria

    2016-02-01

    This study shows that the addition of a consensus 4-locus set of hypervariable mycobacterial interspersed repetitive-unit-variable-number tandem repeat (MIRU-VNTR) loci to the spoligotyping-24-locus MIRU-VNTR typing strategy is a well-standardized approach that can contribute to an improvement of the true cluster definition while retaining high typeability in non-Beijing strains.

  20. Hypermethylated SUPERMAN epigenetic alleles in arabidopsis.

    Science.gov (United States)

    Jacobsen, S E; Meyerowitz, E M

    1997-08-22

    Mutations in the SUPERMAN gene affect flower development in Arabidopsis. Seven heritable but unstable sup epi-alleles (the clark kent alleles) are associated with nearly identical patterns of excess cytosine methylation within the SUP gene and a decreased level of SUP RNA. Revertants of these alleles are largely demethylated at the SUP locus and have restored levels of SUP RNA. A transgenic Arabidopsis line carrying an antisense methyltransferase gene, which shows an overall decrease in genomic cytosine methylation, also contains a hypermethylated sup allele. Thus, disruption of methylation systems may yield more complex outcomes than expected and can result in methylation defects at known genes. The clark kent alleles differ from the antisense line because they do not show a general decrease in genomic methylation.

  1. The interaction of early life experiences with COMT val158met affects anxiety sensitivity.

    Science.gov (United States)

    Baumann, C; Klauke, B; Weber, H; Domschke, K; Zwanzger, P; Pauli, P; Deckert, J; Reif, A

    2013-11-01

    The pathogenesis of anxiety disorders is considered to be multifactorial with a complex interaction of genetic factors and individual environmental factors. Therefore, the aim of this study was to examine gene-by-environment interactions of the genes coding for catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAOA) with life events on measures related to anxiety. A sample of healthy subjects (N = 782; thereof 531 women; mean age M = 24.79, SD = 6.02) was genotyped for COMT rs4680 and MAOA-uVNTR (upstream variable number of tandem repeats), and was assessed for childhood adversities [Childhood Trauma Questionnaire (CTQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] and anxious apprehension [Penn State Worry Questionnaire (PSWQ)]. Main and interaction effects of genotype, environment and gender on measures related to anxiety were assessed by means of regression analyses. Association analysis showed no main gene effect on either questionnaire score. A significant interactive effect of childhood adversities and COMT genotype was observed: Homozygosity for the low-active met allele and high CTQ scores was associated with a significant increment of explained ASI variance [R(2) = 0.040, false discovery rate (FDR) corrected P = 0.04]. A borderline interactive effect with respect to MAOA-uVNTR was restricted to the male subgroup. Carriers of the low-active MAOA allele who reported more aversive experiences in childhood exhibited a trend for enhanced anxious apprehension (R(2) = 0.077, FDR corrected P = 0.10). Early aversive life experiences therefore might increase the vulnerability to anxiety disorders in the presence of homozygosity for the COMT 158met allele or low-active MAOA-uVNTR alleles.

  2. Serotonin transporter gene polymorphisms in patients with chronic tension-type headache: A preliminary study

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    Akcali Aylin

    2008-01-01

    Full Text Available Background and Objectives: This study is designed to understand the pathophysiology of one of the most serious health problems, chronic tension-type headache (CTTH. Two polymorphic sites in serotonin transporter protein gene attracted much interest. These are: the variable number of tandem repeats (VNTR and 5′-flanking promoter region (5-HTTLPR. Materials and Methods: VNTR and 5-HTTLPR polymorphisms were investigated in 126 CTTH patients and 138 healthy control subjects. The patients were being treated with amitripytyline or citalopram or sertraline (SSRI. The polymerase chain reaction (PCR method was used to investigate the polymorphisms in the serotonin transporter protein gene. Results: There were no statistically significant results based on the 5-HTTLPR gene alleles, however, STin 2.12/12 genotype and STin 2.12 allele were seen to predominate the control group. In order to investigate the combined effect of the two polymorphic loci on the 5-HTT gene expression, samples were separated into nine groups. Genotypes (S/S-12/10 and (L/S-12/10 displayed statistically significant frequency in the CTTH group than in the control group. No significant differences were noticed between the 5-HTTLPR and VNTR haplotype groups and success in treatment. Conclusion: It is possible to make reliable comparisons and hypothesis about the homozygous and/or heterozygous presence of S and STin 12/10 alleles which may be in interaction with CTTH. On the other hand, the presence of homozygous L and STin12 alleles may play a protective role against CTTH. It is also possible that heterogeneity among diseases showing the same clinical research will require a lot of effort for individual identification.

  3. Hominoid composite non-LTR retrotransposons-variety, assembly, evolution, and structural determinants of mobilization.

    Science.gov (United States)

    Ianc, Bianca; Ochis, Cornelia; Persch, Robert; Popescu, Octavian; Damert, Annette

    2014-11-01

    SVA (SINE-R-VNTR-Alu) elements constitute the youngest family of composite non-LTR retrotransposons in hominoid primates. The sequence of their assembly, however, remains unclear. Recently, a second family of VNTR-containing composites, LAVA (L1-Alu-VNTR-Alu), has been identified in gibbons. We now report the existence of two additional VNTR composite families, PVA (PTGR2-VNTR-Alu) and FVA (FRAM-VNTR-Alu), in the genome of Nomascus leucogenys. Like LAVA, they share the 5'-Alu-like region and VNTR with SVA, but differ at their 3'-ends. The 3'-end of PVA comprises part of the PTGR2 gene, whereas FVA is characterized by the presence of a partial FRAM element in its 3'-domain. Splicing could be identified as the mechanism of acquisition of the variant 3'-ends in all four families of VNTR composites. SVAs have been shown to be mobilized by the L1 protein machinery in trans. A critical role in this process has been ascribed to their 5'-hexameric repeat/ Alu-like region. The Alu-like region displays specific features in each of the VNTR composite families/subfamilies with characteristic deletions found in the evolutionary younger subfamilies. Using reciprocal exchanges between SVA_E and PVA/FVA elements, we demonstrate that the structure, not the presence of the (CCCTCT)n/ Alu-like region determines mobilization capacity. Combination of LAVA and SVA_E domains does not yield any active elements-suggesting the use of different combinations of host factors for the two major groups of VNTR composites. Finally, we demonstrate that the LAVA 3'-L1ME5 fragment attenuates mobilization capacity. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Determinación de los polimorfismos genéticos taqla (ANKK1), taqlb (DRD2), -141c ins/del (DRD2) y vntr 40pb (DAT1) en población colombiana y evaluación de su asociación con el alcoholismo

    OpenAIRE

    Castro Matiz, Tatiana Ximena

    2013-01-01

    La Organización Mundial de la Salud define a la alcohol dependencia como el consumo crónico y continuado o al consumo periódico de alcohol que se caracteriza por un deterioro del control de la bebida, episodios frecuentes de intoxicación y obsesión por el alcohol y su consumo a pesar de sus consecuencias adversas. La alcohol dependencia es una enfermedad de herencia compleja y amplia heterogeneidad, donde múltiples genes pueden estar involucrados y donde el ambiente juega un rol importante en...

  5. A molecular method for S-allele identification in apple based on allele-specific PCR.

    Science.gov (United States)

    Janssens, G A; Goderis, I J; Broekaert, W F; Broothaerts, W

    1995-09-01

    cDNA sequences corresponding to two self-incompatibility alleles (S-alleles) of the apple cv 'Golden Delicious' have previously been described, and now we report the identification of three additional S-allele cDNAs of apple, one of which was isolated from a pistil cDNA library of cv 'Idared' and two of which were obtained by reverse transcription-PCR (RT-PCR) on pistil RNA of cv 'Queen's Cox'. A comparison of the deduced amino acid sequences of these five S-allele cDNAs revealed an average homology of 69%. Based on the nucleotide sequences of these S-allele cDNAs, we developed a molecular technique for the diagnostic identification of the five different S-alleles in apple cultivars. The method used consists of allele-specific PCR amplification of genomic DNA followed by digestion of the amplification product with an allele-specific restriction endonuclease. Analysis of a number of apple cultivars with known S-phenotype consistently showed coincidence of phenotypic and direct molecular data of the S-allele constitution of the cultivars. It is concluded that the S-allele identification approach reported here provides a rapid and useful method to determine the S-genotype of apple cultivars.

  6. Nucleotide variation and identification of novel blast resistance alleles of Pib by allele mining strategy.

    Science.gov (United States)

    Ramkumar, G; Madhav, M S; Devi, S J S Rama; Prasad, M S; Babu, V Ravindra

    2015-04-01

    Pib is one of significant rice blast resistant genes, which provides resistance to wide range of isolates of rice blast pathogen, Magnaporthe oryzae. Identification and isolation of novel and beneficial alleles help in crop enhancement. Allele mining is one of the best strategies for dissecting the allelic variations at candidate gene and identification of novel alleles. Hence, in the present study, Pib was analyzed by allele mining strategy, and coding and non-coding (upstream and intron) regions were examined to identify novel Pib alleles. Allelic sequences comparison revealed that nucleotide polymorphisms at coding regions affected the amino acid sequences, while the polymorphism at upstream (non-coding) region affected the motifs arrangements. Pib alleles from resistant landraces, Sercher and Krengosa showed better resistance than Pib donor variety, might be due to acquired mutations, especially at LRR region. The evolutionary distance, Ka/Ks and phylogenetic analyzes also supported these results. Transcription factor binding motif analysis revealed that Pib (Sr) had a unique motif (DPBFCOREDCDC3), while five different motifs differentiated the resistance and susceptible Pib alleles. As the Pib is an inducible gene, the identified differential motifs helps to understand the Pib expression mechanism. The identified novel Pib resistant alleles, which showed high resistance to the rice blast, can be used directly in blast resistance breeding program as alternative Pib resistant sources.

  7. Comparison of HLA allelic imputation programs

    Science.gov (United States)

    Shaffer, Christian M.; Bastarache, Lisa; Gaudieri, Silvana; Glazer, Andrew M.; Steiner, Heidi E.; Mosley, Jonathan D.; Mallal, Simon; Denny, Joshua C.; Phillips, Elizabeth J.; Roden, Dan M.

    2017-01-01

    Imputation of human leukocyte antigen (HLA) alleles from SNP-level data is attractive due to importance of HLA alleles in human disease, widespread availability of genome-wide association study (GWAS) data, and expertise required for HLA sequencing. However, comprehensive evaluations of HLA imputations programs are limited. We compared HLA imputation results of HIBAG, SNP2HLA, and HLA*IMP:02 to sequenced HLA alleles in 3,265 samples from BioVU, a de-identified electronic health record database coupled to a DNA biorepository. We performed four-digit HLA sequencing for HLA-A, -B, -C, -DRB1, -DPB1, and -DQB1 using long-read 454 FLX sequencing. All samples were genotyped using both the Illumina HumanExome BeadChip platform and a GWAS platform. Call rates and concordance rates were compared by platform, frequency of allele, and race/ethnicity. Overall concordance rates were similar between programs in European Americans (EA) (0.975 [SNP2HLA]; 0.939 [HLA*IMP:02]; 0.976 [HIBAG]). SNP2HLA provided a significant advantage in terms of call rate and the number of alleles imputed. Concordance rates were lower overall for African Americans (AAs). These observations were consistent when accuracy was compared across HLA loci. All imputation programs performed similarly for low frequency HLA alleles. Higher concordance rates were observed when HLA alleles were imputed from GWAS platforms versus the HumanExome BeadChip, suggesting that high genomic coverage is preferred as input for HLA allelic imputation. These findings provide guidance on the best use of HLA imputation methods and elucidate their limitations. PMID:28207879

  8. Most parsimonious haplotype allele sharing determination

    Directory of Open Access Journals (Sweden)

    Xu Jiaofen

    2009-04-01

    Full Text Available Abstract Background The "common disease – common variant" hypothesis and genome-wide association studies have achieved numerous successes in the last three years, particularly in genetic mapping in human diseases. Nevertheless, the power of the association study methods are still low, in particular on quantitative traits, and the description of the full allelic spectrum is deemed still far from reach. Given increasing density of single nucleotide polymorphisms available and suggested by the block-like structure of the human genome, a popular and prosperous strategy is to use haplotypes to try to capture the correlation structure of SNPs in regions of little recombination. The key to the success of this strategy is thus the ability to unambiguously determine the haplotype allele sharing status among the members. The association studies based on haplotype sharing status would have significantly reduced degrees of freedom and be able to capture the combined effects of tightly linked causal variants. Results For pedigree genotype datasets of medium density of SNPs, we present two methods for haplotype allele sharing status determination among the pedigree members. Extensive simulation study showed that both methods performed nearly perfectly on breakpoint discovery, mutation haplotype allele discovery, and shared chromosomal region discovery. Conclusion For pedigree genotype datasets, the haplotype allele sharing status among the members can be deterministically, efficiently, and accurately determined, even for very small pedigrees. Given their excellent performance, the presented haplotype allele sharing status determination programs can be useful in many downstream applications including haplotype based association studies.

  9. Allele Workbench: transcriptome pipeline and interactive graphics for allele-specific expression.

    Directory of Open Access Journals (Sweden)

    Carol A Soderlund

    Full Text Available Sequencing the transcriptome can answer various questions such as determining the transcripts expressed in a given species for a specific tissue or condition, evaluating differential expression, discovering variants, and evaluating allele-specific expression. Differential expression evaluates the expression differences between different strains, tissues, and conditions. Allele-specific expression evaluates expression differences between parental alleles. Both differential expression and allele-specific expression have been studied for heterosis (hybrid vigor, where the hybrid has improved performance over the parents for one or more traits. The Allele Workbench software was developed for a heterosis study that evaluated allele-specific expression for a mouse F1 hybrid using libraries from multiple tissues with biological replicates. This software has been made into a distributable package, which includes a pipeline, a Java interface to build the database, and a Java interface for query and display of the results. The required input is a reference genome, annotation file, and one or more RNA-Seq libraries with optional replicates. It evaluates allelic imbalance at the SNP and transcript level and flags transcripts with significant opposite directional allele-specific expression. The Java interface allows the user to view data from libraries, replicates, genes, transcripts, exons, and variants, including queries on allele imbalance for selected libraries. To determine the impact of allele-specific SNPs on protein folding, variants are annotated with their effect (e.g., missense, and the parental protein sequences may be exported for protein folding analysis. The Allele Workbench processing results in transcript files and read counts that can be used as input to the previously published Transcriptome Computational Workbench, which has a new algorithm for determining a trimmed set of gene ontology terms. The software with demo files is available

  10. Multiple-locus, variable number of tandem repeat analysis (MLVA of the fish-pathogen Francisella noatunensis

    Directory of Open Access Journals (Sweden)

    Ottem Karl F

    2011-01-01

    Full Text Available Abstract Background Since Francisella noatunensis was first isolated from cultured Atlantic cod in 2004, it has emerged as a global fish pathogen causing disease in both warm and cold water species. Outbreaks of francisellosis occur in several important cultured fish species making a correct management of this disease a matter of major importance. Currently there are no vaccines or treatments available. A strain typing system for use in studies of F. noatunensis epizootics would be an important tool for disease management. However, the high genetic similarity within the Francisella spp. makes strain typing difficult, but such typing of the related human pathogen Francisella tullarensis has been performed successfully by targeting loci with higher genetic variation than the traditional signature sequences. These loci are known as Variable Numbers of Tandem Repeat (VNTR. The aim of this study is to identify possible useful VNTRs in the genome of F. noatunensis. Results Seven polymorphic VNTR loci were identified in the preliminary genome sequence of F. noatunensis ssp. noatunensis GM2212 isolate. These VNTR-loci were sequenced in F. noatunensis isolates collected from Atlantic cod (Gadus morhua from Norway (n = 21, Three-line grunt (Parapristipoma trilineatum from Japan (n = 1, Tilapia (Oreochromis spp. from Indonesia (n = 3 and Atlantic salmon (Salmo salar from Chile (n = 1. The Norwegian isolates presented in this study show both nine allelic profiles and clades, and that the majority of the farmed isolates belong in two clades only, while the allelic profiles from wild cod are unique. Conclusions VNTRs can be used to separate isolates belonging to both subspecies of F. noatunensis. Low allelic diversity in F. noatunensis isolates from outbreaks in cod culture compared to isolates wild cod, indicate that transmission of these isolates may be a result of human activity. The sequence based MLVA system presented in this study should provide a good

  11. Characterization of human lymphoid cell lines GM9947 and GM9948 as intra- and interlaboratory reference standards for DNA typing

    Energy Technology Data Exchange (ETDEWEB)

    Fregeau, C.J.; Elliott, J.C.; Fourney, R.M. [RCMP Central Forensic Laboratory, Ottawa, Ontario (Canada)] [and others

    1995-07-20

    The incorporation of reference DNA is crucial to the validation of any DNA typing protocol. Currently, reference DNA standards are restricted to molecular size DNA ladders and/or tumor cell line DNA. Either of these, however, presents some limitations. We have rigorously characterized two Epstein-Barr virus (EBV)-immortalized human lymphoid cell lines-GM9947 (female) and GM9948 (male)-to determine their suitability as alternative in-line standards for three widely employed allele profiling strategies. Twenty-one highly polymorphic VNTR-based allelic systems (7 RFLPs, 2 AmpFLPs, and 12 STRs) distributed over 12 chromosomes were scrutinized along with 3 gender-based discriminatory systems. The genetic stability of each locus was confirmed over a period of 225 in vitro population doublings. Allele size estimates and degree of informativeness for each of the 21 VNTR systems were compiled. The reproducibility of allele scoring by traditional RFLP analyses, using both cell lines as reference standards, was also verified by an interlaboratory validation study involving 13 analysts from two geographically distinct forensic laboratories. Taken together, our data indicate that GM9947 and GM9948 genomic DNAs could be adopted as reliable reference standards for DNA typing. 82 refs., 3 figs., 8 tabs.

  12. Dopamine system genes are associated with orienting bias among healthy individuals.

    Science.gov (United States)

    Zozulinsky, Polina; Greenbaum, Lior; Brande-Eilat, Noa; Braun, Yair; Shalev, Idan; Tomer, Rachel

    2014-09-01

    Healthy individuals display subtle orienting bias, manifested as a tendency to direct greater attention toward one hemispace, and evidence suggests that this bias reflects an individual trait, which may be modulated by asymmetric dopamine signaling in striatal and frontal regions. The current study examined the hypothesis that functional genetic variants within dopaminergic genes (DAT1 3' VNTR, dopamine D2 receptor Taq1A (rs1800497) and COMT Val158Met (rs4680)) contribute to individual differences in orienting bias, as measured by the greyscales paradigm, in a sample of 197 young healthy Israeli Jewish participants. For the Taq1A variant, homozygous carriers of the A2 allele displayed significantly increased leftward orienting bias compared to the carriers of the A1 allele. Additionally, and as previously reported by others, we found that bias towards leftward orienting of attention was significantly greater among carriers of the 9-repeat allele of the DAT1 3' VNTR as compared to the individuals who were homozygous for the 10-repeat allele. No significant effect of the COMT Val158Met on orienting bias was found. Taken together, our findings support the potential influence of genetic variants on inter-individual differences in orienting bias, a phenotype relevant to both normal and impaired cognitive processes.

  13. [Mono- and dizygotic twins in forensic paternity testing in practice at the Department of Forensic Medicine (Silesian Academy of Medicine, Katowice) in the years 1996-2003].

    Science.gov (United States)

    Raczek, Ewa

    2004-01-01

    Giving an opinion on disputable paternity, concerning monozygotic twins in practice at the Department of Forensic Medicine (Silesian Academy of Medicine, Katowice) demonstrated their ideal agreement according to examined genetic markers possible. Even the mutation, which was revealed using the RFLP-VNTR method was the same for both twin sisters. In the case of dizygotic twins a firm differentiation of paternity index and probability of paternity was proved. This was the consequence of independent features segregation in first, reductive meiotic division. While the rare, out-ladder allele 16 at the CSF1PO locus was transmitted to both twins: a daughter and a son by the putative father.

  14. Real-time molecular epidemiology of tuberculosis by direct genotyping of smear-positive clinical specimens.

    Science.gov (United States)

    Alonso, María; Herranz, Marta; Martínez Lirola, Miguel; González-Rivera, Milagros; Bouza, Emilio; García de Viedma, Darío

    2012-05-01

    We applied MIRU-VNTR (mycobacterial interspersed repetitive-unit-variable-number tandem-repeat typing) to directly analyze the bacilli present in 61 stain-positive specimens from tuberculosis patients. A complete MIRU type (24 loci) was obtained for all but one (no amplification in one locus) of the specimens (98.4%), and the allelic values fully correlated with those obtained from the corresponding cultures. Our study is the first to demonstrate that real-time genotyping of Mycobacterium tuberculosis can be achieved, fully transforming the way in which molecular epidemiology techniques can be integrated into control programs.

  15. Mycobacterium bovis infection in a wild sow (Sus scrofa): first case in Korea.

    Science.gov (United States)

    Ku, Bok Kyung; Jeon, Bo-Young; Kim, Jae Myung; Jang, Young-Boo; Jang, Yunho; Yu, So Yoon; Kim, Jiro; Moon, Oun Kyung; Jung, Suk Chan; Lee, Min Kwon; Jeong, Tae Nam

    2016-09-30

    Mycobacterium (M.) bovis causes tuberculosis and has a broad host range, including humans, livestock, and wild animals. M. bovis infection of wild boar has been reported in several European countries. We report here the first case of M. bovis infection in a domesticated wild sow in Korea. Granulomatous and necrotizing lesions with small numbers of acid-fast bacilli were observed in nodules of the lung of wild sow. Furthermore, the M. bovis isolate from the wild sow had spoligotype SB0140 and a novel MIRU-VNTR allelic profile, which is not found in cattle and deer in Korea.

  16. Diversity of Lactase Persistence Alleles in Ethiopia

    DEFF Research Database (Denmark)

    Jones, BL; Raga, TO; Liebert, Anke

    2013-01-01

    The persistent expression of lactase into adulthood in humans is a recent genetic adaptation that allows the consumption of milk from other mammals after weaning. In Europe, a single allele (−13910∗T, rs4988235) in an upstream region that acts as an enhancer to the expression of the lactase gene...... LCT is responsible for lactase persistence and appears to have been under strong directional selection in the last 5,000 years, evidenced by the widespread occurrence of this allele on an extended haplotype. In Africa and the Middle East, the situation is more complicated and at least three other...... alleles (−13907∗G, rs41525747; −13915∗G, rs41380347; −14010∗C, rs145946881) in the same LCT enhancer region can cause continued lactase expression. Here we examine the LCT enhancer sequence in a large lactose-tolerance-tested Ethiopian cohort of more than 350 individuals. We show that a further SNP...

  17. Forensic Loci Allele Database (FLAD): Automatically generated, permanent identifiers for sequenced forensic alleles.

    Science.gov (United States)

    Van Neste, Christophe; Van Criekinge, Wim; Deforce, Dieter; Van Nieuwerburgh, Filip

    2016-01-01

    It is difficult to predict if and when massively parallel sequencing of forensic STR loci will replace capillary electrophoresis as the new standard technology in forensic genetics. The main benefits of sequencing are increased multiplexing scales and SNP detection. There is not yet a consensus on how sequenced profiles should be reported. We present the Forensic Loci Allele Database (FLAD) service, made freely available on http://forensic.ugent.be/FLAD/. It offers permanent identifiers for sequenced forensic alleles (STR or SNP) and their microvariants for use in forensic allele nomenclature. Analogous to Genbank, its aim is to provide permanent identifiers for forensically relevant allele sequences. Researchers that are developing forensic sequencing kits or are performing population studies, can register on http://forensic.ugent.be/FLAD/ and add loci and allele sequences with a short and simple application interface (API).

  18. Evolutionary dynamics of sporophytic self-incompatibility alleles in plants

    DEFF Research Database (Denmark)

    Schierup, M H; Vekemans, X; Christiansen, F B

    1997-01-01

    The stationary frequency distribution and allelic dynamics in finite populations are analyzed through stochastic simulations in three models of single-locus, multi-allelic sporophytic self-incompatibility. The models differ in the dominance relationships among alleles. In one model, alleles act c...

  19. Quantification of Allele Dosage in tetraploid Roses

    NARCIS (Netherlands)

    Vukosavljev, M.; Guardo, Di M.; Weg, van de W.E.; Arens, P.; Smulders, M.J.M.

    2012-01-01

    Many important crops (wheat, potato, strawberry, rose, etc.) are polyploid. This complicates genetic analyses, as the same locus can be present on multiple homologous or homoeologous chromosomes. SSR markers are suitable for mapping in segregating populations of polyploids as they are multi-allelic,

  20. Association of DC-SIGN and DC-SIGNR Repeat Regions with Susceptibility to Pulmonary Tuberculosis in Zahedan, Southeastern Iran.

    Science.gov (United States)

    Naderi, Mohammad; Hashemi, Mohammad; Soroush, Navid; Amininia, Shadi; Taheri, Mohsen

    2016-05-01

    There are conflicting results concerning DC-SIGN and DC-SIGNR VNTR polymorphisms. The present study aimed to evaluate the possible association between DC-SIGN as well as DC-SIGNR VNTR polymorphisms and pulmonary tuberculosis (PTB) in a sample of Iranian population. This case-control study was done on 171 PTB and 161 healthy subjects. The variants were detected by polymerase chain reaction (PCR). DC-SIGNR VNTR genotypes in cases were 12.7% for 5/5, 2.4% for 6/5, 32.7% for 7/7, 38.2% for 7/5, 5.5% for 7/6, 1.2% for /5, 0.6% for 9/6, 6.7% for 9/7 in PTB patients and 19.7% for 5/5, 2.0% for 6/5, 31.6% for 7/7, 37.5% for 7/5, 5.7% for 7/6, 0.0% for 9/5, 0.7% for 9/6, 2.6% for 9/7 in controls. The findings showed no significant association between DC-SIGNR VNTR polymorphism and PTB. All subjects in cases and controls were 7/7 genotype regarding DC-SIGN VNTR polymorphism. Our data propose that DC-SIGNR VNTR, as well as DC-SIGN VNTR, were not associated with the risk of PTB in a sample of Iranian population.

  1. Molecular Typing of Mycobacterium tuberculosis Based on Variable Number of Tandem DNA Repeats Used Alone and in Association with Spoligotyping

    Science.gov (United States)

    Filliol, Ingrid; Ferdinand, Severine; Negroni, Laetitia; Sola, Christophe; Rastogi, Nalin

    2000-01-01

    Fingerprinting based on variable numbers of tandem DNA repeats (VNTR), a recently described methodology, was evaluated for molecular typing of Mycobacterium tuberculosis in an insular setting. In this study, VNTR fingerprinting was used alone or as a second-line test in association with spoligotyping, double-repetitive-element PCR (DRE-PCR), and IS6110 restriction fragment length polymorphism (RFLP) analysis, and the discriminatory power for each method or the combination of methods was compared by calculating the Hunter-Gaston discriminative index (HGI). The results obtained showed that in 6 out of 12 (50%) cases, VNTR-defined clusters were further subdivided by spoligotyping, compared to 7 out of 18 (39%) cases where spoligotyping-defined clusters were further subdivided by VNTR. When used alone, VNTR was the least discriminatory method (HGI = 0.863). Although VNTR was significantly more discriminatory when used in association with spoligotyping (HGI = 0.982), the combination of spoligotyping and DRE-PCR (HGI = 0.992) was still the most efficient among rapid, PCR-based methodologies, giving results comparable to IS6110 RFLP analysis. Nonetheless, VNTR typing may provide additional phylogenetical information that may be helpful to trace the molecular evolution of tubercle bacilli. PMID:10878036

  2. Differential effects of the HESR/HEY transcription factor family on dopamine transporter reporter gene expression via variable number of tandem repeats.

    Science.gov (United States)

    Kanno, Kouta; Ishiura, Shoichi

    2011-04-01

    The 3'-untranslated region (UTR) of the human dopamine transporter (DAT1) gene contains a variable number of tandem repeats (VNTR) domain, which is thought to be associated with dopamine-related psychiatric disorders, personality, and behavior. However, the molecular and neuronal functions of polymorphisms within the VNTR domain are unknown. We previously identified the transcription factor HESR1 (HEY1) as a VNTR-binding protein. Hesr1 knockout mice exhibit DAT up-regulation in the brain and low levels of spontaneous activity. Other members of the HESR (HEY) family, including HESR2 (HEY2) and 3 (HEYL), have similar DNA-binding domains. In this study, we analyzed the effects of HESR1, -2, and -3 on DAT1 expression in human neuroblastoma SH-SY5Y cells using luciferase reporter assays. We found that the VNTR domain played an inhibitory role in DAT1 reporter gene expression and that HESR1 and -2 inhibited expression via both the core promoter and the VNTR. The inhibitory effects of HESR family members on DAT reporter gene expression differed depending on the number of repeats in the VNTR domain. We also found that each Hesr was expressed in the dopaminergic neurons in the mouse midbrain. These results suggest that the HESR family is involved in DAT expression via the VNTR domain.

  3. Association analysis of nitric oxide synthases: NOS1, NOS2A and NOS3 genes, with multiple sclerosis.

    Science.gov (United States)

    AlFadhli, Suad; Mohammed, Eiman M A; Al Shubaili, Asmahan

    2013-07-01

    Multiple sclerosis (MS) is a chronic inflammatory autoimmune disorder of the central nervous system. To explore the genetic basis of three nitric oxide synthase (NOS) genes: NOS1, NOS2A and NOS3, with susceptibility to MS. A total of 122 MS patients and 118 healthy controls screened for NOS1 (rs2682826, rs41279104), NOS2A (CCTTT)n/(TAAA)n and NOS3 (rs1800783, rs1800779, rs2070744, 27bpVNTR) markers, using TaqMan®SNP Genotyping Assays and fragment analysis were enrolled in this study. QRT-PCR and ELISA were used to analyse the expression of NOS3 mRNA and Nitric Oxide (NO) levels. Two NOS3 markers were associated with susceptibility to MS and early disease development. The NOS3 rs1800779 G-allele (p = 0.04) and GG-genotype (p = 0.02) showed association with susceptibility to MS. Short NOS2 (CCTTT)n (p = 0.03) and short/long repeat (p = 0.04) genotypes also showed associations with MS. These associations were intensified by sub-division of patients into Kuwaiti Arabs and Persians (p NOS3-27 bp-VNTR a-allele was associated with early MS disease onset ≤26 years (p = 0.04). The NOS3-27 bp-VNTR a/b-genotype resulted in 23% lower NO production and the NOS3-rs1800779 AA-genotype resulted in lower NOS3 expression. Haplotypes obtained from NOS2A and NOS3 showed increased susceptibility to MS. NOS1 showed no significant association with MS. This study provides evidence for the association between selected NOS2 and NOS3 markers and MS susceptibility.

  4. Estimating the probability of allelic drop-out of STR alleles in forensic genetics

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Eriksen, Poul Svante; Mogensen, Helle Smidt;

    2009-01-01

    In crime cases with available DNA evidence, the amount of DNA is often sparse due to the setting of the crime. In such cases, allelic drop-out of one or more true alleles in STR typing is possible. We present a statistical model for estimating the per locus and overall probability of allelic drop......-out using the results of all STR loci in the case sample as reference. The methodology of logistic regression is appropriate for this analysis, and we demonstrate how to incorporate this in a forensic genetic framework....

  5. [Construction of eukaryotic expressing vector of multiple myeloma mucin-1 and its expression in COS-7 cells in vitro].

    Science.gov (United States)

    Liu, Kun; Luo, Yun-Jiao; Liu, Yue-Bo; Yao, Jin; Yang, Hong; Mou, Hong; Huang, Gui-Yun; Zhang, You

    2009-08-01

    In order to construct an eukaryotic expression vector for gene of multiple myeloma mucin1 (muc1-2vntr) gene and to express it in COS-7 cells in vitro, so to provide the basic material for further research of multiple myeloma DNA vaccine. muc1-2vntr coding gene was used as a research gene and a KOZAK sequence was inserted before the gene Hind III and XbaI restriction sites were inserted before and after the coding gene. Then the whole sequence was synthesized and inserted into pcDNA3.1/myc-his B vector, and the resulted recombinant vector was transformed into E.coil competent cells to get an engineering strain, the recombinant plasmid pcDNA3.1-2vntr/myc-his B identified by restriction analysis and DNA sequencing were transfected into COS-7 cells by liposome-mediated gene transfer method. Finally, fluorescent microscopy was used to assess GFP expression and Western blot analysis using muc1 monoclonal antibody was used to recognize vntr, confirming the expression of vntr. The results showed that the full length of synthesized muc1-2vntr gene, as expected, was 140 bp. Both restriction analysis and DNA sequencing demonstrated that pcDNA3.1-2vntr/myc-his B included the whole translation frame region and muc1-2vntr gene. Furthermore, the fluorescence microscopy proved that the recombinant plasmid had been successfully transfected into COS-7 cells. The expression of mucin-1 protein was observed both in the transfected cell and the cell supernatant by Western blot. It is concluded that the pcDNA3.1-2vntr/myc-his B has been successfully constructed and expressed in COS-7 cells in vitro, which provides the basic material for further researches of mucin-1 function and possible multiple myloma DNA vaccine.

  6. HLA-B alleles of the Cayapa of Ecuador: New B39 and B15 alleles

    Energy Technology Data Exchange (ETDEWEB)

    Garber, T.L.; Butler, L.M.; Watkins, D.I. [Univ. of Wisconsin, Madison, WI (United States)] [and others

    1995-05-01

    Recent data suggest that HLA-B locus alleles can evolve quickly in native South American populations. To investigate further this phenomenon of new HLA-B variants among Amerindians, we studied samples from another South American tribe, the Cayapa from Ecuador. We selected individuals for HLA-B molecular typing based upon their HLA class II typing results. Three new variants of HLA-B39 and one new variant of HLA-B15 were found in the Cayapa: HLA-B*3905, HLA-B*3906, HLA-B*3907, and HLA-B*1522. A total of thirteen new HLA-B alleles have now been found in the four South American tribes studied. Each of these four tribes studied, including the Cayapa, had novel alleles that were not found in any of the other tribes, suggesting that many of these new HLA-B alleles may have evolved since the Paleo-Indians originally populated South America. Each of these 13 new alleles contained predicted amino acid replacements that were located in the peptide binding site. These amino acid replacements may affect the sequence motif of the bound peptides, suggesting that these new alleles have been maintained by selection. New allelic variants have been found for all common HLA-B locus antigenic groups present in South American tribes with the exception of B48. In spite of its high frequency in South American tribes, no evidence for variants of B48 has been found in all the Amerindians studied, suggesting that B48 may have unique characteristics among the B locus alleles. 70 refs., 2 figs., 2 tabs.

  7. HLA-B alleles of the Cayapa of Ecuador: new B39 and B15 alleles.

    Science.gov (United States)

    Garber, T L; Butler, L M; Trachtenberg, E A; Erlich, H A; Rickards, O; De Stefano, G; Watkins, D I

    1995-01-01

    Recent data suggest that HLA-B locus alleles can evolve quickly in native South American populations. To investigate further this phenomenon of new HLA-B variants among Amerindians, we studied samples from another South American tribe, the Cayapa from Ecuador. We selected individuals for HLA-B molecular typing based upon their HLA class II typing results. Three new variants of HLA-B39 and one new variant of HLA-B15 were found in the Cayapa: HLA-B*3905, HLA-B*3906, HLA-B*3907, and HLA-B*1522. A total of thirteen new HLA-B alleles have now been found in the four South American tribes studied. Each of these four tribes studied, including the Cayapa, had novel alleles that were not found in any of the other tribes, suggesting that many of these new HLA-B alleles may have evolved since the Paleo-Indians originally populated South America. Each of these 13 new alleles contained predicted amino acid replacements that were located in the peptide binding site. These amino acid replacements may affect the sequence motif of the bound peptides, suggesting that these new alleles have been maintained by selection. New allelic variants have been found for all common HLA-B locus antigenic groups present in South American tribes with the exception of B48. In spite of its high frequency in South American tribes, no evidence for variants of B48 has been found in all the Amerindians studied, suggesting that B48 may have unique characteristics among the B locus alleles.

  8. Spatial proximity of homologous alleles and long noncoding RNAs regulate a switch in allelic gene expression

    Science.gov (United States)

    Stratigi, Kalliopi; Kapsetaki, Manouela; Aivaliotis, Michalis; Town, Terrence; Flavell, Richard A.; Spilianakis, Charalampos G.

    2015-01-01

    Physiological processes rely on the regulation of total mRNA levels in a cell. In diploid organisms, the transcriptional activation of one or both alleles of a gene may involve trans-allelic interactions that provide a tight spatial and temporal level of gene expression regulation. The mechanisms underlying such interactions still remain poorly understood. Here, we demonstrate that lipopolysaccharide stimulation of murine macrophages rapidly resulted in the actin-mediated and transient homologous spatial proximity of Tnfα alleles, which was necessary for the mono- to biallelic switch in gene expression. We identified two new complementary long noncoding RNAs transcribed from the TNFα locus and showed that their knockdown had opposite effects in Tnfα spatial proximity and allelic expression. Moreover, the observed spatial proximity of Tnfα alleles depended on pyruvate kinase muscle isoform 2 (PKM2) and T-helper-inducing POZ-Krüppel-like factor (ThPOK). This study suggests a role for lncRNAs in the regulation of somatic homologous spatial proximity and allelic expression control necessary for fine-tuning mammalian immune responses. PMID:25770217

  9. Initial invasion of gametophytic self-incompatibility alleles in the absence of tight linkage between pollen and pistil S alleles.

    Science.gov (United States)

    Sakai, Satoki; Wakoh, Haluka

    2014-08-01

    In homomorphic self-incompatibility (SI) systems of plants, the loci controlling the pollen and pistil types are tightly linked, and this prevents the generation of compatible combinations of alleles expressing pollen and pistil types, which would result in self-fertilization. We modeled the initial invasion of the first pollen and pistil alleles in gametophytic SI to determine whether these alleles can stably coexist in a population without tight linkage. We assume pollen and pistil loci each carry an incompatibility allele S and an allele without an incompatibility function N. We assume that pollen with an S allele are incompatible with pistils carrying S alleles, whereas other crosses are compatible. Ovules in pistils carrying an S allele suffer viability costs because recognition consumes resources. We found that the cost of carrying a pistil S allele allows pollen and pistil S alleles to coexist in a stable equilibrium if linkage is partial. This occurs because parents that carry pistil S alleles but are homozygous for pollen N alleles cannot avoid self-fertilization; however, they suffer viability costs. Hence, pollen N alleles are selected again. When pollen and pistil S alleles can coexist in a polymorphic equilibrium, selection will favor tighter linkage.

  10. Serotonin transporter evolution and impact of polymorphic transcriptional regulation

    DEFF Research Database (Denmark)

    Søeby, Karen; Larsen, Svend Ask; Olsen, Line

    2005-01-01

    extensively across the great apes and monkeys as well as in rodents while it is absent in non-mammals. As in humans, the VNTR sequence may be polymorphic within species and thus it may underlie both inter- and intraspecies differences. Also, we find new putative binding sites for several transcription factors...... in the VNTRs of all mammalian SERT genes. The number of these putative binding sites varies proportionally to the length of the VNTR. We propose that the intronic VNTR have been selectively targeted through mammalian evolution to finetune transcriptional regulation of the serotonin expression....

  11. A functional variant in MIR137, a candidate gene for schizophrenia, affects Stroop test performance in young adults.

    Science.gov (United States)

    González-Giraldo, Yeimy; González-Reyes, Rodrigo E; Forero, Diego A

    2016-02-28

    MIR137, a brain expressed miRNA, has been identified as a top novel susceptibility gene for schizophrenia (SZ). 230 healthy participants completed the Stroop test and were genotyped for a functional Variable Number Tandem Repeat (VNTR) in MIR137 gene. MIR137 VNTR genotypes were associated with differences in Stroop facilitation and accuracies in congruent trials and for the total number of errors. This is the first study of the functional VNTR in MIR137 gene and Stroop test performance in healthy subjects. Our results could have important implications for the identification of genetic candidates for endophenotypes for SZ.

  12. Dopamine Genes (DRD2/ANKK1-TaqA1 and DRD4-7R) and Executive Function: Their Interaction with Obesity

    Science.gov (United States)

    Ariza, Mar; Garolera, Maite; Jurado, Maria Angeles; Garcia-Garcia, Isabel; Hernan, Imma; Sánchez-Garre, Consuelo; Vernet-Vernet, Maria; Sender-Palacios, Maria Jose; Marques-Iturria, Idoia; Pueyo, Roser; Segura, Barbara; Narberhaus, Ana

    2012-01-01

    Obesity is a multifactorial disease caused by the interaction between genotype and environment, and it is considered to be a type of addictive alteration. The A1 allele of the DRD2/ANKK1-TaqIA gene has been associated with addictive disorders, with obesity and with the performance in executive functions. The 7 repeat allele of the DRD4 gene has likewise been associated with the performance in executive functions, as well as with addictive behaviors and impulsivity. Participants were included in the obesity group (N = 42) if their body mass index (BMI) was equal to or above 30, and in the lean group (N = 42) if their BMI was below 25. The DRD2/ANKK1-TaqIA and DRD4 VNTR polymorphisms were obtained. All subjects underwent neuropsychological assessment. Eating behavior traits were evaluated. The ‘DRD2/ANKK1-TaqIA A1-allele status’ had a significant effect on almost all the executive variables, but no significant ‘DRD4 7R-allele status’ effects were observed for any of the executive variables analyzed. There was a significant ‘group’ x ‘DRD2/ANKK1-TaqIA A1-allele status’ interaction effect on LN and ‘group’ x ‘DRD4 7R-allele status’ interaction effect on TMT B-A score. Being obese and a carrier of the A1 allele of DRD2/ANKK1-TaqIA or the 7R allele of DRD4 VNTR polymorphisms could confer a weakness as regards the performance of executive functions. PMID:22848508

  13. Dopamine genes (DRD2/ANKK1-TaqA1 and DRD4-7R and executive function: their interaction with obesity.

    Directory of Open Access Journals (Sweden)

    Mar Ariza

    Full Text Available Obesity is a multifactorial disease caused by the interaction between genotype and environment, and it is considered to be a type of addictive alteration. The A1 allele of the DRD2/ANKK1-TaqIA gene has been associated with addictive disorders, with obesity and with the performance in executive functions. The 7 repeat allele of the DRD4 gene has likewise been associated with the performance in executive functions, as well as with addictive behaviors and impulsivity. Participants were included in the obesity group (N = 42 if their body mass index (BMI was equal to or above 30, and in the lean group (N = 42 if their BMI was below 25. The DRD2/ANKK1-TaqIA and DRD4 VNTR polymorphisms were obtained. All subjects underwent neuropsychological assessment. Eating behavior traits were evaluated. The 'DRD2/ANKK1-TaqIA A1-allele status' had a significant effect on almost all the executive variables, but no significant 'DRD4 7R-allele status' effects were observed for any of the executive variables analyzed. There was a significant 'group' x 'DRD2/ANKK1-TaqIA A1-allele status' interaction effect on LN and 'group' x 'DRD4 7R-allele status' interaction effect on TMT B-A score. Being obese and a carrier of the A1 allele of DRD2/ANKK1-TaqIA or the 7R allele of DRD4 VNTR polymorphisms could confer a weakness as regards the performance of executive functions.

  14. Interleukin-1 Receptor Antagonist and Interleukin-4 Genes Variable Number Tandem Repeats Are Associated with Adiposity in Malaysian Subjects

    Science.gov (United States)

    Kok, Yung-Yean; Ong, Hing-Huat

    2017-01-01

    Interleukin-1 receptor antagonist (IL1RA) intron 2 86 bp repeat and interleukin-4 (IL4) intron 3 70 bp repeat are variable number tandem repeats (VNTRs) that have been associated with various diseases, but their role in obesity is elusive. The objective of this study was to investigate the association of IL1RA and IL4 VNTRs with obesity and adiposity in 315 Malaysian subjects (128 M/187 F; 23 Malays/251 ethnic Chinese/41 ethnic Indians). The allelic distributions of IL1RA and IL4 were significantly different among ethnicities, and the alleles were associated with total body fat (TBF) classes. Individuals with IL1RA I/II genotype or allele II had greater risk of having higher overall adiposity, relative to those having the I/I genotype or I allele, respectively, even after controlling for ethnicity [Odds Ratio (OR) of I/II genotype = 12.21 (CI = 2.54, 58.79; p = 0.002); II allele = 5.78 (CI = 1.73, 19.29; p = 0.004)]. However, IL4 VNTR B2 allele was only significantly associated with overall adiposity status before adjusting for ethnicity [OR = 1.53 (CI = 1.04, 2.23; p = 0.03)]. Individuals with IL1RA II allele had significantly higher TBF than those with I allele (31.79 ± 2.52 versus 23.51 ± 0.40; p = 0.005). Taken together, IL1RA intron 2 VNTR seems to be a genetic marker for overall adiposity status in Malaysian subjects. PMID:28293435

  15. Allele specific expression and methylation in the bumblebee, Bombus terrestris

    Directory of Open Access Journals (Sweden)

    Zoë Lonsdale

    2017-09-01

    Full Text Available The social hymenoptera are emerging as models for epigenetics. DNA methylation, the addition of a methyl group, is a common epigenetic marker. In mammals and flowering plants methylation affects allele specific expression. There is contradictory evidence for the role of methylation on allele specific expression in social insects. The aim of this paper is to investigate allele specific expression and monoallelic methylation in the bumblebee, Bombus terrestris. We found nineteen genes that were both monoallelically methylated and monoallelically expressed in a single bee. Fourteen of these genes express the hypermethylated allele, while the other five express the hypomethylated allele. We also searched for allele specific expression in twenty-nine published RNA-seq libraries. We found 555 loci with allele-specific expression. We discuss our results with reference to the functional role of methylation in gene expression in insects and in the as yet unquantified role of genetic cis effects in insect allele specific methylation and expression.

  16. Alleles versus mutations: Understanding the evolution of genetic architecture requires a molecular perspective on allelic origins.

    Science.gov (United States)

    Remington, David L

    2015-12-01

    Perspectives on the role of large-effect quantitative trait loci (QTL) in the evolution of complex traits have shifted back and forth over the past few decades. Different sets of studies have produced contradictory insights on the evolution of genetic architecture. I argue that much of the confusion results from a failure to distinguish mutational and allelic effects, a limitation of using the Fisherian model of adaptive evolution as the lens through which the evolution of adaptive variation is examined. A molecular-based perspective reveals that allelic differences can involve the cumulative effects of many mutations plus intragenic recombination, a model that is supported by extensive empirical evidence. I discuss how different selection regimes could produce very different architectures of allelic effects under a molecular-based model, which may explain conflicting insights on genetic architecture from studies of variation within populations versus between divergently selected populations. I address shortcomings of genome-wide association study (GWAS) practices in light of more suitable models of allelic evolution, and suggest alternate GWAS strategies to generate more valid inferences about genetic architecture. Finally, I discuss how adopting more suitable models of allelic evolution could help redirect research on complex trait evolution toward addressing more meaningful questions in evolutionary biology. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  17. Relationships between endothelial nitric oxide synthase gene polymorphisms and osteoporosis in postmenopausal women

    Institute of Scientific and Technical Information of China (English)

    Shun-zhi LIU; Hong YAN; Wei-kun HOU; Peng XU; Juan TUN; Li-fang TIAN; Bo-feng ZHU; Jie MA; She-min LU

    2009-01-01

    concentration in the subjects of eNOS 27 bp-VNTR a/a genotype was obviously higher than that in the subjects of b/b genotype (P<0.01). eNOS G/G homozygous frequencies in osteoporosis women, osteopenia women, and normal women were 85.37%, 76.38%, and 83.87%, respectively (P>0.05). 0% osteoporosis woman, 0.79% osteopenia women, and 3.23% normal women were eNOS a/a homozygous (P<0.05). The frequencies of eNOS 27 bp-VNTR a allele were 5.33% in the osteoporosis group, 10.24% in the osteopenia group, and 16.13% in the normal group (P<0.05, odds ratio (OR)=0.29, 95% confidence interval (CI)=0.11~0.77), suggesting that a/a genotype and a allele might have protective effects on osteoporosis. The haplotype analysis showed that G-b was 87.7% (214/244) in the osteoporosis group (P<0.05, OR=2AS, 95% CI=1.18~5.18). G-a was 5.3% (13/244) in the osteoporosis group (P<0.05, OR=0.29, 95% CI=0.11~0.77). G-b was a risk factor for osteoporosis, and G-a a protective factor. Conclusion: eNOS G894T G/T genotype influenced the plasma testosterone and osteocalcin concentrations, and T/T genotype influenced BMD. eNOS 27 bp-VNTR a/a genotype increased plasma estradiol concentration to have a protective effect on osteoporosis.

  18. Dideoxy single allele-specific PCR - DSASP new method to discrimination allelic

    Directory of Open Access Journals (Sweden)

    Eleonidas Moura Lima

    2015-06-01

    Full Text Available Gastric cancer (GC is a multifactorial disease with a high mortality rate in Brazil and worldwide. This work aimed to evaluate single nucleotide polymorphisms (SNP rs1695, in the Glutathione S-Transferase Pi (GSTP1 gene in GC samples by comparative analysis Specific PCR - ASP and Dideoxy Single Allele-Specific PCR - DSASP methods. The DSASP is the proposed new method for allelic discrimination. This work analyzed 60 GC samples, 26 diffuse and 34 intestinal types. The SNP rs1695 of the GSTP1 gene was significantly associated with GC analyzed by DSASP method (χ2 = 9.7, P 0.05. These results suggest that the SNP rs1695 of the GSTP1 gene was a risk factor associated with gastric carcinogens is and the DSASP method was a new successfully low-cost strategy to study allelic discrimination.

  19. Determination of DQB1 alleles using PCR amplification and allele-specific primers.

    Science.gov (United States)

    Lepage, V; Ivanova, R; Loste, M N; Mallet, C; Douay, C; Naoumova, E; Charron, D

    1995-10-01

    Molecular genotyping of HLA class II genes is commonly carried out using polymerase chain reaction (PCR) in combination with sequence-specific oligotyping (PCR-SSO) or a combination of the PCR and restriction fragment length polymorphism methods (PCR-RFLP). However, the identification of the DQB1 type by PCR-SSO and PCR-RFLP is very time-consuming which is disadvantageous for the typing of cadaveric organ donors. We have developed a DQB1 typing method using PCR in combination with allele-specific amplification (PCR-ASA), which allows the identification of the 17 most frequent alleles in one step using seven amplification mixtures. PCR allele-specific amplification HLA-DQB1 typing is easy to perform, and the results are easy to interpret in routine clinical practice. The PCR-ASA method is therefore better suited to DQB1 typing for organ transplantation than other methods.

  20. Allelic genealogies in sporophytic self-incompatibility systems in plants

    DEFF Research Database (Denmark)

    Schierup, M H; Vekemans, X; Christiansen, F B

    1998-01-01

    Expectations for the time scale and structure of allelic genealogies in finite populations are formed under three models of sporophytic self-incompatibility. The models differ in the dominance interactions among the alleles that determine the self-incompatibility phenotype: In the SSIcod model...... action, and the most recessive extant allele is likely to be the most recent common ancestor. Despite these asymmetries, the expected shape of the allele genealogies does not deviate markedly from the shape of a neutral gene genealogy. The application of the results to sequence surveys of alleles...

  1. Laser mass spectrometry for DNA fingerprinting for forensic applications

    Energy Technology Data Exchange (ETDEWEB)

    Chen, C.H.; Tang, K.; Taranenko, N.I.; Allman, S.L.; Chang, L.Y.

    1994-12-31

    The application of DNA fingerprinting has become very broad in forensic analysis, patient identification, diagnostic medicine, and wildlife poaching, since every individual`s DNA structure is identical within all tissues of their body. DNA fingerprinting was initiated by the use of restriction fragment length polymorphisms (RFLP). In 1987, Nakamura et al. found that a variable number of tandem repeats (VNTR) often occurred in the alleles. The probability of different individuals having the same number of tandem repeats in several different alleles is very low. Thus, the identification of VNTR from genomic DNA became a very reliable method for identification of individuals. DNA fingerprinting is a reliable tool for forensic analysis. In DNA fingerprinting, knowledge of the sequence of tandem repeats and restriction endonuclease sites can provide the basis for identification. The major steps for conventional DNA fingerprinting include (1) specimen processing (2) amplification of selected DNA segments by PCR, and (3) gel electrophoresis to do the final DNA analysis. In this work we propose to use laser desorption mass spectrometry for fast DNA fingerprinting. The process and advantages are discussed.

  2. The potential role of myostatin and neurotransmission genes in elite sport performances

    Indian Academy of Sciences (India)

    L Filonzi; N Franchini; M Vaghi; S Chiesa; F Nonnis Marzano

    2015-09-01

    Elite athletes are those who represent their sport at such major competition as the Olympic Games or World contests. The most outstanding athletes appear to emerge as a result of endogenous biologic characteristics interacting with exogenous influences of the environment, often described as a `Nature and Nurture’ struggle. In this work, we assessed the contribution given by 4 genes involved in muscles development (MSTN) and behavioural insights (5HTT, DAT and MAOA) to athletic performances. As for neurotransmission, 5HTT, DAT and MAOA genes have been considered as directly involved in the management of aggressiveness and anxiety. Genotypes and allelic frequencies of 5HTTLPR, MAOA-u VNTR, DAT VNTR and MSTN K153R were determined in 50 elite athletes and compared with 100 control athletes. In this work we found a significant correlation between the dopamine transporter genotype 9/9 and allele 9 and elite sport performances. On the contrary, no association was found between muscle development regulation or serotonin pathway and elite performances. Our data, for the first time, suggest a strong role of dopamine neurotransmitter in determining sport success, highlighting the role of emotional control and psycological management to reach high-level performances.

  3. Identification of gene variants in NOS3, ET-1 and RAS that confer risk and protection against microangiopathy in type 2 diabetic obese subjects.

    Science.gov (United States)

    Manea, Simona-Adriana; Robciuc, Alexandra; Guja, Cristian; Heltianu, Constantina

    2011-04-15

    The study aim was to investigate NOS3 VNTR, NOS3 G894T, EDN1 C8002T, ACE I/D, AGT M235T and AGTR1 A1166C in nonobese and obese T2DM patients, and their interaction with the incidence of microangiopathy. T2DM subjects (n=250; 166 nonobese, and 84 obese) were genotyped for the gene variants by PCR/RFLP. The interaction of these polymorphisms with obesity and their contribution to microangiopathy were analyzed by multivariate regression analysis. A higher frequency of NOS3 4a allele was found in obese (P=0.027) vs. nonobese subjects. ACE D (P=0.009) and AGT 235T (P=0.026) alleles were associated with the reduced risk of diabetic nephropathy in nonobese and obese patients, respectively. In obese subjects, NOS3 4a (P=0.011) had a converse effect to NOS3 894T (P=0.043), and EDN1 8002T (P=0.035) on the prevalence of combined microangiopathy (neuropathy/retinopathy/nephropathy) vs. microangiopathy-negative subjects. The study indicates association of RAS variants with obesity and nephropathy, and an opposite effect of NOS3 VNTR and NOS3 G894T on the occurrence of combined microangiopathy. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. The association study of polymorphisms in DAT, DRD2, and COMT genes and acute extrapyramidal adverse effects in male schizophrenic patients treated with haloperidol.

    Science.gov (United States)

    Zivković, Maja; Mihaljević-Peles, Alma; Bozina, Nada; Sagud, Marina; Nikolac-Perkovic, Matea; Vuksan-Cusa, Bjanka; Muck-Seler, Dorotea

    2013-10-01

    Extrapyramidal symptoms (EPSs) are common adverse effects of antipsychotics. The development of acute EPSs could depend on the activity of dopaminergic system and its gene variants. The aim of this study was to determine the association between dopaminergic type 2 receptor (DRD2) dopamine transporter (SLC6A3) and catechol-O-methyltransferase (COMT) gene polymorphisms and acute EPSs in 240 male schizophrenic patients treated with haloperidol (15-mg/d) over a period of 2 weeks. Acute EPSs were assessed with Simpson-Angus Scale. Three dopaminergic gene polymorphisms, the DRD2 Taq1A, the SLC6A3 VNTR, and the COMT Val158Met, were determined. Extrapyramidal symptoms occurred in 116 (48.3%) of patients. Statistically significant associations were found for SLC6A3 VNTR and COMT Val158Met polymorphisms and EPS susceptibility. Patients with SLC6A3 9/10 genotype had almost twice the odds to develop EPSs compared with those with all other SLC6A3 genotypes (odds ratio, 1.9; 95% confidence interval, 1.13-3.30), and patients with COMT Val/Met genotype had 1.7 times greater odds to develop EPSs than those with all other COMT genotypes (odds ratio, 1.7; 95% confidence interval, 1.01-2.88). There was no statistically significant association between genotype and allele frequencies of DRD2, SLC6A3, or COMT polymorphisms and the development of particular EPSs.In conclusion, the results of the present study showed for the first time the association between acute haloperidol-induced EPSs and SLC6A3 VNTR and COMT Val158Met polymorphisms. Although the precise biological mechanisms underlying these findings are not yet understood, the results suggest that the dopaminergic gene variations could predict the vulnerability to the development of the acute EPSs in haloperidol-treated schizophrenic patients.

  5. Interleukin-1 Gene Cluster Polymorphisms and its Haplotypes may Predict the Risk to Develop Cervical Cancer in Tunisia.

    Science.gov (United States)

    Zidi, Sabrina; Sghaier, Ikram; Zouidi, Ferjeni; Benahmed, Amira; Stayoussef, Mouna; Kochkar, Radhia; Gazouani, Ezzedine; Mezlini, Amel; Yacoubi-Loueslati, Besma

    2015-09-01

    Our study aimed to evaluate the association between IL-1α (4845 G/T), IL-1β (-511C/T) and IL-1RN (VNTR) polymorphisms and risk of cervical cancer. This case-control study investigates three polymorphisms in 130 patients and 260 controls by PCR-restriction fragment length polymorphism (RFLP). The IL-1RN (VNTR) A1/A3 genotype appear as a cervical cancer risk factor (p = 0.048; OR = 2.92; 95 % CI = 1.00-8.74), moreover, the L/2* decreased the risk (p = 0.011; OR = 0.47; 95 % CI = 0.25-0.88) and may be a protective factor against this pathology. Stratified analysis according to the FIGO stage subgroup revealed that the IL-1β-511 T/T genotype and T allele may be a protective factors against cervical cancer development for patients with early stage (p = 0.030; OR = 0.46; 95 % CI = 0.22-0.96) (p = 0.020; OR = 0.68; 95 % CI = 0.48-0.97). However, for the patients with advanced FIGO stage, IL-1RN-VNTR L/2* genotype appear as a protective factor for this pathology (p = 0.023; OR = 0.29; 95 % CI = 0.08-0.99). The (G-T-L) haplotype showed a significant decreased frequency in cervical cancer patients as compared to controls (p = 0.032; OR = 0.53; 95 % CI = 0.29-0.95). In contrast, the (T-T-2*) combination appear a risk factor for the development of cervical cancer (p = 0.018; OR = 1.57; 95 % CI = 1.07-2.30). Our study suggested that IL1 cluster polymorphisms and haplotypes may be a genetic risk factor for cervical cancer.

  6. Polymorphisms in serotonergic pathways influence the outcome of antidepressant therapy in psychiatric inpatients.

    Science.gov (United States)

    Staeker, Julia; Leucht, Stefan; Laika, Barbara; Steimer, Werner

    2014-01-01

    Serotonergic pathways are known to play an essential role in the effects generated by antidepressants. Polymorphisms in serotonin receptor and transporter genes have been identified as an important factor. To investigate which of these polymorphisms may be useful to predict clinical outcome, we assessed their effect in a naturalistic clinical study. We studied the influence of the 5-hydroxytryptamine transporter (5-HTT) variable number of tandem repeats (VNTR), 5-HTTLPR/rs25531 and a 5-HTR2A intron 2 SNP with regard to response and side effects in 273 psychiatric inpatients. Main clinical assessments included Clinical Global Impressions ratings, paranoid depression scale self-rating scale and Dosage Record, and Treatment Emergent Symptoms (DOTES) Scale. We found significant associations between 5-HTTLPR/rs25531 S/L(G) alleles and response and side effects in 100 patients with selective serotonin reuptake inhibitor (SSRI) treatment (p = 0.037, CGI-I ≤ 2: 0% vs. 19% and p = 0.0005, DOTES cluster c: 0.76 vs. 0.19). 5-HTT VNTR and 5-HTR2A intron 2 polymorphisms were associated significantly with adverse effects in patients with selective and nonselective SRI (5-HTT VNTR 12/12: n = 170, p = 0.0001, side effect rates: 51% vs. 19% and rs7997012 [A/A]: n = 50, p = 0.020, side effects rates: 43% vs. 11%). No impact of the polymorphisms on mirtazapine treatment was found. Our study confirms the influence of serotonergic polymorphisms at the receptor and transporter level on SSRI response and side effects, supporting previous reports based on various study designs. The effects were strong enough to be noticed clinically in this naturalistic setting. However, randomized controlled trials are warranted to provide unequivocal evidence of the clinical usefulness of pretherapeutic screening for these polymorphisms.

  7. Plasminogen alleles influence susceptibility to invasive aspergillosis.

    Directory of Open Access Journals (Sweden)

    Aimee K Zaas

    2008-06-01

    Full Text Available Invasive aspergillosis (IA is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855 correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn was also identified in the human homolog (PLG; Gene ID 5340. An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.

  8. Allele-specific KRT1 expression is a complex trait.

    Directory of Open Access Journals (Sweden)

    Heng Tao

    2006-06-01

    Full Text Available The differential expression of alleles occurs commonly in humans and is likely an important genetic factor underlying heritable differences in phenotypic traits. Understanding the molecular basis of allelic expression differences is thus an important challenge. Although many genes have been shown to display differential allelic expression, this is the first study to examine in detail the cumulative effects of multiple cis-regulatory polymorphisms responsible for allele-specific expression differences. We have used a variety of experimental approaches to identify and characterize cis-regulatory polymorphisms responsible for the extreme allele-specific expression differences of keratin-1 (KRT1 in human white blood cells. The combined data from our analyses provide strong evidence that the KRT1 allelic expression differences result from the haplotypic combinations and interactions of five cis-regulatory single nucleotide polymorphisms (SNPs whose alleles differ in their affinity to bind transcription factors and modulate KRT1 promoter activity. Two of these cis-regulatory SNPs bind transcriptional activators with the alleles on the high-expressing KRT1 haplotype pattern having a higher affinity than the alleles on the low-expressing haplotype pattern. In contrast, the other three cis-regulatory SNPs bind transcriptional inhibitors with the alleles on the low-expressing haplotype pattern having a higher affinity than the alleles on the high-expressing haplotype pattern. Our study provides important new insights into the degree of complexity that the cis-regulatory sequences responsible for allele-specific transcriptional regulation have. These data suggest that allelic expression differences result from the cumulative contribution of multiple DNA sequence polymorphisms, with each having a small effect, and that allele-specific expression can thus be viewed as a complex trait.

  9. Allele-specific PCR detection of sweet cherry self-incompatibility (S) alleles S1 to S16 using consensus and allele-specific primers.

    Science.gov (United States)

    Sonneveld, T; Tobutt, K R; Robbins, T P

    2003-10-01

    PCR-based identification of all 13 known self-incompatibility (S) alleles of sweet cherry is reported. Two pairs of consensus primers were designed from our previously published cDNA sequences of S(1) to S(6) S-RNases, the stylar components of self-incompatibility, to reveal length variation of the first and the second introns. With the exception of the first intron of S(13), these also amplified S(7) to S(14) and an allele previously referred to as S(x), which we now label S(16). The genomic PCR products were cloned and sequenced. The partial sequence of S(11) matched that of S(7) and the alleles were shown to have the same functional specificity. Allele-specific primers were designed for S(7) to S(16), so that allele-specific primers are now available for all 13 S alleles of cherry (S(8), S(11) and S(15) are duplicates). These can be used to distinguish between S alleles with introns of similar size and to confirm genotypes determined with consensus primers. The reliability of the PCR with allele-specific primers was improved by the inclusion of an internal control. The use of the consensus and allele-specific primers was demonstrated by resolving conflicting genotypes that have been published recently and by determining genotypes of 18 new cherry cultivars. Two new groups are proposed, Group XXIII (S(3) S(16)), comprising 'Rodmersham Seedling' and 'Strawberry Heart', and Group XXIV (S(6) S(12)), comprising 'Aida' and 'Flamentiner'. Four new self-compatibility genotypes, S(3) S(3)', S(4)' S(6), S(4)' S(9) and S(4)' S(13), were found. The potential use of the consensus primers to reveal incompatibility alleles in other cherry species is also demonstrated.

  10. Evidence that the methylation state of the monoamine oxidase A (MAOA) gene predicts brain activity of MAO A enzyme in healthy men

    National Research Council Canada - National Science Library

    Shumay, Elena; Logan, Jean; Volkow, Nora D; Fowler, Joanna S

    2012-01-01

    ...). PET brain imaging of monoamine oxidase A (MAO A)-an enzyme metabolizing neurotransmitters-revealed that MAO A levels vary widely between healthy men and this variability was not explained by the common MAOA genotype (VNTR genotype...

  11. Snapshot of the genetic diversity of Mycobacterium tuberculosis isolates in Iraq

    Directory of Open Access Journals (Sweden)

    Mohanad Mohsin Ahmed

    2014-01-01

    Conclusion: Iraq is specific in having its own most predominant lineage (SIT1144/T1 which is not found among neighboring countries. The 15-locus MIRU-VNTR can be useful in discriminating M. tuberculosis isolates in Iraq.

  12. The insulin gene variable number tandem repeat class I/III polymorphism is in linkage disequilibrium with birth weight but not Type 2 diabetes in the Pima population.

    Science.gov (United States)

    Lindsay, Robert S; Hanson, Robert L; Wiedrich, Chris; Knowler, William C; Bennett, Peter H; Baier, Leslie J

    2003-01-01

    The insulin gene variable number tandem repeat (INS-VNTR) is proposed to exert pleiotropic genetic effects on birth weight and diabetes susceptibility. In our study, we examined the influence of a polymorphism in tight linkage disequilibrium with INS-VNTR (-23Hph1) on birth weight and type 2 diabetes in the Pima population. A parent-offspring "trio" design was used to assess parent-of-origin effects and population stratification. The presence of the -23Hph1 T-allele was associated with lower birth weight (n = 192; -140 g per copy of the T-allele; P = 0.04), even after adjustment for effects of population stratification (P = 0.03). The effects of paternally transmitted T-alleles were greater than those of maternally transmitted alleles (paternally transmitted: -250 g, P = 0.05; maternally transmitted: -111 g, P = 0.43), but this difference was not statistically significant (P = 0.50). The -23Hph1 T-allele was associated with an increased prevalence of type 2 diabetes (P = 0.009), which family-based association analysis suggested was attributable to population structure (P = 0.04) without significant evidence of linkage disequilibrium between diabetes prevalence and genotype (P = 0.86). Thus allelic variation of the INS gene is associated with lower birth weight and increased prevalence of type 2 diabetes. Significant linkage disequilibrium was found between -23Hph1 and birth weight but not type 2 diabetes, an observation that supports a potential functional role of INS polymorphisms in the regulation of birth weight.

  13. Allele Frequency - JSNP | LSDB Archive [Life Science Database Archive metadata

    Lifescience Database Archive (English)

    Full Text Available nd 39 SNPs are assayed in three (POP_*) and two (RIKEN_japanese_*) panels, respectively. Derived from Flat f... assay (JBIC-allele and RIKEN_japanese_*), TaqMan assay (RIKEN-allele) or direct sequencing / allelic discri...unteers under informed consent RIKEN_japanese_normal_weight - 711 unrelated japanese normal weight volunteer...s ( body mass index RIKEN_japanese_obese - 796 unrelated japanese obese patients

  14. Nitric Oxide Synthase genotype modulation of impulsivity and ventral striatal activity in adult ADHD patients and healthy comparison subjects

    OpenAIRE

    Hoogman, M.; Aarts, E.; Zwiers, M.; Slaats-Willemse, D.; Naber, M.; Onnink, M.; Cools, R; van Kan, C; Buitelaar, J; Franke, B

    2011-01-01

    Objective: Attention deficit hyperactivity disorder (ADHD) is a highly heritable disorder. The NOS1 gene encoding nitric oxide synthase is a candidate gene for ADHD and has been previously linked with impulsivity. In the present study, the authors investigated the effect of a functional variable number of tandem repeats (VNTR) polymorphism in NOS1 (NOS1 exon 1f-VNTR) on the processing of rewards, one of the cognitive deficits in ADHD. Method: A sample of 136 participants, consisting of 87 adu...

  15. DQB1*06:02 allele-specific expression varies by allelic dosage, not narcolepsy status

    DEFF Research Database (Denmark)

    Weiner Lachmi, Karin; Lin, Ling; Kornum, Birgitte Rahbek;

    2012-01-01

    The association of narcolepsy-cataplexy, a sleep disorder caused by the loss of hypocretin/orexin neurons in the hypothalamus, with DQA1*01:02-DQB1*06:02 is one of the tightest known single-allele human leukocyte antigen (HLA) associations. In this study, we explored genome-wide expression...... in peripheral white blood cells of 50 narcolepsy versus 47 controls (half of whom were DQB1*06:02 positive) and observed the largest differences between the groups in the signal from HLA probes. Further studies of HLA-DQ expression (mRNA and protein in a subset) in 125 controls and 147 narcolepsy cases did...... indicate that allelic dosage is transmitted into changes in heterodimer availability, a phenomenon that may explain the increased risk for narcolepsy in DQB1*06:02 homozygotes versus heterozygotes....

  16. New Repeat Polymorphism in the AKT1 Gene Predicts Striatal Dopamine D2/D3 Receptor Availability and Stimulant-Induced Dopamine Release in the Healthy Human Brain.

    Science.gov (United States)

    Shumay, Elena; Wiers, Corinde E; Shokri-Kojori, Ehsan; Kim, Sung Won; Hodgkinson, Colin A; Sun, Hui; Tomasi, Dardo; Wong, Christopher T; Weinberger, Daniel R; Wang, Gene-Jack; Fowler, Joanna S; Volkow, Nora D

    2017-05-10

    The role of the protein kinase Akt1 in dopamine neurotransmission is well recognized and has been implicated in schizophrenia and psychosis. However, the extent to which variants in the AKT1 gene influence dopamine neurotransmission is not well understood. Here we investigated the effect of a newly characterized variant number tandem repeat (VNTR) polymorphism in AKT1 [major alleles: L- (eight repeats) and H- (nine repeats)] on striatal dopamine D2/D3 receptor (DRD2) availability and on dopamine release in healthy volunteers. We used PET and [(11)C]raclopride to assess baseline DRD2 availability in 91 participants. In 54 of these participants, we also measured intravenous methylphenidate-induced dopamine release to measure dopamine release. Dopamine release was quantified as the difference in specific binding of [(11)C]raclopride (nondisplaceable binding potential) between baseline values and values following methylphenidate injection. There was an effect of AKT1 genotype on DRD2 availability at baseline for the caudate (F(2,90) = 8.2, p = 0.001) and putamen (F(2,90) = 6.6, p = 0.002), but not the ventral striatum (p = 0.3). For the caudate and putamen, LL showed higher DRD2 availability than HH; HL were in between. There was also a significant effect of AKT1 genotype on dopamine increases in the ventral striatum (F(2,53) = 5.3, p = 0.009), with increases being stronger in HH > HL > LL. However, no dopamine increases were observed in the caudate (p = 0.1) or putamen (p = 0.8) following methylphenidate injection. Our results provide evidence that the AKT1 gene modulates both striatal DRD2 availability and dopamine release in the human brain, which could account for its association with schizophrenia and psychosis. The clinical relevance of the newly characterized AKT1 VNTR merits investigation.SIGNIFICANCE STATEMENT The AKT1 gene has been implicated in schizophrenia and psychosis. This association is likely to reflect modulation of dopamine signaling by Akt1 kinase

  17. Fitness Costs Associated with Evolved Herbicide Resistance Alleles in Plants

    National Research Council Canada - National Science Library

    Martin M. Vila-Aiub; Paul Neve; Stephen B. Powles

    2009-01-01

    .... There have been many studies quantifying the fitness costs associated with novel herbicide resistance alleles, reflecting the importance of fitness costs in determining the evolutionary dynamics of resistance...

  18. Interleukin-1 Gene Cluster Polymorphisms and Their Association with Coronary Artery Disease: Separate Evidences from the Largest Case-Control Study amongst North Indians and an Updated Meta-Analysis.

    Science.gov (United States)

    Rai, Himanshu; Sinha, Nakul; Kumar, Sudeep; Sharma, Ajay Kumar; Agrawal, Suraksha

    2016-01-01

    Several researchers have reported significant association of numerous single nucleotide polymorphisms (SNPs) residing in the interleukin-1 (IL-1) gene cluster with coronary artery disease (CAD). However, their association status amongst North Indian ancestry (NIA) have never been systematically assessed. Despite a published meta-analysis on this subject, their association status worldwide as well as amongst different major ancestral subgroups still remains unclear. We therefore decided to prospectively test the association of 11 IL-1 gene cluster SNPs with CAD, vide a case-control study amongst a cohort of NIA and attempted to validate our results with the help of an updated meta-analysis of all relevant published association studies. Included studies were segregated into ancestral subgroups and association statuses for each subgroup were determined. A total of 323 cases and 400 healthy, age and sex matched controls belonging to NIA were prospectively enrolled and subsequently genotyped for 11 selected IL-1 gene cluster SNPs. Although results for none of the evaluated IL-1 gene cluster SNPs reached the adjusted level of significance (pT and IL1RN 86bp VNTR in several of the constructed genetic models (p range = 0.01-0.044 and 0.005-0.034 respectively). The presence of >1, 'T' (minor) allele of IL1B -511 C>T in a genotype seemed to provide protection against CAD (OR = 0.62, p = 0.044), while the presence of >1, 'C' (major) allele seemed to increase the risk of CAD (OR = 1.36, p = 0.041). The minor allele (allele 2) of IL1RN 86bp VNTR and its homozygous genotype (2/2 genotype) also seemed to carry an increased risk for CAD (OR = 1.62, p = 0.005 and OR = 2.25, p = 0.031 respectively). On the other hand, several haplotype combinations constructed out of IL1B and IL1RN gene variants clearly showed statistically significant associations with CAD (p0.05). Subgroup analysis, however, yielded interesting results, where significant differences in association statuses were

  19. Identification of Multiple Alleles at the Wx Locus and Development of Single Segment Substitution Lines for the Alleles in Rice

    Institute of Scientific and Technical Information of China (English)

    ZENG Rui-zhen; ZHANG Ze-min; HE Feng-hua; XI Zhang-ying; Akshay TALUKDAR; SHI Jun-qiong; QIN Li-jun; HUANG Chao-feng; ZHANG Gui-quan

    2006-01-01

    The microsatellite markers 484/485 and 484/W2R were used to identify the multiple alleles at the Wx locus in rice germplasm. Fifteen alleles were identified in 278 accessions by using microsatellite class and G-T polymorphism. Among these alleles, (CT)12-G, (CT)15-G, (CT)16-G, (CT)17-G, (CT)18-G and (CT)21-G have not been reported. Seventy-two single-segment substitution lines (SSSLs) carrying different alleles at the Wx locus were developed by using Huajingxian 74 with the (CT)11-G allele as a recipient and 20 accessions containing 12 different alleles at the Wx locus as donors. The estimated length of the substituted segments ranged from 2.2 to 77.3 cM with an average of 17.4 cM.

  20. Distribution of BoLA-DRB3 Allelic Frequencies and Identification of Two New Alleles in Iranian Buffalo Breed

    OpenAIRE

    Mosafer, J.; Heydarpour, M.; Manshad, E.; Russell, G.; Sulimova, G. E.

    2012-01-01

    The role of the major histocompatibility complex (MHC) in the immune response makes it an attractive candidate gene for associations with disease resistance and susceptibility. This study describes genetic variability in the BoLA-DRB3 in Iranian buffaloes. Heminested PCR-RFLP method was used to identify the frequency of BoLA-DRB3 alleles. The BoLA-DRB3 locus is highly polymorphic in the study herd (12 alleles). Almost 63.50% of the alleles were accounted for by four alleles (BoLA-DRB3.2 *48, ...

  1. Identification of the third/extra allele for forensic application in cases with TPOX tri-allelic pattern.

    Science.gov (United States)

    Picanço, Juliane Bentes; Raimann, Paulo Eduardo; Motta, Carlos Henrique Ares Silveira da; Rodenbusch, Rodrigo; Gusmão, Leonor; Alho, Clarice Sampaio

    2015-05-01

    Genotyping of polymorphic short tandem repeats (STRs) loci is widely used in forensic DNA analysis. STR loci eventually present tri-allelic pattern as a genotyping irregularity and, in that situation, the doubt about the tri-allele locus frequency calculation can reduce the analysis strength. In the TPOX human STR locus, tri-allelic genotypes have been reported with a widely varied frequency among human populations. We investigate whether there is a single extra allele (the third allele) in the TPOX tri-allelic pattern, what it is, and where it is, aiming to understand its genomic anatomy and to propose the knowledge of this TPOX extra allele from genetic profile, thus preserving the two standard TPOX alleles in forensic analyses. We looked for TPOX tri-allelic subjects in 75,113 Brazilian families. Considering only the parental generation (mother+father) we had 150,226 unrelated subjects evaluated. From this total, we found 88 unrelated subjects with tri-allelic pattern in the TPOX locus (0.06%; 88/150,226). Seventy three of these 88 subjects (73/88; 83%) had the Clayton's original Type 2 tri-allelic pattern (three peaks of even intensity). The remaining 17% (15/88) show a new Type 2 derived category with heterozygote peak imbalance (one double dose peak plus one regular sized peak). In this paper we present detailed data from 66 trios (mother+father+child) with true biological relationships. In 39 of these families (39/66; 59%) the extra TPOX allele was transmitted either from the mother or from the father to the child. Evidences indicated the allele 10 as the extra TPOX allele, and it is on the X chromosome. The present data, which support the previous Lane hypothesis, improve the knowledge about tri-allelic pattern of TPOX CODIS' locus allowing the use of TPOX profile in forensic analyses even when with tri-allelic pattern. This evaluation is now available for different forensic applications. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Phylogenetic assignment of Mycobacterium tuberculosis Beijing clinical isolates in Japan by maximum a posteriori estimation.

    Science.gov (United States)

    Seto, Junji; Wada, Takayuki; Iwamoto, Tomotada; Tamaru, Aki; Maeda, Shinji; Yamamoto, Kaori; Hase, Atsushi; Murakami, Koichi; Maeda, Eriko; Oishi, Akira; Migita, Yuji; Yamamoto, Taro; Ahiko, Tadayuki

    2015-10-01

    Intra-species phylogeny of Mycobacterium tuberculosis has been regarded as a clue to estimate its potential risk to develop drug-resistance and various epidemiological tendencies. Genotypic characterization of variable number of tandem repeats (VNTR), a standard tool to ascertain transmission routes, has been improving as a public health effort, but determining phylogenetic information from those efforts alone is difficult. We present a platform based on maximum a posteriori (MAP) estimation to estimate phylogenetic information for M. tuberculosis clinical isolates from individual profiles of VNTR types. This study used 1245 M. tuberculosis clinical isolates obtained throughout Japan for construction of an MAP estimation formula. Two MAP estimation formulae, classification of Beijing family and other lineages, and classification of five Beijing sublineages (ST11/26, STK, ST3, and ST25/19 belonging to the ancient Beijing subfamily and modern Beijing subfamily), were created based on 24 loci VNTR (24Beijing-VNTR) profiles and phylogenetic information of the isolates. Recursive estimation based on the formulae showed high concordance with their authentic phylogeny by multi-locus sequence typing (MLST) of the isolates. The formulae might further support phylogenetic estimation of the Beijing lineage M. tuberculosis from the VNTR genotype with various geographic backgrounds. These results suggest that MAP estimation can function as a reliable probabilistic process to append phylogenetic information to VNTR genotypes of M. tuberculosis independently, which might improve the usage of genotyping data for control, understanding, prevention, and treatment of TB.

  3. Optimization of standard in-house 24-locus variable-number tandem-repeat typing for Mycobacterium tuberculosis and its direct application to clinical material.

    Science.gov (United States)

    de Beer, Jessica L; Akkerman, Onno W; Schürch, Anita C; Mulder, Arnout; van der Werf, Tjip S; van der Zanden, Adri G M; van Ingen, Jakko; van Soolingen, Dick

    2014-05-01

    Variable-number tandem-repeat (VNTR) typing with a panel of 24 loci is the current gold standard in the molecular typing of Mycobacterium tuberculosis complex isolates. However, because of technical problems, a part of the loci often cannot be amplified by multiplex PCRs. Therefore, a considerable number of single-locus PCRs have to be performed for the loci with missing results, which impairs the laboratory work flow. Therefore, the original in-house method described by Supply et al. in 2006 was reevaluated. We modified seven primers and the PCR master mixture and obtained a strongly optimized in-house 24-locus VNTR typing method. The percentage of instantly complete 24-locus VNTR patterns detected in the routine flow of typing activities increased to 84.7% from the 72.3% obtained with the typing conducted with the commercially available Genoscreen MIRU-VNTR typing kit. The analytical sensitivity of the optimized in-house method was assessed by serial dilutions of M. tuberculosis in bronchoalveolar lavage fluid. A 1:10 dilution of the different strains tested was the lowest dilution for the detection of a complete 24-locus VNTR pattern. The optimized in-house 24-locus VNTR typing method will reduce the turnaround time of typing significantly and also the financial burden of these activities.

  4. First worldwide proficiency study on variable-number tandem-repeat typing of Mycobacterium tuberculosis complex strains.

    Science.gov (United States)

    de Beer, Jessica L; Kremer, Kristin; Ködmön, Csaba; Supply, Philip; van Soolingen, Dick

    2012-03-01

    Although variable-number tandem-repeat (VNTR) typing has gained recognition as the new standard for the DNA fingerprinting of Mycobacterium tuberculosis complex (MTBC) isolates, external quality control programs have not yet been developed. Therefore, we organized the first multicenter proficiency study on 24-locus VNTR typing. Sets of 30 DNAs of MTBC strains, including 10 duplicate DNA samples, were distributed among 37 participating laboratories in 30 different countries worldwide. Twenty-four laboratories used an in-house-adapted method with fragment sizing by gel electrophoresis or an automated DNA analyzer, nine laboratories used a commercially available kit, and four laboratories used other methods. The intra- and interlaboratory reproducibilities of VNTR typing varied from 0% to 100%, with averages of 72% and 60%, respectively. Twenty of the 37 laboratories failed to amplify particular VNTR loci; if these missing results were ignored, the number of laboratories with 100% interlaboratory reproducibility increased from 1 to 5. The average interlaboratory reproducibility of VNTR typing using a commercial kit was better (88%) than that of in-house-adapted methods using a DNA analyzer (70%) or gel electrophoresis (50%). Eleven laboratories using in-house-adapted manual typing or automated typing scored inter- and intralaboratory reproducibilities of 80% or higher, which suggests that these approaches can be used in a reliable way. In conclusion, this first multicenter study has documented the worldwide quality of VNTR typing of MTBC strains and highlights the importance of international quality control to improve genotyping in the future.

  5. The Role of Interleukin-1 Genotype in the Association between Coronary Heart Disease and Periodontitis in a Syrian Population.

    Science.gov (United States)

    Bashour, Lina; Khattab, Razan; Harfoush, Elham

    2013-01-01

    Objective. To determine whether differences exist between periodontitis subjects with and without Coronary Heart Disease (CHD) in a Syrian population in the distribution of IL-1 alleles at positions IL-1α+4845, IL-1β+3954, IL-1β-511, and IL-1RN VNTR. Background. The role of Interleukin-1 genes in the association between periodontitis and CHD has been demonstrated in previous studies. No study has been carried out on the Syrian population to asses for such a role. Methods. 200 Syrian Arab periodontitis patients (184 males, 16 females; mean age 52.61) were divided into two groups: cases group 100 subjects with CHD (92 males, 8 females; mean age 52.06); controls group 100 subjects without CHD (92 males, 8 females; mean age 53.16). Probing depth (PD), clinical attachment loss (CAL), and alveolar bone loss (ABL) were performed for patients. Blood samples were collected for genotyping analysis of IL-1α+4845, IL-1β+3954, and IL-1β-511 using PCR-RFLP technique and IL-1RN VNTR using normal PCR. Results. An association between both (CAL and ABL) and CHD was shown after adjustment for other confounders (OR: 7.659, P = 0.001; OR: 3.645, P = 0.006, resp.). Also, an association between allele 2 of IL-1α+4845, IL-1β+3954, and IL-1β-511 and ABL was shown. Allele 2 of IL-1α+4845 and IL-1β-511 was associated with ABL among individuals with and without CHD. But after adjustment for other confounders, the association remained only between allele 2 of IL-11α+4845 and both CHD and severe ABL (OR: 0.189, P < 0.001). Conclusion. Allele 2 of IL-11α+4845 may be considered a risk indicator for having both CHD and severe ABL in the investigated Syrian population.

  6. Low Penetrance Alleles in Colorectal Cancer: the arachidonic acid pathway

    NARCIS (Netherlands)

    C.L.E. Siezen

    2006-01-01

    textabstractIn summary, we can conclude that we have successfully identified low penetrance alleles in the PPAR., PLA2G2A and ALOX15 genes, conferring differential colorectal adenoma risk, and two such alleles in the PTGS2 gene, one of which is also involved in colorectal cancer risk. These resul

  7. Allelic imbalance in hereditary and sporadic prostate cancer.

    NARCIS (Netherlands)

    Verhage, B.; Houwelingen, K.P. van; Ruijter, T.E.G.; Kiemeney, L.A.L.M.; Schalken, J.A.

    2003-01-01

    BACKGROUND: In this study, we evaluate the pattern of allelic imbalance (AI) in both sporadic prostate cancer (SPC) and hereditary prostate cancer (HPC) at loci that frequently show allelic imbalance in sporadic prostate cancer, or are believed to have a putative role in the disease. METHODS: DNA ob

  8. Rescue of progeria in trichothiodystrophy by homozygous lethal Xpd alleles.

    Directory of Open Access Journals (Sweden)

    Jaan-Olle Andressoo

    2006-10-01

    Full Text Available Although compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented. This is most likely because of the inherent difficulty in distinguishing specific biallelic effects from differences in environment or genetic background. We addressed the potential of different recessive alleles to contribute to the enigmatic pleiotropy associated with XPD recessive disorders in compound heterozygous mouse models. Alterations in this essential helicase, with functions in both DNA repair and basal transcription, result in diverse pathologies ranging from elevated UV sensitivity and cancer predisposition to accelerated segmental progeria. We report a variety of biallelic effects on organismal phenotype attributable to combinations of recessive Xpd alleles, including the following: (i the ability of homozygous lethal Xpd alleles to ameliorate a variety of disease symptoms when their essential basal transcription function is supplied by a different disease-causing allele, (ii differential developmental and tissue-specific functions of distinct Xpd allele products, and (iii interallelic complementation, a phenomenon rarely reported at clinically relevant loci in mammals. Our data suggest a re-evaluation of the contribution of "null" alleles to XPD disorders and highlight the potential of combinations of recessive alleles to affect both normal and pathological phenotypic plasticity in mammals.

  9. Drop-out probabilities of IrisPlex SNP alleles

    DEFF Research Database (Denmark)

    Andersen, Jeppe Dyrberg; Tvedebrink, Torben; Mogensen, Helle Smidt

    2013-01-01

    -out of true alleles is possible. As part of the validation of the IrisPlex assay in our ISO17025 accredited, forensic genetic laboratory, we estimated the probability of drop-out of specific SNP alleles using 29 and 30 PCR cycles and 25, 50 and 100 Single Base Extension (SBE) cycles. We observed no drop...

  10. Human minisatellite alleles detectable only after PCR amplification.

    Science.gov (United States)

    Armour, J A; Crosier, M; Jeffreys, A J

    1992-01-01

    We present evidence that a proportion of alleles at two human minisatellite loci is undetected by standard Southern blot hybridization. In each case the missing allele(s) can be identified after PCR amplification and correspond to tandem arrays too short to detect by hybridization. At one locus, there is only one undetected allele (population frequency 0.3), which contains just three repeat units. At the second locus, there are at least five undetected alleles (total population frequency 0.9) containing 60-120 repeats; they are not detected because these tandem repeats give very poor signals when used as a probe in standard Southern blot hybridization, and also cross-hybridize with other sequences in the genome. Under these circumstances only signals from the longest tandemly repeated alleles are detectable above the nonspecific background. The structures of these loci have been compared in human and primate DNA, and at one locus the short human allele containing three repeat units is shown to be an intermediate state in the expansion of a monomeric precursor allele in primates to high copy number in the longer human arrays. We discuss the implications of such loci for studies of human populations, minisatellite isolation by cloning, and the evolution of highly variable tandem arrays.

  11. Estimating Relatedness in the Presence of Null Alleles.

    Science.gov (United States)

    Huang, Kang; Ritland, Kermit; Dunn, Derek W; Qi, Xiaoguang; Guo, Songtao; Li, Baoguo

    2016-01-01

    Studies of genetics and ecology often require estimates of relatedness coefficients based on genetic marker data. However, with the presence of null alleles, an observed genotype can represent one of several possible true genotypes. This results in biased estimates of relatedness. As the numbers of marker loci are often limited, loci with null alleles cannot be abandoned without substantial loss of statistical power. Here, we show how loci with null alleles can be incorporated into six estimators of relatedness (two novel). We evaluate the performance of various estimators before and after correction for null alleles. If the frequency of a null allele is 0.5, the potency of estimation is too low and such a locus should be excluded. We make available a software package entitled PolyRelatedness v1.6, which enables researchers to optimize these estimators to best fit a particular data set.

  12. Ethical guideposts for allelic variation databases.

    Science.gov (United States)

    Knoppers, B M; Laberge, C M

    2000-01-01

    Basically, a mutation database (MDB) is a repository where allelic variations are described and assigned within a specific gene locus. The purposes of an MDB may vary greatly and have different content and structure. The curator of an electronic and computer-based MDB will provide expert feedback (clinical and research). This requires ethical guideposts. Going to direct on-line public access for the content of an MDB or to interactive communication also raises other considerations. Currently, HUGO's MDI (Mutation Database Initiative) is the only integrated effort supporting and guiding the coordinated deployment of MDBs devoted to genetic diversity. Thus, HUGO's ethical "Statements" are applicable. Among the ethical principles, the obligation of preserving the confidentiality of information transferred by a collaborator to the curator is particularly important. Thus, anonymization of such data prior to transmission is essential. The 1997 Universal Declaration on the Human Genome and Human Rights of UNESCO addresses the participation of vulnerable persons. Researchers in charge of MDBs should ensure that information received on the testing of children or incompetent adults is subject to ethical review and approval in the country of origin. Caution should be taken against the involuntary consequences of public disclosure of results without complete explanation. Clear and enforceable regulations must be developed to protect the public against misuse of genetic databanks. Interaction with a databank could be seen as creating a "virtual" physician-patient relationship. However, interactive public MDBs should not give medical advice. We have identified new social ethical principles to govern different levels of complexity of genetic information. They are: reciprocity, mutuality, solidarity, and universality. Finally, precaution and prudence at this early stage of the MDI may not only avoid ethically inextricable conundrums but also provide for the respect for the rights

  13. A multi locus variable number of tandem repeat analysis (MLVA scheme for Streptococcus agalactiae genotyping

    Directory of Open Access Journals (Sweden)

    Mereghetti Laurent

    2011-07-01

    Full Text Available Abstract Background Multilocus sequence typing (MLST is currently the reference method for genotyping Streptococcus agalactiae strains, the leading cause of infectious disease in newborns and a major cause of disease in immunocompromised children and adults. We describe here a genotyping method based on multiple locus variable number of tandem repeat (VNTR analysis (MLVA applied to a population of S. agalactiae strains of various origins characterized by MLST and serotyping. Results We studied a collection of 186 strains isolated from humans and cattle and three reference strains (A909, NEM316 and 2603 V/R. Among 34 VNTRs, 6 polymorphic VNTRs loci were selected for use in genotyping of the bacterial population. The MLVA profile consists of a series of allele numbers, corresponding to the number of repeats at each VNTR locus. 98 MLVA genotypes were obtained compared to 51 sequences types generated by MLST. The MLVA scheme generated clusters which corresponded well to the main clonal complexes obtained by MLST. However it provided a higher discriminatory power. The diversity index obtained with MLVA was 0.960 compared to 0.881 with MLST for this population of strains. Conclusions The MLVA scheme proposed here is a rapid, cheap and easy genotyping method generating results suitable for exchange and comparison between different laboratories and for the epidemiologic surveillance of S. agalactiae and analyses of outbreaks.

  14. Development of multiple-locus variable-number tandem-repeat analysis for rapid genotyping of Ehrlichia ruminantium and its application to infected Amblyomma variegatum collected in heartwater endemic areas in Uganda.

    Science.gov (United States)

    Nakao, Ryo; Morrison, Liam J; Zhou, Lijia; Magona, Joseph W; Jongejan, Frans; Sugimoto, Chihiro

    2012-01-01

    The rickettsial bacterium Ehrlichia ruminantium is the causative agent of heartwater, a serious tick-borne disease in ruminants. The genetic diversity of organisms in the field will have implications for cross-protective capacities of any vaccine developed, and for an effective vaccine design strategy proper genotyping and understanding of existing genetic diversity in the field is necessary. We searched for variable-number tandem-repeat (VNTR) loci for use in a multi-locus VNTR analysis (MLVA). Sequencing analysis of 30 potential VNTRs using a panel of 17 reference strains from geographically diverse origins identified 12 VNTRs with allelic profiles differing between strains. Application of MLVA to 38 E. ruminantium-infected Amblyomma variegatum collected from indigenous cattle in 6 different districts of Uganda identified 21 MLVA types. The discriminatory power of MLVA was greater than that of map1 PCR-restriction fragment length polymorphism analysis, with which only 6 genotypes were obtained. The high discriminatory power as well as cost- effective performance of MLVA provide the potential for this technique to be applied in the future with respect to optimizing vaccine trials by identifying local strain diversity, and also raise the possibility of exploring the association between E. ruminantium genotypes and phenotypes such as pathological outcome in the ruminant host.

  15. The polymorphism of dopamine receptor D4 (DRD4) and dopamine transporter (DAT) genes in the men with antisocial behaviour and mixed martial arts fighters.

    Science.gov (United States)

    Cherepkova, Elena V; Maksimov, Vladimir N; Kushnarev, Alexandr P; Shakhmatov, Igor I; Aftanas, Lyubomir I

    2017-09-12

    Variable-number tandem repeat (VNTR) polymorphisms of DRD4 and DAT genes were studied in the Russian and Chechen men convicted of crimes, and two control groups comprised of the MMA fighters and a sample of general population. A group of MMA fighters included only the subjects without history of antisocial behaviour. DNA was isolated by phenol-chloroform extraction from the blood. Genotyping VNTR polymorphisms of the DRD4 and DAT genes were performed by PCR on published methods. Among those convicted of felonies and most grave crimes, carriers of DRD4 long alleles are found more frequently, similarly to the cohort of MMA fighters (lacking criminal record in both paternal lines). The 9/9 DAT genotype carriers are more frequently encountered among the habitual offenders. A frequency of the combination of the DRD4 genotype 4/7 and DAT genotype 10/10 is clearly higher among the convicts of violent crimes and the MMA fighters. One can speculate the presence of a 'controlled aggression' without a predisposition to pathological violence in the MMA fighters. Our study supports the hypothesis of genetic predisposition to different variants of extreme behaviour mediated by genetic determinants involved in the functioning of neuromediator systems including those controlling dopamine pathways.

  16. Transcription Factor Activating Protein-2β (TFAP-2β) genotype and symptoms of attention deficit hyperactivity disorder in relation to symptoms of depression in two independent samples.

    Science.gov (United States)

    Nilsson, Kent W; Sonnby, Karin; Nordquist, Niklas; Comasco, Erika; Leppert, Jerzy; Oreland, Lars; Sjöberg, Rickard L

    2014-04-01

    The Transcription Factor Activating Protein-2β (TFAP-2β) gene has been shown to influence monoaminergic neurotransmission, and several genes important for monoaminergic function have binding sites for TFAP-2β. Familial studies of attention deficit hyperactivity disorder (ADHD) suggest a hereditary-determined subtype of ADHD with comorbid depression. We examined a functional variation of the TFAP-2β gene in the context of co-occurring symptoms of ADHD and depression in two independent population-based samples of adolescents (Group A, n = 175 and Group B, n = 1,506) from Sweden. Results indicated 6.1 to 7.8% of adolescents screened positively for ADHD and depression symptoms. Symptoms of depression were more common among girls who screened positively for ADHD and did not carry the nine-repeat allele of the TFAP-2β intron 1 Variable Number Tandem Repeat (VNTR) polymorphism. The presence of the nine-repeat variant of the TFAP-2β intron 1 VNTR appears to protect girls with ADHD symptoms from the co-expression of symptoms of depression.

  17. Evaluation of the discriminatory power of variable number of tandem repeat typing of Mycobacterium bovis isolates from southern Africa.

    Science.gov (United States)

    Hlokwe, T M; van Helden, P; Michel, A

    2013-11-01

    The usefulness of variable number tandem repeat (VNTR) typing based on limited numbers of loci has previously proven inferior compared to IS6110-RFLP typing when applied to the study of the molecular epidemiology of bovine tuberculosis (BTB) in both livestock and wildlife in southern Africa. In this study, the discriminatory power of 29 published VNTR loci in the characterization of 131 Mycobacterium bovis strains isolated predominantly from wildlife and a smaller number from livestock in southern Africa was assessed. Allelic diversities calculated when loci were evaluated on a selected panel of 23 M. bovis isolates with identified varying degrees of genetic relatedness from different geographic origins as well as M. bovis BCG ranged from 0.00 to 0.63. Of the 29 loci tested, 13 were polymorphic (QUB 11a, QUB 11b, QUB 18, ETR-B and -C, Mtub 21, MIRU 16 and 26, ETR-E, QUB 26, MIRU 23, ETR-A, and Mtub 12). In addition, a comparative evaluation of the 13 loci on a panel of 65 isolates previously characterized by IS6110 restriction fragment length polymorphism (RFLP) typing and further evaluation on 41 isolates with no typing history from Kruger National Park (KNP) highlighted that M. bovis from epidemiologically unrelated cases of BTB in different geographic regions can be adequately distinguished. However, there is a need for improvement of the method to fully discriminate between the parental KNP strain and its clones to allow the detection of evolutionary events causing transmission between and within wildlife species.

  18. Candidate-gene approach in posttraumatic stress disorder after urban violence: association analysis of the genes encoding serotonin transporter, dopamine transporter, and BDNF.

    Science.gov (United States)

    Valente, Nina Leão Marques; Vallada, Homero; Cordeiro, Quirino; Miguita, Karen; Bressan, Rodrigo Affonseca; Andreoli, Sergio Baxter; Mari, Jair Jesus; Mello, Marcelo Feijó

    2011-05-01

    Posttraumatic stress disorder (PTSD) is a prevalent, disabling anxiety disorder marked by behavioral and physiologic alterations which commonly follows a chronic course. Exposure to a traumatic event constitutes a necessary, but not sufficient, factor. There is evidence from twin studies supporting a significant genetic predisposition to PTSD. However, the precise genetic loci still remain unclear. The objective of the present study was to identify, in a case-control study, whether the brain-derived neurotrophic factor (BDNF) val66met polymorphism (rs6265), the dopamine transporter (DAT1) three prime untranslated region (3'UTR) variable number of tandem repeats (VNTR), and the serotonin transporter (5-HTTPRL) short/long variants are associated with the development of PTSD in a group of victims of urban violence. All polymorphisms were genotyped in 65 PTSD patients as well as in 34 victims of violence without PTSD and in a community control group (n = 335). We did not find a statistical significant difference between the BDNF val66met and 5-HTTPRL polymorphism and the traumatic phenotype. However, a statistical association was found between DAT1 3'UTR VNTR nine repeats and PTSD (OR = 1.82; 95% CI, 1.20-2.76). This preliminary result confirms previous reports supporting a susceptibility role for allele 9 and PTSD.

  19. DNA-based genetic markers for Rapid Cycling Brassica rapa (Fast Plants type designed for the teaching laboratory.

    Directory of Open Access Journals (Sweden)

    Eryn E. Slankster

    2012-06-01

    Full Text Available We have developed DNA-based genetic markers for rapid-cycling Brassica rapa (RCBr, also known as Fast Plants. Although markers for Brassica rapa already exist, ours were intentionally designed for use in a teaching laboratory environment. The qualities we selected for were robust amplification in PCR, polymorphism in RCBr strains, and alleles that can be easily resolved in simple agarose slab gels. We have developed two single nucleotide polymorphism (SNP based markers and 14 variable number tandem repeat (VNTR-type markers spread over four chromosomes. The DNA sequences of these markers represent variation in a wide range of genomic features. Among the VNTR-type markers, there are examples of variation in a nongenic region, variation within an intron, and variation in the coding sequence of a gene. Among the SNP-based markers there are examples of polymorphism in intronic DNA and synonymous substitution in a coding sequence. Thus these markers can serve laboratory exercises in both transmission genetics and molecular biology.

  20. [A feasibility analysis on individualized acupuncture treatment of irritable bowel syndrome under help of genetic polymorphism technique].

    Science.gov (United States)

    Wu, Xiao-Liang; Sun, Jian-Hua; Liu, Lan-Ying; Fu, Hai-Yang; Jiao, Dai-Yan; Shu, Yan-Ye; Chen, Dong; Liu, Cheng-Yong; Zhan, Dao-Wei; Zhang, Wei

    2014-06-01

    Along with the application of genetic polymorphism techniques to individualized treatment of clinical disorders, the screening of polymorphisms markers of serotonin (5-HT) transporter (SERT) is a hot-spot of researches on irritable bowel syndrome (IBS). In the present paper, the authors introduce 1) optimized schemes of diagnosis and treatment of IBS on the basis of syndrome-differentiation for acupuncture in combination with Chinese herbal medicines, and application of 5-HT transporter polymorphism, 2) application of genetic polymorphism to researches on IBS, and 3) feasibility of genetic polymorphism techniques for guiding individualized treatment of IBS. Up to now, serotonin transporter length polymorphic region (5-HTTLPR), serotonin transporter intron 2 variable number of tandem repeat (Stin 2 VNTR) and single nucleotide polymorphism rs 25531 in the long allele of the 5-HTTLPR have been identified. On the basis of the treatment of IBS, we need establishing a set of guide lines for the individualized acupuncture treatment. The genotyping methods for genetic polymorphism should be widely used in this research field. 5-HT TLPR/ Stin 2 VNTR/rs 25531 polymorphisms would have a bright future in the field of IBS research and treatment.

  1. Cooperation of Adhesin Alleles in Salmonella-Host Tropism

    Science.gov (United States)

    De Masi, Leon; Yue, Min; Hu, Changmin; Rakov, Alexey V.; Rankin, Shelley C.

    2017-01-01

    ABSTRACT Allelic combinations and host specificities for three fimbrial adhesins, FimH, BcfD, and StfH, were compared for 262 strains of Salmonella enterica serovar Newport, a frequent human and livestock pathogen. Like FimH, BcfD had two major alleles (designated A and B), whereas StfH had two allelic groups, each with two alleles (subgroup A1 and A2 and subgroup B1 and B2). The most prevalent combinations of FimH/BcfD/StfH alleles in S. Newport were A/A/A1 and B/B/B1. The former set was most frequently found in bovine and porcine strains, whereas the latter combination was most frequently found in environmental and human isolates. Bacteria genetically engineered to express Fim, Bcf, or Stf fimbriae on their surface were tested with the different alleles for binding to human, porcine, and bovine intestinal epithelial cells. The major allelic combinations with bovine and porcine strains (A/A/A1) or with human isolates (B/B/B1) provided at least two alleles capable of binding significantly better than the other alleles to an intestinal epithelial cell line from the respective host(s). However, each combination of alleles kept at least one allele mediating binding to an intestinal epithelial cell from another host. These findings indicated that allelic variation in multiple adhesins of S. Newport contributes to bacterial adaptation to certain preferential hosts without losing the capacity to maintain a broad host range. IMPORTANCE Salmonella enterica remains a leading foodborne bacterial pathogen in the United States; infected livestock serve often as the source of contaminated food products. A study estimated that over a billion Salmonella gastroenteritis cases and up to 33 million typhoid cases occur annually worldwide, with 3.5 million deaths. Although many Salmonella strains with a broad host range present preferential associations with certain host species, it is not clear what determines the various levels of host adaptation. Here, causal properties of host

  2. The executive function in Han Chinese children with Tourette's syndrome and its association with the polymorphism of DRD4exonIII48bp VNTR%抽动秽语综合征汉族患者的执行功能及与多巴胺D4受体第3外显子48bp可重复序列多态性

    Institute of Scientific and Technical Information of China (English)

    季卫东; 周家秀; 杨闯; 黄晓琪; 姚静; 郭田友; 郭兰婷; 刘协和

    2010-01-01

    目的:了解多巴胺D4受体基因第3外显子48bp可重复序列多态性(DRD4 exonⅢ NTR)与抽动秽语综合征(Gilles de la Tourette syndrome,GTS)患者执行功能缺陷之间的关系.方法:对86例GTS患者进行威斯康星卡片测验(Modified Wisconsin Card sorting test,WCST)、Stroop色词测验(Stroop test)和连线测验,并和51例正常对照组进行比较;利用PCR技术对GTS患者进行了DRD4 exonⅢ 48bpVNTR分析.结果:与正常对照组比较,GTS组在Stroop测验中的C错误数[(44.39±65.3)vs.(20.50±10.85),P<0.01]等(包括C纠错数、C时间、CW正确数、CW错误数、CW纠错数和CW时间)、连线测验A时间[(69.80±25.84)vs.(35.69±8.25),P<0.01](包括连线B时间、错误数、犯规数)、WCST正确数[(44.39±65.37)vs.(27.49±10.85),P<0.01](错误数、持续错误数、非持续错误数和分类数)等测验项目上成绩较差,从共病情况来看,注意缺陷多动综合征共病组在Stroop测验部分项目上比单纯GTS组要差;从GTS组内分析来看,DRD4exonⅢ48bpVNTR和各神经心理学测验成绩没有关联.结论:抽动秽语综合征患者存在执行功能缺陷,DRD4exonⅢ 48bpVNTR和抽动秽语综合征执行功能缺陷之间可能没有关联.

  3. AllelicImbalance: An R/ bioconductor package for detecting, managing, and visualizing allele expression imbalance data from RNA sequencing

    DEFF Research Database (Denmark)

    Gådin, Jesper R.; van't Hooft, Ferdinand M.; Eriksson, Per

    2015-01-01

    Background: One aspect in which RNA sequencing is more valuable than microarray-based methods is the ability to examine the allelic imbalance of the expression of a gene. This process is often a complex task that entails quality control, alignment, and the counting of reads over heterozygous single......-nucleotide polymorphisms. Allelic imbalance analysis is subject to technical biases, due to differences in the sequences of the measured alleles. Flexible bioinformatics tools are needed to ease the workflow while retaining as much RNA sequencing information as possible throughout the analysis to detect and address...... the possible biases. Results: We present AllelicImblance, a software program that is designed to detect, manage, and visualize allelic imbalances comprehensively. The purpose of this software is to allow users to pose genetic questions in any RNA sequencing experiment quickly, enhancing the general utility...

  4. Assignment of SNP allelic configuration in polyploids using competitive allele-specific PCR: application to citrus triploid progeny

    Science.gov (United States)

    Cuenca, José; Aleza, Pablo; Navarro, Luis; Ollitrault, Patrick

    2013-01-01

    Background Polyploidy is a major component of eukaryote evolution. Estimation of allele copy numbers for molecular markers has long been considered a challenge for polyploid species, while this process is essential for most genetic research. With the increasing availability and whole-genome coverage of single nucleotide polymorphism (SNP) markers, it is essential to implement a versatile SNP genotyping method to assign allelic configuration efficiently in polyploids. Scope This work evaluates the usefulness of the KASPar method, based on competitive allele-specific PCR, for the assignment of SNP allelic configuration. Citrus was chosen as a model because of its economic importance, the ongoing worldwide polyploidy manipulation projects for cultivar and rootstock breeding, and the increasing availability of SNP markers. Conclusions Fifteen SNP markers were successfully designed that produced clear allele signals that were in agreement with previous genotyping results at the diploid level. The analysis of DNA mixes between two haploid lines (Clementine and pummelo) at 13 different ratios revealed a very high correlation (average = 0·9796; s.d. = 0·0094) between the allele ratio and two parameters [θ angle = tan−1 (y/x) and y′ = y/(x + y)] derived from the two normalized allele signals (x and y) provided by KASPar. Separated cluster analysis and analysis of variance (ANOVA) from mixed DNA simulating triploid and tetraploid hybrids provided 99·71 % correct allelic configuration. Moreover, triploid populations arising from 2n gametes and interploid crosses were easily genotyped and provided useful genetic information. This work demonstrates that the KASPar SNP genotyping technique is an efficient way to assign heterozygous allelic configurations within polyploid populations. This method is accurate, simple and cost-effective. Moreover, it may be useful for quantitative studies, such as relative allele-specific expression analysis and bulk segregant analysis

  5. [Future prospects of molecular epidemiology in tuberculosis].

    Science.gov (United States)

    Matsumoto, Tomoshige; Iwamoto, Tomotada

    2009-12-01

    Before the availability of high-resolution genotyping tools in 1990s, there was a prevailing dogma of little genomic sequence diversity in Mycobacterium tuberculosis. Due to the low levels of genetic variation, it was assumed that M. tuberculosis exhibit very little phenotypic variation in immunologic and virulence factors. The fingerprinting method based on restriction fragment length polymorphisms (RFLP) of IS6110 insertion sequences had unveiled the underestimation of the sequence variation in M. tuberculosis and the importance of strain-to-strain variation for understanding pathogenesis, immune mechanisms, bacterial evolution, and host adaptation. This method became a gold standard for strain differentiation in the molecular epidemiological study. It had lead to a profusion of studies in molecular epidemiology such as the detection of unsuspected transmission, the estimation of the extent of recent transmission, the identification of laboratory cross-contamination, the identification of outbreaks, and distinction between reinfection and relapse. This, in 1990s, is the opening of the molecular epidemiology of tuberculosis. After the completion of genome project of the M. tuberculosis laboratory strain H37Rv, some of the clinical isolates were completely sequenced. This prompted the in silico genome comparison and identified various genomic markers which can give a unifying framework for both epidemiology and evolutionary analysis of M. tuberculosis population. Of them, variable numbers of tandem repeats (VNTR) was found as the most promising PCR-based method which can provide adequate discrimination of M. tuberculosis strains in many cases, including the estimation of M. tuberculosis transmission and the identification of genetic lineages. PCR-based VNTR analysis is easy, rapid, and highly specific and can generate portable digit-based data, unlike the analog information obtained from IS6110 RFLP which is labor intensive. In this regards, investigators can

  6. Dopamine transporter DAT and receptor DRD2 variants affect risk of lethal cocaine abuse: a gene-gene-environment interaction.

    Science.gov (United States)

    Sullivan, D; Pinsonneault, J K; Papp, A C; Zhu, H; Lemeshow, S; Mash, D C; Sadee, W

    2013-01-22

    Epistatic gene-gene interactions could contribute to the heritability of complex multigenic disorders, but few examples have been reported. Here, we focus on the role of aberrant dopaminergic signaling, involving the dopamine transporter DAT, a cocaine target, and the dopamine D2 receptor, which physically interacts with DAT. Splicing polymorphism rs2283265 of DRD2, encoding D2 receptors, were shown to confer risk of cocaine overdose/death (odds ratio ∼3) in subjects and controls from the Miami Dade County Brain Bank.(1) Risk of cocaine-related death attributable to the minor allele of rs2283265 was significantly enhanced to OR=7.5 (P=0.0008) in homozygous carriers of the main 6-repeat allele of DAT rs3836790, a regulatory VNTR in intron8 lacking significant effect itself. In contrast, carriers of the minor 5-repeat DAT allele showed no significant risk (OR=1.1, P=0.84). DAT rs3836790 and DRD2 rs2283265 also interacted by modulating DAT protein activity in the ventral putamen of cocaine abusers. In high-linkage disequilibrium with the VNTR, DAT rs6347 in exon9 yielded similar results. Assessing the impact of DAT alone, a rare DAT haplotype formed by the minor alleles of rs3836790 and rs27072, a regulatory DAT variant in the 3'-UTR, occurred in nearly one-third of the cocaine abusers but was absent in African American controls, apparently conferring strong risk. These results demonstrate gene-gene-drug interaction affecting risk of fatal cocaine intoxication.

  7. Estimating and testing the effect of allelic recombination on the ...

    African Journals Online (AJOL)

    Jane

    2011-01-21

    Jan 21, 2011 ... Key words: Allele, genotype, regression, correlation, F-ratio, analysis of ... correlation coefficient. .... from their true values of the measurements using the ... We may also wish to test the null hypothesis that ... Uche PI (2004).

  8. Allelic exclusion of immunoglobulin genes: models and mechanisms.

    Science.gov (United States)

    Vettermann, Christian; Schlissel, Mark S

    2010-09-01

    The allelic exclusion of immunoglobulin (Ig) genes is one of the most evolutionarily conserved features of the adaptive immune system and underlies the monospecificity of B cells. While much has been learned about how Ig allelic exclusion is established during B-cell development, the relevance of monospecificity to B-cell function remains enigmatic. Here, we review the theoretical models that have been proposed to explain the establishment of Ig allelic exclusion and focus on the molecular mechanisms utilized by developing B cells to ensure the monoallelic expression of Ig kappa and Ig lambda light chain genes. We also discuss the physiological consequences of Ig allelic exclusion and speculate on the importance of monospecificity of B cells for immune recognition.

  9. Common breast cancer risk alleles and risk assessment

    DEFF Research Database (Denmark)

    Näslund-Koch, C; Nordestgaard, B G; Bojesen, S E

    2017-01-01

    BACKGROUND: We hypothesized that common breast cancer risk alleles are associated with incidences of breast cancer and other cancers in the general population, and identify low risk women among those invited for screening mammography. PARTICIPANTS AND METHODS: 35,441 individuals from the Danish...... general population were followed in Danish health registries for up to 21 years after blood sampling. After genotyping 72 breast cancer risk loci, each with 0-2 alleles, the sum for each individual was calculated. We used the simple allele sum instead of the conventional polygenic risk score......, as it is likely more sensitive in detecting associations with risks of other endpoints than breast cancer. RESULTS: Breast cancer incidence in the 19,010 women was increased across allele sum quintiles (log-rank trend test; p=1*10(-12)), but not incidence of other cancers (p=0.41). Age- and study-adjusted hazard...

  10. Sequencing of 15 new BoLA-DRB3 alleles.

    Science.gov (United States)

    Wang, K; Sun, D; Zhang, Y

    2008-08-01

    The class II DR of bovine major histocompatibility complex of cattle (BoLA) plays a central role in the regulation of the immune response through their ability to present those peptides to T-cell receptors. In this work, we sequenced the exon2 of DRB3 to identify new alleles in Chinese yellow cattle, a total of 15 new BoLA-DRB3 alleles were found.

  11. Robust identification of local adaptation from allele frequencies.

    Science.gov (United States)

    Günther, Torsten; Coop, Graham

    2013-09-01

    Comparing allele frequencies among populations that differ in environment has long been a tool for detecting loci involved in local adaptation. However, such analyses are complicated by an imperfect knowledge of population allele frequencies and neutral correlations of allele frequencies among populations due to shared population history and gene flow. Here we develop a set of methods to robustly test for unusual allele frequency patterns and correlations between environmental variables and allele frequencies while accounting for these complications based on a Bayesian model previously implemented in the software Bayenv. Using this model, we calculate a set of "standardized allele frequencies" that allows investigators to apply tests of their choice to multiple populations while accounting for sampling and covariance due to population history. We illustrate this first by showing that these standardized frequencies can be used to detect nonparametric correlations with environmental variables; these correlations are also less prone to spurious results due to outlier populations. We then demonstrate how these standardized allele frequencies can be used to construct a test to detect SNPs that deviate strongly from neutral population structure. This test is conceptually related to FST and is shown to be more powerful, as we account for population history. We also extend the model to next-generation sequencing of population pools-a cost-efficient way to estimate population allele frequencies, but one that introduces an additional level of sampling noise. The utility of these methods is demonstrated in simulations and by reanalyzing human SNP data from the Human Genome Diversity Panel populations and pooled next-generation sequencing data from Atlantic herring. An implementation of our method is available from http://gcbias.org.

  12. Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis

    DEFF Research Database (Denmark)

    Jacobsen, Soren; Baslund, Bo; Madsen, Hans O.

    2002-01-01

    OBJECTIVE: To determine whether variant alleles of the mannose-binding lectin (MBL) gene causing low serum concentrations of MBL and/or polymorphisms of HLA-DRB1 are associated with increased susceptibility to polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) or particular clinical...... phenotypes of PMR/GCA. METHODS: MBL and HLA-DRB1 alleles were determined by polymerase chain reaction in 102 Danish patients with PMR (n = 37) or GCA (n = 65). Two hundred fifty and 193 healthy individuals served as controls for MBL and HLA genotyping, respectively. RESULTS: The prevalence of MBL variant...... alleles in controls, patients with PMR only, and patients with GCA was 37, 32, and 53% (p = 0.01), respectively. HLA-DRB1*04 was found in 47% of patients with PMR only and in 54% of patients with GCA, which differed significantly from the 35% found in controls (p = 0.01). HLA-DR4 alleles were...

  13. Distribution of BoLA-DRB3 allelic frequencies and identification of two new alleles in Iranian buffalo breed.

    Science.gov (United States)

    Mosafer, J; Heydarpour, M; Manshad, E; Russell, G; Sulimova, G E

    2012-01-01

    The role of the major histocompatibility complex (MHC) in the immune response makes it an attractive candidate gene for associations with disease resistance and susceptibility. This study describes genetic variability in the BoLA-DRB3 in Iranian buffaloes. Heminested PCR-RFLP method was used to identify the frequency of BoLA-DRB3 alleles. The BoLA-DRB3 locus is highly polymorphic in the study herd (12 alleles). Almost 63.50% of the alleles were accounted for by four alleles (BoLA-DRB3.2 ∗48, ∗20, ∗21, and obe) in Iranian buffalo. The DRB3.2 ∗48 allele frequency (24.20%) was higher than the others. The frequencies of the DRB3.2 ∗20 and DRB3.2 ∗21 are 14.52 and 14.00, respectively, and obe and gbb have a new pattern. Significant distinctions have been found between Iranian buffalo and other cattle breed studied. In the Iranian buffaloes studied alleles associated with resistance to various diseases are found.

  14. Distribution of BoLA-DRB3 Allelic Frequencies and Identification of Two New Alleles in Iranian Buffalo Breed

    Directory of Open Access Journals (Sweden)

    J. Mosafer

    2012-01-01

    Full Text Available The role of the major histocompatibility complex (MHC in the immune response makes it an attractive candidate gene for associations with disease resistance and susceptibility. This study describes genetic variability in the BoLA-DRB3 in Iranian buffaloes. Heminested PCR-RFLP method was used to identify the frequency of BoLA-DRB3 alleles. The BoLA-DRB3 locus is highly polymorphic in the study herd (12 alleles. Almost 63.50% of the alleles were accounted for by four alleles (BoLA-DRB3.2 *48, *20, *21, and obe in Iranian buffalo. The DRB3.2 *48 allele frequency (24.20% was higher than the others. The frequencies of the DRB3.2 *20 and DRB3.2 *21 are 14.52 and 14.00, respectively, and obe and gbb have a new pattern. Significant distinctions have been found between Iranian buffalo and other cattle breed studied. In the Iranian buffaloes studied alleles associated with resistance to various diseases are found.

  15. How the Number of Alleles Influences Gene Expression

    Science.gov (United States)

    Hat, Beata; Paszek, Pawel; Kimmel, Marek; Piechor, Kazimierz; Lipniacki, Tomasz

    2007-07-01

    The higher organisms, eukaryotes, are diploid and most of their genes have two homological copies (alleles). However, the number of alleles in a cell is not constant. In the S phase of the cell cycle all the genome is duplicated and then in the G2 phase and mitosis, which together last for several hours, most of the genes have four copies instead of two. Cancer development is, in many cases, associated with a change in allele number. Several genetic diseases are caused by haploinsufficiency: Lack of one of the alleles or its improper functioning. In the paper we consider the stochastic expression of a gene having a variable number of copies. We applied our previously developed method in which the reaction channels are split into slow (connected with change of gene state) and fast (connected with mRNA/protein synthesis/decay), the later being approximated by deterministic reaction rate equations. As a result we represent gene expression as a piecewise deterministic time-continuous Markov process, which is further related with a system of partial differential hyperbolic equations for probability density functions (pdfs) of protein distribution. The stationary pdfs are calculated analytically for haploidal gene or numerically for diploidal and tetraploidal ones. We distinguished nine classes of simultaneous activation of haploid, diploid and tetraploid genes. This allows for analysis of potential consequences of gene duplication or allele loss. We show that when gene activity is autoregulated by a positive feedback, the change in number of gene alleles may have dramatic consequences for its regulation and may not be compensated by the change of efficiency of mRNA synthesis per allele.

  16. Attention Deficit Hyperactivity Disorder comorbid oppositional defiant disorder and its predominately inattentive type: evidence for an association with COMT but not MAOA in a Chinese sample

    Directory of Open Access Journals (Sweden)

    Wang Yu-Feng

    2009-02-01

    Full Text Available Abstract Background There are three childhood disruptive behavior disorders (DBDs, attention deficit hyperactivity disorder (ADHD, oppositional defiant disorder (ODD, and conduct disorder (CD. The most common comorbid disorder in ADHD is ODD. DSM-IV describes three ADHD subtypes: predominantly inattentive type (ADHD-IA, predominantly hyperactive-impulsive type (ADHD-HI, and combined type (ADHD-C. Prior work suggests that specific candidate genes are associated with specific subtypes of ADHD in China. Our previous association studies between ADHD and functional polymorphisms of COMT and MAOA, consistently showed the low transcriptional activity alleles were preferentially transmitted to ADHD-IA boys. Thus, the goal of the present study is to test the hypothesis that COMT Val158Met and MAOA-uVNTR jointly contribute to the ODD phenotype among Chinese ADHD boys. Methods 171 Chinese boys between 6 and 17.5 years old (mean = 10.3, SD = 2.6 with complete COMT val158met and MAOA-uVNTR genotyping information were studied. We used logistic regression with genotypes as independent variables and the binary phenotype as the dependent variable. We used p Results Our results highlight the potential etiologic role of COMT in the ADHD with comorbid ODD and its predominately inattentive type in male Chinese subjects. ADHD with comorbid ODD was associated with homozygosity of the high-activity Val allele, while the predominantly inattentive ADHD subtype was associated with the low-activity Met allele. We found no evidence of association between the MAOA-uVNTR variant and ADHD with comorbid ODD or the ADHD-IA subtype. Conclusion Our study of attention deficit hyperactivity disorder comorbid oppositional defiant disorder and its predominately inattentive type highlights the potential etiologic role of COMT for ADHD children in China. But we failed to observe an interaction between COMT and MAOA, which suggests that epistasis between COMT and MAOA genes does not

  17. PER3 polymorphism predicts cumulative sleep homeostatic but not neurobehavioral changes to chronic partial sleep deprivation.

    Directory of Open Access Journals (Sweden)

    Namni Goel

    Full Text Available BACKGROUND: The variable number tandem repeat (VNTR polymorphism 5-repeat allele of the circadian gene PERIOD3 (PER3(5/5 has been associated with cognitive decline at a specific circadian phase in response to a night of total sleep deprivation (TSD, relative to the 4-repeat allele (PER3(4/4. PER3(5/5 has also been related to higher sleep homeostasis, which is thought to underlie this cognitive vulnerability. To date, no study has used a candidate gene approach to investigate the response to chronic partial sleep deprivation (PSD, a condition distinct from TSD and one commonly experienced by millions of people on a daily and persistent basis. We evaluated whether the PER3 VNTR polymorphism contributed to cumulative neurobehavioral deficits and sleep homeostatic responses during PSD. METHODOLOGY/PRINCIPAL FINDINGS: PER3(5/5 (n = 14, PER3(4/5 (n = 63 and PER3(4/4 (n = 52 healthy adults (aged 22-45 y demonstrated large, but equivalent cumulative decreases in cognitive performance and physiological alertness, and cumulative increases in sleepiness across 5 nights of sleep restricted to 4 h per night. Such effects were accompanied by increasing daily inter-subject variability in all groups. The PER3 genotypes did not differ significantly at baseline in habitual sleep, physiological sleep structure, circadian phase, physiological sleepiness, cognitive performance, or subjective sleepiness, although during PSD, PER3(5/5 subjects had slightly but reliably elevated sleep homeostatic pressure as measured physiologically by EEG slow-wave energy in non-rapid eye movement sleep compared with PER3(4/4 subjects. PER3 genotypic and allelic frequencies did not differ significantly between Caucasians and African Americans. CONCLUSIONS/SIGNIFICANCE: The PER3 VNTR polymorphism was not associated with individual differences in neurobehavioral responses to PSD, although it was related to one marker of sleep homoeostatic response during PSD. The comparability of PER3

  18. A platform for interrogating cancer-associated p53 alleles.

    Science.gov (United States)

    D'Brot, A; Kurtz, P; Regan, E; Jakubowski, B; Abrams, J M

    2017-01-12

    p53 is the most frequently mutated gene in human cancer. Compelling evidence argues that full transformation involves loss of growth suppression encoded by wild-type p53 together with poorly understood oncogenic activity encoded by missense mutations. Furthermore, distinguishing disease alleles from natural polymorphisms is an important clinical challenge. To interrogate the genetic activity of human p53 variants, we leveraged the Drosophila model as an in vivo platform. We engineered strains that replace the fly p53 gene with human alleles, producing a collection of stocks that are, in effect, 'humanized' for p53 variants. Like the fly counterpart, human p53 transcriptionally activated a biosensor and induced apoptosis after DNA damage. However, all humanized strains representing common alleles found in cancer patients failed to complement in these assays. Surprisingly, stimulus-dependent activation of hp53 occurred without stabilization, demonstrating that these two processes can be uncoupled. Like its fly counterpart, hp53 formed prominent nuclear foci in germline cells but cancer-associated p53 variants did not. Moreover, these same mutant alleles disrupted hp53 foci and inhibited biosensor activity, suggesting that these properties are functionally linked. Together these findings establish a functional platform for interrogating human p53 alleles and suggest that simple phenotypes could be used to stratify disease variants.

  19. Fitness costs associated with evolved herbicide resistance alleles in plants.

    Science.gov (United States)

    Vila-Aiub, Martin M; Neve, Paul; Powles, Stephen B

    2009-12-01

    Predictions based on evolutionary theory suggest that the adaptive value of evolved herbicide resistance alleles may be compromised by the existence of fitness costs. There have been many studies quantifying the fitness costs associated with novel herbicide resistance alleles, reflecting the importance of fitness costs in determining the evolutionary dynamics of resistance. However, many of these studies have incorrectly defined resistance or used inappropriate plant material and methods to measure fitness. This review has two major objectives. First, to propose a methodological framework that establishes experimental criteria to unequivocally evaluate fitness costs. Second, to present a comprehensive analysis of the literature on fitness costs associated with herbicide resistance alleles. This analysis reveals unquestionable evidence that some herbicide resistance alleles are associated with pleiotropic effects that result in plant fitness costs. Observed costs are evident from herbicide resistance-endowing amino acid substitutions in proteins involved in amino acid, fatty acid, auxin and cellulose biosynthesis, as well as enzymes involved in herbicide metabolism. However, these resistance fitness costs are not universal and their expression depends on particular plant alleles and mutations. The findings of this review are discussed within the context of the plant defence trade-off theory and herbicide resistance evolution.

  20. Identification and characterization of variant alleles at CODIS STR loci.

    Science.gov (United States)

    Allor, Catherine; Einum, David D; Scarpetta, Marco

    2005-09-01

    Short tandem repeat (STR) profiles from 32,671 individuals generated by the ABI Profiler Plus and Cofiler systems were screened for variant alleles not represented within manufacturer-provided allelic ladders. A total of 85 distinct variants were identified at 12 of the 13 CODIS loci, most of which involve a truncated tetranucleotide repeat unit. Twelve novel alleles, identified at D3S1358, FGA, D18S51, D5S818, D7S820 and TPOX, were confirmed by nucleotide sequence analysis and include both insertions and deletions involving the repeat units themselves as well as DNA flanking the repeat regions. Population genetic data were collected for all variants and frequencies range from 0.0003 (many single observations) to 0.0042 (D7S820 '10.3' in North American Hispanics). In total, the variant alleles identified in this study are carried by 1.6% of the estimated 1 million individuals tested annually in the U.S. for the purposes of parentage resolution. A paternity case involving a recombination event of paternal origin is presented and demonstrates how variant alleles can significantly strengthen the genetic evidence in troublesome cases. In such instances, increased costs and turnaround time associated with additional testing may be eliminated.

  1. STR allele sequence variation: Current knowledge and future issues.

    Science.gov (United States)

    Gettings, Katherine Butler; Aponte, Rachel A; Vallone, Peter M; Butler, John M

    2015-09-01

    This article reviews what is currently known about short tandem repeat (STR) allelic sequence variation in and around the twenty-four loci most commonly used throughout the world to perform forensic DNA investigations. These STR loci include D1S1656, TPOX, D2S441, D2S1338, D3S1358, FGA, CSF1PO, D5S818, SE33, D6S1043, D7S820, D8S1179, D10S1248, TH01, vWA, D12S391, D13S317, Penta E, D16S539, D18S51, D19S433, D21S11, Penta D, and D22S1045. All known reported variant alleles are compiled along with genomic information available from GenBank, dbSNP, and the 1000 Genomes Project. Supplementary files are included which provide annotated reference sequences for each STR locus, characterize genomic variation around the STR repeat region, and compare alleles present in currently available STR kit allelic ladders. Looking to the future, STR allele nomenclature options are discussed as they relate to next generation sequencing efforts underway.

  2. Multilocus typing and population structure of Cryptosporidium from children in Zaragoza, Spain.

    Science.gov (United States)

    Ramo, Ana; Quílez, Joaquín; Vergara-Castiblanco, Claudia; Monteagudo, Luis; Del Cacho, Emilio; Clavel, Antonio

    2015-04-01

    A multilocus typing approach with eight variable-number tandem-repeat (VNTR) loci and the GP60 gene was used to analyze the inter- and intra-species variation of 44 Cryptosporidium isolates from pediatric patients in Zaragoza city (NE, Spain). Restriction and sequence analyses of the SSU rRNA gene revealed that Cryptosporidium transmission is mostly anthroponotic in this area, with the predominance of Cryptosporidium hominis (n: 41) over Cryptosporidium parvum (n: 3). GP60 subtyping showed limited genetic diversity and four subtypes were identified, including IbA10G2 (n: 35), IaA24R3 (n: 6), IIaA15G1R1 (n: 1) and IIaA15G2R1 (n: 2). Five out of eight VNTR loci showed a discriminatory power higher than the GP60 gene, although each locus had a predominant allele exhibited by more than 50% of isolates. All but four alleles were associated to either C. hominis or C. parvum and linked alleles at different loci were found. Multilocus typing substantially increased the discriminatory power (Hunter-Gaston index: 0.807, 95% CI, 0.683-0.926) and revealed that genetic diversity is much higher than that reported by GP60 sequencing, since 17 multilocus subtypes (MLTs) were identified. Nearly half of the specimens were allocated to a single major MLT. However, no more than three specimens were allocated to each of the remaining MLTs. Both phylogenetic and population analyses revealed a population clustering of C. hominis according to the GP60 subtype, which indicates the robustness of this marker to differentiate genetic subpopulations. Subpopulations had an overall clonal genetic structure, although traces of genetic flow between them were also observed.

  3. DNA Methyltransferase 3B Gene Promoter and Interleukin-1 Receptor Antagonist Polymorphisms in Childhood Immune Thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Margarita Pesmatzoglou

    2012-01-01

    Full Text Available Primary immune thrombocytopenia (ITP is one of the most common blood diseases as well as the commonest acquired bleeding disorder in childhood. Although the etiology of ITP is unclear, in the pathogenesis of the disease, both environmental and genetic factors including polymorphisms of TNF-a, IL-10, and IL-4 genes have been suggested to be involved. In this study, we investigated the rs2424913 single-nucleotide polymorphism (SNP (C46359T in DNA methyltransferase 3B (DNMT3B gene promoter and the VNTR polymorphism of IL-1 receptor antagonist (IL-1 Ra intron-2 in 32 children (17 boys with the diagnosis of ITP and 64 healthy individuals. No significant differences were found in the genotype distribution of DNMT3B polymorphism between the children with ITP and the control group, whereas the frequency of allele T appeared significantly increased in children with ITP (P = 0.03, OR = 2, 95% CI: 1.06–3.94. In case of IL-1 Ra polymorphism, children with ITP had a significantly higher frequency of genotype I/II, compared to control group (P = 0.043, OR = 2.60, 95% CI: 1.02–6.50. Moreover, genotype I/I as well as allele I was overrepresented in the control group, suggesting that allele I may have a decreased risk for development of ITP. Our findings suggest that rs2424913 DNMT3B SNP as well as IL-1 Ra VNTR polymorphism may contribute to the susceptibility to ITP.

  4. High-Throughput Mycobacterial Interspersed Repetitive-Unit–Variable-Number Tandem-Repeat Genotyping for Mycobacterium tuberculosis Epidemiological Studies

    Science.gov (United States)

    Bidault, Floriane; Mosnier, Amandine; Bablishvili, Nino; Tukvadze, Nestani; Somphavong, Silaphet; Paboriboune, Phimpha; Ocheretina, Oksana; Pape, Jean William; Paranhos-Baccala, Glaucia; Berland, Jean-Luc

    2014-01-01

    The emergence of drug-resistant forms of tuberculosis (TB) represents a major public health concern. Understanding the transmission routes of the disease is a key factor for its control and for the implementation of efficient interventions. Mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) marker typing is a well-described method for lineage identification and transmission tracking. However, the conventional manual genotyping technique is cumbersome and time-consuming and entails many risks for errors, thus hindering its implementation and dissemination. We describe here a new approach using the QIAxcel system, an automated high-throughput capillary electrophoresis system that also carries out allele calling. This automated method was assessed on 1,824 amplicons from 82 TB isolates and tested with sets of markers of 15 or 24 loci. Overall allele-calling concordance between the methods from 140 to 1,317 bp was 98.9%. DNA concentrations and repeatability and reproducibility performances showed no biases in allele calling. Furthermore, turnaround time using this automated system was reduced by 81% compared to the conventional manual agarose gel method. In sum, this new automated method facilitates MIRU-VNTR genotyping and provides reliable results. Therefore, it is well suited for field genotyping. The implementation of this method will help to achieve accurate and cost-effective epidemiological studies, especially in countries with a high prevalence of TB, where the high number of strains complicates the surveillance of circulating lineages and requires efficient interventions to be carried out in an urgent manner. PMID:25428144

  5. Implication of HLA-DMA Alleles in Corsican IDDM

    Directory of Open Access Journals (Sweden)

    P. Cucchi-Mouillot

    1998-01-01

    Full Text Available The HLA-DM molecule catalyses the CLIP/antigen peptide exchange in the classical class II peptide-binding groove. As such, DM is an antigen presentation regulator and may be linked to autoimmune diseases. Using PCR derived methods, a relationship was revealed between DM gene polymorphism and IDDM, in a Corsican population. The DMA*0101 allele was observed to confer a significant predisposition to this autoimmune disease while the DMA*0102 allele protected significantly. Experiments examining polymorphism of the HLA-DRB1 gene established that these relationships are not a consequence of linkage disequilibrium with HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore be an additional tool for early IDDM diagnosis in the Corsican population.

  6. Genetic Diversity Based on Allozyme Alleles of Chinese Cultivated Rice

    Institute of Scientific and Technical Information of China (English)

    TANG Sheng-xiang; WEI Xing-hua; JIANG Yun-zhu; D S Brar; G S Khush

    2007-01-01

    Genetic diversity was analyzed with 6 632 core rice cultivars selected from 60 282 Chinese rice accessions on the basis of 12 allozyme loci, Pgil, Pgi2, Ampl, Amp2, Amp3, Amp4, Sdh1, Adh1, Est1, Est2, Est5 and Est9, by starch gel electrophoresis. Among the materials examined, 52 alleles at 12 polymorphic loci were identified, which occupied 96.3% of 54 alleles found in cultivated germplasm of O.sativa L. The number of alleles per locus ranged from 2 to 7 with an average of 4.33. The gene diversity (He) each locus varied considerably from 0.017 for Amp4 to 0.583 for Est2 with an average gene diversity (Ht) 0.271, and Shannon-Wiener index from 0.055 to 0.946 with an average of 0.468. The degree of polymorphism (DP) was in a range from 0.9 to 46.9% with an average of 21.4%. It was found that the genetic diversity in japonica (Keng) subspecies was lower in terms of allele's number, Ht and S-W index, being 91.8, 66.2 and 75.7% of indica (Hsien) one, respectively. Significant genetic differentiation between indica and japonica rice has been appeared in the loci Pgil, Amp2, Pgi2, and Est2, with higher average coefficient of genetic differentiation (Gst) 0.635, 0.626, 0.322 and 0.282, respectively. Except less allele number per locus (3.33) for modern cultivars, being 76.9% of landraces, the Ht and S-W index showed in similar between the modern cultivars and the landraces detected. In terms of allozyme, the rice cultivars in the Southwest Plateau and Central China have richer genetic diversity. The present study reveals again that Chinese cultivated rice germplasm has rich genetic diversity, showed by the allozyme allele variation.

  7. A common mutation associated with the Duarte galactosemia allele

    Energy Technology Data Exchange (ETDEWEB)

    Elsas, L.J.; Dembure, P.P.; Langley, S.; Paulk, E.M.; Hjelm, L.N.; Fridovich-Keil, J. (Emory Univ. School of Medicine, Atlanta, GA (United States))

    1994-06-01

    The human cDNA and gene for galactose-1-phosphate uridyl transferase (GALT) have been cloned and sequenced. A prevalant mutation (Q188R) is known to cause classic galactosemia (G/G). G/G galactosemia has an incidence of 1/38,886 in 1,396,766 Georgia live-born infants, but a more common variant of galactosemia, Duarte, has an unknown incidence. The proposed Duarte biochemical phenotypes of GALT are as follows: D/N, D/D, and D/G, which have [approximately]75%, 50%, and 25% of normal GALT activity, respectively. In addition, the D allele has isoforms of its enzyme that have more acidic pI than normal. Here the authors systematically determine (a) the prevalence of an A-to-G transition at base pair 2744 of exon 10 in the GALT gene, a transition that produces a codon change converting asparagine to aspartic acid at position 314 (N314D), and (b) the association of this mutation with the Duarte biochemical phenotype. The 2744G nucleotide change adds an AvaII (SinI) cut site, which was identified in PCR-amplified DNA. In 111 biochemically unphenotyped controls with no history of galactosemia, 13 N314D alleles were identified (prevalence 5.9%). In a prospective study, 40 D alleles were biochemically phenotyped, and 40 N314D alleles were found. By contrast, in 36 individuals known not to have the Duarte biochemical phenotype, no N314D alleles were found. The authors conclude that the N314D mutation is a common allele that probably causes the Duarte GALT biochemical phenotype and occurs in a predominantly Caucasian, nongalactosemic population, with a prevalence of 5.9%. 36 refs., 3 figs., 2 tabs.

  8. A common allele on chromosome 9 associated with coronary heartdisease

    Energy Technology Data Exchange (ETDEWEB)

    McPherson, Ruth; Pertsemlidis, Alexander; Kavaslar, Nihan; Stewart, Alexandre; Roberts, Robert; Cox, David R.; Hinds, David; Pennachio, Len; Tybjaerg-Hansen, Anne; Folsom, Aaron R.; Boerwinkle,Eric; Hobbs, Helen H.; Cohen, Jonathan C.

    2007-03-01

    Coronary heart disease (CHD) is a major cause of death in Western countries. Here we used genome-wide association scanning to identify a 58 kb interval on chromosome 9 that was consistently associated with CHD in six independent samples. The interval contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension or diabetes. Homozygotes for the risk allele comprise 20-25% of Caucasians and have a {approx}30-40% increased risk of CHD. These data indicate that the susceptibility allele acts through a novel mechanism to increase CHD risk in a large fraction of the population.

  9. Reelin gene alleles and susceptibility to autism spectrum disorders.

    Science.gov (United States)

    Zhang, H; Liu, X; Zhang, C; Mundo, E; Macciardi, F; Grayson, D R; Guidotti, A R; Holden, J J A

    2002-01-01

    A polymorphic trinucleotide repeat (CGG/GCC) within the human Reelin gene (RELN) was examined as a candidate gene for autism spectrum disorders (ASDs). This gene encodes a large extracellular matrix protein that orchestrates neuronal positioning during corticogenesis. The CGG-repeat within the 5' untranslated region of RELN exon 1 was examined in 126 multiple-incidence families. The number of CGG repeats varied from three to 16 in affected individuals and controls, with no expansion or contraction observed during maternal (n = 291) or paternal (n = 287) transmissions in families with autistic probands. Although the frequencies of the RELN alleles and genotypes in affected children were not different from those in the comparison group, a family-based association test (FBAT) showed that the larger RELN alleles (> or = 11 repeats) were transmitted more often than expected to affected children (S = 43, E(S) = 34.5, P = 0.035); this was particularly the case for the 13-repeat RELN allele (S = 22, E(S) = 16, P = 0.034). Affected sib-pair (ASP) analysis found no evidence of excess sharing of RELN alleles in affected siblings. The impact of genotypes with large alleles (> or = 11 repeats) on the phenotypes in individuals with ASD was analyzed by ANOVA in a subset of the families for which results of the Autism Diagnostic Interview-Revised were available. Children with large RELN alleles did not show any difference in scores for questions related to the core symptoms of autistic disorder, but there was a tendency for children with at least one large RELN allele to have an earlier age at first phrase (chi(2) = 3.538, P = 0.06). Thus, although the case-control and affected sib-pair findings did not support a role for RELN in susceptibility to ASD, the more powerful family-based association study demonstrated that RELN alleles with larger numbers of CGG repeats may play a role in the etiology of some cases of ASD, especially in children without delayed phrase speech.

  10. [Allele-specific PCR and its application in forensic science].

    Science.gov (United States)

    Nie, Yan-chai; Wang, Bin; Zhao, Zi-qin; Zhou, Huai-gu

    2014-08-01

    Allele-specific polymerase chain reaction (AS-PCR) is a technique based on allele-specific primers, which can be used to analyze single nucleotide polymorphism (SNP) effectively including the transition, transversion and insertion/deletion polymorphism and has been exploited in the study of diseases research, molecular diagnosis, and forensic biological evidence. The article systematically reviews the principle, the detection methods, improvement of AS-PCR, and its research updates in the fields of autosome, Y chromosome and mitochondrial SNP, as well as its application in forensic science.

  11. Construction of a library of cloned short tandem repeat (STR) alleles as universal templates for allelic ladder preparation.

    Science.gov (United States)

    Wang, Le; Zhao, Xing-Chun; Ye, Jian; Liu, Jin-Jie; Chen, Ting; Bai, Xue; Zhang, Jian; Ou, Yuan; Hu, Lan; Jiang, Bo-Wei; Wang, Feng

    2014-09-01

    Short tandem repeat (STR) genotyping methods are widely used for human identity testing applications, including forensic DNA analysis. Samples of DNA containing the length-variant STR alleles are typically separated and genotyped by comparison to an allelic ladder. Here, we describe a newly devised library of cloned STR alleles. The library covers alleles X and Y for the sex-determining locus Amelogenin and 259 other alleles for 22 autosomal STR loci (TPOX, D3S1358, FGA, D5S818, CSF1PO, D7S820, D8S1179, TH01, vWA, D13S317, D16S539, D18S51, D21S11, D2S1338, D6S1043, D12S391, Penta E, D19S433, D11S4463, D17S974, D3S4529 and D12ATA63). New primers were designed for all these loci to construct recombinant plasmids so that the library retains core repeat elements of STR as well as 5'- and 3'-flanking sequences of ∼500 base pairs. Since amplicons of commercial STR genotyping kits and systems developed in laboratories are usually distributed from 50 to STR alleles. The sequencing results showed all repeat structures we obtained for TPOX, CSF1PO, D7S820, TH01, D16S539, D18S51 and Penta E were the same as reported. However, we identified 102 unreported repeat structures from the other 15 STR loci, supplementing our current knowledge of repeat structures and leading to further understanding of these widely used loci.

  12. Allelic drop-out probabilities estimated by logistic regression

    DEFF Research Database (Denmark)

    Tvedebrink, Torben; Eriksen, Poul Svante; Asplund, Maria

    2012-01-01

    We discuss the model for estimating drop-out probabilities presented by Tvedebrink et al. [7] and the concerns, that have been raised. The criticism of the model has demonstrated that the model is not perfect. However, the model is very useful for advanced forensic genetic work, where allelic dro...

  13. Haplotype allelic classes for detecting ongoing positive selection.

    Science.gov (United States)

    Hussin, Julie; Nadeau, Philippe; Lefebvre, Jean-François; Labuda, Damian

    2010-01-28

    Natural selection eliminates detrimental and favors advantageous phenotypes. This process leaves characteristic signatures in underlying genomic segments that can be recognized through deviations in allelic or haplotypic frequency spectra. To provide an identifiable signature of recent positive selection that can be detected by comparison with the background distribution, we introduced a new way of looking at genomic polymorphisms: haplotype allelic classes. The model combines segregating sites and haplotypic information in order to reveal useful data characteristics. We developed a summary statistic, Svd, to compare the distribution of the haplotypes carrying the selected allele with the distribution of the remaining ones. Coalescence simulations are used to study the distributions under standard population models assuming neutrality, demographic scenarios and selection models. To test, in practice, haplotype allelic class performance and the derived statistic in capturing deviation from neutrality due to positive selection, we analyzed haplotypic variation in detail in the locus of lactase persistence in the three HapMap Phase II populations. We showed that the Svd statistic is less sensitive than other tests to confounding factors such as demography or recombination. Our approach succeeds in identifying candidate loci, such as the lactase-persistence locus, as targets of strong positive selection and provides a new tool complementary to other tests to study natural selection in genomic data.

  14. Haplotype allelic classes for detecting ongoing positive selection

    Directory of Open Access Journals (Sweden)

    Lefebvre Jean-François

    2010-01-01

    Full Text Available Abstract Background Natural selection eliminates detrimental and favors advantageous phenotypes. This process leaves characteristic signatures in underlying genomic segments that can be recognized through deviations in allelic or haplotypic frequency spectra. To provide an identifiable signature of recent positive selection that can be detected by comparison with the background distribution, we introduced a new way of looking at genomic polymorphisms: haplotype allelic classes. Results The model combines segregating sites and haplotypic information in order to reveal useful data characteristics. We developed a summary statistic, Svd, to compare the distribution of the haplotypes carrying the selected allele with the distribution of the remaining ones. Coalescence simulations are used to study the distributions under standard population models assuming neutrality, demographic scenarios and selection models. To test, in practice, haplotype allelic class performance and the derived statistic in capturing deviation from neutrality due to positive selection, we analyzed haplotypic variation in detail in the locus of lactase persistence in the three HapMap Phase II populations. Conclusions We showed that the Svd statistic is less sensitive than other tests to confounding factors such as demography or recombination. Our approach succeeds in identifying candidate loci, such as the lactase-persistence locus, as targets of strong positive selection and provides a new tool complementary to other tests to study natural selection in genomic data.

  15. Drop-out probabilities of IrisPlex SNP alleles

    DEFF Research Database (Denmark)

    Andersen, Jeppe Dyrberg; Tvedebrink, Torben; Mogensen, Helle Smidt;

    2013-01-01

    In certain crime cases, information about a perpetrator's phenotype, including eye colour, may be a valuable tool if no DNA profile of any suspect or individual in the DNA database matches the DNA profile found at the crime scene. Often, the available DNA material is sparse and allelic drop-out o...

  16. Systematic underestimation of the age of selected alleles

    Directory of Open Access Journals (Sweden)

    Joanna L. Kelley

    2012-08-01

    Full Text Available A common interpretation of genome-wide selection scans is that the dispersal of anatomically modern humans out of Africa and into diverse environments led to a number of genetic adaptations. If so, patterns of polymorphism from non-African individuals should show the signature of adaptations dating to 40,000 to 100,000 Kya, coinciding with the main exodus from Africa. However, scans of polymorphism data from a few populations have yielded conflicting results about the chronology of local, population-specific adaptations. In particular, a number of papers report very recent ages for selected alleles in humans, which postdate the development of agriculture 10 Kya, and suggest that adaptive differences among human populations are much more recent. I present analysis of simulations suggesting a downward bias in methods commonly used to estimate the age of alleles. These findings indicate that an estimate of a time to the most recent common ancestor (tMRCA obtained using standard methods (used as a proxy for the age of an allele of less than 10Kya is consistent with an allele that actually became selected before the onset of agriculture and potentially as early as 50 Kya. These findings suggest that the genomic scans for selection may be consistent with selective pressures tied to the Out of Africa expansion of modern human populations.

  17. Rescue of progeria in trichothiodystrophy by homozygous lethal Xpd alleles.

    NARCIS (Netherlands)

    J.-O. Andressoo (Jaan-Olle); J. Jans (Judith); J. de Wit (Jan); F. Coin (Frédéric); D. Hoogstraten (Deborah); H.W.M. van de Ven (Marieke); W. Toussaint (Wendy); J. Huijmans (Jan); H.B. Thio (Bing); W.J. van Leeuwen (Wibeke); J. de Boer (Jan); J.H.J. Hoeijmakers (Jan); G.T.J. van der Horst (Gijsbertus); J.R. Mitchell (James); J-M. Egly (Jean-Marc)

    2006-01-01

    textabstractAlthough compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented. This is most likely because of the inherent difficulty in distinguishing specifi

  18. Rescue of progeria in trichothiodystrophy by homozygous lethal Xpd alleles.

    NARCIS (Netherlands)

    J.-O. Andressoo (Jaan-Olle); J. Jans (Judith); J. de Wit (Jan); F. Coin (Frédéric); D. Hoogstraten (Deborah); H.W.M. van de Ven (Marieke); W. Toussaint (Wendy); J. Huijmans (Jan); H.B. Thio (Bing); W.J. van Leeuwen (Wibeke); J. de Boer (Jan); J.H.J. Hoeijmakers (Jan); G.T.J. van der Horst (Gijsbertus); J.R. Mitchell (James); J-M. Egly (Jean-Marc)

    2006-01-01

    textabstractAlthough compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented. This is most likely because of the inherent difficulty in distinguishing specifi

  19. A genotype probability index for multiple alleles and haplotypes.

    Science.gov (United States)

    Percy, A; Kinghorn, B P

    2005-12-01

    We use linear algebra to calculate an index of information content in genotype probabilities which has previously been calculated using trigonometry. The new method can be generalized allowing the index to be calculated for loci with more than two alleles. Applications of this index include its use in genotyping strategies, strategies to manage genetic disorders and in estimation of genotype effects.

  20. Further evidence for allelic heterogeneity in Hartnup disorder.

    Science.gov (United States)

    Azmanov, Dimitar N; Kowalczuk, Sonja; Rodgers, Helen; Auray-Blais, Christiane; Giguère, Robert; Rasko, John E J; Bröer, Stefan; Cavanaugh, Juleen A

    2008-10-01

    Hartnup disorder is an autosomal recessive impairment of amino acid transport in kidney and intestine. Mutations in SLC6A19 have been shown to cosegregate with the disease in the predicted recessive manner; however, in two previous studies (Seow et al., Nat Genet 2004;36:1003-1007; Kleta et al., Nat Genet 2004;36:999-1002), not all causative alleles were identified in all affected individuals, raising the possibility that other genes may contribute to Hartnup disorder. We have now investigated six newly acquired families of Australian and Canadian (Province of Quebec) origin and resequenced the entire coding region of SLC6A19 in families with only a single disease allele identified. We also studied one American family in whom no mutations had been identified in a previous study (Kleta et al., Nat Genet 2004;36:999-1002). We have identified seven novel mutations in SLC6A19 that show functional obliteration of the protein in vitro, explaining Hartnup disorder in all reported families so far. We demonstrate that Hartnup disorder is allelically heterogeneous with two mutated SLC6A19 alleles, whether identical or not, necessary for manifestation of the characteristic aminoaciduria in affected individuals. This study resolves the previous hypothesis that other genes contribute to the Hartnup phenotype.

  1. Frequent allelic imbalance but infrequent microsatellite instability in gastric lymphoma

    NARCIS (Netherlands)

    Hoeve, M A; Ferreira Mota, S C; Schuuring, E; de Leeuw, W J; Chott, A; Meijerink, J P; Kluin, P M; van Krieken, J H

    1999-01-01

    Specific defects in DNA repair pathways are reflected by DNA microsatellite instability (MSI) and play an important role in carcinogenesis. Reported frequencies in gastric non-Hodgkin's lymphomas (NHL) vary from 14% to as high as 90%. Another form of genetic instability in tumours is allelic imbalan

  2. Allelism and Molecular Mapping of Soybean Necrotic Root Mutants

    Science.gov (United States)

    Mutability of the w4 flower color locus in soybean [Glycine max (L.) Merr.] is conditioned by an allele designated w4-m. Germinal revertants recovered among self-pollinated progeny of mutable plants have been associated with the generation of necrotic root mutations, chlorophyll-deficiency mutation...

  3. Estimating the age of alleles by use of intraallelic variability

    Energy Technology Data Exchange (ETDEWEB)

    Slatkin, M.; Rannala, B. [Univ of California, Berkeley, CA (United States)

    1997-02-01

    A method is presented for estimating the age of an allele by use of its frequency and the extent of variation among different copies. The method uses the joint distribution of the number of copies in a population sample and the coalescence times of the intraallelic gene genealogy conditioned on the number of copies. The linear birth-death process is used to approximate the dynamics of a rare allele in a finite population. A maximum-likelihood estimate of the age of the allele is obtained by Monte Carlo integration over the coalescence times. The method is applied to two alleles at the cystic fibrosis (CFTR) locus, {Delta}F508 and G542X, for which intraallelic variability at three intronic microsatellite loci has been examined. Our results indicate that G542X is somewhat older than {Delta}F508. Although absolute estimates depend on the mutation rates at the microsatellite loci, our results support the hypothesis that {Delta}F508 arose <500 generations ({approx}10,000 years) ago. 32 refs., 4 figs.

  4. QuASAR: quantitative allele-specific analysis of reads.

    Science.gov (United States)

    Harvey, Chris T; Moyerbrailean, Gregory A; Davis, Gordon O; Wen, Xiaoquan; Luca, Francesca; Pique-Regi, Roger

    2015-04-15

    Expression quantitative trait loci (eQTL) studies have discovered thousands of genetic variants that regulate gene expression, enabling a better understanding of the functional role of non-coding sequences. However, eQTL studies are costly, requiring large sample sizes and genome-wide genotyping of each sample. In contrast, analysis of allele-specific expression (ASE) is becoming a popular approach to detect the effect of genetic variation on gene expression, even within a single individual. This is typically achieved by counting the number of RNA-seq reads matching each allele at heterozygous sites and testing the null hypothesis of a 1:1 allelic ratio. In principle, when genotype information is not readily available, it could be inferred from the RNA-seq reads directly. However, there are currently no existing methods that jointly infer genotypes and conduct ASE inference, while considering uncertainty in the genotype calls. We present QuASAR, quantitative allele-specific analysis of reads, a novel statistical learning method for jointly detecting heterozygous genotypes and inferring ASE. The proposed ASE inference step takes into consideration the uncertainty in the genotype calls, while including parameters that model base-call errors in sequencing and allelic over-dispersion. We validated our method with experimental data for which high-quality genotypes are available. Results for an additional dataset with multiple replicates at different sequencing depths demonstrate that QuASAR is a powerful tool for ASE analysis when genotypes are not available. http://github.com/piquelab/QuASAR. fluca@wayne.edu or rpique@wayne.edu Supplementary Material is available at Bioinformatics online. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Segregation of male-sterility alleles across a species boundary.

    Science.gov (United States)

    Weller, S G; Sakai, A K; Culley, T M; Duong, L; Danielson, R E

    2014-02-01

    Hybrid zones may serve as bridges permitting gene flow between species, including alleles influencing the evolution of breeding systems. Using greenhouse crosses, we assessed the likelihood that a hybrid zone could serve as a conduit for transfer of nuclear male-sterility alleles between a gynodioecious species and a hermaphroditic species with very rare females in some populations. Segregation patterns in progeny of crosses between rare females of hermaphroditic Schiedea menziesii and hermaphroditic plants of gynodioecious Schiedea salicaria heterozygous at the male-sterility locus, and between female S. salicaria and hermaphroditic plants from the hybrid zone, were used to determine whether male-sterility was controlled at the same locus in the parental species and the hybrid zone. Segregations of females and hermaphrodites in approximately equal ratios from many of the crosses indicate that the same nuclear male-sterility allele occurs in the parent species and the hybrid zone. These rare male-sterility alleles in S. menziesii may result from gene flow from S. salicaria through the hybrid zone, presumably facilitated by wind pollination in S. salicaria. Alternatively, rare male-sterility alleles might result from a reversal from gynodioecy to hermaphroditism in S. menziesii, or possibly de novo evolution of male sterility. Phylogenetic analysis indicates that some species of Schiedea have probably evolved separate sexes independently, but not in the lineage containing S. salicaria and S. menziesii. High levels of selfing and expression of strong inbreeding depression in S. menziesii, which together should favour females in populations, argue against a reversal from gynodioecy to hermaphroditism in S. menziesii.

  6. Interaction of IL1B and IL1RN polymorphisms, smoking habit, gender, and ethnicity with aggressive and chronic periodontitis susceptibility

    Directory of Open Access Journals (Sweden)

    Magali Silveira Monteiro Ribeiro

    2016-01-01

    Full Text Available Background: Although the interleukin-1 (IL-1 plays a critical role in the pathogenesis of periodontitis, associations between IL1 gene cluster polymorphisms and the disease remains unclear. Aims: To investigate the importance of IL1B-511C>T (rs16944, IL1B +3954C>T (rs1143634, and IL1RN intron 2 variable number tandem repeat (VNTR (rs2234663 polymorphisms, individually or in combination, as the risk factors of periodontitis in a Southeastern Brazilian population with a high degree of miscegenation. Subjects and Methods: A total of 145 individuals, with aggressive (aggressive periodontitis [AgP], n = 43 and chronic (chronic periodontitis [CP], n = 52 periodontitis, and controls (n = 50 were genotyped by polymerase chain reaction (PCR (IL1RN intron 2 VNTR or PCR-restriction fragment length polymorphism (PCR-RFLP (IL1B-511 C>T and IL1B + 3954C>T techniques. Statistical Analysis: The independent t-test, Chi-square, and Fisher′s exact tests were used. The SNPStats program was used for haplotype estimation and multiplicative interaction analyses. Results: The IL1B +3954T allele represented risk for CP (odds ratio [OR] = 2.84, particularly in smokers (OR = 4.43 and females (OR = 6.00. The minor alleles IL1RNFNx012 and FNx013 increased the risk of AgP (OR = 2.18, especially the IL1RNFNx012FNx012 genotype among  white Brazilians (OR = 7.80. Individuals with the combinations of the IL1B + 3954T and IL1RNFNx012 or FNx013-containing genotypes were at increased risk of developing CP (OR = 4.50. Considering the three polymorphisms (rs16944, rs1143634, and rs2234663, the haplotypes TC2 and CT1 represented risk for AgP (OR = 3.41 and CP (OR = 6.39, respectively. Conclusions: Our data suggest that the IL1B +3954C>T and IL1RN intron 2 VNTR polymorphisms are potential candidates for genetic biomarkers of periodontitis, particularly in specific groups of individuals.

  7. Associations between interleukin-1 gene polymorphisms and sepsis risk: a meta-analysis

    Science.gov (United States)

    2014-01-01

    Background Previous epidemiological studies have presented conflicting evidence regarding associations between interleukin-1 (IL-1) polymorphisms and sepsis susceptibility. We have performed a meta-analysis to evaluate possible associations between IL-1 polymorphisms and sepsis risk. Methods Eligible literature was retrieved from PubMed, Embase and Web of Knowledge databases until Jun 15, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random-effects model in the overall and subgroup analysis based on ethnicity, sepsis severity and quality score. Results Eighteen studies addressing five IL-1 polymorphisms were included in this meta-analysis. For IL-1A-889 (rs1800587) polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.47, 95% CI = 1.01-2.13, P = 0.04). There were no significant associations between either IL-1B-511 (rs16944) or IL-1B-31 (rs1143627) and sepsis susceptibility in overall or subgroup analyses. For IL-1B + 3594 (rs143634) polymorphism, genotype TT decreased sepsis risk in overall analysis (OR = 0.59, 95% CI = 0.36-0.97, P = 0.04), as well as in Caucasian (OR = 0.57, 95% CI = 0.34-0.95, P = 0.03) and sepsis (OR = 0.55, 95% CI = 0.31-0.97, P = 0.04) subgroup analysis. For IL-1RN VNTR polymorphism, significant association was observed in overall comparison for allelic effect (OR = 1.40, 95% CI = 1.01-1.95, P = 0.04). Furthermore, the effect sizes of IL-1RN VNTR on sepsis risk increased with disease severity (septic shock OR > severe sepsis OR > sepsis OR). Conclusions Our meta-analysis indicated that IL-1A-889, IL-1B + 3954 and IL-1RN VNTR might be associated with sepsis susceptibility. However, further studies with larger sample sizes and from homogenous populations would be necessary to validate these findings. PMID:24428862

  8. Meta-analysis of associations of IL1 receptor antagonist and estrogen receptor gene polymorphisms with systemic lupus erythematosus susceptibility.

    Directory of Open Access Journals (Sweden)

    Li Cai

    Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disease that affects a number of different organs and tissues. Interleukin-1 (IL1 and estrogen are considered potential elements in the pathology of SLE. Recently, the variable number of tandem repeats (VNTR polymorphism in the IL1 receptor antagonist gene (IL1-RN and PvuII (rs2234693 and XbaI (rs9340799 polymorphisms in the estrogen receptor 1 gene (ESR1 have been associated with a predisposition to SLE. However, the evidence for these associations is inconclusive. We therefore conducted a meta-analysis to validate the roles of these polymorphisms in SLE susceptibility. We searched four databases and identified a total of 17 eligible articles comprising 24 studies. The Newcastle-Ottawa quality assessment scale was used to assess the qualities of the selected studies. We assessed the strengths of the associations using odds ratios (ORs with 95% confidence intervals (95% CIs. Regarding the IL-1RN VNTR, the 2 allele significantly increased SLE susceptibility (2 vs. L: OR = 1.34, 95% CI = 1.03-1.73, P = 0.03. The ESR1 PvuII CC/CT genotype was also associated with SLE susceptibility (CC/CT vs. TT: OR = 1.25, 95% CI = 1.06-1.47, P = 0.01, and the difference was especially pronounced among Asians (CC/CT vs. TT: OR = 1.33, 95% CI = 1.04-1.69, P = 0.02. No significant association between the ESR1 XbaI polymorphism and SLE susceptibility was observed in the overall analysis. However, a marginally significant association between the GG/GA genotype was found in individuals of Asian descent (GG/GA vs. AA: OR = 1.30, 95% CI = 1.01-1.67, P = 0.04. These results indicate that the IL1-RN VNTR 2 allele, ESR1 PvuII CC/CT genotype and ESR1 XbaI GG/GA genotype may increase SLE susceptibility, especially in Asian individuals.

  9. Mannose-binding lectin variant alleles and HLA-DR4 alleles are associated with giant cell arteritis

    DEFF Research Database (Denmark)

    Jacobsen, Soren; Baslund, Bo; Madsen, Hans Ole

    2002-01-01

    To determine whether variant alleles of the mannose-binding lectin (MBL) gene causing low serum concentrations of MBL and/or polymorphisms of HLA-DRB1 are associated with increased susceptibility to polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) or particular clinical phenotypes of PMR/GCA....

  10. Allelic divergence and cultivar-specific SSR alleles revealed by capillary electrophoresis using fluorescence-labeled SSR markers in sugarcane

    Science.gov (United States)

    Though sugarcane cultivars (Saccharum spp. hybrids) are complex aneu-polyploid hybrids, genetic evaluation and tracking of clone- or cultivar-specific alleles become possible due to capillary electrophoregrams (CE) using fluorescence-labeled SSR primer pairs. Twenty-four sugarcane cultivars, 12 each...

  11. CTLA-4 gene polymorphism confers susceptibility to insulin-dependent diabetes mellitus (IDDM) independently from age and from other genetic or immune disease markers. The Belgian Diabetes Registry.

    Science.gov (United States)

    Van der Auwera, B J; Vandewalle, C L; Schuit, F C; Winnock, F; De Leeuw, I H; Van Imschoot, S; Lamberigts, G; Gorus, F K

    1997-10-01

    Apart from genes in the HLA complex (IDDM1) and the variable number of tandem repeats in the 5' region of the insulin gene (INS VNTR, IDDM2), several other loci have been proposed to contribute to IDDM susceptibility. Recently, linkage and association have been shown between the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) gene on chromosome 2q and IDDM. In a registry-based group of 525 recent-onset IDDM patients immune disease markers (autoantibodies against islet cell cytoplasm (ICA); insulin (IAA); glutamate decarboxylase (GAD65-Ab); IA-2 protein tyrosine phosphatase (IA-2-Ab)) determined within the first week of insulin treatment. In new-onset IDDM patients. G-allele-containing CTLA-4 genotypes (relative risk (RR)= 1.5; 95% confidence interval (CI) = 1.2-2.0; P immune disease markers.

  12. Maximizing allele detection: Effects of analytical threshold and DNA levels on rates of allele and locus drop-out.

    Science.gov (United States)

    Rakay, Christine A; Bregu, Joli; Grgicak, Catherine M

    2012-12-01

    Interpretation of DNA evidence depends upon the ability of the analyst to accurately compare the DNA profile obtained from an item of evidence and the DNA profile of a standard. This interpretation becomes progressively more difficult as the number of 'drop-out' and 'drop-in' events increase. Analytical thresholds (AT) are typically selected to ensure the false detection of noise is minimized. However, there exists a tradeoff between the erroneous labeling of noise as alleles and the false non-detection of alleles (i.e. drop-out). In this study, the effect ATs had on both types of error was characterized. Various ATs were tested, where three relied upon the analysis of baseline signals obtained from 31 negative samples. The fourth AT was determined by utilizing the relationship between RFU signal and DNA input. The other ATs were the commonly employed 50, 150 and 200 RFU thresholds. Receiver Operating Characteristic (ROC) plots showed that although high ATs completely negated the false labeling of noise, DNA analyzed with ATs derived using analysis of the baseline signal exhibited the lowest rates of drop-out and the lowest total error rates. In another experiment, the effect small changes in ATs had on drop-out was examined. This study showed that as the AT increased from ∼10 to 60 RFU, the number of heterozygous loci exhibiting the loss of one allele increased. Between ATs of 60 and 150 RFU, the frequency of allelic drop-out remained constant at 0.27 (±0.02) and began to decrease when ATs of 150 RFU or greater were utilized. In contrast, the frequency of heterozygous loci exhibiting the loss of both alleles consistently increased with AT. In summary, for samples amplified with less than 0.5ng of DNA, ATs derived from baseline analysis of negatives were shown to decrease the frequency of drop-out by a factor of 100 without significantly increasing rates of erroneous noise detection.

  13. Tri-allelic pattern at the TPOX locus: a familial study.

    Science.gov (United States)

    Picanço, Juliane Bentes; Raimann, Paulo Eduardo; Paskulin, Giorgio Adriano; Alvarez, Luís; Amorim, António; Batista Dos Santos, Sidney Emanuel; Alho, Clarice Sampaio

    2014-02-10

    Alleles at the TPOX STR locus have 6-14 different numbers of a four-nucleotide (AATG) repeat motif arranged in tandem. Although tri-allelic genotypes are generally rare, the TPOX tri-allelic pattern has a higher frequency, varying widely among populations. Despite this, there are few accurate reports to disclose the nature of the TPOX third allele. In this work we present data obtained from 45 individuals belonging to the same pedigree, in which there are cases of tri-allelic TPOX genotypes. The subjects were apparently healthy with a normal biological development. We noticed six tri-allelic cases in this family, and all of them were women. Karyotype analysis showed no occurrence of partial 2p trisomy. All the tri-allelic cases had the genotype 8-10-11, probably due to three copies of the TPOX STR sequence in all cells (Type 2 tri-allelic pattern). Based on previous data we assumed the allele 10 as the TPOX third allele. The pedigree analyses show evidences that the TPOX extra-allele was the allele10, it is placed far from the main TPOX locus, and that there is a potential linkage of the TPOX extra-allele-10 with Xq. This was the first study that included a large pedigree analysis in order to understand the nature TPOX tri-allelic pattern. © 2013.

  14. Human Leukocyte Antigen Alleles and Cytomegalovirus Infection After Renal Transplantation

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    Futohi

    2015-11-01

    Full Text Available Background Several studies have been conducted on the relationship between a number of human leukocyte antigen (HLA alleles and cytomegalovirus infection (CMV, in kidney transplant recipients, after transplantation. However, only a limited number of HLAs have been investigated, so far, and the results have been contradictory. Objectives This study aimed to investigate the relationship between 59 HLA alleles and the CMV infection, in transplant recipients, after kidney transplantation. Patients and Methods This retrospective cohort study was conducted on 200 patients, receiving a kidney transplant, in Baqiyatallah Hospital, in Tehran, during 2013. Throughout a one-year follow-up of kidney transplant recipients, in case of detecting the CMV antigen in patients’ blood, at any time, they were placed in the group of patients with CMV infection, whereas, if no CMV-specific antigen was developed, over a year, patients were placed in the group of patients without CMV infection, after transplantation. This study investigated the relationship between CMV infection in kidney transplant recipients and 59 HLA alleles, including 14 HLA-A, 28 HLA-B, and 17 HLA-DRB1 cases. Results Of all participants, 104 patients (52% were diagnosed with CMV infection. There was no significant difference between the two groups, with and without CMV infection, in terms of patient’s characteristics. The CMV infection, in patients receiving a transplanted organ from deceased donor, was significantly more prevalent than in those receiving kidney transplant from living donor (63% vs. 39%, respectively, P = 0.001. Recipients with HLA-B44 were more infected with CMV compared with patients without this allele (80% vs. 50%, respectively, P = 0.024; on the contrary, kidney recipients with HLA-DRB1-1 were less infected with CMV than patients without this allele (31% vs. 55%, respectively, P = 0.020. There was no significant relationship between CMV infection and other HLA alleles

  15. Molecular typing methods used in studies of Mycobacterium tuberculosis in Iran: a systematic review

    Science.gov (United States)

    Ravansalar, Hassan; Tadayon3, Keyvan; Ghazvini, Kiarash

    2016-01-01

    Background and Objectives: Molecular typing methods are important and useful tools to assess the transmission, diversity of strains and differentiation between new infections and relapses which can effectively help in controlling infections. The aim of this study was to evaluate the molecular typing methods which have been used in Iran. By evaluating the results and discriminatory power of each method, we can assign appropriate weight to each technique and ultimately offer a common strategy for future epidemiological studies. Method: We searched several databases to identify studies addressing Mycobacterium tuberculosis molecular epidemiology in Iran. Hunter-Gaston discrimination index (HGDI) was used to evaluate the discriminatory power in each method. Relevant articles were selected and analyzed; HGDI index was calculated for each technique. Results: The most common genotyping methods used in the articles were RFLP, MIRU-VNTR, spoligotyping, PFGE and RAPD-PCR. The most frequently techniques were IS6110-RFLP, MIRU-VNTR and spoligotyping alone or in combination. The highest discrimination power (average HGDI: 0.9916) was obtained by RFLP followed by MIRU-VNTR (average HGDI: 0.9638) and spoligotyping (average HGDI: 0.9041) respectively. Conclusion: Combination of MIRU-VNTR with spoligotyping can be recommended for large-scale genotyping in Iran. It seems appropriate to consider spoligotyping as the first technique for screening followed by other techniques with higher discrimination power such as MIRU-VNTR or IS6110-RFLP.

  16. Pros and cons of direct genotyping on tuberculosis clinical samples.

    Science.gov (United States)

    Sadegh, Hamidreza; Kargarpour Kamakoli, Mansour; Farmanfarmaei, Ghazaleh; Masoumi, Morteza; Abdolrahimi, Farid; Fateh, Abolfazl; Ebrahimzadeh, Nayereh; Rahimi Jamnani, Fatemeh; Vaziri, Farzam; Siadat, Seyed Davar

    2017-02-01

    Prompt genotyping of Mycobacterium tuberculosis (M. tuberculosis) is crucial for improving molecular epidemiological investigation of tuberculosis (TB). We performed a retrospective study to evaluate the use of 24 loci MIRU-VNTR (mycobacterial interspersed repetitive unit-variable number of tandem-repeat) directly on 135 clinical samples from 84 TB patients. There was a direct correlation between genotyping on clinical samples by MIRU-VNTR and bacterial load (P = 0.001). VNTR loci were amplified successfully for 41.5% of the clinical samples (19-24 loci), 32.6% (13-18 loci), 23.7% (7-12 loci) and 2.2% (1-6 loci). Loci of 2401, 577, 2996 and 154 had the highest power to show the mixed strains infection in clinical samples. Direct MIRU-VNTR is partially successful in complete genotyping of M. tuberculosis strains. On the other hand, detection of polyclonal infection is undoubtedly reliable based on the direct MIRU-VNTR. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Modification of an HLA-B PCR-SSOP typing system leading to improved allele determination.

    Science.gov (United States)

    Middleton, D; Williams, F; Cullen, C; Mallon, E

    1995-04-01

    Modifications have been introduced to a previously reported HLA-B PCR-SSOP typing system. This has enabled further definition of alleles, determination of the probe pattern of some alleles not previously examined and identification of patterns of possible new alleles. However there are still some alleles that cannot be differentiated and there are several alleles which when present as a homozygote have the same pattern as in combination with another allele. When the method was applied to the typing of 66 consecutive cadaveric donors there were three donors whose type differed from the serological type.

  18. Polymorphisms in the Dopamine D4 and D2 Receptor Genes and Reproductive and Sexual Behaviors

    Directory of Open Access Journals (Sweden)

    Dan T.A. Eisenberg

    2007-10-01

    Full Text Available Human reproductive and sexual behaviors are heritable and may represent integral life history traits that are likely partially subserved by the dopamine system. Two dopamine receptor polymorphisms, DRD4 48bp VNTR and DRD2 TaqI A, were examined in relation to the Sexual-Orientation Inventory (SOI, age at first sexual intercourse, desired age of marriage, and desired age to have children in 195 (45% male individuals from a general student population. As DRD4 7R alleles have been associated with migratory behavior, we also examined whether those with more 7R alleles had a greater frequency of multi-racial ancestries. Minor alleles of both polymorphisms (7R and A1 respectively are believed to decrease the function of their respective receptors. Individuals with DRD4 7R alleles were more likely to have had sexual intercourse and to desire children earlier in life. In addition, DRD4 7R+ individuals were more likely to report multi-racial ancestries. Individuals with DRD2 A1 alleles were more likely to not want children and not want to marry. These results suggest that polymorphisms in the DRD4 and DRD2 genes are meaningfully associated with variation in reproductive and sexual behaviors. These results are provisionally interpreted as consistent with other findings suggesting that DRD4 7R and DRD2 A1 alleles are adaptive for lower offspring investment strategies in dynamic social environments.

  19. Genetic variation among four Mexican populations (Huichol, Purepecha, Tarahumara, and Mestizo) revealed by two VNTRs and four STRs.

    Science.gov (United States)

    Rangel-Villalobos, H; Rivas, F; Sandoval, L; Ibarra, B; Garcìa-Carvajal, Z Y; Cantú, J M; Figuera, L E

    2000-12-01

    Allele distributions of two polymorphisms with variable number of tandem repeats (VNTR), D1S80 and APOB, and four polymorphisms with short tandem repeats (STR), VWA, TH01, CSF1PO, and HPRTB, were analyzed in three Mexican ethnic groups: Huichol, Purepecha, and Tarahumara. Genotype distribution was in agreement with Hardy-Weinberg expectations for each locus and ethnic group. Heterozygosity (H), power of discrimination, and probability of exclusion were estimated. The three groups presented some distinctive genetic features: (1) a diminished genetic diversity (H = 66.8% to 73.4%) and mean number of alleles by locus (5.8 to 6.3) in comparison with Mexican mestizos (H = 78.3%, 10.5 alleles/locus), and (2) uneven allele distributions as evidenced by "distinctive alleles" with high frequencies, especially in the Tarahumara and the Huichol. Genetic relatedness analysis included data from a previously typed mestizo population, the largest and most widely distributed population in Mexico. Allele distribution differentiation was observed among all four groups, except between mestizo and Purepecha (p > 0.05), which was interpreted as indicating a larger Spanish component in the Purepecha as a result of gene flow effects. Although intrapopulation inbreeding (FIS) was not significant, heterozygote deficiency in the total population (FIT) and divergence among populations (FST) were significant (p Purepechas, and Huichols in relation to Tarahumaras. Correlation between the observed genetic features and the geographic isolation level points to genetic drift as the main cause of differentiation among these Mexican populations.

  20. Dynamic of Mutational Events in Variable Number Tandem Repeats of Escherichia coli O157:H7

    Directory of Open Access Journals (Sweden)

    A. V. Bustamante

    2013-01-01

    Full Text Available VNTRs regions have been successfully used for bacterial subtyping; however, the hypervariability in VNTR loci is problematic when trying to predict the relationships among isolates. Since few studies have examined the mutation rate of these markers, our aim was to estimate mutation rates of VNTRs specific for verotoxigenic E. coli O157:H7. The knowledge of VNTR mutational rates and the factors affecting them would make MLVA more effective for epidemiological or microbial forensic investigations. For this purpose, we analyzed nine loci performing parallel, serial passage experiments (PSPEs on 9 O157:H7 strains. The combined 9 PSPE population rates for the 8 mutating loci ranged from 4.4 × 10−05 to 1.8 × 10−03 mutations/generation, and the combined 8-loci mutation rate was of 2.5 × 10−03 mutations/generation. Mutations involved complete repeat units, with only one point mutation detected. A similar proportion between single and multiple repeat changes was detected. Of the 56 repeat mutations, 59% were insertions and 41% were deletions, and 72% of the mutation events corresponded to O157-10 locus. For alleles with up to 13 UR, a constant and low mutation rate was observed; meanwhile longer alleles were associated with higher and variable mutation rates. Our results are useful to interpret data from microevolution and population epidemiology studies and particularly point out that the inclusion or not of O157-10 locus or, alternatively, a differential weighting data according to the mutation rates of loci must be evaluated in relation with the objectives of the proposed study.

  1. Study of the serotonin transporter (SLC6A4 and BDNF genes in French patients with non syndromic mental deficiency

    Directory of Open Access Journals (Sweden)

    Mignon Laurence

    2010-02-01

    Full Text Available Abstract Background Mental deficiency has been linked to abnormalities in cortical neuronal network connectivity and plasticity. These mechanisms are in part under the control of two interacting signalling pathways, the serotonergic and the brain-derived neurotrophic (BDNF pathways. The aim of the current paper is to determine whether particular alleles or genotypes of two crucial genes of these systems, the serotonin transporter gene (SLC6A4 and the brain-derived neurotrophic factor gene (BDNF, are associated with mental deficiency (MD. Methods We analyzed four functional polymorphisms (rs25531, 5-HTTLPR, VNTR, rs3813034 of the SLC6A4 gene and one functional polymorphism (Val66 Met of the BDNF gene in 98 patients with non-syndromic mental deficiency (NS-MD and in an ethnically matched control population of 251 individuals. Results We found no significant differences in allele and genotype frequencies in the five polymorphisms studied in the SLC6A4 and BDNF genes of NS-MD patients versus control patients. While the comparison of the patterns of linkage disequilibrium (D' in the control and NS-MD populations revealed a degree of variability it did not, however, reach significance. No significant differences in frequencies of haplotypes and genotypes for VNTR/rs3813034 and rs25531/5-HTTLPR were observed. Conclusion Altogether, results from the present study do not support a role for any of the five functional polymorphisms of SLC6A4 and BDNF genes in the aetiology of NS-RM. Moreover, they suggest no epistatic interaction in NS-MD between polymorphisms in BDNF and SLC6A4. However, we suggest that further studies on these two pathways in NS-MD remain necessary.

  2. SLC6A3 and body mass index in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

    Directory of Open Access Journals (Sweden)

    Hayes Richard B

    2009-01-01

    Full Text Available Abstract Background To investigate the contribution of the dopamine transporter to dopaminergic reward-related behaviors and anthropometry, we evaluated associations between polymorphisms at the dopamine transporter gene(SLC6A3 and body mass index (BMI, among participants in the Prostate, Lung, Colorectal and Ovarian (PLCO Cancer Screening Trial. Methods Four polymorphisms (rs6350, rs6413429, rs6347 and the 3' variable number of tandem repeat (3' VNTR polymorphism at the SLC6A3 gene were genotyped in 2,364 participants selected from the screening arm of PLCO randomly within strata of sex, age and smoking history. Height and weight at ages 20 and 50 years and baseline were assessed by questionnaire. BMI was calculated and categorized as underweight, normal, overweight and obese (2, respectively. Odds ratios (ORs and 95% confidence intervals (CIs of SLC6A3 genotypes and haplotypes were computed using conditional logistic regression. Results Compared with individuals having a normal BMI, obese individuals at the time of the baseline study questionnaire were less likely to possess the 3' VNTR variant allele with 9 copies of the repeated sequence in a dose-dependent model (** is referent; OR*9 = 0.80, OR99 = 0.47, ptrend = 0.005. Compared with individuals having a normal BMI at age 50, overweight individuals (A-C-G-* is referent; ORA-C-G-9 = 0.80, 95% CI 0.65–0.99, p = 0.04 and obese individuals (A-C-G-* is referent; ORA-C-G-9 = 0.70, 95% CI 0.49–0.99, p = 0.04 were less likely to possess the haplotype with the 3'variant allele (A-C-G-9. Conclusion Our results support a role of genetic variation at the dopamine transporter gene, SLC6A3, as a modifier of BMI.

  3. ABO genotyping in leukemia patients reveals new ABO variant alleles

    OpenAIRE

    Novaretti,M.C.Z.; DOMINGUES, A. E.; MANHANI, R.; Pinto, E M; Dorlhiac-Llacer, P.E.; Chamone, D.A.F.

    2008-01-01

    The ABO blood group is the most important blood group system in transfusion medicine and organ transplantation. To date, more than 160 ABO alleles have been identified by molecular investigation. Almost all ABO genotyping studies have been performed in blood donors and families and for investigation of ABO subgroups detected serologically. The aim of the present study was to perform ABO genotyping in patients with leukemia. Blood samples were collected from 108 Brazilian patients with chronic...

  4. Allele-Specific DNA Methylation Detection by Pyrosequencing®

    DEFF Research Database (Denmark)

    Sommer Kristensen, Lasse; Johansen, Jens Vilstrup; Grønbæk, Kirsten

    2015-01-01

    DNA methylation is an epigenetic modification that plays important roles in healthy as well as diseased cells, by influencing the transcription of genes. In spite the fact that human somatic cells are diploid, most of the currently available methods for the study of DNA methylation do not provide......-effective protocol for allele-specific DNA methylation detection based on Pyrosequencing(®) of methylation-specific PCR (MSP) products including a single nucleotide polymorphism (SNP) within the amplicon....

  5. A survey of FRAXE allele sizes in three populations

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, N.; Ju, W.; Curley, D. [New York State Institute for Basic Research for Developmental Disabilities, Staten Island, NY (United States)] [and others

    1996-08-09

    FRAXE is a fragile site located at Xq27-8, which contains polymorphic triplet GCC repeats associated with a CpG island. Similar to FRAXA, expansion of the GCC repeats results in an abnormal methylation of the CpG island and is associated with a mild mental retardation syndrome (FRAXE-MR). We surveyed the GCC repeat alleles of FRAXE from 3 populations. A total of 665 X chromosomes including 416 from a New York Euro-American sample (259 normal and 157 with FRAXA mutations), 157 from a Chinese sample (144 normal and 13 FRAXA), and 92 from a Finnish sample (56 normal and 36 FRAXA) were analyzed by polymerase chain reaction. Twenty-seven alleles, ranging from 4 to 39 GCC repeats, were observed. The modal repeat number was 16 in the New York and Finnish samples and accounted for 24% of all the chromosomes tested (162/665). The modal repeat number in the Chinese sample was 18. A founder effect for FRAXA was suggested among the Finnish FRAXA samples in that 75% had the FRAXE 16 repeat allele versus only 30% of controls. Sequencing of the FRAXE region showed no imperfections within the GCC repeat region, such as those commonly seen in FRAXA. The smaller size and limited range of repeats and the lack of imperfections suggests the molecular mechanisms underlying FRAXE triplet mutations may be different from those underlying FRAXA. 27 refs., 4 figs., 1 tab.

  6. The protease inhibitor PI*S allele and COPD

    DEFF Research Database (Denmark)

    Hersh, C P; Ly, N P; Berkey, C S

    2005-01-01

    In many countries, the protease inhibitor (SERPINA1) PI*S allele is more common than PI*Z, the allele responsible for most cases of chronic obstructive pulmonary disease (COPD) due to severe alpha 1-antitrypsin deficiency. However, the risk of COPD due to the PI*S allele is not clear. The current...... authors located studies that addressed the risk of COPD or measured lung function in individuals with the PI SZ, PI MS and PI SS genotypes. A separate meta-analysis for each genotype was performed. Aggregating data from six studies, the odds ratio (OR) for COPD in PI SZ compound heterozygotes compared...... with PI MM (normal) individuals was significantly increased at 3.26 (95% confidence intervals (CI): 1.24-8.57). In 17 cross-sectional and case-control studies, the OR for COPD in PI MS heterozygotes was 1.19 (95%CI: 1.02-1.38). However, PI MS genotype was not associated with COPD risk after correcting...

  7. Tracing pastoralist migrations to southern Africa with lactase persistence alleles.

    Science.gov (United States)

    Macholdt, Enrico; Lede, Vera; Barbieri, Chiara; Mpoloka, Sununguko W; Chen, Hua; Slatkin, Montgomery; Pakendorf, Brigitte; Stoneking, Mark

    2014-04-14

    Although southern African Khoisan populations are often assumed to have remained largely isolated during prehistory, there is growing evidence for a migration of pastoralists from eastern Africa some 2,000 years ago, prior to the arrival of Bantu-speaking populations in southern Africa. Eastern Africa harbors distinctive lactase persistence (LP) alleles, and therefore LP alleles in southern African populations may be derived from this eastern African pastoralist migration. We sequenced the lactase enhancer region in 457 individuals from 18 Khoisan and seven Bantu-speaking groups from Botswana, Namibia, and Zambia and additionally genotyped four short tandem repeat (STR) loci that flank the lactase enhancer region. We found nine single-nucleotide polymorphisms, of which the most frequent is -14010(∗)C, which was previously found to be associated with LP in Kenya and Tanzania and to exhibit a strong signal of positive selection. This allele occurs in significantly higher frequency in pastoralist groups and in Khoe-speaking groups in our study, supporting the hypothesis of a migration of eastern African pastoralists that was primarily associated with Khoe speakers. Moreover, we find a signal of ongoing positive selection in all three pastoralist groups in our study, as well as (surprisingly) in two foraging groups.

  8. Large multi-allelic copy number variations in humans

    Science.gov (United States)

    Handsaker, Robert E.; Van Doren, Vanessa; Berman, Jennifer R.; Genovese, Giulio; Kashin, Seva; Boettger, Linda M.; McCarroll, Steven A.

    2015-01-01

    Thousands of genome segments appear to be present in widely varying copy number in different human genomes. We developed ways to use increasingly abundant whole genome sequence data to identify the copy numbers, alleles and haplotypes present at most large, multi-allelic CNVs (mCNVs). We analyzed 849 genomes sequenced by the 1000 Genomes Project to identify most large (>5 kb) mCNVs, including 3,878 duplications, of which 1,356 appear to have three or more segregating alleles. We find that mCNVs give rise to most human gene-dosage variation – exceeding sevenfold the contribution of deletions and biallelic duplications – and that this variation in gene dosage generates abundant variation in gene expression. We describe “runaway duplication haplotypes” in which genes, including HPR and ORM1, have mutated to high copy number on specific haplotypes. We describe partially successful initial strategies for analyzing mCNVs via imputation and provide an initial data resource to support such analyses. PMID:25621458

  9. RNA-FISH to analyze allele-specific expression.

    Science.gov (United States)

    Braidotti, G

    2001-01-01

    One of the difficulties associated with the analysis of imprinted gene expression is the need to distinguish RNA synthesis occurring at the maternal vs the paternally inherited copy of the gene. Most of the techniques used to examine allele-specific expression exploit naturally occurring polymorphisms and measure steady-state levels of RNA isolated from a pool of cells. Hence, a restriction fragment length polymorphism (RFLP) an be exploited in a heterozygote, by a reverse transcriptase polymerase chain reaction (RT-PCR)- based procedure, to analyze maternal vs paternal gene expression. The human IGF2R gene was analyzed in this way. Smrzka et al. (1) were thus able to show that the IGF2R gene possesses a hemimethylated, intronic CpG island analogous to the mouse imprinting box. However, IGF2R mRNA was detected that possessed the RFLP from both the maternal and paternal alleles in all but one of the 70 lymphoblastoid samples. (The one monoallelic sample reactivated its paternal allele with continued cell culturing.) It was concluded that monoallelic expression of the human gene is a polymorphic trait occurring in a small minority of all tested samples (reviewed in refs. 2,3). Although this is a sound conclusion, the question remains: Is the human IGF2R gene imprinted?

  10. TRPV6 alleles do not influence prostate cancer progression

    Directory of Open Access Journals (Sweden)

    Flockerzi Veit

    2009-10-01

    Full Text Available Abstract Background The transient receptor potential, subfamily V, member 6 (TRPV6 is a Ca2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage. Methods Genomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test. Results We first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage. Conclusion Our results show that the frequencies of trpv6

  11. Conditional Allele Mouse Planner (CAMP): software to facilitate the planning and design of breeding strategies involving mice with conditional alleles.

    Science.gov (United States)

    Hoffert, Jason D; Pisitkun, Trairak; Miller, R Lance

    2012-06-01

    Transgenic and conditional knockout mouse models play an important role in biomedical research and their use has grown exponentially in the last 5-10 years. Generating conditional knockouts often requires breeding multiple alleles onto the background of a single mouse or group of mice. Breeding these mice depends on parental genotype, litter size, transmission frequency, and the number of breeding rounds. Therefore, a well planned breeding strategy is critical for keeping costs to a minimum. However, designing a viable breeding strategy can be challenging. With so many different variables this would be an ideal task for a computer program. To facilitate this process, we created a Java-based program called Conditional Allele Mouse Planner (CAMP). CAMP is designed to provide an estimate of the number of breeders, amount of time, and costs associated with generating mice of a particular genotype. We provide a description of CAMP, how to use it, and offer it freely as an application.

  12. Identification of common bean alleles resistant to anthracnose using RAPD

    Directory of Open Access Journals (Sweden)

    Ana L.M. Castanheira

    1999-12-01

    Full Text Available RAPD markers were identified close to common bean alleles responsible for resistance to the fungus Colletotrichum lindemuthianum and may be useful in selecting plants resistant to this pathogen. DNA from F2 plants of the crosses Carioca 300V x P45, Carioca 300V x Ouro and P24 x Ouro was amplified by RAPD. Line P45 has the Co.4 allele for resistance, and the Ouro cultivar has the Co.5 allele. The primer OPC08 amplified a DNA fragment of about 1059 bp linked to the Co.4 allele. The recombination frequency was 0.133 (SE = 0.039; 95% CI = 0.056-0.211. Using the primer OPF10 a DNA fragment of about 912 bp was amplified and found to be associated with the Co.5 allele. The recombination frequency was 0.115 (SE = 0.038; 95% CI = 0.041-0.189. A second marker (1122 pb amplified by the OPR03 primer was identified in the population P24 x Ouro. The recombination frequency for this marker was 0.363 (SE = 0.081; 95% CI = 0.205-0.522. Both these markers flanked the Co.5 allele. The markers identified in this study may be useful in identifying lines with the Co.4 and Co.5 alleles.Marcadores RAPD foram identificados próximos de alelos do feijão responsáveis pela resistência ao Colletotrichum lindemuthianum, visando auxiliar na seleção de plantas resistentes ao patógeno. Empregou-se o método dos bulks segregantes de DNA extraídos de plantas F2 dos seguintes cruzamentos: Carioca 300V x P45, Carioca 300V x Ouro e P24 x Ouro. A linhagem P45 é portadora do alelo Co.4 de resistência e o cultivar Ouro é portador do alelo Co.5, os quais foram marcados. Procedeu-se à reação RAPD dos bulks e foi identificado o iniciador OPC08 que amplificou um fragmento de DNA com cerca de 1059 pb, ligado ao alelo Co.4. A freqüência de recombinação foi de 0,133 (erro padrão 0,039 e o intervalo de confiança foi 0,056 e 0,211, com 95% de probabilidade. Em relação ao alelo Co.5 foi identificado um fragmento de DNA amplificado pelo iniciador OPF10 com cerca de 912 pb, na

  13. Power of IRT in GWAS: successful QTL mapping of sum score phenotypes depends on interplay between risk allele frequency, variance explained by the risk allele, and test characteristics.

    Science.gov (United States)

    van den Berg, Stéphanie M; Service, Susan K

    2012-12-01

    As data from sequencing studies in humans accumulate, rare genetic variants influencing liability to disease and disorders are expected to be identified. Three simulation studies show that characteristics and properties of diagnostic instruments interact with risk allele frequency to affect the power to detect a quantitative trait locus (QTL) based on a test score derived from symptom counts or questionnaire items. Clinical tests, that is, tests that show a positively skewed phenotypic sum score distribution in the general population, are optimal to find rare risk alleles of large effect. Tests that show a negatively skewed sum score distribution are optimal to find rare protective alleles of large effect. For alleles of small effect, tests with normally distributed item parameters give best power for a wide range of allele frequencies. The item-response theory framework can help understand why an existing measurement instrument has more power to detect risk alleles with either low or high frequency, or both kinds.

  14. Lack of polymorphism at MC1R wild-type allele and evidence of domestic allele introgression across European wild boar populations

    DEFF Research Database (Denmark)

    Canu, Antonio; Vilaça, Sibelle T.; Iacolina, Laura

    2016-01-01

    , two loci which have been under strong artificial selection during domestication. These loci influence coat colour and number of vertebrae, respectively. A total of 145 wild boars were sampled throughout Europe, to evaluate frequency and spatial distribution of domestic alleles and patterns...... of hybridization between wild and domestic forms. Most of the wild boars (94%) were homozygous for the European wild-type (E+) MC1R allele. We did not observe any synonymous substitution in the European E+ allele, confirming its monomorphism even in areas known to be hotspots of wild boar genetic diversity....... The remaining wild boars (6%) showed genetic introgression of three different European domestic alleles. No Asian MC1R allele was found in our sample. Furthermore, domestic NR6A1 alleles were observed in 6% of wild boars. Considering jointly the two loci analyzed, 11% of boars, sampled all over Europe, showed...

  15. Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem cells carrying allelic fluorescent protein genes

    Directory of Open Access Journals (Sweden)

    Stringer Saundra L

    2006-10-01

    Full Text Available Abstract Background Loss of heterozygosity (LOH contributes to many cancers, but the rate at which these events occur in normal cells of the body is not clear. LOH would be detectable in diverse cell types in the body if this event were to confer an obvious cellular phenotype. Mice that carry two different fluorescent protein genes as alleles of a locus would seem to be a useful tool for addressing this issue because LOH would change a cell's phenotype from dichromatic to monochromatic. In addition, LOH caused by mitotic crossing over might be discernable in tissues because this event produces a pair of neighboring monochromatic cells that are different colors. Results As a step in assessing the utility of this approach, we derived primary embryonic fibroblast populations and embryonic stem cell lines from mice that carried two different fluorescent protein genes as alleles at the chromosome 6 locus, ROSA26. Fluorescence activated cell sorting (FACS showed that the vast majority of cells in each line expressed the two marker proteins at similar levels, and that populations exhibited expression noise similar to that seen in bacteria and yeast. Cells with a monochromatic phenotype were present at frequencies on the order of 10-4 and appeared to be produced at a rate of approximately 10-5 variant cells per mitosis. 45 of 45 stably monochromatic ES cell clones exhibited loss of the expected allele at the ROSA26 locus. More than half of these clones retained heterozygosity at a locus between ROSA26 and the centromere. Other clones exhibited LOH near the centromere, but were disomic for chromosome 6. Conclusion Allelic fluorescent markers allowed LOH at the ROSA26 locus to be detected by FACS. LOH at this locus was usually not accompanied by LOH near the centromere, suggesting that mitotic recombination was the major cause of ROSA26 LOH. Dichromatic mouse embryonic cells provide a novel system for studying genetic/karyotypic stability and factors

  16. Genotipificación del gen HLA DQB1 en diabetes autoinmune del adulto (lada HLA DQB1 genotyping in latent autoimmune diabetes of adults (LADA

    Directory of Open Access Journals (Sweden)

    Mariela Caputo

    2005-06-01

    Full Text Available La diabetes autoinmune es una enfermedad multifactorial causada por factores genéticos predisponentes y ambientales desencadenantes. Se manifiesta en la edad infantojuvenil (diabetes tipo 1, DMID y en la edad adulta (diabetes autoinmune latente del adulto, LADA. La predisposición genética es de tipo poligénico, se ha establecido asociación con alelos polimórficos del gen DQB del sistema HLA, VNTR del gen de insulina y polimorfismos en el gen CTLA4. En el presente trabajo se analizaron las frecuencias de los alelos polimórficos del gen HLA DQB1 en 63 pacientes LADA, 70 pacientes DMID y 79 individuos normales. La tipificación de los alelos del gen DQB1 se llevó a cabo mediante el Kit SSP TM DQ Olerup. Se observó una mayor frecuencia del genotipo *0201-*0302 y *0201-*0201 en ambas poblaciones diabéticas con respecto a normales (pAutoimmune diabetes is a complex, multifactorial disease caused by the interaction of genetic and environmental factors. This autoimmune diabetes is commonly manifested in childhood and adolescence with a fast onset (type 1 diabetes, IDDM and it can occur in adult patients with a slow onset with delayed insulin requirement, (latent autoimmune diabetes in adults, LADA . Autoimmune diabetes has strong class II HLA association mainly with DQB gene which constitutes the first susceptibility locus. However, association with the 5’INS- VNTR and CTLA-4 genes has been established. In this study, we analysed the polimorphic allele frequencies of DQB HLA gene in 63 LADA patients, 70 IDDM and 79 control subjects. The HLA DQB1 alleles typing was detected through Olerup SSP TM DQ kit using sequence specific primers. We observed a positive association of *0201-*0302 and *0201-*0201 genotypes in both types of diabetic patients compared to the control group (p<0.05. Moreover, *0201-*0302 genotype was higher in IDDM than in LADA (p<0.05. On the other hand, the *0602 protective allele analysis showed a high prevalence in the

  17. The Rh allele frequencies in Gaza city in Palestine

    Directory of Open Access Journals (Sweden)

    Skaik Younis

    2011-01-01

    Full Text Available Background: The Rh blood group system is the second most clinically significant blood group system. It includes 49 antigens, but only five (D, C, E, c and e are the most routinely identified due to their unique relation to hemolytic disease of the newborn (HDN and transfusion reactions. Frequency of the Rh alleles showed variation, with regard to race and ethnic. Objectives: The purpose of the study was to document the Rh alleles′ frequencies amongst males (M and females (F in Gaza city in Palestine. Materials and Methods: Two hundred and thirty-two blood samples (110 M and 122 F were tested against monoclonal IgM anti-C,anti-c, anti-E, anti-e and a blend of monoclonal/polyclonal IgM/IgG anti-D. The expected Rh phenotypes were calculated using gene counting method. Results: The most frequent Rh antigen in the total sample was e, while the least frequent was E.The order of the combined Rh allele frequencies in both M and F was CDe > cDe > cde > CdE > cDE > Cde > CDE. A significant difference was reported between M and F regarding the phenotypic frequencies (P < 0.05. However, no significance (P > 0.05 was reported with reference to the observed and expected Rh phenotypic frequencies in either M or F students. Conclusion: It was concluded that the Rh antigens, alleles and phenotypes in Gaza city have unique frequencies, which may be of importance to the Blood Transfusion Center in Gaza city and anthropology.

  18. Autoimmune disease classification by inverse association with SNP alleles.

    Directory of Open Access Journals (Sweden)

    Marina Sirota

    2009-12-01

    Full Text Available With multiple genome-wide association studies (GWAS performed across autoimmune diseases, there is a great opportunity to study the homogeneity of genetic architectures across autoimmune disease. Previous approaches have been limited in the scope of their analysis and have failed to properly incorporate the direction of allele-specific disease associations for SNPs. In this work, we refine the notion of a genetic variation profile for a given disease to capture strength of association with multiple SNPs in an allele-specific fashion. We apply this method to compare genetic variation profiles of six autoimmune diseases: multiple sclerosis (MS, ankylosing spondylitis (AS, autoimmune thyroid disease (ATD, rheumatoid arthritis (RA, Crohn's disease (CD, and type 1 diabetes (T1D, as well as five non-autoimmune diseases. We quantify pair-wise relationships between these diseases and find two broad clusters of autoimmune disease where SNPs that make an individual susceptible to one class of autoimmune disease also protect from diseases in the other autoimmune class. We find that RA and AS form one such class, and MS and ATD another. We identify specific SNPs and genes with opposite risk profiles for these two classes. We furthermore explore individual SNPs that play an important role in defining similarities and differences between disease pairs. We present a novel, systematic, cross-platform approach to identify allele-specific relationships between disease pairs based on genetic variation as well as the individual SNPs which drive the relationships. While recognizing similarities between diseases might lead to identifying novel treatment options, detecting differences between diseases previously thought to be similar may point to key novel disease-specific genes and pathways.

  19. Common Kibra alleles are associated with human memory performance.

    Science.gov (United States)

    Papassotiropoulos, Andreas; Stephan, Dietrich A; Huentelman, Matthew J; Hoerndli, Frederic J; Craig, David W; Pearson, John V; Huynh, Kim-Dung; Brunner, Fabienne; Corneveaux, Jason; Osborne, David; Wollmer, M Axel; Aerni, Amanda; Coluccia, Daniel; Hänggi, Jürgen; Mondadori, Christian R A; Buchmann, Andreas; Reiman, Eric M; Caselli, Richard J; Henke, Katharina; de Quervain, Dominique J-F

    2006-10-20

    Human memory is a polygenic trait. We performed a genome-wide screen to identify memory-related gene variants. A genomic locus encoding the brain protein KIBRA was significantly associated with memory performance in three independent, cognitively normal cohorts from Switzerland and the United States. Gene expression studies showed that KIBRA was expressed in memory-related brain structures. Functional magnetic resonance imaging detected KIBRA allele-dependent differences in hippocampal activations during memory retrieval. Evidence from these experiments suggests a role for KIBRA in human memory.

  20. Modulation of allele leakiness and adaptive mutability in Escherichia coli

    Indian Academy of Sciences (India)

    R. Jayaraman

    2000-08-01

    It is shown that partial phenotypic suppression of two ochre mutations (argE3 and lacZU118) and an amber mutation (in argE) by sublethal concentrations of streptomycin in an rpsL+ (streptomycin-sensitive) derivative of the Escherichia coli strain AB1157 greatly enhances their adaptive mutability under selection. Streptomycin also increases adaptive mutability brought about by the ppm mutation described earlier. Inactivation of recA affects neither phenotypic suppression by streptomycin nor replication-associated mutagenesis but abolishes adaptive mutagenesis. These results indicate a causal relationship between allele leakiness and adaptive mutability.

  1. Human placental alkaline phosphatase electrophoretic alleles: Quantitative studies

    Science.gov (United States)

    Lucarelli, Paola; Scacchi, Renato; Corbo, Rosa Maria; Benincasa, Alberto; Palmarino, Ricciotti

    1982-01-01

    Human placental alkaline phosphatase (ALP) activity has been determined in specimens obtained from 562 Italian subjects. The mean activities of the three common homozygotes (Pl 2 = 4.70 ± 0.24, Pl 1 = 4.09 ± 0.08, and Pl 3 = 2.15 ± 0.71 μmol of p-nitrophenol produced) were significantly different. The differences among the various allelic forms account for 10% of the total quantitative variation of the human placental alkaline phosphatase. PMID:7072721

  2. Tandem repeat regions within the Burkholderia pseudomallei genome and their application for high resolution genotyping

    Directory of Open Access Journals (Sweden)

    Harvey Steven P

    2007-03-01

    Full Text Available Abstract Background The facultative, intracellular bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a serious infectious disease of humans and animals. We identified and categorized tandem repeat arrays and their distribution throughout the genome of B. pseudomallei strain K96243 in order to develop a genetic typing method for B. pseudomallei. We then screened 104 of the potentially polymorphic loci across a diverse panel of 31 isolates including B. pseudomallei, B. mallei and B. thailandensis in order to identify loci with varying degrees of polymorphism. A subset of these tandem repeat arrays were subsequently developed into a multiple-locus VNTR analysis to examine 66 B. pseudomallei and 21 B. mallei isolates from around the world, as well as 95 lineages from a serial transfer experiment encompassing ~18,000 generations. Results B. pseudomallei contains a preponderance of tandem repeat loci throughout its genome, many of which are duplicated elsewhere in the genome. The majority of these loci are composed of repeat motif lengths of 6 to 9 bp with 4 to 10 repeat units and are predominately located in intergenic regions of the genome. Across geographically diverse B. pseudomallei and B.mallei isolates, the 32 VNTR loci displayed between 7 and 28 alleles, with Nei's diversity values ranging from 0.47 and 0.94. Mutation rates for these loci are comparable (>10-5 per locus per generation to that of the most diverse tandemly repeated regions found in other less diverse bacteria. Conclusion The frequency, location and duplicate nature of tandemly repeated regions within the B. pseudomallei genome indicate that these tandem repeat regions may play a role in generating and maintaining adaptive genomic variation. Multiple-locus VNTR analysis revealed extensive diversity within the global isolate set containing B. pseudomallei and B. mallei, and it detected genotypic differences within clonal lineages of both species that were

  3. 多巴胺转运体基因多态性与异常体液型乳腺癌的相关性%Association analysis between polymorphism of dopamine transporter variable number tandem repeat and breast cancer with abnormal Hilit

    Institute of Scientific and Technical Information of China (English)

    彭晓梅; 哈木拉提·吾甫尔; 多力坤·买买提玉素甫; 代文成; 吐尔逊·买买提

    2010-01-01

    目的 探讨多巴胺转运体基因(DATl)3'端40 bp VNTR多态性与新疆维吾尔自治区汉族人群异常体液型乳腺癌的相关性.方法 按维吾尔医学将乳腺癌患者分为4种体液型,采用聚合酶链式反应(PCR)和VNTR多态性分析技术对新疆汉族144例乳腺癌患者和104名正常对照组DAT1多态性进行检测,比较各组间等位基因和基因型频率分布的差异.结果 所测人群中,DAT1VNTR多态性表现出7、9-11倍重复的4种等位基因,其中最常见的等位基因为10倍重复的480 bp片段,其基因频率为90.9%;共检出7种基因型,其中最常见的基因型为10/10倍重复,占83.1%.异常黏液质型乳腺癌患者的DAT1 VNTR 10倍重复等位基因和10/10倍重复基因型频率显著高于正常对照组(OR=0.127,95%CI为0.016~0.988,P=0.026;OR=0.134,95%CI为0.018-1.016,P=0.020)和异常胆液质型乳腺癌患者组(OR=0.132,95%CI为0.016~1.075,P=0.049;OR=0.132,95%CI为0.017-1.042,P=0.033).结论 多巴胺转运体基冈(DAT1)3'端40 bp VNTR10倍重复等位基因和10/10倍重复基因型可能增加新疆汉族维吾尔医异常黏液质型乳腺癌的发病风险,可能与异常胆液质型乳腺癌易感件无关.%Objective To explore the association between polymorphism of dopamine 1 transporter variable number tandem repeat ( DAT1 VNTR) and breast cancer with abnormal Hilit in Chinese Han population from Xinjiang. Methods The breast caner patients were divided into four body fluids according to Uighur medicine theory. And polymerase chain reaction and VNTR polymorphism technique were employed to detect genotypie and allelie frequencies of a 40 bp VNTR polymorphism situated in 3'untranslated region of DAT1 gene in 144 breast cancer patients with abnormal Hilit and 104 normal control subjects in Han population of Xinjiang province. Results In our sample, the repeat numbers of 40 bp were 7 and 9-11 (PCR product length of 360 bp and 440 bp to 520 bp) and 10-repeat allele (480 bp

  4. A high-throughput method for genotyping S-RNase alleles in apple

    DEFF Research Database (Denmark)

    Larsen, Bjarne; Ørgaard, Marian; Toldam-Andersen, Torben Bo

    2016-01-01

    We present a new efficient screening tool for detection of S-alleles in apple. The protocol using general and multiplexed primers for PCR reaction and fragment detection on an automatized capillary DNA sequencer exposed a higher number of alleles than any previous studies. Analysis of alleles...... is made on basis of three individual fragment sizes making the allele interpretation highly accurate. The method was employed to genotype 432 Malus accessions and exposed 25 different S-alleles in a selection of Malus domestica cultivars of mainly Danish origin (402 accessions) as well as a selection...

  5. Correlation between haplotype of apolipoprotein B gene and natural longevity persons in Uygur Nationality

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This paper investigated the correlation between polymorphisms and haplotypes in the apolipoprotein B (apoB) gene (SP-I/D, XbaI-RFLP, VNTR) and natural longevity persons among the Uygur people in Xin-jiang. For this purpose, 191 healthy Uygur individuals aged above 90 from Hetian area of Xinjiang were recruited, and another 53 persons aged 65—70 from the same nationality, the same region and with the same gender ratio, served as the control group. Genotyping was performed by PCR-SSP, PCR-RFLP and PCR-sequencing methods. Logistic regression analyses revealed that the frequencies of X+X+ genotype, M and L alleles and the genetypes composed of M and L were significantly higher in the longevity group than in the control group. In haplotype analyses, we found that, in the long-lived people, the frequency of haplotypes composed of the X+ and M alleles was significantly higher whereas the frequency of haplotypes composed of the X- and S alleles was significantly lower (both P<0.05) I than those of their controls. These results indicated that the S allele, SS genotype and X+-S, D-S, D-X+-S haplotypes were the possible adverse factors, whereas the M, L alleles, X+X+, MM, ML, LL genotypes and I-X+-M, X+-M haplotypes were the possibe protective factors for the naturally long-lived Uygur people in China.

  6. Correlation between haplotype of apolipoprotein B gene and natural longevity persons in Uygur Nationality

    Institute of Scientific and Technical Information of China (English)

    JIANG WenXi; QIU ChangChun; CHENG ZuHeng; ZHOU WenYu; GU MingLiang; XU Qun; FANG MingWu; NIU WenQuan

    2007-01-01

    This paper investigated the correlation between polymorphisms and haplotypes in the apolipoprotein B (apoB) gene (SP-I/D, XbaI-RFLP, VNTR) and natural longevity persons among the Uygur people in Xinjiang. For this purpose, 191 healthy Uygur individuals aged above 90 from Hetian area of Xinjiang were recruited, and another 53 persons aged 65-70 from the same nationality, the same region and with the same gender ratio, served as the control group. Genotyping was performed by PCR-SSP, PCR-RFLP and PCR-sequencing methods. Logistic regression analyses revealed that the frequencies of X+X+ genotype, M and L alleles and the genetypes composed of M and L were significantly higher in the longevity group than in the control group. In haplotype analyses, we found that, in the long-lived people, the frequency of haplotypes composed of the X+ and M alleles was significantly higher whereas the frequency of haplotypes composed of the X- and S alleles was significantly lower (both P<0.05) I than those of their controls. These results indicated that the S allele, SS genotype and X+-S, D-S, D-X+-S haplotypes were the possible adverse factors, whereas the M, L alleles, X+X+, MM, ML, LL genotypes and I-X+-M, X+-M haplotypes were the possibe protective factors for the naturally long-lived Uygur people in China.

  7. MUC1 gene polymorphism in three Nelore lines selected for growth and its association with growth and carcass traits.

    Science.gov (United States)

    de Souza, Fabio Ricardo Pablos; Maione, Sandra; Sartore, Stefano; Soglia, Dominga; Spalenza, Veronica; Cauvin, Elsa; Martelli, Lucia Regina; Mercadante, Maria Eugênia Zerlotti; Sacchi, Paola; de Albuquerque, Lucia Galvão; Rasero, Roberto

    2012-02-01

    The objective of this study was to describe the VNTR polymorphism of the mucin 1 gene (MUC1) in three Nelore lines selected for yearling weight to determine whether allele and genotype frequencies of this polymorphism were affected by selection for growth. In addition, the effects of the polymorphism on growth and carcass traits were evaluated. Birth, weaning and yearling weights, rump height, Longissimus muscle area, backfat thickness, and rump fat thickness, were analyzed. A total of 295 Nelore heifers from the Beef Cattle Research Center, Instituto de Zootecnia de Sertãozinho, were used, including 41 of the control line, 102 of the selection line and 152 of the traditional. The selection and traditional lines comprise animals selected for higher yearling weight, whereas control line animals are selected for yearling weight close to the average. Five alleles were identified, with allele 1 being the most frequent in the three lines, especially in the lines selected for higher means for yearling weight. Heterozygosity was significantly higher in the control line. Association analyses showed significant effects of allele 1 on birth weight and weaning weight while the allele 3 exert significant effects on yearling weight and back fat thickness. Despite these findings, application of this marker to marker-assisted selection requires more consistent results based on the genotyping of a larger number of animals in order to increase the accuracy of the statistical analyses.

  8. Typing Method for the QUB11a Locus of Mycobacterium tuberculosis: IS6110 Insertions and Tandem Repeat Analysis

    Directory of Open Access Journals (Sweden)

    Eriko Maeda-Mitani

    2016-01-01

    Full Text Available QUB11a is used as a locus for variable number of tandem repeats (VNTR analysis of Mycobacterium tuberculosis Beijing lineage. However, amplification of QUB11a occasionally produces large fragments (>1,400 bp that are not easily measured by capillary electrophoresis because of a lack of the typical stutter peak patterns that are used for counting repeat numbers. IS6110 insertion may complicate VNTR analysis of large QUB11a fragments in M. tuberculosis. We established a method for determining both tandem repeat numbers and IS6110 insertion in the QUB11a locus of M. tuberculosis using capillary electrophoresis analysis and BsmBI digestion. All 29 large QUB11a fragments (>1,200 bp investigated contained IS6110 insertions and varied in the number of repeats (18 patterns and location of IS6110 insertions. This method allows VNTR analysis with high discrimination.

  9. Multiplex agarose gel electrophoresis system for variable number of tandem repeats genotyping: analysis example using Mycobacterium tuberculosis.

    Science.gov (United States)

    Wada, Takayuki; Maeda, Shinji

    2013-04-01

    As one genotyping method for Mycobacterium tuberculosis, variable number of tandem repeats (VNTR) is a promising tool to trace the undefined transmission of tuberculosis, but it often requires large equipment such as a genetic analyzer for DNA fragment analysis or CE system to conduct systematic analyses. For convenient genotyping at low cost in laboratories, we designed a multiplex PCR system that is applicable to agarose gel electrophoresis using fluorescent PCR primers. For tuberculosis genotyping by VNTR, the copy quantities of minisatellite DNA must be determined in more than 12 loci. The system can halve laborious electrophoresis processes by presenting an image of two VNTR amplicons on a single lane. No expensive equipment is necessary for this method. Therefore, it is useful even in developing countries. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. INTERLEUKIN 1 AND INTERLEUKIN 4 GENES POLYMORPHISM ASSOCIATED WITH EARLY AND PRESCHOOL AGE CHILDREN SENSITIZATION TO STREPTOCOCCUS PYOGENES

    Directory of Open Access Journals (Sweden)

    A. V. Shabaldin

    2016-01-01

    Full Text Available Background. Streptococcus pyogenes infection and sensitization to its antigens is considered to be an unfavorable factor for the induction of rheumatic pathology. The search for genetic predictors of rheumatic diseases in general, and sensitization to S. pyogenes, in particular, is of high relevance in modern medicine.Objective. To study the associations between interleukin 1 and interleukin 4 gene polymorphisms and the development of sensitization to antigens of S. pyogenes in toddlers and preschool children.Materials and methods. 771 children aged 2–6 years with recurrent acute respiratory tract infections treated by allergist-immunologist and otorhinolaryngologist were included in the study. Antibodies against S. pyogenes were determined by ELISA using commercial kits “Immunoteks” (Stavropol, Russia in all children. Children with IgG immune response to S. pyogenes were assigned to the study group (n = 306, whereas children without this response were assigned to the control group (n = 465. Both groups underwent gene typing of IL1B (+3953, C→T, rs 114634, IL1Ra (VNTR, intron 2, 89 bp and IL4 (VNTR intron 3, 70 bp gene polymorphisms in the Laboratory for Pharmacogenomics, ICBFM SB RAS. The data were processed using routine statistical methods for genetic analysis and the statistical software package Statistica 6.0. There were no deviations from Hardy–Weinberg equilibrium across all loci, suggesting validity of association studies between individual and combined genotypes and sensitization to antigens of S. pyogenes.Results. Positive association between sensitization to antigens of S. pyogenes and individual genotypes have been found: IL1B (+3953, C→T*C,T (52.6% in the study group vs. 39.8% in the control group, p = 0.001; OR = 2.02; CI(99% 0.47–5.93, IL1Ra (VNTR, intron 2, 89 bp*2r,5r (7.19% in the study group vs. 1.29% in the control group, p = 0.001; OR = 5.59; CI(99% 1.58–19.77, IL4 (VNTR intron 3, 70 bp*2r,2r (6

  11. Polymorphism of Mhc-DRB alleles in Cercopithecus aethiops (green monkey): generation and functionality.

    Science.gov (United States)

    Rosal-Sánchez, M; Paz-Artal, E; Moreno-Pelayo, M A; Martínez-Quiles, N; Martínez-Laso, J; Martín-Villa, J M; Arnaiz-Villena, A

    1998-05-01

    DRB genes have been studied for the first time in green monkeys (Cercopithecus aethiops). Eleven new DRB alleles (exon 2, exon 3) have been obtained and sequenced from cDNA. A limited number of lineages have been identified: DRB1*03 (4 alleles), DRB1*07 (3 alleles), DRB5 (1 allele), DRB*w6 (1 allele), and DRB*w7 (2 alleles). The existence of Ceae-DRB1 duplications is supported by the finding of 3 DRB1 alleles in 3 different individuals. Ceae-DRB1*0701 may be non-functional because it bears serine at position 82, which hinders molecule surface expression in mice; the allele is only found in Ceae-DRB duplicated haplotypes. Base changes in cDNA Ceae-DRB alleles are consistent with the generation of polymorphism by point mutations or short segment exchanges between alleles. The eleven green monkey DRB alleles meet the requirements for functionality as antigen-presenting molecules (perhaps, excluding DRB1*0701), since: 1) they have been isolated from cDNA and do not present deletions, insertions or stop codons: 2) structural motifs necessary for a correct folding of the molecule, for the formation of DR/DR dimers and for CD4 interactions are conserved, and 3) the number of non-synonymous substitutions is higher than the number of synonymous substitutions in the peptide binding region (PBR), while the contrary holds true for the non-PBR region.

  12. Analysis of elite variety tag SNPs reveals an important allele in upland rice.

    Science.gov (United States)

    Lyu, Jun; Zhang, Shilai; Dong, Yang; He, Weiming; Zhang, Jing; Deng, Xianneng; Zhang, Yesheng; Li, Xin; Li, Baoye; Huang, Wangqi; Wan, Wenting; Yu, Yang; Li, Qiong; Li, Jun; Liu, Xin; Wang, Bo; Tao, Dayun; Zhang, Gengyun; Wang, Jun; Xu, Xun; Hu, Fengyi; Wang, Wen

    2013-01-01

    Elite crop varieties usually fix alleles that occur at low frequencies within non-elite gene pools. Dissecting these alleles for desirable agronomic traits can be accomplished by comparing the genomes of elite varieties with those from non-elite populations. Here we deep-sequence six elite rice varieties and use two large control panels to identify elite variety tag single-nucleotide polymorphism alleles (ETASs). Guided by this preliminary analysis, we comprehensively characterize one protein-altering ETAS in the 9-cis-epoxycarotenoid dioxygenase gene of the IRAT104 upland rice variety. This allele displays a drastic frequency difference between upland and irrigated rice, and a selective sweep is observed around this allele. Functional analysis indicates that in upland rice, this allele is associated with significantly higher abscisic acid levels and denser lateral roots, suggesting its association with upland rice suitability. This report provides a potential strategy to mine rare, agronomically important alleles.

  13. Allelic Diversity of Major Histocompatibility Complex Class II DRB Gene in Indian Cattle and Buffalo

    Directory of Open Access Journals (Sweden)

    Sachinandan De

    2011-01-01

    Full Text Available The present study was conducted to study the diversity of MHC-DRB3 alleles in Indian cattle and buffalo breeds. Previously reported BoLA-DRB exon 2 alleles of Indian Zebu cattle, Bos taurus cattle, buffalo, sheep, and goats were analyzed for the identities and divergence among various allele sequences. Comparison of predicted amino acid residues of DRB3 exon 2 alleles with similar alleles from other ruminants revealed considerable congruence in amino acid substitution pattern. These alleles showed a high degree of nucleotide and amino acid polymorphism at positions forming peptide-binding regions. A higher rate of nonsynonymous substitution was detected at the peptide-binding regions, indicating that BoLA-DRB3 allelic sequence evolution was driven by positive selection.

  14. Allelic variation in the NPY gene in 14 Indian populations.

    Science.gov (United States)

    Bhaskar, L V K S; Thangaraj, K; Shah, Anish M; Pardhasaradhi, G; Praveen Kumar, K; Reddy, A G; Papa Rao, A; Mulligan, C J; Singh, Lalji; Rao, V R

    2007-01-01

    NPY is a 36-aminoacid peptide expressed in several areas of the nervous system. Neuropeptide Y (NPY) receptors represent a widely diffused system that is involved in the regulation of multiple biological functions. The human NPY gene is located in chromosome 7. The functional significance of coding Leu7Pro polymorphism in the signal peptide of preproNPY is known. Six hundred and fifty four individuals of 14 ethnic Indian populations were screened for three mutations in the NPY gene, including Leu7Pro. We found that the Pro7 frequencies among the studied populations were much higher than in previous studies from other parts of the world. The highest allele frequency of Pro7 was detected in the Kota population in the Nilgiri Hill region of south India, and this may reflect a founder event in the past or genetic drift. All populations followed the Hardy-Weinberg equilibrium for the assayed markers. A total of five haplotypes were observed, only two of which were found to occur with a high frequency in all populations. No linkage disequilibrium (LD) was observed across the tested alleles in any population with the exception of Leu7Pro and Ser50Ser in the Badaga population (chi(2) = 13.969; p = 0.0001).

  15. Characterization of ROP18 alleles in human toxoplasmosis.

    Science.gov (United States)

    Sánchez, Víctor; de-la-Torre, Alejandra; Gómez-Marín, Jorge Enrique

    2014-04-01

    The role of the virulent gene ROP18 polymorphisms is not known in human toxoplasmosis. A total of 320 clinical samples were analyzed. In samples positive for ROP18 gene, we determined by an allele specific PCR, if patients got the upstream insertion positive ROP18 sequence Toxoplasma strain (mouse avirulent strain) or the upstream insertion negative ROP18 sequence Toxoplasma strain (mouse virulent strain). We designed an ELISA assay for antibodies against ROP18 derived peptides from the three major clonal lineages of Toxoplasma. 20 clinical samples were of quality for ROP18 allele analysis. In patients with ocular toxoplasmosis, a higher inflammatory reaction on eye was associated to a PCR negative result for the upstream region of ROP18. 23.3%, 33% and 16.6% of serums from individuals with ocular toxoplasmosis were positive for type I, type II and type III ROP18 derived peptides, respectively but this assay was affected by cross reaction. The absence of Toxoplasma ROP18 promoter insertion sequence in ocular toxoplasmosis was correlated with severe ocular inflammatory response. Determination of antibodies against ROP18 protein was not useful for serotyping in human toxoplasmosis.

  16. Allele frequency of CODIS 13 in Indonesian population.

    Science.gov (United States)

    Untoro, Evi; Atmadja, Djaja Surya; Pu, Chang-En; Wu, Fang-Chi

    2009-04-01

    Since the first application of DNA technology in 1985 in forensic cases, and the acceptance of this technology in 1988 at court, the DNA typing is widely used in personal identification, parentage cases and tracing the source of biological samples found in the crime scene. The FBI on 1990 had recommended the forensic labs to used 13 loci of Short Tandem Repeats (STR), known as CODIS 13, as the loci of choice for forensic use. The research on the population DNA database on these loci is extremely important for calculating the Paternity Index as well as Matching Probability for forensic application of DNA technology. As many as 402 unrelated persons, consisted of 322 from western part of Indonesia and 80 from eastern part of Indonesia, were chosen as the respondents of this research, after signing the informed consent. The peripheral blood sample was taken using sterile lancets and dropped onto FTA classic cards. The DNA was extracted by FTA purification solution (3x) and TE(-1) (2x), and amplified by PCR mix, either Cofiler or Profiler Plus (Perkin Elmers), followed by sequencing using ABI Prism type 3100 Avant Genetic Analyzer. The analysis showed that the alleles frequencies of Indonesian is specific, different with the other Asian populations with some specific alleles and microvariant were found.

  17. An allele of the crm gene blocks cyanobacterial circadian rhythms.

    Science.gov (United States)

    Boyd, Joseph S; Bordowitz, Juliana R; Bree, Anna C; Golden, Susan S

    2013-08-20

    The SasA-RpaA two-component system constitutes a key output pathway of the cyanobacterial Kai circadian oscillator. To date, rhythm of phycobilisome associated (rpaA) is the only gene other than kaiA, kaiB, and kaiC, which encode the oscillator itself, whose mutation causes completely arrhythmic gene expression. Here we report a unique transposon insertion allele in a small ORF located immediately upstream of rpaA in Synechococcus elongatus PCC 7942 termed crm (for circadian rhythmicity modulator), which results in arrhythmic promoter activity but does not affect steady-state levels of RpaA. The crm ORF complements the defect when expressed in trans, but only if it can be translated, suggesting that crm encodes a small protein. The crm1 insertion allele phenotypes are distinct from those of an rpaA null; crm1 mutants are able to grow in a light:dark cycle and have no detectable oscillations of KaiC phosphorylation, whereas low-amplitude KaiC phosphorylation rhythms persist in the absence of RpaA. Levels of phosphorylated RpaA in vivo measured over time are significantly altered compared with WT in the crm1 mutant as well as in the absence of KaiC. Taken together, these results are consistent with the hypothesis that the Crm polypeptide modulates a circadian-specific activity of RpaA.

  18. Cytochrome allelic variants and clopidogrel metabolism in cardiovascular diseases therapy.

    Science.gov (United States)

    Jarrar, Mohammed; Behl, Shalini; Manyam, Ganiraju; Ganah, Hany; Nazir, Mohammed; Nasab, Reem; Moustafa, Khaled

    2016-06-01

    Clopidogrel and aspirin are among the most prescribed dual antiplatelet therapies to treat the acute coronary syndrome and heart attacks. However, their potential clinical impacts are a subject of intense debates. The therapeutic efficiency of clopidogrel is controlled by the actions of hepatic cytochrome P450 (CYPs) enzymes and impacted by individual genetic variations. Inter-individual polymorphisms in CYPs enzymes affect the metabolism of clopidogrel into its active metabolites and, therefore, modify its turnover and clinical outcome. So far, clinical trials fail to confirm higher or lower adverse cardiovascular effects in patients treated with combinations of clopidogrel and proton pump inhibitors, compared with clopidogrel alone. Such inconclusive findings may be due to genetic variations in the cytochromes CYP2C19 and CYP3A4/5. To investigate potential interactions/effects of these cytochromes and their allele variants on the treatment of acute coronary syndrome with clopidogrel alone or in combination with proton pump inhibitors, we analyze recent literature and discuss the potential impact of the cytochrome allelic variants on cardiovascular events and stent thrombosis treated with clopidogrel. The diversity of CYP2C19 polymorphisms and prevalence span within various ethnic groups, subpopulations and demographic areas are also debated.

  19. Low frequency of the scrapile resistance-associated allele and presence of lysine-171 allele of the prion protein gene in Italian Biellese ovine breed

    NARCIS (Netherlands)

    Acutis, P.L.; Sbaiz, L.; Verburg, F.J.; Riina, M.V.; Ru, G.; Moda, G.; Caramelli, M.; Bossers, A.

    2004-01-01

    Frequencies of polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene were studied in 1207 pure-bred and cross-bred Italian Biellese rams, a small ovine breed of about 65 000 head in Italy. Aside from the five most common alleles (VRQ, ARQ, ARR, AHQ and ARH), the rare ARK allele wa

  20. Low frequency of the scrapile resistance-associated allele and presence of lysine-171 allele of the prion protein gene in Italian Biellese ovine breed

    NARCIS (Netherlands)

    Acutis, P.L.; Sbaiz, L.; Verburg, F.J.; Riina, M.V.; Ru, G.; Moda, G.; Caramelli, M.; Bossers, A.

    2004-01-01

    Frequencies of polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene were studied in 1207 pure-bred and cross-bred Italian Biellese rams, a small ovine breed of about 65 000 head in Italy. Aside from the five most common alleles (VRQ, ARQ, ARR, AHQ and ARH), the rare ARK allele

  1. Epidemiological tracing of bovine tuberculosis in Switzerland, multilocus variable number of tandem repeat analysis of Mycobacterium bovis and Mycobacterium caprae

    Science.gov (United States)

    Scherrer, Simone; Friedel, Ute; Frei, Daniel; Suter, Dominique; Perler, Lukas; Wittenbrink, Max M.

    2017-01-01

    Background After 15 years of absence, in 2013 bovine tuberculosis (bTB), caused by Mycobacterium (M.) bovis and M. caprae, reemerged in the Swiss dairy cattle population. In order to identify the sources of infection as well as the spread of the agents, molecular-epidemiologic tracing by MIRU-VNTR analysis in combination with spoligotyping was performed. A total of 17 M. bovis and 7 M. caprae isolates were cultured from tuberculous bovine lymph nodes and analyzed with a set of 49 genetic markers by using automated capillary electrophoresis. Results The outbreak in the western part of Switzerland was caused by M. bovis spoligotype SB0120. With the exception of four single-locus variations observed in MIRU 20, the MIRU-VNTR profiles of the 17 M. bovis isolates were identical, indicating a single source of infection. M. bovis detected in one archival bovine specimen from the outbreak region showed an identical MIRU-VNTR profile, suggesting persistence of the agent in a dairy herd for nearly fifteen years. The outbreak in the eastern part of Switzerland was caused by M. caprae spoligotype SB0418. All Swiss M. caprae isolates showed the Lechtal-type MIRU-VNTR profile, described as endemic in wild ruminants and in dairy cattle in Austrian bordering regions. This suggests the agent was most likely introduced by Swiss dairy cattle summering on Austrian pastures. Conclusions The present study is the first MIRU-VNTR analysis of Swiss bTB mycobacterial isolates. The genotyping assay was found to be highly discriminating and suitable for the epidemiological tracing of further outbreaks. These findings will contribute to the development of an international MIRU-VNTR database aiming to improve bTB surveillance. PMID:28222182

  2. Distribution of FMR-1 and associated microsatellite alleles in a normal Chinese population

    Energy Technology Data Exchange (ETDEWEB)

    Zhong, N.; Houck, G.E. Jr.; Li, S.; Dobkin, C.; Brown, W.T. [New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY (United States); Xixian Liu; Shen Gou [Tongji Medical Univ., Wuhan (China)

    1994-07-15

    The CGG repeat size distribution of the fragile X mental retardation gene (FMR-1) was studied in a population of normal Chinese X chromosomes along with that of two proximal microsatellite polymorphic markers: FRAXAC1 and DXS548. The most common CGG repeat allele was 29 (47.2%) with 30 being second most common (26%). This distribution was different from that seen in Caucasian controls, where the most common allele was 30 repeats. Other differences with Caucasian controls included a secondary model peak at 36 repeats and the absence of peaks at 20 or 23 repeats. There were only two FRAXAC1 and five DXS548 alleles found in the Chinese sample. A striking linkage disequilibrium of FMR-1 alleles with FRAXAC1 alleles was observed, in that 90% of the 29 CGG repeat alleles but only 41% of the 30 CGG repeat alleles had the FRAXAC1 152 bp allele (18 AC repeats). This disequilibrium suggests that slippage between the closely spaced normal CGG repeat alleles, 29 and 30, and between 152 and 154 FRAXAC1 alleles is very rare. This study lays the groundwork for an understanding of founder chromosome effects in comparing Asian and Caucasian populations. 29 refs., 5 tabs.

  3. A new analysis tool for individual-level allele frequency for genomic studies

    Directory of Open Access Journals (Sweden)

    Pan Wen-Harn

    2010-07-01

    Full Text Available Abstract Background Allele frequency is one of the most important population indices and has been broadly applied to genetic/genomic studies. Estimation of allele frequency using genotypes is convenient but may lose data information and be sensitive to genotyping errors. Results This study utilizes a unified intensity-measuring approach to estimating individual-level allele frequencies for 1,104 and 1,270 samples genotyped with the single-nucleotide-polymorphism arrays of the Affymetrix Human Mapping 100K and 500K Sets, respectively. Allele frequencies of all samples are estimated and adjusted by coefficients of preferential amplification/hybridization (CPA, and large ethnicity-specific and cross-ethnicity databases of CPA and allele frequency are established. The results show that using the CPA significantly improves the accuracy of allele frequency estimates; moreover, this paramount factor is insensitive to the time of data acquisition, effect of laboratory site, type of gene chip, and phenotypic status. Based on accurate allele frequency estimates, analytic methods based on individual-level allele frequencies are developed and successfully applied to discover genomic patterns of allele frequencies, detect chromosomal abnormalities, classify sample groups, identify outlier samples, and estimate the purity of tumor samples. The methods are packaged into a new analysis tool, ALOHA (Allele-frequency/Loss-of-heterozygosity/Allele-imbalance. Conclusions This is the first time that these important genetic/genomic applications have been simultaneously conducted by the analyses of individual-level allele frequencies estimated by a unified intensity-measuring approach. We expect that additional practical applications for allele frequency analysis will be found. The developed databases and tools provide useful resources for human genome analysis via high-throughput single-nucleotide-polymorphism arrays. The ALOHA software was written in R and R GUI and

  4. Substrate specificity of allelic variants of the TAP peptide transporter.

    Science.gov (United States)

    Heemels, M T; Ploegh, H L

    1994-12-01

    The transporter associated with antigen processing (TAP) translocates peptides from the cytosol into the lumen of the endoplasmic reticulum (ER). An important determinant for the specificity of translocation is the identity of the C-terminal residue of the peptide substrate. In the rat, a suitable C terminus is necessary but not always sufficient for a peptide to be selected for translocation. Here we show that sequence constraints within a peptide of optimal length (9 residues) may interfere with transport; that the transporter selectively translocates shorter derivatives of a 16-mer peptide rather than the 16-mer itself; and that the transporter cimb allele, which is most selective in the C termini it will tolerate, is more relaxed in peptide length preference than is the clma variant.

  5. The microcephalin ancestral allele in a Neanderthal individual.

    Directory of Open Access Journals (Sweden)

    Martina Lari

    Full Text Available BACKGROUND: The high frequency (around 0.70 worldwide and the relatively young age (between 14,000 and 62,000 years of a derived group of haplotypes, haplogroup D, at the microcephalin (MCPH1 locus led to the proposal that haplogroup D originated in a human lineage that separated from modern humans >1 million years ago, evolved under strong positive selection, and passed into the human gene pool by an episode of admixture circa 37,000 years ago. The geographic distribution of haplogroup D, with marked differences between Africa and Eurasia, suggested that the archaic human form admixing with anatomically modern humans might have been Neanderthal. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the first PCR amplification and high-throughput sequencing of nuclear DNA at the microcephalin (MCPH1 locus from Neanderthal individual from Mezzena Rockshelter (Monti Lessini, Italy. We show that a well-preserved Neanderthal fossil dated at approximately 50,000 years B.P., was homozygous for the ancestral, non-D, allele. The high yield of Neanderthal mtDNA sequences of the studied specimen, the pattern of nucleotide misincorporation among sequences consistent with post-mortem DNA damage and an accurate control of the MCPH1 alleles in all personnel that manipulated the sample, make it extremely unlikely that this result might reflect modern DNA contamination. CONCLUSIONS/SIGNIFICANCE: The MCPH1 genotype of the Monti Lessini (MLS Neanderthal does not prove that there was no interbreeding between anatomically archaic and modern humans in Europe, but certainly shows that speculations on a possible Neanderthal origin of what is now the most common MCPH1 haplogroup are not supported by empirical evidence from ancient DNA.

  6. Characteristics and distribution of 11 variable number tandem repeats of Bacillus anthracis in China%中国炭疽芽胞杆菌中11个串联重复序列位点的特征和分布

    Institute of Scientific and Technical Information of China (English)

    魏建春; 张恩民; 张慧娟; 张建华

    2012-01-01

    目的 检测炭疽芽胞杆菌中可变数量串联重复序列(VNTR)的变化,分析我国菌株中VNTR的特征和分布规律.方法 PCR扩增.琼脂糖电泳和毛细管电泳,测序验证,BLAST比对等.结果 11个VNTR位点中有4个在所有菌株中没有差别,另外7个位点只在个别菌株中检测到差别,有差别的菌株多分布在新疆;11个VNTR位点均位于基因编码区内,编码对细菌生存重要的蛋白和一些功能不明蛋白.结论 结果提示新疆的菌株类型较复杂;本研究中的VNTR位点比较保守,可能不能用于区别不同的炭疽芽胞杆菌,但对于了解炭疽芽胞杆菌的基因组特征以及鉴定炭疽芽胞杆菌具有一定的作用.%To study the characteristics and distribution of the variable number tandem repeat (VNTR) of Bacillus an-thracis in China, we selected 109 strains isolated from 17 provinces, and the polymorphism of 11 VNTR loci were studied by polymerase chain reaction (PCR). The PCR products were detected by agarose electrophoresis or capillary electrophoresis, and different DNA fragment in each VNTR locus were sequenced. The results showed no difference was found in 4 of 11 VNTR loci in tested strains; a few strains were detected different from most strains in 7 VNTR loci. All of VNTR loci were located in genes encoding important protein and some hypothetical protein. The results suggest that these strains isolated from Xinjiang were complicated. Although these VNTR loci varied too lightly to distinguish Bacillus anthracis strains, it's useful to understand the genome characteristics and identify Bacillus anthracis strains from other Bacillus species.

  7. X-linked nephrogenic diabetes insipidus: From the ship Hopewell to RFLP studies

    Energy Technology Data Exchange (ETDEWEB)

    Bichet, D.G.; Lonergan, M.; Arthus, M.F.; Ligier, S.; Kluge, R. (Universite de Montreal (Canada)); Hendy, G.N.; Pausova, Z.; Zingg, H.; Morgan, K.; Saenger, P. (McGill Univ., Montreal (Canada)) (and others)

    1992-11-01

    Nephrogenic diabetes insipidus (NDI; designated 304800 in Mendelian Inheritance in Man) is an X-linked disorder with abnormal renal and extrarenal V[sub 2] vasopression receptor responses. The mutant gene has been mapped to Xq28 by analysis of RFLPs, and tight linkage between DXS52 and DNI has been reported. In 1969, Bode and Crawford proposed, under the term, the Hopewell hypothesis' that most cases in North America could be traced to descendants of Ulster Scots who arrived in Nova Scotia in 1761 on the ship Hopewell. They also suggested a link between this family and a large Mormon pedigree. DNA samples obtained from 13 independent affected families, including 42 members of the Hopewell and Mormon pedigrees, were analyzed with probes in the Xq28 region. Genealogical reconstructions were performed. Linkage between NDI and DXS304 (probe U6:2.spl), DXS305 (St35-691), DXS52 (St14-1), DXS15 (DX13), and F8C (F814) showed no recombination in 12 families, with a maximum lod score of 13.5 for DXS52. A recombinant between NDI and DXS304, DXS305, was identified in one family. The haplotype segregating with the disease in the Hopewell pedigree was not shared by other North American families. PCR analysis of the St14 VNTR allowed the distinction of two alleles that were not distinguishable by Southern analysis. Carrier status was predicted in 24 of 26 at-risk females. The Hopewell hypothesis cannot explain the origin of NDI in many of the North American families, since they have no apparent relationship with the Hopewell earlier settlers, either by haplotype or by genealogical analysis. PCR analysis of the DXS52 VNTR in NDI families is very useful for carrier testing and presymptomatic diagnosis, which can prevent the first manifestations of dehydration. 39 refs., 7 figs., 3 tabs.

  8. MLVA for Salmonella enterica subsp. enterica Serovar Dublin: Development of a Method Suitable for Inter-Laboratory Surveillance and Application in the Context of a Raw Milk Cheese Outbreak in France in 2012

    Science.gov (United States)

    Vignaud, Marie-Léone; Cherchame, Emeline; Marault, Muriel; Chaing, Emilie; Le Hello, Simon; Michel, Valerie; Jourdan-Da Silva, Nathalie; Lailler, Renaud; Brisabois, Anne; Cadel-Six, Sabrina

    2017-01-01

    Salmonella enterica subspecies enterica serovar Dublin (S. Dublin) figures among the most frequently isolated Salmonella strains in humans in France. This serovar may affect production and animal health mainly in cattle herds with corresponding high economic losses. Given that the current gold standard method, pulsed-field gel electrophoresis (PFGE), provides insufficient discrimination for epidemiological investigations, we propose a standard operating procedure in this study for multiple-locus variable number tandem repeat analysis (MLVA) of S. Dublin, suitable for inter-laboratory surveillance. An in silico analysis on the genome of S. Dublin strains CT_02021853 was performed to identify appropriate microsatellite regions. Of 21 VNTR loci screened, six were selected and 401 epidemiologically unrelated and related strains, isolated from humans, food and animals were analyzed to assess performance criteria such as typeability, discriminatory power and epidemiological concordance. The MLVA scheme developed was applied to an outbreak involving Saint-Nectaire cheese for which investigations were conducted in France in 2012, making it possible to discriminate between epidemiologically related strains and sporadic case strains, while PFGE assigned only a single profile. The six loci selected were sequenced on a large set of strains to determine the sequence of the repeated units and flanking regions, and their stability was evaluated in vivo through the analysis of the strains investigated from humans, food and the farm environment during the outbreak. The six VNTR selected were found to be stable and the discriminatory power of the MLVA method developed was calculated to be 0.954 compared with that for PFGE, which was only 0.625. Twenty-four reference strains were selected from the 401 examined strains in order to represent most of the allele diversity observed for each locus. This reference set can be used to harmonize MLVA results and allow data exchange between

  9. Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study

    Directory of Open Access Journals (Sweden)

    Srinouanprachan Sengkeo

    2007-04-01

    Full Text Available Abstract Background Genes involved in dopaminergic neurotransmission have been suggested as candidates for involvement in smoking behavior. We hypothesized that alleles associated with reduced dopaminergic neurotransmission would be more common in continuing smokers than among women who quit smoking. Methods The study included 593 women aged 26–65 years who participated in a twelve month smoking cessation trial conducted in 1993–1994. Participants were contacted three years after the trial to obtain updated smoking history and biological specimens. Seven polymorphisms were assessed in genes involved in dopamine synthesis (tyrosine hydoxylase [TH], receptor activation (dopamine receptors [DRD2, DRD3, DRD4], reuptake (dopamine transporter [SLC6A3], and metabolism (catechol-o-methyltransferase [COMT]. Smoking cessation was assessed as "short-term" quitting (abstinence for the seven days before the conclusion of the trial and "long-term" quitting (abstinence for the six months before a subsequent interview conducted several years later. Results We observed no association of any polymorphism with either short- or long-term quitting. Although some relative risk estimates were consistent with weak associations, either the direction of effect was opposite of that hypothesized, or results of the short- and long-term cessation endpoints differed. However, effect modification on smoking cessation was observed between DRD2 Taq1A and SLC6A3 VNTR polymorphisms, DRD3 Ser/Gly and d,1-fenfluramine, and DRD4 VNTR and d,1-fenfluramine. Conclusion Although these results fail to support prior findings of independent associations of these polymorphisms with smoking status, our exploratory findings suggestive of gene-gene and gene-treatment interactions warrants further investigation.

  10. Multicapillary gel electrophoresis based analysis of genetic variants in the WFS1 gene.

    Science.gov (United States)

    Elek, Zsuzsanna; Dénes, Réka; Prokop, Susanne; Somogyi, Anikó; Yowanto, Handy; Luo, Jane; Souquet, Manfred; Guttman, András; Rónai, Zsolt

    2016-09-01

    The WFS1 gene is one of the thoroughly investigated targets in diabetes research, variants of the gene were suggested to be the genetic components of the common forms (type 1 and type 2) of diabetes. Our project focused on the analysis of polymorphisms (rs4689388, rs148797429, rs4273545) localized in the WFS1 promoter region. Although submarine gel electrophoresis based approaches were also employed in the genetic tests, it was demonstrated that multicapillary electrophoresis offers a state of the art approach for reliable high-throughput SNP and VNTR analysis. Association studies were carried out in a case-control setup. Luciferase reporter assay was employed to test the effect of the investigated loci on the activity of gene expression in vitro. Significant association could be demonstrated between all three polymorphisms and type 2 diabetes in both allele- and genotype-wise settings even using Bonferroni correction. It is notable; however, that the three loci were in strong linkage disequilibrium, thus the observed associations cannot be considered as separate effects. Molecular analyses showed that the rs4273545 GT SNP played a role in the regulation of transcription in vitro. However, this effect took place only in the presence of the region including the rs148797429 site, although this latter locus did not have its own impact on the regulation of gene expression. The paper provides genotyping protocols readily applicable in any multiplex SNP and VNTR analyses, moreover confirms and extends previous results about the role of WFS1 polymorphisms in the genetic risk of diabetes mellitus. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. The Analysis of Genetic Polymorphism. The Relationship between Interleukin – 4 Polymorphisms and Intraepithelial Cervical Neoplasia

    Directory of Open Access Journals (Sweden)

    Florin STAMATIAN

    2010-09-01

    Full Text Available Objectives: Interleukin 4 plays a critical role in T helper 2 responses to HPV infection and angiogenesis. The present study aim to study the association between the IL4 promoter polymorphism – 590 C>T, respectively VNTR intron 2 polymorphism and cervical intraepithelial neoplasia. Material and method: We have realized a prospective case controls study that included 128 cases of intraepithelial neoplasia positive for HPV HR testing and 111 controls negative for intraepithelial lesion and also negative for HPV HR. Clinical examination was performed on each patient; blood and cervical sample were obtained. Cervical probes were analyzed regarding cytology and HPV HR testing. From peripheral blood DNA sample was obtain followed by genotype analysis for IL4 -590 C>T using PCR RFLP, respectively IL4 70 bp VNTR determined by PCR. Results: The absolute frequency of genotypes for IL4 -590 C>T was T/T-5, C/T-42, C/C-81 in the cases group respectively T/T-2, C/T-32, C/C-77 in the control group. The chi-square test had a value of 0.983 (p=0.321 while considering the presence of a minimum one single variant allele as a risk factor for cervical cancer, respectively 0.926 (p=0.336 for homozygous variant genotype. Odds ratio was 0.761 (95%CI [0.443-1.306] while considering C/T+T/T respectively 2R/3R, 2R/2R as a risk factor, and 0.451 (95%CI 95% [0.086-2.374] - TT respectively 2R/2R as a risk factor. Conclusion: No linear statistical significant association has been found between IL4 polymorphism and cervical neoplasia (p = 0.322.

  12. 血友病A家系ST14位点多态性检测及分析%Detection and analysis of polymorphism of ST14 site in hemophilia A patients and their family

    Institute of Scientific and Technical Information of China (English)

    冯大伟; 杨林花; 郭志萍

    2011-01-01

    目的 探讨提高血友病A患者及家系成员的基因诊断及携带者检出诊断率的途径.方法 对3个血友病A家系17例进行ST14可变数目串联重复序列多态位点检测.结果 ST14位点等位基因片段介于700~1700 bp,以700 bp最多,占39%,杂合率为88%.2个血友病A家系可以用该位点提供诊断信息.结论 ST14多态位点用于血友病A携带者检测是一个特异性高、信息量大的分子诊断标志.%Objective To explore for an approach that improves the gene diagnosis and carrier detection rates for hemophilia A patients and their family members. Methods Polymorphism detection of ST14 variable number tan dem repeats (VNTR) was performed in 3 hemophilia A families, with 17 cases in total. Result At ST14 VNTR, allelic fragments ranged from 700 to 1700 bp in size, and mostly at 700 bp, counting for 39%, and the heterozygosity rate was 88%. Diagnosis information of 2 families was made according to this site. Conclusion ST14 polymorphic site is a molecular diagnosis marker with high specificity and vast information in carrier detection of hemophilia A.

  13. Association between monoamine oxidase A gene promoter 30 bp repeat polymorphism and tardive dyskinesia in Chinese schizophrenics

    Institute of Scientific and Technical Information of China (English)

    Changhe Fan; Lihua Li; Yan Fu; Hehuang Deng; Xiangjiao Liao; Youcai Zhou

    2006-01-01

    with and without TD. ③ The differences in genotype and allele frequencies between two groups were compared with chi-square test and severity of TD rated by Abnormal Involuntary Movement Scale (AIMS) among TD patients with different genotypes or alleles were compared with one way ANOVA test or independent-samples t test. MAIN OUTCOME MEASURES: Demographic and clinical variables including sex, age, duration of illness, cumulative exposure to neuroleptic drugs, times of hospitalization, of all patients; AIMS scores in TD patients; MAOA gene polymorphic allelic and genotypic frequencies in all subjects. RESULTS: All 179 subjects were involved in the final analysis. No one was dropped out in this study. Only 3- and 4-fold repeat alleles were observed in all subjects. Data was stratified and analyzed by gender because MAOA gene was located on the X chromosome. No significant differences were found in genotypic (χ2=2.437, P > 0.05) nor allelic (χ2=2.233, P > 0.05) frequencies of MAOA gene between patients with TD and without TD in female subjects, and no significant differences in allelic frequencies between male TD and non-TD patients (χ2 =1.750, P > 0.05). And there were no significant differences in mean AIMS scores among female TD patients with different MAOA genotypes (F=1.190, P > 0.05) and between male TD patients carrying different alleles (t=0.378, P> 0.05).CONCLUSION: The results do not support any associations between MAOA gene 30 bp VNTR polymorphism and susceptibility nor severity of TD in schizophrenia in Chinese Han people.

  14. An Allele Real-Coded Quantum Evolutionary Algorithm Based on Hybrid Updating Strategy.

    Science.gov (United States)

    Zhang, Yu-Xian; Qian, Xiao-Yi; Peng, Hui-Deng; Wang, Jian-Hui

    2016-01-01

    For improving convergence rate and preventing prematurity in quantum evolutionary algorithm, an allele real-coded quantum evolutionary algorithm based on hybrid updating strategy is presented. The real variables are coded with probability superposition of allele. A hybrid updating strategy balancing the global search and local search is presented in which the superior allele is defined. On the basis of superior allele and inferior allele, a guided evolutionary process as well as updating allele with variable scale contraction is adopted. And H ε gate is introduced to prevent prematurity. Furthermore, the global convergence of proposed algorithm is proved by Markov chain. Finally, the proposed algorithm is compared with genetic algorithm, quantum evolutionary algorithm, and double chains quantum genetic algorithm in solving continuous optimization problem, and the experimental results verify the advantages on convergence rate and search accuracy.

  15. An Allele Real-Coded Quantum Evolutionary Algorithm Based on Hybrid Updating Strategy

    Directory of Open Access Journals (Sweden)

    Yu-Xian Zhang

    2016-01-01

    Full Text Available For improving convergence rate and preventing prematurity in quantum evolutionary algorithm, an allele real-coded quantum evolutionary algorithm based on hybrid updating strategy is presented. The real variables are coded with probability superposition of allele. A hybrid updating strategy balancing the global search and local search is presented in which the superior allele is defined. On the basis of superior allele and inferior allele, a guided evolutionary process as well as updating allele with variable scale contraction is adopted. And Hε gate is introduced to prevent prematurity. Furthermore, the global convergence of proposed algorithm is proved by Markov chain. Finally, the proposed algorithm is compared with genetic algorithm, quantum evolutionary algorithm, and double chains quantum genetic algorithm in solving continuous optimization problem, and the experimental results verify the advantages on convergence rate and search accuracy.

  16. The number of self-incompatibility alleles in a finite, subdivided population

    DEFF Research Database (Denmark)

    Schierup, M H

    1998-01-01

    the applicability of the results to include proposed models for the major histocompatibility (MHC) loci. For a subdivided population over a large range of migration rates, it appears that the number of self-incompatibility alleles (or MHC-alleles) observed can provide a rough estimate of the total number......The actual and effective number of gametophytic self-incompatibility alleles maintained at mutation-drift-selection equilibrium in a finite population subdivided as in the island model is investigated by stochastic simulations. The existing theory founded by Wright predicts that for a given...... population size the number of alleles maintained increases monotonically with decreasing migration as is the case for neutral alleles. The simulation results here show that this is not true. At migration rates above Nm = 0.01-0.1, the actual and effective number of alleles is lower than for an undivided...

  17. Tailor-made RNAi knockdown against triplet repeat disease-causing alleles.

    Science.gov (United States)

    Takahashi, Masaki; Watanabe, Shoko; Murata, Miho; Furuya, Hirokazu; Kanazawa, Ichiro; Wada, Keiji; Hohjoh, Hirohiko

    2010-12-14

    Nucleotide variations, including SNPs, in the coding regions of disease genes are important targets for RNAi treatment, which is a promising medical treatment for intractable diseases such as triplet repeat diseases. However, the identification of such nucleotide variations and the design of siRNAs conferring disease allele-specific RNAi are quite difficult. In this study we developed a pull-down method to rapidly identify coding SNP (cSNP) haplotypes of triple repeat, disease-causing alleles, and we demonstrated disease allele-specific RNAi that targeted cSNP sites in mutant Huntingtin alleles, each of which possessed a different cSNP haplotype. Therefore, the methods presented here allow for allele-specific RNAi knockdown against disease-causing alleles by using siRNAs specific to disease-linked cSNP haplotypes, and advanced progress toward tailor-made RNAi treatments for triplet repeat diseases.

  18. DEMETER DNA glycosylase establishes MEDEA polycomb gene self-imprinting by allele-specific demethylation.

    Science.gov (United States)

    Gehring, Mary; Huh, Jin Hoe; Hsieh, Tzung-Fu; Penterman, Jon; Choi, Yeonhee; Harada, John J; Goldberg, Robert B; Fischer, Robert L

    2006-02-10

    MEDEA (MEA) is an Arabidopsis Polycomb group gene that is imprinted in the endosperm. The maternal allele is expressed and the paternal allele is silent. MEA is controlled by DEMETER (DME), a DNA glycosylase required to activate MEA expression, and METHYLTRANSFERASE I (MET1), which maintains CG methylation at the MEA locus. Here we show that DME is responsible for endosperm maternal-allele-specific hypomethylation at the MEA gene. DME can excise 5-methylcytosine in vitro and when expressed in E. coli. Abasic sites opposite 5-methylcytosine inhibit DME activity and might prevent DME from generating double-stranded DNA breaks. Unexpectedly, paternal-allele silencing is not controlled by DNA methylation. Rather, Polycomb group proteins that are expressed from the maternal genome, including MEA, control paternal MEA silencing. Thus, DME establishes MEA imprinting by removing 5-methylcytosine to activate the maternal allele. MEA imprinting is subsequently maintained in the endosperm by maternal MEA silencing the paternal allele.

  19. Allelic diversity and molecular characterization of puroindoline genes in five diploid species of the Aegilops genus.

    Science.gov (United States)

    Cuesta, Susana; Guzmán, Carlos; Alvarez, Juan B

    2013-11-01

    Grain hardness is an important quality trait in wheat. This trait is related to the variation in, and the presence of, puroindolines (PINA and PINB). This variation can be increased by the allelic polymorphism present in the Aegilops species that are related to wheat. This study evaluated allelic Pina and Pinb gene variability in five diploid species of the Aegilops genus, along with the molecular characterization of the main allelic variants found in each species. This polymorphism resulted in 16 alleles for the Pina gene and 24 alleles for the Pinb gene, of which 10 and 17, respectively, were novel. Diverse mutations were detected in the deduced mature proteins of these alleles, which could influence the hardness characteristics of these proteins. This study shows that the diploid species of the Aegilops genus could be a good source of genetic variability for both Pina and Pinb genes, which could be used in breeding programmes to extend the range of different textures in wheat.

  20. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Timm, Sally; Wang, August G;

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission......-onset schizophrenia) and healthy subjects differed significantly. This was reflected in an increased frequency of the deletion allele in the patient subgroup. Patients with ages at first admission below and above 40 years significantly differed in distribution of genotypes and alleles, with an overrepresentation...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  1. Enhancement of allele discrimination by introduction of nucleotide mismatches into siRNA in allele-specific gene silencing by RNAi.

    Directory of Open Access Journals (Sweden)

    Yusuke Ohnishi

    Full Text Available Allele-specific gene silencing by RNA interference (RNAi is therapeutically useful for specifically inhibiting the expression of disease-associated alleles without suppressing the expression of corresponding wild-type alleles. To realize such allele-specific RNAi (ASP-RNAi, the design and assessment of small interfering RNA (siRNA duplexes conferring ASP-RNAi is vital; however, it is also difficult. In a previous study, we developed an assay system to assess ASP-RNAi with mutant and wild-type reporter alleles encoding the Photinus and Renilla luciferase genes. In line with experiments using the system, we realized that it is necessary and important to enhance allele discrimination between mutant and corresponding wild-type alleles. Here, we describe the improvement of ASP-RNAi against mutant alleles carrying single nucleotide variations by introducing base substitutions into siRNA sequences, where original variations are present in the central position. Artificially mismatched siRNAs or short-hairpin RNAs (shRNAs against mutant alleles of the human Prion Protein (PRNP gene, which appear to be associated with susceptibility to prion diseases, were examined using this assessment system. The data indicates that introduction of a one-base mismatch into the siRNAs and shRNAs was able to enhance discrimination between the mutant and wild-type alleles. Interestingly, the introduced mismatches that conferred marked improvement in ASP-RNAi, appeared to be largely present in the guide siRNA elements, corresponding to the 'seed region' of microRNAs. Due to the essential role of the 'seed region' of microRNAs in their association with target RNAs, it is conceivable that disruption of the base-pairing interactions in the corresponding seed region, as well as the central position (involved in cleavage of target RNAs, of guide siRNA elements could influence allele discrimination. In addition, we also suggest that nucleotide mismatches at the 3'-ends of sense

  2. Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population.

    Science.gov (United States)

    Coffee, Erin M; Yerkes, Laura; Ewen, Elizabeth P; Zee, Tiffany; Tolan, Dean R

    2010-02-01

    Mutations in the aldolase B gene (ALDOB) impairing enzyme activity toward fructose-1-phosphate cleavage cause hereditary fructose intolerance (HFI). Diagnosis of the disease is possible by identifying known mutant ALDOB alleles in suspected patients; however, the frequencies of mutant alleles can differ by population. Here, 153 American HFI patients with 268 independent alleles were analyzed to identify the prevalence of seven known HFI-causing alleles (A149P, A174D, N334K, Delta4E4, R59Op, A337V, and L256P) in this population. Allele-specific oligonucleotide hybridization analysis was performed on polymerase chain reaction (PCR)-amplified genomic DNA from these patients. In the American population, the missense mutations A149P and A174D are the two most common alleles, with frequencies of 44% and 9%, respectively. In addition, the nonsense mutations Delta4E4 and R59Op are the next most common alleles, with each having a frequency of 4%. Together, the frequencies of all seven alleles make up 65% of HFI-causing alleles in this population. Worldwide, these same alleles make up 82% of HFI-causing mutations. This difference indicates that screening for common HFI alleles is more difficult in the American population. Nevertheless, a genetic screen for diagnosing HFI in America can be improved by including all seven alleles studied here. Lastly, identification of HFI patients presenting with classic symptoms and who have homozygous null genotypes indicates that aldolase B is not required for proper development or metabolic maintenance.

  3. Allelic and non-allelic heterogeneities in pyridoxine dependent seizures revealed by ALDH7A1 mutational analysis.

    Science.gov (United States)

    Kanno, Junko; Kure, Shigeo; Narisawa, Ayumi; Kamada, Fumiaki; Takayanagi, Masaru; Yamamoto, Katsuya; Hoshino, Hisao; Goto, Tomohide; Takahashi, Takao; Haginoya, Kazuhiro; Tsuchiya, Shigeru; Baumeister, Fritz A M; Hasegawa, Yuki; Aoki, Yoko; Yamaguchi, Seiji; Matsubara, Yoichi

    2007-08-01

    Pyridoxine dependent seizure (PDS) is a disorder of neonates or infants with autosomal recessive inheritance characterized by seizures, which responds to pharmacological dose of pyridoxine. Recently, mutations have been identified in the ALDH7A1 gene in Caucasian families with PDS. To elucidate further the genetic background of PDS, we screened for ALDH7A1 mutations in five PDS families (patients 1-5) that included four Orientals. Diagnosis as having PDS was confirmed by pyridoxine-withdrawal test. Exon sequencing analysis of patients 1-4 revealed eight ALDH7A1 mutations in compound heterozygous forms: five missense mutations, one nonsense mutation, one point mutation at the splicing donor site in intron 1, and a 1937-bp genomic deletion. The deletion included the entire exon 17, which was flanked by two Alu elements in introns 16 and 17. None of the mutations was found in 100 control chromosomes. In patient 5, no mutation was found by the exon sequencing analysis. Furthermore, expression level or nucleotide sequences of ALDH7A1 mRNA in lymphoblasts were normal. Plasma pipecolic acid concentration was not elevated in patient 5. These observations suggest that ALDH7A1 mutation is unlikely to be responsible for patient 5. Abnormal metabolism of GABA/glutamate in brain has long been suggested as the underlying pathophysiology of PDS. CSF glutamate concentration was elevated during the off-pyridoxine period in patient 3, but not in patient 2 or 5. These results suggest allelic and non-allelic heterogeneities of PDS, and that the CSF glutamate elevation does not directly correlate with the presence of ALDH7A1 mutations.

  4. Creation and functional analysis of new Puroindoline alleles in Triticum aestivum.

    Science.gov (United States)

    Feiz, L; Martin, J M; Giroux, M J

    2009-01-01

    The Hardness (Ha) locus controls grain texture and affects many end-use properties of wheat (Triticum aestivum L.). The Ha locus is functionally comprised of the Puroindoline a and b genes, Pina and Pinb, respectively. The lack of Pin allelic diversity is a major factor limiting Ha functional analyses and wheat quality improvement. In order to create new Ha alleles, a 630 member M(2) population was produced in the soft white spring cultivar Alpowa using ethylmethane sulfonate mutagenesis. The M(2) population was screened to identify new alleles of Pina and Pinb. Eighteen new Pin alleles, including eight missense alleles, were identified. F(2) populations for four of the new Pin alleles were developed after crossing each back to non-mutant Alpowa. Grain hardness was then measured on F(2:3) seeds and the impact of each allele on grain hardness was quantified. The tested mutations were responsible for between 28 and 94% of the grain hardness variation and seed weight and vigor of all mutation lines was restored among the F(2) populations. Selection of new Pin alleles following direct phenotyping or direct sequencing is a successful approach to identify new Ha alleles useful in improving wheat product quality and understanding Ha locus function.

  5. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, H.B.; Timm, S.; Wang, A.G.;

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  6. Allele-specific enzymatic amplification of. beta. -globin genomic DNA for diagnosis of sickle cell anemia

    Energy Technology Data Exchange (ETDEWEB)

    Wu, D.Y.; Ugozzoli, L.; Pal, B.K.; Wallace, B. (Beckman Research Institute of the City of Hope, Duarte, CA (USA))

    1989-04-01

    A rapid nonradioactive approach to the diagnosis of sickle cell anemia is described based on an allele-specific polymerase chain reaction (ASPCR). This method allows direct detection of the normal or the sickle cell {beta}-globin allele in genomic DNA without additional steps of probe hybridization, ligation, or restriction enzyme cleavage. Two allele-specific oligonucleotide primers, one specific for the sickle cell allele and one specific for the normal allele, together with another primer complementary to both alleles were used in the polymerase chain reaction with genomic DNA templates. The allele-specific primers differed from each other in their terminal 3{prime} nucleotide. Under the proper annealing temperature and polymerase chain reaction conditions, these primers only directed amplification on their complementary allele. In a single blind study of DNA samples from 12 individuals, this method correctly and unambiguously allowed for the determination of the genotypes with no false negatives or positives. If ASPCR is able to discriminate all allelic variation (both transition and transversion mutations), this method has the potential to be a powerful approach for genetic disease diagnosis, carrier screening, HLA typing, human gene mapping, forensics, and paternity testing.

  7. Allele specific expression in worker reproduction genes in the bumblebee Bombus terrestris

    Directory of Open Access Journals (Sweden)

    Harindra E. Amarasinghe

    2015-07-01

    Full Text Available Methylation has previously been associated with allele specific expression in ants. Recently, we found methylation is important in worker reproduction in the bumblebee Bombus terrestris. Here we searched for allele specific expression in twelve genes associated with worker reproduction in bees. We found allele specific expression in Ecdysone 20 monooxygenase and IMP-L2-like. Although we were unable to confirm a genetic or epigenetic cause for this allele specific expression, the expression patterns of the two genes match those predicted for imprinted genes.

  8. Tracking origins and spread of sulfadoxine-resistant Plasmodium falciparum dhps alleles in Thailand.

    Science.gov (United States)

    Alam, Md Tauqeer; Vinayak, Sumiti; Congpuong, Kanungnit; Wongsrichanalai, Chansuda; Satimai, Wichai; Slutsker, Laurence; Escalante, Ananias A; Barnwell, John W; Udhayakumar, Venkatachalam

    2011-01-01

    The emergence and spread of drug-resistant Plasmodium falciparum have been a major impediment for the control of malaria worldwide. Earlier studies have shown that similar to chloroquine (CQ) resistance, high levels of pyrimethamine resistance in P. falciparum originated independently 4 to 5 times globally, including one origin at the Thailand-Cambodia border. In this study we describe the origins and spread of sulfadoxine-resistance-conferring dihydropteroate synthase (dhps) alleles in Thailand. The dhps mutations and flanking microsatellite loci were genotyped for P. falciparum isolates collected from 11 Thai provinces along the Burma, Cambodia, and Malaysia borders. Results indicated that resistant dhps alleles were fixed in Thailand, predominantly being the SGEGA, AGEAA, and SGNGA triple mutants and the AGKAA double mutant (mutated codons are underlined). These alleles had different geographical distributions. The SGEGA alleles were found mostly at the Burma border, while the SGNGA alleles occurred mainly at the Cambodia border and nearby provinces. Microsatellite data suggested that there were two major genetic lineages of the triple mutants in Thailand, one common for SGEGA/SGNGA alleles and another one independent for AGEAA. Importantly, the newly reported SGNGA alleles possibly originated at the Thailand-Cambodia border. All parasites in the Yala province (Malaysia border) had AGKAA alleles with almost identical flanking microsatellites haplotypes. They were also identical at putatively neutral loci on chromosomes 2 and 3, suggesting a clonal nature of the parasite population in Yala. In summary, this study suggests multiple and independent origins of resistant dhps alleles in Thailand.

  9. Allelic-specific expression in relation to Bombyx mori resistance to Bt toxin.

    Science.gov (United States)

    Chen, Yazhou; Li, Muwang; Islam, Iftakher; You, Lang; Wang, Yueqiang; Li, Zhiqian; Ling, Lin; Zeng, Baosheng; Xu, Jun; Huang, Yongping; Tan, Anjiang

    2014-11-01

    Understanding the mechanism of Bt resistance is one of the key elements of the effective application of Bt in pest control. The lepidopteran model insect, the silkworm, demonstrates qualities that make it an ideal species to use in achieving this understanding. We screened 45 strains of silkworm (Bombyx mori) using a Cry1Ab toxin variant. The sensitivity levels of the strains varied over a wide range. A resistant strain (P50) and a phylogenetically related susceptible strain (Dazao) were selected to profile the expressions of 12 Bt resistance-related genes. The SNPs in these genes were detected based on EST analysis and were validated by allelic-specific PCR. A comparison of allelic-specific expression between P50 and Dazao showed that the transcript levels of heterozygous genes containing two alleles rather than an imbalanced allelic expression contribute more to the resistance of P50 against Bt. The responses of the allelic-specific expression to Bt in hybrid larvae were then investigated. The results showed that the gene expression pattern of an ATP-binding cassette transporter C2 (ABCC2) and an aminopeptidase N (APN3), changed in an allelic-specific manner, with the increase of the resistant allele expression correlated with larval survival. The results suggest that a trans-regulatory mechanism in ABCC2 and APN3 allelic-specific expression is involved in the insect's response to the Bt toxin. The potential role of allelic-specific gene regulation in insect resistance to Bt toxins is discussed.

  10. FMR1 alleles in Tasmania: a screening study of the special educational needs population.

    Science.gov (United States)

    Mitchell, R J; Holden, J J A; Zhang, C; Curlis, Y; Slater, H R; Burgess, T; Kirkby, K C; Carmichael, A; Heading, K D; Loesch, D Z

    2005-01-01

    The distribution of fragile X mental retardation-1 (FMR1) allele categories, classified by the number of CGG repeats, in the population of Tasmania was investigated in 1253 males with special educational needs (SEN). The frequencies of these FMR1 categories were compared with those seen in controls as represented by 578 consecutive male births. The initial screening was based on polymerase chain reaction analysis of dried blood spots. Inconclusive results were verified by Southern analysis of a venous blood sample. The frequencies of common FMR1 alleles in both samples, and of grey zone alleles in the controls, were similar to those in other Caucasian populations. Consistent with earlier reports, we found some (although insignificant) increase of grey zone alleles in SEN subjects compared with controls. The frequencies of predisposing flanking haplotypes among grey zone males FMR1 alleles were similar to those seen in other Caucasian SEN samples. Contrary to expectation, given the normal frequency of grey zone alleles, no premutation (PM) or full mutation (FM) allele was detected in either sample, with only 15 fragile X families diagnosed through routine clinical admissions registered in Tasmania up to 2002. An explanation of this discrepancy could be that the C19th founders of Tasmania carried few PM or FM alleles. The eight to ten generations since white settlement of Tasmania has been insufficient time for susceptible grey zone alleles to evolve into the larger expansions.

  11. A novel HLA-B*57 (B*5714) allele in a healthy male Caucasian individual.

    Science.gov (United States)

    Altermann, W W; Grondkowski, V; Reichert, S; Seliger, B; Schlaf, G

    2008-03-01

    A novel human leucocyte antigen (HLA)-B57 (HLA-B*5714) allele has been identified in a male Caucasian individual from Middle Europe using single allele-specific sequencing strategy. This allele is identical to the HLA-B*570101 allele except for two point mutations in exon 3 at codon 138 (ACG-->ACC) with no amino acid change [persisting threonine (T)] and at codon 171 (TAC-->CAC), resulting in an amino acid change from tyrosine (Y) to histidine (H).

  12. Bipolar disorder and the pseudoautosomal region: An association study

    Energy Technology Data Exchange (ETDEWEB)

    Parsian, A.; Todd, R.D. [Washington Univ. School of Medicine, St. Louis, MO (United States)

    1994-03-15

    From family, adoption, and twin studies it is clear that genetic factors play an important role in the etiology of bipolar disorder (McGuffin and Katz: The Biology of Depression, Gaskell, London, 1986). Recently Yoneda et al. reported an association between an allele (A4) of a VNTR marker (DXYS20) for the pseudoautosomal region and bipolar disorder in a Japanese population. In order to test for this association in a Caucasian population, we have typed a sample of 52 subjects with bipolar disorder and 61 normal controls. The bipolar subjects are probands of multiple incidence families. The normal controls are an epidemiologically ascertained sample of middle-aged, unrelated individuals. The two groups were matched for sex and ethnic background. There were no significant differences in the allele or genotype frequencies of DXYS20 between the two groups. In particular, there was no significant difference in the frequency of the A4 allele in normal controls and bipolar patients (0.377 vs. 0.317, respectively). The prevalence of the A4 allele in bipolar patients and normal controls was 0.567 and 0.622, respectively. We were not able to replicate the results of the 1992 Yoneda et al. study. 15 refs., 2 tabs.

  13. Is there a genetic contribution to cultural differences? Collectivism, individualism and genetic markers of social sensitivity.

    Science.gov (United States)

    Way, Baldwin M; Lieberman, Matthew D

    2010-06-01

    Genes and culture are often thought of as opposite ends of the nature-nurture spectrum, but here we examine possible interactions. Genetic association studies suggest that variation within the genes of central neurotransmitter systems, particularly the serotonin (5-HTTLPR, MAOA-uVNTR) and opioid (OPRM1 A118G), are associated with individual differences in social sensitivity, which reflects the degree of emotional responsivity to social events and experiences. Here, we review recent work that has demonstrated a robust cross-national correlation between the relative frequency of variants in these genes and the relative degree of individualism-collectivism in each population, suggesting that collectivism may have developed and persisted in populations with a high proportion of putative social sensitivity alleles because it was more compatible with such groups. Consistent with this notion, there was a correlation between the relative proportion of these alleles and lifetime prevalence of major depression across nations. The relationship between allele frequency and depression was partially mediated by individualism-collectivism, suggesting that reduced levels of depression in populations with a high proportion of social sensitivity alleles is due to greater collectivism. These results indicate that genetic variation may interact with ecological and social factors to influence psychocultural differences.

  14. Allele-specific enzymatic amplification of beta-globin genomic DNA for diagnosis of sickle cell anemia.

    OpenAIRE

    1989-01-01

    A rapid nonradioactive approach to the diagnosis of sickle cell anemia is described based on an allele-specific polymerase chain reaction (ASPCR). This method allows direct detection of the normal or the sickle cell beta-globin allele in genomic DNA without additional steps of probe hybridization, ligation, or restriction enzyme cleavage. Two allele-specific oligonucleotide primers, one specific for the sickle cell allele and one specific for the normal allele, together with another primer co...

  15. The contribution of SAA1 polymorphisms to Familial Mediterranean fever susceptibility in the Japanese population.

    Directory of Open Access Journals (Sweden)

    Kiyoshi Migita

    Full Text Available BACKGROUND/AIMS: Familial Mediterranean Fever (FMF has traditionally been considered to be an autosomal-recessive disease, however, it has been observed that substantial numbers of patients with FMF possess only 1 demonstrable MEFV mutation. The clinical profile of familial Mediterranean fever (FMF may be influenced by MEFV allelic heterogeneity and other genetic and/or environmental factors. METHODOLOGY/PRINCIPAL FINDINGS: In view of the inflammatory nature of FMF, we investigated whether serum amyloid A (SAA and interleukin-1 beta (IL-1β gene polymorphisms may affect the susceptibility of Japanese patients with FMF. The genotypes of the -13C/T SNP in the 5'-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms were determined in 83 Japanese patients with FMF and 200 healthy controls. The same samples were genotyped for IL-1β-511 (C/T and IL-1 receptor antagonist (IL-1Ra variable number of tandem repeat (VNTR polymorphisms. There were no significant differences between FMF patients and healthy subjects in the genotypic distribution of IL-1β -511 (C/T, IL-1Ra VNTR and SAA2 polymorphisms. The frequencies of SAA1.1 allele were significantly lower (21.7% versus 34.0%, and inversely the frequencies of SAA1.3 allele were higher (48.8% versus 37.5% in FMF patients compared with healthy subjects. The frequency of -13T alleles, associated with the SAA1.3 allele in the Japanese population, was significantly higher (56.0% versus 41.0%, p=0.001 in FMF patients compared with healthy subjects. CONCLUSIONS/SIGNIFICANCE: Our data indicate that SAA1 gene polymorphisms, consisting of -13T/C SNP in the 5'-flanking region and SNPs within exon 3 (2995C/T and 3010C/T polymorphisms of SAA1 gene, are associated with susceptibility to FMF in the Japanese population.

  16. A novel B(var) allele (547 G>A) demonstrates differential expression depending on the co-inherited ABO allele.

    Science.gov (United States)

    Cho, D; Kim, S H; Ki, C S; Choi, K L; Cho, Y G; Song, J W; Shin, J H; Suh, S P; Yazer, M H; Ryang, D W

    2004-10-01

    Genetic analysis of group B donors in Korea was performed. Exons 6 and 7 were sequenced in 12 phenotypically B3 donors 6 B3, 6 A1B3. Consensus sequences all B3 and 2/6 A1B3 donors were present. Four A1B3 donors demonstrated a novel B allele, B(var), in the context of A101/ or A102/B(var) genotypes. Family studies based on an A1B3 donor with the B(var) allele and on another unrelated subject with identical genotype and phenotype revealed B(var)/O01 genotypes with full B-antigen expression. B(var) allele is subject to differential expression, depending on the co-inherited ABO allele.

  17. Distribution of BoLA-DRB3 allelic frequencies and identification of a new allele in the iranian cattle breed sistani (Bos indicus).

    Science.gov (United States)

    Mohammadi, A; Nassiry, M R; Mosafer, J; Mohammadabadi, M R; Sulimova, G E

    2009-02-01

    The distribution of the frequencies of BoLA-DRB3 gene alleles in the Iranian cattle breed Sistani was studied by the PCR-RFLP ("hemi-nested") assay using restriction endonucleases RsaI, HaeIII and BstYI. In the examined cattle breed (65 animals) 32 alleles have been identified one of which being described for the first time (6.15% frequency). The nucleotide sequence of the polymorphic region of exon 2 of this allele has been determined and submitted in the GeneBank database under accession number DQ486519. The submitted sequence has maximum homology (92%) with the previously described sequence DRB3-mRNA from Bos indicus (AccN X79346) and differs from it by 24 nucleotide substitutions which result in 16 amino acid substitutions. The peptide (on the basis of the reconstructed amino acid sequence) has 89% identity to the sequence encoded by the BIDRBF 188 locus (Bos indicus). The results obtained permit the sequence described by us to be considered as a new allele of the BoLA-DRB3 gene (DRB3.2**X). The total frequency of the main six alleles (DRB3.2*X, *10, *11, *20, *34 and *X) occurring with a frequency of over 5% is about 60% in Iranian Sistani cattle. Fifteen alleles have DRB3.2*8 allele (21.54%) like in other previously described breeds of Bos indicus (up to 23.07%). The Iranian breed Sistani has a high level of similarity by the spectrum of BoLA-DRB3 alleles and their frequencies to other Bos indicus breeds and significantly differs by these criteria from the Bos taurus breeds. The Iranian Sistani herd under study includes alleles associated with to resistance to leukemia (DRB3.2*ll and *23) and to different forms of mastitis (DRB3.2*2, *7, *11, *23 and *24) although their frequencies are low (from 0.77 to 5.37%). On the whole, a high level of diversity of BoLA-DRB3 gene alleles and the availability of alleles associated with resistance to different diseases makes this breed of interest for breeding practice.

  18. Disagreement in genotyping results of drug resistance alleles of the Plasmodium falciparum dihydrofolate reductase (Pfdhfr) gene by allele-specific PCR (ASPCR) assays and Sanger sequencing.

    Science.gov (United States)

    Sharma, Divya; Lather, Manila; Dykes, Cherry L; Dang, Amita S; Adak, Tridibes; Singh, Om P

    2016-01-01

    The rapid spread of antimalarial drug resistance in Plasmodium falciparum over the past few decades has necessitated intensive monitoring of such resistance for an effective malaria control strategy. P. falciparum dihydropteroate synthase (Pfdhps) and P. falciparum dihydrofolate reductase (Pfdhfr) genes act as molecular markers for resistance against the antimalarial drugs sulphadoxine and pyrimethamine, respectively. Resistance to pyrimethamine which is used as a partner drug in artemisinin combination therapy (ACT) is associated with several mutations in the Pfdhfr gene, namely A16V, N51I, C59R, S108N/T and I164L. Therefore, routine monitoring of Pfdhfr-drug-resistant alleles in a population may help in effective drug resistance management. Allele-specific PCR (ASPCR) is one of the commonly used methods for molecular genotyping of these alleles. In this study, we genotyped 55 samples of P. falciparum for allele discrimination at four codons of Pfdhfr (N51, C59, S108 and I164) by ASPCR using published methods and by Sanger's DNA sequencing method. We found that the ASPCR identified a significantly higher number of mutant alleles as compared to the DNA sequencing method. Such discrepancies arise due to the non-specificity of some of the allele-specific primer sets and due to the lack of sensitivity of Sanger's DNA sequencing method to detect minor alleles present in multiple clone infections. This study reveals the need of a highly specific and sensitive method for genotyping and detecting minor drug-resistant alleles present in multiple clonal infections.

  19. Major histocompatibility complex class I chain related (MIC) A gene, TNFa microsatellite alleles and TNFB alleles in juvenile idiopathic arthritis patients from Latvia.

    Science.gov (United States)

    Nikitina Zake, Liene; Cimdina, Ija; Rumba, Ingrida; Dabadghao, Preethi; Sanjeevi, Carani B

    2002-05-01

    In order to analyze involvement of major histocompatibility complex class I chain-related gene A (MICA) and tumor necrosis factor a (TNFa) microsatellite polymorphisms as well as TNFB gene in juvenile idiopathic arthritis (JIA), we studied 128 patients divided into groups according to clinical features [monoarthritis (n = 14), oligoarthritis (n = 58), polyarthritis (n = 50), and systemic (n = 6)], and 114 age- and sex-matched healthy controls from Latvia. DNA samples were amplified with specific primers and used for genotyping of MICA and TNFa microsatellite. Typing for a biallelic NcoI polymerase chain reaction RFLP polymorphism located at the first intron of TNFB gene was done as follows: restriction digests generated fragments of 555bp and 185bp for TNFB*1 allele, and 740bp for TNFB*2 allele. The results were compared between cases and controls. We found significant increase of MICA allele A4 (p = 0.009; odds ratio [OR] = 2.3) and allele TNFa2 (p = 0.0001; OR = 4.4) in patients compared with controls. The frequency of allele TNFa9 was significantly decreased (p = 0.0001; OR = 0.1) in patients with JIA. No significant differences of TNFB allele frequency were found. Our data suggest that MICA and TNFa microsatellite polymorphisms may be used as markers for determination of susceptibility and protection from JIA.

  20. Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.

    Directory of Open Access Journals (Sweden)

    Rong Chen

    Full Text Available Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may

  1. Type 2 diabetes risk alleles demonstrate extreme directional differentiation among human populations, compared to other diseases.

    Science.gov (United States)

    Chen, Rong; Corona, Erik; Sikora, Martin; Dudley, Joel T; Morgan, Alex A; Moreno-Estrada, Andres; Nilsen, Geoffrey B; Ruau, David; Lincoln, Stephen E; Bustamante, Carlos D; Butte, Atul J

    2012-01-01

    Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D) demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may contribute to the observed

  2. Apolipoprotein E alleles in Alzheimer`s and Parkinson`s patients

    Energy Technology Data Exchange (ETDEWEB)

    Poduslo, S.E. [Texas Tech Univ., Lubbock, TX (United States); Schwankhaus, J.D. [Department of Veterans Affairs, Lubbock, TX (United States)

    1994-09-01

    A number of investigators have found an association between the apolipoprotein E4 allele and Alzheimer`s disease. The E4 allele appears at a higher frequency in late onset familial Alzheimer`s patients. In our studies we obtained blood samples from early and late onset familial and sporadic Alzheimer`s patients and spouses, as well as from Parkinson`s patients. The patients were diagnosed as probable Alzheimer`s patients after a neurological examination, extensive blood work, and a CAT scan. The diagnosis was made according to the NINCDS-ADRDA criteria. The apolipoprotein E4 polymorphism was detected after PCR amplification of genomic DNA, restriction enzyme digestion with Hhal, and polyacrylamide gel electrophoresis. Ethidium bromide-stained bands at 91 bp were designated as allele 3, at 83 bp as allele 2, and at 72 bp as allele 4. Of the 84 probable Alzheimer`s patients (all of whom were Caucasian), 47 were heterozygous and 13 were homozygous for the E4 allele. There were 26 early onset patients; 13 were heterozygous and 7 homozygous for the E4 allele. The frequencies for the E4 allele for late onset familial patients was 0.45 and for sporadic patients was 0.37. We analyzed 77 spouses with an average age of 71.9 {plus_minus} 7.4 years as controls, and 15 were heterozygous for the E4 allele for an E4 frequency of 0.097. Of the 53 Parkinson`s patients, 11 had the E4 allele for a frequency of 0.113. Thus our findings support the association of the ApoE4 allele with Alzheimer`s disease.

  3. Salmonella Typhi shdA: pseudogene or allelic variant?

    Science.gov (United States)

    Urrutia, I M; Fuentes, J A; Valenzuela, L M; Ortega, A P; Hidalgo, A A; Mora, G C

    2014-08-01

    ShdA from Salmonella Typhimurium (ShdASTm) is a large outer membrane protein that specifically recognizes and binds to fibronectin. ShdASTm is involved in the colonization of the cecum and the Peyer's patches of terminal ileum in mice. On the other hand, shdA gene from Salmonella Typhi (shdASTy) has been considered a pseudogene (i.e. a nonfunctional sequence of genomic DNA) due to the presence of deletions and mutations that gave rise to premature stop codons. In this work we show that, despite the deletions and mutations, shdASTy is fully functional. S. Typhi ΔshdA mutants presented an impaired adherence and invasion of HEp-2 pre-treated with TGF-β1, an inducer of fibronectin production. Moreover, shdA from S. Typhi and S. Typhimurium seem to be equivalent since shdASTm restored the adherence and invasion of S. Typhi ΔshdA mutant to wild type levels. In addition, anti-FLAG mAbs interfered with the adherence and invasion of the S. Typhi shdA-3xFLAG strain. Finally, shdASTy encodes a detectable protein when heterologously expressed in Escherichia coli DH5α. The data presented here show that shdASTy is not a pseudogene, but a different functional allele compared with shdASTm.

  4. Prevalence of URAT1 allelic variants in the Roma population.

    Science.gov (United States)

    Stiburkova, Blanka; Gabrikova, Dana; Čepek, Pavel; Šimek, Pavel; Kristian, Pavol; Cordoba-Lanus, Elizabeth; Claverie-Martin, Felix

    2016-12-01

    The Roma represents a transnational ethnic group, with a current European population of 8-10 million. The evolutionary process that had the greatest impact on the gene pool of the Roma population is called the founder effect. Renal hypouricemia (RHUC) is a rare heterogenous inherited disorder characterized by impaired renal urate reabsorption. The affected individuals are predisposed to recurrent episodes of exercise-induced nonmyoglobinuric acute kidney injury and nephrolithiasis. To date, more than 150 patients with a loss-of-function mutation for the SLC22A12 (URAT1) gene have been found, most of whom are Asians. However, RHUC 1 patients have been described in a variety of ethnic groups (e.g., Arab Israelis, Iraqi Jews, Caucasians, and Roma) and in geographically noncontiguous countries. This study confirms our previous findings regarding the high frequency of SLC22A12 variants observed. Frequencies of the c.1245_1253del and c.1400C>T variants were found to be 1.92% and 5.56%, respectively, in a subgroup of the Roma population from five regions in three countries: Slovakia, Czech Republic, and Spain. Our findings suggested that the common dysfunction allelic variants of URAT1 exist in the general Roma population and thus renal hypouricemia should be kept in differential diagnostic algorithm on Roma patients with defect in renal tubular urate transport. This leads to confirm that the genetic drift in the Roma have increased the prevalence of hereditary disorders caused by very rare variants in major population.

  5. Study on the association of BoLA-DRB3.2 alleles with clinical ...

    African Journals Online (AJOL)

    USER

    2010-04-12

    Apr 12, 2010 ... previously reported 13 alleles of BoLA-DRB3.2 gene across both studied breeds. However, 3 new ... DRB3.2 alleles potentially affect many traits related to immunity, milk ... In the first step, multi-primer target polymerase chain reaction ... Genomic DNA was isolated from total blood, drawn in Vacutainer.

  6. Correlation in chicken between the marker LEI0258 alleles and Major Histocompatibility Complex sequences

    DEFF Research Database (Denmark)

    Chazara, Olympe; Juul-Madsen, Helle Risdahl; Chang, Chi-Seng

    Background The LEI0258 marker is located within the B region of the chicken Major Histocompatibility Complex (MHC), and is surprisingly well associated with serology. Therefore, the correlation between the LEI0258 alleles and the MHC class I and the class II alleles at the level of sequences is w...

  7. Overdispersion in allelic counts and θ-correction in forensic genetics

    DEFF Research Database (Denmark)

    Tvedebrink, Torben

    2010-01-01

    We present a statistical model for incorporating the extra variability in allelic counts due to subpopulation structures. In forensic genetics, this effect is modelled by the identical-by-descent parameter θ, which measures the relationship between pairs of alleles within a population relative...

  8. Microsatellite allele dose and configuration establishment (MADCE): an integrated approach for genetic studies in allopolyploids

    NARCIS (Netherlands)

    Dijk, van T.; Noordijk, Y.; Dubos, T.; Bink, M.C.A.M.; Visser, R.G.F.; Weg, van de W.E.

    2012-01-01

    BACKGROUND: Genetic studies in allopolyploid plants are challenging because of the presence of similar sub-genomes, which leads to multiple alleles and complex segregation ratios. In this study, we describe a novel method for establishing the exact dose and configuration of microsatellite alleles fo

  9. Revealing the Genetic Variation and Allele Heterozygote Javanese and Arab Families in Malang East Java Indonesia

    Directory of Open Access Journals (Sweden)

    Nila Kartika Sari

    2014-02-01

    Results: Our result showed that the genetic variability and heterozygote allele increasing by using the 13 CODIS markers from the first generation to the next generation with paternity testing from each family were matched. Conclusion: We can conclude that in a Javanese-Arab family ethnic seems stimulate the increasing genetic variation and allele heterozygote.

  10. The effect of wild card designations and rare alleles in forensic DNA database searches.

    Science.gov (United States)

    Tvedebrink, Torben; Bright, Jo-Anne; Buckleton, John S; Curran, James M; Morling, Niels

    2015-05-01

    Forensic DNA databases are powerful tools used for the identification of persons of interest in criminal investigations. Typically, they consist of two parts: (1) a database containing DNA profiles of known individuals and (2) a database of DNA profiles associated with crime scenes. The risk of adventitious or chance matches between crimes and innocent people increases as the number of profiles within a database grows and more data is shared between various forensic DNA databases, e.g. from different jurisdictions. The DNA profiles obtained from crime scenes are often partial because crime samples may be compromised in quantity or quality. When an individual's profile cannot be resolved from a DNA mixture, ambiguity is introduced. A wild card, F, may be used in place of an allele that has dropped out or when an ambiguous profile is resolved from a DNA mixture. Variant alleles that do not correspond to any marker in the allelic ladder or appear above or below the extent of the allelic ladder range are assigned the allele designation R for rare allele. R alleles are position specific with respect to the observed/unambiguous allele. The F and R designations are made when the exact genotype has not been determined. The F and R designation are treated as wild cards for searching, which results in increased chance of adventitious matches. We investigated the probability of adventitious matches given these two types of wild cards.

  11. Characterization of the novel HLA-Cw*0624 allele identified by sequence-based typing.

    Science.gov (United States)

    Deng, Z-H; Wang, D-M; Gao, S-Q; Xu, Y-P

    2010-01-01

    A novel HLA-Cw*0624 variant allele differs from the closest allele Cw*06020101 by single nucleotide change at genomic nt 923 T>C (CDS nt 547 T>C, codon 159 TAC>CAC) in exon 3, which results in an amino acid change Tyr159His.

  12. A novel HLA-Cw*01 variant allele, HLA-Cw*0130.

    Science.gov (United States)

    Deng, Z-H; Wang, D-M

    2009-12-01

    The novel HLA-Cw*0130 variant allele differs from the closest allele Cw*010201 by single nucleotide change at genomic nt 959 T>C (CDS nt 583 T>C, codon 171 TAC>CAC) in exon 3, which causes an amino acid change Tyr171His.

  13. Extinction time and age of an allele in a large finite population

    NARCIS (Netherlands)

    Herwaarden, van O.A.; Wal, van der N.J.

    2002-01-01

    For a single locus with two alleles we study the expected extinction and fixation times of the alleles under the influence of selection and genetic drift. Using a diffusion model we derive asymptotic approximations for these expected exit times for large populations. We consider the case where the f

  14. Mannose-binding lectin variant alleles and the risk of arterial thrombosis in systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Øhlenschlaeger, Tommy; Garred, Peter; Madsen, Hans O

    2004-01-01

    Cardiovascular disease is an important complication in patients with systemic lupus erythematosus (SLE). Variant alleles of the mannose-binding lectin gene are associated with SLE as well as with severe atherosclerosis. We determined whether mannose-binding lectin variant alleles were associated...

  15. A new mutation for Huntington disease following maternal transmission of an intermediate allele

    NARCIS (Netherlands)

    Semaka, Alicia; Kay, Chris; Belfroid, Rene D. M.; Bijlsma, Emilia K.; Losekoot, Monique; van Langen, Irene M.; van Maarle, Merel C.; Oosterloo, Mayke; Hayden, Michael R.; van Belzen, Martine J.

    2015-01-01

    New mutations for Huntington disease (HD) originate from CAG repeat expansion of intermediate alleles (27-35 CAG). Expansions of such alleles into the pathological range (>= 36 CAG) have been exclusively observed in paternal transmission. We report the occurrence of a new mutation that defies the pa

  16. Effects of the APOE ε2 Allele on Mortality and Cognitive Function in the Oldest Old

    DEFF Research Database (Denmark)

    Lindahl-Jacobsen, Rune; Tan, Qihua; Mengel-From, Jonas;

    2013-01-01

    Some studies indicate that the APOE ε2 allele may have a protective effect on mortality and mental health among the elderly adults. We investigated the effect of the APOE ε2 allele on cognitive function and mortality in 1651 members of the virtually extinct Danish 1905 birth cohort. We found...

  17. Possible interaction between MAOA and DRD2 genes associated with antisocial alcoholism among Han Chinese men in Taiwan.

    Science.gov (United States)

    Wang, Tso-Jen; Huang, San-Yuan; Lin, Wei-Wen; Lo, Hsin-Yi; Wu, Pei-Lin; Wang, Yu-Shan; Wu, Yi-Syuan; Ko, Huei-Chen; Shih, Jean-Chen; Lu, Ru-Band

    2007-01-30

    Both monoamine oxidase A (MAOA) and dopamine D(2) receptor (DRD2) genes have been considered as candidate genes for antisocial personality disorder with alcoholism (Antisocial ALC) [Parsian, A., 1999. Sequence analysis of exon 8 of MAO-A gene in alcoholics with antisocial personality and normal controls. Genomics. 45, 290-295.; Samochowiec, J., Lesch, K.P., Rottmann, M., Smolka, M., Syagailo, Y.V., Okladnova, O., Rommelspacher, H., Winterer, G., Schmidt, L.G., Sander, T., 1999. Association of a regulatory polymorphism in the promoter region of the monoamine oxidase A gene with antisocial alcoholism. Psychiatry. Res. 86, 67-72.; Schmidt, L.vG., Sander, T., Kuhn, S., Smolka, M., Rommelspacher, H., Samochowiec, J., Lesch, K.P., 2000. Different allele distribution of a regulatory MAO-A gene promotor polymorphism in antisocial and anxious-depressive alcoholics. J. Neural .Transm. 107, 681-689.]. However, the association between alcoholism and MAOA or DRD2 gene has not been universally accepted [Lee, J.F., Lu, R.B., Ko, H.C., Chang, F.M., Yin, S.J., Pakstis, A.J., Kidd, K.K., 1999. No association between DRD(2) locus and alcoholism after controlling the ADH and ALDH genotypes in Chinese Han population. Alcohol. Clin. Exp. Res. 23, 592-599.; Lu, R.B., Lin, W.W., Lee, J.F., Ko, H.C., Shih, J.C., 2003. Neither antisocial personality disorder nor antisocial alcoholism association with MAOA gene among Han Chinese males in Taiwan. Alcohol. Clin. Exp. Res. 27, 889-893.]. Since dopamine is metabolized to 3,4-dihydroxyphenyl-acetaldehyde (DOPAL) via monoamine oxidase (MAO) [Westerink, B.H., de Vries, J.B., 1985. On the origin of dopamine and its metabolite in predominantly noradrenergic innervated brain areas. Brain. Res. 330, 164-166.], the interaction between MAOA and DRD2 genes might be related to Antisocial ALC. The present study aimed to determine whether Antisocial ALC might be associated with the possible interactions of DRD2 gene with MAOA gene. Of the 231 Han Chinese

  18. Inter-allelic interactions play a major role in microsatellite evolution.

    Science.gov (United States)

    Amos, William; Kosanović, Danica; Eriksson, Anders

    2015-11-07

    Microsatellite mutations identified in pedigrees confirm that most changes involve the gain or loss of single repeats. However, an unexpected pattern is revealed when the resulting data are plotted on standardized scales that range from the shortest to longest allele at a locus. Both mutation rate and mutation bias reveal a strong dependency on allele length relative to other alleles at the same locus. We show that models in which alleles mutate independently cannot explain these patterns. Instead, both mutation probability and direction appear to involve interactions between homologues in heterozygous individuals. Simple models in which the longer homologue in heterozygotes is more likely to mutate and/or biased towards contraction readily capture the observed trends. The exact model remains unclear in all its details but inter-allelic interactions are a vital component, implying a link between demographic history and the mode and tempo of microsatellite evolution.

  19. Multi-primer target PCR for rapid identification of bovine DRB3 alleles.

    Science.gov (United States)

    Ledwidge, S A; Mallard, B A; Gibson, J P; Jansen, G B; Jiang, Z H

    2001-08-01

    Multi-primer target polymerase chain reaction (MPT-PCR) is a rapid method for the identification of specific BoLA-DRB3 alleles. In a single PCR reaction, the presence of two alleles associated with increased risk, DRB3.2*23 (DRB3*2701-2703, 2705-2707) and decreased risk, DRB3.2*16 (DRB3*1501, 1502), of mastitis in Canadian Holstein can be detected. Two outer primers amplify exon 2 of DRB3. Simultaneously, two inner, allele-specific primers amplify individual alleles. Initially, 40 cows previously typed by PCR-restriction fragment length polymorphism (PCR-RFLP) were genotyped using the multi-primer approach. An additional 30 cows were first genotyped by multi-primer target PCR, then by PCR-RFLP. All animals were correctly identified and there were no false positives. This technique can readily be modified to identify other BoLA alleles of interest.

  20. The number of self-incompatibility alleles in a finite, subdivided population

    DEFF Research Database (Denmark)

    Schierup, M H

    1998-01-01

    The actual and effective number of gametophytic self-incompatibility alleles maintained at mutation-drift-selection equilibrium in a finite population subdivided as in the island model is investigated by stochastic simulations. The existing theory founded by Wright predicts that for a given...... population size the number of alleles maintained increases monotonically with decreasing migration as is the case for neutral alleles. The simulation results here show that this is not true. At migration rates above Nm = 0.01-0.1, the actual and effective number of alleles is lower than for an undivided...... population with the same number of individuals, and, contrary to Wright's theoretical expectation, the number of alleles is not much higher than for an undivided population unless Nm

  1. BaalChIP: Bayesian analysis of allele-specific transcription factor binding in cancer genomes.

    Science.gov (United States)

    de Santiago, Ines; Liu, Wei; Yuan, Ke; O'Reilly, Martin; Chilamakuri, Chandra Sekhar Reddy; Ponder, Bruce A J; Meyer, Kerstin B; Markowetz, Florian

    2017-02-24

    Allele-specific measurements of transcription factor binding from ChIP-seq data are key to dissecting the allelic effects of non-coding variants and their contribution to phenotypic diversity. However, most methods of detecting an allelic imbalance assume diploid genomes. This assumption severely limits their applicability to cancer samples with frequent DNA copy-number changes. Here we present a Bayesian statistical approach called BaalChIP to correct for the effect of background allele frequency on the observed ChIP-seq read counts. BaalChIP allows the joint analysis of multiple ChIP-seq samples across a single variant and outperforms competing approaches in simulations. Using 548 ENCODE ChIP-seq and six targeted FAIRE-seq samples, we show that BaalChIP effectively corrects allele-specific analysis for copy-number variation and increases the power to detect putative cis-acting regulatory variants in cancer genomes.

  2. Demographic history and rare allele sharing among human populations

    Science.gov (United States)

    Gravel, Simon; Henn, Brenna M.; Gutenkunst, Ryan N.; Indap, Amit R.; Marth, Gabor T.; Clark, Andrew G.; Yu, Fuli; Gibbs, Richard A.; Bustamante, Carlos D.; Altshuler, David L.; Durbin, Richard M.; Abecasis, Gonçalo R.; Bentley, David R.; Chakravarti, Aravinda; Clark, Andrew G.; Collins, Francis S.; De La Vega, Francisco M.; Donnelly, Peter; Egholm, Michael; Flicek, Paul; Gabriel, Stacey B.; Gibbs, Richard A.; Knoppers, Bartha M.; Lander, Eric S.; Lehrach, Hans; Mardis, Elaine R.; McVean, Gil A.; Nickerson, Debbie A.; Peltonen, Leena; Schafer, Alan J.; Sherry, Stephen T.; Wang, Jun; Wilson, Richard K.; Gibbs, Richard A.; Deiros, David; Metzker, Mike; Muzny, Donna; Reid, Jeff; Wheeler, David; Wang, Jun; Li, Jingxiang; Jian, Min; Li, Guoqing; Li, Ruiqiang; Liang, Huiqing; Tian, Geng; Wang, Bo; Wang, Jian; Wang, Wei; Yang, Huanming; Zhang, Xiuqing; Zheng, Huisong; Lander, Eric S.; Altshuler, David L.; Ambrogio, Lauren; Bloom, Toby; Cibulskis, Kristian; Fennell, Tim J.; Gabriel, Stacey B.; Jaffe, David B.; Shefler, Erica; Sougnez, Carrie L.; Bentley, David R.; Gormley, Niall; Humphray, Sean; Kingsbury, Zoya; Koko-Gonzales, Paula; Stone, Jennifer; McKernan, Kevin J.; Costa, Gina L.; Ichikawa, Jeffry K.; Lee, Clarence C.; Sudbrak, Ralf; Lehrach, Hans; Borodina, Tatiana A.; Dahl, Andreas; Davydov, Alexey N.; Marquardt, Peter; Mertes, Florian; Nietfeld, Wilfiried; Rosenstiel, Philip; Schreiber, Stefan; Soldatov, Aleksey V.; Timmermann, Bernd; Tolzmann, Marius; Egholm, Michael; Affourtit, Jason; Ashworth, Dana; Attiya, Said; Bachorski, Melissa; Buglione, Eli; Burke, Adam; Caprio, Amanda; Celone, Christopher; Clark, Shauna; Conners, David; Desany, Brian; Gu, Lisa; Guccione, Lorri; Kao, Kalvin; Kebbel, Andrew; Knowlton, Jennifer; Labrecque, Matthew; McDade, Louise; Mealmaker, Craig; Minderman, Melissa; Nawrocki, Anne; Niazi, Faheem; Pareja, Kristen; Ramenani, Ravi; Riches, David; Song, Wanmin; Turcotte, Cynthia; Wang, Shally; Mardis, Elaine R.; Wilson, Richard K.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Weinstock, George; Durbin, Richard M.; Burton, John; Carter, David M.; Churcher, Carol; Coffey, Alison; Cox, Anthony; Palotie, Aarno; Quail, Michael; Skelly, Tom; Stalker, James; Swerdlow, Harold P.; Turner, Daniel; De Witte, Anniek; Giles, Shane; Gibbs, Richard A.; Wheeler, David; Bainbridge, Matthew; Challis, Danny; Sabo, Aniko; Yu, Fuli; Yu, Jin; Wang, Jun; Fang, Xiaodong; Guo, Xiaosen; Li, Ruiqiang; Li, Yingrui; Luo, Ruibang; Tai, Shuaishuai; Wu, Honglong; Zheng, Hancheng; Zheng, Xiaole; Zhou, Yan; Li, Guoqing; Wang, Jian; Yang, Huanming; Marth, Gabor T.; Garrison, Erik P.; Huang, Weichun; Indap, Amit; Kural, Deniz; Lee, Wan-Ping; Leong, Wen Fung; Quinlan, Aaron R.; Stewart, Chip; Stromberg, Michael P.; Ward, Alistair N.; Wu, Jiantao; Lee, Charles; Mills, Ryan E.; Shi, Xinghua; Daly, Mark J.; DePristo, Mark A.; Altshuler, David L.; Ball, Aaron D.; Banks, Eric; Bloom, Toby; Browning, Brian L.; Cibulskis, Kristian; Fennell, Tim J.; Garimella, Kiran V.; Grossman, Sharon R.; Handsaker, Robert E.; Hanna, Matt; Hartl, Chris; Jaffe, David B.; Kernytsky, Andrew M.; Korn, Joshua M.; Li, Heng; Maguire, Jared R.; McCarroll, Steven A.; McKenna, Aaron; Nemesh, James C.; Philippakis, Anthony A.; Poplin, Ryan E.; Price, Alkes; Rivas, Manuel A.; Sabeti, Pardis C.; Schaffner, Stephen F.; Shefler, Erica; Shlyakhter, Ilya A.; Cooper, David N.; Ball, Edward V.; Mort, Matthew; Phillips, Andrew D.; Stenson, Peter D.; Sebat, Jonathan; Makarov, Vladimir; Ye, Kenny; Yoon, Seungtai C.; Bustamante, Carlos D.; Clark, Andrew G.; Boyko, Adam; Degenhardt, Jeremiah; Gravel, Simon; Gutenkunst, Ryan N.; Kaganovich, Mark; Keinan, Alon; Lacroute, Phil; Ma, Xin; Reynolds, Andy; Clarke, Laura; Flicek, Paul; Cunningham, Fiona; Herrero, Javier; Keenen, Stephen; Kulesha, Eugene; Leinonen, Rasko; McLaren, William M.; Radhakrishnan, Rajesh; Smith, Richard E.; Zalunin, Vadim; Zheng-Bradley, Xiangqun; Korbel, Jan O.; Stütz, Adrian M.; Humphray, Sean; Bauer, Markus; Cheetham, R. Keira; Cox, Tony; Eberle, Michael; James, Terena; Kahn, Scott; Murray, Lisa; Chakravarti, Aravinda; Ye, Kai; De La Vega, Francisco M.; Fu, Yutao; Hyland, Fiona C. L.; Manning, Jonathan M.; McLaughlin, Stephen F.; Peckham, Heather E.; Sakarya, Onur; Sun, Yongming A.; Tsung, Eric F.; Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.; Sudbrak, Ralf; Albrecht, Marcus W.; Amstislavskiy, Vyacheslav S.; Herwig, Ralf; Parkhomchuk, Dimitri V.; Sherry, Stephen T.; Agarwala, Richa; Khouri, Hoda M.; Morgulis, Aleksandr O.; Paschall, Justin E.; Phan, Lon D.; Rotmistrovsky, Kirill E.; Sanders, Robert D.; Shumway, Martin F.; Xiao, Chunlin; McVean, Gil A.; Auton, Adam; Iqbal, Zamin; Lunter, Gerton; Marchini, Jonathan L.; Moutsianas, Loukas; Myers, Simon; Tumian, Afidalina; Desany, Brian; Knight, James; Winer, Roger; Craig, David W.; Beckstrom-Sternberg, Steve M.; Christoforides, Alexis; Kurdoglu, Ahmet A.; Pearson, John V.; Sinari, Shripad A.; Tembe, Waibhav D.; Haussler, David; Hinrichs, Angie S.; Katzman, Sol J.; Kern, Andrew; Kuhn, Robert M.; Przeworski, Molly; Hernandez, Ryan D.; Howie, Bryan; Kelley, Joanna L.; Melton, S. Cord; Abecasis, Gonçalo R.; Li, Yun; Anderson, Paul; Blackwell, Tom; Chen, Wei; Cookson, William O.; Ding, Jun; Kang, Hyun Min; Lathrop, Mark; Liang, Liming; Moffatt, Miriam F.; Scheet, Paul; Sidore, Carlo; Snyder, Matthew; Zhan, Xiaowei; Zöllner, Sebastian; Awadalla, Philip; Casals, Ferran; Idaghdour, Youssef; Keebler, John; Stone, Eric A.; Zilversmit, Martine; Jorde, Lynn; Xing, Jinchuan; Eichler, Evan E.; Aksay, Gozde; Alkan, Can; Hajirasouliha, Iman; Hormozdiari, Fereydoun; Kidd, Jeffrey M.; Sahinalp, S. Cenk; Sudmant, Peter H.; Mardis, Elaine R.; Chen, Ken; Chinwalla, Asif; Ding, Li; Koboldt, Daniel C.; McLellan, Mike D.; Dooling, David; Weinstock, George; Wallis, John W.; Wendl, Michael C.; Zhang, Qunyuan; Durbin, Richard M.; Albers, Cornelis A.; Ayub, Qasim; Balasubramaniam, Senduran; Barrett, Jeffrey C.; Carter, David M.; Chen, Yuan; Conrad, Donald F.; Danecek, Petr; Dermitzakis, Emmanouil T.; Hu, Min; Huang, Ni; Hurles, Matt E.; Jin, Hanjun; Jostins, Luke; Keane, Thomas M.; Le, Si Quang; Lindsay, Sarah; Long, Quan; MacArthur, Daniel G.; Montgomery, Stephen B.; Parts, Leopold; Stalker, James; Tyler-Smith, Chris; Walter, Klaudia; Zhang, Yujun; Gerstein, Mark B.; Snyder, Michael; Abyzov, Alexej; Balasubramanian, Suganthi; Bjornson, Robert; Du, Jiang; Grubert, Fabian; Habegger, Lukas; Haraksingh, Rajini; Jee, Justin; Khurana, Ekta; Lam, Hugo Y. K.; Leng, Jing; Mu, Xinmeng Jasmine; Urban, Alexander E.; Zhang, Zhengdong; Li, Yingrui; Luo, Ruibang; Marth, Gabor T.; Garrison, Erik P.; Kural, Deniz; Quinlan, Aaron R.; Stewart, Chip; Stromberg, Michael P.; Ward, Alistair N.; Wu, Jiantao; Lee, Charles; Mills, Ryan E.; Shi, Xinghua; McCarroll, Steven A.; Banks, Eric; DePristo, Mark A.; Handsaker, Robert E.; Hartl, Chris; Korn, Joshua M.; Li, Heng; Nemesh, James C.; Sebat, Jonathan; Makarov, Vladimir; Ye, Kenny; Yoon, Seungtai C.; Degenhardt, Jeremiah; Kaganovich, Mark; Clarke, Laura; Smith, Richard E.; Zheng-Bradley, Xiangqun; Korbel, Jan O.; Humphray, Sean; Cheetham, R. Keira; Eberle, Michael; Kahn, Scott; Murray, Lisa; Ye, Kai; De La Vega, Francisco M.; Fu, Yutao; Peckham, Heather E.; Sun, Yongming A.; Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.; Xiao, Chunlin; Iqbal, Zamin; Desany, Brian; Blackwell, Tom; Snyder, Matthew; Xing, Jinchuan; Eichler, Evan E.; Aksay, Gozde; Alkan, Can; Hajirasouliha, Iman; Hormozdiari, Fereydoun; Kidd, Jeffrey M.; Chen, Ken; Chinwalla, Asif; Ding, Li; McLellan, Mike D.; Wallis, John W.; Hurles, Matt E.; Conrad, Donald F.; Walter, Klaudia; Zhang, Yujun; Gerstein, Mark B.; Snyder, Michael; Abyzov, Alexej; Du, Jiang; Grubert, Fabian; Haraksingh, Rajini; Jee, Justin; Khurana, Ekta; Lam, Hugo Y. K.; Leng, Jing; Mu, Xinmeng Jasmine; Urban, Alexander E.; Zhang, Zhengdong; Gibbs, Richard A.; Bainbridge, Matthew; Challis, Danny; Coafra, Cristian; Dinh, Huyen; Kovar, Christie; Lee, Sandy; Muzny, Donna; Nazareth, Lynne; Reid, Jeff; Sabo, Aniko; Yu, Fuli; Yu, Jin; Marth, Gabor T.; Garrison, Erik P.; Indap, Amit; Leong, Wen Fung; Quinlan, Aaron R.; Stewart, Chip; Ward, Alistair N.; Wu, Jiantao; Cibulskis, Kristian; Fennell, Tim J.; Gabriel, Stacey B.; Garimella, Kiran V.; Hartl, Chris; Shefler, Erica; Sougnez, Carrie L.; Wilkinson, Jane; Clark, Andrew G.; Gravel, Simon; Grubert, Fabian; Clarke, Laura; Flicek, Paul; Smith, Richard E.; Zheng-Bradley, Xiangqun; Sherry, Stephen T.; Khouri, Hoda M.; Paschall, Justin E.; Shumway, Martin F.; Xiao, Chunlin; McVean, Gil A.; Katzman, Sol J.; Abecasis, Gonçalo R.; Blackwell, Tom; Mardis, Elaine R.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Koboldt, Daniel C.; Durbin, Richard M.; Balasubramaniam, Senduran; Coffey, Allison; Keane, Thomas M.; MacArthur, Daniel G.; Palotie, Aarno; Scott, Carol; Stalker, James; Tyler-Smith, Chris; Gerstein, Mark B.; Balasubramanian, Suganthi; Chakravarti, Aravinda; Knoppers, Bartha M.; Abecasis, Gonçalo R.; Bustamante, Carlos D.; Gharani, Neda; Gibbs, Richard A.; Jorde, Lynn; Kaye, Jane S.; Kent, Alastair; Li, Taosha; McGuire, Amy L.; McVean, Gil A.; Ossorio, Pilar N.; Rotimi, Charles N.; Su, Yeyang; Toji, Lorraine H.; TylerSmith, Chris; Brooks, Lisa D.; Felsenfeld, Adam L.; McEwen, Jean E.; Abdallah, Assya; Juenger, Christopher R.; Clemm, Nicholas C.; Collins, Francis S.; Duncanson, Audrey; Green, Eric D.; Guyer, Mark S.; Peterson, Jane L.; Schafer, Alan J.; Abecasis, Gonçalo R.; Altshuler, David L.; Auton, Adam; Brooks, Lisa D.; Durbin, Richard M.; Gibbs, Richard A.; Hurles, Matt E.; McVean, Gil A.

    2011-01-01

    High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2–4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence. PMID:21730125

  3. Diversity of HLA-B17 alleles and haplotypes in East Asians and a novel Cw6 allele (Cw*0604) associated with B*5701.

    Science.gov (United States)

    Inoue, T; Ogawa, A; Tokunaga, K; Ishikawa, Y; Kashiwase, K; Tanaka, H; Park, M H; Jia, G J; Chimge, N O; Sideltseva, E W; Akaza, T; Tadokoro, K; Takahashi, T; Juji, T

    1999-06-01

    The distribution of HLA-B17 alleles and their association with HLA-A, -C and -DRB1 alleles were investigated in seven East Asian populations Japanese, South Korean, Chinese-Korean, Man, Northern Han, Mongolian and Buryat populations). The B17 alleles were identified from genomic DNA using group-specific polymerase chain reaction (PCR) followed by hybridization with sequence-specific oligonucleotide probes (SSOP). In all of these East Asian populations, except Japanese and Chinese-Koreans, B*5701 was detected and strongly associated with A*0101, Cw*0602 and DRB1*0701. In contrast, B*5801 was detected in all the seven populations and strongly associated with A*3303, Cw*0302, DRB1*0301 and DRB1*1302. The A*3303-Cw*0302-B*5801-DRB1*1302 haplotype was observed in South Korean, Chinese-Korean, Buryat and Japanese populations, while A*3303-Cw*0302-B*5801-DRB1*0301 was predominantly observed in the Mongolian population. A similar haplotype, A*0101-Cw*0302-B*5801-DRB1*1302, was observed in the Buryat population. A novel Cw6 allele, Cw*0604, was identified in the Man population. This Cw allele was observed on the haplotype A*0101-B*5701-DRB1*0701. Thus, we confirmed, at the sequence level, that the common haplotypes carrying B*5701 and B*5801 have been conserved and shared in East Asian populations.

  4. Determination of allele frequency in pooled DNA: comparison of three PCR-based methods.

    Science.gov (United States)

    Wilkening, Stefan; Hemminki, Kari; Thirumaran, Ranjit Kumar; Bermejo, Justo Lorenzo; Bonn, Stefan; Försti, Asta; Kumar, Rajiv

    2005-12-01

    Determination of allele frequency in pooled DNA samples is a powerful and efficient tool for large-scale association studies. In this study, we tested and compared three PCR-based methods for accuracy, reproducibility, cost, and convenience. The methods compared were: (i) real-time PCR with allele-specific primers, (ii) real-time PCR with allele-specific TaqMan probes, and (iii) quantitative sequencing. Allele frequencies of three single nucleotide polymorphisms in three different genes were estimated from pooled DNA. The pools were made of genomic DNA samples from 96 cases with basal cell carcinoma of the skin and 96 healthy controls with known genotypes. In this study, the allele frequency estimation made by real-time PCR with allele-specific primers had the smallest median deviation (MD) from the real allele frequency with 1.12% (absolute percentage points) and was also the cheapest method. However; this method required the most time for optimization and showed the highest variation between replicates (SD = 6.47%). Quantitative sequencing, the simplest method, was found to have intermediate accuracies (MD = 1.44%, SD = 4.2%). Real-time PCR with TaqMan probes, a convenient but very expensive method, had an MD of 1.47% and the lowest variation between replicates (SD = 3.18%).

  5. Allelic discrimination in naturalized ovine from Pantanal Sul-Matogrossense by means of microsatellite markers

    Directory of Open Access Journals (Sweden)

    Crispim Bruno do Amaral

    2012-08-01

    Full Text Available The molecular biology techniques that are used in allelic discrimination for individual and sheep breeds characterization are important tools in breeding programs and conservation of genetic resources. The use of microsatellite markers allows allelic differentiation, which in turn allows us to infer the genetic variability of sample populations. The study aimed to test the sensitivity and efficiency of fluorescent capillary electrophoresis, using microsatellite primers, for allelic discrimination of the Crioulo breed from Pantanal sul-matogrossense, as well as verify the possibility of using the products of sequencing in genetic variability analysis. For this test, were used blood samples from Pantaneira breed sheep. The allelic discrimination of eight microsatellites was determined by capillary electrophoresis in automatic sequencer and the results analyses were performed on the programs CERVUS and Dendro-UPGMA. The results indicated the possibility of using this technique for the individual genotyping of all loci tested in electrophoretic analysis and its potential to allelic discrimination even in case of difference between two pairs of bases between the alleles. The resulting dendrogram based on the distance matrix by the UPGMA assembly method, indicated medium similarity coefficient of 0.72 in the group of animals. It was concluded that there is the viability and efficiency of the microsatellite molecular markers technique using capillary electrophoresis for allelic discrimination and the utility of results for studies of genetic variability, paternity diagnosis and characterization of the Crioulo sheep herd from Pantanal sul-matogrossense.

  6. Functional conservation and coherence of HIV-1 subtype A Vpu alleles

    Science.gov (United States)

    Romani, Bizhan; Kavyanifard, Amirarsalan; Allahbakhshi, Elham

    2017-01-01

    Functional studies of HIV-1 proteins are normally conducted using lab adapted strains of HIV-1. The extent of those functions in clinical strains is sometimes unknown. In this study, we amplified and sequenced HIV-1 Vpu from 10 Iranian patients infected with HIV-1. Phylogenetic analysis indicated that the Vpu alleles were closely related to the CRF35_AD from Iran and subtype A Vpu. We addressed some of the well-established functions of the HIV-1 Vpu, as well as some of its recently reported functions. Ability of the clinical strains of subtype A Vpu alleles for downregulation of CD4 was similar to that of the lab adapted NL4.3 Vpu. Majority of the subtype A Vpu alleles performed stronger than NL4.3 Vpu for downregulation of SNAT1. The Vpu alleles differentially induced downregulation of HLA-C, ranging from no effect to 88% downregulation of surface HLA-C. Downregulation of tetherin and enhancement of virus release was similar for the subtype A Vpu alleles and NL4.3. Subtype A Vpu alleles were more potent when compared with NL4.3 for inhibition of NF-κB activation. Our study shows that subtype A Vpu alleles exert the classical functions of HIV-1 Vpu. PMID:28317943

  7. Sensory gating and alpha-7 nicotinic receptor gene allelic variants in schizoaffective disorder, bipolar type.

    Science.gov (United States)

    Martin, Laura F; Leonard, Sherry; Hall, Mei-Hua; Tregellas, Jason R; Freedman, Robert; Olincy, Ann

    2007-07-05

    Single nucleotide allelic variants in the promoter region of the chromosome 15 alpha-7 acetylcholine nicotinic receptor gene (CHRNA7) are associated with both schizophrenia and the P50 auditory evoked potential sensory gating deficit. The purpose of this study was to determine if CHRNA7 promoter allelic variants are also associated with abnormal P50 ratios in persons with schizoaffective disorder, bipolar type. P50 auditory evoked potentials were recorded in a paired stimulus paradigm in 17 subjects with schizoaffective disorder, bipolar type. The P50 test to conditioning ratio was used as the measure of sensory gating. Mutation screening of the CHRNA7 promoter region was performed on the subjects' DNA samples. Comparisons to previously obtained data from persons with schizophrenia and controls were made. Subjects with schizophrenia, regardless of allele status, had an abnormal mean P50 ratio. Subjects with schizoaffective disorder, bipolar type and a variant allele had an abnormal mean P50 ratio, whereas those schizoaffective subjects with the common alleles had a normal mean P50 ratio. Normal control subjects had a normal mean ratio, but controls with variant alleles had higher P50 ratios. In persons with bipolar type schizoaffective disorder, CHRNA7 promoter region allelic variants are linked to the capacity to inhibit the P50 auditory evoked potential and thus are associated with a type of illness genetically and biologically more similar to schizophrenia.

  8. APOL1 null alleles from a rural village in India do not correlate with glomerulosclerosis.

    Directory of Open Access Journals (Sweden)

    Duncan B Johnstone

    Full Text Available BACKGROUND: Among African-Americans, genome wide association revealed a strong correlation between the G1 and G2 alleles of APOL1 (apolipoproteinL1, also called trypanolytic factor and kidney diseases including focal and segmental glomerulosclerosis, HIV-associated nephropathy and hypertensive nephrosclerosis. In the prevailing hypothesis, heterozygous APOL1 G1 and G2 alleles increase resistance against Trypanosoma that cause African sleeping sickness, resulting in positive selection of these alleles, but when homozygous the G1 and G2 alleles predispose to glomerulosclerosis. While efforts are underway to screen patients for G1 and G2 alleles and to better understand "APOL1 glomerulopathy," no data prove that these APOL1 sequence variants cause glomerulosclerosis. G1 and G2 correlate best with glomerulosclerosis as recessive alleles, which suggests a loss of function mutation for which proof of causality is commonly tested with homozygous null alleles. This test cannot be performed in rodents as the APOL gene cluster evolved only in primates. However, there is a homozygous APOL1 null human being who lives in a village in rural India. This individual and his family offer a unique opportunity to test causality between APOL1 null alleles and glomerulosclerosis. METHODS AND FINDINGS: We obtained clinical data, blood and urine from this APOL1 null patient and 50 related villagers. Based on measurements of blood pressure, BUN, creatinine, albuminuria, genotyping and immunoblotting, this APOL1 null individual does not have glomerulosclerosis, nor do his relatives who carry APOL1 null alleles. CONCLUSIONS: This small study cannot provide definitive conclusions but the absence of glomerulosclerosis in this unique population is consistent with the possibility that African-American glomerulosclerosis is caused, not by loss of APOL1 function, but by other mechanisms including a subtle gain of function or by the "genetic hitchhiking" of deleterious mutations

  9. Multiple origins of Plasmodium falciparum dihydropteroate synthetase mutant alleles associated with sulfadoxine resistance in India.

    Science.gov (United States)

    Lumb, Vanshika; Das, Manoj K; Singh, Neeru; Dev, Vas; Khan, Wajihullah; Sharma, Yagya D

    2011-06-01

    With the spread of chloroquine (CQ)-resistant malaria in India, sulfadoxine-pyrimethamine (SP) alone or in combination with artesunate is used as an alternative antimalarial drug. Due to continuous drug pressure, the Plasmodium falciparum parasite is exhibiting resistance to antifolates because of mutations in candidate genes dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps). Our earlier study on flanking microsatellite markers of dhfr mutant alleles from India had shown a single origin of the pyrimethamine resistance and some minor haplotypes which shared haplotypes with Southeast Asian (Thailand) strains. In the present study, we have analyzed 193 of these Indian P. falciparum isolates for 15 microsatellite loci around dhps to investigate the genetic lineages of the mutant dhps alleles in different parts of the country. Eighty-one of these samples had mutant dhps alleles, of which 62 were from Andaman and Nicobar Islands and the remaining 19 were from mainland India. Of 112 isolates with a wild-type dhps allele, 109 were from mainland India and only 3 were from Andaman and Nicobar Islands. Consistent with the model of selection, the mean expected heterozygosity (H(e)) around mutant dhps alleles (H(e) = 0.55; n = 81) associated with sulfadoxine resistance was lower (P ≤ 0.05) than the mean H(e) around the wild-type dhps allele (H(e) = 0.80; n = 112). There was more genetic diversity in flanking microsatellites of dhps than dhfr among these isolates, which confirms the assertion that dhps mutations are at a very early stage of fixation in the parasite population. Microsatellite haplotypes around various mutant dhps alleles suggest that the resistant dhps alleles have multiple independent origins in India, especially in Andaman and Nicobar Islands. Determining the genetic lineages of the resistant dhps alleles on Andaman and Nicobar Islands and mainland India is significant, given the role of Asia in the intercontinental spread of chloroquine

  10. Complex and multi-allelic copy number variation in human disease.

    Science.gov (United States)

    Usher, Christina L; McCarroll, Steven A

    2015-09-01

    Hundreds of copy number variants are complex and multi-allelic, in that they have many structural alleles and have rearranged multiple times in the ancestors who contributed chromosomes to current humans. Not only are the relationships of these multi-allelic CNVs (mCNVs) to phenotypes generally unknown, but many mCNVs have not yet been described at the basic levels-alleles, allele frequencies, structural features-that support genetic investigation. To date, most reported disease associations to these variants have been ascertained through candidate gene studies. However, only a few associations have reached the level of acceptance defined by durable replications in many cohorts. This likely stems from longstanding challenges in making precise molecular measurements of the alleles individuals have at these loci. However, approaches for mCNV analysis are improving quickly, and some of the unique characteristics of mCNVs may assist future association studies. Their various structural alleles are likely to have different magnitudes of effect, creating a natural allelic series of growing phenotypic impact and giving investigators a set of natural predictions and testable hypotheses about the extent to which each allele of an mCNV predisposes to a phenotype. Also, mCNVs' low-to-modest correlation to individual single-nucleotide polymorphisms (SNPs) may make it easier to distinguish between mCNVs and nearby SNPs as the drivers of an association signal, and perhaps, make it possible to preliminarily screen candidate loci, or the entire genome, for the many mCNV-disease relationships that remain to be discovered.

  11. A majority of Huntington's disease patients may be treatable by individualized allele-specific RNA interference.

    Science.gov (United States)

    Lombardi, Maria Stella; Jaspers, Leonie; Spronkmans, Christine; Gellera, Cinzia; Taroni, Franco; Di Maria, Emilio; Donato, Stefano Di; Kaemmerer, William F

    2009-06-01

    Use of RNA interference to reduce huntingtin protein (htt) expression in affected brain regions may provide an effective treatment for Huntington disease (HD), but it remains uncertain whether suppression of both wild-type and mutant alleles in a heterozygous patient will provide more benefit than harm. Previous research has shown suppression of just the mutant allele is achievable using siRNA targeted to regions of HD mRNA containing single nucleotide polymorphisms (SNPs). To determine whether more than a minority of patients may be eligible for an allele-specific therapy, we genotyped DNA from 327 unrelated European Caucasian HD patients at 26 SNP sites in the HD gene. Over 86% of the patients were found to be heterozygous for at least one SNP among those tested. Because the sites are genetically linked, one cannot use the heterozygosity rates of the individual SNPs to predict how many sites (and corresponding allele-specific siRNA) would be needed to provide at least one treatment possibility for this percentage of patients. By computing all combinations, we found that a repertoire of allele-specific siRNA corresponding to seven sites can provide at least one allele-specific siRNA treatment option for 85.6% of our sample. Moreover, we provide evidence that allele-specific siRNA targeting these sites are readily identifiable using a high throughput screening method, and that allele-specific siRNA identified using this method indeed show selective suppression of endogenous mutant htt protein in fibroblast cells from HD patients. Therefore, allele-specific siRNA are not so rare as to be impractical to find and use therapeutically.

  12. Reliability assessment of null allele detection: inconsistencies between and within different methods.

    Science.gov (United States)

    Dąbrowski, M J; Pilot, M; Kruczyk, M; Żmihorski, M; Umer, H M; Gliwicz, J

    2014-03-01

    Microsatellite loci are widely used in population genetic studies, but the presence of null alleles may lead to biased results. Here, we assessed five methods that indirectly detect null alleles and found large inconsistencies among them. Our analysis was based on 20 microsatellite loci genotyped in a natural population of Microtus oeconomus sampled during 8 years, together with 1200 simulated populations without null alleles, but experiencing bottlenecks of varying duration and intensity, and 120 simulated populations with known null alleles. In the natural population, 29% of positive results were consistent between the methods in pairwise comparisons, and in the simulated data set, this proportion was 14%. The positive results were also inconsistent between different years in the natural population. In the null-allele-free simulated data set, the number of false positives increased with increased bottleneck intensity and duration. We also found a low concordance in null allele detection between the original simulated populations and their 20% random subsets. In the populations simulated to include null alleles, between 22% and 42% of true null alleles remained undetected, which highlighted that detection errors are not restricted to false positives. None of the evaluated methods clearly outperformed the others when both false-positive and false-negative rates were considered. Accepting only the positive results consistent between at least two methods should considerably reduce the false-positive rate, but this approach may increase the false-negative rate. Our study demonstrates the need for novel null allele detection methods that could be reliably applied to natural populations.

  13. Ambiguous allele combinations in HLA Class I and Class II sequence-based typing: when precise nucleotide sequencing leads to imprecise allele identification

    Directory of Open Access Journals (Sweden)

    Larsen Paula

    2004-09-01

    Full Text Available Abstract Sequence-based typing (SBT is one of the most comprehensive methods utilized for HLA typing. However, one of the inherent problems with this typing method is the interpretation of ambiguous allele combinations which occur when two or more different allele combinations produce identical sequences. The purpose of this study is to investigate the probability of this occurrence. We performed HLA-A,-B SBT for Exons 2 and 3 on 676 donors. Samples were analyzed with a capillary sequencer. The racial distribution of the donors was as follows: 615-Caucasian, 13-Asian, 23-African American, 17-Hispanic and 8-Unknown. 672 donors were analyzed for HLA-A locus ambiguities and 666 donors were analyzed for HLA-B locus ambiguities. At the HLA-A locus a total of 548 total ambiguous allele combinations were identified (548/1344 = 41%. Most (278/548 = 51% of these ambiguities were due to the fact that Exon 4 analysis was not performed. At the HLA-B locus 322 total ambiguous allele combinations were found (322/1332 = 24%. The HLA-B*07/08/15/27/35/44 antigens, common in Caucasians, produced a large portion of the ambiguities (279/322 = 87%. A large portion of HLA-A and B ambiguous allele combinations can be addressed by utilizing a group-specific primary amplification approach to produce an unambiguous homozygous sequence. Therefore, although the prevalence of ambiguous allele combinations is high, if the resolution of these ambiguities is clinically warranted, methods exist to compensate for this problem.

  14. Systematic Functional Interrogation of Rare Cancer Variants Identifies Oncogenic Alleles | Office of Cancer Genomics

    Science.gov (United States)

    Cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. However, most point mutations occur at low frequency, and the function of these alleles remains undefined. We have developed a scalable systematic approach to interrogate the function of cancer-associated gene variants. We subjected 474 mutant alleles curated from 5,338 tumors to pooled in vivo tumor formation assays and gene expression profiling. We identified 12 transforming alleles, including two in genes (PIK3CB, POT1) that have not been shown to be tumorigenic.

  15. THE USE OF NEW REAGENT KITS FOR DETECTION AND DESCRIPTION OF ADDITIONAL ALLELES

    Directory of Open Access Journals (Sweden)

    M. A. Loginova

    2011-01-01

    Full Text Available During the screening typing of recruited volunteers with Volga Federal District for unrelated hematopoietic stem cell registry on the loci (HLA-A, B, DRB1, DRB345 in sample No 1758 identified a new allele at locus A. The use of basic kit AlleleSEQR HLA-A Sequencing in combination with HARP – A2F98A allowed to determine the genotype of this sample – А*30:01:01, a new allele А*25, В*13, 44, DRB1*03, 09, DRB3*02, DRB4*01. 

  16. Estimating Y-STR allelic drop-out rates and adjusting for interlocus balances.

    Science.gov (United States)

    Andersen, Mikkel Meyer; Mogensen, Helle Smidt; Eriksen, Poul Svante; Olofsson, Jill Katharina; Asplund, Maria; Morling, Niels

    2013-05-01

    Y chromosome short tandem repeats (Y-STRs) are valuable genetic markers in certain areas of forensic case-work. However, when the Y-STR DNA profile is weak, the observed Y-STR profile may not be complete--i.e. locus drop-out may have occurred. Another explanation could be that the stain DNA did not have a Y-STR allele that was detectable with the method used (the allele is a 'null allele'). If the Y-STR profile of a stain is strong, one would be reluctant to consider drop-out as a reasonable explanation of lack of a Y-STR allele and would maybe consider 'null allele' as an explanation. On the other hand, if the signal strengths are weak, one would most likely accept drop-out as a possible explanation. We created a logistic regression model to estimate the probability of allele drop-out with the Life Technologies/Applied Biosystems AmpFlSTR(®) Yfiler(®) kit such that the trade-off between drop-outs and null alleles could be quantified using a statistical model. The model to estimate the probability of drop-out uses information about locus imbalances, signal strength, the number of PCR cycles, and the fragment size of Yfiler. We made two temporarily separated experiments and found no evidence of temporal variation in the probability of drop-out. Using our model, we found that for 30 PCR cycles with a 150 bp allele, the probability of drop-out was 1:5000 corresponding to the average estimate of the probability of Y-STR null alleles at a signal strength of 1249 RFU. This means that the probability of a null allele is higher than that of an allele drop-out at e.g. 4000 RFU and the probability of drop-out is higher than that of a null allele at e.g. 75 RFU. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. A New Strategy to Reduce Allelic Bias in RNA-Seq Readmapping

    Science.gov (United States)

    2012-01-01

    Williams,B.A., McCue,K., Schaeffer,L. and Wold ,B. (2008) Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat. Methods, 5, 621–628. 2. Trapnell...Hunt,K.A., Bockett,N., Franke,L., Dubois,P.C., Mein,C.A., Dobson,R.J. et al. (2010) Genome- wide analysis of allelic expression imbalance in human...K.W. (2002) Allelic variation in human gene expression. Science , 297, 1143. 6. Knight,J.C. (2004) Allele-specific gene expression uncovered. Trends

  18. DRD4 polymorphism moderates the effect of alcohol consumption on social bonding.

    Directory of Open Access Journals (Sweden)

    Kasey G Creswell

    Full Text Available Development of interpersonal relationships is a fundamental human motivation, and behaviors facilitating social bonding are prized. Some individuals experience enhanced reward from alcohol in social contexts and may be at heightened risk for developing and maintaining problematic drinking. We employed a 3 (group beverage condition ×2 (genotype design (N = 422 to test the moderating influence of the dopamine D4 receptor gene (DRD4 VNTR polymorphism on the effects of alcohol on social bonding. A significant gene x environment interaction showed that carriers of at least one copy of the 7-repeat allele reported higher social bonding in the alcohol, relative to placebo or control conditions, whereas alcohol did not affect ratings of 7-absent allele carriers. Carriers of the 7-repeat allele were especially sensitive to alcohol's effects on social bonding. These data converge with other recent gene-environment interaction findings implicating the DRD4 polymorphism in the development of alcohol use disorders, and results suggest a specific pathway by which social factors may increase risk for problematic drinking among 7-repeat carriers. More generally, our findings highlight the potential utility of employing transdisciplinary methods that integrate genetic methodologies, social psychology, and addiction theory to improve theories of alcohol use and abuse.

  19. DRD4 polymorphism moderates the effect of alcohol consumption on social bonding.

    Science.gov (United States)

    Creswell, Kasey G; Sayette, Michael A; Manuck, Stephen B; Ferrell, Robert E; Hill, Shirley Y; Dimoff, John D

    2012-01-01

    Development of interpersonal relationships is a fundamental human motivation, and behaviors facilitating social bonding are prized. Some individuals experience enhanced reward from alcohol in social contexts and may be at heightened risk for developing and maintaining problematic drinking. We employed a 3 (group beverage condition) ×2 (genotype) design (N = 422) to test the moderating influence of the dopamine D4 receptor gene (DRD4 VNTR) polymorphism on the effects of alcohol on social bonding. A significant gene x environment interaction showed that carriers of at least one copy of the 7-repeat allele reported higher social bonding in the alcohol, relative to placebo or control conditions, whereas alcohol did not affect ratings of 7-absent allele carriers. Carriers of the 7-repeat allele were especially sensitive to alcohol's effects on social bonding. These data converge with other recent gene-environment interaction findings implicating the DRD4 polymorphism in the development of alcohol use disorders, and results suggest a specific pathway by which social factors may increase risk for problematic drinking among 7-repeat carriers. More generally, our findings highlight the potential utility of employing transdisciplinary methods that integrate genetic methodologies, social psychology, and addiction theory to improve theories of alcohol use and abuse.

  20. HGD-Chn: The Database of Genome Diversity and Variation for Chinese Populations.

    Science.gov (United States)

    Hong-Sheng, Gui; Peng, Zhou; Cheng-Bo, Yang; Sheng-Bin, Li

    2009-04-01

    The Database of Genome Diversity and Variation for Chinese Populations is toward a more efficient utilization and sharing of the valuable yet diminishing genetic resources in China (including sample information of healthy populations, healthy pedigrees, disease population and disease pedigrees; genomic diversity data; disease-related allelic and haplotype data). Organization of the database can be divided into two parts: (1) Genetic resources of healthy people--Organizing genetic resources of healthy people. A variety of genetic markers (VNTR, STR, SNP, HLA, and enzyme markers, etc.) are chosen for their diversity among populations, with their distribution among different ethnic groups in China stored in the form of allelic frequency. A further analysis as well as an overall description of the Chinese population genetic structure is also being made possible. (2) Disease genetic resources--Four categories are mainly concerned: chromosomal diseases, monogenic diseases, polygenic diseases, and birth defects. For each kind of disease, the basic introduction and description, sample information, and allelic data of related gene are involved. Aside from research-oriented information, introductory courses oriented at general public covering fields of genomic diversity and variation, the related experimental techniques, standards and specifications could also be accessed in our website. Further more, flexible query and submit system with user-friendly interfaces are also integrated in our website to simplify the process of user-query and administrators' database maintenance work. Online data analyzing and managing tools are developed using bioinformatics algorithm and programming language for a better interpretation of the biological data.

  1. Serotonin transporter gene polymorphism and schizoid personality traits in the patients with psychosis and psychiatrically well subjects.

    Science.gov (United States)

    Golimbet, Vera E; Alfimova, Margarita V; Shcherbatikh, Tatyana; Kaleda, Vasili G; Abramova, Lilia I; Rogaev, Evgeni I

    2003-01-01

    serotonin transporter (5-HTT) gene allelic variants were shown to be associated with Neuroticism and Harm Avoidance but the results were not replicated in other studies. The current investigation was undertaken in a further attempt to study the relationship between 5-HTT polymorphism and personality traits. to evaluate a spectrum of personality traits, MMPI was administered to a sample including patients with affective disorders (n=114), patients with schizophrenia spectrum illnesses (n=110) and psychiatrically well controls (n=124). All groups were genotyped for VNTR-17 and functional insertion-deletion (5-HTTLPR) polymorphisms. an association was found between 5-HTTLPR polymorphism and scores on three MMPI scales: Psychopathic deviance, Paranoia and Schizophrenia in patients with affective disorders and S chizophrenia in normal subjects. Both affected and control individuals with 'ss' genotype exhibited lower scores on these scales. we demonstrated that functional deletion/insertion allelic variation associated with decreased expression of serotonin transporter ('s' allele or 'ss' genotype) may restrict expression of schizoid traits in normal subjects and patients with affective disorders.

  2. Identification of 2127 new HLA class I alleles in potential stem cell donors from Germany, the United States and Poland.

    Science.gov (United States)

    Hernández-Frederick, C J; Giani, A S; Cereb, N; Sauter, J; Silva-González, R; Pingel, J; Schmidt, A H; Ehninger, G; Yang, S Y

    2014-03-01

    We describe 2127 new human leukocyte antigen (HLA) class I alleles found in registered stem cell donors. These alleles represent 28.9% of the currently known class I alleles. Comparing new allele sequences to homologous sequences, we found 68.1% nonsynonymous nucleotide substitutions, 28.9% silent mutations and 3.0% nonsense mutations. Many substitutions occurred at positions that have not been known to be polymorphic before. A large number of HLA alleles and nucleotide variations underline the extreme diversity of the HLA system. Strikingly, 156 new alleles were found not only multiple times, but also in carriers of various parentage, suggesting that some new alleles are not necessarily rare. Moreover, new alleles were found especially often in minority donors. This emphasizes the benefits of specifically recruiting such groups of individuals.

  3. Analysis of a Larger SNP Dataset from the HapMap Project Confirmed That the Modern Human A Allele of the ABO Blood Group Genes Is a Descendant of a Recombinant between B and O Alleles.

    Science.gov (United States)

    Itou, Masaya; Sato, Mitsuharu; Kitano, Takashi

    2013-01-01

    The human ABO blood group gene consists of three main alleles (A, B, and O) that encode a glycosyltransferase. The A and B alleles differ by two critical amino acids in exon 7, and the major O allele has a single nucleotide deletion (Δ261) in exon 6. Previous evolutionary studies have revealed that the A allele is the most ancient, B allele diverged from the A allele with two critical amino acid substitutions in exon 7, and the major O allele diverged from the A allele with Δ261 in exon 6. However, a recent phylogenetic network analysis study showed that the A allele of humans emerged through a recombination between the B and O alleles. In the previous study, a restricted dataset from only two populations was used. In this study, therefore, we used a large single nucleotide polymorphism (SNP) dataset from the HapMap Project. The results indicated that the A101-A201-O09 haplogroup was a recombinant lineage between the B and O haplotypes, containing the intact exon 6 from the B allele and the two critical A type sites in exon 7 from the major O allele. Its recombination point was assumed to be located just behind Δ261 in exon 6.

  4. Analysis of a Larger SNP Dataset from the HapMap Project Confirmed That the Modern Human A Allele of the ABO Blood Group Genes Is a Descendant of a Recombinant between B and O Alleles

    Directory of Open Access Journals (Sweden)

    Masaya Itou

    2013-01-01

    Full Text Available The human ABO blood group gene consists of three main alleles (A, B, and O that encode a glycosyltransferase. The A and B alleles differ by two critical amino acids in exon 7, and the major O allele has a single nucleotide deletion (Δ261 in exon 6. Previous evolutionary studies have revealed that the A allele is the most ancient, B allele diverged from the A allele with two critical amino acid substitutions in exon 7, and the major O allele diverged from the A allele with Δ261 in exon 6. However, a recent phylogenetic network analysis study showed that the A allele of humans emerged through a recombination between the B and O alleles. In the previous study, a restricted dataset from only two populations was used. In this study, therefore, we used a large single nucleotide polymorphism (SNP dataset from the HapMap Project. The results indicated that the A101-A201-O09 haplogroup was a recombinant lineage between the B and O haplotypes, containing the intact exon 6 from the B allele and the two critical A type sites in exon 7 from the major O allele. Its recombination point was assumed to be located just behind Δ261 in exon 6.

  5. Distribution of apolipoprotein E alleles in coras and huicholes from Nayarit and Nahuas and Mestizos from Veracruz, Mexico.

    Science.gov (United States)

    Cruz-Fuentes, Carlos S; González-Sobrino, Blanca Zoila; Gómez-Sanchez, Ariadna; Martínez Rueda, Hortencia; Chávez-Eakle, Rosa Aurora; Serrano Sánchez, Carlos

    2005-12-01

    We report allele frequencies for the most common polymorphism of the APOE gene in Mexican individuals from two regions not previously described: Coras and Huicholes from Nayarit, and Nahuas and mestizos from Veracruz. We also report APOE allele frequencies for inhabitants of Mexico City. These descriptive data underscore the allelic heterogeneity for this particular locus in Mexico.

  6. Identification of a new HLA-DPB1 allele (DPB1*5101) by oligotyping and nucleotide sequencing

    Energy Technology Data Exchange (ETDEWEB)

    Argyris, E.G.; Cizman, B.; Kamoun, M.; Zmijewski, C.M.; Monos, D.S. [Univ. of Pennsylvania Medical Center, Philadelphia, PA (United States); Gibson, C.G.; Williams, T.M. [Univ. of New Mexico School of Medicine, Albuquerque, NM (United States)

    1994-12-31

    DNA sequence analysis of DPB1 second exons shows great variability with over 50 alleles. This report describes a new HLA-DPB1 allele present in a Caucasoid donor bearing the class II alleles DRB1*0901/1301, DRB3*0101, DRB4*0101, DQB1*0603/0303, and DPB1*1101. 6 refs., 1 fig.

  7. 'True' null allele detection in microsatellite loci: a comparison of methods, assessment of difficulties and survey of possible improvements.

    Science.gov (United States)

    Dąbrowski, M J; Bornelöv, S; Kruczyk, M; Baltzer, N; Komorowski, J

    2015-05-01

    Null alleles are alleles that for various reasons fail to amplify in a PCR assay. The presence of null alleles in microsatellite data is known to bias the genetic parameter estimates. Thus, efficient detection of null alleles is crucial, but the methods available for indirect null allele detection return inconsistent results. Here, our aim was to compare different methods for null allele detection, to explain their respective performance and to provide improvements. We applied several approaches to identify the 'true' null alleles based on the predictions made by five different methods, used either individually or in combination. First, we introduced simulated 'true' null alleles into 240 population data sets and applied the methods to measure their success in detecting the simulated null alleles. The single best-performing method was ML-NullFreq_frequency. Furthermore, we applied different noise reduction approaches to improve the results. For instance, by combining the results of several methods, we obtained more reliable results than using a single one. Rule-based classification was applied to identify population properties linked to the false discovery rate. Rules obtained from the classifier described which population genetic estimates and loci characteristics were linked to the success of each method. We have shown that by simulating 'true' null alleles into a population data set, we may define a null allele frequency threshold, related to a desired true or false discovery rate. Moreover, using such simulated data sets, the expected null allele homozygote frequency may be estimated independently of the equilibrium state of the population.

  8. Population estimators or progeny tests: what is the best method to assess null allele frequencies at SSR loci?

    NARCIS (Netherlands)

    Oddou-Muratorio, S.; Vendramin, G.G.; Buiteveld, J.; Fady, B.

    2009-01-01

    Nuclear SSRs are notorious for having relatively high frequencies of null alleles, i.e. alleles that fail to amplify and are thus recessive and undetected in heterozygotes. In this paper, we compare two kinds of approaches for estimating null allele frequencies at seven nuclear microsatellite marker

  9. Quantification of allele-specific expression of a gene encoding strawberry polygalacturonase-inhibiting protein (PGIP) using Pyrosequencing((TM))

    NARCIS (Netherlands)

    Schaart, J.G.; Mehli, L.; Schouten, H.J.

    2005-01-01

    Recent studies indicate that allele-specific differences in gene expression are a common phenomenon. The extent to which differential allelic expression exists might be underestimated, due to the limited accuracy of the methods used so far. To demonstrate allele-specific expression, we investigated

  10. Genotyping Mycobacterium bovis from cattle in the Central Pampas of Argentina: temporal and regional trends

    Directory of Open Access Journals (Sweden)

    Ernesto Shimizu

    2014-04-01

    Full Text Available Mycobacterium bovis is the causative agent of bovine tuberculosis (TB, a disease that affects approximately 5% of Argentinean cattle. Among the molecular methods for genotyping, the most convenient are spoligotyping and variable number of tandem repeats (VNTR. A total of 378 samples from bovines with visible lesions consistent with TB were collected at slaughterhouses in three provinces, yielding 265 M. bovis spoligotyped isolates, which were distributed into 35 spoligotypes. In addition, 197 isolates were also typed by the VNTR method and 54 combined VNTR types were detected. There were 24 clusters and 27 orphan types. When both typing methods were combined, 98 spoligotypes and VNTR types were observed with 27 clusters and 71 orphan types. By performing a meta-analysis with previous spoligotyping results, we identified regional and temporal trends in the population structure of M. bovis. For SB0140, the most predominant spoligotype in Argentina, the prevalence percentage remained high during different periods, varying from 25.5-57.8% (1994-2011. By contrast, the second and third most prevalent spoligotypes exhibited important fluctuations. This study shows that there has been an expansion in ancestral lineages as demonstrated by spoligotyping. However, exact tandem repeat typing suggests dynamic changes in the clonal population of this microorganism.

  11. GENETIC DIVERSITY OF TYPHA LATIFOLIA (TYPHACEAE) AND THE IMPACT OF POLLUTANTS EXAMINED WITH TANDEM-REPETITIVE DNA PROBES

    Science.gov (United States)

    Genetic diversity at variable-number-tandem-repeat (VNTR) loci was examined in the common cattail, Typha latifolia (Typhaceae), using three synthetic DNA probes composed of tandemly repeated "core" sequences (GACA, GATA, and GCAC). The principal objectives of this investigation w...

  12. GENETIC VARIATION IN RED RASPBERRIES (RUBUS IDAEUS L.; ROSACEAE) FROM SITES DIFFERING IN ORGANIC POLLUTANTS COMPARED WITH SYNTHETIC TANDEM REPEAT DNA PROBES

    Science.gov (United States)

    Two synthetic tandem repetitive DNA probes were used to compare genetic variation at variable-number-tandem-repeat (VNTR) loci among Rubus idaeus L. var. strigosus (Michx.) Maxim. (Rosaceae) individuals sampled at eight sites contaminated by pollutants (N = 39) and eight adjacent...

  13. Clustering of Tuberculosis Cases Based on Variable-Number Tandem-Repeat Typing in Relation to the Population Structure of Mycobacterium tuberculosis in the Netherlands

    NARCIS (Netherlands)

    Sloot, R.; Borgdorff, M.W.; Beer, J.L. de; Ingen, J. van; Supply, P.; Soolingen, D. van

    2013-01-01

    The population structure of 3,776 Mycobacterium tuberculosis isolates was determined using variable-number tandem-repeat (VNTR) typing. The degree of clonality was so high that a more relaxed definition of clustering cannot be applied. Among recent immigrants with non-Euro-American isolates, transmi

  14. Multiple-locus variable-number tandem repeat analysis of Neisseria meningitidis yields groupings similar to those obtained by multilocus sequence typing

    NARCIS (Netherlands)

    L.M. Schouls; A. van der Ende; M. Damen; I. van de Pol

    2006-01-01

    We identified many variable-number tandem repeat (VNTR) loci in the genomes of Neisseria meningitidis serogroups A, B, and C and utilized a number of these loci to develop a multiple-locus variable-number tandem repeat analysis (MLVA). Eighty-five N. meningitidis serogroup B and C isolates obtained

  15. Clustering of Beijing genotype Mycobacterium tuberculosis isolates from the Mekong delta in Vietnam on the basis of variable number of tandem repeat versus restriction fragment length polymorphism typing.

    NARCIS (Netherlands)

    Huyen, M.N.; Kremer, K.; Lan, N.T.; Buu, T.N.; Cobelens, F.G.; Tiemersma, E.W.; Haas, P. de; Soolingen, D. van

    2013-01-01

    BACKGROUND: In comparison to restriction fragment length polymorphism (RFLP) typing, variable number of tandem repeat (VNTR) typing is easier to perform, faster and yields results in a simple, numerical format. Therefore, this technique has gained recognition as the new international gold standard i

  16. Genetic diversity of multidrug-resistant tuberculosis in a resource-limited region of China

    Directory of Open Access Journals (Sweden)

    Dan Zhang

    2014-12-01

    Conclusions: Beijing genotype was the predominant genotype among the isolates from MDR-TB cases in Chongqing. The re-treated MDR-TB cases were more likely to be attributed to Beijing genotype infection. The 10-locus VNTR set demonstrated a good discrimination power for genotyping MDR M. tuberculosis isolates circulating in Chongqing Municipality.

  17. A Trio of Human Molecular Genetics PCR Assays

    Science.gov (United States)

    Reinking, Jeffrey L.; Waldo, Jennifer T.; Dinsmore, Jannett

    2013-01-01

    This laboratory exercise demonstrates three different analytical forms of the polymerase chain reaction (PCR) that allow students to genotype themselves at four different loci. Here, we present protocols to allow students to a) genotype a non-coding polymorphic Variable Number of Tandem Repeat (VNTR) locus on human chromosome 5 using conventional…

  18. Non HLA genetic markers association with type 1-diabetes mellitus

    African Journals Online (AJOL)

    Soheir S. Abou El-Ella

    a minisatellite variable number of tandem repeats (VNTR) locus in the insulin gene (INS) promoter region is likely to ... genes in the cen- tral, class I [2] and extended class I regions may also increase .... lele as shown by percentage value of (42%) in mothers in ..... T1D risk in Czech population and they recommended using.

  19. DNA fingerprinting of Mycobacterium tuberculosis: from phage typing to whole-genome sequencing.

    NARCIS (Netherlands)

    Schurch, A.C.; Soolingen, D. van

    2012-01-01

    Current typing methods for Mycobacterium tuberculosis complex evolved from simple phenotypic approaches like phage typing and drug susceptibility profiling to DNA-based strain typing methods, such as IS6110-restriction fragment length polymorphisms (RFLP) and variable number of tandem repeats (VNTR)

  20. Association of ADHD, Tics, and Anxiety with Dopamine Transporter ("DAT1") Genotype in Autism Spectrum Disorder

    Science.gov (United States)

    Gadow, Kenneth D.; Roohi, Jasmin; DeVincent, Carla J.; Hatchwell, Eli

    2008-01-01

    Background: Autism spectrum disorder (ASD) is associated with high rates of psychiatric disturbance to include attention-deficit/hyperactivity disorder (ADHD), tic disorder, and anxiety disorders. The aim of the present study was to examine the association between a variable number tandem repeat (VNTR) functional polymorphism located in the…

  1. Relevance of MUC1 mucin variable number of tandem repeats polymorphism in H pylori adhesion to gastric epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Natália R Costa; Nuno Mendes; Nuno T Marcos; Celso A Reis; Thomas Caffrey; Michael A Hollingsworth; Filipe Santos-Silva

    2008-01-01

    AIM:To evaluate the influence of MUC1 mucin variable number of tandem repeats (VNTR) variability on H pylori adhesion to gastric cells.METHODS:Enzyme linked immunosorbent assay (ELISA)-based adhesion assays were performed to measure the adhesion of different H pylori strains (HP26695 and HPTx30a) to gastric carcinoma cell lines (GP202 and MKN45) and GP202 clones expressing recombinant MUC1 with different VNTR lengths.RESULTS:Evaluation of adhesion results shows that H pylori pathogenic strain HP26695 has a significantly higher (P<0.05) adhesion to all the cell lines and clones tested,when compared to the non-pathogenic strain HPTx30a.Bacteria showed a significantly higher (P<0.05)adhesion to the GP202 cell line,when compared to the MKN45 cell line.Furthermore,both strains showed a significantly higher (P<0.05) adhesion to GP202 clones with larger MUC1 VNTR domains.CONCLUSION:This work shows that MUC1 mucin variability conditions H pylori binding to gastric cells.The extent of bacterial adhesion depends on the size of the MUC1 VNTR domain.The adhesion is further dependent on bacterial pathogenicity and the gastric cell line.MUC1 mucin variability may contribute to determine H pylori colonization of the gastric mucosa.

  2. A Trio of Human Molecular Genetics PCR Assays

    Science.gov (United States)

    Reinking, Jeffrey L.; Waldo, Jennifer T.; Dinsmore, Jannett

    2013-01-01

    This laboratory exercise demonstrates three different analytical forms of the polymerase chain reaction (PCR) that allow students to genotype themselves at four different loci. Here, we present protocols to allow students to a) genotype a non-coding polymorphic Variable Number of Tandem Repeat (VNTR) locus on human chromosome 5 using conventional…

  3. Association of a Monoamine Oxidase-A Gene Promoter Polymorphism with ADHD and Anxiety in Boys with Autism Spectrum Disorder

    Science.gov (United States)

    Roohi, Jasmin; DeVincent, Carla J.; Hatchwell, Eli; Gadow, Kenneth D.

    2009-01-01

    The aim of the present study was to examine the association between a variable number tandem repeat (VNTR) functional polymorphism in the promoter region of the MAO-A gene and severity of ADHD and anxiety in boys with ASD. Parents and teachers completed a DSM-IV-referenced rating scale for 5- to 14-year-old boys with ASD (n = 43). Planned…

  4. The DRD4 Gene and Severity of Tics and Comorbid Symptoms : Main Effects and Interactions with Delivery Complications

    NARCIS (Netherlands)

    Bos-Veneman, Netty G. P.; Minderaa, Ruud B.; Hoekstra, Pieter J.

    2010-01-01

    In this study, we investigated the role of the dopamine receptor D4 (DRD4) 48-base pairs (bp) variable number of tandem repeats (VNTR) and perinatal adversities regarding severity of tics and comorbid symptoms in children with tic disorders. We genotyped 110 children with tics with regard to the

  5. Novel multiplex format of an extended multilocus variable-number-tandem-repeat analysis of Clostridium difficile correlates with tandem repeat sequence typing.

    Science.gov (United States)

    Jensen, Mie Birgitte Frid; Engberg, Jørgen; Larsson, Jonas T; Olsen, Katharina E P; Torpdahl, Mia

    2015-03-01

    Subtyping of Clostridium difficile is crucial for outbreak investigations. An extended multilocus variable-number tandem-repeat analysis (eMLVA) of 14 variable number tandem repeat (VNTR) loci was validated in multiplex format compatible with a routine typing laboratory and showed excellent concordance with tandem repeat sequence typing (TRST) and high discriminatory power.

  6. The DRD4 Gene and Severity of Tics and Comorbid Symptoms : Main Effects and Interactions with Delivery Complications

    NARCIS (Netherlands)

    Bos-Veneman, Netty G. P.; Minderaa, Ruud B.; Hoekstra, Pieter J.

    2010-01-01

    In this study, we investigated the role of the dopamine receptor D4 (DRD4) 48-base pairs (bp) variable number of tandem repeats (VNTR) and perinatal adversities regarding severity of tics and comorbid symptoms in children with tic disorders. We genotyped 110 children with tics with regard to the 48-

  7. Multiple-locus variable-number tandem repeat analysis of Neisseria meningitidis yields groupings similar to those obtained by multilocus sequence typing.

    NARCIS (Netherlands)

    Schouls, Leo M; Ende, Arie van der; Damen, Marjolein; Pol, Ingrid van de

    2006-01-01

    We identified many variable-number tandem repeat (VNTR) loci in the genomes of Neisseria meningitidis serogroups A, B, and C and utilized a number of these loci to develop a multiple-locus variable-number tandem repeat analysis (MLVA). Eighty-five N. meningitidis serogroup B and C isolates obtained

  8. White spot syndrome virus (WSSV) genome stability maintained over six passages through three different penaeid shrimp species.

    Science.gov (United States)

    Sindhupriya, M; Saravanan, P; Otta, S K; Amarnath, C Bala; Arulraj, R; Bhuvaneswari, T; Praveena, P Ezhil; Jithendran, K P; Ponniah, A G

    2014-08-21

    White spot syndrome virus (WSSV) replicates rapidly, can be extremely pathogenic and is a common cause of mass mortality in cultured shrimp. Variable number tandem repeat (VNTR) sequences present in the open reading frame (ORF)94, ORF125 and ORF75 regions of the WSSV genome have been used widely as genetic markers in epidemiological studies. However, reports that VNTRs might evolve rapidly following even a single transmission through penaeid shrimp or other crustacean hosts have created confusion as to how VNTR data is interpreted. To examine VNTR stability again, 2 WSSV strains (PmTN4RU and LvAP11RU) with differing ORF94 tandem repeat numbers and slight differences in apparent virulence were passaged sequentially 6 times through black tiger shrimp Penaeus monodon, Indian white shrimp Feneropenaeus indicus or Pacific white leg shrimp Litopenaeus vannamei. PCR analyses to genotype the ORF94, ORF125 and ORF75 VNTRs did not identify any differences from either of the 2 parental WSSV strains after multiple passages through any of the shrimp species. These data were confirmed by sequence analysis and indicate that the stability of the genome regions containing these VNTRs is quite high at least for the WSSV strains, hosts and number of passages examined and that the VNTR sequences thus represent useful genetic markers for studying WSSV epidemiology.

  9. Mixed-Strain Mycobacterium tuberculosis Infections among Patients Dying in a Hospital in KwaZulu-Natal, South Africa▿

    OpenAIRE

    Cohen, Ted; Wilson, Douglas; Wallengren, Kristina; Samuel, Elizabeth Y.; Murray, Megan

    2010-01-01

    We performed spoligotyping and 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing on M. tuberculosis culture-positive biopsy specimens collected from adults dying in a hospital in KwaZulu-Natal. Of 56 culture-positive samples genotyped, we detected mixed strains in five (9%) and clonal heterogeneity in an additional four (7%).

  10. Relatedness of Mycobacterium avium subspecies hominissuis clinical isolates of human and porcine origins assessed by MLVA.

    Science.gov (United States)

    Leão, Célia; Canto, Ana; Machado, Diana; Sanches, Ilda Santos; Couto, Isabel; Viveiros, Miguel; Inácio, João; Botelho, Ana

    2014-09-17

    Mycobacterium avium subsp. hominissuis (MAH) is an important opportunistic pathogen, infecting humans and animals, notably pigs. Several methods have been used to characterize MAH strains. RFLP and PFGE typing techniques have been used as standard methods but are technically demanding. In contrast, the analysis of VNTR loci is a simpler, affordable and highly reliable PCR-based technique, allowing a numerical and reproductive digitalization of typing data. In this study, the analysis of Mycobacterium avium tandem repeats (MATRs) loci was adapted to evaluate the genetic diversity of epidemiological unrelated MAH clinical strains of human (n=28) and porcine (n=69) origins, collected from diverse geographical regions across mainland Portugal. These MAH isolates were found to be genetically diverse and genotypes are randomly distributed across the country. Some of the human strains shared identical VNTR profiles with porcine isolates. Our study shows that the VNTR genotyping using selected MATR loci is a useful analysis technique for assessing the genetic diversity of MAH isolates from Portugal. This typing method could be successfully applied in other countries toward the implementation of a worldwide open-access database of MATR-VNTR profiles of MAH isolates, allowing a better assessment of the global epidemiology traits of this important pathogenic species.

  11. Reintroduction of a Homocysteine Level-Associated Allele into East Asians by Neanderthal Introgression.

    Science.gov (United States)

    Hu, Ya; Ding, Qiliang; He, Yungang; Xu, Shuhua; Jin, Li

    2015-12-01

    In this study, we present an analysis of Neanderthal introgression at the dipeptidase 1 gene, DPEP1. A Neanderthal origin for the putative introgressive haplotypes was demonstrated using an established three-step approach. This introgression was under positive natural selection, reached a frequency of >50%, and introduced a homocysteine level- and pigmentation-associated allele (rs460879-T) into East Asians. However, the same allele was also found in non-East Asians, but not from Neanderthal introgression. It is likely that rs460879-T was lost in East Asians and was reintroduced subsequently through Neanderthal introgression. Our findings suggest that Neanderthal introgression could reintroduce an important previously existing allele into populations where the allele had been lost. This study sheds new light on understanding the contribution of Neanderthal introgression to the adaptation of non-Africans.

  12. Adaptation of Drosophila to a novel laboratory environment reveals temporally heterogeneous trajectories of selected alleles.

    Science.gov (United States)

    Orozco-terWengel, Pablo; Kapun, Martin; Nolte, Viola; Kofler, Robert; Flatt, Thomas; Schlötterer, Christian

    2012-10-01

    The genomic basis of adaptation to novel environments is a fundamental problem in evolutionary biology that has gained additional importance in the light of the recent global change discussion. Here, we combined laboratory natural selection (experimental evolution) in Drosophila melanogaster with genome-wide next generation sequencing of DNA pools (Pool-Seq) to identify alleles that are favourable in a novel laboratory environment and traced their trajectories during the adaptive process. Already after 15 generations, we identified a pronounced genomic response to selection, with almost 5000 single nucleotide polymorphisms (SNP; genome-wide false discovery rates heterogeneous, with the alleles falling into two distinct classes: (i) alleles that continuously rise in frequency; and (ii) alleles that at first increase rapidly but whose frequencies then reach a plateau. Our data thus suggest that the genomic response to selection can involve a large number of selected SNPs that show unexpectedly complex evolutionary trajectories, possibly due to nonadditive effects.

  13. Genetic heterogeneity within electrophoretic "alleles" of xanthine dehydrogenase in Drosophila pseudoobscura.

    Science.gov (United States)

    Singh, R S; Lewontin, R C; Felton, A A

    1976-11-01

    An experimental plan for an exhaustive determination of genic variation at structural gene loci is presented. In the initial steps of this program, 146 isochromosomal lines from 12 geographic populations of D. pseudoobscura were examined for allelic variation of xanthine dehydrogenase by the serial use of 4 different electrophoretic conditions and a head stability test. The 5 criteria revealed a total of 37 allelic classes out of the 146 genomes examined where only 6 had been previously revealed by the usual method of gel electrophoresis. This immense increase in genic variation also showed previously unsuspected population differences between the main part of the species distribution and the isolated population of Bogotá population. The average heterozygosity at the Xdh locus is at least 72% in natural populations. This result, together with the very large number of alleles segregating and the pattern of allelic frequencies, has implications for theories of genetic polymorphism which are discussed.

  14. Allele frequency changes due to hitch-hiking in genomic selection programs

    DEFF Research Database (Denmark)

    Liu, Huiming; Sørensen, Anders Christian; Meuwissen, Theo H E

    2014-01-01

    Background Genomic selection makes it possible to reduce pedigree-based inbreeding over best linear unbiased prediction (BLUP) by increasing emphasis on own rather than family information. However, pedigree inbreeding might not accurately reflect the loss of genetic variation and the true level...... of inbreeding due to changes in allele frequencies and hitch-hiking. This study aimed at understanding the impact of using long-term genomic selection on changes in allele frequencies, genetic variation and the level of inbreeding. Methods Selection was performed in simulated scenarios with a population of 400......-BLUP, Genomic BLUP and Bayesian Lasso. Changes in allele frequencies at QTL, markers and linked neutral loci were investigated for the different selection criteria and different scenarios, along with the loss of favourable alleles and the rate of inbreeding measured by pedigree and runs of homozygosity. Results...

  15. Filaggrin null alleles are not associated with hand eczema or contact allergy

    DEFF Research Database (Denmark)

    Jørkov, Anne Lerbæk; Bisgaard, H; Agner, T;

    2007-01-01

    association with hand eczema or contact allergy are unexplored. OBJECTIVES: To explore associations between the variant alleles, hand eczema, contact allergy and atopic dermatitis. METHODS: In total, 183 adult individuals participated in a clinical examination of the hands, patch testing and filaggrin...... genotyping. Children without any evidence of atopic dermatitis from the Copenhagen Prospective Study on Asthma in Childhood (COPSAC) study were used as controls. The chi(2) test was used for comparison of allele frequencies. RESULTS: The majority (73%) had hand eczema, 25% had contact allergy and 14% had...... a diagnosis of atopic dermatitis. The association between atopic dermatitis and the filaggrin variant alleles was confirmed (odds ratio 3.5, P = 0.015). Allele frequencies in individuals with hand eczema or contact allergy were not statistically significantly increased. CONCLUSION: There is no association...

  16. Using multi-locus allelic sequence data to estimate genetic divergence among four Lilium (Liliaceae) cultivars.

    Science.gov (United States)

    Shahin, Arwa; Smulders, Marinus J M; van Tuyl, Jaap M; Arens, Paul; Bakker, Freek T

    2014-01-01

    Next Generation Sequencing (NGS) may enable estimating relationships among genotypes using allelic variation of multiple nuclear genes simultaneously. We explored the potential and caveats of this strategy in four genetically distant Lilium cultivars to estimate their genetic divergence from transcriptome sequences using three approaches: POFAD (Phylogeny of Organisms from Allelic Data, uses allelic information of sequence data), RAxML (Randomized Accelerated Maximum Likelihood, tree building based on concatenated consensus sequences) and Consensus Network (constructing a network summarizing among gene tree conflicts). Twenty six gene contigs were chosen based on the presence of orthologous sequences in all cultivars, seven of which also had an orthologous sequence in Tulipa, used as out-group. The three approaches generated the same topology. Although the resolution offered by these approaches is high, in this case there was no extra benefit in using allelic information. We conclude that these 26 genes can be widely applied to construct a species tree for the genus Lilium.

  17. Using multi-locus allelic sequence data to estimate genetic divergence among four Lilium (Liliaceae cultivars

    Directory of Open Access Journals (Sweden)

    Arwa eShahin

    2014-10-01

    Full Text Available Next Generation Sequencing (NGS may enable estimating relationships among genotypes using allelic variation of multiple nuclear genes simultaneously. We explored the potential and caveats of this strategy in four genetically distant Lilium cultivars to estimate their genetic divergence from transcriptome sequences using three approaches: POFAD (Phylogeny of Organisms from Allelic Data, uses allelic information of sequence data, RAxML (Randomized Accelerated Maximum Likelihood, tree building based on concatenated consensus sequences and Consensus Network (constructing a network summarizing among gene tree conflicts. Twenty six gene contigs were chosen based on the presence of orthologous sequences in all cultivars, seven of which also had an orthologous sequence in Tulipa, used as out-group. The three approaches generated the same topology. Although the resolution offered by these approaches is high, in this case there was no extra benefit in using allelic information. We conclude that these 26 genes can be widely applied to construct a species tree for the genus Lilium.

  18. Using multi-locus allelic sequence data to estimate genetic divergence among four Lilium (Liliaceae) cultivars

    NARCIS (Netherlands)

    Shahin, A.; Smulders, M.J.M.; Tuyl, van J.M.; Arens, P.F.P.; Bakker, F.T.

    2014-01-01

    Next Generation Sequencing (NGS) may enable estimating relationships among genotypes using allelic variation of multiple nuclear genes simultaneously. We explored the potential and caveats of this strategy in four genetically distant Lilium cultivars to estimate their genetic divergence from transcr

  19. Laboratory techniques in plant molecular biology taught with UniformMu insertion alleles of maize

    Science.gov (United States)

    An undergraduate course - Laboratory Techniques in Plant Molecular Biology - was organized around our research application of UniformMu insertion alleles to investigate mitochondrial functions in plant reproduction. The course objectives were to develop students’ laboratory, record keeping, bioinfor...

  20. Allele-specific interactions between CAST AWAY and NEVERSHED control abscission in Arabidopsis flowers

    Directory of Open Access Journals (Sweden)

    William D. Groner

    2016-10-01

    Full Text Available An advantage of analyzing abscission in genetically tractable model plants is the ability to make use of classic genetic tools such as suppression analysis. We have investigated the regulation of organ abscission by carrying out suppression analysis in Arabidopsis flowers. Plants carrying mutations in the NEVERSHED (NEV gene, which encodes an ADP-ribosylation factor GTPase-activating protein, retain their outer floral organs after fertilization. Mutant alleles of CAST AWAY (CST, which encodes a receptor-like cytoplasmic kinase, were found to restore organ abscission in nev flowers in an allele-specific manner. To further explore the basis of the interactions between CST and NEV, we tested whether the site of a nev mutation is predictive of its ability to be suppressed. Our results suggest instead that the strength of a nev allele influences whether organ abscission can be rescued by a specific allele of CST.

  1. A new mutation for Huntington disease following maternal transmission of an intermediate allele.

    Science.gov (United States)

    Semaka, Alicia; Kay, Chris; Belfroid, René D M; Bijlsma, Emilia K; Losekoot, Monique; van Langen, Irene M; van Maarle, Merel C; Oosterloo, Mayke; Hayden, Michael R; van Belzen, Martine J

    2015-01-01

    New mutations for Huntington disease (HD) originate from CAG repeat expansion of intermediate alleles (27-35 CAG). Expansions of such alleles into the pathological range (≥ 36 CAG) have been exclusively observed in paternal transmission. We report the occurrence of a new mutation that defies the paternal expansion bias normally observed in HD. A maternal intermediate allele with 33 CAG repeats expanded in transmission to 48 CAG repeats causing a de novo case of HD in the family. Retrospectively, the mother presented with cognitive decline, but HD was never considered in the differential diagnosis. She was diagnosed with dementia and testing for HD was only performed after her daughter had been diagnosed. This observation of an intermediate allele expanding into the full penetrance HD range after maternal transmission has important implications for genetic counselling of females with intermediate repeats. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. Interrogation of allelic chromatin states in human cells by high-density ChIP-genotyping.

    Science.gov (United States)

    Light, Nicholas; Adoue, Véronique; Ge, Bing; Chen, Shu-Huang; Kwan, Tony; Pastinen, Tomi

    2014-09-01

    Allele-specific (AS) assessment of chromatin has the potential to elucidate specific cis-regulatory mechanisms, which are predicted to underlie the majority of the known genetic associations to complex disease. However, development of chromatin landscapes at allelic resolution has been challenging since sites of variable signal strength require substantial read depths not commonly applied in sequencing based approaches. In this study, we addressed this by performing parallel analyses of input DNA and chromatin immunoprecipitates (ChIP) on high-density Illumina genotyping arrays. Allele-specificity for the histone modifications H3K4me1, H3K4me3, H3K27ac, H3K27me3, and H3K36me3 was assessed using ChIP samples generated from 14 lymphoblast and 6 fibroblast cell lines. AS-ChIP SNPs were combined into domains and validated using high-confidence ChIP-seq sites. We observed characteristic patterns of allelic-imbalance for each histone-modification around allele-specifically expressed transcripts. Notably, we found H3K4me1 to be significantly anti-correlated with allelic expression (AE) at transcription start sites, indicating H3K4me1 allelic imbalance as a marker of AE. We also found that allelic chromatin domains exhibit population and cell-type specificity as well as heritability within trios. Finally, we observed that a subset of allelic chromatin domains is regulated by DNase I-sensitive quantitative trait loci and that these domains are significantly enriched for genome-wide association studies hits, with autoimmune disease associated SNPs specifically enriched in lymphoblasts. This study provides the first genome-wide maps of allelic-imbalance for five histone marks. Our results provide new insights into the role of chromatin in cis-regulation and highlight the need for high-depth sequencing in ChIP-seq studies along with the need to improve allele-specificity of ChIP-enrichment.

  3. Analysis of FBN1 allele expression by dermal fibroblasts from Marfan syndrome patients

    Energy Technology Data Exchange (ETDEWEB)

    Putman, E.A.; Cao, S.N.; Milewicz, D.M. [Univ. of Texas Medical School, Houston, TX (United States)

    1994-09-01

    Screening for mutations in the FBN1 cDNA from Marfan patient cell strains has detected mutations in only 10-15% of patients. In an attempt to explain this poor detection rate, we examined FBN1 allele expression and fibrillin synthesis by 26 cell strains from Marfan patients. DNA from the patients and 10 controls was assessed for the presence of a polymorphic Rsa I restriction site in the 3{prime} untranslated region of the FBN1 gene. T