Sample records for european ccr5-delta32 allele

  1. Could FIV zoonosis responsible of the breakdown of the pathocenosis which has reduced the European CCR5-Delta32 allele frequencies?

    PubMed Central

    Faure, Eric

    2008-01-01

    Background In Europe, the north-south downhill cline frequency of the chemokine receptor CCR5 allele with a 32-bp deletion (CCR5-?32) raises interesting questions for evolutionary biologists. We had suggested first that, in the past, the European colonizers, principally Romans, might have been instrumental of a progressively decrease of the frequencies southwards. Indeed, statistical analyses suggested strong negative correlations between the allele frequency and historical parameters including the colonization dates by Mediterranean civilisations. The gene flows from colonizers to native populations were extremely low but colonizers are responsible of the spread of several diseases suggesting that the dissemination of parasites in naive populations could have induced a breakdown rupture of the fragile pathocenosis changing the balance among diseases. The new equilibrium state has been reached through a negative selection of the null allele. Results Most of the human diseases are zoonoses and cat might have been instrumental in the decrease of the allele frequency, because its diffusion through Europe was a gradual process, due principally to Romans; and that several cat zoonoses could be transmitted to man. The possible implication of a feline lentivirus (FIV) which does not use CCR5 as co-receptor is discussed. This virus can infect primate cells in vitro and induces clinical signs in macaque. Moreover, most of the historical regions with null or low frequency of CCR5-?32 allele coincide with historical range of the wild felid species which harbor species-specific FIVs. Conclusion We proposed the hypothesis that the actual European CCR5 allelic frequencies are the result of a negative selection due to a disease spreading. A cat zoonosis, could be the most plausible hypothesis. Future studies could provide if CCR5 can play an antimicrobial role in FIV pathogenesis. Moreover, studies of ancient DNA could provide more evidences regarding the implications of zoonoses in the actual CCR5-?32 distribution. PMID:18925940

  2. Association between chemokine receptor 5 (CCR5) delta32 gene variant and atherosclerosis: a meta-analysis of 13 studies

    PubMed Central

    Zhang, Zhongwen; Liu, Ju; Wang, Huanjun; Wu, Hongxia; Wu, Xuanmei; Dong, Jianjun; Liao, Lin

    2015-01-01

    Background: Chemokine receptor 5 (CCR5) is one of the pro-inflammatory G protein coupled receptors. Many studies have accessed the association between CCR5 gene polymorphism and atherosclerotic disease. However, the results are conflicting and inconclusive. The aim of this study was to evaluate the association more precisely. Research Design and Methods: Trials were retrieved through Pubmed, Embase, Medline, China National Knowledge Infrastructure, Web of Science, and Cochrane database without restrictions on language. The pooled odds ratio (OR) and 95% confidence interval (CI) were used to describe the strength of association with atherosclerotic disease. The subgroup analysis was used to explore the heterogeneity bias among studies. Results: Data were obtained from 13 case-control studies that included 5321 patients with atherosclerotic disease and 4283 control subjects. In the overall analysis, the CCR5-delta32 (?32) genetic variants was not associated with increased the risk of atherosclerotic disease (dominant model: OR = 0.93, 95% CI = 0.69-1.24, I2 = 77%, P = 0.60; recessive model: OR = 1.01, 95% CI = 0.61-1.65, I2 = 0%, P = 0.98), even after stratification for the status of CCR5-delta32 allele. However, in subgroup analysis, the association was significant for Asians population (OR: 2.29, 95% CI: 1.44-3.64, P = 0.0004). Conclusions: Our studies add to the evidence that CCR5 ?32-positive genotype (?32/?32 or wt/?32) increases the risk of atherosclerotic disease in Asian population. Ethnicity difference might contribute to the inconsistency in isolated studies. PMID:25785041

  3. Distribution of CCR5-Delta32, CCR5 promoter 59029 A/G, CCR2-64I and SDF1-3’A genetic polymorphisms in HIV-1 infected and uninfected patients in the West Region of Cameroon

    PubMed Central

    2013-01-01

    Background Genetic variants of the genes encoding Human Immunodeficiency Virus-1 (HIV-1) co-receptors and their ligands, like CC-Chemokine Receptor 5 delta 32 mutation (CCR5-Delta32), CCR5 promoter A/G (Adenine/Guanine), CC-Chemokine Receptor 2 mutation 64 isoleucine (CCR2-64I) and the Stromal cell-derived Factor 3’A mutation (SDF1-3’A), are involved in the susceptibility to HIV-1 infection and progression. The prevalence of these mutations varies by Region. However, little is known about their distribution in the population of Dschang, located in the West Region of Cameroon. The prevalence of HIV in the West Region of Cameroon is lower than elsewhere in Cameroon. The objectives of this study were to determine the distribution of four AIDS Related Gene (ARG) variants in HIV-infected and non-infected population of Cameroon especially in the West Region and to estimate the contribution of these variants to the susceptibility or resistance to HIV infection. We also aimed to evaluate the effectiveness of genotyping using dried blood spot (DBS) samples. Methods A total of 179 participants were recruited from two hospitals in Dschang in the West Region of Cameroon. Their genotypes for CCR5-Delta32, CCR5 promoter 59029A/G, CCR2-64I and SDF1-3’A were analyzed using polymerase chain reaction (PCR) and restriction fragment length polymorphisms. Results A total of 179 participants were enrolled in the study. Among them, 32 (17.9%) were HIV positive and 147 (82.1%) were HIV negative. The allelic frequencies of these genes were: 0%, 49.72%, 17.6% and 100% respectively for CCR5-Delta32, CCR5 promoter 59029A/G, CCR2-64I and SDF1-3’A. No individual was found to carry the CCR5-Delta 32 mutation. All participants recruited were heterozygous for the SDF1-3’A allele. Conclusion Our data suggest that the CCR5-Delta32 cannot account for the protection as it was completely absent in our population. SDF1-3’A variants, may be in association with other polymorphisms, may account for the overall protection from HIV-1 infection in participants recruited as everyone carries this allele. The CCR5 promoter 59029 G/G genotype may be associated with the risk for HIV-1 infection in this population, while the CCR2-64I (A/A genotype) may account for the protection against HIV infection. The results of genotyping from fresh blood and DBS were comparable. PMID:23880174

  4. Host inflammatory response and development of complications of Chlamydia trachomatis genital infection in CCR5-deficient mice and subfertile women with the CCR5delta32 gene deletion

    Microsoft Academic Search

    Erika L. Barr; Sander Ouburg; Joseph U. Igietseme; Servaas A. Morré; Edith Okwandu; Francis O. Eko; Godwin Ifere; Tesfaye Belay; Qing He; Deborah Lyn; Gift Nwankwo; James Lillard; Carolyn M. Black; Godwin A. Ananaba

    T cell immunity protects against diseases caused by the obligate intracellular bacterium Chlamydia trachomatis. Incidentally, host inflammatory response that includes T cells appears to also contribute to the pathogenesis of chlamydial diseases such as trachoma and tubal factor infertility (TFI). Therefore, designing effective prevention strategies requires a delineation of immune processes responsible for pathology and those mediating immunity, and identification

  5. Exclusive and persistent use of the entry coreceptor CXCR4 by human immunodeficiency virus type 1 from a subject homozygous for CCR5 delta32.

    PubMed

    Michael, N L; Nelson, J A; KewalRamani, V N; Chang, G; O'Brien, S J; Mascola, J R; Volsky, B; Louder, M; White, G C; Littman, D R; Swanstrom, R; O'Brien, T R

    1998-07-01

    Individuals who are homozygous for the 32-bp deletion in the gene coding for the chemokine receptor and major human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5 (CCR5 -/-) lack functional cell surface CCR5 molecules and are relatively resistant to HIV-1 infection. HIV-1 infection in CCR5 -/- individuals, although rare, has been increasingly documented. We now report that the viral quasispecies from one such individual throughout disease is homogenous, T cell line tropic, and phenotypically syncytium inducing (SI); exclusively uses CXCR4; and replicates well in CCR5 -/- primary T cells. The recently discovered coreceptors BOB and Bonzo are not used. Although early and persistent SI variants have been described in longitudinal studies, this is the first demonstration of exclusive and persistent CXCR4 usage. With the caveat that the earliest viruses available from this subject were from approximately 4 years following primary infection, these data suggest that HIV-1 infection can be mediated and persistently maintained by viruses which exclusively utilize CXCR4. The lack of evolution toward the available minor coreceptors in this subject underscores the dominant biological roles of the major coreceptors CCR5 and CXCR4. This and two similar subjects (R. Biti, R. Ffrench, J. Young, B. Bennetts, G. Stewart, and T. Liang, Nat. Med. 3:252-253, 1997; I. Theodoreu, L. Meyer, M. Magierowska, C. Katlama, and C. Rouzioux, Lancet 349:1219-1220, 1997) showed relatively rapid CD4+ T-cell declines despite average or low initial viral RNA load. Since viruses which use CXCR4 exclusively cannot infect macrophages, these data have implications for the relative infection of the T-cell compartment versus the macrophage compartment in vivo and for the development of CCR5-based therapeutics. PMID:9621067

  6. Distinguishing species of European sturgeons Acipenser spp. using microsatellite allele sequences.

    PubMed

    Chassaing, O; Hänni, C; Berrebi, P

    2011-01-01

    Five microsatellite markers were analysed and their alleles were sequenced for the three sturgeon species that lived in western Europe: the European sturgeon Acipenser sturio, the Atlantic sturgeon Acipenser oxyrinchus and the Adriatic sturgeon Acipenser naccarii. A total of 94 different allele sequences were obtained. Fixed mutations in the flanking regions or in the core repeat of microsatellites provided a clear distinction between the different species. Comparison of allele sequences also provided some insights into microsatellites and the evolution of Acipenser species. These nuclear markers can be used to solve species determination problems, and combined with mitochondrial markers, will be useful to identify introgression and hybridization among the three species. Moreover, because they are short and with a limited allele size range, they are particularly suited for analysis of museum specimens or archaeological remains. PMID:21235556

  7. Genotypic and Allelic Variability in CYP19A1 among Populations of African and European Ancestry

    PubMed Central

    Starlard-Davenport, Athena; Orloff, Mohammed S.; Dhakal, Ishwori; Penney, Rosalind B.; Kadlubar, Susan A.

    2015-01-01

    CYP19A1 facilitates the bioconversion of estrogens from androgens. CYP19A1 intron single nucleotide polymorphisms (SNPs) may alter mRNA splicing, resulting in altered CYP19A1 activity, and potentially influencing disease susceptibility. Genetic studies of CYP19A1 SNPs have been well documented in populations of European ancestry; however, studies in populations of African ancestry are limited. In the present study, ten ‘candidate’ intronic SNPs in CYP19A1 from 125 African Americans (AA) and 277 European Americans (EA) were genotyped and their frequencies compared. Allele frequencies were also compared with HapMap and ASW 1000 Genomes populations. We observed significant differences in the minor allele frequencies between AA and EA in six of the ten SNPs including rs10459592 (p<0.0001), rs12908960 (p<0.0001), rs1902584 (p = 0.016), rs2470144 (p<0.0001), rs1961177 (p<0.0001), and rs6493497 (p = 0.003). While there were no significant differences in allele frequencies between EA and CEU in the HapMap population, a 1.2- to 19-fold difference in allele frequency for rs10459592 (p = 0.004), rs12908960 (p = 0.0006), rs1902584 (p<0.0001), rs2470144 (p = 0.0006), rs1961177 (p<0.0001), and rs6493497 (p = 0.0092) was observed between AA and the Yoruba (YRI) population. Linkage disequilibrium (LD) blocks and haplotype clusters that is unique to the EA population but not AA was also observed. In summary, we demonstrate that differences in the allele frequencies of CYP19A1 intron SNPs are not consistent between populations of African and European ancestry. Thus, investigations into whether CYP19A1 intron SNPs contribute to variations in cancer incidence, outcomes and pharmacological response seen in populations of different ancestry may prove beneficial. PMID:25647083

  8. Allele frequencies of the new European Standard Set (ESS) loci in the population of Czech Republic

    Microsoft Academic Search

    Daniel Vaneka; Marcela Silerova; Vladislava Urbanova; Jitka Dubska; Lenka Saskova; Edvard Ehler

    120 unrelated individuals from the population sample of the Czech Republic were genotyped using the AmpF?STR® NGM™ PCR amplification kit (Applied Biosystems). The population study was conducted to evaluate the usefulness of the five new STR loci (D10S1248, D22S1045, D2S441, D1S1656, and D12S391) included in the new European Standard Set and to establish the allele frequencies.

  9. Absence of the lactase-persistence-associated allele in early Neolithic Europeans

    PubMed Central

    Burger, J.; Kirchner, M.; Bramanti, B.; Haak, W.; Thomas, M. G.

    2007-01-01

    Lactase persistence (LP), the dominant Mendelian trait conferring the ability to digest the milk sugar lactose in adults, has risen to high frequency in central and northern Europeans in the last 20,000 years. This trait is likely to have conferred a selective advantage in individuals who consume appreciable amounts of unfermented milk. Some have argued for the “culture-historical hypothesis,” whereby LP alleles were rare until the advent of dairying early in the Neolithic but then rose rapidly in frequency under natural selection. Others favor the “reverse cause hypothesis,” whereby dairying was adopted in populations with preadaptive high LP allele frequencies. Analysis based on the conservation of lactase gene haplotypes indicates a recent origin and high selection coefficients for LP, although it has not been possible to say whether early Neolithic European populations were lactase persistent at appreciable frequencies. We developed a stepwise strategy for obtaining reliable nuclear ancient DNA from ancient skeletons, based on (i) the selection of skeletons from archaeological sites that showed excellent biomolecular preservation, (ii) obtaining highly reproducible human mitochondrial DNA sequences, and (iii) reliable short tandem repeat (STR) genotypes from the same specimens. By applying this experimental strategy, we have obtained high-confidence LP-associated genotypes from eight Neolithic and one Mesolithic human remains, using a range of strict criteria for ancient DNA work. We did not observe the allele most commonly associated with LP in Europeans, thus providing evidence for the culture-historical hypothesis, and indicating that LP was rare in early European farmers. PMID:17360422

  10. Comparison of allele frequencies of eight STR loci from Argentinian Amerindian and European populations.

    PubMed

    Sala, A; Penacino, G; Corach, D

    1998-10-01

    Eight STR systems (THO1, FABP, VWA, FES/FPS, HPRTB, F13A1, CSF1PO, and D6S366) were investigated in different ethnic groups of Argentina. Allele and genotype frequencies, power of exclusion, and discriminative power were investigated. Hardy-Weinberg expectations were calculated from heterozygosity levels. FST and G tests demonstrated that significant differences exist among the investigated populations for some of the eight STRs markers. The Wichi Indians are clearly separated from the Mapuche and Tehuelche, who in turn are closer to the European population, suggesting non-Amerindian admixture. PMID:9780520

  11. Derived Immune and Ancestral Pigmentation Alleles in a 7,000-Year-old Mesolithic European

    PubMed Central

    Olalde, Iñigo; Allentoft, Morten E.; Sánchez-Quinto, Federico; Santpere, Gabriel; Chiang, Charleston W. K.; DeGiorgio, Michael; Prado-Martínez, Javier; Rodríguez, Juan Antonio; Rasmussen, Simon; Quilez, Javier; Ramírez, Oscar; Marigorta, Urko M.; Fernández-Callejo, Marcos; Prada, María Encina; Encinas, Julio Manuel Vidal; Nielsen, Rasmus; Netea, Mihai G.; Novembre, John; Sturm, Richard A.; Sabeti, Pardis; Marquès-Bonet, Tomàs; Navarro, Arcadi; Willerslev, Eske; Lalueza-Fox, Carles

    2014-01-01

    Ancient genomic sequences have started revealing the origin and the demographic impact of Neolithic farmers spreading into Europe1–3. The adoption of farming, stock breeding and sedentary societies during the Neolithic may have resulted in adaptive changes in genes associated with immunity and diet4. However, the limited data available from earlier hunter-gatherers precludes an understanding of the selective processes associated with this crucial transition to agriculture in recent human evolution. By sequencing a ~7,000-year-old Mesolithic skeleton discovered at the La Braña-Arintero site in León (Spain), we retrieved the first complete pre-agricultural European human genome. Analysis of this genome in the context of other ancient samples suggests the existence of a common ancient genomic signature across Western and Central Eurasia from the Upper Paleolithic to the Mesolithic. The La Braña individual carries ancestral alleles in several skin pigmentation genes, suggesting that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. Moreover, we provide evidence that a significant number of derived, putatively adaptive variants associated with pathogen resistance in modern Europeans were already present in this hunter-gatherer. Hence, these genomic variants cannot represent novel mutations that occurred during the adaptation to the farming lifestyle. PMID:24463515

  12. Derived immune and ancestral pigmentation alleles in a 7,000-year-old Mesolithic European.

    PubMed

    Olalde, Iñigo; Allentoft, Morten E; Sánchez-Quinto, Federico; Santpere, Gabriel; Chiang, Charleston W K; DeGiorgio, Michael; Prado-Martinez, Javier; Rodríguez, Juan Antonio; Rasmussen, Simon; Quilez, Javier; Ramírez, Oscar; Marigorta, Urko M; Fernández-Callejo, Marcos; Prada, María Encina; Encinas, Julio Manuel Vidal; Nielsen, Rasmus; Netea, Mihai G; Novembre, John; Sturm, Richard A; Sabeti, Pardis; Marquès-Bonet, Tomàs; Navarro, Arcadi; Willerslev, Eske; Lalueza-Fox, Carles

    2014-03-13

    Ancient genomic sequences have started to reveal the origin and the demographic impact of farmers from the Neolithic period spreading into Europe. The adoption of farming, stock breeding and sedentary societies during the Neolithic may have resulted in adaptive changes in genes associated with immunity and diet. However, the limited data available from earlier hunter-gatherers preclude an understanding of the selective processes associated with this crucial transition to agriculture in recent human evolution. Here we sequence an approximately 7,000-year-old Mesolithic skeleton discovered at the La Braña-Arintero site in León, Spain, to retrieve a complete pre-agricultural European human genome. Analysis of this genome in the context of other ancient samples suggests the existence of a common ancient genomic signature across western and central Eurasia from the Upper Paleolithic to the Mesolithic. The La Braña individual carries ancestral alleles in several skin pigmentation genes, suggesting that the light skin of modern Europeans was not yet ubiquitous in Mesolithic times. Moreover, we provide evidence that a significant number of derived, putatively adaptive variants associated with pathogen resistance in modern Europeans were already present in this hunter-gatherer. PMID:24463515

  13. Absence of the lactase-persistence-associated allele in early Neolithic Europeans J. Burger, M. Kirchner, B. Bramanti, W. Haak, and M. G. Thomas

    E-print Network

    Absence of the lactase-persistence-associated allele in early Neolithic Europeans J. Burger, M.pnas.org/misc/reprints.shtml To order reprints, see: Notes: #12;Absence of the lactase-persistence-associated allele in early Neolithic LP alleles were rare until the advent of dairying early in the Neolithic but then rose rapidly

  14. Concordance study and allele frequencies for 5 new European standard set (ESS) loci in the North-East Italian population

    Microsoft Academic Search

    Stefania Turrina; Giulia Filippini; Domenico De Leo

    In this work we performed a concordance study using four different commercial kits that contain five new short tandem repeat (STR) loci (D1S1656, D2S441, D10S1248, D12S391 and D22S1045), included in the new European Standard Set (ESS). Moreover we determined allele frequencies and statistical parameters of forensic interest in a population sample of 266 unrelated healthy individuals living in the North-East

  15. [Geographical variation of allele frequencies at the LDH-A* locus in the arctic grayling Thymallus arcticus Pall. and in the European grayling Thymallus arcticus L].

    PubMed

    Shubin, P N; Efimtseva, é A; shubin, Iu P; Chelpanova, T I

    2004-10-01

    The allele frequencies of LDH-A* locus were studied in the population of Siberian grayling from the Kozhym River (Pechora basin) and in the population of European grayling from Pechora, Mezen', and Vym' rivers (Northern Dvina basin). In samples of both species (n = 134), three LDH-A phenotypes have been identified in total, which proved to be under the control of two alleles: LDH-A*100 and LDH-A*50. The alternative alleles of LDH-A* locus were identified in the populations of Siberian grayling from Kozhym River and in the population of European grayling from the same river and other Pechora tributaries, namely, LDH-A*100 and LDH-A*50 in the Siberian and the European grayling, respectively. However, in the European grayling populations from the Mezen' and Vym' rivers, both alleles occur at the frequencies of the rare LDH-A*100 allele of 0.143 and 0.222, respectively. According to the published data, the frequency of LDH-A*100 allele increases in the European grayling populations of northwestern (Finland) and southern (France) rivers, reaching 0.872 and 1.000 in Rhone and Loire, respectively, i.e., the values characteristic of the Siberian grayling populations. PMID:15575515

  16. The Light Skin Allele of SLC24A5 in South Asians and Europeans Shares Identity by Descent

    PubMed Central

    Möls, Märt; Hill, Sarah; Tamang, Rakesh; Chaubey, Gyaneshwer; Goto, Rie; Ho, Simon Y. W.; Gallego Romero, Irene; Crivellaro, Federica; Hudjashov, Georgi; Rai, Niraj; Metspalu, Mait; Mascie-Taylor, C. G. Nicholas; Pitchappan, Ramasamy; Singh, Lalji; Mirazon-Lahr, Marta; Thangaraj, Kumarasamy; Villems, Richard; Kivisild, Toomas

    2013-01-01

    Skin pigmentation is one of the most variable phenotypic traits in humans. A non-synonymous substitution (rs1426654) in the third exon of SLC24A5 accounts for lighter skin in Europeans but not in East Asians. A previous genome-wide association study carried out in a heterogeneous sample of UK immigrants of South Asian descent suggested that this gene also contributes significantly to skin pigmentation variation among South Asians. In the present study, we have quantitatively assessed skin pigmentation for a largely homogeneous cohort of 1228 individuals from the Southern region of the Indian subcontinent. Our data confirm significant association of rs1426654 SNP with skin pigmentation, explaining about 27% of total phenotypic variation in the cohort studied. Our extensive survey of the polymorphism in 1573 individuals from 54 ethnic populations across the Indian subcontinent reveals wide presence of the derived-A allele, although the frequencies vary substantially among populations. We also show that the geospatial pattern of this allele is complex, but most importantly, reflects strong influence of language, geography and demographic history of the populations. Sequencing 11.74 kb of SLC24A5 in 95 individuals worldwide reveals that the rs1426654-A alleles in South Asian and West Eurasian populations are monophyletic and occur on the background of a common haplotype that is characterized by low genetic diversity. We date the coalescence of the light skin associated allele at 22–28 KYA. Both our sequence and genome-wide genotype data confirm that this gene has been a target for positive selection among Europeans. However, the latter also shows additional evidence of selection in populations of the Middle East, Central Asia, Pakistan and North India but not in South India. PMID:24244186

  17. Allele frequencies of the new European Standard Set (ESS) loci in a population of Apulia (Southern Italy).

    PubMed

    Piglionica, M; Baldassarra, S Lonero; Giardina, E; Tonino Marsella, L; Resta, N; Dell'Erba, A

    2013-02-01

    Allele frequencies of five miniSTRs loci (D1S1656, D2S441, D12S391, D10S1248 and D22S1045) included in the new European Standard Set (ESS) were calculated from a sample of 150 unrelated individuals from Apulia, a Region of Southern Italy. Two different PCR Amplification Kits were used, in order to evaluate the concordance of the genotypes. The results obtained with the two kits showed no differences in all genotype profiles. No deviation from Hardy-Weinberg expectations was detected at either locus. Moreover genetic analysis using Fst estimation showed no evidence for differentiation at the five new loci between Apulia and Italian populations. The high levels of polymorphisms of the analyzed markers in the Apulian population allow to confirm that these markers are useful tools in paternity and forensic analysis from degraded DNA samples. PMID:23127759

  18. Absence of the lactase-persistence-associated allele in early Neolithic Europeans

    Microsoft Academic Search

    J. Burger; M. Kirchner; B. Bramanti; W. Haak; M. G. Thomas

    2007-01-01

    Lactase persistence (LP), the dominant Mendelian trait conferring the ability to digest the milk sugar lactose in adults, has risen to high frequency in central and northern Europeans in the last 20,000 years. This trait is likely to have conferred a selective advantage in individuals who consume appreciable amounts of unfermented milk. Some have argued for the ''culture-historical hypothesis,'' whereby

  19. Geographical Variation of Allele Frequencies at the LDH-A* Locus in the Arctic Grayling Thymallus arcticus Pall. and in the European Grayling Thymallus thymallus L

    Microsoft Academic Search

    P. N. Shubin; E. A. Efimtzeva; Yu. P. Shubin; T. I. Chelpanova

    2004-01-01

    The allele frequencies of LDH-A* locus were studied in the populations of Siberian grayling from the Kozhym River (Pechora basin) and in the population of European grayling from Pechora, Mezen', and Vym' rivers (Northern Dvina basin). In samples of both species (n = 134), three LDH-A phenotypes have been identified in total, which proved to be under the control of

  20. [Allelic variants of the gene bamyl barley in Eastern European and central Asian areas].

    PubMed

    Stratula, O R; Kalendar, R N; Sivolap, Yu M

    2015-01-01

    The collections of varieties of spring barley cultivars from the Eastern European and Central Asian areas were analyzed by exonpecific PCR (EPIC) for beta-amylase genes. The endosperm beta-amylase gene (bamyl) was differentiated by the presence of 126 bp MITE insertion into intron 3 that is associated with low activity beta-amylase. The findings suggest that a low level of genetic variation for bamylgene within climatic zones is associated with individual breeding program for each climatic zone. PMID:26030968

  1. Identification of functionally variant MDR1 alleles among European Americans and African Americans

    Microsoft Academic Search

    Richard B. Kim; Brenda F. Leake; Edna F. Choo; George K. Dresser; Samir V. Kubba; Ute I. Schwarz; Amanda Taylor; Hong-Guang Xie; Joel McKinsey; Sheng Zhou; Lu-Bin Lan; John D. Schuetz; Erin G. Schuetz; Grant R. Wilkinson

    2001-01-01

    MDR1 (P-glycoprotein) is an important factor in the disposition of many drugs, and the involved processes often exhibit considerable interindividual variability that may be genetically determined. Single-strand conformational polymorphism analysis and direct sequencing of exonic MDR1 deoxyribonucleic acid from 37 healthy European American and 23 healthy African American subjects identified 10 single nucleotide polymorphisms (SNPs), including 6 nonsynonymous variants, occurring

  2. The Contribution of Common UGT2B10 and CYP2A6 Alleles to Variation in Nicotine Glucuronidation among European Americans

    PubMed Central

    Bloom, A. Joseph; von Weymarn, Linda B.; Martinez, Maribel; Bierut, Laura J.; Goate, Alison; Murphy, Sharon E.

    2014-01-01

    UDP-glucuronosytransferase-2B10 (UGT2B10) is the primary catalyst of nicotine glucuronidation. To develop a predictive genetic model of nicotine metabolism, the conversion of deuterated (D2)-nicotine to D2-nicotine-glucuronide, D2-cotinine, D2-cotinine-glucuronide, and D2-trans-3'-hydroxycotinine were quantified in 188 European Americans, and the contribution of UGT2B10 genotype to variability in first-pass nicotine glucuronidation assessed, following a procedure previously applied to nicotine C-oxidation. The proportion of total nicotine converted to nicotine-glucuronide (D2-nicotine-glucuronide/ (D2-nicotine +D2-nicotine-glucuronide +D2-cotinine +D2-cotinine-glucuronide +D2-trans-3'-hydroxycotinine)) was the primary phenotype. The variant, rs61750900T (D67Y) (minor allele frequency (MAF) = 10%), is confirmed to abolish nicotine glucuronidation activity. Another variant, rs112561475G (N397D) (MAF = 2%), is significantly associated with enhanced glucuronidation. rs112561475G is the ancestral allele of a well-conserved amino acid, indicating that the majority of human UGT2B10 alleles are derived hypomorphic alleles. CYP2A6 and UGT2B10 genotype explain 53% of the variance in oral nicotine glucuronidation in this sample. CYP2A6 and UGT2B10 genetic variants are also significantly associated with un-deuterated (D0) nicotine glucuronidation in subjects smoking ad libitum. We find no evidence for further common variation markedly influencing hepatic UGT2B10 expression in European Americans. PMID:24192532

  3. The Interplay between Natural Selection and Susceptibility to Melanoma on Allele 374F of SLC45A2 Gene in a South European Population

    PubMed Central

    López, Saioa; García, Óscar; Yurrebaso, Iñaki; Flores, Carlos; Acosta-Herrera, Marialbert; Chen, Hua; Gardeazabal, Jesús; Careaga, Jesús María; Boyano, María Dolores; Sánchez, Ana; Ratón-Nieto, Juan Antonio; Sevilla, Arrate; Smith-Zubiaga, Isabel; de Galdeano, Alicia García; Martinez-Cadenas, Conrado; Izagirre, Neskuts; de la Rúa, Concepción; Alonso, Santos

    2014-01-01

    We aimed to study the selective pressures interacting on SLC45A2 to investigate the interplay between selection and susceptibility to disease. Thus, we enrolled 500 volunteers from a geographically limited population (Basques from the North of Spain) and by resequencing the whole coding region and intron 5 of the 34 most and the 34 least pigmented individuals according to the reflectance distribution, we observed that the polymorphism Leu374Phe (L374F, rs16891982) was statistically associated with skin color variability within this sample. In particular, allele 374F was significantly more frequent among the individuals with lighter skin. Further genotyping an independent set of 558 individuals of a geographically wider population with known ancestry in the Spanish population also revealed that the frequency of L374F was significantly correlated with the incident UV radiation intensity. Selection tests suggest that allele 374F is being positively selected in South Europeans, thus indicating that depigmentation is an adaptive process. Interestingly, by genotyping 119 melanoma samples, we show that this variant is also associated with an increased susceptibility to melanoma in our populations. The ultimate driving force for this adaptation is unknown, but it is compatible with the vitamin D hypothesis. This shows that molecular evolution analysis can be used as a useful technology to predict phenotypic and biomedical consequences in humans. PMID:25093503

  4. Ancient DNA Analysis Reveals High Frequency of European Lactase Persistence Allele (T-13910) in Medieval Central Europe

    PubMed Central

    Akgül, Gülfirde; Della Casa, Philippe; Rühli, Frank; Warinner, Christina

    2014-01-01

    Ruminant milk and dairy products are important food resources in many European, African, and Middle Eastern societies. These regions are also associated with derived genetic variants for lactase persistence. In mammals, lactase, the enzyme that hydrolyzes the milk sugar lactose, is normally down-regulated after weaning, but at least five human populations around the world have independently evolved mutations regulating the expression of the lactase-phlorizin-hydrolase gene. These mutations result in a dominant lactase persistence phenotype and continued lactase tolerance in adulthood. A single nucleotide polymorphism (SNP) at C/T-13910 is responsible for most lactase persistence in European populations, but when and where the T-13910 polymorphism originated and the evolutionary processes by which it rose to high frequency in Europe have been the subject of strong debate. A history of dairying is presumed to be a prerequisite, but archaeological evidence is lacking. In this study, DNA was extracted from the dentine of 36 individuals excavated at a medieval cemetery in Dalheim, Germany. Eighteen individuals were successfully genotyped for the C/T-13910 SNP by molecular cloning and sequencing, of which 13 (72%) exhibited a European lactase persistence genotype: 44% CT, 28% TT. Previous ancient DNA-based studies found that lactase persistence genotypes fall below detection levels in most regions of Neolithic Europe. Our research shows that by AD 1200, lactase persistence frequency had risen to over 70% in this community in western Central Europe. Given that lactase persistence genotype frequency in present-day Germany and Austria is estimated at 71–80%, our results suggest that genetic lactase persistence likely reached modern levels before the historic population declines associated with the Black Death, thus excluding plague-associated evolutionary forces in the rise of lactase persistence in this region. This new evidence sheds light on the dynamic evolutionary history of the European lactase persistence trait and its global cultural implications. PMID:24465990

  5. Role of chemokine and cytokine polymorphisms in the progression of HIV-1 disease.

    PubMed

    Mahajan, Supriya D; Agosto-Mojica, Anardi; Aalinkeel, Ravikumar; Reynolds, Jessica L; Nair, Bindukumar B; Sykes, Donald E; Martinez, Jeffery; Adams, Joshua; Singh, Neha; Bernstein, Zale; Hsiao, Chiu-bin; Schwartz, Stanley A

    2010-05-28

    Allelic variants of the genes for chemokine receptors and their natural ligands, the chemokines, and cytokines can affect HIV-1 disease progression. This study investigates the level of expression of the CCR5-Delta32, CCR2b-641, RANTES In1.1C, SDF-1 3'A, IL-10-5'-592A and IL-4-589T alleles in two unique HIV-1 infected patient cohorts that represent the two distinct stages of disease progression, namely rapid progressors (RPs) and long term non-progressors (LTNPs) (n=12/group) were recruited. Quantitation of the gene expression of CCR5-Delta32, CCR2b-641, RANTES In1.1C, SDF-1 3'A, IL-10-5'-592A and IL-4-589T in peripheral blood mononuclear leukocytes (PBML) isolated from patients was performed by real time, quantitative (Q)-PCR using DNA was isolated from PBML. We observed that expression of these HIV-protective alleles was generally greater in the LTNP cohort than the RP cohort. LTNPs expressed more of the protective chemokine, SDF-1alpha than RPs, and no statistically significant difference was observed in RANTES production between the LTNPs and RPs. The LTNPs expressed significantly less amounts of cytokines IL-10 and IL-4 as compared to the RPs. Our results demonstrate that gene polymorphisms for CCR5-Delta32, CCR2b-641, RANTES In1.1C, SDF-1 3'A, IL-10-5'-592A and IL-4-589T may be used as clinical markers to predict progression of HIV-1 infections. PMID:20416280

  6. Genetic parameters and allele frequencies of five new European Standard Set STR loci (D10S1248, D22S1045, D2S441, D1S1656, D12S391) in the population of Romania

    PubMed Central

    Stanciu, Florin; Vladu, Simona; Cu??r, Veronica; Cocioab?, Daniela; Iancu, Florentina; Cotolea, Adnana; Stoian, Ionel Marius

    2013-01-01

    Aim To establish allele frequencies and genetic parameters for 5 new European Standard Set short tandem repeat (STR) loci in the population of Romania and to compare them with those in other populations. Methods DNA was isolated using QIAamp 96 DNA Swab BioRobot Kit and Chelex 100 methods. Polymerase chain reaction amplification was done using Investigator ESSplexPlus Kit (D1S1656, D2S441, D2S1338, D3S1358, D8S1179, D10S1248, D12S391, D16S539, D18S51, D19S433, D21S11, D22S1045, FGA, TH01, and vWA). For DNA typing, Applied Biosystems 3500/3500xL Genetic Analyzer was used. Statistical analysis was done using Powerstats, GDA, and Arlequin software. Results Power of discrimination and polymorphism information content was highest for two new ESS loci, D1S1656 and D12S391. Comparison of allele frequencies for 5 new ESS loci in Romanian population with previously published population data showed significant differences for all compared populations, with the exception of Hungary. Geographically more distant populations, such as Spain, Sweden, United Kingdom, Germany, and Portugal differed more than closer populations. Conclusion New ESS STR loci are very useful for the analysis of forensic samples (persons or traces) due to their characteristics (shortness and high polymorphism). In comparisons with other common STR markers, they have a higher power of discrimination and also higher polymorphism information content, and could be used in any national DNA database. PMID:23771753

  7. Allele age and a test for selection on rare alleles.

    PubMed Central

    Slatkin, M

    2000-01-01

    An approximate expression for the probability distribution of the age of a neutral allele as a function of its frequency is derived for a population undergoing arbitrary changes in population size. A simple maximum-likelihood estimator of allele age based on frequency is also obtained. The distribution of allele age, combined with a model predicting the extent of intra-allelic variability generated by mutation and recombination, leads to a statistical test of whether a rare allele has experienced natural selection. The test is based on finding whether there is too little or too much intra-allelic variability to be consistent with the observed frequency. The test is applied to the locus, BRCA1, associated with early-onset breast cancer in humans and shows that two common disease-associated alleles (5382insC and 185delAG) appear to have been subject to natural selection. PMID:11127913

  8. Minisatellite MS32 Alleles Show Population Specificity Among Thai, Chinese, and Japanese

    Microsoft Academic Search

    Qing-Hua Yuan; Azusa Tanaka; Richard H. Kaszynski; Morio Iino; Tomoko Okuno; Tatsuaki Tsuruyama; Toshimichi Yamamoto; Alec J. Jeffreys; Keiji Tamaki

    2009-01-01

    Lineages of structurally related alleles at minisatellite MS32 in human populations show considerable differentiation at the\\u000a continental level. However, the regional specificity of these lineages remains unknown. We now describe the comparison of\\u000a allele structures in Thai, Han Chinese, and Japanese populations with lineages previously established for North Europeans\\u000a and Africans. The great majority of alignable Asian alleles showed their

  9. Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East Asians than

    E-print Network

    Reich, David

    Measurement of the human allele frequency spectrum demonstrates greater genetic drift in East report large subsets of SNPs from the International HapMap Project1,2 that allow us to overcome variation: the allele frequency spectrum. Our analysis shows that East Asian and northern European ancestors

  10. Stability of Iso-alleles

    Microsoft Academic Search

    Aloha M. Hannah; Curt Stern

    1956-01-01

    THE high stability of most genes when kept under natural conditions is deduced from the relative rarity of spontaneous mutations which produce striking deviations from normality. The existence of wild-type iso-alleles, that is, of different alleles usually causing the same normal phenotype although distinguishable by their effects under special conditions, raises the question whether mutations from one iso-allele to another

  11. Allele coding in genomic evaluation

    PubMed Central

    2011-01-01

    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 the best. Conclusions Different allele coding methods lead to the same inference in the marker-based and equivalent models when a fixed general mean is included in the model. However, reliabilities of genomic breeding values are affected by the allele coding method used. The centered coding has some numerical advantages when Markov chain Monte Carlo methods are used. PMID:21703021

  12. Microsatellite Variation in Honey Bee (Apis MeZZfera L.) Populations: Hierarchical Genetic Structure and Test of the Infinite Allele and Stepwise Mutation Models

    Microsoft Academic Search

    Lionel Garnery; Michel Solignac; Jean-Marie Cornuett

    Samples from nine populations belonging to three African (intmissa, scutellata and capensis) and four European (mellijima, liptica, carnica and cecropia) Apis mellifea subspecies were scored for seven microsatellite loci. A large amount of genetic variation (between seven and 30 alleles per locus) was detected. Average heterozygosity and average number of alleles were significantly higher in African than in European subspecies,

  13. Allele age and a test for selection on rare alleles

    E-print Network

    Slatkin, Montgomery

    frequency. The test is applied to the locus, BRCA1, associated with early-onset breast cancer in humans reduce average allele age from the value in equation (1) but that overdominance in ¢tness greatly

  14. DLA-DRB1, DQA1, and DQB1 Alleles and Haplotypes in North American Gray Wolves

    Microsoft Academic Search

    LORNA J. KENNEDY; J. M. Angles; A. Barnes; L. E. Carmichael; A. D. Radford; W. E. R. Ollier; G. M. Happ

    2007-01-01

    The canine major histocompatibility complex contains highly polymorphic genes, many of which are critical in regulating immune response. Since domestic dogs evolved from Gray Wolves (Canis lupus), common DLA class II alleles should exist. Sequencing was used to characterize 175 Gray Wolves for DLA class II alleles, and data from 1856 dogs, covering 85 different breeds of mostly European origin,

  15. Delimiting Allelic Imbalance of TYMS by Allele-Specific Analysis.

    PubMed

    Balboa-Beltrán, Emilia; Cruz, Raquel; Carracedo, Angel; Barros, Francisco

    2015-07-01

    Allelic imbalance of thymidylate synthase (TYMS) is attributed to polymorphisms in the 5'- and 3'-untranslated region (UTR). These polymorphisms have been related to the risk of suffering different cancers, for example leukemia, breast or gastric cancer, and response to different drugs, among which are methotrexate glutamates, stavudine, and specifically 5-fluorouracil (5-FU), as TYMS is its direct target. A vast literature has been published in relation to 5-FU, even suggesting the sole use of these polymorphisms to effectively manage 5-FU dosage. Estimates of the extent to which these polymorphisms influence in TYMS expression have in the past been based on functional analysis by luciferase assays and quantification of TYMS mRNA, but both these studies, as the association studies with cancer risk or with toxicity or response to 5-FU, are very contradictory. Regarding functional assays, the artificial genetic environment created in luciferase assay and the problems derived from quantitative polymerase chain reactions (qPCRs), for example the use of a reference gene, may have distorted the results. To avoid these sources of interference, we have analyzed the allelic imbalance of TYMS by allelic-specific analysis in peripheral blood mononuclear cells (PBMCs) from patients.Allelic imbalance in PBMCs, taken from 40 patients with suspected myeloproliferative haematological diseases, was determined by fluorescent fragment analysis (for the 3'-UTR polymorphism), Sanger sequencing and allelic-specific qPCR in multiplex (for the 5'-UTR polymorphisms).For neither the 3'- nor the 5'-UTR polymorphisms did the observed allelic imbalance exceed 1.5 fold. None of the TYMS polymorphisms is statistically associated with allelic imbalance.The results acquired allow us to deny the previously established assertion of an influence of 2 to 4 fold of the rs45445694 and rs2853542 polymorphisms in the expression of TYMS and narrow its allelic imbalance to 1.5 fold, in our population. These data circumscribe the influence of these polymorphisms in the clinical outcome of 5-FU and question their use for establishing 5-FU dosage, above all when additional genetic factors are not considered. PMID:26166093

  16. Epigenetic regulation of differential HLA-A allelic expression levels.

    PubMed

    Ramsuran, Veron; Kulkarni, Smita; O'huigin, Colm; Yuki, Yuko; Augusto, Danillo G; Gao, Xiaojiang; Carrington, Mary

    2015-08-01

    MHC class I expression levels influence the strength of immune responses and represent another variable in determining outcome to disease beyond peptide binding alone. Identification of the HLA loci that vary in allelic expression levels and delineating the mechanism responsible for expression variation may provide the opportunity to modify their expression therapeutically. We have examined the expression levels of allelic lineages at the HLA-A locus in a sample of 216 European Americans using a real-time polymerase chain reaction assay, which amplifies all HLA-A lineages specifically with equal efficiency, and observed a gradient of expression that associates with HLA-A allelic lineage (R = 0.6, P = 5 × 10(-25)). DNA methylation of the HLA-A gene appears to contribute to the variation in HLA-A mRNA expression levels, as a significant inverse correlation was observed between HLA-A mRNA expression levels in untreated cells and the degree to which expression is increased after treatment of the cells with a DNA methyltransferase inhibitor (R = 0.6, P = 2.8 × 10(-6)). Further, deep-sequencing and immunoprecipitation assays revealed allelic lineage-specific methylation patterns within the HLA-A promoter region where increased DNA methylation levels correlated significantly with reduced HLA-A expression levels (R = 0.89, P = 3.7 × 10(-9)). These data demonstrate HLA-A allelic lineage-specific variation in expression levels, and DNA methylation as a likely factor in contributing to this variation. PMID:25935001

  17. Prediction of deleterious human alleles.

    PubMed

    Sunyaev, S; Ramensky, V; Koch, I; Lathe, W; Kondrashov, A S; Bork, P

    2001-03-15

    Single nucleotide polymorphisms (SNPs) constitute the bulk of human genetic variation, occurring with an average density of approximately 1/1000 nucleotides of a genotype. SNPs are either neutral allelic variants or are under selection of various strengths, and the impact of SNPs on fitness remains unknown. Identification of SNPs affecting human phenotype, especially leading to risks of complex disorders, is one of the key problems of medical genetics. SNPs in protein-coding regions that cause amino acid variants (non-synonymous cSNPs) are most likely to affect phenotypes. We have developed a straightforward and reliable method based on physical and comparative considerations that estimates the impact of an amino acid replacement on the three-dimensional structure and function of the protein. We estimate that approximately 20% of common human non-synonymous SNPs damage the protein. The average minor allele frequency of such SNPs in our data set was two times lower than that of benign non-synonymous SNPs. The average human genotype carries approximately 10(3) damaging non-synonymous SNPs that together cause a substantial reduction in fitness. PMID:11230178

  18. Genetically Determined Amerindian Ancestry Correlates with Increased Frequency of Risk Alleles for Systemic Lupus Erythematosus

    PubMed Central

    Sanchez, E; Webb, R; Rasmussen, A.; Kelly, J.A; Riba, L.; Kaufman, K.M.; Garcia-de la Torre, I.; Moctezuma, J.F.; Maradiaga-Ceceña, M.A.; Cardiel, M.; Acevedo, E.; Cucho-Venegas, M.; Garcia, M.A.; Gamron, S.; Pons-Estel, B.A.; Vasconcelos, C.; Martin, J.; Tusié-Luna, T.; Harley, J.B.; Richardson, B.; Sawalha, A.H.; Alarcón-Riquelme, M.E.

    2011-01-01

    Objectives To analyze if genetically determined Amerindian ancestry predicts the increased presence of risk alleles of known susceptibility genes for systemic lupus erythematosus. Methods Single nucleotide polymorphisms within 16 confirmed genetic susceptibility loci for SLE were genotyped in a set of 804 Mestizo lupus patients and 667 Mestizo normal healthy controls. In addition, 347 admixture informative markers were genotyped. Individual ancestry proportions were determined using STRUCTURE. Association analysis was performed using PLINK, and correlation of the presence of risk alleles with ancestry was done using linear regression. Results A meta-analysis of the genetic association of the 16 SNPs across populations showed that TNFSF4, STAT4, PDCD1, ITGAM, and IRF5 were associated with lupus in a Hispanic-Mestizo cohort enriched for European and Amerindian ancestry. In addition, two SNPs within the MHC region, previously associated in a genome-wide association study in Europeans, were also associated in Mestizos. Using linear regression we predict an average increase of 2.34 risk alleles when comparing a lupus patient with 100% Amerindian ancestry to an SLE patient with 0% American Indian Ancestry (p<0.0001). SLE patients with 43% more Amerindian ancestry are predicted to carry one additional risk allele. Conclusion Amerindian ancestry increased the number of risk alleles for lupus. PMID:20848568

  19. Allele and haplotype frequencies at human leukocyte antigen class I and II genes in Venezuela's population.

    PubMed

    Del Pilar Fortes, María; Gill, Gisselle; Paredes, María Elena; Gamez, Ligia Elena; Palacios, Marina; Blanca, Isaac; Tassinari, Paolo

    2012-01-01

    Population studies represent an integral part and link in understanding the complex chain of host-pathogen interactions, disease pathogenesis, and MHC gene polymorphisms. Genes of Mongoloid, Caucasoid, and Negroid populations have created a distinctive HLA genetic profile in the Venezuelan population. Our objective was to determine the predominant HLA class I and II alleles and haplotype frequencies in the hybrid population of Venezuela. The study population consisted of 486 healthy unrelated native Venezuelans and 180 families. We examined the frequency of HLA A-B-C, HLA-DQ and HLA-DR genes by polymerase chain reaction and subsequent hybridization with sequence-specific oligonucleotide probes. Phenotypic, allelic and haplotype frequencies were estimated by direct counting and using the maximum-likelihood method. The predominant HLA class I alleles were A*02, A*24, A*68, B*35, B*44, B*51, B*07, B*15 and Cw*07. Regarding HLA class II, the most frequent alleles were DQB1*03 and DRB1*04, DRB1*15, DRB1*13, DRB1*07. The prevailing haplotype was HLA-A*02B*35 DQB1*03 DRB1*04. Some of these alleles and haplotype frequencies were predominantly present in Amerindians (A*02, A*24, B*35, Cw*07, DRB1*04, A*24 B*35). Previous reports have shown high incidence of A*02, B*44, B*51, DRB1*15, DRB1*13, DRB1*07 alleles in several European populations and A*68, B*07, B*15 alleles in African Americans, which could have contributed to the ethnic admixture of the Venezuelan population. We conclude that our results provide strong evidence that Venezuela's population represents an admixture of the primitive Mongoloid Aborigines, Caucasoid Europeans and Western African Negroid migrants. PMID:22484528

  20. European Mink-Polecat Hybridization Events: Hazards From Natural Process?

    Microsoft Academic Search

    T. LODE; G. GUIRAL; D. PELTIER

    2005-01-01

    Determining the significance of hybridization events raises essential issues both in conservation and in evolutionary biology. Here, we report a genetic investigation of sympatric polecat and endangered European mink populations. Although the two species were morphologically very similar, the European mink and the polecat were easily discriminated from allozymes and microsatellites and showed a high level of private alleles (effective

  1. Characterization of the treefrog null allele

    SciTech Connect

    Guttman, S.I. (Miami Univ., Oxford, OH (USA). Dept. of Zoology)

    1990-12-01

    As part of the authors intensive year-long baseline ecological study, they characterized the degree of genetic polymorphism and heterozygosity in selected Feed Materials Production Center (FMPC) populations using electrophoretic techniques. These data are being used as an indicator of stress by comparing populations on and off the FMPC site. The current study was initiated to determine whether this GPI null allele is lethal, when homozygous, in spring peepers. Also, a sampling protocol was implemented to determine whether a linear effect occurs relative to the frequency of the null allele offsite and to determine the origination site of the null allele. 18 refs., 2 figs., 4 tabs.

  2. Characterization of the treefrog null allele, 1991

    SciTech Connect

    Guttman, S.I. [Miami Univ., Oxford, OH (United States). Dept. of Zoology

    1992-04-01

    Spring peeper (Hyla crucifer) tadpoles collected from the waste storage area during the Biological and Ecological Site Characterization of the Feed Materials Production Center (FEMP) in 1986 and 1987 appeared to be unique. A null (inactive) allele was found at the glucose phosphate isomerase enzyme locus in significant frequencies (approximately 20%) each year; this allele did not appear to occur in the offsite sample collected approximately 15km from the FEMP. Null alleles at this locus have not been reported in other amphibian populations; when they have been found in other organisms they have invariably been lethal in the homozygous condition.

  3. Allele Workbench: Transcriptome Pipeline and Interactive Graphics for Allele-Specific Expression

    PubMed Central

    Soderlund, Carol A.; Nelson, William M.; Goff, Stephen A.

    2014-01-01

    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 from https://code.google.com/p/allele-workbench. Additionally, all software is ready for immediate use from an Atmosphere Virtual Machine Image available from the iPlant Collaborative (www.iplantcollaborative.org). PMID:25541944

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

    PubMed

    Soderlund, Carol A; Nelson, William M; Goff, Stephen A

    2014-01-01

    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 from https://code.google.com/p/allele-workbench. Additionally, all software is ready for immediate use from an Atmosphere Virtual Machine Image available from the iPlant Collaborative (www.iplantcollaborative.org). PMID:25541944

  5. Transformation of QTL genotypic effects to allelic effects

    PubMed Central

    Nagamine, Yoshitaka

    2005-01-01

    The genotypic and allelic effect models are equivalent in terms of QTL detection in a simple additive model, but the QTL allelic model has the advantage of providing direct information for marker-assisted selection. However, the allelic matrix is four times as large as the genotypic IBD matrix, causing computational problems, especially in genome scans examining multiple positions. Transformation from genotypic to allelic effects, after estimating the genotypic effects with a smaller IBD matrix, can solve this problem. Although the validity of transformation from genotypic to allelic effects has been disputed, this work proves that transformation can successfully yield unique allelic effects when genotypic and allelic IBD matrixes exist. PMID:16093016

  6. Functional analysis of 11 novel GBA alleles

    PubMed Central

    Malini, Erika; Grossi, Serena; Deganuto, Marta; Rosano, Camillo; Parini, Rossella; Dominisini, Silvia; Cariati, Roberta; Zampieri, Stefania; Bembi, Bruno; Filocamo, Mirella; Dardis, Andrea

    2014-01-01

    Gaucher disease is the most frequent lysosomal storage disorder due to the deficiency of the acid ?-glucosidase, encoded by the GBA gene. In this study, we report the structural and functional characterization of 11 novel GBA alleles. Seven single missense alleles, P159S, N188I, E235K, P245T, W312S, S366R and W381C, and two alleles carrying in cis mutations, (N188S; G265R) and (E326K; D380N), were studied for enzyme activity in transiently transfected cells. All mutants were inactive except the P159S, which retained 15% of wild-type activity. To further characterize the alleles carrying two in cis mutations, we expressed constructs bearing singly each mutation. The presence of G265R or D380N mutations completely abolished enzyme activity, while N188S and E326K mutants retained 25 and 54% of wild-type activity, respectively. Two mutations, affecting the acceptor splice site of introns 5 (c.589-1G>A) and 9 (c.1389-1G>A), led to the synthesis of aberrant mRNA. Unpredictably, family studies showed that two alleles resulted from germline or ‘de novo' mutations. These results strengthen the importance of performing a complete and accurate molecular analysis of the GBA gene in order to avoid misleading conclusions and provide a comprehensive functional analysis of new GBA mutations. PMID:24022302

  7. Three allele combinations associated with Multiple Sclerosis

    PubMed Central

    Favorova, Olga O; Favorov, Alexander V; Boiko, Alexey N; Andreewski, Timofey V; Sudomoina, Marina A; Alekseenkov, Alexey D; Kulakova, Olga G; Gusev, Eugenyi I; Parmigiani, Giovanni; Ochs, Michael F

    2006-01-01

    Background Multiple sclerosis (MS) is an immune-mediated disease of polygenic etiology. Dissection of its genetic background is a complex problem, because of the combinatorial possibilities of gene-gene interactions. As genotyping methods improve throughput, approaches that can explore multigene interactions appropriately should lead to improved understanding of MS. Methods 286 unrelated patients with definite MS and 362 unrelated healthy controls of Russian descent were genotyped at polymorphic loci (including SNPs, repeat polymorphisms, and an insertion/deletion) of the DRB1, TNF, LT, TGF?1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. Each allele carriership in patients and controls was compared by Fisher's exact test, and disease-associated combinations of alleles in the data set were sought using a Bayesian Markov chain Monte Carlo-based method recently developed by our group. Results We identified two previously unknown MS-associated tri-allelic combinations: -509TGF?1*C, DRB1*18(3), CTLA4*G and -238TNF*B1,-308TNF*A2, CTLA4*G, which perfectly separate MS cases from controls, at least in the present sample. The previously described DRB1*15(2) allele, the microsatellite TNFa9 allele and the biallelic combination CCR5?32, DRB1*04 were also reidentified as MS-associated. Conclusion These results represent an independent validation of MS association with DRB1*15(2) and TNFa9 in Russians and are the first to find the interplay of three loci in conferring susceptibility to MS. They demonstrate the efficacy of our approach for the identification of complex-disease-associated combinations of alleles. PMID:16872485

  8. Demographic history and rare allele sharing among human populations.

    PubMed

    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

    2011-07-19

    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

  9. Crohn's disease risk alleles on the NOD2 locus have been maintained by natural selection on standing variation.

    PubMed

    Nakagome, Shigeki; Mano, Shuhei; Kozlowski, Lukasz; Bujnicki, Janusz M; Shibata, Hiroki; Fukumaki, Yasuaki; Kidd, Judith R; Kidd, Kenneth K; Kawamura, Shoji; Oota, Hiroki

    2012-06-01

    Risk alleles for complex diseases are widely spread throughout human populations. However, little is known about the geographic distribution and frequencies of risk alleles, which may contribute to differences in disease susceptibility and prevalence among populations. Here, we focus on Crohn's disease (CD) as a model for the evolutionary study of complex disease alleles. Recent genome-wide association studies and classical linkage analyses have identified more than 70 susceptible genomic regions for CD in Europeans, but only a few have been confirmed in non-European populations. Our analysis of eight European-specific susceptibility genes using HapMap data shows that at the NOD2 locus the CD-risk alleles are linked with a haplotype specific to CEU at a frequency that is significantly higher compared with the entire genome. We subsequently examined nine global populations and found that the CD-risk alleles spread through hitchhiking with a high-frequency haplotype (H1) exclusive to Europeans. To examine the neutrality of NOD2, we performed phylogenetic network analyses, coalescent simulation, protein structural prediction, characterization of mutation patterns, and estimations of population growth and time to most recent common ancestor (TMRCA). We found that while H1 was significantly prevalent in European populations, the H1 TMRCA predated human migration out of Africa. H1 is likely to have undergone negative selection because 1) the root of H1 genealogy is defined by a preexisting amino acid substitution that causes serious conformational changes to the NOD2 protein, 2) the haplotype has almost become extinct in Africa, and 3) the haplotype has not been affected by the recent European expansion reflected in the other haplotypes. Nevertheless, H1 has survived in European populations, suggesting that the haplotype is advantageous to this group. We propose that several CD-risk alleles, which destabilize and disrupt the NOD2 protein, have been maintained by natural selection on standing variation because the deleterious haplotype of NOD2 is advantageous in diploid individuals due to heterozygote advantage and/or intergenic interactions. PMID:22319155

  10. HLA genes in the Chuvashian population from European Russia: admixture of Central European and Mediterranean populations.

    PubMed

    Arnaiz-Villena, Antonio; Martinez-Laso, Jorge; Moscoso, Juan; Livshits, Gregory; Zamora, Jorge; Gomez-Casado, Eduardo; Silvera-Redondo, Carlos; Melvin, Kristin; Crawford, Michael H

    2003-06-01

    HLA alleles have been determined for the first time in individuals from the Chuvashian population by DNA typing and sequencing. HLA-A, -B, -DR, and -DQ allele frequencies and extended haplotypes have also been determined, and the results compared to those for Central Europeans, Siberians and other Asians, Caucasians, Middle Easterners, and Mediterranean peoples. Genetic distances, neighbor-joining dendrograms, and correspondence analysis have been performed. Present-day Chuvash speak an Altaic-Turkic language and are genetically related to Caucasians (Georgians), Mediterraneans, and Middle Easterners, and not only to Central or Northern Europeans; Chuvash contain little indications of Central Asian-Altaic gene flow. Thus, present-day Chuvash who speak an Altaic-Turkic language are probably more closely related to ancient Mesopotamian-Hittites and northern European populations than to central Asia-Altaic people. PMID:14527201

  11. Population stratification and spurious allelic association

    Microsoft Academic Search

    Lon R Cardon

    3-8 Considerable effort is being expended in attempts to detect genetic loci contributing to complex diseases. 9 Association and linkage studies comprise the two dominant strategies: association studies aim to find disease-predisposing alleles at the population level; and linkage studies focus on familial segregation. Although both strategies have compelling strengths, association analyses are more widely done and likely to spread

  12. Tetrasomic segregation for multiple alleles in alfalfa.

    PubMed

    Quiros, C F

    1982-05-01

    Evidence of tetrasomic inheritance in alfalfa, Medicago sativa L. and M. falcata L., for multiple codominant alleles at three isozymic loci is reported in this study. The locus Prx-1 governing anodal peroxidase and the loci Lap-1 and Lap-2 governing anodal leucine-aminopeptidase were studied by starch gel electrophoresis in seedling root tissue or seeds. The progenies from several di-, tri- or tetra-allelic plants belong to the species M. sativa and M. falcata and their hybrids were studied for the segregation of the three genes. In all cases, tetrasomic inheritance of chromosomal-type segregation was observed. In another progeny resulting from the crossing of two plants involving four different alleles at locus Lap-2, tetrasomic segregation with the possible occurrence of double reduction was observed. This study presents direct evidence of autotetraploidy and the existence of tetra-allelic loci in alfalfa. It also supports the concept that the species M. sativa and M. falcata are genetically close enough to be considered biotypes of a common species. PMID:17246077

  13. Ethnic variation in allele distribution of the androgen receptor (AR) (CAG)n repeat.

    PubMed

    Ackerman, Christine M; Lowe, Lynn P; Lee, Hoon; Hayes, M Geoffrey; Dyer, Alan R; Metzger, Boyd E; Lowe, William L; Urbanek, Margrit

    2012-01-01

    The androgen receptor (AR) is important in reproductive organ development, as well as tissue homeostasis of the pancreas, liver, and skeletal muscle in adulthood. The trinucleotide (CAG)(n) repeat polymorphism in exon 1 of the AR gene is thought to regulate AR activity, with longer alleles conferring reduced receptor activity. Therefore, the evaluation of the allelic distribution of the AR (CAG)(n) repeat in various ethnic groups is crucial in understanding the interindividual variability in AR activity. We evaluated ethnic variation of this AR polymorphism by genotyping individuals from the multiethnic Hyperglycemia and Adverse Pregnancy Outcome study cohort. We genotyped 4421 Caucasian mothers and 3365 offspring of European ancestry; 1494 Thai mothers and 1742 offspring; 1119 Afro-Caribbean mothers and 1142 offspring; and 780 Hispanic mothers and 770 offspring of Mexican ancestry from Bellflower, California. The distributions of (CAG)(n) alleles among all 4 ethnic groups are significantly different (P < .0001). Pairwise tests confirmed significant differences between each pair of ethnicities tested (P < 10(-28)). The relative AR (CAG)(n) repeat length in the different groups was as follows: Afro-Caribbean (shortest repeat lengths and greatest predicted AR activity) < Caucasian < Hispanic < Thai (longest repeat length and lowest predicted AR activity). Significant interethnic differences in the allele frequencies of the AR exon 1 (CAG)(n) polymorphism exist. Our results suggest that there may be potential ethnic differences in androgenic pathway activity and androgen sensitivity. PMID:21597087

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

    PubMed Central

    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 Tnf? alleles, which was necessary for the mono- to biallelic switch in gene expression. We identified two new complementary long noncoding RNAs transcribed from the TNF? locus and showed that their knockdown had opposite effects in Tnf? spatial proximity and allelic expression. Moreover, the observed spatial proximity of Tnf? 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

  15. Evaluation of Allele-Specific Somatic Changes of Genome-Wide Association Study Susceptibility Alleles in Human Colorectal Cancers

    PubMed Central

    Gerber, Madelyn M.; Hampel, Heather; Schulz, Nathan P.; Fernandez, Soledad; Wei, Lai; Zhou, Xiao-Ping; de la Chapelle, Albert; Toland, Amanda Ewart

    2012-01-01

    Background Tumors frequently exhibit loss of tumor suppressor genes or allelic gains of activated oncogenes. A significant proportion of cancer susceptibility loci in the mouse show somatic losses or gains consistent with the presence of a tumor susceptibility or resistance allele. Thus, allele-specific somatic gains or losses at loci may demarcate the presence of resistance or susceptibility alleles. The goal of this study was to determine if previously mapped susceptibility loci for colorectal cancer show evidence of allele-specific somatic events in colon tumors. Methods We performed quantitative genotyping of 16 single nucleotide polymorphisms (SNPs) showing statistically significant association with colorectal cancer in published genome-wide association studies (GWAS). We genotyped 194 paired normal and colorectal tumor DNA samples and 296 paired validation samples to investigate these SNPs for allele-specific somatic gains and losses. We combined analysis of our data with published data for seven of these SNPs. Results No statistically significant evidence for allele-specific somatic selection was observed for the tested polymorphisms in the discovery set. The rs6983267 variant, which has shown preferential loss of the non-risk T allele and relative gain of the risk G allele in previous studies, favored relative gain of the G allele in the combined discovery and validation samples (corrected p-value?=?0.03). When we combined our data with published allele-specific imbalance data for this SNP, the G allele of rs6983267 showed statistically significant evidence of relative retention (p-value?=?2.06×10?4). Conclusions Our results suggest that the majority of variants identified as colon cancer susceptibility alleles through GWAS do not exhibit somatic allele-specific imbalance in colon tumors. Our data confirm previously published results showing allele-specific imbalance for rs6983267. These results indicate that allele-specific imbalance of cancer susceptibility alleles may not be a common phenomenon in colon cancer. PMID:22629442

  16. Mutant maize variety containing the glt1-1 allele

    DOEpatents

    Nelson, Oliver E. (Cross Plains, WI); Pan, David (Madison, WI)

    1994-01-01

    A maize plant has in its genome a non-mutable form of a mutant allele designated vitX-8132. The allele is located at a locus designated as glt which conditions kernels having an altered starch characteristic. Maize plants including such a mutant allele produce a starch that does not increase in viscosity on cooling, after heating.

  17. Mutant maize variety containing the glt1-1 allele

    DOEpatents

    Nelson, O.E.; Pan, D.

    1994-07-19

    A maize plant has in its genome a non-mutable form of a mutant allele designated vitX-8132. The allele is located at a locus designated as glt which conditions kernels having an altered starch characteristic. Maize plants including such a mutant allele produce a starch that does not increase in viscosity on cooling, after heating. 2 figs.

  18. Genetic Differences between Five European Populations

    Microsoft Academic Search

    Valentina Moskvina; Michael Smith; Dobril Ivanov; Douglas Blackwood; David StClair; Christina Hultman; Draga Toncheva; Michael Gill; Aiden Corvin; Colm O’Dushlaine; Derek W. Morris; Naomi R. Wray; Patrick Sullivan; Carlos Pato; Michele T. Pato; Pamela Sklar; Shaun Purcell; Peter Holmans; Michael C. O’Donovan; Michael J. Owen; George Kirov

    2010-01-01

    Aims: We sought to examine the magnitude of the differences in SNP allele frequencies between five European populations (Scotland, Ireland, Sweden, Bulgaria and Portugal) and to identify the loci with the greatest differences. Methods: We performed a population-based genome-wide association analysis with Affymetrix 6.0 and 5.0 arrays. We used a 4 degrees of freedom ?2 test to determine the magnitude

  19. Allelic frequencies and statistical data obtained from 12 codis STR loci in an admixed population of the Brazilian Amazon

    PubMed Central

    da Costa Francez, Pablo Abdon; Rodrigues, Elzemar Martins Ribeiro; Frazão, Gleycianne Furtado; dos Reis Borges, Nathalia Danielly; dos Santos, Sidney Emanuel Batista

    2011-01-01

    The allelic frequencies of 12 short tandem repeat loci were obtained from a sample of 307 unrelated individuals living in Macapá, a city in the northern Amazon region, Brazil. These loci are the most commonly used in forensics and paternity testing. Based on the allele frequency obtained for the population of Macapá, we estimated an interethnic admixture for the three parental groups (European, Native American and African) of, respectively, 46%, 35% and 19%. Comparing these allele frequencies with those of other Brazilian populations and of the Iberian Peninsula population, no significant distances were observed. The interpopulation genetic distances (FST coefficients) to the present database ranged from FST = 0.0016 between Macapá and Belém to FST = 0.0036 between Macapá and the Iberian Peninsula. PMID:21637540

  20. Sequence of a new DR12 allele with two silent mutations that affect PCR-SSP typing.

    PubMed

    Zanone, R; Bettens, F; Tiercy, J-M

    2002-02-01

    A new HLA-DR12 allele has been identified in a European Caucasoid bone marrow donor. The DRB1*12012 allele differs from DRB1*12011 by two silent substitutions at codons 72 and 78, two polymorphic positions used for DNA subtyping of the DR12 serotype. The co-occurence of the two nucleotide changes is unique to the DR12 group and results in a new PCR-SSP typing pattern. The complete HLA type of the donor is A24, A68; B55, B61; Cw*01, Cw*0304; DRB1*12012, DRB1*1402; DRB3*0101, DRB3*0202; DQB1*0301. HLA-DRB1*12012 is a rare allele as it occurs in < 0.2% of DR12 donors. PMID:12028552

  1. Development of microsatellite loci in the European Dipper, Cinclus cinclus

    Microsoft Academic Search

    T. B. Bucher; P. Wandeler; J. Hegelbach; L. F. Keller

    2009-01-01

    Eighteen polymorphic microsatellite DNA loci were isolated in the Central European subspecies of the European Dipper (Cinclus cinclus aquaticus). The loci were tested for polymorphism using a test panel of 24 breeding birds. Numbers of alleles ranged from 2 to 21 per\\u000a locus and expected heterozygosities varied between 0.47 and 0.83. Two loci (Cici10 and Cici12) proved to be Z-linked.

  2. Original investigation Genetic diversity within Anatolian brown hares (Lepus europaeus Pallas, 1778) and differentiation among Anatolian and European populations

    Microsoft Academic Search

    H. Sert; F. Suchentrunk; A. Erdog

    2005-01-01

    Genetic variability of Anatolian hares and relationships between Anatolian and European populations were assessed by a multilocus allozyme approach to infer evolutionary relationships between hares from Asia Minor and Europe. Of the 48 loci assayed, 19 (39.6%) were polymorphic with two to four alleles in the Anatolian hares. Among all Anatolian alleles, 14 were so far not found in the

  3. Distribution of CYP2D6 Alleles and Phenotypes in the Brazilian Population

    PubMed Central

    Sortica, Vinicius A.; Suarez-Kurtz, Guilherme; de Moraes, Maria Elizabete; Pena, Sergio D. J.; dos Santos, Ândrea K. Ribeiro; Romano-Silva, Marco A.; Hutz, Mara H.

    2014-01-01

    Abstract The CYP2D6 enzyme is one of the most important members of the cytochrome P450 superfamily. This enzyme metabolizes approximately 25% of currently prescribed medications. The CYP2D6 gene presents a high allele heterogeneity that determines great inter-individual variation. The aim of this study was to evaluate the variability of CYP2D6 alleles, genotypes and predicted phenotypes in Brazilians. Eleven single nucleotide polymorphisms and CYP2D6 duplications/multiplications were genotyped by TaqMan assays in 1020 individuals from North, Northeast, South, and Southeast Brazil. Eighteen CYP2D6 alleles were identified in the Brazilian population. The CYP2D6*1 and CYP2D6*2 alleles were the most frequent and widely distributed in different geographical regions of Brazil. The highest number of CYPD6 alleles observed was six and the frequency of individuals with more than two copies ranged from 6.3% (in Southern Brazil) to 10.2% (Northern Brazil). The analysis of molecular variance showed that CYP2D6 is homogeneously distributed across different Brazilian regions and most of the differences can be attributed to inter-individual differences. The most frequent predicted metabolic status was EM (83.5%). Overall 2.5% and 3.7% of Brazilians were PMs and UMs respectively. Genomic ancestry proportions differ only in the prevalence of intermediate metabolizers. The IM predicted phenotype is associated with a higher proportion of African ancestry and a lower proportion of European ancestry in Brazilians. PM and UM classes did not vary among regions and/or ancestry proportions therefore unique CYP2D6 testing guidelines for Brazilians are possible and could potentially avoid ineffective or adverse events outcomes due to drug prescriptions. PMID:25329392

  4. DERIVED SNP ALLELES ARE USED MORE FREQUENTLY THAN ANCESTRAL ALLELES AS RISK-ASSOCIATED VARIANTS IN COMMON HUMAN DISEASES

    PubMed Central

    GORLOVA, OLGA Y.; YING, JUN; AMOS, CHRISTOPHER I.; SPITZ, MARGARET R.; PENG, BO; GORLOV, IVAN P.

    2013-01-01

    Evolutionary aspects of the genetic architecture of common human diseases remain enigmatic. The results of more than 200 genome-wide association studies published to date were compiled in a catalog (http://www.genome.gov/26525384/). We used cataloged data to determine whether derived (mutant) alleles are associated with higher risk of human disease more frequently than ancestral alleles. We placed all allelic variants into ten categories of population frequency (0%–100%) in 10% increments. We then analyzed the relationship between allelic frequency, evolutionary status of the polymorphic site (ancestral versus derived), and disease risk status (risk versus protection). Given the same population frequency, derived alleles are more likely to be risk associated than ancestral alleles, as are rarer alleles. The common interpretation of this association is that negative selection prevents fixation of the risk variants. However, disease stratification as early or late onset suggests that weak selection against risk-associated alleles is unlikely a major factor shaping genetic architecture of common diseases. Our results clearly suggest that the duration of existence of an allele in a population is more important. Alleles existing longer tend to show weaker linkage disequilibrium with neighboring alleles, including the causal alleles, and are less likely to tag a SNP-disease association. PMID:22809343

  5. Derived SNP alleles are used more frequently than ancestral alleles as risk-associated variants in common human diseases.

    PubMed

    Gorlova, Olga Y; Ying, Jun; Amos, Christopher I; Spitz, Margaret R; Peng, Bo; Gorlov, Ivan P

    2012-04-01

    Evolutionary aspects of the genetic architecture of common human diseases remain enigmatic. The results of more than 200 genome-wide association studies published to date were compiled in a catalog (). We used cataloged data to determine whether derived (mutant) alleles are associated with higher risk of human disease more frequently than ancestral alleles. We placed all allelic variants into ten categories of population frequency (0%-100%) in 10% increments. We then analyzed the relationship between allelic frequency, evolutionary status of the polymorphic site (ancestral versus derived), and disease risk status (risk versus protection). Given the same population frequency, derived alleles are more likely to be risk associated than ancestral alleles, as are rarer alleles. The common interpretation of this association is that negative selection prevents fixation of the risk variants. However, disease stratification as early or late onset suggests that weak selection against risk-associated alleles is unlikely a major factor shaping genetic architecture of common diseases. Our results clearly suggest that the duration of existence of an allele in a population is more important. Alleles existing longer tend to show weaker linkage disequilibrium with neighboring alleles, including the causal alleles, and are less likely to tag a SNP-disease association. PMID:22809343

  6. Biased Gene Conversion Skews Allele Frequencies in Human Populations, Increasing the Disease Burden of Recessive Alleles

    PubMed Central

    Lachance, Joseph; Tishkoff, Sarah A.

    2014-01-01

    Gene conversion results in the nonreciprocal transfer of genetic information between two recombining sequences, and there is evidence that this process is biased toward G and C alleles. However, the strength of GC-biased gene conversion (gBGC) in human populations and its effects on hereditary disease have yet to be assessed on a genomic scale. Using high-coverage whole-genome sequences of African hunter-gatherers, agricultural populations, and primate outgroups, we quantified the effects of GC-biased gene conversion on population genomic data sets. We find that genetic distances (FST and population branch statistics) are modified by gBGC. In addition, the site frequency spectrum is left-shifted when ancestral alleles are favored by gBGC and right-shifted when derived alleles are favored by gBGC. Allele frequency shifts due to gBGC mimic the effects of natural selection. As expected, these effects are strongest in high-recombination regions of the human genome. By comparing the relative rates of fixation of unbiased and biased sites, the strength of gene conversion was estimated to be on the order of Nb ? 0.05 to 0.09. We also find that derived alleles favored by gBGC are much more likely to be homozygous than derived alleles at unbiased SNPs (+42.2% to 62.8%). This results in a curse of the converted, whereby gBGC causes substantial increases in hereditary disease risks. Taken together, our findings reveal that GC-biased gene conversion has important population genetic and public health implications. PMID:25279983

  7. Diversity of alleles encoding HLA-B40: relative frequencies in united states populations and description of five novel alleles.

    PubMed

    Pimtanothai, N; Rizzuto, G A; Slack, R; Steiner, N K; Kosman, C A; Jones, P F; Koester, R; Ng, J; Hartzman, R J; Katovich Hurley, C

    2000-08-01

    The frequency of each B*40 allele was determined by DNA sequencing in four major United States populations: Caucasians, African Americans, Asians/Pacific Islanders, and Hispanics. Thirty-two individuals from each ethnic group, who were previously described serologically as B40, B60, or B61, were randomly selected out of a pool of 82,979 unrelated individuals for allele characterization. Out of nine different B*40 alleles identified in this study, B*4001 and B*4002 were the two most frequent B*40 alleles in all the population groups. B*4001 was the primary B*40 allele seen in Caucasians (83%) and African Americans (76%), while B*4002 was found in the majority of Hispanics (62%). The distributions of both alleles were comparable in the Asian/Pacific Islander population. These two alleles were the only B*40 alleles detected in Caucasians while four to five additional B*40 alleles were seen in the other population groups. The other B*40 alleles detected in this study included: B*4003 and B*4010 in Asian/Pacific Islanders; B*4012 and B*4016 in African Americans; and B*4004, B*4006, and B*4027 in Hispanics. Analysis revealed significant differences between Hispanics and all other groups as well as between African Americans and Asian/Pacific Islanders. This report also describes five novel B*40 alleles: B*4019, B*4020, B*4024, B*4027, and B*4028. PMID:10980391

  8. AlleleRetain: a program to assess management options for conserving allelic diversity in small, isolated populations.

    PubMed

    Weiser, E L; Grueber, C E; Jamieson, I G

    2012-11-01

    Preserving genetic health is an important aspect of species conservation. Allelic diversity is particularly important to conserve, as it provides capacity for adaptation and thus enables long-term population viability. Allele retention is difficult to predict beyond one generation for real populations with complex demography and life-history traits, so we developed a computer model to simulate allele retention in small populations. AlleleRetain is an individual-based model implemented in r and can be applied to assess management options for conserving allelic diversity in small populations of animals with overlapping generations. AlleleRetain remedies the limitations of similar existing software, and its source code is freely available for further modification. AlleleRetain and its supporting materials can be downloaded from https://sites.google.com/site/alleleretain/ or CRAN (http://cran.r-project.org). PMID:22925629

  9. Further data on the microsatellite locus D12S67 in worldwide populations: an unusual distribution of D12S67 alleles in Native Americans.

    PubMed

    Mitchell, R J; Federle, L; Sofro, A S; Papiha, S S; Briceno, I; Bernal, J E

    2000-08-01

    We report the frequencies of alleles at the microsatellite locus D12S67 in 2 widely separated ethnic groups of the world: 2 populations from Sulawesi, an island in the Indonesian archipelago, and 5 Native American tribes of Colombia, South America. The allele frequencies in the Minihasans and Torajans of Sulawesi are similar to each other (but the modal class allele is different) and in general agreement with those reported in mainland Asian groups, but different from both Europeans and Chinese Han of Taiwan. The 5 Native American tribes (Arsario, Kogui, Ijka, Wayuu, and Coreguaje) display different allele frequencies from those seen in Sulawesi populations, in other groups from Europe and mainland Asia, and in Chinese Han of Taiwan. Native Americans exhibit a bimodal distribution of alleles, unlike other groups, with significant differences among the tribes. The Arsario and Kogui have no admixture with Europeans or Africans and are the most distinctive, while the Wayuu have the most admixture and show most similarity to other groups. The data suggest that nonadmixed Native Americans may be quite distinctive with respect to this marker. The most common allele varies across the 5 tribes, from 249 base pairs to 261 base pairs. All samples exhibit Hardy-Weinberg genotype proportions; heterozygosities are lowest in the 2 nonadmixed Native American tribes. Examination of all the available data indicates that some east Asian and southeast Asian groups are characterized by a high frequency of smaller sized D12S67 alleles, while other populations have a greater proportion of the larger sized alleles. The cumulative, though still highly restricted, population data on locus D12S67 demonstrate that it may be of considerable value in anthropological genetic studies of ethnic groups. Data are required on Native Americans outside Colombia before this marker can be used in admixture studies of this group. PMID:11048795

  10. Construction of Bald Eagle (Haliaeetus leucocephalus) Hal01 Locus Allelic Ladder

    Microsoft Academic Search

    Manali Patel

    2012-01-01

    Allelic ladders contain all the alleles at a given locus and since the components of the allelic ladder and the sample fragments have the same length and sequence, sizing is very accurate when conducted with an allelic ladder. Allelic ladders are therefore very useful in population genetics studies. For this study, an allelic ladder for the Bald Eagle, Haliaeetus leucocephalus,

  11. Demography can favour female-advantageous alleles.

    PubMed

    Harts, Anna M F; Schwanz, Lisa E; Kokko, Hanna

    2014-09-01

    When female fecundity is relatively independent of male abundance, while male reproduction is proportional to female abundance, females have a larger effect on population dynamics than males (i.e. female demographic dominance). This population dynamic phenomenon might not appear to influence evolution, because male and female genomes still contribute equally much to the next generation. However, here we examine two evolutionary scenarios to provide a proof of principle that spatial structure can make female demographic dominance matter. Our two simulation models combine dispersal evolution with local adaptation subjected to intralocus sexual conflict and environmentally driven sex ratio biases, respectively. Both models have equilibria where one environment (without being intrinsically poorer) has so few reproductive females that trait evolution becomes disproportionately determined by those environments where females survive better (intralocus sexual conflict model), or where daughters are overproduced (environmental sex determination model). Surprisingly, however, the two facts that selection favours alleles that benefit females, and population growth is improved when female fitness is high, together do not imply that all measures of population performance are improved. The sex-specificity of the source-sink dynamics predicts that populations can evolve to fail to persist in habitats where alleles do poorly when expressed in females. PMID:25056617

  12. Exquisite allele discrimination by toehold hairpin primers

    PubMed Central

    Byrom, Michelle; Bhadra, Sanchita; Jiang, Yu Sherry; Ellington, Andrew D.

    2014-01-01

    The ability to detect and monitor single nucleotide polymorphisms (SNPs) in biological samples is an enabling research and clinical tool. We have developed a surprising, inexpensive primer design method that provides exquisite discrimination between SNPs. The field of DNA computation is largely reliant on using so-called toeholds to initiate strand displacement reactions, leading to the execution of kinetically trapped circuits. We have now similarly found that the short toehold sequence to a target of interest can initiate both strand displacement within the hairpin and extension of the primer by a polymerase, both of which will further stabilize the primer:template complex. However, if the short toehold does not bind, neither of these events can readily occur and thus amplification should not occur. Toehold hairpin primers were used to detect drug resistance alleles in two genes, rpoB and katG, in the Mycobacterium tuberculosis genome, and ten alleles in the Escherichia coli genome. During real-time PCR, the primers discriminate between mismatched templates with Cq delays that are frequently so large that the presence or absence of mismatches is essentially a ‘yes/no’ answer. PMID:24990378

  13. Wheat alleles introgress into selfing wild relatives: empirical estimates from approximate Bayesian computation in Aegilops triuncialis.

    PubMed

    Pajkovic, Mila; Lappe, Sylvain; Barman, Rachel; Parisod, Christian; Neuenschwander, Samuel; Goudet, Jerome; Alvarez, Nadir; Guadagnuolo, Roberto; Felber, François; Arrigo, Nils

    2014-10-01

    Extensive gene flow between wheat (Triticum sp.) and several wild relatives of the genus Aegilops has recently been detected despite notoriously high levels of selfing in these species. Here, we assess and model the spread of wheat alleles into natural populations of the barbed goatgrass (Aegilops triuncialis), a wild wheat relative prevailing in the Mediterranean flora. Our sampling, based on an extensive survey of 31 Ae. triuncialis populations collected along a 60 km × 20 km area in southern Spain (Grazalema Mountain chain, Andalousia, totalling 458 specimens), is completed with 33 wheat cultivars representative of the European domesticated pool. All specimens were genotyped with amplified fragment length polymorphism with the aim of estimating wheat admixture levels in Ae. triuncialis populations. This survey first confirmed extensive hybridization and backcrossing of wheat into the wild species. We then used explicit modelling of populations and approximate Bayesian computation to estimate the selfing rate of Ae. triuncialis along with the magnitude, the tempo and the geographical distance over which wheat alleles introgress into Ae. triuncialis populations. These simulations confirmed that extensive introgression of wheat alleles (2.7 × 10(-4) wheat immigrants for each Ae. triuncialis resident, at each generation) into Ae. triuncialis occurs despite a high selfing rate (Fis ? 1 and selfing rate = 97%). These results are discussed in the light of risks associated with the release of genetically modified wheat cultivars in Mediterranean agrosystems. PMID:25223217

  14. Allelic variants in TLR10 gene may influence bilateral affectation and clinical course of Meniere's disease.

    PubMed

    Requena, Teresa; Gazquez, Irene; Moreno, Antonia; Batuecas, Angel; Aran, Ismael; Soto-Varela, Andres; Santos-Perez, Sofia; Perez, Nicolas; Perez-Garrigues, Herminio; Lopez-Nevot, Alicia; Martin, Eduardo; Sanz, Ricardo; Perez, Paz; Trinidad, Gabriel; Alarcon-Riquelme, Marta E; Teggi, Roberto; Zagato, Laura; Lopez-Nevot, Miguel A; Lopez-Escamez, Jose A

    2013-05-01

    Toll-like receptors trigger the innate immune response by activating various cell types such us macrophages and lymphocytes. We genotyped SNV of TLR3, TRL7, TLR8 and TLR10 in 863 Spanish and 150 Italian patients with Meniere's disease (MD) and 1,013 controls by using Taqman assays. Real-Time qPCR was used to measure the expression level of TLR10 in peripheral blood leukocytes. The overall dataset showed that the C allele and the CC genotype of rs11096955 in TLR10 gene were more commonly observed in controls than patients (corrected p = 1 × 10(-3), OR = 0.68 [95 % confidence interval, 0.54-0.84] for CC genotype; corrected p = 1.5 × 10(-5), OR = 0.75 [0.66-0.85] for allele C). Moreover, the CC genotype was more frequent in patients with uni- (19 %) than bilateral sensorineural hearing loss (SNHL) (13 %). Logistic regression demonstrated that the time since the onset of MD, Tumarkin crises, hearing stage and rs11096955 were independent factors influencing the risk of bilateral SNHL. In addition, rs11096955 influenced hearing loss progression in patients with bilateral MD. No change in expression of TLR10 was observed according to CC, CA or AA genotypes. Our data suggest that allelic variants of TLR10 gene may influence the susceptibility and time-course of hearing loss of MD in the European population. PMID:23370977

  15. Nomenclature for human CYP2D6 alleles.

    PubMed

    Daly, A K; Brockmöller, J; Broly, F; Eichelbaum, M; Evans, W E; Gonzalez, F J; Huang, J D; Idle, J R; Ingelman-Sundberg, M; Ishizaki, T; Jacqz-Aigrain, E; Meyer, U A; Nebert, D W; Steen, V M; Wolf, C R; Zanger, U M

    1996-06-01

    To standardize CYP2D6 allele nomenclature, and to conform with international human gene nomenclature guidelines, an alternative to the current arbitrary system is described. Based on recommendations for human genome nomenclature, we propose that alleles be designated by CYP2D6 followed by an asterisk and a combination of roman letters and arabic numerals distinct for each allele with the number specifying the key mutation and, where appropriate, a letter specifying additional mutations. Criteria for classification as a separate allele and protein nomenclature are also presented. PMID:8807658

  16. Allelic heterogeneity in NCF2 associated with systemic lupus erythematosus (SLE) susceptibility across four ethnic populations

    PubMed Central

    Kim-Howard, Xana; Sun, Celi; Molineros, Julio E.; Maiti, Amit K.; Chandru, Hema; Adler, Adam; Wiley, Graham B.; Kaufman, Kenneth M.; Kottyan, Leah; Guthridge, Joel M.; Rasmussen, Astrid; Kelly, Jennifer; Sánchez, Elena; Raj, Prithvi; Li, Quan-Zhen; Bang, So-Young; Lee, Hye-Soon; Kim, Tae-Hwan; Kang, Young Mo; Suh, Chang-Hee; Chung, Won Tae; Park, Yong-Beom; Choe, Jung-Yoon; Shim, Seung Cheol; Lee, Shin-Seok; Han, Bok-Ghee; Olsen, Nancy J.; Karp, David R.; Moser, Kathy; Pons-Estel, Bernardo A.; Wakeland, Edward K.; James, Judith A.; Harley, John B.; Bae, Sang-Cheol; Gaffney, Patrick M.; Alarcón-Riquelme, Marta; Looger, Loren L.; Nath, Swapan K.; Acevedo, Eduardo; Acevedo, Eduardo; La Torre, Ignacio García-De; Maradiaga-Ceceña, Marco A.; Cardiel, Mario H.; Esquivel-Valerio, Jorge A.; Rodriguez-Amado, Jacqueline; Moctezuma, José Francisco; Miranda, Pedro; Perandones, Carlos; Aires, Buenos; Castel, Cecilia; Laborde, Hugo A.; Alba, Paula; Musuruana, Jorge; Goecke, Annelise; Foster, Carola; Orozco, Lorena; Baca, Vicente

    2014-01-01

    Recent reports have associated NCF2, encoding a core component of the multi-protein NADPH oxidase (NADPHO), with systemic lupus erythematosus (SLE) susceptibility in individuals of European ancestry. To identify ethnicity-specific and -robust variants within NCF2, we assessed 145 SNPs in and around the NCF2 gene in 5325 cases and 21 866 controls of European-American (EA), African-American (AA), Hispanic (HS) and Korean (KR) ancestry. Subsequent imputation, conditional, haplotype and bioinformatic analyses identified seven potentially functional SLE-predisposing variants. Association with non-synonymous rs17849502, previously reported in EA, was detected in EA, HS and AA (PEA = 1.01 × 10?54, PHS = 3.68 × 10?10, PAA = 0.03); synonymous rs17849501 was similarly significant. These SNPs were monomorphic in KR. Novel associations were detected with coding variants at rs35937854 in AA (PAA = 1.49 × 10?9), and rs13306575 in HS and KR (PHS = 7.04 × 10?7, PKR = 3.30 × 10?3). In KR, a 3-SNP haplotype was significantly associated (P = 4.20 × 10?7), implying that SLE predisposing variants were tagged. Significant SNP–SNP interaction (P = 0.02) was detected between rs13306575 and rs17849502 in HS, and a dramatically increased risk (OR = 6.55) with a risk allele at each locus. Molecular modeling predicts that these non-synonymous mutations could disrupt NADPHO complex assembly. The risk allele of rs17849501, located in a conserved transcriptional regulatory region, increased reporter gene activity, suggesting in vivo enhancer function. Our results not only establish allelic heterogeneity within NCF2 associated with SLE, but also emphasize the utility of multi-ethnic cohorts to identify predisposing variants explaining additional phenotypic variance (‘missing heritability’) of complex diseases like SLE. PMID:24163247

  17. Allelic heterogeneity in NCF2 associated with systemic lupus erythematosus (SLE) susceptibility across four ethnic populations.

    PubMed

    Kim-Howard, Xana; Sun, Celi; Molineros, Julio E; Maiti, Amit K; Chandru, Hema; Adler, Adam; Wiley, Graham B; Kaufman, Kenneth M; Kottyan, Leah; Guthridge, Joel M; Rasmussen, Astrid; Kelly, Jennifer; Sánchez, Elena; Raj, Prithvi; Li, Quan-Zhen; Bang, So-Young; Lee, Hye-Soon; Kim, Tae-Hwan; Kang, Young Mo; Suh, Chang-Hee; Chung, Won Tae; Park, Yong-Beom; Choe, Jung-Yoon; Shim, Seung Cheol; Lee, Shin-Seok; Han, Bok-Ghee; Olsen, Nancy J; Karp, David R; Moser, Kathy; Pons-Estel, Bernardo A; Wakeland, Edward K; James, Judith A; Harley, John B; Bae, Sang-Cheol; Gaffney, Patrick M; Alarcón-Riquelme, Marta; Looger, Loren L; Nath, Swapan K

    2014-03-15

    Recent reports have associated NCF2, encoding a core component of the multi-protein NADPH oxidase (NADPHO), with systemic lupus erythematosus (SLE) susceptibility in individuals of European ancestry. To identify ethnicity-specific and -robust variants within NCF2, we assessed 145 SNPs in and around the NCF2 gene in 5325 cases and 21 866 controls of European-American (EA), African-American (AA), Hispanic (HS) and Korean (KR) ancestry. Subsequent imputation, conditional, haplotype and bioinformatic analyses identified seven potentially functional SLE-predisposing variants. Association with non-synonymous rs17849502, previously reported in EA, was detected in EA, HS and AA (P(EA) = 1.01 × 10(-54), PHS = 3.68 × 10(-10), P(AA) = 0.03); synonymous rs17849501 was similarly significant. These SNPs were monomorphic in KR. Novel associations were detected with coding variants at rs35937854 in AA (PAA = 1.49 × 10(-9)), and rs13306575 in HS and KR (P(HS) = 7.04 × 10(-7), P(KR) = 3.30 × 10(-3)). In KR, a 3-SNP haplotype was significantly associated (P = 4.20 × 10(-7)), implying that SLE predisposing variants were tagged. Significant SNP-SNP interaction (P = 0.02) was detected between rs13306575 and rs17849502 in HS, and a dramatically increased risk (OR = 6.55) with a risk allele at each locus. Molecular modeling predicts that these non-synonymous mutations could disrupt NADPHO complex assembly. The risk allele of rs17849501, located in a conserved transcriptional regulatory region, increased reporter gene activity, suggesting in vivo enhancer function. Our results not only establish allelic heterogeneity within NCF2 associated with SLE, but also emphasize the utility of multi-ethnic cohorts to identify predisposing variants explaining additional phenotypic variance ('missing heritability') of complex diseases like SLE. PMID:24163247

  18. Increased prevalence of the HFE C282Y hemochromatosis allele in women with breast cancer.

    PubMed

    Kallianpur, Asha R; Hall, Lynn D; Yadav, Meeta; Christman, Brian W; Dittus, Robert S; Haines, Jonathan L; Parl, Fritz F; Summar, Marshall L

    2004-02-01

    Individuals with the major hemochromatosis (HFE) allele C282Y and iron overload develop hepatocellular and some extrahepatic malignancies at increased rates. No association has been previously reported between the C282Y allele and breast cancer. We hypothesized that due to the pro-oxidant properties of iron, altered iron metabolism in C282Y carriers may promote breast carcinogenesis. Because 1 in 10 Caucasians of Northern European ancestry carries this allele, any impact it may have on breast cancer burden is potentially great. We determined C282Y genotypes in 168 patients who underwent high-dose chemotherapy and blood cell transplantation for cancer: 41 with breast cancer and 127 with predominantly hematological cancers (transplant cohort). Demographic, clinical, and tumor characteristics were reviewed in breast cancer patients. The frequency of C282Y genotypes in breast cancers was compared with the frequency in nonbreast cancers, an outpatient sample from Tennessee (n = 169), and a published United States national sample. The frequency of at least one C282Y allele in breast cancers was higher (36.6%, 5 homozygotes/10 heterozygotes) than frequencies in Tennessee (12.7%, P < 0.001), the general population (12.4%, P < 0.001), and similarly selected nonbreast cancers (17.0%, P = 0.008). The likelihood of breast cancer in the transplant cohort increased with C282Y allele dose (P(trend) = 0.010). These results were supported by the finding in a nontransplant cohort of a higher frequency of C282Y mutations in Caucasian (18.4%, P = 0.039) and African-American (8.5%, P = 0.005) women with breast cancer than race-specific national frequency estimates. A high prevalence of C282Y alleles in women with breast cancer with and without poor risk features suggests that altered iron metabolism in C282Y carriers may promote the development of breast cancer and/or more aggressive forms of the disease. PMID:14973098

  19. Diversity of alleles encoding HLA-B40: relative frequencies in United States populations and description of five novel alleles

    Microsoft Academic Search

    Nattiya Pimtanothai; Gabrielle A Rizzuto; Rebecca Slack; Noriko K Steiner; Carol A Kosman; Patrick F Jones; Ruth Koester; Jennifer Ng; Robert J Hartzman; Carolyn Katovich Hurley

    2000-01-01

    The frequency of each B?40 allele was determined by DNA sequencing in four major United States populations: Caucasians, African Americans, Asians\\/Pacific Islanders, and Hispanics. Thirty-two individuals from each ethnic group, who were previously described serologically as B40, B60, or B61, were randomly selected out of a pool of 82,979 unrelated individuals for allele characterization. Out of nine different B?40 alleles

  20. Investigation of CYP2C19 allele and genotype frequencies in Iranian population using experimental and computational approaches.

    PubMed

    Saber, Morteza Mahmoudi; Boroumand, Mohammadali; Behmanesh, Mehrdad

    2014-02-01

    CytochromeP4502C19 is a genetically polymorphic gene with prominent role in drug metabolism. Regarding its critical medical importance, this study was conducted to achieve accurate CYP2C19allele frequencies in Iranian population and hereby paving the way for a tailor-made CYP2C19 DNA test. Iran is a large multi-ethnic country, however, its population structure for CYP2C19 alleles is calculated as nearly zero (Fwc (st)=0.001). The Study was conducted on 691 individuals in Tehran, the conurbation in which total population structure is significantly eroded by massive immigration and DNA was analyzed by TaqMan SNP genotyping assay. A cumulative meta-analysis was then conducted to achieve less than five percent variation range in allele frequencies with 99.9% confidence level. High degree of Hardy-Weinberg equilibrium in pooled data proved the authenticity of meta-analysis. By cumulative meta-analysis the average frequencies of CYP2C19*2 and CYP2C19*3 alleles were calculated as 0.125[99.9% CI, 0.112-0.139] and 0.006[99.9% CI, 0.004-0.009], respectively. According to the solid frequency data obtained by pooling the data and meta-analysis and comparing with other ethnicities, Iranian population's CYP2C19 allele frequencies completely differ from other Asian ethnicities and matches African and European ethnicities the most. Since this is the biggest CYP2C19 allele frequency study in the Middle East, the results of this study will also be useful in cross-population and regional CYP2C19 genetic variation studies. PMID:24315317

  1. Mexican American ancestry-informative markers: examination of population structure and marker characteristics in European Americans, Mexican Americans, Amerindians and Asians

    Microsoft Academic Search

    Heather E. Collins-Schramm; Bill Chima; Takanobu Morii; Kimberly Wah; Yolanda Figueroa; Lindsey A. Criswell; Robert L. Hanson; William C. Knowler; Gabriel Silva; John W. Belmont; Michael F. Seldin

    2004-01-01

    Markers with large differences in allele frequencies between ethnicities provide ancestry information that can be applied to genetic studies. We identified over 100 biallelic ancestry informative markers (AIMs) with large allele frequency differences between European Americans (EA) and Pima Amerindians from laboratory and database screens. For 35 of these markers, Mayan, Yavapai and Quechuan Amerindians were genotyped and compared with

  2. Genome-Wide Allelic Imbalance Analysis of Pediatric Gliomas by Single Nucleotide Polymorphic Allele Array

    Microsoft Academic Search

    Kwong-Kwok Wong; Yvonne T. M. Tsang; Yi-Mieng Chang; Jack Su; Angela M. Di Francesco; Daniela Meco; Riccardo Riccardi; Laszlo Perlaky; Robert C. Dauser; Adekunle Adesina; Meenakshi Bhattacharjee; Murali Chintagumpala; Ching C. Lau

    2006-01-01

    Using single nucleotide polymorphic (SNP) allele arrays, we analyzed 28 pediatric gliomas consisting of 14 high-grade gliomas and 14 low-grade gliomas. Most of the low-grade gliomas had no detectable loss of heterozygosity (LOH) in any of the 11,562 SNP loci; exceptions were two gangliogliomas (3q and 9p), one astrocytoma (6q), and two subependymal giant cell astrocytomas (16p and 21q). On

  3. [Allele frequency distributions of -174G/C polymorphism in regulatory region of interleukin 6 gene (IL6) in Russian and worldwide populations].

    PubMed

    Borinskaya, S A; Gureev, A S; Orlova, A A; Sanina, E D; Kim, A A; Gasemianrodsari, F; Shirmanov, V I; Balanovsky, O P; Rebrikov, D V; Koshechkin, A V; Yankovsky, N K

    2013-01-01

    Allele and genotype frequencies of the -174G/C polymorphism (rs1800795) in the regulatory region of the IL6 gene, which encode anti-inflammatory cytokine interleukin 6, were determined in seven populations representing five ethnic groups from the European part of Russia (440 individuals), as well as in small cohorts that represent populations from 24 countries of Africa and Eurasia (365 individuals). The maps of the geographic distribution of the -174G/C allele frequencies were constructed based on personal (22 populations) and the literature data (66 populations), and the data from dbSNP database obtained by the HapMap project (10 populations). The frequency of the -174G allele varied from 45 to 100% and was characterized by nonrandom geographic distribution. These data could reflect the adaptive load of the alleles examined, which was different in different regions of the world. It is suggested that the level of pathogen prevalence is one of the environmental factors that determine different adaptive values of the IL6*--174G/C alleles. This suggestion is supported by a positive correlation between the -174G allele frequency and level of pathogen prevalence calculated based on historical data (R = 0.768; p < 0.0001). PMID:23662429

  4. Asynchronous replication of alleles in genomes carrying an extra autosome

    Microsoft Academic Search

    Aliza Amiel; Avital Korenstein; Elena Gaber; Lydia Avivi

    1999-01-01

    Transcriptional activity of genes appears to be highly related to their replication timing; alleles showing the common biallelic mode of expression replicate highly synchronously, whereas those with a monoallelic mode of expression replicate asynchronously. Here we used FISH to determine the level of synchronisation in replication timing of alleles in amniotic fluid cells derived from normal foetuses and from those

  5. Interpreting simple STR mixtures using allele peak areas

    Microsoft Academic Search

    P. Gill; R. Sparkes; R. Pinchin; T. Clayton; J. Whitaker; J. Buckleton

    1998-01-01

    Although existing statistical models can interpret mixtures qualitatively based upon the alleles present, the use of automated sequencers opens the opportunity to take account of quantitative aspects embodied by the peak area. One step in understanding simple mixtures consisting of just two donors is to estimate the mixture ratio. This is relatively easy to do when four-allele mixtures are evident

  6. cause of mortality. However, another hemoglobin allele C

    E-print Network

    Morgan, David

    the selected locus. Balancing selection, on the other hand, brings the favored allele to an intermediate-cell polymorphism may be evolutionarily short-lived. When alleles are maintained by balancing selection for a long determination (csd) locus that determines sex in a number of hymenoptera species. How is balancing selection

  7. Statistical Studies on Protein Polymorphism in Natural Populations. III. Distribution of Allele Frequencies and the Number of Alleles per Locus

    PubMed Central

    Chakraborty, Ranajit; Fuerst, Paul A.; Nei, Masatoshi

    1980-01-01

    With the aim of understanding the mechanism of maintenance of protein polymorphism, we have studied the properties of allele frequency distribution and the number of alleles per locus, using gene-frequency data from a wide range of organisms (mammals, birds, reptiles, amphibians, Drosophila and non-Drosophila invertebrates) in which 20 or more loci with at least 100 genes were sampled. The observed distribution of allele frequencies was U-shaped in all of the 138 populations (mostly species or subspecies) examined and generally agreed with the theoretical distribution expected under the mutation-drift hypothesis, though there was a significant excess of rare alleles (gene frequency, 0 ? 0.05) in about a quarter of the populations. The agreement between the mutation-drift theory and observed data was quite satisfactory for the numbers of polymorphic (gene frequency, 0.05 ? 0.95) and monomorphic (0.95 ? 1.0) alleles.—The observed pattern of allele-frequency distribution was incompatible with the prediction from the overdominance hypothesis. The observed correlations of the numbers of rare alleles, polymorphic alleles and monomorphic alleles with heterozygosity were of the order of magnitude that was expected under the mutation-drift hypothesis. Our results did not support the view that intracistronic recombination is an important source of genetic variation. The total number of alleles per locus was positively correlated with molecular weight in most of the species examined, and the magnitude of the correlation was consistent with the theoretical prediction from mutation-drift hypothesis. The correlation between molecular weight and the number of alleles was generally higher than the correlation between molecular weight and heterozygosity, as expected. PMID:17249018

  8. MicroRNA-3148 Modulates Allelic Expression of Toll-Like Receptor 7 Variant Associated with Systemic Lupus Erythematosus

    PubMed Central

    Sakurai, Daisuke; Kaufman, Kenneth M.; Edberg, Jeffrey C.; Kimberly, Robert P.; Kamen, Diane L.; Gilkeson, Gary S.; Jacob, Chaim O.; Scofield, R. Hal; Langefeld, Carl D.; Kelly, Jennifer A.; Ramsey-Goldman, Rosalind; Petri, Michelle A.; Reveille, John D.; Vilá, Luis M.; Alarcón, Graciela S.; Vyse, Timothy J.; Pons-Estel, Bernardo A.; Freedman, Barry I.; Gaffney, Patrick M.; Sivils, Kathy Moser; James, Judith A.; Gregersen, Peter K.; Anaya, Juan-Manuel; Niewold, Timothy B.; Merrill, Joan T.; Criswell, Lindsey A.; Stevens, Anne M.; Boackle, Susan A.; Cantor, Rita M.; Chen, Weiling; Grossman, Jeniffer M.; Hahn, Bevra H.; Harley, John B.; Alarc?n-Riquelme, Marta E.; Brown, Elizabeth E.; Tsao, Betty P.

    2013-01-01

    We previously reported that the G allele of rs3853839 at 3?untranslated region (UTR) of Toll-like receptor 7 (TLR7) was associated with elevated transcript expression and increased risk for systemic lupus erythematosus (SLE) in 9,274 Eastern Asians [P?=?6.5×10?10, odds ratio (OR) (95%CI)?=?1.27 (1.17–1.36)]. Here, we conducted trans-ancestral fine-mapping in 13,339 subjects including European Americans, African Americans, and Amerindian/Hispanics and confirmed rs3853839 as the only variant within the TLR7-TLR8 region exhibiting consistent and independent association with SLE (Pmeta?=?7.5×10?11, OR?=?1.24 [1.18–1.34]). The risk G allele was associated with significantly increased levels of TLR7 mRNA and protein in peripheral blood mononuclear cells (PBMCs) and elevated luciferase activity of reporter gene in transfected cells. TLR7 3?UTR sequence bearing the non-risk C allele of rs3853839 matches a predicted binding site of microRNA-3148 (miR-3148), suggesting that this microRNA may regulate TLR7 expression. Indeed, miR-3148 levels were inversely correlated with TLR7 transcript levels in PBMCs from SLE patients and controls (R2?=?0.255, P?=?0.001). Overexpression of miR-3148 in HEK-293 cells led to significant dose-dependent decrease in luciferase activity for construct driven by TLR7 3?UTR segment bearing the C allele (P?=?0.0003). Compared with the G-allele construct, the C-allele construct showed greater than two-fold reduction of luciferase activity in the presence of miR-3148. Reduced modulation by miR-3148 conferred slower degradation of the risk G-allele containing TLR7 transcripts, resulting in elevated levels of gene products. These data establish rs3853839 of TLR7 as a shared risk variant of SLE in 22,613 subjects of Asian, EA, AA, and Amerindian/Hispanic ancestries (Pmeta?=?2.0×10?19, OR?=?1.25 [1.20–1.32]), which confers allelic effect on transcript turnover via differential binding to the epigenetic factor miR-3148. PMID:23468661

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

    PubMed Central

    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 [? 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. PMID:23422023

  10. European Central Bank

    NSDL National Science Digital Library

    Together with the national central banks of the European Union, the European Central Bank (ECB) collects statistical information and governs the European System of Central Banks (ESCB). Legal texts about the ECB, the ESCB, and the European Monetary Union (EMI) are provided in addition to press releases, speeches, euro area statistics and selected publications of the EMI (in eleven European languages).

  11. European solar thermal market

    Microsoft Academic Search

    Gerhard Stryi-Hipp

    2001-01-01

    The first comprehensive study about the European solar thermal market came out in 1996. The European Solar Industry Federation (ESIF) had conducted it within the framework of the ALTENER program of the European Commission and published it with the title “Sun in Action.” Experts from 10 countries collated descriptions of the European and some non-European markets. The market data published

  12. CGG allele size somatic mosaicism and methylation in FMR1 premutation alleles

    PubMed Central

    Pretto, Dalyir I.; Mendoza-Morales, Guadalupe; Lo, Joyce; Cao, Ru; Hadd, Andrew; Latham, Gary J.; Durbin-Johnson, Blythe; Hagerman, Randi; Tassone, Flora

    2014-01-01

    Background Greater than 200 CGG repeats in the 5?UTR of the FMR1 gene leads to epigenetic silencing and lack of the FMR1 protein, causing Fragile X Syndrome. Individuals carriers of a premutation (PM) allele with 55–200 CGG repeats are typically unmethylated and can present with clinical features defined as FMR1 associated conditions. Methods Blood samples from 17 male PM carriers were assessed clinically and molecularly by Southern Blot, Western Blot, PCR and QRT-PCR. Blood and brain tissue from additional 18 PM males were also similarly examined. Continuous outcomes were modeled using linear regression and binary outcomes were modeled using logistic regression. Results Methylated alleles were detected in different fractions of blood cells in all PM cases (n= 17). CGG repeat numbers correlated with percent of methylation and mRNA levels and, especially in the upper PM range, with greater number of clinical involvements. Inter/intra- tissue somatic instability and differences in percent methylation were observed between blood and fibroblasts (n=4) and also observed between blood and different brain regions in three of the 18 premutation cases examined. CGG repeat lengths in lymphocytes remained unchanged over a period of time ranging from 2–6 years, three cases for whom multiple samples were available. Conclusion In addition to CGG size instability, individuals with a PM expanded alleles can exhibit methylation and display more clinical features likely due to RNA toxicity and/or FMR1 silencing. The observed association between CGG repeat length and percent of methylation with the severity of the clinical phenotypes underscores the potential value of methylation in affected PM to further understand penetrance, inform diagnosis and to expand treatment options. PMID:24591415

  13. Allele frequencies of six STR loci in Argentine populations.

    PubMed

    Tourret, N; López Camelo, J; Vidal-Rioja, L

    1999-11-01

    Allele frequencies of six short tandem repeat (STR) loci were determined in a Caucasian urban sample of La Plata city and three Amerindian sample populations of Argentina. Allele frequencies showed differences between urbans and Amerindians, and among Amerindians as well. The degree of genetic differentiation of subpopulations was mainly due to the Amerindian contribution. Mapuche, Mocovi, and pooled Amerindian populations showed little evidence of HW disequilibrium, and association of alleles. In the urban sample, there is no evidence of population substructuring. Forensic probabilities of exclusion and matching showed high differences between the population groups. Finally, La Plata sample did not show differences with Caucasians from other geographic regions. PMID:10582366

  14. Role of GBSS allelic diversity in rice grain quality

    E-print Network

    Dobo, Macaire

    2009-05-15

    exons 1, 6 and 10) GAC-glab O. glaberrima version of GBSS GAC allele (Adenine in exon 12 & no transposon in intron 10) GAC-sat O. sativa version of GBSS GAC allele (Guanine in exons 12 & transposon in intron 10). This base is also found... in other O. sativa GBSS alleles at the same position. GAT Guanine, Adenine and Thymine (SNP in GBSS exons 1, 6 and 10) GCC Guanine, Cytosine and Cytosine (SNP in GBSS exons 1, 6 and 10) G#1;T or G/T Base change guanine to thymine...

  15. Uneven segregation of sporophytic self-incompatibility alleles in Arabidopsis lyrata

    Microsoft Academic Search

    J. B ECHSGAARD; T. BATAILLON; M. H. SCHIERUP

    2004-01-01

    Self-incompatibility in Arabidopsis lyrata is sporophytically controlled by the multi-allelic S-locus. Self-incompatibility alleles (S-alleles) are under strong negative frequency dependent selection because pollen carrying common S-alleles have fewer mating opportunities. Population genetics theory predicts that deleterious alleles can accumulate if linked to the S-locus. This was tested by studying segregation of S-alleles in 11 large full sib families in A.

  16. Allelic Polymorphism within the TAS1R3 Promoter is Associated with Human Taste Sensitivity to Sucrose

    PubMed Central

    Fushan, Alexey A; Simons, Christopher T; Slack, Jay P; Manichaikul, Ani; Drayna, Dennis

    2009-01-01

    Summary Human sweet taste perception is mediated by the heterodimeric G-protein coupled receptor complex encoded by the TAS1R2 and TAS1R3 genes [1-7]. The extent of variation in these genes has been recently characterized [8], but the functional consequences of such variation are unknown. In this study we report that two C/T single nucleotide polymorphisms located at positions ?1572 (rs307355) and ?1266 (rs35744813) upstream of the TAS1R3 coding sequence strongly correlate with human taste sensitivity to sucrose, and explain 16% of population variability in perception. Individuals who carry T alleles display reduced sensitivity to sucrose compared to those who carry C alleles at these nucleotide positions. Using a luciferase reporter assay, we demonstrate that the T allele of each SNP results in reduced promoter activity in comparison to the C alleles, consistent with the phenotype observed in humans. We also found that the TAS1R3 promoter region extending from position ?1700 to ?1000 harbors a novel composite cis-acting element that has a strong silencing effect on promoter activity. We conclude that the rs307355 and rs35744813 SNPs affect gene transcription by altering the function of this regulatory element. A worldwide population survey reveals that the T alleles of rs307355 and rs35744813 occur at lowest frequencies in European populations. We propose that inherited differences in TAS1R3 transcription account for a substantial fraction of worldwide differences in human sweet taste perception. PMID:19559618

  17. Numerical and exact solutions for continuum of alleles models.

    PubMed

    Waxman, D

    2003-03-01

    Two results are presented for problems involving alleles with a continuous range of effects. The first result is a simple yet highly accurate numerical method that determines the equilibrium distribution of allelic effects, moments of this distribution, and the mutational load. The numerical method is explicitly applied to the mutation-selection balance problem of stabilising selection. The second result is an exact solution for the distribution of allelic effects under weak stabilising selection for a particular distribution of mutant effects. The exact solution is shown to yield a distribution of allelic effects that, depending on the mutation rate, interpolates between the "House of Cards" approximation and the Gaussian approximation. The exact solution is also used to test the accuracy of the numerical method. PMID:12728334

  18. Performance of HLA allele prediction methods in African Americans for class II genes HLA-DRB1, ?DQB1, and –DPB1

    PubMed Central

    2014-01-01

    Background The expense of human leukocyte antigen (HLA) allele genotyping has motivated the development of imputation methods that use dense single nucleotide polymorphism (SNP) genotype data and the region’s haplotype structure, but the performance of these methods in admixed populations (such as African Americans) has not been adequately evaluated. We compared genotype-based—derived from both genome-wide genotyping and targeted sequencing—imputation results to existing allele data for HLA–DRB1, ?DQB1, and –DPB1. Results In European Americans, the newly-developed HLA Genotype Imputation with Attribute Bagging (HIBAG) method outperformed HLA*IMP:02. In African Americans, HLA*IMP:02 performed marginally better than HIBAG pre-built models, but HIBAG models constructed using a portion of our African American sample with both SNP genotyping and four-digit HLA class II allele typing had consistently higher accuracy than HLA*IMP:02. However, HIBAG was significantly less accurate in individuals heterozygous for local ancestry (p??0.04). Accuracy improved in models with equal numbers of African and European chromosomes. Variants added by targeted sequencing and SNP imputation further improved both imputation accuracy and the proportion of high quality calls. Conclusion Combining the HIBAG approach with local ancestry and dense variant data can produce highly-accurate HLA class II allele imputation in African Americans. PMID:24935557

  19. European Space Agency European Space Exploration

    E-print Network

    Crawford, Ian

    European Space Agency Aurora European Space Exploration Programme EXECUTIVE SUMMARY #12;2 Aurora Programme EXECUTIVE SUMMARY 1. What is Aurora? A European Space Exploration Programme based on a road map economically and politically as a leading world power, it cannot leave space exploration to the other space

  20. European Dialogue: The Magazine for European Integration

    NSDL National Science Digital Library

    This new bimonthly magazine published by the European Commission is targeted at "decision-makers/opinion formers having an impact on European Integration" in the ten Central European and Baltic countries that have applied to join the EU. The electronic version of the first issue contains articles on humanitarian aid, membership negotiations, pensions, and economic forecasts.

  1. Robust Identification of Local Adaptation from Allele Frequencies

    PubMed Central

    Günther, Torsten; Coop, Graham

    2013-01-01

    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. PMID:23821598

  2. Selective detection of parental alleles in imprinted gene, H19

    Microsoft Academic Search

    Nori Nakayashiki; Jun Kanetake; Masataka Takamiya; Yasuhiro Aoki

    2004-01-01

    An autosomal polymorphism, designated H19FR which located upstream of imprinted H19 gene, was investigated. Three allelic bands of H19FR system were detected by PCR amplification followed by constant denaturing gel electrophoresis (CDGE). In digested genomic DNA by methylation-sensitive endonuclease or McrBC, paternal or maternal allele of H19FR was selectively detectable, respectively. This parental typing was applicable to the DNA isolated

  3. Association of smoking behavior with an odorant receptor allele telomeric to the human major histocompatibility complex.

    PubMed

    Santos, Pablo Sandro Carvalho; Füst, George; Prohászka, Zoltán; Volz, Armin; Horton, Roger; Miretti, Marcos; Yu, Chack-Yung; Beck, Stephan; Uchanska-Ziegler, Barbara; Ziegler, Andreas

    2008-12-01

    Smoking behavior has been associated in two independent European cohorts with the most common Caucasian human leukocyte antigen (HLA) haplotype (A1-B8-DR3). We aimed to test whether polymorphic members of the two odorant receptor (OR) clusters within the extended HLA complex might be responsible for the observed association, by genotyping a cohort of Hungarian women in which the mentioned association had been found. One hundred and eighty HLA haplotypes from Centre d'Etude du Polymorphisme Humain families were analyzed in silico to identify single-nucleotide polymorphisms (SNPs) within OR genes that are in linkage disequilibrium with the A1-B8-DR3 haplotype, as well as with two other haplotypes indirectly linked to smoking behavior. A nonsynonymous SNP within the OR12D3 gene (rs3749971(T)) was found to be linked to the A1-B8-DR3 haplotype. This polymorphism leads to a (97)Thr --> Ile exchange that affects a putative ligand binding region of the OR12D3 protein. Smoking was found to be associated in the Hungarian cohort with the rs3749971(T) allele (p = 1.05 x 10(-2)), with higher significance than with A1-B8-DR3 (p = 2.38 x 10(-2)). Our results link smoking to a distinct OR allele, and demonstrate that the rs3749971(T) polymorphism is associated with the HLA haplotype-dependent differential recognition of cigarette smoke components, at least among Caucasian women. PMID:18939942

  4. Replication of a rare protective allele in the noradrenaline transporter gene and ADHD

    PubMed Central

    Xu, X; Hawi, Z; Brookes, KJ; Anney, R; Bellgrove, M; Franke, B; Barry, E; Chen, W; Kuntsi, J; Banaschewski, T; Buitelaar, J; Ebstein, R; Fitzgerald, M; Miranda, A; Oades, RD; Roeyers, H; Rothenberger, A; Sergeant, J; Sonuga-Barke, E; Steinhausen, H-C; Faraone, SV; Gill, M

    2008-01-01

    Objective Replication is a key to resolving whether a reported genetic association represents a false positive finding or an actual genetic risk factor. In a previous study screening 51 candidate genes for association with ADHD in a multi-centre European sample (the IMAGE project), two single nucleotide polymorphisms (SNPs) within the norepinephrine transporter (SLC6A2) gene were found to be associated with attention deficit hyperactivity disorder (ADHD). The same SNP alleles were also reported to be associated with ADHD in a separate study from the Massachusetts General Hospital in the US. Method Using two independent samples of ADHD DSM-IV combined subtype trios we attempted to replicate the reported associations with SNPs rs11568324 and rs3785143 in SLC6A2. Results Significant association of the two markers was not observed in the two independent replication samples. However, across all four datasets the overall evidence of association with ADHD was significant (for SNP rs11568324 P=0.0001; average odds ratio=0.33; for SNP rs3785143 P=0.008; average odds ratio=1.3). Conclusions The data were consistent for rs11568324, suggesting the existence of a rare allele conferring protection for ADHD within the SLC6A2 gene. Further investigations should focus on identifying the mechanisms underlying the protective effect. PMID:18937296

  5. Regression Modeling of Allele Frequencies and Testing Hardy Weinberg Equilibrium

    PubMed Central

    Schaid, Daniel J.; Sinnwell, Jason P.; Jenkins, Gregory D.

    2013-01-01

    Background/Aims Tests for whether observed genotype proportions fit Hardy Weinberg Equilibrium (HWE) are widely used in population genetics analyses, as well as to evaluate quality of genotype data. To date, all methods testing for HWE require subjects to be classified into discrete categories, yet it is becoming clear that the distribution of allele frequencies tends to be smooth over geographic regions. Methods To evaluate the HWE assumption, we develop new approaches to model allele frequencies as functions of covariates, and use these models to test whether there is residual correlation between the two alleles of subjects; lack of residual correlation supports the null hypothesis of HWE, but conditional on how the covariates influence the allele frequencies. Results By simulations, we illustrate that a simple statistical test of residual correlation of alleles adequately controls the Type-I error rate, while maintaining power that is comparable to standard tests for HWE. Conclusion Our approach can be implemented in standard software, enabling more flexible and powerful ways to evaluate the association of covariates with allele frequencies, and whether these associations “explain” departures from HWE when the covariates are ignored, opening new strategies to evaluate the quality of genotype data generated by next-generation sequencing assays. PMID:23328647

  6. Digital single-nucleotide polymorphism analysis for allelic imbalance.

    PubMed

    Chang, Hsueh-Wei; Shih, Ie-Ming

    2005-01-01

    Digital single-nucleotide polymorphism (SNP) analysis is developed to amplify a single template from a pool of DNA samples, thereby generating the amplicons that are homogeneous in sequence. Different fluorophores are then applied as probes to detect and discriminate different alleles (paternal vs maternal alleles or wild-type vs mutant), which can be readily counted. In this way, digital SNP analysis transforms the exponential and analog signals from conventional polymerase chain reaction (PCR) to linear and digital ones. Digital SNP analysis has the following advantages. First, statistical analysis of the PCR products becomes available as the alleles can be directly counted. Second, this technology is designed to generate PCR products of the same size; therefore, DNA degradation would not be a problem as it commonly occurs when microsatellite markers are used to assess allelic status in clinical samples. Last, digital SNP analysis is designed to amplify a relatively small amount of DNA samples, which is available in some clinical samples. Digital SNP analysis has been applied in quantification of mutant alleles and detection of allelic imbalance in clinical specimens and it represents another example of the power of PCR and provides unprecedented opportunities for molecular genetic analysis. PMID:15542903

  7. MIF, MIF Alleles, and Prospects for Therapeutic Intervention in Autoimmunity

    PubMed Central

    2012-01-01

    Macrophage migration inhibitory factor (MIF) is an innate cytokine whose main actions include counter-regulating the immunosuppressive action of glucocorticoids and inhibiting activation-induced apoptosis. MIF is encoded in a functionally polymorphic locus and human genetic studies have shown significant relationships between high-expression MIF alleles, host inflammatory responses, and improved clinical outcome from infections. A recently completed candidate gene association study in the autoimmune disease systemic lupus erythematosus (SLE) indicates that individuals with a high-expression MIF allele have reduced incidence of SLE. Among patients with established disease however, those with end-organ complications have increased frequency of high-expression MIF alleles. Plasma MIF levels and Toll-like receptor (TLR) stimulated MIF production also reflect the underlying MIF genotype. These data suggest that MIF exerts a dual influence on the immunopathogenesis of SLE: high-expression MIF alleles are associated with a reduced susceptibility to SLE, perhaps by enhancing clearance of autoimmunogenic pathogens; once SLE develops however, low-expression MIF alleles protect from ensuing inflammatory end-organ damage. These data thus provide an example of the potential evolutionary advantage of maintaining an autoimmunity susceptibility gene in the population in that high-expression MIF alleles may allow for a maximal anti-infective response despite risk of autoimmunity. These results also support the clinical feasibility of pharmacologic MIF antagonism as such therapies may be most effectively applied in those individuals who, on the basis of their genotype, manifest a MIF dependent form of autoimmunity. PMID:22968741

  8. ALEA: a toolbox for allele-specific epigenomics analysis.

    PubMed

    Younesy, Hamid; Möller, Torsten; Heravi-Moussavi, Alireza; Cheng, Jeffrey B; Costello, Joseph F; Lorincz, Matthew C; Karimi, Mohammad M; Jones, Steven J M

    2014-01-21

    The assessment of expression and epigenomic status using sequencing based methods provides an unprecedented opportunity to identify and correlate allelic differences with epigenomic status. We present ALEA, a computational toolbox for allele-specific epigenomics analysis, which incorporates allelic variation data within existing resources, allowing for the identification of significant associations between epigenetic modifications and specific allelic variants in human and mouse cells. ALEA provides a customizable pipeline of command line tools for allele-specific analysis of next-generation sequencing data (ChIP-seq, RNA-seq, etc.) that takes the raw sequencing data and produces separate allelic tracks ready to be viewed on genome browsers. The pipeline has been validated using human and hybrid mouse ChIP-seq and RNA-seq data.Availability: The package, test data and usage instructions are available online at http://www.bcgsc.ca/platform/bioinfo/software/alea.Contact: mkarimi1@interchange.ubc.ca or sjones@bcgsc.ca SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID:24371156

  9. Dissecting Allele Architecture of Early Onset IBD Using High-Density Genotyping

    PubMed Central

    Prahalad, Sampath; Walters, Thomas; Guthery, Stephen L.; Dubinsky, Marla; Baldassano, Robert; Crandall, Wallace V.; Rosh, Joel; Markowitz, James; Stephens, Michael; Kellermayer, Richard; Pfefferkorn, Marian; Heyman, Melvin B.; LeLeiko, Neal; Mack, David; Moulton, Dedrick; Kappelman, Michael D.; Kumar, Archana; Prince, Jarod; Bose, Promita; Mondal, Kajari; Ramachandran, Dhanya; Bohnsack, John F.; Griffiths, Anne M.; Haberman, Yael; Essers, Jonah; Thompson, Susan D.; Aronow, Bruce; Keljo, David J.; Hyams, Jeffrey S.; Denson, Lee A.; Kugathasan, Subra

    2015-01-01

    Background The inflammatory bowel diseases (IBD) are common, complex disorders in which genetic and environmental factors are believed to interact leading to chronic inflammatory responses against the gut microbiota. Earlier genetic studies performed in mostly adult population of European descent identified 163 loci affecting IBD risk, but most have relatively modest effect sizes, and altogether explain only ~20% of the genetic susceptibility. Pediatric onset represents about 25% of overall incident cases in IBD, characterized by distinct disease physiology, course and risks. The goal of this study is to compare the allelic architecture of early onset IBD with adult onset in population of European descent. Methods We performed a fine mapping association study of early onset IBD using high-density Immunochip genotyping on 1008 pediatric-onset IBD cases (801 Crohn’s disease; 121 ulcerative colitis and 86 IBD undetermined) and 1633 healthy controls. Of the 158 SNP genotypes obtained (out of the 163 identified in adult onset), this study replicated 4% (5 SNPs out of 136) of the SNPs identified in the Crohn’s disease (CD) cases and 0.8% (1 SNP out of 128) in the ulcerative colitis (UC) cases. Replicated SNPs implicated the well known NOD2 and IL23R. The point estimate for the odds ratio (ORs) for NOD2 was above and outside the confidence intervals reported in adult onset. A polygenic liability score weakly predicted the age of onset for a larger collection of CD cases (p< 0.03, R2= 0.007), but not for the smaller number of UC cases. Conclusions The allelic architecture of common susceptibility variants for early onset IBD is similar to that of adult onset. This immunochip genotyping study failed to identify additional common variants that may explain the distinct phenotype that characterize early onset IBD. A comprehensive dissection of genetic loci is necessary to further characterize the genetic architecture of early onset IBD. PMID:26098103

  10. Gene expression profile in long-term non progressor HIV infected patients: in search of potential resistance factors.

    PubMed

    Luque, Maria Carolina; Santos, Camila C; Mairena, Eliane C; Wilkinson, Peter; Boucher, Genèvieve; Segurado, Aluisio C; Fonseca, Luiz A; Sabino, Ester; Kalil, Jorge E; Cunha-Neto, Edecio

    2014-11-01

    Long-term non-progressors (LTNP) represent a minority (1-5%) of HIV-infected individuals characterized by documented infection for more than 7-10 years, a stable CD4+ T cell count over 500/mm(3) and low viremia in the absence of antiretroviral treatment. Protective factors described so far such as the CCR5delta32 deletion, protective HLA alleles, or defective viruses fail to fully explain the partial protection phenotype. The existence of additional host resistance mechanisms in LTNP patients was investigated here using a whole human genome microarray study comparing gene expression profiles of unstimulated peripheral blood mononuclear cells from LTNP patients, HIV-1 infected patients under antiretroviral therapy with CD4+ T cell levels above 500/mm(3) (ST), as well as healthy individuals. Genes that were up- or downregulated exclusively in LTNP, ST or in both groups in comparison to controls were identified and classified in functional categories using Ingenuity Pathway Analysis. ST and LTNP patient groups revealed distinct genetic profiles, regarding gene number in each category and up- or downregulation of specific genes, which could have a bearing on the outcome of each group. We selected some relevant genes to validate the differential expression using quantitative real-time qRT-PCR. Among others, we found several genes related to the canonical Wnt/beta-catenin signaling pathway. Our results identify new possible host genes and molecules that could be involved in the mechanisms leading to the slower progression to AIDS and sustained CD4+ T cell counts that is peculiar to LTNP patients. PMID:24967879

  11. Angiotensin-converting enzyme deletion allele is beneficial for the longevity of Europeans

    Microsoft Academic Search

    Matea Zajc Petranovi?; Tatjana Škari?-Juri?; Nina Smolej Naran?i?; Željka Tomas; Petra Kraja?i?; Jasna Mili?i?; Maja Barbali?; Spomenka Tomek-Roksandi?

    The human angiotensin converting enzyme (ACE) gene is one of the most investigated candidate genes for cardiovascular diseases\\u000a (CVD), but the understanding of its role among the elderly is vague. Therefore, this study focuses at: (a) testing the association\\u000a of ACE polymorphism with CVD risk factors among the elderly, and (b) detecting the possible unequal distribution of ACE genotypes\\u000a between

  12. European Freedom of Establishing

    Microsoft Academic Search

    Krzysztof Wach

    2007-01-01

    The European Union creates new opportunities and possibilities for Polish entrepreneurs especially in the field of international entrepreneurship activities. The paper elaborates on the freedom of establishment in the European Union, which makes friendly environment for Polish enterprises to globalize and especially Europeanize their activities. The paper discuss the legal and organizational dimensions of European freedom of establishment.

  13. Imprinting of human H19: allele-specific CpG methylation, loss of the active allele in Wilms tumor, and potential for somatic allele switching.

    PubMed Central

    Zhang, Y; Shields, T; Crenshaw, T; Hao, Y; Moulton, T; Tycko, B

    1993-01-01

    Genomic imprinting and monoallelic gene expression appear to play a role in human genetic disease and tumorigenesis. The human H19 gene, at chromosome 11p15, has previously been shown to be monoallelically expressed. Since CpG methylation has been implicated in imprinting, we analyzed methylation of H19 DNA. In fetal and adult organs the transcriptionally silent H19 allele was extensively hypermethylated through the entire gene and its promoter, and, consistent with a functional role for DNA methylation, expression of an H19 promoter-reporter construct was inhibited by in vitro methylation. Gynogenetic ovarian teratomas were found to contain only hypomethylated H19 DNA, suggesting that the expressed H19 allele might be maternal. This was confirmed by analysis of 11p15 polymorphisms in a patient with Wilms tumor. The tumor had lost the maternal 11p15, and H19 expression in the normal kidney was exclusively from this allele. Imprinting of human H19 appears to be susceptible to tissue-specific modulation in somatic development; in one individual, cerebellar cells were found to express only the otherwise silent allele. Implications of these findings for the role of DNA methylation in imprinting and for H19 as a candidate imprinted tumor-suppressor gene are discussed. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8391213

  14. Microsatellite null alleles in parentage analysis EE Dakin and JC Avise

    E-print Network

    Avise, John

    is the presence of null alleles that fail to amplify to detected levels in the PCR assays. Here we examine 233 alleles, and we review how these purported nulls were detected and handled in the data analyses. We also the human ABO blood group system, wherein the O allele is a null allele that produces no phenotype (ie

  15. An Evaluation of Evolutionary Constraints on Microsatellite Loci Using Nd Alleles

    Microsoft Academic Search

    Tovi Lehmann; William A. Hawley

    1996-01-01

    A test to evaluate constraints on the evolution of single microsatellite loci is described. The test assumes that microsatellite alleles that share the same flanking sequence constitute a series of alleles with a common descent that is distinct from alleles with a mutation in the flanking sequence. Thus two or more different series of alleles at a given locus represent

  16. Distribution of the FYBES and RHCE*ce(733C>G) alleles in an Argentinean population: Implications for transfusion medicine

    PubMed Central

    Cotorruelo, Carlos M; Fiori, Silvana V; Borrás, Silvia E García; Racca, Liliana L; Biondi, Claudia S; Racca, Amelia L

    2008-01-01

    Background The understanding of the molecular bases of blood groups makes possible the identification of red cell antigens and antibodies using molecular approaches, especially when haemagglutination is of limited value. The practical application of DNA typing requires the analysis of the polymorphism and allele distribution of the blood group genes under study since genetic variability was observed among different ethnic groups. Urban populations of Argentina are assumed to have a white Caucasian European genetic component. However, historical and biological data account for the influence of other ethnic groups. In this work we analyse FY and RH blood group alleles attributed to Africans and that could have clinical implications in the immune destruction of erythrocytes. Methods We studied 103 white trios (father, mother and child, 309 samples) from the city of Rosario by allele specific PCRs and serological methods. The data obtained were analysed with the appropriate statistical test considering only fathers and mothers (n = 206). Results We found the presence of the FY*BES and RHCE*ce(733C>G) alleles and an elevated frequency (0.0583) for the Dce haplotype. The number of individuals with a concomitant occurrence of both alleles was significantly higher than that expected by chance. We found that 4.68% of the present gene pool is composed by alleles primarily associated with African ancestry and about 10% of the individuals carried at least one RH or FY allele that is predominantly observed among African populations. Thirteen percent of Fy(b-) subjects were FY*A/FY*BES. Conclusion Taken together, the results suggest that admixture events between African slaves and European immigrants at the beginning of the 20th century made the physical characteristics of black Africans to be invisible nowadays. Considering that it was a recent historical event, the FY*BES and RHCE*ce(733C>G) alleles did not have time to become widespread but remain concentrated within families. These findings have considerable impact for typing and transfusion strategy in our population, increasing the pool of compatible units for Fy(b-) individuals requiring chronic transfusion. Possible difficulties in transfusion therapy and in genotyping could be anticipated and appropriately improved strategies devised, allowing a better management of the alloimmunization in the blood bank. PMID:18460195

  17. Clines of Nuclear DNA Markers Suggest a Largely Neolithic Ancestry of the European Gene Pool

    Microsoft Academic Search

    Lounes Chikhi; Giovanni Destro-Bisol; Giorgio Bertorelle; Vincenzo Pascali; Guido Barbujani

    1998-01-01

    Comparisons between archaeological findings and allele frequencies at protein loci suggest that most genes of current Europeans descend from populations that have been expanding in Europe in the last 10,000 years, in the Neolithic period. Recent mitochondrial data have been interpreted as indicating a much older, Paleolithic ancestry. In a spatial autocorrelation study at seven hypervariable loci in Europe (four

  18. An allelic series for the chalcone synthase locus in Arabidopsis.

    PubMed

    Saslowsky, D E; Dana, C D; Winkel-Shirley, B

    2000-09-19

    Five new alleles of the Arabidopsis chalcone synthase (CHS) locus, tt4, have been characterized at the gene, protein, and end product levels as a genetic approach to understanding structure-function relationships in a key enzyme of plant secondary metabolism. Together with two previously described mutants, these tt4 lines represent one of the first allelic series for a central enzyme of the flavonoid pathway and include both null alleles and alleles with leaky, apparently temperature-sensitive, phenotypes. A variety of effects on accumulation of CHS protein and flavonoid glycosides were observed among these lines, including alterations in the apparent stability and activity of the enzyme. Assembly of the CHS homodimer also appeared to be impacted in several cases. A three-dimensional model of the Arabidopsis CHS protein, based on the recently determined structure for alfalfa CHS, predicts significant effects on protein structure or folding for several of the mutations. This allelic series should provide a useful genetic resource for ongoing studies of flavonoid enzyme structure, function, and subcellular organization. PMID:11024274

  19. Molecular evolution of alleles of the glycophorin A gene.

    PubMed

    Mizukami, Hajime; Akane, Atsushi; Shiono, Hiroshi; Ogawa, Kento

    2002-03-01

    Highly-homologous Glycophorin A (GPA), B and E genes are triplicate genes, and involve many subtypes and minor antigens constructing the Miltenberger subsystem. These genes and most of the variants are hypothesized to arise by recombination, because hot spots are located in the gene sequences. By sequencing exons 1-7 and introns 1-3 of standard alleles of GPA gene, M and N alleles were classified into six variations: provisionally called MN*M101, M102, M201, M202, N101 and N102 in our previous study. Here we further investigated the sequences of introns 4-6 using GPA gene-specific primers and by DNA sequencing, and found eight, five and nine new nucleotide substitutions or deletions in introns 4, 5 and 6, respectively. Using the computer program PHYLIP 3.5, the phylogenetic trees were reconstructed. Phylogenetic analysis of the allele sequences revealed that M200s alleles arose from M101 after the separation of M101 and N101 and branched to M201 and M202 via the accumulation of point mutations. M102 and N102 alleles were estimated to generate via recombination between M101 and N101 occurred around the hot spot. The findings also suggested the existence of other GPA variants with normal antigenicity, and are quite useful in the forensic and anthropological fields. PMID:12935686

  20. HLA-A?3101 and Carbamazepine-Induced Hypersensitivity Reactions in Europeans

    PubMed Central

    McCormack, Mark; Alfirevic, Ana; Bourgeois, Stephane; Farrell, John J.; Kasperavi?i?t?, Dalia; Carrington, Mary; Sills, Graeme J.; Marson, Tony; Jia, Xiaoming; de Bakker, Paul I.W.; Chinthapalli, Krishna; Molokhia, Mariam; Johnson, Michael R.; O’Connor, Gerard D.; Chaila, Elijah; Alhusaini, Saud; Shianna, Kevin V.; Radtke, Rodney A.; Heinzen, Erin L.; Walley, Nicole; Pandolfo, Massimo; Pichler, Werner; Park, B. Kevin; Depondt, Chantal; Sisodiya, Sanjay M.; Goldstein, David B.; Deloukas, Panos; Delanty, Norman; Cavalleri, Gianpiero L.; Pirmohamed, Munir

    2011-01-01

    BACKGROUND Carbamazepine causes various forms of hypersensitivity reactions, ranging from maculopapular exanthema to severe blistering reactions. The HLA-B?1502 allele has been shown to be strongly correlated with carbamazepine-induced Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS–TEN) in the Han Chinese and other Asian populations but not in European populations. METHODS We performed a genomewide association study of samples obtained from 22 subjects with carbamazepine-induced hypersensitivity syndrome, 43 subjects with carbamazepine-induced maculopapular exanthema, and 3987 control subjects, all of European descent. We tested for an association between disease and HLA alleles through proxy single-nucleotide polymorphisms and imputation, confirming associations by high-resolution sequence-based HLA typing. We replicated the associations in samples from 145 subjects with carbamazepine-induced hypersensitivity reactions. RESULTS The HLA-A?3101 allele, which has a prevalence of 2 to 5% in Northern European populations, was significantly associated with the hypersensitivity syndrome (P = 3.5×10?8). An independent genomewide association study of samples from subjects with maculopapular exanthema also showed an association with the HLA-A?3101 allele (P = 1.1×10?6). Follow-up genotyping confirmed the variant as a risk factor for the hypersensitivity syndrome (odds ratio, 12.41; 95% confidence interval [CI], 1.27 to 121.03), maculopapular exanthema (odds ratio, 8.33; 95% CI, 3.59 to 19.36), and SJS–TEN (odds ratio, 25.93; 95% CI, 4.93 to 116.18). CONCLUSIONS The presence of the HLA-A?3101 allele was associated with carbamazepine-induced hypersensitivity reactions among subjects of Northern European ancestry. The presence of the allele increased the risk from 5.0% to 26.0%, whereas its absence reduced the risk from 5.0% to 3.8%. (Funded by the U.K. Department of Health and others.) PMID:21428769

  1. Investigator HDplex markers: allele frequencies and mutational events in a North Italian population.

    PubMed

    Turrina, Stefania; Ferrian, Melissa; Caratti, Stefano; De Leo, Domenico

    2015-07-01

    Autosomal short tandem repeats (STRs) analysis represents the method of election in forensic genetics and up to now, 23 STRs are available for these purposes. However, in particular circumstances such as human identification or complex kinship cases, examination of additional STRs may be required in order to obtain reliable conclusions. For this purpose, a new multiplex STR system, namely Investigator® HDplex kit (QIAGEN) that coamplifies a set of 12 autosomal loci, 9 of which, represents novel supplementary STRs, was recently developed. A population sample of 359 unrelated healthy subjects residing in North Italy was typed to determine allele frequencies, forensic parameters and genetic distances among European populations. Furthermore, to evaluate the suitability of the HDplex kit as an auxiliary tool for paternity testing, mutation rates were estimated on 84 confirmed family trios. The 12 loci resulted highly informative with a combined power of discrimination of 0.999998 and no departures from Hardy-Weinberg equilibrium were observed with the sole exception of locus D4S2366. From the comparison of our population sample and European reference populations, a single significant difference was revealed with the Poland population at D4S2366 locus. With regard to the mutation rate study, on a total of 2,016 meioses considered, six single-step mutational events were observed and the average mutation rate calculated was of 2.94?×?10(-3) per locus per generation (95 % confidence interval, 1.08?×?10(-3)-6.39?×?10(-3)). PMID:25205546

  2. Human allelic variation: perspective from protein function, structure, and evolution

    PubMed Central

    Jordan, Daniel M.; Ramensky, Vasily E.; Sunyaev, Shamil R.

    2010-01-01

    It is widely anticipated that the coming year will be marked by the complete characterization of DNA sequence of protein coding regions of thousands of human individuals. A number of existing computational methods use comparative protein sequence analysis and analysis of protein structure to predict the functional effect of coding human alleles. Functional and structural analysis of coding allelic variants can inform various aspects of research on human genetic variation. In population and evolutionary genetics it helps estimating the strength of purifying selection against deleterious missense mutations and study the imprint of demographic history on deleterious genetic variation. In medical genetics it may assist in the interpretation of uncharacterized mutations in genes involved in monogenic and oligogenic diseases. It has a potnetial to facilitate medical sequencing studies searching for genes underlying Mendelian diseases or harboring rare alleles involved in complex traits. PMID:20399638

  3. Deletion of immunoglobulin heavy chain genes from expressed allelic chromosome.

    PubMed

    Yaoita, Y; Honjo, T

    1980-08-28

    We have studied the organization of immunoglobulin heavy-chain genes in a gamma 2b-chain (BALB/c allotype)-producing myeloma BKC F1 # 15 induced in a F1 mouse between C57BL and BALB/c. Southern blot hybridization studies using cloned mu, gamma 1 and gamma 2b-chain genes as probes demonstrate that the mu- and gamma 1-chain genes of the expressed chromosome are deleted while these genes of the unexpressed chromosome are retained. The gamma 2b-chain gene of the expressed allele is rearranged while that gene of the unexpressed allele seems unchanged, as do the gamma 2a-chain genes. These results support the allelic deletion mechanism in heavy-chain class switch and the order of H chain genes. PMID:6774261

  4. Distribution of a pseudodeficiency allele among Tay-Sachs carriers

    SciTech Connect

    Tomczak, J.; Grebner, E.E. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Boogen, C. (Univ. of Essen Medical School (Germany))

    1993-08-01

    Recently Triggs-Raine et al. (1992) identified a new mutation in the gene coding for the [alpha]-subunit of [beta]-hexosaminidase A (hex A), the enzyme whose deficiency causes Tay-Sachs disease. This mutation, a C[sub 739]-to-T transition in exon 7, results in an altered enzyme that is active (albeit at reduced levels) in cells but that has essentially no activity in serum. This so-called pseudodeficient allele was first detected in compound heterozygotes who also carried a Tay-Sachs disease allele and therefore had no detectable hex A in their serum but who were in good health. Carriers of this apparently benign mutation are generally indistinguishable from carriers of a lethal mutation by means of routine enzyme-based screening tests, because the product of the pseudodeficient allele is not detectable in serum and has decreased activity in cells. This suggests that some individuals who have been classified as Tay-Sachs carriers are actually carriers of the pseudodeficient allele and are not at risk to have a child affected with Tay-Sachs disease. The pseudodeficient allele may also be responsible for some inconclusive diagnoses, where leukocyte values fall below the normal range but are still above the carrier range. The fact that there are now two mutant alleles (the psuedodeficient and the adult) that are indistinguishable from the lethal infantile mutations by means of enzyme assay yet that are phenotypically very different and that together may account for as much as 12% of enzyme-defined carriers on the basis of the data here suggests that DNA analysis should be part of a comprehensive screening program. It will be particularly useful to identify the mutations in couples at risk, before they undergo prenatal diagnosis. DNA analysis will also resolve some inconclusive diagnoses.

  5. Major histocompatibility complex haplotypes and complement C4 alleles in systemic lupus erythematosus. Results of a multicenter study.

    PubMed Central

    Hartung, K; Baur, M P; Coldewey, R; Fricke, M; Kalden, J R; Lakomek, H J; Peter, H H; Schendel, D; Schneider, P M; Seuchter, S A

    1992-01-01

    In a multicenter study more than 300 central European systemic lupus erythematosus (SLE) patients were examined for HLA-B, HLA-DR, and complement C4 phenotypes. For 174 SLE patients MHC haplotypes were determined by family segregation analysis, and for 155 patients C4 gene deletions were determined by TaqI restriction fragment length polymorphism. Two haplotypes, B8-C4AQ0-C4B1-DR3 and B7-C4A3-C4B1-DR2, were identified as risk factors for SLE. These findings were confirmed by applying the haplotype frequency difference (HFD) method, which uses nontransmitted haplotypes from the family study as internal controls. Furthermore, only HLA-DR2, but not DR3, B7, or B8, was significantly increased in SLE patients independently of the two risk haplotypes. C4A gene deletions, but not silent C4AQ0 alleles, were increased in SLE patients and neither C4BQ0 alleles nor C4B gene deletions were increased. The observed frequencies of homozygosity and heterozygosity for the two haplotypes and the frequencies of homozygotes for C4AQ0 and C4A deletions did not differ from the expected values, indicating that the risk for SLE is conveyed by single allele effects. In conclusion, there are two MHC-linked susceptibility factors for Caucasian SLE patients carried by the haplotypes B7-DR2 and B8-DR3. The results argue against C4Q0 alleles being the decisive factors increasing susceptibility to SLE. PMID:1401069

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

    SciTech Connect

    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.

  7. European mink-polecat hybridization events: hazards from natural process?

    PubMed

    Lodé, T; Guiral, G; Peltier, D

    2005-01-01

    Determining the significance of hybridization events raises essential issues both in conservation and in evolutionary biology. Here, we report a genetic investigation of sympatric polecat and endangered European mink populations. Although the two species were morphologically very similar, the European mink and the polecat were easily discriminated from allozymes and microsatellites and showed a high level of private alleles (effective number of alleles: mink=1.45 and polecat=3.09). Nevertheless, the allozymic polymorphism remained lower in the European mink (4 loci, 10.5%) than in polecat (9 loci, 23.7%). Similarly, from microsatellite data, the polymorphism only reached 36% at 0.99 in the European mink; whereas in the polecat, the polymorphism reached 82% at 0.99. Natural hybridization events between two native species were detected. Because of the low fertility of hybrids, interbreeding could be regarded as producing "hybrid sink" that leads to a progressive assimilation of mink by polecat. Nonetheless, pure mink populations inhabited streams in western France, and hybridization events were only detected in areas where mink were rare and now presumed disappeared. Rather than revealing the poor efficiency of the specific recognition system, our results suggest that hybridization is associated with the scarcity of mating partners. PMID:15653561

  8. The Maintenance of Single-Locus Polymorphism. IV. Models with Mutation from Existing Alleles

    PubMed Central

    Spencer, H. G.; Marks, R. W.

    1992-01-01

    The ability of viability selection to maintain allelic polymorphism is investigated using a constructionist approach. In extensions to the models we have previously proposed, a population is bombarded with a series of mutations whose fitnesses in conjunction with other alleles are functions of the corresponding fitnesses with a particular allele, the parent allele, already in the population. Allele frequencies are iterated simultaneously, thus allowing alleles to be driven to extinction by selection. Such models allow very high levels of polymorphism to evolve: up to 38 alleles in one case. Alleles that are lethal as homozygotes can evolve to surprisingly high frequencies. The joint evolution of allele frequencies and viabilities highlights the necessity to consider more than the current morphology of a population. Comparisons are made with the neutral theory of evolution and it is suggested that failure to reject neutrality using the Ewens-Watterson test cannot be regarded as evidence for the neutral theory. PMID:1732162

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

    PubMed

    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. PMID:24144843

  10. Paternal alleles enhance female reproductive success in tropical pythons

    Microsoft Academic Search

    THOMAS MADSEN; BEATA UJVARI; MATS OLSSON; RICHARD SHINE

    2005-01-01

    The conventional view that female reproductive success is unlikely to benefit from multiple mating has come under strong challenge in recent years. In the present study, we demon- strate that the time wild-caught reproductive female water pythons ( Liasis fuscus ) spent in the laboratory prior to oviposition affected both hatching success and the number of male microsatellite alleles detected

  11. RECOVERY OF EXOTIC ALLELES IN ENHANCED TROPICAL YELLOW GERMPLASM

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Enhancement of overall diversity levels and the incorporation of new favorable traits are major benefits of using exotic germplasm in elite breeding programs. Agronomic deficiencies and poor adaptation often limits use of exotic germplasm in plant breeding programs. To introgress exotic alleles into...

  12. Allelic diversity of the population of Phytophthora infestans in China

    Microsoft Academic Search

    Y. Li; S. Huang; Lee van der T; G. J. T. Kessel; E. Jacobsen; R. Zhang; G. Jin; C. Lan; Z. Zhao; S. Kamoun

    2009-01-01

    Introduction of resistance genes from wild Solanum species into potato cultivars is considered the most promising and environmentally safe approach to achieve late blight resistance. An R-gene stacking breeding program using cisgenesis is planning to trial its products in China. To adapt this approach to local conditions, we propose to assess the allelic diversity of known avirulent genes of P.

  13. Rapid screening for temperature-sensitive alleles in plants.

    PubMed

    Vidali, Luis; Augustine, Robert C; Fay, Scotty N; Franco, Paula; Pattavina, Kelli A; Bezanilla, Magdalena

    2009-10-01

    We developed a simple and fast method to identify temperature-sensitive alleles of essential plant genes. We used primary and tertiary structure information to identify residues in the core of the protein of interest. These residues were mutated and tested for temperature sensitivity, taking advantage of the exceptionally rapid 1-week complementation assay in the moss Physcomitrella patens. As test molecules, we selected the actin-binding proteins profilin and actin-depolymerizing factor, because they are essential and their loss-of-function phenotype can be fully rescued. Screening a small number of candidate mutants, we successfully identified temperature-sensitive alleles of both profilin and actin-depolymerizing factor. Plants harboring these alleles grew well at the permissive temperature of 20 degrees C to 25 degrees C but showed a complete loss of function at the restrictive temperature of 32 degrees C. Notably, the profilin mutation identified in the moss gene can be transferred to profilins from other plant species, also rendering them temperature sensitive. The ability to routinely generate temperature-sensitive alleles of essential plant proteins provides a powerful tool for the study of gene function in plants. PMID:19666707

  14. Distribution of forensic marker allelic frequencies in Pernambuco, Northestern Brazil.

    PubMed

    Santos, S M; Souza, C A; Rabelo, K C N; Souza, P R E; Moura, R R; Oliveira, T C; Crovella, S

    2015-01-01

    Pernambuco is one of the 27 federal units of Brazil, ranking seventh in the number of inhabitants. We examined the allele frequencies of 13 short tandem repeat loci (CFS1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, TH01, vWA, and TPOX), the minimum recommended by the Federal Bureau of Investigation and commonly used in forensic genetics laboratories in Brazil, in a sample of 609 unrelated individuals from all geographic regions of Pernambuco. The allele frequencies ranged from 5 to 47.2%. No significant differences for any loci analyzed were observed compared with other publications in other various regions of Brazil. Most of the markers observed were in Hardy-Weinberg equilibrium. The occurrence of the allele 47.2 (locus FGA) and alleles 35.1 and 39 (locus D21S11), also described in a single study of the Brazilian population, was observed. The other forensic parameters analyzed (matching probability, power of discrimination, polymorphic information content, paternity exclusion, complement factor I, observed heterozygosity, expected heterozygosity) indicated that the studied markers are very informative for human forensic identification purposes in the Pernambuco population. PMID:25966202

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

    SciTech Connect

    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.

  16. Multifragment alleles in DNA fingerprints of the parrot, Amazona ventralis

    USGS Publications Warehouse

    Brock, M.K.; White, B.N.

    1991-01-01

    Human DNA probes that identify variable numbers of tandem repeat loci are being used to generate DNA fingerprints in many animal and plant species. In most species the majority of the sc rable autoradiographic bands of the DNA fingerprint represent alleles from numerous unlinked loci. This study was initiated to use DNA fingerprints to determine the amount of band-sharing among captive Hispaniolan parrots (Amazona ventralis) with known genetic relationships. This would form the data base to examine DNA fingerprints of the closely related and endangered Puerto Rican parrot (A. vittata) and to estimate the degree of inbreeding in the relic population. We found by segregation analysis of the bands scored in the DNA fingerprints of the Hispaniolan parrots that there may be as few as two to five loci identified by the human 33.15 probe. Furthermore, at one locus we identified seven alleles, one of which is represented by as many as 19 cosegregating bands. It is unknown how common multiband alleles might be in natural populations, and their existence will cause problems in the assessment of relatedness by band-sharing analysis. We believe, therefore, that a pedigree analysis should be included in all DNA fingerprinting studies, where possible, in order to estimate the number of loci identified by a minisatellite DNA probe and to examine the nature of their alleles.

  17. Cancer Cell Allele-Specific p53 Mutant Reactivation

    E-print Network

    Vazquez, Alexei

    the National Cancer Institute's anticancer drug screen data, we identified two compounds from, these properties make mutant p53 an attractive target for drug development. The National Cancer Institute's (NCICancer Cell Article Allele-Specific p53 Mutant Reactivation Xin Yu,1,4,6 Alexei Vazquez,1

  18. Allelic somatic mutations may explain vascular twin nevi

    Microsoft Academic Search

    Rudolf Happle

    1991-01-01

    Vascular twin nevi, i.e., telangiectatic nevus and nevus anemicus occurring together and adjacent to each other, can be explained as twin spots resulting from a somatic recombination. It is so far unclear, however, whether the postulated underlying autosomal recessive mutations are allelic. This problem can be approached by studying another cutaneous phenotype, phacomatosis pigmentovascularis. Within this diagnosis, several authors have

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

    PubMed Central

    Slatkin, M; Rannala, B

    1997-01-01

    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, deltaF508 and G542X, for which intraallelic variability at three intronic microsatellite loci has been examined. Our results indicate that G542X is somewhat older than deltaF508. Although absolute estimates depend on the mutation rates at the microsatellite loci, our results support the hypothesis that deltaF508 arose < 500 generations (approximately 10,000 years) ago. PMID:9012419

  20. A measure of population subdivision based on microsatellite allele frequencies

    Microsoft Academic Search

    Montgomery Slatkin

    1995-01-01

    Microsatellite loci, loci that vary in the number of repeats of a simple DNA sequence, are becoming commonly used in the analysis of natural populations. Microsatellite loci are often highly polymorphic and relatively easy to survey and hence offer the hope of greater understanding of population structure. The question is how to make the best use of allele frequencies at

  1. SHORT REVIEW Evolution of allelic dimorphism in malarial surface

    E-print Network

    Hartl, Daniel L.

    Plasmodium, P. falciparum, P. vivax, P. malariae and P. ovale, whose complex life cycle comprises several of Plasmodium falciparum is one of the major factors why clinical immunity to malaria develops only after Keywords: malaria; Plasmodium falciparum; antigenic diversity; allelic dimorphism; merozoite surface

  2. Number of incompatibility alleles in clover and other species

    Microsoft Academic Search

    M J Lawrence

    1996-01-01

    Atwood’s (1942, 1944) data on Trifolium repens, those of Williams & Williams (1947) on T. pratense and those of Williams (1951) on T. hybridum have been re-analysed to provide maximum likelihood estimates of the number of incompatibility alleles in the populations or breeders' stocks from which the samples investigated were obtained. These new estimates suggest that populations of T. repens

  3. However, the European Union

    E-print Network

    However, the European Union presidency Monday pointed to a new willingness by Japan to compromise talks with the European Union, which has been supporting France's bid. As a result, the Yomiuri said, China and Russia backed France. However, the European Union presidency Monday pointed to a new

  4. Why European Commissioners Matter

    Microsoft Academic Search

    Andy Smith

    2003-01-01

    Discussions of the role European Commissioners play in European Union politics are shaped by three powerful implicit assumptions. These posit a causal relationship between a Commissioner's behaviour and previous career, portfolio and national origin. In addition, Commissioners are seen as exacerbating the fragmentation of the European Commission as a whole. Based on an empirical study of eight Commissioners from the

  5. ESSCIRC' 85 European Conference

    E-print Network

    Paris-Sud XI, Université de

    ESSCIRC' 85 European Conference on Solid State Circuits Fo reword The 11th European Conference participants from 28 countries. This Conference is the European annual meeting for presentation and discussion of the latest news in the area of integrated circuit techniques. The covered subjects in this conference are key

  6. Amerindians show no association of PC-1 gene Gln121 allele and obesity: a thrifty gene population genetics.

    PubMed

    Rey, Diego; Fernandez-Honrado, Mercedes; Areces, Cristina; Algora, Manuel; Abd-El-Fatah-Khalil, Sedeka; Enriquez-de-Salamanca, Mercedes; Coca, Carmen; Arribas, Ignacio; Arnaiz-Villena, Antonio

    2012-07-01

    PC-1 Gln121 gene is a risk factor for type 2 diabetes, obesity and insulin resistance in European/American Caucasoids and Orientals. We have aimed to correlate for the first time this gene in Amerindians with obesity and their corresponding individuals genotypes with obesity in order to establish preventive medicine programs for this population and also studying the evolution of gene frequencies in world populations. Central obesity was diagnosed by waist circumference perimeter and food intake independent HDL-cholesterol plasma levels were measured. HLA genes were determined in order to more objectively ascertain participants Amerindians origin. 321 Amerindian blood donors who were healthy according to the blood doning parameters were studied. No association was found between PC-1 Gln121 variant and obesity. Significant HDL-cholesterol lower values were found in the PC-1 Lys121 bearing gene individuals versus PC-1 Gln121 bearing gene ones (45.1 ± 12.7 vs. 48.7 ± 15.2 mg/dl, p < 0.05). Population analyses showed a world geographical gradient in the PC-1 Gln121 allele frequency: around 9% in Orientals, 15% in European Caucasoids and 76% in Negroids. The conclusions are: (1) No association of PC-1 Gln121 gene is found with obesity in Amerindians when association is well established in Europeans. (2) PC-1 Gln121 gene is associated to higher levels of HDL-cholesterol than the alternative PC-1 Lys121 allele. This may be specific for Amerindians. (3) Amerindians have an intermediate frequency of this possible PC-1 Gln121 thrifty gene when compared with Negroid African Americans (78.5%) or Han Chinese (7.5%, p < 0.0001). Historical details of African and other groups may support the hypothesis that PC-1 Gln121 is indeed a thrifty gene. PMID:22327785

  7. Microsatellite Variation in Honey Bee (Apis Mellifera L.) Populations: Hierarchical Genetic Structure and Test of the Infinite Allele and Stepwise Mutation Models

    PubMed Central

    Estoup, A.; Garnery, L.; Solignac, M.; Cornuet, J. M.

    1995-01-01

    Samples from nine populations belonging to three African (intermissa, scutellata and capensis) and four European (mellifera, ligustica, carnica and cecropia) Apis mellifera subspecies were scored for seven microsatellite loci. A large amount of genetic variation (between seven and 30 alleles per locus) was detected. Average heterozygosity and average number of alleles were significantly higher in African than in European subspecies, in agreement with larger effective population sizes in Africa. Microsatellite analyses confirmed that A. mellifera evolved in three distinct and deeply differentiated lineages previously detected by morphological and mitochondrial DNA studies. Dendrogram analysis of workers from a given population indicated that super-sisters cluster together when using a sufficient number of microsatellite data whereas half-sisters do not. An index of classification was derived to summarize the clustering of different taxonomic levels in large phylogenetic trees based on individual genotypes. Finally, individual population X loci data were used to test the adequacy of the two alternative mutation models, the infinite allele model (IAM) and the stepwise mutation models. The better fit overall of the IAM probably results from the majority of the microsatellites used including repeats of two or three different length motifs (compound microsatellites). PMID:7498746

  8. Nomenclature for alleles of the thiopurine methyltransferase gene.

    PubMed

    Appell, Malin L; Berg, Jonathan; Duley, John; Evans, William E; Kennedy, Martin A; Lennard, Lynne; Marinaki, Tony; McLeod, Howard L; Relling, Mary V; Schaeffeler, Elke; Schwab, Matthias; Weinshilboum, Richard; Yeoh, Allen E J; McDonagh, Ellen M; Hebert, Joan M; Klein, Teri E; Coulthard, Sally A

    2013-04-01

    The drug-metabolizing enzyme thiopurine methyltransferase (TPMT) has become one of the best examples of pharmacogenomics to be translated into routine clinical practice. TPMT metabolizes the thiopurines 6-mercaptopurine, 6-thioguanine, and azathioprine, drugs that are widely used for treatment of acute leukemias, inflammatory bowel diseases, and other disorders of immune regulation. Since the discovery of genetic polymorphisms in the TPMT gene, many sequence variants that cause a decreased enzyme activity have been identified and characterized. Increasingly, to optimize dose, pretreatment determination of TPMT status before commencing thiopurine therapy is now routine in many countries. Novel TPMT sequence variants are currently numbered sequentially using PubMed as a source of information; however, this has caused some problems as exemplified by two instances in which authors' articles appeared on PubMed at the same time, resulting in the same allele numbers given to different polymorphisms. Hence, there is an urgent need to establish an order and consensus to the numbering of known and novel TPMT sequence variants. To address this problem, a TPMT nomenclature committee was formed in 2010, to define the nomenclature and numbering of novel variants for the TPMT gene. A website (http://www.imh.liu.se/tpmtalleles) serves as a platform for this work. Researchers are encouraged to submit novel TPMT alleles to the committee for designation and reservation of unique allele numbers. The committee has decided to renumber two alleles: nucleotide position 106 (G>A) from TPMT*24 to TPMT*30 and position 611 (T>C, rs79901429) from TPMT*28 to TPMT*31. Nomenclature for all other known alleles remains unchanged. PMID:23407052

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

    PubMed

    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. PMID:24417506

  10. Cystic fibrosis allele frequency, sex ratio anomalies and fertility: a new theory for the dissemination of mutant alleles

    Microsoft Academic Search

    Dorian J. Pritchard

    1991-01-01

    The observation that mothers of cystic fibrosis patients come from sibships that are larger than those of the fathers is explained by a decrease in sex ratio with increasing size of parental sibships. This feature also provides the basis for a new theory for the dissemination of the major mutant allele, deduced to have arisen 2700–5000 years ago, in accordance

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

    PubMed

    Chandra, Amaresh; Grisham, Michael P; Pan, Yong-Bao

    2014-06-01

    Though sugarcane cultivars (Saccharum spp. hybrids) are complex aneupolyploid hybrids, genetic evaluation and tracking of clone- or cultivar-specific alleles become possible through capillary electrophoresis (CE) using fluorescence-labeled SSR markers. Twenty-four sugarcane cultivars, 12 each from India and the USA, were genetically assessed using 21 fluorescence-labeled polymorphic SSR markers. These markers primed the amplification of 213 alleles. Of these alleles, 161 were common to both Indian and US cultivars, 25 were specific to the Indian cultivars, and 27 were observed only in the US cultivars. Only 10 alleles were monomorphic. A high level of heterozygosity was observed in both Indian (82.4%) and US (91.1%) cultivars resulting in average polymorphism information content (PIC) values of 0.66 and 0.77 and marker index (MI) values of 5.07 and 5.58, respectively. Pearson correlation between PIC and MI was significant in both sets of cultivars (r = 0.58 and 0.69). UPGMA clustering separated cultivars into three distinct clusters at 59% homology level. These results propose the potential utility of six Indian cultivar-specific SSR alleles (mSSCIR3_182, SMC486CG_229, SMC36BUQ_125, mSSCIR74_216, SMC334BS_154, and mSSCIR43_238) in sugarcane breeding, vis a vis transporting CE-based evaluation in clone or variety identity testing, cross fidelity assessments, and genetic relatedness among species of the genus Saccharum and related genera. PMID:25247737

  12. Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y.

    PubMed

    Wilde, Sandra; Timpson, Adrian; Kirsanow, Karola; Kaiser, Elke; Kayser, Manfred; Unterländer, Martina; Hollfelder, Nina; Potekhina, Inna D; Schier, Wolfram; Thomas, Mark G; Burger, Joachim

    2014-04-01

    Pigmentation is a polygenic trait encompassing some of the most visible phenotypic variation observed in humans. Here we present direct estimates of selection acting on functional alleles in three key genes known to be involved in human pigmentation pathways--HERC2, SLC45A2, and TYR--using allele frequency estimates from Eneolithic, Bronze Age, and modern Eastern European samples and forward simulations. Neutrality was overwhelmingly rejected for all alleles studied, with point estimates of selection ranging from around 2-10% per generation. Our results provide direct evidence that strong selection favoring lighter skin, hair, and eye pigmentation has been operating in European populations over the last 5,000 y. PMID:24616518

  13. Direct evidence for positive selection of skin, hair, and eye pigmentation in Europeans during the last 5,000 y

    PubMed Central

    Wilde, Sandra; Timpson, Adrian; Kirsanow, Karola; Kaiser, Elke; Kayser, Manfred; Unterländer, Martina; Hollfelder, Nina; Potekhina, Inna D.; Schier, Wolfram; Thomas, Mark G.; Burger, Joachim

    2014-01-01

    Pigmentation is a polygenic trait encompassing some of the most visible phenotypic variation observed in humans. Here we present direct estimates of selection acting on functional alleles in three key genes known to be involved in human pigmentation pathways—HERC2, SLC45A2, and TYR—using allele frequency estimates from Eneolithic, Bronze Age, and modern Eastern European samples and forward simulations. Neutrality was overwhelmingly rejected for all alleles studied, with point estimates of selection ranging from around 2–10% per generation. Our results provide direct evidence that strong selection favoring lighter skin, hair, and eye pigmentation has been operating in European populations over the last 5,000 y. PMID:24616518

  14. NUMBER OF SEX ALLELES IN A SAMPLE OF HONEYBEE COLONIES Jean-Marie CORNUET Franck ARIES

    E-print Network

    Paris-Sud XI, Université de

    NUMBER OF SEX ALLELES IN A SAMPLE OF HONEYBEE COLONIES Jean-Marie CORNUET Franck ARIES Station of bree- ding work, this paper gives the theoretical distribution of the number of sex alleles in a sample the factors interfering with this trait, there is the possible identity of sex alleles of the workers' parents

  15. Network algorithm for the exact test of HardyWeinberg proportion for multiple alleles

    E-print Network

    Yamamoto, Hirosuke

    as a basis for genetic inference (see, for example, Crow, 1988). This law states that in a large random are constant from generation to generation and that there is a simple relationship between the allele number of alleles and Emith (1980) used Levene's distribution for the case of two alleles in his

  16. Survival and Growth of Subyearling Steelhead Homozygous for Alternative Alleles at the Dipeptidase Locus

    Microsoft Academic Search

    G. L. Chandler; T. C. Bjornn

    1989-01-01

    Juvenile steelhead Oncorhynchus mykiss (formerly Salmo gairdneri) that were homozygous for two alternative alleles at the dipeptidase locus were released into stream sections of the Palouse River drainage, Idaho, to test the neutrality of the alleles with respect to survival or growth. After 4 months in the stream sections, juveniles homozygous for either of the two major alleles did not

  17. VNTR allele frequency distributions under the stepwise mutation model: A computer simulation approach

    Microsoft Academic Search

    Mark D. Shriver; Li Jin; Ranajit Chakraborty; Eric Boerwinkle

    1993-01-01

    Variable numbers of tandem repeats (VNTRs) are a class of highly informative and widely dispersed genetic markers. Despite their wide application in biological science, little is known about their mutational mechanisms or population dynamics. The objective of this work was to investigate four summary measures of VNTR allele frequency distributions: number of alleles, number of modes, range in allele size,

  18. A Quasi-equilibrium theory of the distribution of rare alleles in a subdivided population

    Microsoft Academic Search

    N H Barton; M Slatkin

    1986-01-01

    The conditional average frequency of rare alleles has been shown in simulations to provide a simple and robust estimator of the number of individuals exchanged between local populations in an island model (Nm). This statistic is defined as the average frequency of an allele in those samples in which the allele is present. Here, we show that the conditional average

  19. Identification of New World monkey MHC-DRB alleles using PCR, DGGE and direct sequencing

    Microsoft Academic Search

    Simon A. Middleton; Gustl Anzenberger; Leslie A. Knapp

    2004-01-01

    Identification of New World monkey MHC-DRB alleles has previously relied upon labor-intensive cloning and sequencing techniques. Here we describe a rapid and unambiguous way to distinguish DRB alleles in New World monkeys using the polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE), and direct sequencing. The highly variable second exon of New World monkey DRB alleles was amplified using

  20. Prediction of bone density from vitamin D receptor alleles

    Microsoft Academic Search

    Nigel A. Morrison; Jian Cheng Qi; Akifumi Tokita; Paul J. Kelly; Linda Crofts; Tuan V. Nguyen; Philip N. Sambrook; John A. Eisman

    1994-01-01

    BONE density achieved in early adulthood is the major determinant of risk of osteoporotic fracture. Up to 60% of women1,2 suffer osteoporotic fractures as a result of low bone density2, which is under strong genetic control3-6 acting through effects on bone turnover7,8. Here we show that common allelic variants in the gene encoding the vitamin D receptor9 can be used

  1. The Friedreich ataxia GAA triplet repeat: premutation and normal alleles

    Microsoft Academic Search

    Laura Montermini; Eva Andermann; Margaret Labuda; Andrea Richter; Massimo Pandolfo; Luigi Pianese; Luisa Iodice; Gerardina Farina; Antonella Monticelli; Mimmo Turano; Alessandro Filla; Sergio Cocozza; Québec Montréal

    1997-01-01

    The most common mutation causing Friedreich ataxia (FRDA), an autosomal recessive neurodegenerative disease, is the hyperexpansion of a polymorphic GAA triplet repeat localized within an Alu sequence (GAA-Alu) in the first intron of the frataxin (X25) gene. GAA-Alu belongs to the AluSx subfamily and contains several polymorphisms in strong linkage disequili- brium either with a subgroup of normal alleles, or

  2. TETRASOMIC SEGREGATION FOR MULTIPLE ALLELES IN ALFALFA1

    Microsoft Academic Search

    CARLOS F. QUIROSZ

    Evidence of tetrasomic inheritance in alfalfa, Medicago sativa L. and M. falcata L., for multiple codominant alleles at three isozymic loci is reported in this study. The locus Prx-I governing anodal peroxidase and the loci Lap-I and Lap2 governing anodal leucine-aminopeptidase were studied by starch gel electrophoresis in seedling root tissue or seeds. The progenies from several di-, tri- or

  3. Teratogenic Alleles in Autism and Other Neurodevelopmental Disorders

    Microsoft Academic Search

    William G. Johnson; Madhura Sreenath; Steven Buyske; Edward S. Stenroos

    \\u000a Genes for neurodevelopmental disorders have proven difficult to find. In the case of autism, even though a number of genes\\u000a associated with the disorder have been identified, the cause of the disorder is far from clear. We discuss here a new category\\u000a of genetic contribution to human disorders, i.e., gene variants (alleles) that act in mothers during pregnancy to contribute

  4. CHARACTERIZATION AND EVALUATION OF MICROSATELLITE LOCI IN EUROPEAN HAZELNUT (CORYLUS AVELLANA L.) AND THEIR TRANSFERABILITY TO OTHER CORYLUS SPECIES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this work, 18 microsatellite loci were developed in the European hazelnut (Corylus avellana L.) using three enriched genomic libraries. They were evaluated on a set of 20 accessions of this species on the basis of number of alleles (mean: 7.1), expected heterozygosity (mean: 0.67), power of discr...

  5. Paternal alleles enhance female reproductive success in tropical pythons.

    PubMed

    Madsen, Thomas; Ujvari, Beata; Olsson, Mats; Shine, Richard

    2005-05-01

    The conventional view that female reproductive success is unlikely to benefit from multiple mating has come under strong challenge in recent years. In the present study, we demonstrate that the time wild-caught reproductive female water pythons (Liasis fuscus) spent in the laboratory prior to oviposition affected both hatching success and the number of male microsatellite alleles detected in the broods. A negative correlation between time in captivity and number of male alleles observed in the broods suggests that reduced hatching success was most likely not caused by environmental factors such as non-optimal temperatures, but rather by restricted mating opportunities. Maternal nutritional status and mean hatchling mass did not affect brood viability. However, our results revealed a positive correlation between number of male microsatellite alleles observed in the broods and hatching success, suggesting that increased paternal genetic variability enhanced female reproductive success. As microsatellite loci are unlikely to be direct targets of selection, we suggest that variability at these loci may cosegregate with other polymorphic genes directly linked to fitness. PMID:15836649

  6. Allelic variant in CTLA4 alters T cell phosphorylation patterns

    PubMed Central

    Maier, Lisa M.; Anderson, David E.; De Jager, Philip L.; Wicker, Linda S.; Hafler, David A.

    2007-01-01

    Little is known regarding the functional effects of common autoimmune susceptibility variants on human immune cells. The SNP CT60 (rs3087243; A/G) located in the 3? UTR of the CTLA4 gene has been associated with autoimmune diseases. We examined a cohort of healthy individuals stratified by genotypes at CTLA4 to gain insight into the functional effects of allelic variation on T cell signaling. Using phospho-site-specific mAbs, we tested the hypothesis that the CT60 genotype at CTLA4 is associated with altered T cell antigen receptor (TCR) signaling in naive and/or memory T cells. By normalizing for the extent of the initial TCR signaling event at CD3?, we observed that the relative responsiveness to TCR stimulation as assessed by phosphorylation levels of downstream signaling molecules was altered in naive (CD4+CD45RAhigh) and memory (CD4+CD45RAlow) T cells obtained from individuals with the disease-susceptibility allele at CTLA4. Thus, allelic variation associated with autoimmune disease can alter the signaling threshold of CD4+ T cells. These experiments provide a rational approach for the dissection of T cell-susceptibility genes in autoimmune diseases. PMID:18000051

  7. Allele-specific tumor spectrum in Pten knockin mice

    PubMed Central

    Wang, Hui; Karikomi, Matt; Naidu, Shan; Rajmohan, Ravi; Caserta, Enrico; Chen, Hui-Zi; Rawahneh, Maysoon; Moffitt, Julie; Stephens, Julie A.; Fernandez, Soledad A.; Weinstein, Michael; Wang, Danxin; Sadee, Wolfgang; La Perle, Krista; Stromberg, Paul; Rosol, Thomas J.; Eng, Charis; Ostrowski, Michael C.; Leone, Gustavo

    2010-01-01

    Germline mutations in the tumor suppressor gene PTEN (phosphatase and tensin homology deleted on chromosome 10) cause Cowden and Bannayan–Riley–Ruvalcaba (BRR) syndromes, two dominantly inherited disorders characterized by mental retardation, multiple hamartomas, and variable cancer risk. Here, we modeled three sentinel mutant alleles of PTEN identified in patients with Cowden syndrome and show that the nonsense Pten?4–5 and missense PtenC124R and PtenG129E alleles lacking lipid phosphatase activity cause similar developmental abnormalities but distinct tumor spectra with varying severity and age of onset. Allele-specific differences may be accounted for by loss of function for Pten?4–5, hypomorphic function for PtenC124R, and gain of function for PtenG129E. These data demonstrate that the variable tumor phenotypes observed in patients with Cowden and BRR syndromes can be attributed to specific mutations in PTEN that alter protein function through distinct mechanisms. PMID:20194734

  8. Allele-specific tumor spectrum in pten knockin mice.

    PubMed

    Wang, Hui; Karikomi, Matt; Naidu, Shan; Rajmohan, Ravi; Caserta, Enrico; Chen, Hui-Zi; Rawahneh, Maysoon; Moffitt, Julie; Stephens, Julie A; Fernandez, Soledad A; Weinstein, Michael; Wang, Danxin; Sadee, Wolfgang; La Perle, Krista; Stromberg, Paul; Rosol, Thomas J; Eng, Charis; Ostrowski, Michael C; Leone, Gustavo

    2010-03-16

    Germline mutations in the tumor suppressor gene PTEN (phosphatase and tensin homology deleted on chromosome 10) cause Cowden and Bannayan-Riley-Ruvalcaba (BRR) syndromes, two dominantly inherited disorders characterized by mental retardation, multiple hamartomas, and variable cancer risk. Here, we modeled three sentinel mutant alleles of PTEN identified in patients with Cowden syndrome and show that the nonsense Pten(4-5) and missense Pten(C124R) and Pten(G129E) alleles lacking lipid phosphatase activity cause similar developmental abnormalities but distinct tumor spectra with varying severity and age of onset. Allele-specific differences may be accounted for by loss of function for Pten(4-5), hypomorphic function for Pten(C124R), and gain of function for Pten(G129E). These data demonstrate that the variable tumor phenotypes observed in patients with Cowden and BRR syndromes can be attributed to specific mutations in PTEN that alter protein function through distinct mechanisms. PMID:20194734

  9. Pollution-tolerant allele in fingernail clams (Musculium transversum).

    PubMed

    Sloss, B L; Romano, M A; Anderson, R V

    1998-08-01

    For nearly 50 years, the fingernail clam (Musculium transversum) was believed to be virtually eliminated from the Illinois River. In 1991, workers began finding substantial populations of M. transversum in the Illinois River including several beds in and around the highly polluted Chicago Sanitary District. In order to determine if populations of M. transversum from polluted sites exhibited any genetic response to the high levels of toxins and to examine the genetic structure of several populations of M. transversum for any changes due to the population crash, starch-gel electrophoresis was performed on M. transversum from three Illinois River localities and four Mississippi River basin locations. The sampled populations produced an inbreeding coefficient (FIS) of 0.929, indicating that the populations were highly inbred. The results of a suspected founder effect due to a bottleneck was suggested by an FST = 0.442. The isozyme Glucose-6-phosphate isomerase-2 (Gpi-2) produced allelic frequency patterns that were consistent with expected patterns of a pollution-tolerant allele. Polluted sites exhibited elevated frequencies of Gpi-2(100) whereas nonpolluted sites exhibited elevated frequencies of Gpi-2(74). This frequency pattern suggested that natural selection was occurring in populations under severe toxic pressures, leading to an increase in the frequency of the allele Gpi-2(100). Therefore, Gpi-2(100) is a possible pollution-tolerant mutation in M. transversum. PMID:9680522

  10. A survey of FRAXE allele sizes in three populations

    SciTech Connect

    Zhong, N.; Ju, W.; Curley, D. [New York State Institute for Basic Research for Developmental Disabilities, Staten Island, NY (United States)] [and others] [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.

  11. Mapping a disease locus by allelic?association

    PubMed Central

    Collins, A.; Morton, N. E.

    1998-01-01

    Allelic association provides a means to map disease genes that, in a dense map of polymorphic markers, has considerably higher resolution than linkage methods. We describe here a composite likelihood estimate of location for a disease gene against a high-resolution marker map by using allele frequencies at linked loci. Data may be family-based, as in the transmission disequilibrium test, or from a case-control study. ?2 tests, logarithm of odds, standard errors, and information weights are provided. The method is illustrated by analysis of published cystic fibrosis haplotypes, in which ?F508 is more accurately localized than by other association studies. This differs from current approaches by adopting a more general Malecot model for isolation by distance, where distance here is between marker and disease locus, allowance for errors in the map and model, and freedom from assumptions about demography, systematic pressures, and the ratio of physical to genetic distance. When these assumptions are introduced the number of generations since the original mutation may be estimated, but this is not required to determine location and its standard error, so that evidence from allelic association may be efficiently combined with linkage evidence to identify a region for positional cloning of a disease gene. PMID:9465087

  12. Identification of New World monkey MHC-DRB alleles using PCR, DGGE and direct sequencing.

    PubMed

    Middleton, Simon A; Anzenberger, Gustl; Knapp, Leslie A

    2004-02-01

    Identification of New World monkey MHC-DRB alleles has previously relied upon labor-intensive cloning and sequencing techniques. Here we describe a rapid and unambiguous way to distinguish DRB alleles in New World monkeys using the polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGGE), and direct sequencing. The highly variable second exon of New World monkey DRB alleles was amplified using generic DRB primers and alleles were separated by DGGE. DNA was then reamplified from plugs removed from the gel and alleles were determined using fluorescent-based sequencing. The validity of this typing procedure was confirmed by the identification of all DRB alleles previously characterized by cloning and sequencing techniques from an individual cotton-top tamarin. Importantly, our analysis revealed DRB alleles not previously identified in this reference animal. Following validation of our technique, the protocol was employed for the characterization of MHC-DRB alleles in four other species of New World monkey: the pygmy marmoset, white-faced saki monkey, long-haired spider monkey and owl monkey. Using this technique, we identified five alleles from the cotton-top tamarin, five alleles from the owl monkey, three alleles from the long-haired spider monkey, three alleles from the white-faced saki monkey and two alleles from the pygmy marmoset. On the basis of phylogenetic tree analyses, 13 new DRB alleles were assigned to eight different MHC-DRB lineages. Whereas traditional DRB typing via cloning and sequencing provides limited information, our new technique provides a simple and relatively rapid way of identifying New World monkey MHC-DRB alleles. PMID:14714152

  13. HLA-B*40 Allele Plays a Role in the Development of Acute Leukemia in Mexican Population: A Case-Control Study

    PubMed Central

    Fernández-Torres, Javier; Flores-Jiménez, Denhi; Arroyo-Pérez, Antonio; Granados, Julio; López-Reyes, Alberto

    2013-01-01

    Among oncohematological diseases, acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) are characterized by the uncontrolled production and accumulation of blasts that can lead to death. Although the physiopathology of these diseases is multifactorial, a genetic factor seems to be at play. Several studies worldwide have shown association of ALL and AML with several alleles of the major histocompatibility complex (MHC). Objective. To determine gene frequencies of HLA-B alleles in Mexicans (individuals with Native American genetic background admixed with European descent) with ALL and AML. Methods. We compared the HLA-B alleles in 213 patients with ALL and 85 patients with AML to those present in 731 umbilical cord blood (UCB) samples as a control group; this was done by means of the PCR-SSP technique. Results. We found an increased frequency of the HLA-B*40 allele in ALL patients as compared to the control group (14.5% versus 9.84%, P = 0.003, OR = 1.67); this was particularly evident in a subgroup of young (less than 18?years old) ALL patients (P = 0.002, OR = 1.76); likewise, a decreased frequency of HLA-B*40 allele in AML patients was observed as compared to the control group (4.70% versus 9.84%, P = 0.02, OR = 0.42). Conclusions. These results might suggest opposing effects of the HLA-B*40 in the genetic susceptibility to develop ALL or AML and offer the possibility to study further the molecular mechanisms of cell differentiation within the bone marrow lineage. PMID:24364037

  14. Autoantibodies, autoimmune risk alleles and clinical associations in rheumatoid arthritis cases and non-RA controls in the electronic medical records

    PubMed Central

    Liao, Katherine P.; Kurreeman, Fina; Li, Gang; Duclos, Grant; Murphy, Shawn; Raul Guzman, P; Cai, Tianxi; Gupta, Namrata; Gainer, Vivian; Schur, Peter; Cui, Jing; Denny, Joshua C.; Szolovits, Peter; Churchill, Susanne; Kohane, Isaac; Karlson, Elizabeth W.; Plenge, Robert M.

    2012-01-01

    Objectives The significance of non-RA autoantibodies in patients with rheumatoid arthritis (RA) is unclear. We studied associations between autoimmune risk alleles and autoantibodies in RA cases and non-RA controls, and autoantibodies and clinical diagnoses from the electronic medical records (EMR). Methods We studied 1,290 RA cases and 1,236 non-RA controls of European genetic ancestry from the EMR from two large academic centers. We measured antibodies to citrullinated peptides (ACPA), anti-nuclear antibodies (ANA), antibodies to tissue transglutaminase (anti-tTG), antibodies to thyroid peroxidase (anti-TPO). We genotyped subjects for autoimmune risk alleles, and studied the association between number of autoimmune risk alleles and number of types of autoantibodies present. We conducted a phenome-wide association study (PheWAS) to study potential associations between autoantibodies and clinical diagnoses among RA cases and controls. Results Mean age was 60.7 in RA and 64.6 years in controls, and both were 79% female. The prevalence of ACPA and ANA was higher in RA cases compared to controls (p<0.0001, both); we observed no difference in anti-TPO and anti-tTG. Carriage of higher numbers of autoimmune risk alleles was associated with increasing types of autoantibodies in RA cases (p=4.4x10?6) and controls (p=0.002). From the PheWAS, ANA was significantly associated with Sjogren’s/siccain RA cases. Conclusion The increased frequency of autoantibodies in RA cases and controls was associated with the number of autoimmune risk alleles carried by an individual. PheWAS analyses within the EMR linked to blood samples provide a novel method to test for the clinical significance of biomarkers in disease. PMID:23233247

  15. MICA and MICB microsatellite alleles in HLA extended haplotypes.

    PubMed

    Bolognesi, E; Dalfonso, S; Rolando, V; Fasano, M E; Praticò, L; Momigliano-Richiardi, P

    2001-10-01

    The present study is a contribution to the definition of the linkage disequilibrium relationship of MICA and MICB with adjacent loci and to the characterization of extended HLA haplotypes. These issues are of importance for the identification of disease associations and for a better definition of donor-recipient compatibility in bone-marrow grafts through the typing of haplospecific markers. The distribution of the five alleles of MICA and the 13 alleles of MICB microsatellites, located, respectively, in MICA transmembrane exon 5 and in MICB intron 1, was examined in 133 healthy Italian individuals previously typed for HLA class I, class II and complement loci and for the TNFa microsatellite. The MICB microsatellite was also analysed in 49 HTCLs for which MICA typing was already available. Very strong linkage disequilibria with HLA-B and TNFa were detected in the Italian population for both MICA and MICB microsatellite alleles, in spite of the high mutability rate of the larger MICB alleles. Some strong associations were also detected between MICB and DRB1. The strongest associations (P < 0.001, D' > 0.7) were those of MICA-A4 with HLA-B18, B27 and TNFa1, MICA-A5 with HLA-B35, B61 and B62, MICA-A5.1 with HLA-B7, B8, B13, B63 and MICB-CA24, MICA-A6 with HLA-B51, MICA-A9 with HLA-B39, B57 and TNFa2, MICB-CA14 with HLA-B14, B27 and TNFa1, MICB-CA15 with HLA-B52, TNFa4 and TNFa13, MICB-CA17 with HLA-B7 and TNFa11, MICB-CA18 with HLA-B13 and TNFa7, MICB-CA22 with HLA-B57, and MICB-CA24 with HLA-B8 and TNFa2. From pairwise associations in the random panel and results for the homozygous cell lines it was possible to deduce the MICA and MICB microsatellite alleles present in many of the well-known Caucasoid extended haplotypes. PMID:11881819

  16. A family with two female compound heterozygous for the FMR1 premutation alleles

    PubMed Central

    Basuta, Kirin; Lozano, Reymundo; Schneider, Andrea; Yrigollen, Carolyn M.; Hessl, David; Hagerman, Randi J.; Tassone, Flora

    2014-01-01

    Premutation alleles (55-200 CGG repeats) of the fragile X mental retardation (FMR1) gene have been linked to various types of clinical involvement ranging from mood and anxiety disorders to immunological disorders and executive function deficits. Carrier females typically have a premutation allele and a normal allele (<55 CGG repeats). Although rare, 7 cases of females that carry two expanded alleles (compound heterozygous premutation) have been reported. Here we report on four members of a family including two compound heterozygous premutation sisters with similar CGG allele sizes, affected with different levels of clinical severity. PMID:23786467

  17. [Double mutant alleles in the EXT1 gene not previously reported in a teenager with hereditary multiple exostoses].

    PubMed

    Cammarata-Scalisi, Francisco; Cozar, Mónica; Grinberg, Daniel; Balcells, Susana; Asteggiano, Carla G; Martínez-Domenech, Gustavo; Bracho, Ana; Sánchez, Yanira; Stock, Frances; Delgado-Luengo, Wilmer; Zara-Chirinos, Carmen; Chacín, José Antonio

    2015-04-01

    Hereditary forms of multiple exostoses, now called EXT1/EXT2-CDG within Congenital Disorders of Glycosylation, are the most common benign bone tumors in humans and clinical description consists of the formation of several cartilage-capped bone tumors, usually benign and localized in the juxta-epiphyseal region of long bones, although wide body dissemination in severe cases is not uncommon. Onset of the disease is variable ranging from 2-3 years up to 13-15 years with an estimated incidence ranging from 1/18,000 to 1/50,000 cases in European countries. We present a double mutant alleles in the EXT1 gene not previously reported in a teenager and her family with hereditary multiple exostoses. PMID:25727835

  18. Expression and loss of alleles in cultured mouse embryonic fibroblasts and stem cells carrying allelic fluorescent protein genes

    PubMed Central

    Larson, Jon S; Yin, Moying; Fischer, Jared M; Stringer, Saundra L; Stringer, James R

    2006-01-01

    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 influencing expression from allelic genes. Similar approaches will allow these phenomena to be studied in tissues. PMID:17042952

  19. Immunogenicity of Single versus Mixed Allele Vaccines of Plasmodium vivax Duffy Binding Protein Region II

    PubMed Central

    Ntumngia, Francis B.; Schloegel, Jesse; McHenry, Amy M.; Barnes, Samantha J.; George, Miriam T.; Kennedy, Sandra; Adams, John H.

    2015-01-01

    The Duffy Binding protein (DBP) of Plasmodium vivax is vital for host erythrocyte invasion. DBP region II (DBPII) contains critical residues for receptor recognition and anti-DBPII antibodies have been shown to inhibit erythrocyte binding and invasion, thereby making the molecule an attractive vaccine candidate against P. vivax blood stages. Similar to other blood-stage antigens, allelic variation within the DBPII and associated strain-specific immunity is a major challenge for development of a broadly effective vaccine against P. vivax malaria. We hypothesized that immunization with a vaccine composed of multiple DBP alleles or a modified epitope DBP (DEKnull) will be more effective in producing a broadly reactive and inhibitory antibody response to diverse DBPII alleles than a single allele vaccine. In this study, we compared single, naturally occurring DBPII allele immunizations (Sal1, 7.18, P) and DEKnull with a combination of (Sal1, 7.18, P) alleles. Quantitative analysis by ELISA demonstrated that the multiple allele vaccine tend to be more immunogenic than any of the single allele vaccines when tested for reactivity against a panel of DBPII allelic variants whereas DEKnull was less immunogenic than the mixed-allele vaccine but similar in reactivity to the single allele vaccines. Further analysis for functional efficacy by in vitro erythrocyte-binding inhibition assays demonstrated that the multiple allele immunization produced a stronger strain-neutralizing response than the other vaccination strategies even though inhibition remained biased toward some alleles. Overall, there was no correlation between antibody titer and functional inhibition. These data suggest that a multiple allele vaccine may enhance immunogenicity of a DBPII vaccine but further investigation is required to optimize this vaccine strategy to achieve broader coverage against global P. vivax strains. PMID:23916294

  20. Towards European urinalysis guidelines

    Microsoft Academic Search

    Timo T Kouri; Vanya A Gant; Giovanni B Fogazzi; Walter Hofmann; Hans O Hallander; Walter G Guder

    2000-01-01

    Improved standardized performance is needed because urinalysis continues to be one of the most frequently requested laboratory tests. Since 1997, the European Confederation of Laboratory Medicine (ECLM) has been supporting an interdisciplinary project aiming to produce European urinalysis guidelines. More than seventy clinical chemists, microbiologists and ward-based clinicians, as well as representatives of manufacturers are taking part. These guidelines aim

  1. European auxiliary propulsion, 1972

    NASA Technical Reports Server (NTRS)

    Holcomb, L. B.

    1972-01-01

    The chemical and electric auxiliary propulsion technology of the United Kingdom, France, and West Germany is discussed in detail, and the propulsion technology achievements of Italy, India, Japan, and Russia are reviewed. A comparison is presented of Shell 405 catalyst and a European spontaneous hydrazine catalyst called CNESRO I. Finally, conclusions are drawn regarding future trends in European auxiliary propulsion technology development.

  2. European Studies Undergraduate Studies

    E-print Network

    Royal Holloway, University of London

    and humanities. Our 8,500 students work with internationally renowned scholars in 20 academic departments for university study. Campus life revolves around the Students' Union, which runs over 100 societies and sports clubs, and we are recognised as London's best sporting college. #12;3European Studies European Studies

  3. European Biodiesel Board

    NSDL National Science Digital Library

    The European Biodiesel Board (EBB), a nonprofit organization, works to promote biodiesel use in the European Union (EU). The EBB website offers downloadable articles regarding biodiesel in the EU, downloadable reports from EU member states, a list of upcoming events, an EBB email information service, and basic statistical tables representing biodiesel production by country.

  4. European logistics beyond 2000

    Microsoft Academic Search

    Tage Skjoett-Larsen

    2000-01-01

    European companies are facing new challenges in the next millennium. Seven trends in international logistics are outlined. These are supply chain management, globalisation of the supply chain, virtual enterprises, e-business, green logistics, strategic partnerships and new management principles. The implications for European companies are discussed and illustrated by examples from advanced companies. Asserts that it is employees and not the

  5. European Commission: Public Opinion

    NSDL National Science Digital Library

    Some Scout Report readers might be wondering "How do Europeans feel about the euro?" or even "What do Europeans think about the effectiveness of different energy policies?" All of the answers to these questions (and many more) can be found on the European Commission's Public Opinion site. The site contains the results from surveys conducted with Europeans on their attitudes towards alcohol, the role of the European Union in formulating security policy, and a number of other topics. Visitors will definitely want to make their way to the Eurobarometer Interactive Search System, which allows them to choose a subject or country which is of interest to them. Visitors should also take a look at their very fine "Qualitative Studies" section, which includes reports such as "The Future of Europe" and "Integrating Gender Mainstreaming into Employment Policies". Needless to say, summaries of the reports are available in a wide range of languages, including Dutch, German, Italian, and French.

  6. Mapping rare and common causal alleles for complex human diseases

    PubMed Central

    Raychaudhuri, Soumya

    2011-01-01

    Advances in genotyping and sequencing technologies have revolutionized the genetics of complex disease by locating rare and common variants that influence an individual’s risk for diseases, such as diabetes, cancers, and psychiatric disorders. However, to capitalize on this data for prevention and therapies requires the identification of causal alleles and a mechanistic understanding for how these variants contribute to the disease. After discussing the strategies currently used to map variants for complex diseases, this Primer explores how variants may be prioritized for follow-up functional studies and the challenges and approaches for assessing the contributions of rare and common variants to disease phenotypes. PMID:21962507

  7. CONSULTANT REPORT EUROPEAN RENEWABLE DISTRIBUTED

    E-print Network

    CONSULTANT REPORT EUROPEAN RENEWABLE DISTRIBUTED distributed electricity generation. As reflected in the California Energy Commission's previous how certain European countries integrate large quantities of intermittent distributed

  8. Distribution of Mytilus taxa in European coastal areas as inferred from molecular markers

    NASA Astrophysics Data System (ADS)

    Kijewski, T.; ?mietanka, B.; Zbawicka, M.; Gosling, E.; Hummel, H.; Wenne, R.

    2011-02-01

    The genetic constitution of mussels ( Mytilus spp.) was studied by means of three nuclear (Me 15/16, EF-bis, ITS) and one mtDNA (ND2-COIII) marker on a large European scale. In addition to a sharp cline between Atlantic and Mediterranean M. galloprovincialis, we observed a clear genetic distinction between the Black Sea and Mediterranean populations and a higher incidence of M. trossulus than reported so far in northern European populations. The frequency of M. galloprovincialis nuclear alleles was high along the Iberian Peninsula and decreased abruptly along the French coasts with a high frequency of M. edulis alleles in the Bay of Biscay, The Netherlands, Germany, Iceland, Barents and White Seas, and with little evidence of introgression between the two taxa. M. trossulus alleles were observed in the Baltic Sea and Danish Straits as expected. In addition, occurrence of M. trossulus alleles in cold waters of Iceland, Barents Sea and White Sea is reported for the first time.

  9. Distribution of FMR-1 and associated microsatellite alleles in a normal Chinese population

    SciTech Connect

    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.

  10. Maize ARGOS1 (ZAR1) transgenic alleles increase hybrid maize yield

    PubMed Central

    Guo, Mei

    2014-01-01

    Crop improvement for yield and drought tolerance is challenging due to the complex genetic nature of these traits and environmental dependencies. This study reports that transgenic over-expression of Zea mays ARGOS1 (ZAR1) enhanced maize organ growth, grain yield, and drought-stress tolerance. The ZAR1 transgene exhibited environmental interactions, with yield increase under Temperate Dry and yield reduction under Temperate Humid or High Latitude environments. Native ZAR1 allele variation associated with drought-stress tolerance. Two founder alleles identified in the mid-maturity germplasm of North America now predominate in Pioneer’s modern breeding programme, and have distinct proteins, promoters and expression patterns. These two major alleles show heterotic group partitioning, with one predominant in Pioneer’s female and the other in the male heterotic groups, respectively. These two alleles also associate with favourable crop performance when heterozygous. Allele-specific transgene testing showed that, of the two alleles discussed here, each allele differed in their impact on yield and environmental interactions. Moreover, when transgenically stacked together the allelic pair showed yield and environmental performance advantages over either single allele, resembling heterosis effects. This work demonstrates differences in transgenic efficacy of native alleles and the differences reflect their association with hybrid breeding performance. PMID:24218327

  11. Investigating the allelic evolution of an imperfect microsatellite locus in the Hawaiian mushroom Rhodocollybia laulaha.

    PubMed

    Keirle, Matthew R; Avis, Peter G; Feldheim, Kevin A; Hemmes, Don E; Mueller, Gregory M

    2011-01-01

    The evolutionary mechanisms that give rise to microsatellite alleles remain poorly understood in general and are especially understudied for fungal microsatellite loci. The unusual G28 microsatellite locus was developed from the Hawaiian mushroom Rhodocollybia laulaha. Here, we employ a novel approach to test for allele size homoplasy and examine competing mechanistic models of microsatellite evolution in the context of biogeographic expectations for this locus based on Hawaiian geologic history. Seven G28 alleles have been identified from a sampling of 153 individuals. The G28 locus is composed of a trinucleotide imperfect motif, which permits examination of the relationships between alleles and allows for detection of potential size homoplasy within the repetitive element. Alignment of G28 allele sequence data across multiple unrelated individuals suggests that alleles of like size are homologous within Hawaii. A variety of gap coding methods are explored in the inference of allele evolution. Length differences between alleles appear to be the result of polymerase slippage at multiple positions in the repetitive element, suggesting an intricate process of allelic evolution, which is not necessarily stepwise. Complex migration scenarios must be invoked to explain the current geographic distribution of alleles if their evolution was in fact sequential (from longest to shortest or from shortest to longest) as predicted by the "progression rule." PMID:21914665

  12. Characterization of 13 polymorphic microsatellite loci in the European pine marten Martes martes

    Microsoft Academic Search

    Chiara Natali; Elisa Banchi; Claudio Ciofi; Emiliano Manzo; Paola Bartolommei; Roberto Cozzolino

    2010-01-01

    A set of 13 polymorphic microsatellite markers were isolated and characterized from a genomic library enriched for dinucleotide\\u000a repeats in the European pine marten Martes martes. Microsatellite loci amplification was tested on a panel of 12 tissue samples and 9 distinct hair samples collected from\\u000a either road-killed or trapped animals in Tuscany, Italy. Allelic diversity was 6 and the number

  13. Genomic landscape of human allele-specific DNA methylation

    PubMed Central

    Fang, Fang; Hodges, Emily; Molaro, Antoine; Dean, Matthew; Hannon, Gregory J.; Smith, Andrew D.

    2012-01-01

    DNA methylation mediates imprinted gene expression by passing an epigenomic state across generations and differentially marking specific regulatory regions on maternal and paternal alleles. Imprinting has been tied to the evolution of the placenta in mammals and defects of imprinting have been associated with human diseases. Although recent advances in genome sequencing have revolutionized the study of DNA methylation, existing methylome data remain largely untapped in the study of imprinting. We present a statistical model to describe allele-specific methylation (ASM) in data from high-throughput short-read bisulfite sequencing. Simulation results indicate technical specifications of existing methylome data, such as read length and coverage, are sufficient for full-genome ASM profiling based on our model. We used our model to analyze methylomes for a diverse set of human cell types, including cultured and uncultured differentiated cells, embryonic stem cells and induced pluripotent stem cells. Regions of ASM identified most consistently across methylomes are tightly connected with known imprinted genes and precisely delineate the boundaries of several known imprinting control regions. Predicted regions of ASM common to multiple cell types frequently mark noncoding RNA promoters and represent promising starting points for targeted validation. More generally, our model provides the analytical complement to cutting-edge experimental technologies for surveying ASM in specific cell types and across species. PMID:22523239

  14. Characterization of ROP18 alleles in human toxoplasmosis.

    PubMed

    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. PMID:24177250

  15. The European Values Study

    NSDL National Science Digital Library

    Curious minds want to know: "What exactly do Europeans believe?" It's an important and interesting question, and the directors and researchers in charge of the European Values Study (EVS) have been looking into this subject since the early 1980s. Based in the Netherlands the EVS concerns itself with asking Europeans about religion and morality, politics, work and leisure, and relationships. On their homepage, visitors can learn about their work and view previous and current surveys. While visitors do not have access to the raw data on the site, they can look at the questionnaires and read publications based on this research.

  16. Allelic diversity at the DLA-88 locus in Golden Retriever and Boxer breeds is limited

    PubMed Central

    Ross, Peter; Buntzman, Adam S.; Vincent, Benjamin G.; Grover, Elise N.; Gojanovich, Gregory S.; Collins, Edward J.; Frelinger, Jeffrey A.; Hess, Paul R.

    2012-01-01

    In the dog, previous analyses of major histocompatibility complex (MHC) class I genes suggest a single polymorphic locus, Dog Leukocyte Antigen (DLA)-88. While 51 alleles have been reported, estimates of prevalence have not been made. We hypothesized that, within a breed, DLA-88 diversity would be restricted, and one or more dominant alleles could be identified. Accordingly, we determined allele usage in 47 Golden Retrievers and 39 Boxers. In each population, 10 alleles were found; 4 were shared. Seven novel alleles were identified. DLA-88*05101 and *50801 predominated in Golden Retrievers, while most Boxers carried *03401. In these breeds DLA-88 polymorphisms are limited and largely non-overlapping. The finding of highly prevalent alleles fulfills an important prerequisite for studying canine CD8+ T-cell responses. PMID:22571293

  17. European Molecular Biology Laboratory

    E-print Network

    1973-01-01

    On 10 May an Agreement was signed at CERN setting up a new European Laboratory. It will be concerned with research in molecularbiology and will be located at Heidelberg in the Federal Republic of Germany.

  18. European Space Agency (ESA)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    An international organization whose task is `to provide for and to promote, for exclusively peaceful purposes, cooperation among European states in space research and technology and their space applications'....

  19. European Judicial Network

    NSDL National Science Digital Library

    2007-01-01

    As a part of the European Commission, the European Judicial Network is primarily concerned with providing information about community law, European law, and various aspects of civil and commercial law. The homepage is well-organized, and visitors can start by clicking on the topic page sections, which cover everything from bringing a case to court to alternative dispute resolutions. On the right-side of the homepage, visitors can click on the flags of member states to learn more about each nation's legal system. The site will certainly be of interest to those with a legal background, but the main stated objective of the site is "to make life easier for people facing litigation of whatever kind where there is a transnational element." Not surprisingly, all of this information is available in the twenty official languages of the European Union.

  20. Cuckoo parasitism and productivity in different magpie subpopulations predict frequencies of the 457bp allele: a mosaic of coevolution at a small geographic scale.

    PubMed

    Martín-Gálvez, David; Soler, Juan J; Martínez, Juan Gabriel; Krupa, Andrew P; Soler, Manuel; Burke, Terry

    2007-10-01

    The level of defense against great spotted cuckoo (Clamator glandarius) parasitism in different European populations of magpie (Pica pica) depends on selection pressures due to parasitism and gene flow between populations, which suggests the existence of coevolutionary hot spots within a European metapopulation. A mosaic of coevolution is theoretically possible at small geographical scales and with strong gene flow, because, among other reasons, plots may differ in productivity (i.e., reproductive success of hosts in the absence of parasitism) and defensive genotypes theoretically should be more common in plots of high productivity. Here, we tested this prediction by exploring the relationship between parasitism rate, level of defense against parasitism (estimated as both rejection rate and the frequency of the 457bp microsatellite allele associated with foreign egg rejection in magpies), and some variables related to the productivity (average laying date, clutch size, and number of hatchlings per nest) of magpies breeding in different subpopulations. We found that both estimates of defensive ability (egg rejection rate and frequency of the 457bp allele) covaried significantly with between-plot differences in probability of parasitism, laying date, and number of hatchlings per nest. Moreover, the parasitism rate was larger in more productive plots. These results confirm the existence of a mosaic of coevolution at a very local geographical scale, and the association between laying date and number of hatchlings with variables related to defensive ability and the selection pressure arising from parasitism supports the prediction of coevolutionary gradients in relation to host productivity. PMID:17711473

  1. Allelic Combinations of Promoter and Exon 2 in DQB1 in Dogs and Wolves

    Microsoft Academic Search

    Karin T. Berggren; Jennifer M. Seddon

    2008-01-01

    Polymorphism of PBRs of the major histocompatibility complex (MHC) genes is well recognized, but the polymorphism also extends\\u000a to proximal promoter regions. Examining DQB1 variability in dogs and wolves, we identified 7 promoter variants and 13 exon 2 alleles among 89 dogs, including a previously\\u000a unknown DQB1 exon 2 allele, and 8 promoter variants and 9 exon 2 alleles among

  2. Analysis of hopQ alleles in East Asian and Western strains of Helicobacter pylori

    Microsoft Academic Search

    Ping Cao; Kerry Jo Lee; Martin J. Blaser

    2005-01-01

    Helicobacter pylori hopQ (omp27) alleles exhibit a high level of genetic diversity, and certain hopQ genotypes have been associated with an increased risk for peptic ulcer disease. In this study, we analyzed hopQ alleles in H. pylori strains from East Asia and the United States. Phylogenetic analysis indicated the presence of two highly divergent families of hopQ alleles, without evidence

  3. Apolipoprotein E4 allele in a population-based study of early-onset Alzheimer's disease

    Microsoft Academic Search

    Duijn van C. M; Peter de Knijff; Marc Cruts; Anita Wehnert; Louis M. Havekes; Broeckhoven van C; A. Hofman

    1994-01-01

    Several studies have reported an association of the apolipoprotein E allele epsilon 4 (APOE*4) to familial and sporadic late-onset Alzheimer's disease (LOAD). Here we report on the relationship between APOE*4 and early-onset Alzheimer's disease (EOAD) in a Dutch population-based study. The frequency of the APOE*4 allele was 2.3 times higher among EOAD cases compared to controls. Among patients, the allele

  4. HLA-B typing by allele separation followed by direct sequencing.

    PubMed

    Eberle, M; Knapp, L A; Iwanaga, K K; Domanico, M J; Aiyer, K; Watkins, D I

    1997-04-01

    Due to the enormous allelic diversity of the HLA-B locus, it has been difficult to design an unambiguous molecular typing method for the alleles at this locus. Here we describe a technique for the direct sequencing of HLA-B alleles. Initially, HLA-B alleles were PCR-amplified after locus-specific reverse transcription of RNA. Alleles were then separated using denaturing gradient gel electrophoresis (DGGE), which separates DNA fragments based on their sequence composition. Amplification products were excised from the gel and eluted DNA was reamplified and directly sequenced. The derived sequences were aligned to a database of published HLA-B sequences, and an initial allele assignment was made. This approach was theoretically sufficient to type 92 of the 118 known HLA-B alleles. The majority of the remaining 26 alleles contain differences at the beginning of exon 2, a region outside the DGGE-separated PCR products. Therefore, we used heterozygous sequencing of this region to identify 19 of these 26 alleles, raising the resolution power to 111 alleles. Using this technique, we analyzed immortalized cell lines and blood samples from several different sources. Nine immortalized cell lines were obtained from the 10th International Histocompatibility Workshop (IHWS) and nine were derived from aboriginal peoples. Additionally, 25 blood samples were acquired from a panel of donors previously shown to be difficult to type using serological techniques. Altogether, using this new method of allele separation by DGGE followed by direct sequencing, we typed 52 different alleles from 57 individuals, covering 40 serological specificities. PMID:9151388

  5. Genetic diversity of French common wheat germplasm based on gliadin alleles

    Microsoft Academic Search

    E. V. Metakovsky; G. Branlard

    1998-01-01

    Analysis of gliadin electrophoretic (APAGE) patterns made it possible to identify 79 alleles at six Gli-1 and Gli-2 loci (from 9 to 18 per locus) and 173 gliadin genotypes in the 187 French common wheat cultivars considered. Six new alleles\\u000a were registered in the catalogue of gliadin alleles. The genetic diversity of French common wheats was found to be high

  6. APOE ?4 allele and CSF APOE on Cognition in HIV-Infected Subjects

    Microsoft Academic Search

    Marilou A. Andres; Ute Feger; Avindra Nath; Sody Munsaka; Caroline S. Jiang; Linda Chang

    The significance of the cerebrospinal fluid (CSF) Apolipoprotein E (APOE) level and whether it might have differential effects\\u000a on brain function due to the presence of APOE ?4 allele(s) in HIV-infected patients are unknown. However, APOE ?4 allele has been associated with greater incidence of HIV-associated dementia and accelerated progression of HIV infection.\\u000a Here, we show further evidence for the

  7. HLA-DR2-associated DRB1 and DRB5 alleles and haplotypes in Koreans

    Microsoft Academic Search

    Eun Young Song; Su Jin Kang; Young-Joon Lee; Myoung Hee Park

    2000-01-01

    There are considerable racial differences in the distribution of HLA-DR2-associated DRB1 and DRB5 alleles and the characteristics of linkage disequilibrium between these alleles. In this study, the frequencies of DR2-associated DRB1 and DRB5 alleles and related haplotypes were analyzed in 186 DR2-positive individuals out of 800 normal Koreans registered for unrelated bone marrow donors. HLA class I antigen typing was

  8. Four p67 alleles identified in South African Theileria parva field samples

    Microsoft Academic Search

    Kgomotso P. Sibeko; Dirk Geysen; Marinda C. Oosthuizen; Conrad A. Matthee; Milana Troskie; Frederick T. Potgieter; Jacobus A. W. Coetzer; Nicola E. Collins

    2010-01-01

    Previous studies characterizing the Theileria parva p67 gene in East Africa revealed two alleles. Cattle-derived isolates associated with East Coast fever (ECF) have a 129bp deletion in the central region of the p67 gene (allele 1), compared to buffalo-derived isolates with no deletion (allele 2). In South Africa, Corridor disease outbreaks occur if there is contact between infected buffalo and

  9. European PTTI report

    NASA Technical Reports Server (NTRS)

    Cordara, Franco; Grimaldi, Sabrina; Leschiutta, Sigfrido

    1994-01-01

    Time and frequency metrology in Europe presents some peculiar features in its three main components: research on clocks, comparisons and dissemination methods, and dissemination services. Apart from the usual activities of the national metrological laboratories, an increasing number of cooperation between the European countries are promoted inside some European organizations, such as the ECC, EFTA, EUROMET, and WECC. Cooperation between these organizations is covered. The present, evolving situation will be further influenced by the recent political changes in Eastern Europe.

  10. Archive of European Integration

    NSDL National Science Digital Library

    The creation of a so-called â??common marketâ? and throughout the European countries has taken decades, and this valuable scholarly resource created by a team of academics will be of great interest to anyone with a penchant for this subject. The idea for this archive of European Integration was devised by Phil Wilkin (who now serves as its editor), and over the years, his efforts have been aided by a team of other dedicated individuals. Simply put, the Archive of European Integration (AEI) is â??an electronic repository and archive for research materials on the topic of European integration and unification.â? As such, it is primarily concerned with collecting official European Community/European Union documents and certain independently-produced research materials. First-time visitors to the site can search the archive by six different methods, view a list of the latest additions, and also register at no charge for an account that will let them submit items to the archive. All told, the archive currently contains over 4800 documents ranging from working papers on topics such as the common agricultural policy as well as cultural policy.

  11. Allele specific expression in worker reproduction genes in the bumblebee Bombus terrestris

    PubMed Central

    Nathanael, Despina

    2015-01-01

    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.

  12. How-To-Do-It: Multiple Allelic Frequencies in Populations at Equilibrium: Algorithms and Applications.

    ERIC Educational Resources Information Center

    Nussbaum, Francis, Jr.

    1988-01-01

    Presents an algorithm for solving problems related to multiple allelic frequencies in populations at equilibrium. Considers sample problems and provides their solution using this tabular algorithm. (CW)

  13. Allele-specific enzymatic amplification of. beta. -globin genomic DNA for diagnosis of sickle cell anemia

    SciTech Connect

    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.

  14. The presence of FCGR2B promoter or transmembrane region variant alleles leads to reduced serum IL-6 levels in rheumatoid arthritis.

    PubMed

    Meister, Stefanie; Engelmann, Robby; Kneitz, Christian; Müller-Hilke, Brigitte

    2015-08-01

    The inhibitory Fc?RIIB plays an important role for the peripheral B cell tolerance and plasma cell homeostasis, and any malfunctioning is predicted to result in humoral autoimmunity. An association between rheumatoid arthritis (RA) and FCGR2B promoter and TM region variant alleles, both of which result in a reduced functionality, is only insufficiently elucidated. We here set out to investigate the impact of these variants on disease progression in European RA patients. One hundred and five ACPA-positive RA patients were genotyped for the FCGR2B -386G>C promoter and the 695T>C transmembrane region variants. Moreover, serum titers for IL-6, TNF?, CTX-1 and ACPAs were measured and peripheral blood T cell and B cell populations analyzed for expression of the activation markers CTLA-4 and CD86. The presence of an FCGR2B variant allele results in reduced serum IL-6, a trend toward later disease onset and reduced requirement for biological treatment, but does not seem to aggravate RA. Likewise, the presence of the TM region variant allele is associated with a lower activation state of the Tregs and of naïve and memory B cells. The observation of a malfunctioning Fc?RIIb not aggravating RA is counterintuitive at first. However, the etiology of RA is linked to inflammatory episodes, and the lack of B cell inhibition may support an accelerated antibody-mediated clearance of the disease initiating and perpetuating agents. It would thereby shorten inflammatory episodes, postpone the onset of disease and result in a less severe course of RA in carriers of FCGR2B variant alleles. PMID:25630523

  15. Maruyama's allelic age revised by whole-genome GEMA simulations.

    PubMed

    Qiu, Shuhao; Fedorov, Alexei

    2015-05-01

    In 1974, Takeo Maruyama deduced that neutral mutations should, on average, be older than deleterious or beneficial ones. This theory is based on the diffusion approximation for a branching process, which considers mutations independently of one another and not as multiple groups of interconnected mutations with strong linkage disequilibrium (haplotypes). However, mammalian genomes contain thousands of haplotypes, in which beneficial, neutral, and deleterious mutations are tightly linked to each other. This complex haplotype organization should not be ignored for estimation of allelic ages. We employed our GEMA computer simulation program for genome evolution to re-evaluate Maruyama's phenomenon in modeled populations that include haplotypes approximating real genomes. We determined that only under specific conditions (high recombination rates and abundance of neutral mutations), the deleterious and beneficial mutations are younger than neutral ones as predicted by Maruyama. Under other conditions, the ages of negative, neutral, and beneficial mutations were almost the same. PMID:25708667

  16. ALADYN – a spatially explicit, allelic model for simulating adaptive dynamics

    PubMed Central

    Schiffers, Katja H; Travis, Justin MJ

    2014-01-01

    ALADYN is a freely available cross-platform C++ modeling framework for stochastic simulation of joint allelic and demographic dynamics of spatially-structured populations. Juvenile survival is linked to the degree of match between an individual’s phenotype and the local phenotypic optimum. There is considerable flexibility provided for the demography of the considered species and the genetic architecture of the traits under selection. ALADYN facilitates the investigation of adaptive processes to spatially and/or temporally changing conditions and the resulting niche and range dynamics. To our knowledge ALADYN is so far the only model that allows a continuous resolution of individuals’ locations in a spatially explicit landscape together with the associated patterns of selection. PMID:25698848

  17. A measure of population subdivision based on microsatellite allele frequencies

    SciTech Connect

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

    1995-01-01

    Microsatellite loci, loci that vary in the number of repeats of a simple DNA sequence, are becoming commonly used in the analysis of natural populations. Microsatellite loci are often highly polymorphic and relatively easy to survey and hence offer the hope of greater understanding of population structure. The question is how to make the best use of allele frequencies at microsatellite loci. This paper, like the accompanying paper by Goldstein et al. (1995), discusses how information about the mutation process at microsatellite loci can suggest statistics that are more appropriate for the analysis of microsatellite loci than are existing statistics. In this paper, I will introduce a new statistic analogous to Wright`s (1951) F{sub ST} that can be used to estimate effective migration rates or times since population divergence. This statistic is closely related to the distance measures introduced by Goldstein et al. (1995). 15 refs., 15 figs., 1 tab.

  18. European Union Scandal

    NSDL National Science Digital Library

    Osmond, Andrew.

    This week's In the News examines the recent high-level corruption scandal in the European Union. Last Tuesday, the European Commission -- the executive body that initiates and implements EU legislation -- resigned en masse, plunging the supranational organization into unprecedented political chaos. All 20 commissioners, led by commission President Jacques Santer of Luxembourg, abdicated their positions the day after the release of a scathing report by the Committee of Independent Experts. The independent panel of experts, who were appointed by the European Parliament, had investigated allegations of bureaucratic malfeasance perpetrated by the European Commission. The committee's report collectively accused the commission of financial "fraud, mismanagement, and nepotism." In the wake of the incriminating report and subsequent resignations, EU foreign ministers are scrambling to find successors for the commissioners to placate the bewildered European citizenry and return to business as usual. This political upheaval happened at a crucial transitional time in the EU's 42-year history, undermining its credibility at a time when it plans to expand into eastern Europe. The current tumult occurred just three months after launching a new unified currency, seven weeks before the new Treaty of Amsterdam commences, and three months before the next European Parliamentary elections, which will determine the future composition of the EU's 626-member assembly. During the next two days, distracted leaders from all fifteen EU member states will meet in Berlin to discuss the reconstruction of the European Commission and formulate a seven-year budget for the entire EU, an organization with about 18,000 officials who administer nearly $100 billion annually. The eight resources discussed provide news, commentary, and analysis.

  19. Additive contribution of HLA class I alleles in the immune control of HIV-1 infection.

    PubMed

    Leslie, Alasdair; Matthews, Philippa C; Listgarten, Jennifer; Carlson, Jonathan M; Kadie, Carl; Ndung'u, Thumbi; Brander, Christian; Coovadia, Hoosen; Walker, Bruce D; Heckerman, David; Goulder, Philip J R

    2010-10-01

    Previous studies have identified a central role for HLA-B alleles in influencing control of HIV infection. An alternative possibility is that a small number of HLA-B alleles may have a very strong impact on HIV disease outcome, dominating the contribution of other HLA alleles. Here, we find that even following the exclusion of subjects expressing any of the HLA-B class I alleles (B*57, B*58, and B*18) identified to have the strongest influence on control, the dominant impact of HLA-B alleles on virus set point and absolute CD4 count variation remains significant. However, we also find that the influence of HLA on HIV control in this C-clade-infected cohort from South Africa extends beyond HLA-B as HLA-Cw type remains a significant predictor of virus and CD4 count following exclusion of the strongest HLA-B associations. Furthermore, there is evidence of interdependent protective effects of the HLA-Cw*0401-B*8101, HLA-Cw*1203-B*3910, and HLA-A*7401-B*5703 haplotypes that cannot be explained solely by linkage to a protective HLA-B allele. Analysis of individuals expressing both protective and detrimental alleles shows that even the strongest HLA alleles appear to have an additive rather than dominant effect on HIV control at the individual level. Finally, weak but significant frequency-dependent effects in this cohort can be detected only by looking at an individual's combined HLA allele frequencies. Taken together, these data suggest that although individual HLA alleles, particularly HLA-B, can have a strong impact, HIV control overall is likely to be influenced by the additive effect of some or all of the other HLA alleles present. PMID:20660184

  20. Genotypic and phenotypic analysis of the polymorphic thiopurine S-methyltransferase gene (TPMT) in a European population

    PubMed Central

    Spire-Vayron de la Moureyre, Catherine; Debuysere, Hervé; Mastain, Bruno; Vinner, Elizabeth; Marez, Delphine; Lo Guidice, Jean-Marc; Chevalier, Dany; Brique, Serge; Motte, Kokou; Colombel, Jean-Frédéric; Turck, Dominique; Noel, Christian; Flipo, René-Marc; Pol, Annie; Lhermitte, Michel; Lafitte, Jean-Jacques; Libersa, Christian; Broly, Franck

    1998-01-01

    Characterization of allelic variants of the TPMT gene (TPMT) responsible for changes in TPMT activity, and elucidation of the mechanism by which these alleles act, are required because of the clinical importance of this polymorphism for patients receiving thiopurine drugs.We defined the mutational and allelic spectrum of TPMT in a group of 191 Europeans. Using PCR–SSCP, we screened for mutation the entire coding sequence, the exon-intron boundaries, the promoter region and the 3?-flanking region of the gene. Six mutations were detected throughout the ten exons and seven TPMT alleles were characterized. Four of them, TPMT*2, *3A, *3C and *7, harbouring the known mutations, G238C, G460A, A719G or T681G, were nonfunctional and accounted for 0.5, 5.7, 0.8 and 0.3% of the allele totality, respectively.Within the promoter region, six alleles corresponding to a variable number of tandem repeats (VNTR), were identified. VNTR*V4 and *V5a which harbour four or five repeats of a 17–18?bp unit, were the most frequent (55% and 34%, respectively). The other VNTR alleles, having from five to eight repeats, were rarer.The TPMT phenotype was correctly predicted by genotyping for 87% of individuals. A clear negative correlation between the total number of repeats from both alleles and the TPMT activity level was observed, indicating that VNTRs contribute to interindividual variations of TPMT activity. Therefore, additional analysis of the promoter region of TPMT can improve the phenotype prediction rate by genotyping. PMID:9831928

  1. Investigating the relationship between FMR1 allele length and cognitive ability in children: a subtle effect of the normal allele range on the normal ability range?

    PubMed

    Loat, C S; Craig, G; Plomin, R; Craig, I W

    2006-09-01

    The FMR1 gene contains a trinucleotide repeat tract which can expand from a normal size of around 30 repeats to over 200 repeats, causing mental retardation (Fragile X Syndrome). Evidence suggests that premutation males (55-200 repeats) are susceptible to a late-onset tremor/ataxia syndrome and females to premature ovarian failure, and that intermediate alleles ( approximately 41-55 repeats) and premutations may be in excess in samples with special educational needs. We explored the relationship between FMR1 allele length and cognitive ability in 621 low ability and control children assessed at 4 and 7 years, as well as 122 students with high IQ. The low and high ability and control samples showed no between-group differences in incidence of longer alleles. In males there was a significant negative correlation between allele length and non-verbal ability at 4 years (p = 0.048), academic achievement in maths (p = 0.003) and English (p = 0.011) at 7 years, and IQ in the high ability group (p = 0.018). There was a significant negative correlation between allele length and a standardised score for IQ and general cognitive ability at age 7 in the entire male sample (p = 0.002). This suggests that, within the normal spectrum of allele length, increased repeat numbers may have a limiting influence on cognitive performance. PMID:16907702

  2. Suppression among alleles encoding nucleotide-binding-leucine-rich repeat resistance proteins interferes with resistance in F1 hybrid and allele-pyramided wheat plants.

    PubMed

    Stirnweis, Daniel; Milani, Samira D; Brunner, Susanne; Herren, Gerhard; Buchmann, Gabriele; Peditto, David; Jordan, Tina; Keller, Beat

    2014-09-01

    The development of high-yielding varieties with broad-spectrum durable disease resistance is the ultimate goal of crop breeding. In plants, immune receptors of the nucleotide-binding-leucine-rich repeat (NB-LRR) class mediate race-specific resistance against pathogen attack. When employed in agriculture this type of resistance is often rapidly overcome by newly adapted pathogen races. The stacking of different resistance genes or alleles in F1 hybrids or in pyramided lines is a promising strategy for achieving more durable resistance. Here, we identify a molecular mechanism which can negatively interfere with the allele-pyramiding approach. We show that pairwise combinations of different alleles of the powdery mildew resistance gene Pm3 in F1 hybrids and stacked transgenic wheat lines can result in suppression of Pm3-based resistance. This effect is independent of the genetic background and solely dependent on the Pm3 alleles. Suppression occurs at the post-translational level, as levels of RNA and protein in the suppressed alleles are unaffected. Using a transient expression system in Nicotiana benthamiana, the LRR domain was identified as the domain conferring suppression. The results of this study suggest that the expression of closely related NB-LRR resistance genes or alleles in the same genotype can lead to dominant-negative interactions. These findings provide a molecular explanation for the frequently observed ineffectiveness of resistance genes introduced from the secondary gene pool into polyploid crop species and mark an important step in overcoming this limitation. PMID:24942051

  3. Long-term persistence of crop alleles in weedy populations of wild radish (Raphanus raphanistrum)

    E-print Network

    Snow, Allison A.

    Long-term persistence of crop alleles in weedy populations of wild radish (Raphanus raphanistrum) A (Raphanus raphanistrum). Summary · Hybridization allows transgenes and other crop alleles to spread to wild-seeding, hybrid populations of Raphanus raphani- strum · Raphanus sativus (radish) in Michigan, USA, over a decade

  4. High frequency of HLA-A*0103 allele in a Somali population.

    PubMed

    Poland, G A; Sohni, Y; Domanico, M; Kroning, C M; DeGoey, S R; Jimale, M; Jacobson, R M; Moore, S B

    2001-02-01

    We report the existence of class I HLA allele A*0103 in an ethnic group (Somali) where this allele has not been reported. This allele was discovered in a study to examine the relationship between HLA alleles and humoral antibody response to measles vaccine among recent immigrants from Somalia to Olmsted County, Minnesota. We initially used polymerase chain reaction-sequence-specific primers (PCR-SSP) to carry out HLA class I typing. Based on PCR-SSP, 55 subjects were assigned the allele HLA-A*0101. Following direct DNA sequencing of the PCR products, 37 of the 55 subjects (67.3%) that were initially assigned the A*0101 allele were found to actually be A*0103. Our data are significant because it demonstrates that many of the previously typed A*0101 individuals are actually A*0103 as the SSP or sequence-specific oligonucleotide probes method cannot distinguish between the two alleles. Lastly, this is the first identification of this allele in the homozygous state. PMID:11182232

  5. Molecular and physiological characterization of Arabidopsis GAI alleles obtained in targeted Ds -tagging experiments

    Microsoft Academic Search

    Jinrong Peng; Donald E. Richards; Thomas Moritz; Hiroshi Ezura; Pierre Carol; Nicholas P. Harberd

    2002-01-01

    Bioactive gibberellin (GA) is an essential regulator of vascular plant development. The GAI gene of Arabidopsis thaliana (L.) Heynh. encodes a product (GAI) that is involved in GA signalling. The dominant mutant gai allele encodes an altered product (gai) that confers reduced GA responses, dwarfism, and elevated endogenous GA levels. Recessive, presumed loss-of-function alleles of GAI confer normal height and

  6. Uneven segregation of sporophytic self-incompatibility alleles in Arabidopsis lyrata

    E-print Network

    Bataillon, Thomas

    -alleles exists in both pollen and stigma in SSI systems, whereas both alleles are always expressed in the stigma). The SI locus consists of at least one `female' and one `male' gene expressed respectively in the stigma system of Brassicaceae, about which most is known, the stigma gene (SRK, Schopfer et al., 1999) acts

  7. Variation of Herbivore-Induced Volatile Terpenes among Arabidopsis Ecotypes Depends on Allelic Differences

    E-print Network

    Tholl, Dorothea

    Variation of Herbivore-Induced Volatile Terpenes among Arabidopsis Ecotypes Depends on Allelic Differences and Subcellular Targeting of Two Terpene Synthases, TPS02 and TPS031[W][OA] Mengsu Huang-duplicated terpene synthase genes, TPS02 and TPS03. The Ws genome contains a functional allele of TPS02

  8. Stem Cell Reports Single-Cell Analysis of Proxy Reporter Allele-Marked Epithelial Cells

    E-print Network

    Jensen, Shane T.

    Stem Cell Reports Resource Single-Cell Analysis of Proxy Reporter Allele-Marked Epithelial Cells Establishes Intestinal Stem Cell Hierarchy Ning Li,1 Maryam Yousefi,1,5 Angela Nakauka-Ddamba,1 Rajan Jain,2 development of targeted murine reporter alleles as proxies for intestinal stem cell activity has led

  9. Theoretical Population Biology 52, 216 223 (1997) On the Genealogy of a Rare Allele

    E-print Network

    1997-01-01

    Theoretical Population Biology 52, 216 223 (1997) On the Genealogy of a Rare Allele Bruce Rannala 31, 1996 The gene genealogy is derived for a rare allele that is descended from a mutant ancestor is described for rapidly simulating these coalescence times. The relationship between the genealogical

  10. Gene and Allelic Genealogies at a Gametophytic Self-Incompatibility Locus

    Microsoft Academic Search

    Xavier Vekemans; Montgomery Slatkin

    1994-01-01

    The properties of gene and allelic genealogies at a gametophytic self-incompatibility locus in plants have been investigated analytically and checked against extensive numerical simulations. It is found that, as with overdominant loci, there are two genealogical processes with markedly different time scales. First, func- tionally distinct allelic lines diverge on an extremely long time scale which is inversely related to

  11. Diversity of HLA-B61 alleles and haplotypes in East Asians and Spanish Gypsies.

    PubMed

    Ogawa, A; Tokunaga, K; Lin, L; Kashiwase, K; Tanaka, H; Herrero, M J; Vilches, C; Park, M H; Jia, G J; Chimge, N O; Sideltseva, E W; Ishikawa, Y; Akaza, T; Tadokoro, K; Juji, T

    1998-04-01

    The distribution of HLA-B61 alleles and their association with HLA-C and DRB1 alleles were investigated in six East Asian populations (South Korean, Chinese Korean, Man (Manchu), Northern Han, Mongolian and Buryat) and Spanish Gypsies and compared to our previous report on the Japanese population. The alleles were identified using a group-specific polymerase chain reaction (PCR) and genomic DNA followed by hybridization with sequence-specific oligonucleotide probes (SSOP). Both HLA-B*4002 and B*4006 were commonly detected in the South Korean, Chinese Korean, Man, Northern Han and Japanese populations, while HLA-B*4002 was predominant in the Mongolian and Buryat populations. Strong associations of B*4002 with Cw*0304 and of B*4006 with Cw*0801 were commonly observed in these East Asian populations. In contrast, in Spanish Gypsies, only HLA-B*4006 was found and the allele exhibited a strong association with Cw*1502. HLA-B*4003 was also identified in the South Korean, Chinese Korean, Northern Han, Mongolian and Japanese populations at relatively low frequencies, and exhibited an association with Cw*0304. Moreover, the association of these B61 alleles with the DRB1 alleles revealed considerable diversity among the different populations. HLA-B*4004 and B*4009 were not observed in these populations. Consequently, the frequencies of the B61 alleles varied among the different East Asian populations, but the individual B61 alleles were carried by specific haplotypes often regardless of the ethnic differences. PMID:9583807

  12. PREDICTION OF PEPTIDES BINDING TO MHC CLASS I ALLELES BY PARTIAL PERIODIC PATTERN MINING

    E-print Network

    Yanikoglu, Berrin

    PREDICTION OF PEPTIDES BINDING TO MHC CLASS I ALLELES BY PARTIAL PERIODIC PATTERN MINING Cem Meydan peptides will bind to a spe- cific MHC allele and which will not, creating possibilities for controlling in the computational binding prediction methods for MHC class I is the presence of bulges and loops in the peptides

  13. Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function

    Microsoft Academic Search

    L S Robbins; J H Nadeau; K R Johnson; M A Kelly; Rehfuss L Roselli; E Baack; K G Mountjoy; R D Cone

    1993-01-01

    Coat colors in the chestnut horse, the yellow Labrador retriever, the red fox, and one type of yellow mouse are due to recessive alleles at the extension locus. Similarly, dominant alleles at this locus are often responsible for dark coat colors in mammals, such as the melanic form of the leopard, Panthera pardus. We show here that the murine extension

  14. Comparison of Prion Allele Frequency found in Suffolk and Targhee Sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Scrapie is a class of Transmissible Spongiform Encephalopathy that affects sheep and goats. The objective of this study was to compare genotypic and allelic frequencies among USSES Targhee and Suffolk sheep. A total of 122 sheep were genotyped for codon 171 with allele specific primers in 2 separate...

  15. Molecular markers and allelic relationships of anthracnose resistance gene cluster B4 in common bean

    Microsoft Academic Search

    Belén Méndez-Vigo; Cristina Rodríguez-Suárez; Astrid Pañeda; Juan José Ferreira; Ramón Giraldez

    2005-01-01

    Allelism tests and molecular marker analyses were combined to characterize the genes that, proceeding from the germplasm lines ‘A493’ and ‘A321’, confer resistance to bean anthracnose in the new breeding lines ‘A1220’ and ‘A1231’, respectively, developed through backcross breeding, using the dry bean landrace ‘Andecha’ as the recurrent parent. Allelism tests indicate that resistance to race 38 of anthracnose in

  16. Comparing computational methods for identification of allele-specific expression based on next generation sequencing data.

    PubMed

    Liu, Zhi; Yang, Jing; Xu, Huayong; Li, Chao; Wang, Zhen; Li, Yuanyuan; Dong, Xiao; Li, Yixue

    2014-11-01

    Allele-specific expression (ASE) studies have wide-ranging implications for genome biology and medicine. Whole transcriptome RNA sequencing (RNA-Seq) has emerged as a genome-wide tool for identifying ASE, but suffers from mapping bias favoring reference alleles. Two categories of methods are adopted nowadays, to reduce the effect of mapping bias on ASE identification-normalizing RNA allelic ratio with the parallel genomic allelic ratio (pDNAar) and modifying reference genome to make reads carrying both alleles with the same chance to be mapped (mREF). We compared the sensitivity and specificity of both methods with simulated data, and demonstrated that the pDNAar, though ideally practical, was lower in sensitivity, because of its lower mapping rate of reads carrying nonreference (alternative) alleles, although mREF achieved higher sensitivity and specificity for its efficiency in mapping reads carrying both alleles. Application of these two methods in real sequencing data showed that mREF were able to identify more ASE loci because of its higher mapping efficiency, and able to correcting some seemly incorrect ASE loci identified by pDNAar due to the inefficiency in mapping reads carrying alternative alleles of pDNAar. Our study provides useful information for RNA sequencing data processing in the identification of ASE. PMID:25183311

  17. Surrogate Genetics and Metabolic Profiling for Characterization of Human Disease Alleles

    PubMed Central

    Mayfield, Jacob A.; Davies, Meara W.; Dimster-Denk, Dago; Pleskac, Nick; McCarthy, Sean; Boydston, Elizabeth A.; Fink, Logan; Lin, Xin Xin; Narain, Ankur S.; Meighan, Michael; Rine, Jasper

    2012-01-01

    Cystathionine-?-synthase (CBS) deficiency is a human genetic disease causing homocystinuria, thrombosis, mental retardation, and a suite of other devastating manifestations. Early detection coupled with dietary modification greatly reduces pathology, but the response to treatment differs with the allele of CBS. A better understanding of the relationship between allelic variants and protein function will improve both diagnosis and treatment. To this end, we tested the function of 84 CBS alleles previously sequenced from patients with homocystinuria by ortholog replacement in Saccharomyces cerevisiae. Within this clinically associated set, 15% of variant alleles were indistinguishable from the predominant CBS allele in function, suggesting enzymatic activity was retained. An additional 37% of the alleles were partially functional or could be rescued by cofactor supplementation in the growth medium. This large class included alleles rescued by elevated levels of the cofactor vitamin B6, but also alleles rescued by elevated heme, a second CBS cofactor. Measurement of the metabolite levels in CBS-substituted yeast grown with different B6 levels using LC–MS revealed changes in metabolism that propagated beyond the substrate and product of CBS. Production of the critical antioxidant glutathione through the CBS pathway was greatly decreased when CBS function was restricted through genetic, cofactor, or substrate restriction, a metabolic consequence with implications for treatment. PMID:22267502

  18. INVOLVEMENT OF THE FGFR4 Arg388 ALLELE IN HEAD AND NECK SQUAMOUS CELL CARCINOMA

    E-print Network

    Ullrich, Axel

    INVOLVEMENT OF THE FGFR4 Arg388 ALLELE IN HEAD AND NECK SQUAMOUS CELL CARCINOMA Sylvia STREIT 1/Arg polymorphism (388) in head and neck squamous cell carcinomas (HNSCCs) of the oral cavity and the oropharynx squamous cell carcinoma; FGFR4 Arg388 allele After decades of rigorous investigations of chemotherapeutic

  19. WFPDB: European Plate Archives

    NASA Astrophysics Data System (ADS)

    Tsvetkov, Milcho

    2007-08-01

    The Wide-Field Plate Database (WFPDB) gives an inventory of all wide-field (>~ 1 sq. deg) photographic observations archived in astronomical institutions over the world. So it facilitates and stimulates their use and preservation as a valuable source of information for future investigations in astronomy. At present WFPDB manages plate-index information for 25% of all existing plates providing on-line access from Sofia (http://www.skyarchive.org/search) and in CDS, Strasbourg. Here we present the new development of WFPDB as an instrument for searching of long term brightness variations of different sky objects stressing on the European photographic plate collections (from existing 2 million wide-field plates more than 55% are in Europe: Germany, Russia, Ukraine, Italy, Czech Republic, etc.). We comment examples of digitization (with flatbed scanners) of the European plate archives in Sonneberg, Pulkovo, Asiago, Byurakan, Bamberg, etc. and virtual links of WFPDB with European AVO, ADS, IBVS.

  20. European Universe Awareness

    NASA Astrophysics Data System (ADS)

    Russo, P.; Miley, G.; Westra van Holthe, F.; Schrier, W.; Reed, S.

    2011-10-01

    The European Universe Awareness (EU-UNAWE) programme uses the beauty and grandeur of the cosmos to encourage young children, particularly those from underprivileged backgrounds, to develop an interest in science and technology and to foster a sense of global citizenship. EU-UNAWE is already active in 40 countries and comprises a global network of almost 500 astronomers, teachers and other educators. The programme was recently awarded a grant of 1.9 million euros by the European Union so that it can be further developed in five European countries and South Africa. The grant will be used to organise teacher training workshops and to develop educational materials, such as an astronomy news service for children and games. During this presentation we will outline some of the biggest achievements of EU-UNAWE to date and discuss future plans for the programme.

  1. Global distribution of allele frequencies at the human dopamine D4 receptor locus

    SciTech Connect

    Chang, F.M.; Kidd, J.R. [Yale Univ. School of Medicine, New Haven, CT (United States); Livak, K.J. [DuPont-Merch Pharmaceutical Company, Wilmington, DE (United States)] [and others

    1994-09-01

    The dopamine D4 receptor (DRD4) is a candidate gene for schizophrenia because the dopaminergic system has been implicated in this neuropsychiatric disorder. Several research groups have reported an association between allelic variants at DRD4 and schizophrenia, while others have been unable to replicate that finding. Knowledge of the appropriate gene frequencies in the underlying populations may resolve these inconsistencies. We have determined the frequencies of 8 different alleles of the 48 bp imperfect tandem repeat of exon 3 at the DRD4 locus in samples from 33 populations around the world. The frequencies vary considerably in the different populations with the most common allele ranging from 16% to 95%. Frequencies and Fst values will be presented for the 3 most common alleles (4-, 7-, and 2- repeat) by continental groupings, but the individual populations vary significantly around the averages. The populations averaged 4.3 alleles (range 2 to 7).

  2. Independent recruitment of Igh alleles in V(D)J recombination

    PubMed Central

    Alves-Pereira, Clara F.; de Freitas, Raquel; Lopes, Telma; Gardner, Rui; Marta, Filipa; Vieira, Paulo; Barreto, Vasco M.

    2014-01-01

    How the vast majority of B cells express only one of the two alleles at their immunoglobulin loci remains a biological puzzle. Here, in mice reconstituted with a single haematopoietic stem cell, we demonstrate that each of the two immunoglobulin heavy chain (Igh) alleles has a similar probability to be the first to undergo VH to DJH rearrangement. We also observe this similar probability in clones from multipotent and common lymphoid precursors. The extreme biases in the expression of the alleles that we find in more differentiated subsets are mostly due to constraints imposed by early rearrangements. Our data demonstrate that each of the two Igh alleles in a B cell behaves independently of the other, up to the moment when a successful rearrangement in one allele triggers a feedback mechanism that prevents further recombination. PMID:25517887

  3. Analysis of DQB1 allele frequencies in pulmonary tuberculosis: preliminary report

    PubMed Central

    Dubaniewicz, A; Moszkowska, G; Szczerkowska, Z; Hoppe, A

    2003-01-01

    Method: The DQB1 alleles of 38 patients with TB and 58 healthy university staff volunteers were determined by a PCR-SSP low resolution method. Results: The DQB1*05 allele occurred more frequently (p adjusted for multiple comparison=0.002, OR=2.84, 95% CI 1.57 to 5.15) and the DQB1*02 allele occurred less frequently (p=0.01, OR=0.39, 95% CI 0.21 to 0.71) in patients with TB than in controls. The occurrence of DQB1*03,*04,*06 alleles was similar in the two populations. Conclusions: The occurrence of specific DQB1 alleles may be linked to susceptibility/resistance to tuberculosis. PMID:14514946

  4. A method for detecting recent selection in the human genome from allele age estimates.

    PubMed Central

    Toomajian, Christopher; Ajioka, Richard S; Jorde, Lynn B; Kushner, James P; Kreitman, Martin

    2003-01-01

    Mutations that have recently increased in frequency by positive natural selection are an important component of naturally occurring variation that affects fitness. To identify such variants, we developed a method to test for recent selection by estimating the age of an allele from the extent of haplotype sharing at linked sites. Neutral coalescent simulations are then used to determine the likelihood of this age given the allele's observed frequency. We applied this method to a common disease allele, the hemochromatosis-associated HFE C282Y mutation. Our results allow us to reject neutral models incorporating plausible human demographic histories for HFE C282Y and one other young but common allele, indicating positive selection at HFE or a linked locus. This method will be useful for scanning the human genome for alleles under selection using the haplotype map now being constructed. PMID:14504236

  5. Genetic tools for allelic replacement in Burkholderia species.

    PubMed

    Barrett, Ashley R; Kang, Yun; Inamasu, Ken S; Son, Mike S; Vukovich, Joseph M; Hoang, Tung T

    2008-07-01

    Allelic replacement in the Burkholderia genus has been problematic due to the lack of appropriate counter-selectable and selectable markers. The counter-selectable marker sacB, commonly used in gram-negative bacteria, is nonselective on sucrose in many Burkholderia species. In addition, the use of antibiotic resistance markers of clinical importance for the selection of desirable genetic traits is prohibited in the United States for two potential bioterrorism agents, Burkholderia mallei and Burkholderia pseudomallei. Here, we engineered a mutated counter-selectable marker based on the B. pseudomallei PheS (the alpha-subunit of phenylalanyl tRNA synthase) protein and tested its effectiveness in three different Burkholderia species. The mutant PheS protein effectively killed 100% of the bacteria in the presence of 0.1% p-chlorophenylalanine. We assembled the mutant pheS on several allelic replacement vectors, in addition to constructing selectable markers based on tellurite (Tel(r)) and trimethoprim (Tp(r)) resistance that are excisable by flanking unique FLP recombination target (FRT) sequences. As a proof of concept, we utilized one of these gene replacement vectors (pBAKA) and the Tel(r)-FRT cassette to produce a chromosomal mutation in the Burkholderia thailandensis betBA operon, which codes for betaine aldehyde dehydrogenase and choline dehydrogenase. Chromosomal resistance markers could be excised by the introduction of pFLP-AB5 (Tp(r)), which is one of two constructed flp-containing plasmids, pFLP-AB4 (Tel(r)) and pFLP-AB5 (Tp(r)). These flp-containing plasmids harbor the mutant pheS gene and allow self curing on media that contain p-chlorophenylalanine after Flp-FRT excision. The characterization of the Delta betBA::Tel(r)-FRT and Delta betBA::FRT mutants indicated a defect in growth with choline as a sole carbon source, while these mutants grew as well as the wild type with succinate and glucose as alternative carbon sources. PMID:18502918

  6. Chromosome-Wide Analysis of Parental Allele-Specific Chromatin and DNA Methylation ? §

    PubMed Central

    Singh, Purnima; Wu, Xiwei; Lee, Dong-Hoon; Li, Arthur X.; Rauch, Tibor A.; Pfeifer, Gerd P.; Mann, Jeffrey R.; Szabó, Piroska E.

    2011-01-01

    To reveal the extent of domain-wide epigenetic features at imprinted gene clusters, we performed a high-resolution allele-specific chromatin analysis of over 100 megabases along the maternally or paternally duplicated distal chromosome 7 (Chr7) and Chr15 in mouse embryo fibroblasts (MEFs). We found that reciprocal allele-specific features are limited to imprinted genes and their differentially methylated regions (DMRs), whereas broad local enrichment of H3K27me3 (BLOC) is a domain-wide feature at imprinted clusters. We uncovered novel allele-specific features of BLOCs. A maternally biased BLOC was found along the H19-Igf2 domain. A paternal allele-specific gap was found along Kcnq1ot1, interrupting a biallelic BLOC in the Kcnq1-Cdkn1c domain. We report novel allele-specific chromatin marks at the Peg13 and Slc38a4 DMRs, Cdkn1c upstream region, and Inpp5f_v2 DMR and paternal allele-specific CTCF binding at the Peg13 DMR. Additionally, we derived an imprinted gene predictor algorithm based on our allele-specific chromatin mapping data. The binary predictor H3K9ac and CTCF or H3K4me3 in one allele and H3K9me3 in the reciprocal allele, using a sliding-window approach, recognized with precision the parental allele specificity of known imprinted genes, H19, Igf2, Igf2as, Cdkn1c, Kcnq1ot1, and Inpp5f_v2 on Chr7 and Peg13 and Slc38a4 on Chr15. Chromatin features, therefore, can unequivocally identify genes with imprinted expression. PMID:21321082

  7. Distinct allelic patterns of nanog expression impart embryonic stem cell population heterogeneity.

    PubMed

    Wu, Jincheng; Tzanakakis, Emmanuel S

    2013-01-01

    Nanog is a principal pluripotency regulator exhibiting a disperse distribution within stem cell populations in vivo and in vitro. Increasing evidence points to a functional role of Nanog heterogeneity on stem cell fate decisions. Allelic control of Nanog gene expression was reported recently in mouse embryonic stem cells. To better understand how this mode of regulation influences the observed heterogeneity of NANOG in stem cell populations, we assembled a multiscale stochastic population balance equation framework. In addition to allelic control, gene expression noise and random partitioning at cell division were considered. As a result of allelic Nanog expression, the distribution of Nanog exhibited three distinct states but when combined with transcriptional noise the profile became bimodal. Regardless of their allelic expression pattern, initially uniform populations of stem cells gave rise to the same Nanog heterogeneity within ten cell cycles. Depletion of NANOG content in cells switching off both gene alleles was slower than the accumulation of intracellular NANOG after cells turned on at least one of their Nanog gene copies pointing to Nanog state-dependent dynamics. Allelic transcription of Nanog also raises issues regarding the use of stem cell lines with reporter genes knocked in a single allelic locus. Indeed, significant divergence was observed in the reporter and native protein profiles depending on the difference in their half-lives and insertion of the reporter gene in one or both alleles. In stem cell populations with restricted Nanog expression, allelic regulation facilitates the maintenance of fractions of self-renewing cells with sufficient Nanog content to prevent aberrant loss of pluripotency. Our findings underline the role of allelic control of Nanog expression as a prime determinant of stem cell population heterogeneity and warrant further investigation in the contexts of stem cell specification and cell reprogramming. PMID:23874182

  8. Distribution of repeat unit differences between alleles at tandem repeat microsatellite loci

    SciTech Connect

    Jin, L. [Univ. Texas Houston Health Science Center, Houston, TX (United States)]|[Univ. Medical School, Stanford, CA (United States); Zhong, Y.; Chakraborty, R. [Univ. Texas Houston Health Center, Houston, TX (United States)] [and others

    1994-09-01

    PCR-based assays of tandemly repeated microsatellite loci detect genetic variation from which alleles may be scored by their repeat unit lengths. Comparison of allele sizes from such data yields a probability distribution (P{sub k}) of repeat unit differences (k) between alleles segregating in a population. We show that this distribution (P{sub k}; k = 0, 1,2,...) provides insight regarding the mechanism of production of new alleles at such loci and the demographic history of populations, far better than that obtained from other summary measures (e.g., heterozygosity, number of alleles, and the range of allele sizes). The distributions of P{sub k} under multi-step stepwise models of mutation are analytically derived, which show that when a population is at equilibrium under the mutation-drift balance, the distribution of repeat unit differences between alleles is positively skewed with a mode larger than zero. However, when the heterozygosity at a locus is low (say, less than 40%), P{sub k} is a monotonically decreasing function of k. Applications of this theory to data on repeat unit sizes at over 1,240 microsatellite loci from the Caucasians, categorized by the average heterozygosity of loci, indicate that at most microsatellite loci new alleles are produced by stepwise mutations, and this is consistent with the replication slippage mechanism of mutations. The repeat size changes of mutants are probably within one or two units of alleles from which the mutants arise. Distributions of P{sub k} at microsatellite loci located within genes show evidence of allele size constraints. No significant evidence of recent expansion of population sizes in the Caucasians is detected by the distribution of P{sub k}.

  9. Comparative analysis of type 2 diabetes-associated SNP alleles identifies allele-specific DNA-binding proteins for the KCNQ1 locus.

    PubMed

    Hiramoto, Masaki; Udagawa, Haruhide; Watanabe, Atsushi; Miyazawa, Keisuke; Ishibashi, Naoko; Kawaguchi, Miho; Uebanso, Takashi; Nishimura, Wataru; Nammo, Takao; Yasuda, Kazuki

    2015-07-01

    Although recent genome-wide association studies (GWAS) have been extremely successful, it remains a big challenge to functionally annotate disease?associated single nucleotide polymorphisms (SNPs), as the majority of these SNPs are located in non?coding regions of the genome. In this study, we described a novel strategy for identifying the proteins that bind to the SNP?containing locus in an allele?specific manner and successfully applied this method to SNPs in the type 2 diabetes mellitus susceptibility gene, potassium voltage?gated channel, KQT?like subfamily Q, member 1 (KCNQ1). DNA fragments encompassing SNPs, and risk or non?risk alleles were immobilized onto the novel nanobeads and DNA?binding proteins were purified from the nuclear extracts of pancreatic ? cells using these DNA?immobilized nanobeads. Comparative analysis of the allele-specific DNA-binding proteins indicated that the affinities of several proteins for the examined SNPs differed between the alleles. Nuclear transcription factor Y (NF?Y) specifically bound the non?risk allele of the SNP rs2074196 region and stimulated the transcriptional activity of an artificial promoter containing SNP rs2074196 in an allele?specific manner. These results suggest that SNP rs2074196 modulates the affinity of the locus for NF?Y and possibly induces subsequent changes in gene expression. The findings of this study indicate that our comparative method using novel nanobeads is effective for the identification of allele?specific DNA?binding proteins, which may provide important clues for the functional impact of disease?associated non?coding SNPs. PMID:25955334

  10. Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans

    Microsoft Academic Search

    Giriraj R Chandak; Kirsten J Ward; Chittaranjan S Yajnik; Anand N Pandit; Ashish Bavdekar; Charu V Joglekar; Caroline HD Fall; P Mohankrishna; Terence J Wilkin; Bradley S Metcalf; Michael N Weedon; Timothy M Frayling; Andrew T Hattersley

    2006-01-01

    Background  The APOA5 gene variants, -1131T>C and S19W, are associated with altered triglyceride concentrations in studies of subjects of Caucasian\\u000a and East Asian descent. There are few studies of these variants in South Asians. We investigated whether the two APOA5 variants also show similar association with various lipid parameters in Indian population as in the UK white subjects.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We genotyped 557

  11. High-Density Genotyping of Immune Loci in Koreans and Europeans Identifies Eight New Rheumatoid Arthritis Risk Loci

    PubMed Central

    Kim, Kwangwoo; Bang, So-Young; Lee, Hye-Soon; Cho, Soo-Kyung; Choi, Chan-Bum; Sung, Yoon-Kyoung; Kim, Tae-Hwan; Jun, Jae-Bum; Yoo, Dae Hyun; Kang, Young Mo; Kim, Seong-Kyu; Suh, Chang-Hee; Shim, Seung-Cheol; Lee, Shin-Seok; Lee, Jisoo; Chung, Won Tae; Choe, Jung-Yoon; Shin, Hyoung Doo; Lee, Jong-Young; Han, Bok-Ghee; Nath, Swapan K.; Eyre, Steve; Bowes, John; Pappas, Dimitrios A.; Kremer, Joel M.; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Ärlestig, Lisbeth; Okada, Yukinori; Diogo, Dorothée; Liao, Katherine P.; Karlson, Elizabeth W.; Raychaudhuri, Soumya; Rantapää-Dahlqvist, Solbritt; Martin, Javier; Klareskog, Lars; Padyukov, Leonid; Gregersen, Peter K.; Worthington, Jane; Greenberg, Jeffrey D.; Plenge, Robert M.; Bae, Sang-Cheol

    2015-01-01

    Objective A highly polygenic etiology and high degree of allele-sharing between ancestries have been well-elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. Methods We analyzed Korean rheumatoid arthritis case-control samples using the Immunochip and GWAS array to search for new risk alleles of rheumatoid arthritis with anti-citrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data, for a total sample size of 9,299 Korean and 45,790 European case-control samples. Results We identified 8 new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1–FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5×10?8), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the 7 new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of SNPs that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. Conclusion This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases. PMID:24532676

  12. Sequence Variation within the KIV-2 Copy Number Polymorphism of the Human LPA Gene in African, Asian, and European Populations

    PubMed Central

    Noureen, Asma; Fresser, Friedrich; Utermann, Gerd; Schmidt, Konrad

    2015-01-01

    Amazingly little sequence variation is reported for the kringle IV 2 copy number variation (KIV 2 CNV) in the human LPA gene. Apart from whole genome sequencing projects, this region has only been analyzed in some detail in samples of European populations. We have performed a systematic resequencing study of the exonic and flanking intron regions within the KIV 2 CNV in 90 alleles from Asian, European, and four different African populations. Alleles have been separated according to their CNV length by pulsed field gel electrophoresis prior to unbiased specific PCR amplification of the target regions. These amplicons covered all KIV 2 copies of an individual allele simultaneously. In addition, cloned amplicons from genomic DNA of an African individual were sequenced. Our data suggest that sequence variation in this genomic region may be higher than previously appreciated. Detection probability of variants appeared to depend on the KIV 2 copy number of the analyzed DNA and on the proportion of copies carrying the variant. Asians had a high frequency of so-called KIV 2 type B and type C (together 70% of alleles), which differ by three or two synonymous substitutions respectively from the reference type A. This is most likely explained by the strong bottleneck suggested to have occurred when modern humans migrated to East Asia. A higher frequency of variable sites was detected in the Africans. In particular, two previously unreported splice site variants were found. One was associated with non-detectable Lp(a). The other was observed at high population frequencies (10% to 40%). Like the KIV 2 type B and C variants, this latter variant was also found in a high proportion of KIV 2 repeats in the affected alleles and in alleles differing in copy numbers. Our findings may have implications for the interpretation of SNP analyses in other repetitive loci of the human genome. PMID:25822457

  13. Mutator specificity of Escherichia coli alkB117 allele.

    PubMed

    Nieminuszczy, Jadwiga; Janion, Celina; Grzesiuk, Elzbieta

    2006-01-01

    The Escherichia coli AlkB protein encoded by alkB gene was recently found to repair cytotoxic DNA lesions 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) by using a novel iron-catalysed oxidative demethylation mechanism that protects the cell from the toxic effects of methylating agents. Mutation in alkB results in increased sensitivity to MMS and elevated level of MMS-induced mutations. The aim of this study was to analyse the mutational specificity of alkB117 in a system developed by J.H. Miller involving two sets of E. coli lacZ mutants, CC101-106 allowing the identification of base pair substitutions, and CC107-CC111 indicating frameshift mutations. Of the six possible base substitutions, the presence of alkB117 allele led to an increased level of GC-->AT transitions and GC-->TA and AT-->TA transversions. After MMS treatment the level of GC-->AT transitions increased the most, 22-fold. Among frameshift mutations, the most numerous were -2CG, -1G, and -1A deletions and +1G insertion. MMS treatment appreciably increased all of the above types of frameshifts, with additional appearance of the +1A insertion. PMID:16733554

  14. Salmonella Typhi shdA: pseudogene or allelic variant?

    PubMed

    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 ?shdA mutants presented an impaired adherence and invasion of HEp-2 pre-treated with TGF-?1, 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 ?shdA 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 DH5?. The data presented here show that shdASTy is not a pseudogene, but a different functional allele compared with shdASTm. PMID:24859062

  15. Alleles underlying larval foraging behaviour influence adult dispersal in nature.

    PubMed

    Edelsparre, Allan H; Vesterberg, Anders; Lim, Jang H; Anwari, Milad; Fitzpatrick, Mark J

    2014-03-01

    The dispersal and migration of organisms have resulted in the colonisation of nearly every possible habitat and ultimately the extraordinary diversity of life. Animal dispersal tendencies are commonly heterogeneous (e.g. long vs. short) and non-random suggesting that phenotypic and genotypic variability between individuals can contribute to population-level heterogeneity in dispersal. Using laboratory and field experiments, we demonstrate that natural allelic variation in a gene underlying a foraging polymorphism in larval fruit flies (for), also influences their dispersal tendencies as adults. Rover flies (for(R) ; higher foraging activity) have consistently greater dispersal tendencies and are more likely to disperse longer distances than sitter flies (for(s) ; lower foraging activity). Increasing for expression in the brain and nervous system increases dispersal in sitter flies. Our study supports the notion that variation in dispersal can be driven by intrinsic variation in food-dependent search behaviours and confirms that single gene pleiotropic effects can contribute to population-level heterogeneity in dispersal. PMID:24386971

  16. Microsatellite allele dose and configuration establishment (MADCE): an integrated approach for genetic studies in allopolyploids

    PubMed Central

    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 for any accession of an allopolyploid plant species. The method, named Microsatellite Allele Dose and Configuration Establishment (MADCE), can be applied to mapping populations and pedigreed (breeding) germplasm in allopolyploids. Results Two case studies are presented to demonstrate the power and robustness of the MADCE method. In the mapping case, five microsatellites were analysed. These microsatellites amplified 35 different alleles based on size. Using MADCE, we uncovered 30 highly informative segregating alleles. A conventional approach would have yielded only 19 fully informative and six partially informative alleles. Of the ten alleles that were present in all progeny (and thereby ignored or considered homozygous when using conventional approaches), six were found to segregate by dosage when analysed with MADCE. Moreover, the full allelic configuration of the mapping parents could be established, including null alleles, homozygous loci, and alleles that were present on multiple homoeologues. In the second case, 21 pedigreed cultivars were analysed using MADCE, resulting in the establishment of the full allelic configuration for all 21 cultivars and a tracing of allele flow over multiple generations. Conclusions The procedure described in this study (MADCE) enhances the efficiency and information content of mapping studies in allopolyploids. More importantly, it is the first technique to allow the determination of the full allelic configuration in pedigreed breeding germplasm from allopolyploid plants. This enables pedigree-based marker-trait association studies the use of algorithms developed for diploid crops, and it may increase the effectiveness of LD-based association studies. The MADCE method therefore enables researchers to tackle many of the genotyping problems that arise when performing mapping, pedigree, and association studies in allopolyploids. We discuss the merits of MADCE in comparison to other marker systems in polyploids, including SNPs, and how MADCE could aid in the development of SNP markers in allopolyploids. PMID:22340438

  17. Institutional Report: European Union

    E-print Network

    Boyer, Edmond

    Institutional Report: European Union Florence Bergeaud-Blackler CRIC, University of Manchester #12-Blackler CRIC, University of Manchester Working Paper Prepared by Partner No. 4 July 2004 #12;P R E FA C E (CRIC) at the University of Manchester. The various country teams in the TRUSTINFOOD project have

  18. Eastern European Cinema.

    ERIC Educational Resources Information Center

    Iordanova, Dina

    1999-01-01

    Presents a structure for a course that highlights the best cinemas of Eastern European countries, in order to acquaint students with cinematic traditions of the region. Discusses course activities, coursework and evaluation, and resources. Advocates structuring the course around the film of experience of Eastern Europe, and presents and discusses…

  19. European inflation dynamics

    Microsoft Academic Search

    Jordi Gal??; Mark Gertler; J. David López-Salido

    2001-01-01

    We provide evidence on the fit of the New Phillips Curve (NPC) for the Euro area over the period 1970–1998, and use it as a tool to compare the characteristics of European inflation dynamics with those observed in the U.S. We also analyze the factors underlying inflation inertia by examining the cyclical behavior of marginal costs, as well as that

  20. The European Union

    Microsoft Academic Search

    Ali M. El-Agraa

    1990-01-01

    The European Union has established itself as a leading text that provides readers from all disciplines with a sound understanding of the economics and policies of the EU. Its wealth of information, detail and analysis has ensured that previous editions have been read by a generation of students, researchers and policy makers. It covers all major EU policy areas as

  1. European Music Year 1985.

    ERIC Educational Resources Information Center

    Alexanderson, Thomas; And Others

    1984-01-01

    Articles concerning music are included in this newsletter dedicated to cultural venture to be jointly carried out by the Council of Europe and the European communities. Many events will mark Music Year 1985, including concerts, dance performances, operas, publications, recordings, festivals, exhibitions, competitions, and conferences on musical…

  2. Multilingualism in European Workplaces

    ERIC Educational Resources Information Center

    Gunnarsson, Britt-Louise

    2014-01-01

    This state-of-the-art article includes a review of past and recent studies on multilingualism at work in European environments. One aim is to provide the reader with a cross-cultural picture of workplace studies on various languages in Europe, another to discuss both positive and problem-based accounts of multilingualism at work. The overview…

  3. European Commission Agriculture and

    E-print Network

    European Commission Agriculture and Rural Development Good practice guidance on the sustainable Commission (EC) DG Agriculture and Rural Development 130, Rue de la Loi B ­ 1049 Brussels, Belgium Phone: +32 (0) 2-2969909 Fax: +32 (0) 2-29211 33 E-mail: info@ec.europa.eu Web: https://www.ec.europa.eu/agriculture

  4. European Civilization. Teacher's Manual.

    ERIC Educational Resources Information Center

    Leppert, Ella C.; Halac, Dennis

    The instructional materials in this teaching guide for Course II, Unit IV, follow and build upon a previous sequential course described in SO 003 169 offering ninth grade students a study on the development of Western European Civilization. Focus is upon four periods of high development: The High Middle Ages (12th Century), The Renaissance (15th…

  5. European Corporate Sustainability Framework

    Microsoft Academic Search

    Marcel Van Marrewijk; Teun W. Hardjono

    abstract The European Corporate Sustainability Framework (ECSF) is a new generation management framework, aimed to meet increased corporate complexity and support corporate transformation towards more sustainable ways of doing business. It is a multi-layer, integral business framework with an analytical, contextual, situational and dynamic dimension. Analytically, the framework is structured according to four focus points - the constitutional, conceptual, behavioural

  6. Systematic Cell-Based Phenotyping of Missense Alleles Empowers Rare Variant Association Studies: A Case for LDLR and Myocardial Infarction

    E-print Network

    Thormaehlen, Aenne S.

    A fundamental challenge to contemporary genetics is to distinguish rare missense alleles that disrupt protein functions from the majority of alleles neutral on protein activities. High-throughput experimental tools to ...

  7. The European Dimension in Education.

    ERIC Educational Resources Information Center

    Council of Europe, Strasbourg (France). Directorate of Education, Culture and Sport, Documentation Section.

    This paper addresses concerns about a European dimension in education that has been created by the enlargement of the European Union (EU) (the inclusion of Austria, Finland, and Sweden) and the gradual transformations of institutions into a future federal state. Sections of the paper include: (1) "Introduction"; (2) "Defining the European…

  8. Proportionally more deleterious genetic variation in European than in African populations.

    PubMed

    Lohmueller, Kirk E; Indap, Amit R; Schmidt, Steffen; Boyko, Adam R; Hernandez, Ryan D; Hubisz, Melissa J; Sninsky, John J; White, Thomas J; Sunyaev, Shamil R; Nielsen, Rasmus; Clark, Andrew G; Bustamante, Carlos D

    2008-02-21

    Quantifying the number of deleterious mutations per diploid human genome is of crucial concern to both evolutionary and medical geneticists. Here we combine genome-wide polymorphism data from PCR-based exon resequencing, comparative genomic data across mammalian species, and protein structure predictions to estimate the number of functionally consequential single-nucleotide polymorphisms (SNPs) carried by each of 15 African American (AA) and 20 European American (EA) individuals. We find that AAs show significantly higher levels of nucleotide heterozygosity than do EAs for all categories of functional SNPs considered, including synonymous, non-synonymous, predicted 'benign', predicted 'possibly damaging' and predicted 'probably damaging' SNPs. This result is wholly consistent with previous work showing higher overall levels of nucleotide variation in African populations than in Europeans. EA individuals, in contrast, have significantly more genotypes homozygous for the derived allele at synonymous and non-synonymous SNPs and for the damaging allele at 'probably damaging' SNPs than AAs do. For SNPs segregating only in one population or the other, the proportion of non-synonymous SNPs is significantly higher in the EA sample (55.4%) than in the AA sample (47.0%; P < 2.3 x 10(-37)). We observe a similar proportional excess of SNPs that are inferred to be 'probably damaging' (15.9% in EA; 12.1% in AA; P < 3.3 x 10(-11)). Using extensive simulations, we show that this excess proportion of segregating damaging alleles in Europeans is probably a consequence of a bottleneck that Europeans experienced at about the time of the migration out of Africa. PMID:18288194

  9. Pharmacogenomic diversity in Singaporean populations and Europeans.

    PubMed

    Brunham, L R; Chan, S L; Li, R; Aminkeng, F; Liu, X; Saw, W Y; Ong, R T H; Pillai, E N; Carleton, B C; Toh, D; Tan, S H; Koo, S H; Lee, E J D; Chia, K S; Ross, C J D; Hayden, M R; Sung, C; Teo, Y Y

    2014-12-01

    Differences in the frequency of pharmacogenomic variants may influence inter-population variability in drug efficacy and risk of adverse drug reactions (ADRs). We investigated the diversity of ? 4500 genetic variants in key drug-biotransformation and -response genes among three South East Asian populations compared with individuals of European ancestry. We compared rates of reported ADRs in these Asian populations to determine if the allelic differentiation corresponded to an excess of the associated ADR. We identified an excess of ADRs related to clopidogrel in Singaporean Chinese, consistent with a higher frequency of a known risk variant in CYP2C19 in that population. We also observed an excess of ADRs related to platinum compounds in Singaporean CHS, despite a very low frequency of known ADR risk variants, suggesting the presence of additional genetic and non-genetic risk factors. Our results point to substantial diversity at specific pharmacogenomic loci that may contribute to inter-population variability in drug response phenotypes. PMID:24861855

  10. Studies of self-incompatibility in wild tomatoes: I. S-allele diversity in Solanum chilense Dun. (Solanaceae)

    Microsoft Academic Search

    B Igic; W A Smith; K A Robertson; B A Schaal; J R Kohn

    2007-01-01

    We characterized the molecular allelic variation of RNases at the self-incompatibility (SI) locus of Solanum chilense Dun. We recovered 30 S-RNase allele sequences from 34 plants representing a broad geographic sample. This yielded a species-wide estimate of 35 (95% likelihood interval 31–40) S-alleles. We performed crosses to confirm the association with SI function of 10 of the putative S-RNase allele

  11. Quantification of allele-specific expression of a gene encoding strawberry polygalacturonase-inhibiting protein (PGIP) using Pyrosequencing((TM))

    Microsoft Academic Search

    J. G. Schaart; L. Mehli; H. J. Schouten

    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 the transcript abundance of six individual, highly homologous alleles of a polygalacturonase-inhibiting protein gene (FaPGIP) from octoploid strawberry (Fragaria

  12. HLA-A*02 allele frequencies and haplotypic associations in Koreans.

    PubMed

    Park, M H; Whang, D H; Kang, S J; Han, K S

    2000-03-01

    We have investigated the frequencies of HLA-A*02 alleles and their haplotypic associations with HLA-B and -DRB1 loci in 439 healthy unrelated Koreans, including 214 parents from 107 families. All of the 227 samples (51.7%) typed as A2 by serology were analyzed for A*02 alleles using polymerase chain reaction (PCR)-low ionic strength-single-strand conformation polymorphism (LIS-SSCP) method. A total of six different A*02 alleles were detected (A*02 allele frequency 29.6%): A*0201/9 (16.6%), *0203 (0.5%), *0206 (9.3%), *0207 (3.0%), and one each case of *0210 and *02 undetermined type. Two characteristic haplotypes showing the strongest linkage disequilibrium were A*0203-B38-DRB]*1502 and A*0207-B46-DRB1*0803. Besides these strong associations, significant two-locus associations (P<0.001) were observed for A*0201 with B61, DRB1*0901 and DRB1*1401, and for A*0206 with B48 and B61. HLA haplotypes carrying HLA-A2 showed a variable distribution of A*02 alleles, and all of the eight most common A2-B-DR haplotypes occurring at frequencies of > or =1% were variably associated with two different A*02 alleles. These results demonstrate that substantial heterogeneity is present in the distribution of HLA-A*02 alleles and related haplotypes in Koreans. PMID:10777100

  13. The frequency of HLA alleles in a population of Inuit women of northern Quebec

    PubMed Central

    Metcalfe, Stephanie; Roger, Michel; Faucher, Marie-Claude; Coutlée, François; Franco, Eduardo L.; Brassard, Paul

    2013-01-01

    Background Human leukocyte antigen (HLA) alleles code for proteins that are involved in the recognition of foreign antigens and activation of the immune system. The frequency of HLA alleles varies across different populations. Objective To describe the frequency of HLA alleles in a population of Inuit women of Nunavik, Quebec, Canada. Design A cohort of women was recruited from 4 different communities between January 2002 and December 2007. HLA-B*07, HLA-DQB1*03, DQB1*06:02, DRB1*13 and DRB1*15:01 alleles were typed by PCR sequence-specific primers (PCR-SSP) and HLA-E and G alleles were type by DNA-sequencing procedures. Results We obtained data on 524 participants. The most frequent HLA alleles in this population were HLA-E*01:03, HLA-G*01:04:01 and HLA-DQB1*03, and they were found in 89, 75 and 94% of the population, respectively. Conclusions The distribution of HLA alleles in Nunavik, Quebec is unique when compared to other populations in Canada or around the world. PMID:23986892

  14. Yy1 Gene Dosage Effect and Bi-Allelic Expression of Peg3

    PubMed Central

    Perera, Bambarendage P. U.; Teruyama, Ryoichi; Kim, Joomyeong

    2015-01-01

    In the current study, we tested the in vivo effects of Yy1 gene dosage on the Peg3 imprinted domain with various breeding schemes utilizing two sets of mutant alleles. The results indicated that a half dosage of Yy1 coincides with the up-regulation of Peg3 and Zim1, suggesting a repressor role of Yy1 in this imprinted domain. This repressor role of Yy1 is consistent with the observations derived from previous in vitro studies. The current study also provided an unexpected observation that the maternal allele of Peg3 is also normally expressed, and thus the expression of Peg3 is bi-allelic in the specific areas of the brain, including the choroid plexus, the PVN (Paraventricular Nucleus) and the SON (Supraoptic Nucleus) of the hypothalamus. The exact roles of the maternal allele of Peg3 in these cell types are currently unknown, but this new finding confirms the previous prediction that the maternal allele may be functional in specific cell types based on the lethality associated with the homozygotes for several mutant alleles of the Peg3 locus. Overall, these results confirm the repressor role of Yy1 in the Peg3 domain and also provide a new insight regarding the bi-allelic expression of Peg3 in mouse brain. PMID:25774914

  15. Effects of sequence variation on differential allelic transcription factor occupancy and gene expression

    PubMed Central

    Reddy, Timothy E.; Gertz, Jason; Pauli, Florencia; Kucera, Katerina S.; Varley, Katherine E.; Newberry, Kimberly M.; Marinov, Georgi K.; Mortazavi, Ali; Williams, Brian A.; Song, Lingyun; Crawford, Gregory E.; Wold, Barbara; Willard, Huntington F.; Myers, Richard M.

    2012-01-01

    A complex interplay between transcription factors (TFs) and the genome regulates transcription. However, connecting variation in genome sequence with variation in TF binding and gene expression is challenging due to environmental differences between individuals and cell types. To address this problem, we measured genome-wide differential allelic occupancy of 24 TFs and EP300 in a human lymphoblastoid cell line GM12878. Overall, 5% of human TF binding sites have an allelic imbalance in occupancy. At many sites, TFs clustered in TF-binding hubs on the same homolog in especially open chromatin. While genetic variation in core TF binding motifs generally resulted in large allelic differences in TF occupancy, most allelic differences in occupancy were subtle and associated with disruption of weak or noncanonical motifs. We also measured genome-wide differential allelic expression of genes with and without heterozygous exonic variants in the same cells. We found that genes with differential allelic expression were overall less expressed both in GM12878 cells and in unrelated human cell lines. Comparing TF occupancy with expression, we found strong association between allelic occupancy and expression within 100 bp of transcription start sites (TSSs), and weak association up to 100 kb from TSSs. Sites of differential allelic occupancy were significantly enriched for variants associated with disease, particularly autoimmune disease, suggesting that allelic differences in TF occupancy give functional insights into intergenic variants associated with disease. Our results have the potential to increase the power and interpretability of association studies by targeting functional intergenic variants in addition to protein coding sequences. PMID:22300769

  16. VNTR allele frequency distributions under the stepwise mutation model: A computer simulation approach

    SciTech Connect

    Shriver, M.D.; Jin, L.; Chakraborty, R.; Boerwinkle, E. (Univ. of Texas Health Science Center, Houston (United States))

    1993-07-01

    Variable numbers of tandem repeats (VNTRs) are a class of highly informative and widely dispersed genetic markers. Despite their wide application in biological science, little is known about their mutational mechanisms or population dynamics. The objective of this work was to investigate four summary measures of VNTR allele frequency distributions: number of alleles, number of modes, range in allele size, and heterozygosity, using computer simulations of the one-step stepwise mutation model (SMM). The authors estimated these measures and their probability distributions for a wide range of mutation rates and compared the simulation results with predictions from analytical formulations of the one-step SMM. The average heterozygosity from the simulations agreed with the analytical expectation under the SMM. The average number of alleles, however, was larger in the simulations than the analytical expectation of the SMM. The authors then compared simulation expectations with actual data reported in the literature. They used the sample size and observed heterozygosity to determine the expected value, 5th and 95th percentiles for the other three summary measures, allelic size range, number of modes and number of alleles. The loci analyzed were classified into three groups based on the size of the repeat unit: microsatellites (1-2 base pair (bp) repeat unit), short tandem repeats [(STR) 3-5 bp repeat unit], and minisatellites (15-70 bp repeat unit). In general, STR loci were most similar to the simulation results under the SMM for the three summary measures (number of alleles, number of modes and range in allele size), followed by the microsatellite loci and then by the minisatellite loci, which showed deviations in the direction of the infinite allele model (IAM). Based on these differences, it is hypothesized that these three classes of loci are subject to different mutational forces.

  17. Selection and reduced population size cannot explain higher amounts of Neandertal ancestry in East Asian than in European human populations.

    PubMed

    Kim, Bernard Y; Lohmueller, Kirk E

    2015-03-01

    It has been hypothesized that the greater proportion of Neandertal ancestry in East Asians than in Europeans is due to the fact that purifying selection is less effective at removing weakly deleterious Neandertal alleles from East Asian populations. Using simulations of a broad range of models of selection and demography, we have shown that this hypothesis cannot account for the higher proportion of Neandertal ancestry in East Asians than in Europeans. Instead, more complex demographic scenarios, most likely involving multiple pulses of Neandertal admixture, are required to explain the data. PMID:25683122

  18. Population Genetic Analysis ofHelicobacter pyloriby Multilocus Enzyme Electrophoresis: Extensive Allelic Diversity and Recombinational Population Structure

    Microsoft Academic Search

    MAE F. GO; VIVEK KAPUR; DAVID Y. GRAHAM; ANDJAMES M. MUSSER

    Genetic diversity and relationships in 74 Helicobacter pylori isolates recovered from patients assigned to distinct clinical categories were estimated by examination of allelic variation in six genes encoding metabolic housekeeping enzymes by multilocus enzyme electrophoresis. Seventy-three distinct allele profiles, represent- ing multilocus chromosomal genotypes, were identified. All six loci were highly polymorphic, with an average of 11.2 alleles per locus.

  19. Identification of pologyne and mongyne fire ant colonies (Solenopsis invivta) by multiplex PCR of GP-9 alleles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oligonucleotide primers were designed to discriminate between the Gp-9B and Gp-9b alleles found in the two social forms (monogyne and polygyne) of Solenopsis invicta. Primers specific for the Gp-9B allele produced a 518 bp amplicon and primers specific for Gp-9b allele produced a 423 bp amplicon. ...

  20. No association between an allele at the D sub 2 dopamine receptor gene (DRD2) and alcoholism

    SciTech Connect

    Gelernter, J.; Krystal, J.; Kennedy, J.L. (Yale Univ., New Haven, CT (United States) West Haven Dept. of Veterans Affairs Medical Center, CT (United States)); O'Malley, S.; Risch, N.; Merikangas, K.; Kidd, K.K. (Yale Univ., New Haven, CT (United States)); Kranzler, H.R. (Univ. of Connecticut, Farmington (United States))

    1991-10-02

    The author attempted to replicate a positive allelic association between the A1 allele of DRD2 (the D{sub 2} dopamine receptor locus) and alcoholism that has been reported. They compared allele frequencies at the previously described Taq I restriction fragment length polymorphism system of DRD2 in alcoholics and random population controls.

  1. Genome-wide Association Study of Subtype-Specific Epithelial Ovarian Cancer Risk Alleles Using Pooled DNA

    PubMed Central

    Earp, Madalene A.; Kelemen, Linda E.; Magliocco, Anthony M.; Swenerton, Kenneth D.; Chenevix–Trench, Georgia; Lu, Yi; Hein, Alexander; Ekici, Arif B.; Beckmann, Matthias W.; Fasching, Peter A.; Lambrechts, Diether; Despierre, Evelyn; Vergote, Ignace; Lambrechts, Sandrina; Doherty, Jennifer A.; Rossing, Mary Anne; Chang-Claude, Jenny; Rudolph, Anja; Friel, Grace; Moysich, Kirsten B.; Odunsi, Kunle; Sucheston-Campbell, Lara; Lurie, Galina; Goodman, Marc T.; Carney, Michael E.; Thompson, Pamela J.; Runnebaum, Ingo B.; Dürst, Matthias; Hillemanns, Peter; Dörk, Thilo; Antonenkova, Natalia; Bogdanova, Natalia; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.; Butzow, Ralf; Bunker, Clareann H.; Modugno, Francesmary; Edwards, Robert P.; Ness, Roberta B.; du Bois, Andreas; Heitz, Florian; Schwaab, Ira; Harter, Philipp; Karlan, Beth Y.; Walsh, Christine; Lester, Jenny; Jensen, Allan; Kjær, Susanne K.; Høgdall, Claus K.; Høgdall, Estrid; Lundvall, Lene; Sellers, Thomas A.; Fridley, Brooke L.; Goode, Ellen L.; Cunningham, Julie M.; Vierkant, Robert A.; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca; Southey, Melissa C.; Liang, Dong; Wu, Xifeng; Lu, Karen; Hildebrandt, Michelle A.T.; Levine, Douglas A.; Bisogna, Maria; Schildkraut, Joellen M.; Iversen, Edwin S.; Weber, Rachel Palmieri; Berchuck, Andrew; Cramer, Daniel W.; Terry, Kathryn L.; Poole, Elizabeth M.; Tworoger, Shelley S.; Bandera, Elisa V.; Chandran, Urmila; Orlow, Irene; Olson, Sara H.; Wik, Elisabeth; Salvesen, Helga B.; Bjorge, Line; Halle, Mari K.; van Altena, Anne M.; Aben, Katja K.H.; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; Pejovic, Tanja; Bean, Yukie T.; Cybulski, Cezary; Gronwald, Jacek; Lubinski, Jan; Wentzensen, Nicolas; Brinton, Louise A.; Lissowska, Jolanta; Garcia–Closas, Montserrat; Dicks, Ed; Dennis, Joe; Easton, Douglas F.; Song, Honglin; Tyrer, Jonathan P.; Pharoah, Paul D. P.; Eccles, Diana; Campbell, Ian G.; Whittemore, Alice S.; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph H.; Flanagan, James M.; Paul, James; Brown, Robert; Phelan, Catherine M.; Risch, Harvey A.; McLaughlin, John R.; Narod, Steven A.; Ziogas, Argyrios; Anton-Culver, Hoda; Gentry-Maharaj, Aleksandra; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Wu, Anna H.; Pearce, Celeste L.; Pike, Malcolm C.; Dansonka-Mieszkowska, Agnieszka; Rzepecka, Iwona K; Szafron, Lukasz M; Kupryjanczyk, Jolanta; Cook, Linda S.; Le, Nhu D.; Brooks–Wilson, Angela

    2014-01-01

    Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS (56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low malignant potential (LMP) serous, and 24 for invasive serous EOC), selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95% confidence intervals are reported. Nine variants tagging 6 loci were associated with subtype-specific EOC risk at P<0.05, and had an OR that agreed in direction of effect with the GWAS results. Several of these variants are in or near genes with a biological rationale for conferring EOC risk, including ZFP36L1 and RAD51B for mucinous EOC (rs17106154, OR=1.17, P=0.029, n=1,483 cases), GRB10 for endometrioid and clear cell EOC (rs2190503, P=0.014, n=2,903 cases), and C22orf26/BPIL2 for LMP serous EOC (rs9609538, OR=0.86, P=0.0043, n=892 cases). In analyses that included the 75 GWAS samples, the association between rs9609538 (OR=0.84, P=0.0007) and LMP serous EOC risk remained statistically significant at P<0.0012 adjusted for multiple testing. Replication in additional samples will be important to verify these results for the less-common EOC subtypes. PMID:24190013

  2. A Novel Simple Method for Determining CYP2D6 Gene Copy Number and Identifying Allele(s) with Duplication/Multiplication

    PubMed Central

    Langaee, Taimour; Hamadeh, Issam; Chapman, Arlene B.; Gums, John G.; Johnson, Julie A.

    2015-01-01

    Background Cytochrome P450 2D6 (CYP2D6) gene duplication and multiplication can result in ultrarapid drug metabolism and therapeutic failure or excessive response in patients. Long range polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) and sequencing are usually used for genotyping CYP2D6 duplication/multiplications and identification, but are labor intensive, time consuming, and costly. Methods We developed a simple allele quantification-based Pyrosequencing genotyping method that facilitates CYP2D6 copy number variation (CNV) genotyping while also identifying allele-specific CYP2D6 CNV in heterozygous samples. Most routine assays do not identify the allele containing a CNV. A total of 237 clinical and Coriell DNA samples with different known CYP2D6 gene copy numbers were genotyped for CYP2D6 *2, *3, *4, *6, *10, *17, *41 polymorphisms and CNV determination. Results The CYP2D6 gene allele quantification/identification were determined simultaneously with CYP2D6*2, *3, *4, *6, *10, *17, *41 genotyping. We determined the exact CYP2D6 gene copy number, identified which allele had the duplication or multiplication, and assigned the correct phenotype and activity score for all samples. Conclusions Our method can efficiently identify the duplicated CYP2D6 allele in heterozygous samples, determine its copy number in a fraction of time compared to conventional methods and prevent incorrect ultrarapid phenotype calls. It also greatly reduces the cost, effort and time associated with CYP2D6 CNV genotyping. PMID:25625348

  3. PCSK9 polymorphism in a Tunisian cohort: identification of a new allele, L8, and association of allele L10 with reduced coronary heart disease risk.

    PubMed

    Slimani, Afef; Hrira, Mohamed Yahia; Najah, Mohamed; Jomaa, Walid; Maatouk, Faouzi; Hamda, Khaldoun Ben; Abifadel, Marianne; Rabès, Jean-Pierre; Boileau, Catherine; Rouis, Mustapha; Slimane, Mohamed Naceur; Varret, Mathilde

    2015-02-01

    The c.61_63dupCTG (L10) allele of rs72555377 polymorphism in PCSK9 has been reported to be associated with low-density lipoprotein-cholesterol (LDL-C) levels and with a decreased risk of coronary artery disease (CAD). We investigated the effect of two known alleles for rs72555377, L10 and L11, on the risk of CAD in a Tunisian cohort (218 patients diagnosed by angiography and 125 control subjects). Two subgroups of patients were defined by their level of stenosis: ?50% for CAD and <50% for no-CAD. The genotypes were obtained by the size measurement of fluorescent-labeled PCR products. We identified a novel allele for the rs72555377 polymorphism: an in-frame deletion, c.61_63delCTG (L8). The frequency of the L10 allele was significantly higher in the no-CAD subgroup than in the CAD subgroup (0.210 vs 0.114, p = 0.045), and than in the subgroup of CAD patients presenting a stenosis ?50% in two or three major coronary arteries (0.210 vs 0.125, p = 0.028). Multiple regression analysis showed that the L10 allele was significantly associated with a reduced risk of CAD (p = 0.049, OR = 0.51[0.26-1.00]), and with its reduced severity (p = 0.045, OR = 0.44[0.20-0.98]). The L10 allele is associated with a reduced risk and severity of CAD, seemingly independently of its LDL-lowering effect, suggesting a direct effect of PCSK9 on atherogenesis. PMID:25239117

  4. Nice European Council

    NSDL National Science Digital Library

    EU members met last week in Nice, France to revise the manner in which the European Union reaches decisions in preparation for the entry of new member countries. Among the key provisions of the Treaty of Nice are a new formula for qualified majority voting (QMV), majority voting in some areas will now override individual country vetoes, and a reduction in the size of the European Commission. Background information on the meeting, progress reports, photos, speeches, and other materials are available at the official site of the Nice Council. Most of these resources are available in multiple languages. The full text of the Treaty itself is available in .pdf format from the main page.

  5. European Space Agency

    NSDL National Science Digital Library

    This is the home page of the European Space Agency (ESA), the European equivalent to NASA, formed of 16 member countries. Users can access information on ESA's activities, including such topics as Earth observation, human spaceflight, and various aspects of space science. The educational section includes exercises for high school and college students and a teachers' section with projects, classroom tools, and training information. The kids' section includes lab activities, games, and news articles written for younger students. A multimedia gallery is provided that contains imagery of Mars, Earth, and other objects in the solar system, artists' conceptions of spacecraft, and others. There is also a media center which provides press releases, information notes, and information on ESA television broadcasts. Miscellaneous services include an events calendar, list of publications, and a "frequently asked questions" section. The site can be translated into a variety of languages.

  6. European Environment Agency (EEA)

    NSDL National Science Digital Library

    The European Environment Agency (EEA) Website contains a huge selection of online environmental information, data, and reports pertaining to all fifteen EU states, as well as Iceland, Lichtenstein, and Norway. Information is organized by themes, and the site employs a powerful multilingual search feature. Themes include environmental issues, sectors and activities, information related to specific media, regions, and actions for environmental improvement. The site also contains EEA publications and reports, as well as a data service providing access to data sets covering at least all EU member states. Finally, the European Environment Information and Observation Network (EIONET) provides a network which "facilitates co-operation and flow of data and information between EIONET partners and with the EEA." The EEA Website is a large, research-oriented repository of information.

  7. Hunting for the LCT-13910*T allele between the Middle Neolithic and the Middle Ages suggests its absence in dairying LBK people entering the Kuyavia region in the 8th millennium BP.

    PubMed

    Witas, Henryk W; P?oszaj, Tomasz; J?drychowska-Da?ska, Krystyna; Witas, Piotr J; Mas?owska, Alicja; Jerszy?ska, Blandyna; Koz?owski, Tomasz; Osipowicz, Grzegorz

    2015-01-01

    Populations from two medieval sites in Central Poland, Stary Brze?? Kujawski-4 (SBK-4) and Gruczno, represented high level of lactase persistence (LP) as followed by the LCT-13910*T allele's presence (0.86 and 0.82, respectively). It was twice as high as in contemporaneous Cedynia (0.4) and ?ródka (0.43), both located outside the region, higher than in modern inhabitants of Poland (0.51) and almost as high as in modern Swedish population (0.9). In an attempt to explain the observed differences its frequency changes in time were followed between the Middle Neolithic and the Late Middle Ages in successive dairying populations on a relatively small area (radius ?60km) containing the two sites. The introduction of the T allele to Kuyavia 7.4 Ka BP by dairying LBK people is not likely, as suggested by the obtained data. It has not been found in any of Neolithic samples dated between 6.3 and 4.5 Ka BP. The identified frequency profile indicates that both the introduction and the beginning of selection could have taken place approx. 4 millennia after first LBK people arrived in the region, shifting the value of LP frequency from 0 to more than 0.8 during less than 130 generations. We hypothesize that the selection process of the T allele was rather rapid, starting just after its introduction into already milking populations and operated via high rates of fertility and mortality on children after weaning through life-threatening conditions, favoring lactose-tolerant individuals. Facing the lack of the T allele in people living on two great European Neolithization routes, the Danubian and Mediterranean ones, and based on its high frequency in northern Iberia, its presence in Scandinavia and estimated occurrence in Central Poland, we propose an alternative Northern Route of its spreading as very likely. None of the successfully identified nuclear alleles turned out to be deltaF508 CFTR. PMID:25853887

  8. Predicting European Takeover Targets

    Microsoft Academic Search

    Gurvinder Brar; Daniel Giamouridis; Manolis Liodakis

    2009-01-01

    AbstractThis article extends the Palepu (1986) acquisition likelihood model by incorporating measures of a technical nature, e.g. momentum, trading volume as well as a measure of market sentiment. We use the proposed model to predict takeover targets in a large sample of European and cross-border merger and acquisition deals and validate its performance on an in- and out-of-sample basis. The

  9. The European Spallation Source

    SciTech Connect

    Peggs, S; Eshraqi, M; Hahn, H; Jansson, A; Lindroos, M; Ponton, A; Rathsman, K; Trahern, G; Bousso, S; Calaga, R; Devanz, G; Duperrier, R D; Eguia, J; Gammino, S; Moller, S P; Oyon, C; Ruber, R.J.M.Y.

    2011-03-01

    The European Spallation Source (ESS) is a 5 MW, 2.5 GeV long pulse proton linac, to be built and commissioned in Lund, Sweden. The Accelerator Design Update (ADU) project phase is under way, to be completed at the end of 2012 by the delivery of a Technical Design Report. Improvements to the 2003 ESS design will be summarised, and the latest design activities will be presented.

  10. European Monetary Union

    NSDL National Science Digital Library

    The EMU site was created by a group of students at the King's Hospital Secondary School in Palmerston, Dublin, Ireland. Their site discusses the potential positive and negative effects of the EMU, popular opinion on the Euro, and the possible side effects for Ireland, which will join, when its neighbor Britain does not join. After months of doubt and political difficulties in France, Germany, and most recently, Italy, it now appears that the unified European currency, the Euro, will indeed begin on January 1, 1999 to replace the national currencies of as many as 10 or 11 countries. The path to a unified currency is by no means smooth, however. Many European Union member states are finding it politically difficult to reduce their budget deficit to 3 percent of gross domestic product and other states, such as Britain and Denmark, are choosing to remain out for now regardless. On the other hand, European economic growth will apparently exceed earlier expectations, allowing leaders to use increased tax revenues instead of cutting social services to qualify.

  11. Genetic diversity of European spelt wheat ( Triticum aestivum ssp. spelta L. em. Thell.) revealed by glutenin subunit variations at the Glu1 and Glu3 loci

    Microsoft Academic Search

    Xueli An; Qiaoyun Li; Yueming Yan; Yinghua Xiao; S. L. K. Hsam; F. J. Zeller

    2005-01-01

    Summary  High and low molecular weight glutenin subunit (HMW-GS and LMW-GS) compositions of 270 European spelts, 15 Iranian spelts\\u000a and 25 bread wheat cultivars were analyzed by one- and two-dimensional gel electrophoresis. The results revealed a total of\\u000a 22 HMW-GS alleles (4 at Glu-A1, 11 at Glu-B1 and 7 at Glu-D1) and 32 allele combinations among the three Glu-1 loci. Two

  12. The ADA*2 allele of the adenosine deaminase gene (20q13.11) and recurrent spontaneous abortions: an age-dependent association

    PubMed Central

    Nunes, Daniela Prudente Teixeira; Spegiorin, Lígia Cosentino Junqueira Franco; de Mattos, Cinara Cássia Brandão; Oliani, Antonio Helio; Vaz-Oliani, Denise Cristina Mós; de Mattos, Luiz Carlos

    2011-01-01

    OBJECTIVE: Adenosine deaminase acts on adenosine and deoxyadenosine metabolism and modulates the immune response. The adenosine deaminase G22A polymorphism (20q.11.33) influences the level of adenosine deaminase enzyme expression, which seems to play a key role in maintaining pregnancy. The adenosine deaminase 2 phenotype has been associated with a protective effect against recurrent spontaneous abortions in European Caucasian women. The aim of this study was to investigate whether the G22A polymorphism of the adenosine deaminase gene is associated with recurrent spontaneous abortions in Brazilian women. METHODS: A total of 311 women were recruited to form two groups: G1, with a history of recurrent spontaneous abortions (N?=?129), and G2, without a history of abortions (N?=?182). Genomic DNA was extracted from peripheral blood with a commercial kit and PCR-RFLP analysis was used to identify the G22A genetic polymorphism. Fisher's exact test and odds ratio values were used to compare the proportions of adenosine deaminase genotypes and alleles between women with and without a history of recurrent spontaneous abortion (p<0.05). The differences between mean values for categorical data were calculated using unpaired t tests. The Hardy-Weinberg equilibrium was assessed with a chi-square test. RESULTS: Statistically significant differences were identified for the frequencies of adenosine deaminase genotypes and alleles between the G1 and G2 groups when adjusted for maternal age. CONCLUSIONS: The results suggest that the adenosine deaminase *2 allele is associated with a low risk for recurrent spontaneous abortions, but this association is dependent on older age. PMID:22086524

  13. Contemporary evolution, allelic recycling, and adaptive radiation of the threespine stickleback

    E-print Network

    Aguirre, Windsor E.

    not attempt to study natural selection and evolution in contemporary natural populations. Darwin's successors, invasive species, parallelism, recessive allele, threespine stickleback. INTRODUCTION Charles Darwin (1859 to exaggerate the necessary slowness of the action of natural selection,' and subsequent empirical evidence

  14. Temporal Allele Frequency Change and Estimation of Effective Size in Populations with Overlapping Generations

    PubMed Central

    Jorde, P. E.; Ryman, N.

    1995-01-01

    In this paper we study the process of allele frequency change in finite populations with overlapping generations with the purpose of evaluating the possibility of estimating the effective size from observations of temporal frequency shifts of selectively neutral alleles. Focusing on allele frequency changes between successive cohorts (individuals born in particular years), we show that such changes are not determined by the effective population size alone, as they are when generations are discrete. Rather, in populations with overlapping generations, the amount of temporal allele frequency change is dependent on the age-specific survival and birth rates. Taking this phenomenon into account, we present an estimator for effective size that can be applied to populations with overlapping generations. PMID:7713410

  15. Using multi-locus allelic sequence data to estimate genetic divergence among four Lilium (Liliaceae) cultivars.

    PubMed

    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. PMID:25368628

  16. A human-specific allelic group of the MHC DRB1 gene in primates

    PubMed Central

    2014-01-01

    Background Diversity among human leukocyte antigen (HLA) molecules has been maintained by host-pathogen coevolution over a long period of time. Reflecting this diversity, the HLA loci are the most polymorphic in the human genome. One characteristic of HLA diversity is long-term persistence of allelic lineages, which causes trans-species polymorphisms to be shared among closely related species. Modern humans have disseminated across the world after their exodus from Africa, while chimpanzees have remained in Africa since the speciation event between humans and chimpanzees. It is thought that modern humans have recently acquired resistance to novel pathogens outside Africa. In the present study, we investigated HLA alleles that could contribute to this local adaptation in humans and also studied the contribution of natural selection to human evolution by using molecular data. Results Phylogenetic analysis of HLA-DRB1 genes identified two major groups, HLA Groups A and B. Group A formed a monophyletic clade distinct from DRB1 alleles in other Catarrhini, suggesting that Group A is a human-specific allelic group. Our estimates of divergence time suggested that seven HLA-DRB1 Group A allelic lineages in humans have been maintained since before the speciation event between humans and chimpanzees, while chimpanzees possess only one DRB1 allelic lineage (Patr-DRB1*03), which is a sister group to Group A. Experimental data showed that some Group A alleles bound to peptides derived from human-specific pathogens. Of the Group A alleles, three exist at high frequencies in several local populations outside Africa. Conclusions HLA Group A alleles are likely to have been retained in human lineages for a long period of time and have not expanded since the divergence of humans and chimpanzees. On the other hand, most orthologs of HLA Group A alleles may have been lost in the chimpanzee due to differences in selective pressures. The presence of alleles with high frequency outside of Africa suggests these HLA molecules result from the local adaptations of humans. Our study helps elucidate the mechanism by which the human adaptive immune system has coevolved with pathogens over a long period of time. PMID:24928070

  17. Genetic diversity in European red deer (Cervus elaphus L.): anthropogenic influences on natural populations.

    PubMed

    Hartl, Günther B; Zachos, Frank; Nadlinger, Karl

    2003-08-01

    Allozyme, microsatellite and mtDNA (RFLP and sequence) data of European red deer populations were examined as to their capability of indicating anthropogenic influences such as the keeping of animals in enclosures, selective hunting for trophies translocation of specimens to improve trophy quality and habitat fragmentation. Deer in enclosures revealed considerable deviations of allele frequencies from isolation-by-distance expectations but no remarkable loss of genetic diversity. Particular allozyme genotypes were associated with antler morphology, and selective hunting was shown to alter allele frequencies in the expected direction. Habitat fragmentation is reflected by various kinds of genetic markers but due to the lack of information on population histories no unequivocal evidence on particular human activities could be obtained. PMID:14558447

  18. Common and well-documented HLA alleles: 2012 update to the CWD catalogue.

    PubMed

    Mack, S J; Cano, P; Hollenbach, J A; He, J; Hurley, C K; Middleton, D; Moraes, M E; Pereira, S E; Kempenich, J H; Reed, E F; Setterholm, M; Smith, A G; Tilanus, M G; Torres, M; Varney, M D; Voorter, C E M; Fischer, G F; Fleischhauer, K; Goodridge, D; Klitz, W; Little, A-M; Maiers, M; Marsh, S G E; Müller, C R; Noreen, H; Rozemuller, E H; Sanchez-Mazas, A; Senitzer, D; Trachtenberg, E; Fernandez-Vina, Marcelo

    2013-04-01

    We have updated the catalogue of common and well-documented (CWD) human leukocyte antigen (HLA) alleles to reflect current understanding of the prevalence of specific allele sequences. The original CWD catalogue designated 721 alleles at the HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, and -DPB1 loci in IMGT (IMmunoGeneTics)/HLA Database release 2.15.0 as being CWD. The updated CWD catalogue designates 1122 alleles at the HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1 and -DPB1 loci as being CWD, and represents 14.3% of the HLA alleles in IMGT/HLA Database release 3.9.0. In particular, we identified 415 of these alleles as being 'common' (having known frequencies) and 707 as being 'well-documented' on the basis of ~140,000 sequence-based typing observations and available HLA haplotype data. Using these allele prevalence data, we have also assigned CWD status to specific G and P designations. We identified 147/151 G groups and 290/415 P groups as being CWD. The CWD catalogue will be updated on a regular basis moving forward, and will incorporate changes to the IMGT/HLA Database as well as empirical data from the histocompatibility and immunogenetics community. This version 2.0.0 of the CWD catalogue is available online at cwd.immunogenomics.org, and will be integrated into the Allele Frequencies Net Database, the IMGT/HLA Database and National Marrow Donor Program's bioinformatics web pages. PMID:23510415

  19. Development of a standard set of microsatellite reference alleles for identification of grape cultivars

    Microsoft Academic Search

    P. This; A. Jung; P. Boccacci; J. Borrego; R. Botta; L. Costantini; M. Crespan; G. S. Dangl; C. Eisenheld; F. Ferreira-Monteiro; S. Grando; J. Ibáñez; T. Lacombe; V. Laucou; R. Magalhães; C. P. Meredith; N. Milani; E. Peterlunger; F. Regner; L. Zulini; E. Maul

    2004-01-01

    In order to investigate the comparability of microsatellite profiles obtained in different laboratories, ten partners in seven countries analyzed 46 grape cultivars at six loci (VVMD5, VVMD7, VVMD27, VVS2, VrZAG62, and VrZAG79). No effort was made to standardize equipment or protocols. Although some partners obtained very similar results, in other cases different absolute allele sizes and, sometimes, different relative allele

  20. Allele frequencies for six miniSTR loci of two ethnic populations in China

    Microsoft Academic Search

    Rufeng Bai; Meisen Shi; Xiaojun Yu; Junyao Lv; Youhua Tu

    2007-01-01

    Allele frequencies and forensic parameters for the six miniSTR loci D1S1677, D2S441, D4S2364, D10S1248, D14S1434, and D22S1045 were investigated in two ethnic China populations. Allele frequencies for each locus are reported along with nomenclature based on sequence analysis. The polymerase chain reaction (PCR) products contained within the six loci were less than 125bp in size. All loci showed a moderate

  1. Identification and functional characterization of three novel alleles for the serotonin transporter-linked polymorphic region

    Microsoft Academic Search

    E A Ehli; Y Hu; T Lengyel-Nelson; J J Hudziak; G E Davies

    2012-01-01

    A promoter polymorphism in the serotonin transporter gene (5-HTTLPR) has been reported to confer relative risk for phenotypes (depression\\/anxiety) and endophenotypes (amygdala reactivity). In this report, we identify and characterize three rare 5-HTTLPR alleles not previously described in the human literature. The three novel alleles were identified while genotyping 5-HTTLPR in a family-based attention deficit hyperactivity disorder clinical population. Two

  2. Mitochondrial DNA haplogroups and APOE4 allele are non-independent variables in sporadic Alzheimer's disease

    Microsoft Academic Search

    Giuseppina Carrieri; Massimiliano Bonafè; Maria De Luca; Giuseppina Rose; Ottavia Varcasia; Amalia Bruni; Raffaele Maletta; Benedetta Nacmias; Sandro Sorbi; Francesco Corsonello; Emidio Feraco; Kirill F. Andreev; Anatoli I. Yashin; Claudio Franceschi; Giovanna De Benedictis

    2001-01-01

    Allele ƞ of the nuclear APOE gene is a leading genetic risk factor for sporadic Alzheimer's disease (AD). Moreover, an allele-specific effect of APOE isoforms on neuronal cell oxidative death is known. Because of the role of the mitochondrial genome (mtDNA) in oxidative phosphorylation and oxidative stress, an interaction between APOE polymorphism and mtDNA inherited variability in the genetic susceptibility

  3. Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility

    Microsoft Academic Search

    Taane G Clark; Andrew E Fry; Sarah Auburn; Susana Campino; Mahamadou Diakite; Angela Green; Anna Richardson; Yik Y Teo; Kerrin Small; Jonathan Wilson; Muminatou Jallow; Fatou Sisay-Joof; Margaret Pinder; Pardis Sabeti; Dominic P Kwiatkowski; Kirk A Rockett

    2009-01-01

    Several lines of evidence link glucose-6-phosphate dehydrogenase (G6PD) deficiency to protection from severe malaria. Early reports suggested most G6PD deficiency in sub-Saharan Africa was because of the 202A\\/376G G6PD A? allele, and recent association studies of G6PD deficiency have employed genotyping as a convenient way to determine enzyme status. However, further work has suggested that other G6PD deficiency alleles are

  4. Two different primate species express an identical functional MHC class I allele

    Microsoft Academic Search

    David T. Evans; Marian S. Piekarczyk; Luis Cadavid; Virginia S. Hinshaw; D. I. Watkins

    1998-01-01

    The products of the highly polymorphic and variable major histocompatibility complex (MHC) class I loci play a crucial role\\u000a in host defenses against infectious disease. While similar alleles have been found in closely related species, sharing of\\u000a a functional MHC class I allele between two species has never been reported. Here we show that an identical functional MHC\\u000a class I

  5. Quantitative Restriction Fragment Length Polymorphism: A Procedure for Quantitation of Diphtheria Toxin Gene CRM197 Allele

    Microsoft Academic Search

    Elena A. Pushnova; Yu Sheng Zhu

    1998-01-01

    Here we present an assay for quantitation of a particular gene allele in DNA mixtures by means of restriction fragment length polymorphism (RFLP) in combination with polymerase chain reaction (PCR). We applied the quantitative RFLP principle for estimation of the relative amount of diphtheria toxin gene CRM197 allele inCorynebacterium diphtheriaeculture DNA samples. The procedure is based on PCR-mediated generation of

  6. The inheritance, linkage, and fiber development of a new mutant allele in cotton, Gossypium hirsutum L. 

    E-print Network

    Narbuth, Edward Vernon

    1989-01-01

    THE INHERITANCE, LINKAGE, AND FIBER DEVELOPMENT OF A NEW MUTANT ALLELE IN COTTON, GOSSYPIUM HIRSUTUM L. A Thesis by EDWARD VERNON NARBUTH Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment... of the requirements for the degree of MASTER OF SCIENCE May 1989 Major Subject: Plant Breeding THE INHERITANCE, LINKAGE, AND FIBER DEVELOPMENT OF A NEW MUTANT ALLELE IN COTTON, GOSSYPIUM HIRSUTUM L. A Thesis by EDWARD VERNON NARBUTH Ap d as to st...

  7. Immature Thymocytes Employ Distinct Signaling Pathways for Allelic Exclusion versus Differentiation and Expansion

    Microsoft Academic Search

    Frank Gärtner; Frederick W Alt; Robert Monroe; Micheline Chu; Barry P Sleckman; Laurie Davidson; Wojciech Swat

    1999-01-01

    T cell receptor (TCR) ? chain allelic exclusion occurs at the thymocyte CD4?8? (double-negative, or DN) to CD4+8+ (double-positive, or DP) transition, concurrently with differentiation and cellular expansion, and is imposed by a negative feedback loop in which a product of the first rearranged TCR? allele arrests further recombination in the TCR? locus. All of the major events associated with

  8. The intermediate alleles of the fragile X CGG repeat in patients with mental retardation.

    PubMed

    Mornet, E; Chateau, C; Simon-Bouy, B; Serre, J L

    1998-03-01

    We have analysed the size of the non-expanded FRAXA CGG repeat in 385 male patients affected by mental retardation and in 182 unrelated normal chromosomes as control. The results show that intermediate alleles with more than 40 repeats were not significantly more frequent in patients than in controls. These data do not corroborate previous findings supporting the idea that intermediate alleles may have a deleterious effect on mental retardation. PMID:9630074

  9. cDNA cloning and molecular analysis of two self-incompatibility alleles from apple

    Microsoft Academic Search

    Wim Broothaerts; Greet A. Janssens; Paul Proost; Willem F. Broekaert

    1995-01-01

    Complementary DNA clones representing two alleles of the self-incompatibility (S) locus of apple (Malus × domestica Borkh.) have been isolated and characterised. One of the alleles corresponds to a 29 kDa ribonuclease (S-RNase) that was purified from pistil tissue. On northern blots, both cDNAs hybridized to a transcript that was only present in pistils and not in the other plant

  10. Quantification of allele-specific expression of a gene encoding strawberry polygalacturonase-inhibiting protein (PGIP) using Pyrosequencing.

    PubMed

    Schaart, Jan G; Mehli, Lisbeth; Schouten, Henk J

    2005-02-01

    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 the transcript abundance of six individual, highly homologous alleles of a polygalacturonase-inhibiting protein gene (FaPGIP) from octoploid strawberry (Fragaria x ananassa). We applied the highly quantitative Pyrosequencing method which, for the gene under study, detected allele frequency differences as small as 4.0 +/- 2.8%. Pyrosequencing of RT-PCR products showed that one FaPGIP allele was preferentially expressed in leaf tissue, while two other alleles were expressed in a fruit-specific way. For fruits that were inoculated with Botrytis cinerea a strong increase in overall FaPGIP gene expression was observed. This upregulation was accompanied by a significant change in FaPGIP allele frequencies when compared with non-treated fruits. Remarkably, in the five cultivars tested, the allele frequency in cDNA from the inoculated fruits was similar to that in genomic DNA, suggesting uniform upregulation of all FaPGIP alleles present as a result of pathogenesis-related stress. The results demonstrate that when Pyrosequencing of RT-PCR products is performed, novel allele-specific gene regulation can be detected and quantified. PMID:15659106

  11. Association of somatotrophinomas with loss of alleles on chromosome 11 and with gsp mutations.

    PubMed Central

    Thakker, R V; Pook, M A; Wooding, C; Boscaro, M; Scanarini, M; Clayton, R N

    1993-01-01

    The molecular pathology of somatotrophinomas has been investigated by a combined search for dominant mutations of the gene encoding the Gs alpha protein and for recessive mutations involving chromosome 11q13, which contains the gene causing multiple endocrine neoplasia type 1 (MEN1). Somatotrophinomas and peripheral leukocytes were obtained from thirteen patients with acromegaly; one patient also suffered from MEN1. Five DNA probes identifying restriction fragment length polymorphisms from 11q revealed allele loss in pituitary tumors from five (four non-MEN1 and one MEN1) patients. Deletion mapping revealed that the region of allele loss common to the somatotrophinomas involved 11q13. An analysis for similar allelic deletions at 12 other loci from chromosomes 1-5, 7-9, 12-14, and 17 did not reveal generalized allele loss in the somatotrophinomas. These results, which represent the first report of chromosome 11 allele loss occurring in non-MEN1 somatotrophinomas, indicate that a recessive oncogene on 11q13 is specifically involved in the monoclonal development of somatotrophinomas. In addition Gs alpha mutations were detected in two non-MEN1 somatotrophinomas, one of which also revealed allele loss of chromosome 11. Thus, our results reveal that the development of somatotrophinomas is associated with alterations in both dominant and recessive oncogenes and further characterization of these genetic abnormalities will help to elucidate the multistep etiology and progression of somatotrophinomas. Images PMID:8514889

  12. Interspecific Backcross Mice Show Sex-Specific Differences in Allelic Inheritance

    PubMed Central

    Siracusa, L. D.; Alvord, W. G.; Bickmore, W. A.; Jenkins, N. A.; Copeland, N. G.

    1991-01-01

    Transmission distortion is identified as a difference in transmission frequency of two alleles from the normal 1:1 Mendelian segregation in diploid organisms. Transmission distortion can extend over part or all of a chromosome. The recent development of interspecific mouse backcrosses has provided a powerful method for multilocus mapping of entire chromosomes in a single cross, and consequently for identifying distortions in allelic inheritance. We used an interspecific backcross of [(C57BL/6J X Mus spretus)F(1) X C57BL/6J] mice to map molecular loci to mouse chromosome 2 and had previously found that the distal region of the chromosome showed distortions in allelic inheritance. We now report the mapping of five loci (Actc-1, D2Hgu1, His-1, Hox-4.1 and Neb) to chromosome 2, which, in addition to the Abl, Ada, B2m, Bmp-2a, Hc, Emv-15, Fshb, Hck-1, Pax-1, Pck-1, Spna-2 and Vim loci previously mapped in our interspecific backcross, serve as markers to measure allelic inheritance along ~75% of mouse chromosome 2. Statistical analyses are used to identify and delimit chromosomal regions showing transmission distortion and to determine whether there are sex-specific differences in allelic inheritance. These studies provide evidence for sex-specific differences in allelic inheritance for chromosome 2 and suggest biological explanations for this form of transmission distortion. PMID:1916246

  13. Activation of the Arabidopsis thaliana Immune System by Combinations of Common ACD6 Alleles

    PubMed Central

    Todesco, Marco; Kim, Sang-Tae; Chae, Eunyoung; Bomblies, Kirsten; Zaidem, Maricris; Smith, Lisa M.; Weigel, Detlef; Laitinen, Roosa A. E.

    2014-01-01

    A fundamental question in biology is how multicellular organisms distinguish self and non-self. The ability to make this distinction allows animals and plants to detect and respond to pathogens without triggering immune reactions directed against their own cells. In plants, inappropriate self-recognition results in the autonomous activation of the immune system, causing affected individuals to grow less well. These plants also suffer from spontaneous cell death, but are at the same time more resistant to pathogens. Known causes for such autonomous activation of the immune system are hyperactive alleles of immune regulators, or epistatic interactions between immune regulators and unlinked genes. We have discovered a third class, in which the Arabidopsis thaliana immune system is activated by interactions between natural alleles at a single locus, ACCELERATED CELL DEATH 6 (ACD6). There are two main types of these interacting alleles, one of which has evolved recently by partial resurrection of a pseudogene, and each type includes multiple functional variants. Most previously studies hybrid necrosis cases involve rare alleles found in geographically unrelated populations. These two types of ACD6 alleles instead occur at low frequency throughout the range of the species, and have risen to high frequency in the Northeast of Spain, suggesting a role in local adaptation. In addition, such hybrids occur in these populations in the wild. The extensive functional variation among ACD6 alleles points to a central role of this locus in fine-tuning pathogen defenses in natural populations. PMID:25010663

  14. Frequency of alleles and haplotypes of the human leukocyte antigen system in Bauru, São Paulo, Brazil

    PubMed Central

    Salvadori, Luana de Cassia; Santana, Fabiana Covolo de Souza; Marcos, Elaine Valim Camarinha

    2014-01-01

    Background: HLA allele identification is used in bone marrow transplant programs as HLA compatibility between the donor and recipient may prevent graft rejection. Objective: This study aimed to estimate the frequency of alleles and haplotypes of the HLA system in the region of Bauru and compare these with the frequencies found in other regions of the country. Methods: HLA-A*, HLA-B*, and HLA-DRB1* allele frequencies and haplotypes were analyzed in a sample of 3542 volunteer donors at the National Registry of Voluntary Bone Marrow Donors (REDOME) in Bauru. HLA low resolution typing was performed using reverse line blot with the Dynal Reli(tm) SSO-HLA Typing Kit and automated Dynal AutoReli(tm)48 device (Invitrogen, USA). Results: Twenty, 36, and 13 HLA-A*, HLA-B*, and HLA-DRB1* allele groups, respectively, were identified. The most common alleles for each locus were HLA-A*02, HLA-B*35, and HLA-DRB1*07. The most frequent haplotype was A*01-B*08-DRB1*03. Allele and haplotype frequencies were compared to other regions in Brazil and the similarities and differences among populations are shown. Conclusion: The knowledge of the immunogenic profile of a population contributes to the comprehension of the historical and anthropological aspects of different regions. Moreover, this helps to find suitable donors quickly, thereby shortening waiting lists for transplants and thus increasing survival rates among recipients. PMID:24790535

  15. Natural selection for the Duffy-null allele in the recently admixed people of Madagascar.

    PubMed

    Hodgson, Jason A; Pickrell, Joseph K; Pearson, Laurel N; Quillen, Ellen E; Prista, António; Rocha, Jorge; Soodyall, Himla; Shriver, Mark D; Perry, George H

    2014-08-22

    While gene flow between distantly related populations is increasingly recognized as a potentially important source of adaptive genetic variation for humans, fully characterized examples are rare. In addition, the role that natural selection for resistance to vivax malaria may have played in the extreme distribution of the protective Duffy-null allele, which is nearly completely fixed in mainland sub-Saharan Africa and absent elsewhere, is controversial. We address both these issues by investigating the evolution of the Duffy-null allele in the Malagasy, a recently admixed population with major ancestry components from both East Asia and mainland sub-Saharan Africa. We used genome-wide genetic data and extensive computer simulations to show that the high frequency of the Duffy-null allele in Madagascar can only be explained in the absence of positive natural selection under extreme demographic scenarios involving high genetic drift. However, the observed genomic single nucleotide polymorphism diversity in the Malagasy is incompatible with such extreme demographic scenarios, indicating that positive selection for the Duffy-null allele best explains the high frequency of the allele in Madagascar. We estimate the selection coefficient to be 0.066. Because vivax malaria is endemic to Madagascar, this result supports the hypothesis that malaria resistance drove fixation of the Duffy-null allele in mainland sub-Saharan Africa. PMID:24990677

  16. Grouping of class I HLA alleles using electrostatic distribution maps of the peptide binding grooves.

    PubMed

    Kangueane, Pandjassarame; Sakharkar, Meena Kishore

    2007-01-01

    Human leukocyte antigen (HLA) molecules involved in immune function by binding to short peptides (8-20 residues) have different sequences in different individuals belonging to distinct ethnic population. Hence, the peptide-binding function of HLA alleles is specific. Class I HLA alleles (alternative forms of a gene) are associated with CD8+ T cells, and their allele-specific sequence information is available at the IMGT/HLA database. The available sequences are one-dimensional (ID), and the peptide-binding functional inference often requires 3-dimensional (3D) structural models of respective alleles. Hence, 3D structures were constructed for 1,000 class I HLA alleles (310 A, 570 B, and 120 C) using MODELLER (a comparative protein modeling program for modeling protein structures). The electrostatic distribution maps were generated for each modeled structure using Deep View (Swiss PDB Viewer Version 3.7). The 1,000 models were then grouped into different categories by visual inspection of their electrostatic distribution maps in the peptide binding grooves. The distribution of the models based on electrostatic distribution was 30% negative (300), 1% positive (12), 8% neutral (84), and 60% (604) mixed (random mixture of negative, positive, and neutral). This grouping provides insight toward the inference for functional overlap among HLA alleles. PMID:18450000

  17. First experiences using the new Powerplex® ESX17 and ESI17 kits in casework analysis and allele frequencies for two different regions in Germany.

    PubMed

    Poetsch, Micaela; Bayer, Katharina; Ergin, Zeynep; Milbrath, Marco; Schwark, Thorsten; von Wurmb-Schwark, Nicole

    2011-09-01

    DNA databases are the most efficient tools in criminal investigations with unknown perpetrators. Due to a significant number of random matches in cross-border DNA profile exchanges, the European Network of Forensic Science Institutes (ENFSI) proposed the addition of further short tandem repeats (STRs) to European DNA databases. Therefore, the new Powerplex® ESX17 and Powerplex® ESI17 kits from Promega comprised the 11 established DNA database STRs and additionally the well-known loci D1S1656 and D12S391, as well as D2S441, D10S1248, and D22S1045. The latter three STRs are thereby established as so-called mini-STRs to fulfill the increasing requirements regarding sensitivity and reproducibility for analysis of minute amounts of DNA. Here, we provide allele frequencies for the five additional STRs from two populations from Germany. A test regarding suitability and robustness of the new kits for routine trace analysis showed that it is more likely to obtain a meaningful profile using Powerplex® ESX17 and Powerplex® ESI17 kits compared to the Powerplex® ES kit. However, for both new kits the range of template DNA amount is rather small, e.g., slightly more DNA than recommended resulted in DNA profiles which could not be reliably evaluated due to allelic drop-in or imbalances and overshoots. In our opinion, the new kits are very promising new tools in forensic trace analysis even though handling and evaluation should yet be carried out with great caution. PMID:20567841

  18. Inheritance of resistance to Fusarium head blight in three European winter wheat populations.

    PubMed

    Holzapfel, Josef; Voss, Hans-Henning; Miedaner, Thomas; Korzun, Viktor; Häberle, Jennifer; Schweizer, Günther; Mohler, Volker; Zimmermann, Gerhard; Hartl, Lorenz

    2008-11-01

    Fusarium head blight (FHB) resistance is of particular importance in wheat breeding programmes due to the detrimental effects of this fungal disease on human and animal health, yield and grain quality. Segregation for FHB resistance in three European winter wheat populations enabled the identification of resistance loci in well-adapted germplasm. Populations obtained from crosses of resistant cultivars Apache, History and Romanus with susceptible semi-dwarfs Biscay, Rubens and Pirat, respectively, were mapped and analysed to identify quantitative trait loci (QTL) for FHB severity, ear emergence time and plant height. The results of the present study together with previous studies in UK winter wheat indicated that the semi-dwarfing allele Rht-D1b seems to be the major source for FHB susceptibility in European winter wheat. The high resistance level of the cultivars Romanus and History was conditioned by several minor resistance QTL interacting with the environment and the absence of Rht-D1b. In contrast, the semi-dwarf parents contributed resistance alleles of major effects apparently compensating the negative effects of Rht-D1b on FHB reaction. The moderately resistant cultivar Apache contributed a major QTL on chromosome 6A in a genome region previously shown to carry resistance loci to FHB. A total of 18 genomic regions were repeatedly associated with FHB resistance. The results indicate that common resistance-associated genes or genomic regions are present in European winter wheats. PMID:18670751

  19. European Union: Constraints vs. Opportunities

    E-print Network

    Kahiha, Nguvitjita

    2007-12-17

    in the late 1950s, more than 20 other European countries have applied for membership, with most applications granted. In 1973, the United Kingdom, Ireland and Denmark entered the European alliance. Over the following thirteen years, three southern European... in private households and excludes those in collective households such as boarding houses, halls of residence and hospitals. Employed population consists of those persons who during the reference week did any work for pay or profit for at least one hour...

  20. Enhanced low-template DNA analysis conditions and investigation of allele dropout patterns.

    PubMed

    Hedell, Ronny; Dufva, Charlotte; Ansell, Ricky; Mostad, Petter; Hedman, Johannes

    2015-01-01

    Forensic DNA analysis applying PCR enables profiling of minute biological samples. Enhanced analysis conditions can be applied to further push the limit of detection, coming with the risk of visualising artefacts and allele imbalances. We have evaluated the consecutive increase of PCR cycles from 30 to 35 to investigate the limitations of low-template (LT) DNA analysis, applying the short tandem repeat (STR) analysis kit PowerPlex ESX 16. Mock crime scene DNA extracts of four different quantities (from around 8-84 pg) were tested. All PCR products were analysed using 5, 10 and 20 capillary electrophoresis (CE) injection seconds. Bayesian models describing allele dropout patterns, allele peak heights and heterozygote balance were developed to assess the overall improvements in EPG quality with altered PCR/CE settings. The models were also used to evaluate the impact of amplicon length, STR marker and fluorescent label on the risk for allele dropout. The allele dropout probability decreased for each PCR cycle increment from 30 to 33 PCR cycles. Irrespective of DNA amount, the dropout probability was not affected by further increasing the number of PCR cycles. For the 42 and 84 pg samples, mainly complete DNA profiles were generated applying 32 PCR cycles. For the 8 and 17 pg samples, the allele dropouts decreased from 100% using 30 cycles to about 75% and 20%, respectively. The results for 33, 34 and 35 PCR cycles indicated that heterozygote balance and stutter ratio were mainly affected by DNA amount, and not directly by PCR cycle number and CE injection settings. We found 32 and 33 PCR cycles with 10 CE injection seconds to be optimal, as 34 and 35 PCR cycles did not improve allele detection and also included CE saturation problems. We find allele dropout probability differences between several STR markers. Markers labelled with the fluorescent dyes CXR-ET (red in electropherogram) and TMR-ET (shown as black) generally have higher dropout risks compared with those labelled with JOE (green) and fluorescein (blue). Overall, the marker D10S1248 has the lowest allele dropout probability and D8S1179 the highest. The marker effect is mainly pronounced for 30-32 PCR cycles. Such effects would not be expected if the amplification efficiencies were identical for all markers. Understanding allele dropout risks and the variability in peak heights and balances is important for correct interpretation of forensic DNA profiles. PMID:25282604

  1. HLA-DR alleles in amyloid beta-peptide autoimmunity: a highly immunogenic role for the DRB1*1501 allele.

    PubMed

    Zota, Victor; Nemirovsky, Anna; Baron, Rona; Fisher, Yair; Selkoe, Dennis J; Altmann, Daniel M; Weiner, Howard L; Monsonego, Alon

    2009-09-01

    Active amyloid beta-peptide (Abeta) immunization of patients with Alzheimer's disease (AD) caused meningoencephalitis in approximately 6% of immunized patients in a clinical trial. In addition, long-term studies of AD patients show varying degrees of Abeta Ab responses, which correlate with the extent of Abeta clearance from the brain. In this study, we examined the contribution of various HLA-DR alleles to these immune-response variations by assessing Abeta T cell reactivity, epitope specificity, and immunogenicity. Analysis of blood samples from 133 individuals disclosed that the abundant DR haplotypes DR15 (found in 36% of subjects), DR3 (in 18%), DR4 (12.5%), DR1 (11%), and DR13 (8%) were associated with Abeta-specific T cell responses elicited via distinct T cell epitopes within residues 15-42 of Abeta. Because the HLA-DRB1*1501 occurred most frequently, we examined the effect of Abeta challenge in humanized mice bearing this allele. The observed T cell response was remarkably strong, dominated by secretion of IFN-gamma and IL-17, and specific to the same T cell epitope as that observed in the HLA-DR15-bearing humans. Furthermore, following long-term therapeutic immunization of an AD mouse model bearing the DRB1*1501 allele, Abeta was effectively cleared from the brain parenchyma and brain microglial activation was reduced. The present study thus characterizes HLA-DR alleles directly associated with specific Abeta T cell epitopes and demonstrates the highly immunogenic properties of the abundant allele DRB1*1501 in a mouse model of AD. This new knowledge enables us to explore the basis for understanding the variations in naturally occurring Abeta-reactive T cells and Abeta immunogenicity among humans. PMID:19675171

  2. Polarisation of Major Histocompatibility Complex II Host Genotype with Pathogenesis of European Brown Hare Syndrome Virus

    PubMed Central

    Iacovakis, Christos; Mamuris, Zissis; Moutou, Katerina A.; Touloudi, Antonia; Hammer, Anne Sofie; Valiakos, George; Giannoulis, Themis; Stamatis, Costas; Spyrou, Vassiliki; Athanasiou, Labrini V.; Kantere, Maria; Asferg, Tommy; Giannakopoulos, Alexios; Salomonsen, Charlotte M.; Bogdanos, Dimitrios; Birtsas, Periklis; Petrovska, Liljana; Hannant, Duncan; Billinis, Charalambos

    2013-01-01

    A study was conducted in order to determine the occurrence of European Brown Hare Syndrome virus (EBHSV) in Denmark and possible relation between disease pathogenesis and Major Histocompatibility Complex (MHC) host genotype. Liver samples were examined from 170 brown hares (hunted, found sick or dead), collected between 2004 and 2009. Macroscopical and histopathological findings consistent with EBHS were detected in 24 (14.1%) hares; 35 (20.6%) had liver lesions not typical of the syndrome, 50 (29.4%) had lesions in other tissues and 61 (35.9%) had no lesions. Sixty five (38.2%) of 170 samples were found to be EBHSV-positive (RT-PCR, VP60 gene). In order to investigate associations between viral pathogenesis and host genotype, variation within the exon 2 DQA gene of MHC was assessed. DQA exon 2 analysis revealed the occurrence of seven different alleles in Denmark. Consistent with other populations examined so far in Europe, observed heterozygosity of DQA (Ho?=?0.1180) was lower than expected (He?=?0.5835). The overall variation for both nucleotide and amino acid differences (2.9% and 14.9%, respectively) were lower in Denmark than those assessed in other European countries (8.3% and 16.9%, respectively). Within the peptide binding region codons the number of nonsynonymous substitutions (dN) was much higher than synonymous substitutions (dS), which would be expected for MHC alleles under balancing selection. Allele frequencies did not significantly differ between EBHSV-positive and -negative hares. However, allele Leeu-DQA*30 was detected in significantly higher (P?=?0.000006) frequency among the positive hares found dead with severe histopathological lesions than among those found sick or apparently healthy. In contrast, the latter group was characterized by a higher frequency of the allele Leeu-DQA*14 as well as the proportion of heterozygous individuals (P?=?0.000006 and P?=?0.027). These data reveal a polarisation between EBHSV pathogenesis and MHC class II genotype within the European brown hare in Denmark. PMID:24069299

  3. Eastern European risk management

    SciTech Connect

    Honey, J.A. (American Nuclear Insurers, Farmington, CT (United States))

    1992-01-01

    Here the authors assess Eastern European risk management practices through the evaluation of the nuclear power plants in the region. This evaluation is limited to the Soviet-designed and -built VVER-440 pressurized water reactors (PWRs) that are currently operating in Bulgaria, Czechoslovakia, Hungary, Russia, and the Ukraine and until recently operated at Greifswald in the former East Germany. This evaluation is based on the basic design of the plants, a safety evaluation of the Greifswald facility by representatives from the Federal Republic of Germany and personal visits by the author to Greifswald and Loviisa.

  4. Researching the European Union

    NSDL National Science Digital Library

    This site is the European Union's official and comprehensive guide for scholars and researchers studying its institutions. Users will find information on document access, treaties and institutions, legislation, and EU publishing operations. The site also provides overviews of official and related institutions and the legislative process in the Union. Researchers will be especially interested in the sections on Legislative Documents and Print Research Tools, Using Annual Reports and Informational Documents, and Bibliographic and Other Guides. The synoptic tables of basic documents, quick visual guides to the documents described on the site and their availability, are additional valuable tools.

  5. European Space Agency: Rosetta

    NSDL National Science Digital Library

    Rosetta is the European Space Agency's comet exploration spacecraft. Materials presented here describe the space craft and its mission, which is to rendezvous with and orbit Comet 67 P/Churyumov-Gerasimenko, and soft-land an instrument package on the comet's nucleus. En route to the comet, it will perform fly-bys of two asteroids, Steins and Lutetia. Topics include a mission summary, background science, information on the orbiter and lander, and a mission schedule. An image gallery is also provided that contains pictures of the spacecraft, imagery taken by the spacecraft, pictures of the launch, and others.

  6. Biophotonics: a European perspective

    NASA Astrophysics Data System (ADS)

    Robin, Thierry; Cochard, Jacques; Breussin, Frédéric

    2013-03-01

    The objective of the present work is to determine the opportunities and challenges for Biophotonics business development in Europe for the next five years with a focus on sensors and systems: for health diagnostics and monitoring; for air, water and food safety and quality control. The development of this roadmap was initiated and supported by EPIC (The European Photonics Industry Consortium). We summarize the final roadmap data: market application segments and trends, analysis of the market access criteria, analysis of the technology trends and major bottlenecks and challenges per application.

  7. Diversity of immune genes and associated gill microbes of European plaice Pleuronectes platessa

    NASA Astrophysics Data System (ADS)

    Wegner, K. Mathias; Shama, Lisa N. S.; Kellnreitner, Florian; Pockberger, Moritz

    2012-08-01

    Genetic variability of marine fish species is much higher than in most other vertebrates. Nevertheless, some species with large population sizes including flatfish such as European plaice Pleuronectes platessa show signs of population collapse and inbreeding. Taking plaice as a flagship example for fisheries-induced genetic changes also affecting the Wadden Sea, we determined the amount of genetic variability at antigen-presenting genes of the Major Histocompatibility Complex (MHC) and its potential interaction with the microbiota associated to gill tissue using a next-generation parallel tag sequencing approach. Genetic variation at MHC class IIB genes was extremely large, with 97 alleles found in 40 fish from different age cohorts. Although a strong signal of positive selection was present (dN/dS = 4.01) and we found significantly higher allelic diversity in 0+ fish than in older age classes, the amount of genetic variation maintained within the population may not have exceeded neutral expectations derived from mitochondrial markers. Associated microbes revealed significant spatiotemporal structure with 0+ fish displaying the highest microbial diversity as well as the highest diversity of potentially pathogenic genera. Overall the correlation between MHC genotypes and bacterial abundance was weak, and only few alleles significantly correlated with certain bacterial genera. These associations all conferred susceptibility (i.e. presence of an allele correlated to higher number of bacteria), either suggesting age-dependent selection on common alleles or weak selection on resistance against these bacterial genera. Taken together, our data suggest that selection coefficients of balancing selection maintaining immunogenetic diversity may be relatively small in large marine populations. However, if population sizes are further reduced by overharvesting, the response to increasing balancing selection coefficients will be largely unpredictable and may also negatively influence the adaptive potential of populations.

  8. European Industrial Relations Observatory Online

    NSDL National Science Digital Library

    The European Industrial Relations Observatory Online (EIROnline) was developed by the European Foundation for the Improvement of Living and Working Conditions, an autonomous body created by the European Community. The aim of the site is to "initiate, collect, store, disseminate and provide access to information and analysis on developments in industrial relations" in the 15 European Union member states and Norway. Visitors will find the latest industrial relations news and feature articles arranged by country. There is also a bimonthly publication called the EIRObserver summarizing the news and items over the past two months.

  9. European hair and eye color

    Microsoft Academic Search

    Peter Frost

    2006-01-01

    Human hair and eye color is unusually diverse in northern and eastern Europe. The many alleles involved (at least seven for hair color) and their independent origin over a short span of evolutionary time indicate some kind of selection. Sexual selection is particularly indicated because it is known to favor color traits and color polymorphisms. In addition, hair and eye

  10. Two Different Families of hopQ Alleles in Helicobacter pylori

    PubMed Central

    Cao, Ping; Cover, Timothy L.

    2002-01-01

    Helicobacter pylori genomes contain about 30 different hop genes, which encode outer membrane proteins. In this study, we analyzed genetic diversity in the H. pylori hopQ (omp27) locus, which corresponds to HP1177 in the genome of H. pylori reference strain 26695. hopQ and its flanking genes were PCR amplified from multiple H. pylori strains, and the nucleotide sequences were determined. This analysis revealed the existence of two different families of hopQ alleles. Type I hopQ alleles are present in the genomes of two fully sequenced H. pylori strains, whereas the existence of type II hopQ alleles has not previously been recognized. Type I and type II hopQ alleles are 75 to 80% identical in nucleotide sequences and encode predicted outer membrane proteins that are 68 to 72% identical in amino acid sequences. PCR-based methods were developed to enable rapid differentiation between type I and type II hopQ alleles. Type I hopQ alleles were found significantly more commonly in cag+/type s1-vacA strains from patients with peptic ulcer disease than in cag-negative/s2-vacA strains from patients without ulcer disease (P < 0.001). Determination of hopQ allelic types provides a new method for classification of H. pylori strains. Further studies in multiple populations of patients are indicated to evaluate the usefulness of this approach for distinguishing potentially ulcerogenic H. pylori strains from less virulent strains. PMID:12454143

  11. Characterizing HMW-GS alleles of decaploid Agropyron elongatum in relation to evolution and wheat breeding

    PubMed Central

    Liu, Shuwei; Gao, Xin

    2007-01-01

    Bread wheat quality is mainly correlated with high molecular weight glutenin subunits (HMW-GS) of endosperm. The number of HMW-GS alleles with good processing quality is limited in bread wheat cultivars, while there are plenty of HMW-GS alleles in wheat-related grasses to exploit. We report here on the cloning and characterization of HMW-GS alleles from the decaploid Agropyron elongatum. Eleven novel HMW-GS alleles were cloned from the grass. Of them, five are x-type and six y-type glutenin subunit genes. Three alleles Aex4, Aey7, and Aey9 showed high similarity with another three alleles from the diploid Lophopyrum elongatum, which provided direct evidence for the Ee genome origination of A. elongatum. It was noted that C-terminal regions of three alleles of the y-type genes Aey8, Aey9, and Aey10 showed more similarity with x-type genes than with other y-type genes. This demonstrates that there is a kind of intermediate state that appeared in the divergence between x- and y-type genes in the HMW-GS evolution. One x-type subunit, Aex4, with an additional cysteine residue, was speculated to be correlated with the good processing quality of wheat introgression lines. Aey4 was deduced to be a chimeric gene from the recombination between another two genes. How the HMW-GS genes of A. elongatum may contribute to the improvement of wheat processing quality are discussed. PMID:17992503

  12. Allele-Biased Expression in Differentiating Human Neurons: Implications for Neuropsychiatric Disorders

    PubMed Central

    Lin, Mingyan; Hrabovsky, Anastasia; Pedrosa, Erika; Wang, Tao; Zheng, Deyou; Lachman, Herbert M.

    2012-01-01

    Stochastic processes and imprinting, along with genetic factors, lead to monoallelic or allele-biased gene expression. Stochastic monoallelic expression fine-tunes information processing in immune cells and the olfactory system, and imprinting plays an important role in development. Recent studies suggest that both stochastic events and imprinting may be more widespread than previously considered. We are interested in allele-biased gene expression occurring in the brain because parent-of-origin effects suggestive of imprinting appear to play a role in the transmission of schizophrenia (SZ) and autism spectrum disorders (ASD) in some families. In addition, allele-biased expression could help explain monozygotic (MZ) twin discordance and reduced penetrance. The ability to study allele-biased expression in human neurons has been transformed with the advent of induced pluripotent stem cell (iPSC) technology and next generation sequencing. Using transcriptome sequencing (RNA-Seq) we identified 801 genes in differentiating neurons that were expressed in an allele-biased manner. These included a number of putative SZ and ASD candidates, such as A2BP1 (RBFOX1), ERBB4, NLGN4X, NRG1, NRG3, NRXN1, and NLGN1. Overall, there was a modest enrichment for SZ and ASD candidate genes among those that showed evidence for allele-biased expression (chi-square, p?=?0.02). In addition to helping explain MZ twin discordance and reduced penetrance, the capacity to group many candidate genes affecting a variety of molecular and cellular pathways under a common regulatory process – allele-biased expression – could have therapeutic implications. PMID:22952857

  13. Consecutive Mutational Events in a TSHR Allele of Arab Families with Resistance to Thyroid Stimulating Hormone

    PubMed Central

    Sriphrapradang, Chutintorn; German, Alina; Dumitrescu, Alexandra M.

    2012-01-01

    Background Our laboratory identified six distinct inactivating TSHR gene mutations in Arab tribes living in Israel. We recently reported three nucleotide substitutions in exon 3 producing p.[L89L;Q90P] and one in exon 9 of the same allele producing p.P264S in Family A. Family B, reported herein, harbors the identical mutation in exon 3 only. We set to determine whether the mutations have common ancestral origin. Methods Coding regions of the TSHR were sequenced and flanking microsatellite markers spanning 5.3 cM were used for haplotyping. Results Two siblings of Family B were compound heterozygous for TSHR gene mutations. The paternal allele contained the exon 3 mutation and the maternal allele harbored a mutation in exon 10 (p.L653V). We investigated the possibility of a founder effect with subsequent mutational events for the presence of the same exon 3 mutation in different families. The haplotype of the allele harboring the exon 3 mutation in Family B was identical to that of Family A, also harboring the exon 9 mutation on the same allele, indicating that the latter occurred subsequently. The ancestral wild-type TSHR was present in Family B, suggesting that the mutation in exon 3 was also new in the history of that population. Conclusions It is more likely that two consecutive mutational events occurred on the ancestral wild-type allele instead of a recombination bringing exon 3 and exon 9 mutations together on the same allele. New mutational events contribute to the high prevalence of TSHR mutations in this population in addition to a founder effect and limited gene pool due to inbreeding. PMID:22313426

  14. Allelic associations of two polymorphic microsatellites in intron 40 of the human von Willebrand factor gene

    SciTech Connect

    Pena, S.D.J.; De Souza, K.T. (Nucleo de Genetica Medica de Minas Gerais, Belo Horizonte (Brazil)); De Andrade, M.; Chakraborty, R. (Univ. of Texas Graduate School of Biomedical Sciences, Houston, TX (United States))

    1994-01-18

    At intron 40 of the von Willebrand factor (vWF) gene, two GATA-repeat polymorphic sites exist that are physically separated by 212 bp. At the first site (vWF1 locus), seven segregating repeat alleles were observed in a Brazilian Caucasian population, and at the second (vWF2 locus) there were eight alleles, detected through PCR amplifications of this DNA region. Haplotype analysis of individuals revealed 36 different haplotypes in a sample of 338 chromosomes examined. Allele frequencies between generations and gender at each locus were not significantly different, and the genotype frequencies were consistent with their Hardy-Weinberg expectations. Linkage disequilibrium between loci is highly significant with positive allele size association; that is, large alleles at the loci tend to occur together, and so do the same alleles. Variability at each locus appeared to have arisen in a stepwise fashion, suggesting replication slippage as a possible mechanism of production of new alleles. However, the authors observed an increased number of haplotypes, in contrast with the predictions of a stepwise production of variation in the entire region, suggesting some form of cooperative changes between loci that could be due to either gene conversion, or a common control mechanism of production of new variation at these repeat polymorphism sites. The high degree of polymorphism (gene diversity values of 72% and 78% at vWF1 and vWF2, respectively, and of 93% at the haplotype level) makes these markers informative for paternity testing, genetic counseling, and individual-identification purposes.

  15. Direct Fluorescence Detection of Allele-Specific PCR Products Using Novel Energy-Transfer Labeled Primers.

    PubMed

    Winn-Deen

    1998-12-01

    Background: Currently analysis of point mutations can be done by allele-specific polymerase chain reaction (PCR) followed by gel analysis or by gene-specific PCR followed by hybridization with an allele-specific probe. Both of these mutation detection methods require post-PCR laboratory time and run the risk of contaminating subsequent experiments with the PCR product liberated during the detection step. The author has combined the PCR amplification and detection steps into a single procedure suitable for closed-tube analysis. Methods and Results: Allele-specific PCR primers were designed as Sunrise energy-transfer primers and contained a 3' terminal mismatch to distinguish between normal and mutant DNA. Cloned normal (W64) and mutant (R64) templates of the beta3-adrenergic receptor gene were tested to verify amplification specificity and yield. A no-target negative control was also run with each reaction. After PCR, each reaction was tested for fluorescence yield by measuring fluorescence on a spectrofluorimeter or fluorescent microtitreplate reader. The cloned controls and 24 patient samples were tested for the W64R mutation by two methods. The direct fluorescence results with the Sunrise allele-specific PCR method gave comparable genotypes to those obtained with the PCR/ restriction digest/gel electrophoresis control method. No PCR artifacts were observed in the negative controls or in the PCR reactions run with the mismatched target. Conclusions: The results of this pilot study indicate good PCR product and fluorescence yield from allele-specific energy-transfer labeled primers, and the capability of distinguishing between normal and mutant alleles based on fluorescence alone, without the need for restriction digestion, gel electrophoresis, or hybridization with an allele-specific probe. PMID:10089280

  16. Allelic Analysis of Sheath Blight Resistance with Association Mapping in Rice

    PubMed Central

    Jia, Limeng; Yan, Wengui; Zhu, Chengsong; Agrama, Hesham A.; Jackson, Aaron; Yeater, Kathleen; Li, Xiaobai; Huang, Bihu; Hu, Biaolin; McClung, Anna; Wu, Dianxing

    2012-01-01

    Sheath blight (ShB) caused by the soil-borne pathogen Rhizoctonia solani is one of the most devastating diseases in rice world-wide. Global attention has focused on examining individual mapping populations for quantitative trait loci (QTLs) for ShB resistance, but to date no study has taken advantage of association mapping to examine hundreds of lines for potentially novel QTLs. Our objective was to identify ShB QTLs via association mapping in rice using 217 sub-core entries from the USDA rice core collection, which were phenotyped with a micro-chamber screening method and genotyped with 155 genome-wide markers. Structure analysis divided the mapping panel into five groups, and model comparison revealed that PCA5 with genomic control was the best model for association mapping of ShB. Ten marker loci on seven chromosomes were significantly associated with response to the ShB pathogen. Among multiple alleles in each identified loci, the allele contributing the greatest effect to ShB resistance was named the putative resistant allele. Among 217 entries, entry GSOR 310389 contained the most putative resistant alleles, eight out of ten. The number of putative resistant alleles presented in an entry was highly and significantly correlated with the decrease of ShB rating (r?=??0.535) or the increase of ShB resistance. Majority of the resistant entries that contained a large number of the putative resistant alleles belonged to indica, which is consistent with a general observation that most ShB resistant accessions are of indica origin. These findings demonstrate the potential to improve breeding efficiency by using marker-assisted selection to pyramid putative resistant alleles from various loci in a cultivar for enhanced ShB resistance in rice. PMID:22427867

  17. Quantification of BRAF V600E alleles predicts papillary thyroid cancer progression.

    PubMed

    Kim, Min-Hee; Bae, Ja Seong; Lim, Dong-Jun; Lee, Hyoungnam; Jeon, So Ra; Park, Gyeong Sin; Jung, Chan Kwon

    2014-12-01

    The BRAF V600E mutation is the most common genetic alteration in thyroid cancer. However, its clinicopathological significance and clonal mutation frequency remain unclear. To clarify the inconsistent results, we investigated the association between the allelic frequency of BRAF V600E and the clinicopathological features of classic papillary thyroid carcinoma (PTC). Tumour tissues from two independent sets of patients with classic PTC were manually microdissected and analysed for the presence or absence of the BRAF mutation and the mutant allelic frequency using quantitative pyrosequencing. For external validation, the Cancer Genome Atlas (TCGA) data were analysed. The BRAF V600E mutation was found in 264 (82.2%) out of 321 classic PTCs in the training set. The presence of BRAF V600E was only associated with extrathyroidal extension and the absence of thyroiditis. In BRAF V600E-positive tumours, the mutant allelic frequency varied from 8 to 41% of the total BRAF alleles (median, 20%) and directly correlated with tumour size and the number of metastatic lymph nodes. Lymph node metastases were more frequent in PTCs with a high (?20%) abundance of mutant alleles than in those with a low abundance of mutant alleles (P=0.010). These results were reinforced by validation dataset (n=348) analysis but were not reproduced in the TCGA dataset. In a population with prevalent BRAF mutations, quantitative analysis of the BRAF mutation could provide additional information regarding tumour behaviour, which is not reflected by qualitative analysis. Nonetheless, prospective studies are needed before the mutated allele percentage can be considered as a prognostic factor. PMID:25266729

  18. Allelic analysis of sheath blight resistance with association mapping in rice.

    PubMed

    Jia, Limeng; Yan, Wengui; Zhu, Chengsong; Agrama, Hesham A; Jackson, Aaron; Yeater, Kathleen; Li, Xiaobai; Huang, Bihu; Hu, Biaolin; McClung, Anna; Wu, Dianxing

    2012-01-01

    Sheath blight (ShB) caused by the soil-borne pathogen Rhizoctonia solani is one of the most devastating diseases in rice world-wide. Global attention has focused on examining individual mapping populations for quantitative trait loci (QTLs) for ShB resistance, but to date no study has taken advantage of association mapping to examine hundreds of lines for potentially novel QTLs. Our objective was to identify ShB QTLs via association mapping in rice using 217 sub-core entries from the USDA rice core collection, which were phenotyped with a micro-chamber screening method and genotyped with 155 genome-wide markers. Structure analysis divided the mapping panel into five groups, and model comparison revealed that PCA5 with genomic control was the best model for association mapping of ShB. Ten marker loci on seven chromosomes were significantly associated with response to the ShB pathogen. Among multiple alleles in each identified loci, the allele contributing the greatest effect to ShB resistance was named the putative resistant allele. Among 217 entries, entry GSOR 310389 contained the most putative resistant alleles, eight out of ten. The number of putative resistant alleles presented in an entry was highly and significantly correlated with the decrease of ShB rating (r?=?-0.535) or the increase of ShB resistance. Majority of the resistant entries that contained a large number of the putative resistant alleles belonged to indica, which is consistent with a general observation that most ShB resistant accessions are of indica origin. These findings demonstrate the potential to improve breeding efficiency by using marker-assisted selection to pyramid putative resistant alleles from various loci in a cultivar for enhanced ShB resistance in rice. PMID:22427867

  19. Association of human leukocyte antigen class II alleles with pemphigus vulgaris in a Turkish population.

    PubMed

    Tunca, Mustafa; Musabak, Ugur; Sagkan, Rah?an Ilikci; Koc, Erol; Akar, Ahmet

    2010-03-01

    Pemphigus vulgaris (PV) is a severe autoimmune blistering skin disorder that is strongly associated with major histocompatibility complex class II alleles. Human leukocyte antigen (HLA) subtypes vary with racial/ethnic backgrounds. The purpose of this study was to determine the association of HLA class II alleles and haplotypes with PV in Turkish patients. Twenty-five patients with PV and 113 healthy transplant donors were genotyped for HLA class II alleles. HLA DNA typing was performed by the polymerase chain reaction/sequence specific primer method. The frequency of HLA DRB1*04 allele was 68.00% in patients compared to 30.97% in controls (P = 0.0012) and the frequency of HLA DRB1*14 allele was 32.00% in the patient group compared to 8.85% in the control group (P = 0.0054). Also, the frequency of HLA DRB1*04/DQB1*03 and HLA DRB1*14/DQB1*05 haplotypes in PV patients was significantly higher than controls (32.0% vs 6.2%, chi(2) = 28.142, P < 0.001; and 16% vs 2.7%, chi(2) = 15.143, P = 0.001, respectively). A preventive allele or haplotype for the manifestation of PV has not been identified in this study. Our findings suggest that HLA DRB1*04 and DRB1*14 alleles, and HLA DRB1*04/DQB1*03 and HLA DRB1*14/DQB1*05 haplotypes are genetic markers for general susceptibility to PV in the Turkish population. PMID:20507388

  20. MHC class II alleles and haplotypes in patients with pemphigus vulgaris from India.

    PubMed

    Delgado, J C; Yunis, D E; Bozón, M V; Salazar, M; Deulofeut, R; Turbay, D; Mehra, N K; Pasricha, J S; Raval, R S; Patel, H; Shah, B K; Bhol, K; Alper, C A; Ahmed, A R; Yunis, E J

    1996-12-01

    Pemphigus vulgaris (PV) is a blistering disease of the skin and mucous membranes characterized by an autoantibody response against a keratinocyte adhesion molecule, desmoglein 3, causing acantholysis and blister formation. We compared high resolution MHC class II alleles and haplotype frequencies (HLA-DRB, DQA1 and DQB1) in 37 patients with PV to 89 haplotypes of normal relatives from New Delhi and Ahmedabad. We found that PV patients had significantly increased frequencies of DRB1*1404 (P < 0.0001), DQA1*0101 (P = 0.001), and DQB1*0503 (P < 0.0001). These associations were due to the increased frequencies of the haplotype HLA-DRB1*1404, DRB3*0202, DQA1*0101, DQB1*0503 in patients compared to control haplotypes (p < 0.0001). Also, patients from Ahmedabad had a significant increase in HLA-DQB1*0302 (p = 0.03). An identical amino acid sequence (Leu-Leu-Glu-Arg-Arg-Arg-Ala-Glu), in positions 67-74 of the beta domain of DRB alleles is restricted to some DR14 alleles. Therefore, there are three possible explanations for class II allele involvement in autoantibody in PV patients with class II haplotypes marked by HLA-DR14. First, the class II alleles could be markers for an unidentified susceptibility gene in linkage disequilibrium with them. Second, the primary association could be with DQB1*0503 and the association with HLA-DR14 alleles would be the result of linkage disequilibrium. Third, the HLA-DRB1 locus susceptibility could involve a specific amino acid sequence in the third hypervariable region shared by several HLA-DR14 alleles. PMID:9008309

  1. HLA alleles associated with the adaptive immune response to smallpox vaccine: a replication study.

    PubMed

    Ovsyannikova, Inna G; Pankratz, V Shane; Salk, Hannah M; Kennedy, Richard B; Poland, Gregory A

    2014-09-01

    We previously reported HLA allelic associations with vaccinia virus (VACV)-induced adaptive immune responses in a cohort of healthy individuals (n = 1,071 subjects) after a single dose of the licensed smallpox (Dryvax) vaccine. This study demonstrated that specific HLA alleles were significantly associated with VACV-induced neutralizing antibody (NA) titers (HLA-B*13:02, *38:02, *44:03, *48:01, and HLA-DQB1*03:02, *06:04) and cytokine (HLA-DRB1*01:03, *03:01, *10:01, *13:01, *15:01) immune responses. We undertook an independent study of 1,053 healthy individuals and examined associations between HLA alleles and measures of adaptive immunity after a single dose of Dryvax-derived ACAM2000 vaccine to evaluate previously discovered HLA allelic associations from the Dryvax study and determine if these associations are replicated with ACAM2000. Females had significantly higher NA titers than male subjects in both study cohorts [median ID50 discovery cohort 159 (93, 256) vs. 125 (75, 186), p < 0.001; replication cohort 144 (82, 204) vs. 110 (61, 189), p = 0.024]. The association between the DQB1*03:02 allele (median ID50 discovery cohort 152, p = 0.015; replication cohort 134, p = 0.010) and higher NA titers was replicated. Two HLA associations of comparable magnitudes were consistently found between DRB1*04:03 and DRB1*08:01 alleles and IFN-? ELISPOT responses. The association between the DRB1*15:01 allele with IFN-? secretion was also replicated (median pg/mL discovery cohort 182, p = 0.052; replication cohort 203, p = 0.014). Our results suggest that smallpox vaccine-induced adaptive immune responses are significantly influenced by HLA gene polymorphisms. These data provide information for functional studies and design of novel candidate smallpox vaccines. PMID:24880604

  2. Characterizing HMW-GS alleles of decaploid Agropyron elongatum in relation to evolution and wheat breeding.

    PubMed

    Liu, Shuwei; Gao, Xin; Xia, Guangmin

    2008-02-01

    Bread wheat quality is mainly correlated with high molecular weight glutenin subunits (HMW-GS) of endosperm. The number of HMW-GS alleles with good processing quality is limited in bread wheat cultivars, while there are plenty of HMW-GS alleles in wheat-related grasses to exploit. We report here on the cloning and characterization of HMW-GS alleles from the decaploid Agropyron elongatum. Eleven novel HMW-GS alleles were cloned from the grass. Of them, five are x-type and six y-type glutenin subunit genes. Three alleles Aex4, Aey7, and Aey9 showed high similarity with another three alleles from the diploid Lophopyrum elongatum, which provided direct evidence for the Ee genome origination of A. elongatum. It was noted that C-terminal regions of three alleles of the y-type genes Aey8, Aey9, and Aey10 showed more similarity with x-type genes than with other y-type genes. This demonstrates that there is a kind of intermediate state that appeared in the divergence between x- and y-type genes in the HMW-GS evolution. One x-type subunit, Aex4, with an additional cysteine residue, was speculated to be correlated with the good processing quality of wheat introgression lines. Aey4 was deduced to be a chimeric gene from the recombination between another two genes. How the HMW-GS genes of A. elongatum may contribute to the improvement of wheat processing quality are discussed. PMID:17992503

  3. EUROPEAN ORGANIZATION FOR NUCLEAR RESEARCH European Laboratory for Particle Physics

    E-print Network

    Paris-Sud XI, Université de

    -leak by radiation is reduced by employing multilayer insulation wrapped around the cold mass and an actively cooled-leak by radiation is reduced by employing multilayer insulation wrapped around the cold mass and an actively cooledEUROPEAN ORGANIZATION FOR NUCLEAR RESEARCH European Laboratory for Particle Physics THERMAL

  4. A New Impetus for European Youth. European Commission White Paper.

    ERIC Educational Resources Information Center

    Commission of the European Communities, Brussels (Belgium).

    Despite their highly divergent situations, young people largely share the same values, ambitions, and difficulties. Despite the more complex social and economic context in which young Europeans are currently living, they are well equipped to adapt. National and European policymakers must facilitate this process of change by making young people…

  5. Association of the HLA-B*52 allele with non-progression to AIDS in Brazilian HIV-1-infected individuals.

    PubMed

    Teixeira, S L M; de Sá, N B R; Campos, D P; Coelho, A B; Guimarães, M L; Leite, T C N F; Veloso, V G; Morgado, M G

    2014-04-01

    Several human leukocyte antigen (HLA) class I alleles are associated with the susceptibility to human immunodeficiency virus-1 (HIV-1) infection and/or AIDS progression. Of these, the HLA-B alleles are considered the strongest genetic determinant of disease outcome. We evaluated the influence of the HLA-B alleles on AIDS progression among HIV-1-positive individuals from Rio de Janeiro, Brazil, who were categorized as rapid progressors (RPs), typical progressors (TPs) or long-term non-progressors (LTNPs). In this study, significant differences in HLA-B allele frequencies were observed among the three progression groups for the B*48, B*49 and B*52 alleles. After controlling for other factors associated with AIDS progression, the presence of the B*52 allele was shown to be a significant protective factor (hazard ratio (HR) 0.49 (95% confidence interval (CI) 0.27-0.90) P<0.03). Although no direct association was observed between the presence of the B*27 or B*57 allele and the LTNP profile compared with the TP or RP groups, the adjusted model confirmed that these alleles are protective factors against AIDS progression (HR 0.62 (95% CI 0.38-0.99) P<0.05), as previously described. These data corroborate the existence of significant differences in HLA-B allele frequencies among the distinct AIDS progression profiles and further elucidate the role of HLA alleles in the outcome of HIV infections in diverse populations. PMID:24718028

  6. European drought trends

    NASA Astrophysics Data System (ADS)

    Gudmundsson, L.; Seneviratne, S. I.

    2015-06-01

    Recent climate projections suggest pronounced changes in European drought frequency. In the north, increased precipitation volumes are likely to reduce drought occurrence, whereas more frequent droughts are expected for southern Europe. To assess whether this pattern of changes in drought frequency can already be identified for the past decades, we analyse trends in a recently developed pan-European drought climatology that is based on the Standardized Precipitation Index (SPI). The index is derived on multiple time scales, ranging from 1 to 36 months, which allows the assessment of trends in both short term and multi-year droughts. Trends are quantified using the Theil-Sen trend estimator combined with an extension of the Mann-Kendal test (p < 0.05) that accounts for serial correlation. Field significance is assessed on the basis of techniques that control the false discovery rate in a multiple testing setting. The trend analysis indicates that changes in drought frequency are more pronounced on time scales of one year and longer. The analysis also reveals that there has been a tendency for decreased drought frequency in northern Europe in the past decades, whereas droughts have likely become more frequent in selected southern regions.

  7. Characterization of microsatellite loci in the European pond turtle Emys orbicularis.

    PubMed

    Ciofi, Claudio; Tzika, Athanasia C; Natali, Chiara; Chelazzi, Guido; Naziridis, Theodorus; Milinkovitch, Michel C

    2009-01-01

    A set of eight highly polymorphic microsatellite markers was isolated and characterized from a genomic library enriched for dinucleotide repeats in the European pond turtle, Emys orbicularis. The markers were tested for polymorphism in a total of 33 turtles sampled in two natural ponds in the nature reserve of Kerkini, northern Greece. Number of alleles varied from 10 to 18, and expected heterozygosity ranged between 0.738 and 0.921. This novel set of loci will be particularly useful to assess fine-scale population structure and for parentage analysis in E. orbicularis. PMID:21564599

  8. Lack of association between allelic status and myostatin content in lambs with the myostatin g+6723G>A allele.

    PubMed

    Haynes, F E M; Greenwood, P L; McDonagh, M B; McMahon, C D; Nicholas, G D; Berry, C J; Oddy, V H

    2013-01-01

    Lambs with the myostatin (MSTN) g+6723G>A mutation have a greater muscle mass, which is believed to be associated with reduced myostatin protein abundance. This experiment was designed to determine if differences in allelic frequency of the MSTN g+6723G>A mutation affected abundance of myostatin protein from birth to 24 wk of age. A Poll Dorset cross White Suffolk ram (MSTN A/G) was mated to 35 White Suffolk cross Border Leicester cross Merino ewes (MSTN A/G, n=21, and MSTN G/G, n=14). The progeny of these matings delivered 44 lambs with MSTN A/A (n=9), MSTN A/G (n=21), and MSTN G/G (n=14) genotypes. At approximately 1, 4, and 12 wk of age, a biopsy sample was collected and a blood sample was taken to measure the abundance of myostatin protein in muscle and plasma. At approximately 24 wk of age, the wether lambs were slaughtered to determine carcass characteristics and muscle samples were taken from the bicep femoris. The abundance of mature myostatin protein in muscle from 1 wk old lambs was less (P=0.05) in MSTN A/A and MSTN A/G compared with MSTN G/G lambs. However, at 4 and 24 wk the MSTN A/A lambs had a greater (P=0.04) abundance of myostatin protein compared with the MSTN A/G and MSTN G/G lambs. The abundance of mature myostatin did not differ between genotypes in plasma but the myostatin protein did increase as the lambs aged. At slaughter the MSTN A/A wether lambs had greater dressing percentages (P=0.04), shortloin (P=0.01), topside (P<0.001), and round (P=0.01) weights but did not differ in final BW or HCW (P>0.05). The MSTN A/A lambs had more muscle fibers (P=0.02) in the cross-section of LM between the 12th and 13th rib. The MSTN A/A lambs also had greater lean (P=0.002), less fat (P=0.009), and reduced organ (heart, liver, spleen, and kidneys) mass as determined by computed tomography scanning than MSTN G/G lambs. The results of this study demonstrated that lambs homozygous for the MSTN g+6723G>A mutation have changes in carcass characteristics (dressing and total lean), organ weights, and muscle fiber number. This may be due to reduced myostatin protein early in utero, but after 4 wk of age there was no difference in the abundance of mature myostatin protein in muscle or plasma among MSTN A/A, MSTN A/G, and MSTN G/G genotypes. PMID:23048142

  9. European Schoolnet: Enabling School Networking

    ERIC Educational Resources Information Center

    Scimeca, Santi; Dumitru, Petru; Durando, Marc; Gilleran, Anne; Joyce, Alexa; Vuorikari, Riina

    2009-01-01

    School networking is increasingly important in a globalised world, where schools themselves can be actors on an international stage. This article builds on the activities and experience of the longest established European initiative in this area, European Schoolnet (EUN), a network of 31 Ministries of Education. First, we offer an introduction…

  10. European Union and Racial Discrimination.

    ERIC Educational Resources Information Center

    Commission for Racial Equality, London (England).

    The European Community (EC) has the power to pass laws based on the Community Treaty. Since 1989, the EC's Commission for Racial Equality has called for an amendment to the European Treaty that would provide basic protection against racial discrimination throughout the EC and legal remedies for those who suffer discrimination. Tracing the history…

  11. Market forces in European soccer

    Microsoft Academic Search

    Marco Haan; Ruud H. Koning; Arjen van Witteloostuijn

    2002-01-01

    Recent decades have witnessed major changes in the market for European soccer. The most profound were the Bosman ruling, which lifted restrictions in the European labor market for soccer talent, and the introduction of the Champions' League, a high-profile international competition that generates high revenues for participating clubs. This paper studies the effects of these changes on the closeness of

  12. The European Picture Book Collection.

    ERIC Educational Resources Information Center

    Cottom, Penni

    1999-01-01

    Outlines the European Picture Book Collection project designed to help young children understand more about Europe. Contains preparatory stages of the project, discussing the first symposium in France (1966), the establishment of a European picture book collection, the initial evaluation of the materials in U.K. schools, the second symposium in…

  13. Premutation and intermediate-size FMR1 alleles in 10 572 males from the general population: loss of an AGG interruption is a late event in the generation of fragile X syndrome alleles

    Microsoft Academic Search

    C. Dombrowski; S. Lévesque; M. L. Morel; P. Rouillard; K. Morgan; F. Rousseau

    2002-01-01

    We previously reported a 1:259 prevalence of female carriers of FMR1 premutation-size alleles (greater than 54 triplet repeats) in the general population. We now have screened 10 572 independent males from the same population for similar alleles using high-throughput Southern blotting. We identified 13 male carriers of an allele with more than 54 repeats. This corresponds to a prevalence of

  14. Alleles versus genotypes: Genetic interactions and the dynamics of selection in sexual populations

    NASA Astrophysics Data System (ADS)

    Neher, Richard

    2010-03-01

    Physical interactions between amino-acids are essential for protein structure and activity, while protein-protein interactions and regulatory interactions are central to cellular function. As a consequence of these interactions, the combined effect of two mutations can differ from the sum of the individual effects of the mutations. This phenomenon of genetic interaction is known as epistasis. However, the importance of epistasis and its effects on evolutionary dynamics are poorly understood, especially in sexual populations where recombination breaks up existing combinations of alleles to produce new ones. Here, we present a computational model of selection dynamics involving many epistatic loci in a recombining population. We demonstrate that a large number of polymorphic interacting loci can, despite frequent recombination, exhibit cooperative behavior that locks alleles into favorable genotypes leading to a population consisting of a set of competing clones. As the recombination rate exceeds a certain critical value this ``genotype selection'' phase disappears in an abrupt transition giving way to ``allele selection'' - the phase where different loci are only weakly correlated as expected in sexually reproducing populations. Clustering of interacting sets of genes on a chromosome leads to the emergence of an intermediate regime, where localized blocks of cooperating alleles lock into genetic modules. Large populations attain highest fitness at a recombination rate just below critical, suggesting that natural selection might tune recombination rates to balance the beneficial aspect of exploration of genotype space with the breaking up of synergistic allele combinations.

  15. A Y-associated allele is shared among a few ethnic groups of Asia.

    PubMed

    Lin, S J; Tanaka, K; Leonard, W; Gerelsaikhan, T; Dashnyam, B; Nyamkhishig, S; Hida, A; Nakahori, Y; Omoto, K; Crawford, M H

    1994-09-01

    In our previous study, both of Y-associated alleles, Y1 and Y2, were detected in Japanese and Koreans, but only the Y1 allele was detected in each of other populations including Chinese in both Beijin and Guangzhou areas, Caucasians, Africans, and Jewish. In the present study, these observations were extended to other ethnic groups in East Asia. Evenks in central Siberia and Khalkhs in Mongolia had only the Y1 allele. On the other hand, two ethnic groups, Fo-lo and Hakka, in Taiwan had both of the Y1 and the Y2 alleles. Three of the eight Y2-positive men, 2 Fo-lo and a Hakka, shared family name Chen. Both Hakka people and ancestors of Chen families could be traced to the Province of Henan in northern China in early 4th century. They arrived in Fujian/Guangdong area in the south-east China via various routes and then some of them migrated to Taiwan in the 18th century. It is tempting to speculate that the Y2 allele may be originated from an ancestral population in Henan from which, Japanese, Koreans, and some of the Taiwanese diverged. PMID:7841440

  16. Ancestral Alleles in the Human Genome Based on Population Sequencing Data

    PubMed Central

    Park, Leeyoung

    2015-01-01

    Ancestral allele information is useful for genetics studies. Previously, the identification of ancestral alleles was primarily based on sequence alignments between species. Alternative ways to identify ancestral alleles were proposed in this study based on population sequencing data. The methods described here utilized the diversity between haplotypes harboring ancestral and newly emerged alleles. Simulations showed that these methods were reliable for identifying ancestral alleles when the variants had not aged too greatly. Application to the human genome sequencing data suggested the role of indels in maintaining the GC content in the human genome. The deletion-to-insertion ratios and GC proportions were correlated depending on the sizes of insertions and deletions in the direction of increasing GC content. There were GC-biased fixations in single base-pair insertions and AT-biased fixations in single base-pair deletions in the results based on the proposed methods. In the current study, GC-biased gene conversions in nucleotide substitutions were very slight or insignificant. In the variants of several quantitative trait loci (QTLs), slight GC-biased gene conversion was observed in nucleotide substitutions. For the QTL indels, insertions were observed more often than deletions, and deletion-biased fixation was observed, providing new insights into the evolution of functional genes. PMID:26020928

  17. Transcripts of paternal and maternal actin gene alleles are present in interspecific sea urchin embryo hybrids.

    PubMed

    Crain, W R; Bushman, F D

    1983-11-01

    Analysis of actin-coding RNAs in interspecific hybrid sea urchin embryos of Strongylocentrotus purpuratus and Lytechinus variegatus, and S. purpuratus and S. droebachienis has revealed the presence of transcripts from both paternal and maternal S. purpuratus actin gene alleles. In the L. variegatus female X S. purpuratus male embryos transcripts from at least two different paternal actin gene alleles are present in both the blastula and prism stages. In the reciprocal S. purpuratus female X L. variegatus male embryos, the same two maternal (S. purpuratus) alleles were also expressed as RNA in blastula. The S. droebachiensis female X S. purpuratus male embryos appear to contain transcripts from at least one paternal actin gene allele at the blastula stage. The paternally derived actin-coding RNAs are the same size as the mature actin mRNAs expressed in normal S. purpuratus embryos. Since all known S. purpuratus actin genes contain at least two introns, the paternal alleles are not only transcribed in the hybrid embryos, but also the primary transcripts are probably processed to mature mRNA. An explanation of the diversity of observations in the literature on paternal genome expression in hybrid sea urchin embryos is discussed. PMID:6617991

  18. Allele-specific copy number profiling by next-generation DNA sequencing.

    PubMed

    Chen, Hao; Bell, John M; Zavala, Nicolas A; Ji, Hanlee P; Zhang, Nancy R

    2015-02-27

    The progression and clonal development of tumors often involve amplifications and deletions of genomic DNA. Estimation of allele-specific copy number, which quantifies the number of copies of each allele at each variant loci rather than the total number of chromosome copies, is an important step in the characterization of tumor genomes and the inference of their clonal history. We describe a new method, falcon, for finding somatic allele-specific copy number changes by next generation sequencing of tumors with matched normals. falcon is based on a change-point model on a bivariate mixed Binomial process, which explicitly models the copy numbers of the two chromosome haplotypes and corrects for local allele-specific coverage biases. By using the Binomial distribution rather than a normal approximation, falcon more effectively pools evidence from sites with low coverage. A modified Bayesian information criterion is used to guide model selection for determining the number of copy number events. Falcon is evaluated on in silico spike-in data and applied to the analysis of a pre-malignant colon tumor sample and late-stage colorectal adenocarcinoma from the same individual. The allele-specific copy number estimates obtained by falcon allows us to draw detailed conclusions regarding the clonal history of the individual's colon cancer. PMID:25477383

  19. Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles

    PubMed Central

    1993-01-01

    Naturally processed peptides were acid extracted from immunoaffinity- purified HLA-DR2, DR3, DR4, DR7, and DR8. Using the complementary techniques of mass spectrometry and Edman microsequencing, > 200 unique peptide masses were identified from each allele, ranging from 1,200 to 4,000 daltons (10-34 residues in length), and a total of 201 peptide sequences were obtained. These peptides were derived from 66 different source proteins and represented sets nested at both the amino- and carboxy-terminal ends with an average length of 15-18 amino acids. Strikingly, most of the peptides (> 85%) were derived from endogenous proteins that intersect the endocytic/class II pathway, even though class II molecules are thought to function mainly in the presentation of exogenous foreign peptide antigens. The predominant endogenous peptides were derived from major histocompatibility complex-related molecules. A few peptides derived from exogenous bovine serum proteins were also bound to every allele. Four prominent promiscuous self- peptide sets (capable of binding to multiple HLA-DR alleles) as well as 84 allele-specific peptide sets were identified. Binding experiments confirmed that the promiscuous peptides have high affinity for the binding groove of all HLA-DR alleles examined. A potential physiologic role for these endogenous self-peptides as immunomodulators of the cellular immune response is discussed. PMID:8315383

  20. Identification of two novel waxy alleles and development of their molecular markers in sorghum.

    PubMed

    Lu, Yuangen; Zhao, Ganlin; Li, Yan; Fan, Jing; Ding, Guoxiang; Zhao, Jiqun; Ni, Xianlin; Xu, Yongju; Wang, Wenming

    2013-05-01

    High amylopectin grains of waxy sorghum have a high economic value in the food and bioenergy industries because of their increased starch digestibility and higher ethanol conversion rate compared with wild-type sorghum grains. Mutation in the granule-bound starch synthase (GBSS) gene contributes to the waxy phenotype. Two classes of waxy alleles, wx(a) and wx(b), have been characterized previously. In the present work, we identified two novel types of waxy mutations in the sorghum GBSS gene, designated as wx(c) and wx(d). The wx(c) allele has a G deletion at the 5' splicing site of the ninth intron, causing a shift of the 5' cleavage site; in turn, a reading frame shift occurred and resulted in an early translation termination. The wx(d) allele contained a mutation at the 3' splicing site of the 10th intron, which led to a splicing site shift and resulted in the deletion of five amino acids (GTGKK) in the predicted translation product. Furthermore, cleaved amplified polymorphic sequence (CAPS) markers were developed to detect the wx(c) and wx(d) alleles. With these markers, classification of waxy alleles was performed in nearly 100 sorghum accessions from our breeding program. Most waxy sorghum cultivars in China were either wx(a) or wx(c), implying that these two mutations are preferentially maintained during domestic selection in glutinous sorghum production. PMID:23789996

  1. Allele frequency and its forensic application of STR Y27 in Korean males.

    PubMed

    Lee, S D; Lee, J B

    1996-10-01

    The allele frequency and mutation rate in a Short Tandem Repeat locus, Y27 were studied in 247 unrelated Korean males using polymerase chain reaction followed by high-resolution polyacrylamide gel electrophoresis, a procedure called the amplification fragment length polymorphism technique. Six alleles were noted ranging from 190 bp to 210 bp. They existed as discrete bands with 4 bp discrepancy. Among which DY3(198 bp), DY4(202 bp) were common with the frequencies of 0.408, 0.356 respectively. Other alleles, DY1(190 bp, frequency 0.020), DY2(194 bp, frequency 0.121), DY5(206 bp, frequency 0.089), DY6(210 bp, frequency 0.004) were relatively uncommon. In a 78 subject father-son study with parenthood confirmed through other genetic studies, no case of mutation was noted. As the allele number was not as large as 6 and two alleles were dominant, the discrimination power in routine individual identification was thought to be low. But in selective cases such as father-son determination or sex determination, this locus could be a valuable genetic marker and we thought these results to be common for the Korean population. These results were also compared with that of other race. PMID:8934392

  2. Allele frequency and its forensic application of STR Y27 in Korean males.

    PubMed Central

    Lee, S. D.; Lee, J. B.

    1996-01-01

    The allele frequency and mutation rate in a Short Tandem Repeat locus, Y27 were studied in 247 unrelated Korean males using polymerase chain reaction followed by high-resolution polyacrylamide gel electrophoresis, a procedure called the amplification fragment length polymorphism technique. Six alleles were noted ranging from 190 bp to 210 bp. They existed as discrete bands with 4 bp discrepancy. Among which DY3(198 bp), DY4(202 bp) were common with the frequencies of 0.408, 0.356 respectively. Other alleles, DY1(190 bp, frequency 0.020), DY2(194 bp, frequency 0.121), DY5(206 bp, frequency 0.089), DY6(210 bp, frequency 0.004) were relatively uncommon. In a 78 subject father-son study with parenthood confirmed through other genetic studies, no case of mutation was noted. As the allele number was not as large as 6 and two alleles were dominant, the discrimination power in routine individual identification was thought to be low. But in selective cases such as father-son determination or sex determination, this locus could be a valuable genetic marker and we thought these results to be common for the Korean population. These results were also compared with that of other race. PMID:8934392

  3. Allele-specific copy number profiling by next-generation DNA sequencing

    PubMed Central

    Chen, Hao; Bell, John M.; Zavala, Nicolas A.; Ji, Hanlee P.; Zhang, Nancy R.

    2015-01-01

    The progression and clonal development of tumors often involve amplifications and deletions of genomic DNA. Estimation of allele-specific copy number, which quantifies the number of copies of each allele at each variant loci rather than the total number of chromosome copies, is an important step in the characterization of tumor genomes and the inference of their clonal history. We describe a new method, falcon, for finding somatic allele-specific copy number changes by next generation sequencing of tumors with matched normals. falcon is based on a change-point model on a bivariate mixed Binomial process, which explicitly models the copy numbers of the two chromosome haplotypes and corrects for local allele-specific coverage biases. By using the Binomial distribution rather than a normal approximation, falcon more effectively pools evidence from sites with low coverage. A modified Bayesian information criterion is used to guide model selection for determining the number of copy number events. Falcon is evaluated on in silico spike-in data and applied to the analysis of a pre-malignant colon tumor sample and late-stage colorectal adenocarcinoma from the same individual. The allele-specific copy number estimates obtained by falcon allows us to draw detailed conclusions regarding the clonal history of the individual's colon cancer. PMID:25477383

  4. A pseudodeficiency allele common in non-Jewish Tay-Sachs carriers: Implications for carrier screening

    SciTech Connect

    Triggs-Raine, B.L.; Akerman, B.R.; Gravel, R.A. (McGill Univ.-Montreal Children's Hospital Research Institute, Montreal, Quebec (Canada)); Mules, E.H.; Thomas, G.H.; Dowling, C.E. (Johns Hopkins School of Medicine, Baltimore, MD (United States)); Kaback, M.M.; Lim-Steele, J.S.T. (Univ. of California, San Diego, CA (United States)); Natowicz, M.R. (Eunice Kennedy Shriver Center for Mental Retardation, Waltham, MA (United States)); Grebner, E.E. (Thomas Jefferson Univ., Philadelphia, PA (United States)); Navon, R.R. (Tel-Aviv Univ., Kfar-Sava (Israel)); Welch, J.P. (Dalhousie Univ., Halifax, Nova, Scotia (Canada)); Greenberg, C.R. (Univ. of Manitoba, Winnipeg (Canada))

    1992-10-01

    Deficiency of [beta]-hexosaminidase A (Hex A) activity typically results in Tay-Sachs disease. However, healthy subjects found to be deficient in Hex A activity (i.e., pseudodeficient) by means of in vitro biochemical tests have been described. The authors analyzed the HEXA gene of one pseudodeficient subject and identified both a C[sub 739]-to-T substitution that changes Arg[sub 247][yields]Trp on one allele and a previously identified Tay-Sachs disease mutation of the second allele. Six additional pseudodeficient subjects were found to have the C[sub 739]-to-T but for none of 36 Jewish enzyme-defined carries who did not have one of three known mutations common to this group. The C[sub 739]-to-T allele, together with a [open quotes]true[close quotes] Tay-Sachs disease allele, causes Hex A pseudodeficiency. Given both the large proportion of non-Jewish carriers with this allele and that standard biochemical screening cannot differentiate between heterozygotes for the C[sub 739]-to-T mutations and Tay-Sachs disease carriers, DNA testing for this mutation in at-risk couples is essential. This could prevent unnecessary or incorrect prenatal diagnoses. 40 refs., 3 figs., 4 tabs.

  5. Both XPD alleles contribute to the phenotype of compound heterozygote xeroderma pigmentosum patients

    PubMed Central

    Ueda, Takahiro; Compe, Emmanuel; Catez, Philippe; Kraemer, Kenneth H.

    2009-01-01

    Mutations in the XPD subunit of the DNA repair/transcription factor TFIIH result in the rare recessive genetic disorder xeroderma pigmentosum (XP). Many XP patients are compound heterozygotes with a “causative” XPD point mutation R683W and different second mutant alleles, considered “null alleles.” However, there is marked clinical heterogeneity (including presence or absence of skin cancers or neurological degeneration) in these XPD/R683W patients, thus suggesting a contribution of the second allele. Here, we report XP patients carrying XPD/R683W and a second XPD allele either XPD/Q452X, /I455del, or /199insPP. We performed a systematic study of the effect of these XPD mutations on several enzymatic functions of TFIIH and found that each mutation exhibited unique biochemical properties. Although all the mutations inhibited the nucleotide excision repair (NER) by disturbing the XPD helicase function, each of them disrupted specific molecular steps during transcription: XPD/Q452X hindered the transactivation process, XPD/I455del disturbed RNA polymerase II phosphorylation, and XPD/199insPP inhibited kinase activity of the cdk7 subunit of TFIIH. The broad range and severity of clinical features in XP patients arise from a broad set of deficiencies in NER and transcription that result from the combination of mutations found on both XPD alleles. PMID:19934020

  6. Multi-allelic phenotyping – A systematic approach for the simultaneous analysis of multiple induced mutations?

    PubMed Central

    Dooley, Christopher M.; Scahill, Catherine; Fényes, Fruzsina; Kettleborough, Ross N.W.; Stemple, Derek L.; Busch-Nentwich, Elisabeth M.

    2013-01-01

    The zebrafish mutation project (ZMP) aims to generate a loss of function allele for every protein-coding gene, but importantly to also characterise the phenotypes of these alleles during the first five days of development. Such a large-scale screen requires a systematic approach both to identifying phenotypes, and also to linking those phenotypes to specific mutations. This phenotyping pipeline simultaneously assesses the consequences of multiple alleles in a two-step process. First, mutations that do not produce a visible phenotype during the first five days of development are identified, while a second round of phenotyping focuses on detailed analysis of those alleles that are suspected to cause a phenotype. Allele-specific PCR single nucleotide polymorphism (SNP) assays are used to genotype F2 parents and individual F3 fry for mutations known to be present in the F1 founder. With this method specific phenotypes can be linked to induced mutations. In addition a method is described for cryopreserving sperm samples of mutagenised males and their subsequent use for in vitro fertilisation to generate F2 families for phenotyping. Ultimately this approach will lead to the functional annotation of the zebrafish genome, which will deepen our understanding of gene function in development and disease. PMID:23624102

  7. Molecular and physiological characterization of arabidopsis GAI alleles obtained in targeted Ds-tagging experiments.

    PubMed

    Peng, Jinrong; Richards, Donald E; Moritz, Thomas; Ezura, Hiroshi; Carol, Pierre; Harberd, Nicholas P

    2002-02-01

    Bioactive gibberellin (GA) is an essential regulator of vascular plant development. The GAI gene of Arabidopsis thaliana (L.) Heynh. encodes a product (GAI) that is involved in GA signalling. The dominant mutant gai allele encodes an altered product (gai) that confers reduced GA responses, dwarfism, and elevated endogenous GA levels. Recessive, presumed loss-of-function alleles of GAI confer normal height and resistance to the GA biosynthesis inhibitor paclobutrazol. One explanation for these observations is that GAI is a growth repressor whose activity is opposed by GA, whilst gai retains a constitutive repressor activity that is less affected by GA. Previously, we described gai-t6, a mutant allele which contains an insertion of a maize Ds transposable element into gai. Here we describe the molecular and physiological characterization of two further alleles (gai-t5, gai-t7) identified during the Ds mutagenesis experiment. These alleles confer paclobutrazol resistance and normal endogenous GA levels. Thus the phenotype conferred by gai-t5, gai-t6 and gai-t7 is not due to elevated GA levels, but is due to loss of gai, a constitutively active plant growth repressor. PMID:11925042

  8. Allelic configuration and polysomic inheritance of highly variable microsatellites in tetraploid gynodioecious Thymus praecox agg.

    PubMed

    Landergott, Urs; Naciri, Yamama; Schneller, J Jakob; Holderegger, Rolf

    2006-08-01

    Polyploidy plays a pivotal role in plant evolution. However, polyploids with polysomic inheritance have hitherto been severely underrepresented in plant population genetic studies, mainly due to a lack of appropriate molecular genetic markers. Here we report the establishment and experimental validation of six fully informative microsatellite markers in tetraploid gynodioecious Thymus praecox agg. Sequence data of 150 microsatellite alleles and their flanking regions revealed high variation, which may be characteristic for polyploids with a reticulate evolutionary history. Understanding the patterns of mutation (indels and substitutions) in microsatellite flanking-sequences was a prerequisite for the development of co-dominant markers for fragment analyses. Allelic segregation patterns among progeny arrays from ten test crosses revealed tetrasomic inheritance in T. praecox agg. No evidence of frequent double reduction was detected. Polymerase chain reaction (PCR) based dosage effects allowed for precise assignment of allelic configuration at all six microsatellite loci. The quantification of allele copy numbers in PCR was verified by comparisons of observed and expected gametic allele frequencies and heterozygosities in test crosses. Our study illustrates how PCR based markers can provide reliable estimates of heterozygosity and, thus, powerful tools for breeding system and population genetic analyses in polyploid organisms. PMID:16786342

  9. Genetic factors required to maintain repression of a paramutagenic maize pl1 allele.

    PubMed Central

    Hollick, J B; Chandler, V L

    2001-01-01

    A genetic screen identified two novel gene functions required to maintain mitotically and meiotically heritable gene silencing associated with paramutation of the maize purple plant 1 (pl1) locus. Paramutation at pl1 leads to heritable alterations of pl1 gene regulation; the Pl-Rhoades (Pl-Rh) allele, which typically confers strong pigmentation to juvenile and adult plant structures, changes to a lower expression state termed Pl'-mahogany (Pl'). Paramutation spontaneously occurs at low frequencies in Pl-Rh homozygotes but always occurs when Pl-Rh is heterozygous with Pl'. We identified four mutations that caused increased Pl' pigment levels. Allelism tests revealed that three mutations identified two new maize loci, required to maintain repression 1 (rmr1) and rmr2 and that the other mutation represents a new allele of the previously described mediator of paramutation 1 (mop1) locus. RNA levels from Pl' are elevated in rmr mutants and genetic tests demonstrate that Pl' can heritably change back to Pl-Rh in rmr mutant individuals at variable frequencies. Pigment levels controlled by two pl1 alleles that do not participate in paramutation are unaffected in rmr mutants. These results suggest that RMR functions are intimately involved in maintaining the repressed expression state of paramutant Pl' alleles. Despite strong effects on Pl' repression, rmr mutant plants have no gross developmental abnormalities even after several generations of inbreeding, implying that RMR1 and RMR2 functions are not generally required for developmental homeostasis. PMID:11139517

  10. Allele-specific cytokine responses at the HLA-C locus, implications for psoriasis

    PubMed Central

    Hundhausen, Christian; Bertoni, Anna; Mak, Rose K; Botti, Elisabetta; Di Meglio, Paola; Clop, Alex; Laggner, Ute; Chimenti, Sergio; Hayday, Adrian C; Barker, Jonathan N; Trembath, Richard C; Capon, Francesca; Nestle, Frank O

    2011-01-01

    Psoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide-range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to TNF-? (rs2524094) and IFN-? (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-? and IFN-?. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-? levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to up-regulation by key pro-inflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele. PMID:22113476

  11. Allele-specific cytokine responses at the HLA-C locus: implications for psoriasis.

    PubMed

    Hundhausen, Christian; Bertoni, Anna; Mak, Rose K; Botti, Elisabetta; Di Meglio, Paola; Clop, Alex; Laggner, Ute; Chimenti, Sergio; Hayday, Adrian C; Barker, Jonathan N; Trembath, Richard C; Capon, Francesca; Nestle, Frank O

    2012-03-01

    Psoriasis is an inflammatory skin disorder that is inherited as a complex trait. Genetic studies have repeatedly highlighted HLA-C as the major determinant for psoriasis susceptibility, with the Cw*0602 allele conferring significant disease risk in a wide range of populations. Despite the potential importance of HLA-C variation in psoriasis, either via an effect on peptide presentation or immuno-inhibitory activity, allele-specific expression patterns have not been investigated. Here, we used reporter assays to characterize two regulatory variants, which virtually abolished the response to tumor necrosis factor (TNF)-? (rs2524094) and IFN-? (rs10657191) in HLA-Cw*0602 and a cluster of related alleles. We validated these findings through the analysis of HLA-Cw*0602 expression in primary keratinocytes treated with TNF-? and IFN-?. Finally, we showed that HLA-Cw*0602 transcripts are not increased in psoriatic skin lesions, despite highly elevated TNF-? levels. Thus, our findings demonstrate the presence of allele-specific differences in HLA-C expression and indicate that HLA-Cw*0602 is unresponsive to upregulation by key proinflammatory cytokines in psoriasis. These data pave the way for functional studies into the pathogenic role of the major psoriasis susceptibility allele. PMID:22113476

  12. Spatial heterogeneity in the strength of selection against deleterious alleles and the mutation load.

    PubMed

    Roze, D

    2012-09-01

    According to current estimates of genomic deleterious mutation rates (which are often of the order 0.1-1) the mutation load (defined as a reduction in the average fitness of a population due to the presence of deleterious alleles) may be important in many populations. In this paper, I use multilocus simulations to explore the effect of spatial heterogeneity in the strength of selection against deleterious alleles on the mutation load (for example, it has been suggested that stressful environments may increase the strength of selection). These simulations show contrasted results: in some situations, spatial heterogeneity may greatly reduce the mutation load, due to the fact that migrants coming from demes under stronger selection carry relatively few deleterious alleles, and benefit from a strong advantage within demes under weaker selection (where individuals carry many more deleterious alleles); in other situations, however, deleterious alleles accumulate within demes under stronger selection, due to migration pressure from demes under weaker selection, leading to fitness erosion within those demes. This second situation is more frequent when the productivity of the different demes is proportional to their mean fitness. The effect of spatial heterogeneity is greatly reduced, however, when the response to environmental differences is inconsistent across loci. PMID:22588129

  13. COMMUNICATION (European Clinical Research Infrastructures Network)

    E-print Network

    Paris-Sud XI, Université de

    COMMUNICATION ECRIN (European Clinical Research Infrastructures Network) et la structuration de la recherche clinique en Europe Mots clés : Recherche biomédicale. Europe ECRIN (European Clinical Research Infrastructures Network), a pan-european infrastructure for clinical research Key-words (Index medicus

  14. Allelic variability in the third intron of the fibroin light chain gene in Bombyx mori (Lepidoptera: Bombycidae).

    PubMed

    Barbosa, J F; Bravo, J P; Zanatta, D B; Silva, J L C; Fernandez, M A

    2009-01-01

    Conformation-sensitive gel electrophoresis is a useful method for identifying allele polymorphism; it provides co-dominant molecular markers. Using this method, we identified genetic variability in the third intron of the fibroin light chain gene, fib-L, in six Bombyx mori strains. Only Chinese C21A strain did not demonstrate allelic alterations, showing only homoduplex DNA molecules. We found distinct heteroduplex profiles in the Japanese HAA, M12B and M19-2 and the Chinese C25B and C24-2 strains. Analysis with restriction endonuclease fingerprinting conformation-sensitive gel electrophoresis demonstrated the potential of this method for the identification of allelic variability in B. mori; this was confirmed by cloning and sequencing the different alleles. The main alteration was a 12-bp deletion in two alleles of the C24-2 strain and one allele of the HAA strain; this deletion results in specific heteroduplex DNA molecule profiles. PMID:19283686

  15. A proposal for standardization in forensic equine DNA typing: allele nomenclature for 17 equine-specific STR loci.

    PubMed

    van de Goor, L H P; Panneman, H; van Haeringen, W A

    2010-04-01

    In this study, a proposal is presented for the allele nomenclature of 17 polymorphic STR loci (AHT4, AHT5, ASB2, ASB17, ASB23, CA425, HMS1, HMS2, HMS3, HMS6, HMS7, HTG4, HTG6, HTG7, HTG10, LEX3 and VHL20) for equine genotyping (Equus caballus). The nomenclature is based on sequence data of the polymorphic region of the STR loci as recommended by the DNA commission of the International Society for Forensic Genetics for human DNA typing. For each STR locus, several alleles were selected and animals homozygous for those alleles were subjected to sequence analysis. The alleles of the 17 STR loci consisted either of simple (10), compound (6) or complex repeat patterns (1). Only a limited number of alleles with the same fragment size showed different repeat structures. The allele designation described here was based on the number of repeats, including all variable regions within the amplified fragment. PMID:19821810

  16. Diagnostic value of a microsatellite DNA marker for copper toxicosis in West-European Bedlington terriers and incidence of the disease.

    PubMed

    Rothuizen, J; Ubbink, G J; van Zon, P; Teske, E; van den Ingh, T S; Yuzbasiyan-Gurkan, V

    1999-06-01

    Recently, linkage of a DNA microsatellite marker to inherited copper toxicosis has been reported in American Bedlington terrier families. Due to the fact that there is little exchange of breeding stock between the USA and Europe, it remains to be investigated whether in Europe the marker is informative and is linked with the disease. We have therefore examined the diagnostic value of the microsatellite marker in the European Bedlington. In 130 dogs at least one year of age (62 from The Netherlands, 35 from Belgium, and 33 from Germany) histo- or cytochemical staining of copper was done in liver biopsies. Based on liver histo- or cytochemistry, 51 dogs were obligate carriers, and 25 dogs had copper toxicosis. The inferred genotypes of these 76 dogs were compared with the marker genotypes. All dogs with the disease were homozygous for the 167 bp marker allele. All obligate carriers were heterozygotes with the 167 bp and a 163-bp alleles. All phenotypically healthy dogs were either homozygous for the 163 bp allele or heterozygous. Thus, the marker was in complete linkage disequilibrium with the putative copper toxicosis gene with the 167 bp allele in phase with the disease allele. The frequencies of the 167 bp and the 163 bp allele, respectively, were 0.33 and 0.67 in Dutch dogs, 0.31 and 0.69 in German dogs, and 0.57 and 0.43 in Belgian dogs. We have confirmed the utility of this marker for diagnosis of inherited copper toxicosis in European Bedlington terriers. PMID:10442980

  17. The European nanometrology landscape

    NASA Astrophysics Data System (ADS)

    Leach, Richard K.; Boyd, Robert; Burke, Theresa; Danzebrink, Hans-Ulrich; Dirscherl, Kai; Dziomba, Thorsten; Gee, Mark; Koenders, Ludger; Morazzani, Valérie; Pidduck, Allan; Roy, Debdulal; Unger, Wolfgang E. S.; Yacoot, Andrew

    2011-02-01

    This review paper summarizes the European nanometrology landscape from a technical perspective. Dimensional and chemical nanometrology are discussed first as they underpin many of the developments in other areas of nanometrology. Applications for the measurement of thin film parameters are followed by two of the most widely relevant families of functional properties: measurement of mechanical and electrical properties at the nanoscale. Nanostructured materials and surfaces, which are seen as key materials areas having specific metrology challenges, are covered next. The final section describes biological nanometrology, which is perhaps the most interdisciplinary applications area, and presents unique challenges. Within each area, a review is provided of current status, the capabilities and limitations of current techniques and instruments, and future directions being driven by emerging industrial measurement requirements. Issues of traceability, standardization, national and international programmes, regulation and skills development will be discussed in a future paper.

  18. The European nanometrology landscape.

    PubMed

    Leach, Richard K; Boyd, Robert; Burke, Theresa; Danzebrink, Hans-Ulrich; Dirscherl, Kai; Dziomba, Thorsten; Gee, Mark; Koenders, Ludger; Morazzani, Valérie; Pidduck, Allan; Roy, Debdulal; Unger, Wolfgang E S; Yacoot, Andrew

    2011-02-11

    This review paper summarizes the European nanometrology landscape from a technical perspective. Dimensional and chemical nanometrology are discussed first as they underpin many of the developments in other areas of nanometrology. Applications for the measurement of thin film parameters are followed by two of the most widely relevant families of functional properties: measurement of mechanical and electrical properties at the nanoscale. Nanostructured materials and surfaces, which are seen as key materials areas having specific metrology challenges, are covered next. The final section describes biological nanometrology, which is perhaps the most interdisciplinary applications area, and presents unique challenges. Within each area, a review is provided of current status, the capabilities and limitations of current techniques and instruments, and future directions being driven by emerging industrial measurement requirements. Issues of traceability, standardization, national and international programmes, regulation and skills development will be discussed in a future paper. PMID:21212479

  19. The effect of the Neolithic expansion on European molecular diversity

    PubMed Central

    Currat, Mathias; Excoffier, Laurent

    2005-01-01

    We performed extensive and realistic simulations of the colonization process of Europe by Neolithic farmers, as well as their potential admixture and competition with local Palaeolithic hunter–gatherers. We find that minute amounts of gene flow between Palaeolithic and Neolithic populations should lead to a massive Palaeolithic contribution to the current gene pool of Europeans. This large Palaeolithic contribution is not expected under the demic diffusion (DD) model, which postulates that agriculture diffused over Europe by a massive migration of individuals from the Near East. However, genetic evidence in favour of this model mainly consisted in the observation of allele frequency clines over Europe, which are shown here to be equally probable under a pure DD or a pure acculturation model. The examination of the consequence of range expansions on single nucleotide polymorphism (SNP) diversity reveals that an ascertainment bias consisting of selecting SNPs with high frequencies will promote the observation of genetic clines (which are not expected for random SNPs) and will lead to multimodal mismatch distributions. We conclude that the different patterns of molecular diversity observed for Y chromosome and mitochondrial DNA can be at least partly owing to an ascertainment bias when selecting Y chromosome SNPs for studying European populations. PMID:15870030

  20. European project ISAWARE

    NASA Astrophysics Data System (ADS)

    Kaiser, Jochen; Smietanski, Guillaume; Kubbat, Wolfgang

    2001-08-01

    As air traffic is increasing, the probability of encountering 'surveillance' alerts during flight is also increasing. In order to ensure safety, new on board systems need to be developed to provide the crew with a better 'situation awareness' (SA) about its external environment and potential hazards. In addition, the means to manage the data generated by these new systems needs to be build up. Despite the tremendous amount of information, crew workload must not increase. This is where the ISAWARE project comes in with the Integrated Situation Awareness System (ISAS) concept. ISAWARE (Increasing Safety through collision Avoidance WARning intEgration) is a project partly funded by the European Community, executed by a well balanced composition of several European aerospace companies (airframers, a helicopter manufacturer, avionics suppliers, airlines), one research laboratory and one university. The overall objective of the ISAWARE project is to conduct research into the potential improvements to flight safety that can be achieved by providing the pilot with complete predictive situation awareness during all phases of the flight. The Integrated Situational Awareness System (ISAS) merges data from different safety systems concerning terrain, traffic, weather and other. The system ensures the alerts consistency, prioritises alerts and anticipates threats along a predicted trajectory earlier than current systems can provide. The second main axis of the research is the development of synthetic vision displays (PFD, ND and HUD) to enhance the Human-Machine Interface (HMI). The key focus of the project is the development of a ground-based demonstrator rig which is interfaced to a dynamic flight simulator. This rig is used for the evaluation of the ISAWARE concept by a representative range of active airline crews.

  1. Effects of Deletions of High Molecular Weight Glutenin Subunit Alleles on Dough Properties and Wheat Flour Tortilla Quality 

    E-print Network

    Tuncil, Yunus

    2012-10-19

    .............................................. 51 6 Effect of deletions and variations in high molecular weight glutenin allelic composition on tortilla deformation modulus ................................. 56 7 Effect of deletions and variations in high molecular weight glutenin allelic... of wheat cultivars with optimum gluten functionality for tortillas. RESEARCH OBJECTIVES 1) Determine the effect of deletions at different HMW -GS alleles at homologous loci on A, B, and D genomes, on dough properties 3 2) Evaluate the tortilla...

  2. EUROPEAN IDENTITY AND EUROPEAN CITIZENSHIP IN THREE "EUROCITIES" : A SOCIOLOGICAL APPROACH TO THE EUROPEAN

    E-print Network

    Boyer, Edmond

    of quantitative research on European identity linked to official sources of data such as Eurobarometer, there has and Eurocities: Free Movement and Mobility in an Integrating Europe (Favell, 2008), as well as data from an accom. The European Union's big mistake was to try to market the many supplementary individual rights of free movement

  3. Allelic expression at the sorbitol dehydrogenase and glucosephosphate isomerase loci in an interspecific hybrid ricefish.

    PubMed

    Frankel, J S

    1989-01-01

    1. The expression of alleles encoding the enzymes sorbitol dehydrogenase (SDH; EC 1.1.1.14) and glucosephosphate isomerase (GPI; EC 5.3.1.9) was investigated in Oryzias melastigma, O. javanicus and in O. melastigma female x O. javanicus male hybrids by acrylamide gel electrophoresis. 2. It was not possible to investigate the expression of SDH or GPI in reciprocal hybrids as these fry failed to develop past the stage of embryonic body formation. 3. The delay in appearance of isozymes of paternal SDH subunit composition, and paternal and maternal GPI-B subunit composition is in keeping with observed effects of gene regulatory divergence where alleles of maternal origin interact more effectively with maternal cytoplasmic regulatory factors than do alleles of paternal origin. PMID:2706942

  4. TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum.

    PubMed

    Davis, Erica E; Zhang, Qi; Liu, Qin; Diplas, Bill H; Davey, Lisa M; Hartley, Jane; Stoetzel, Corinne; Szymanska, Katarzyna; Ramaswami, Gokul; Logan, Clare V; Muzny, Donna M; Young, Alice C; Wheeler, David A; Cruz, Pedro; Morgan, Margaret; Lewis, Lora R; Cherukuri, Praveen; Maskeri, Baishali; Hansen, Nancy F; Mullikin, James C; Blakesley, Robert W; Bouffard, Gerard G; Gyapay, Gabor; Rieger, Susanne; Tönshoff, Burkhard; Kern, Ilse; Soliman, Neveen A; Neuhaus, Thomas J; Swoboda, Kathryn J; Kayserili, Hulya; Gallagher, Tomas E; Lewis, Richard A; Bergmann, Carsten; Otto, Edgar A; Saunier, Sophie; Scambler, Peter J; Beales, Philip L; Gleeson, Joseph G; Maher, Eamonn R; Attié-Bitach, Tania; Dollfus, Hélène; Johnson, Colin A; Green, Eric D; Gibbs, Richard A; Hildebrandt, Friedhelm; Pierce, Eric A; Katsanis, Nicholas

    2011-03-01

    Ciliary dysfunction leads to a broad range of overlapping phenotypes, collectively termed ciliopathies. This grouping is underscored by genetic overlap, where causal genes can also contribute modifier alleles to clinically distinct disorders. Here we show that mutations in TTC21B, which encodes the retrograde intraflagellar transport protein IFT139, cause both isolated nephronophthisis and syndromic Jeune asphyxiating thoracic dystrophy. Moreover, although resequencing of TTC21B in a large, clinically diverse ciliopathy cohort and matched controls showed a similar frequency of rare changes, in vivo and in vitro evaluations showed a significant enrichment of pathogenic alleles in cases (P < 0.003), suggesting that TTC21B contributes pathogenic alleles to ?5% of ciliopathy cases. Our data illustrate how genetic lesions can be both causally associated with diverse ciliopathies and interact in trans with other disease-causing genes and highlight how saturated resequencing followed by functional analysis of all variants informs the genetic architecture of inherited disorders. PMID:21258341

  5. Heritable Individual-Specific and Allele-Specific Chromatin Signatures in Humans

    PubMed Central

    McDaniell, Ryan; Lee, Bum-Kyu; Song, Lingyun; Liu, Zheng; Boyle, Alan P.; Erdos, Michael R.; Scott, Laura J.; Morken, Mario A.; Kucera, Katerina S.; Battenhouse, Anna; Keefe, Damian; Collins, Francis S.; Willard, Huntington F.; Lieb, Jason D.; Furey, Terrence S.; Crawford, Gregory E.; Iyer, Vishwanath R.; Birney, Ewan

    2010-01-01

    The extent to which variation in chromatin structure and transcription factor binding may influence gene expression, and thus underlie or contribute to variation in phenotype, is unknown. To address this question, we cataloged both individual-to-individual variation and differences between homologous chromosomes within the same individual (allele-specific variation) in chromatin structure and transcription factor binding in lymphoblastoid cells derived from individuals of geographically diverse ancestry. Ten percent of active chromatin sites were individual-specific; a similar proportion were allele-specific. Both individual-specific and allele-specific sites were commonly transmitted from parent to child, which suggests that they are heritable features of the human genome. Our study shows that heritable chromatin status and transcription factor binding differ as a result of genetic variation and may underlie phenotypic variation in humans. PMID:20299549

  6. Model-Integrated Estimation of Normal Tissue Contamination for Cancer SNP Allelic Copy Number Data

    PubMed Central

    Stjernqvist, Susann; Rydén, Tobias; Greenman, Chris D.

    2011-01-01

    SNP allelic copy number data provides intensity measurements for the two different alleles separately. We present a method that estimates the number of copies of each allele at each SNP position, using a continuous-index hidden Markov model. The method is especially suited for cancer data, since it includes the fraction of normal tissue contamination, often present when studying data from cancer tumors, into the model. The continuous-index structure takes into account the distances between the SNPs, and is thereby appropriate also when SNPs are unequally spaced. In a simulation study we show that the method performs favorably compared to previous methods even with as much as 70% normal contamination. We also provide results from applications to clinical data produced using the Affymetrix genome-wide SNP 6.0 platform. PMID:21695067

  7. Single-cell transcriptogenomics reveals transcriptional exclusion of ENU-mutated alleles.

    PubMed

    Li, Wenge; Calder, R Brent; Mar, Jessica C; Vijg, Jan

    2015-02-01

    Recently, great progress has been made in single cell genomics and transcriptomics. Here, we present an integrative method, termed single-cell transcriptogenomics (SCTG), in which whole exome sequencing and RNA-seq is performed concurrently on single cells. This methodology enables one to track germline and somatic variants directly from the genome to the transcriptome in individual cells. Mouse embryonic fibroblasts were treated with the powerful mutagen ethylnitrosourea (ENU) and subjected to SCTG. Interestingly, while germline variants were found to be transcribed in an allelically balanced fashion, a significantly different pattern of allelic exclusion was observed for ENU-mutant variants. These results suggest that the adverse effects of induced mutations, in contrast to germline variants, may be mitigated by allelically biased transcription. They also illustrate how SCTG can be instrumental in the direct assessment of phenotypic consequences of genomic variants. PMID:25733965

  8. Transcription efficiency of different chicken mannose-binding lectin promoter alleles.

    PubMed

    Kjærup, R M; Dalgaard, T S; Norup, L R; Goto, R M; Miller, M M; Sørensen, P; Juul-Madsen, H R

    2014-12-01

    The serum collectin mannose-binding lectin (MBL) plays a major role in innate immunity by activation of the lectin complement pathway or by acting as an opsonin. The serum levels of human and animal MBL are associated with susceptibility to a wide range of infections, and the variation of MBL in serum is genetically determined. In the chicken, 14 single nucleotide polymorphisms (SNPs) have so far been found in the MBL promoter region. In this study, the transcription activity of a 670-bp promoter region covering all 14 SNPs from the four MBL promoter alleles A1 to A4 was assessed using a dual-luciferase assay. Of the analysed alleles, A1 showed the highest transcription activity although this allele is frequently found in chickens with low MBL mRNA expression. PMID:25186068

  9. Differential allelic expression of a fibrillin gene (FBNI) in patients with Marfan syndrome

    SciTech Connect

    Hewett, D.; Lynch, J.; Sykes, B. [Univ. of Oxford (United Kingdom); Firth, H. [Churchill Hospital, Oxford (United Kingdom); Child, A. [St. George`s Hospital Medical School, London (United Kingdom)

    1994-09-01

    Marfan syndrome is a connective-tissue disorder affecting cardiovascular, skeletal, and ocular systems. The major Marfan locus has been identified as the FBN1 gene on chromosome 15; this codes for the extracellular-matrix protein fibrillin, a 350-kD constituent of the 8-10-nm elastin-associated microfibrils. The authors identified five MFS patients who were heterozygous for an RsaI restriction-site dimorphism in the 3{prime} UTR of the FBN1 gene. This expressed variation was used to distinguish the mRNA output from each of the two FBN1 alleles in fibroblast cultures from these five patients. Three of the patients were shown to produce <5% of the normal level of FBN1 transcripts from one of their alleles. This null-allele phenotype was not observed in 10 nonmarfanoid fibroblast cell lines. 26 refs., 4 figs.

  10. Transgene- and locus-dependent imprinting reveals allele-specific chromosome conformations

    PubMed Central

    Lonfat, Nicolas; Montavon, Thomas; Jebb, David; Tschopp, Patrick; Nguyen Huynh, Thi Hanh; Zakany, Jozsef; Duboule, Denis

    2013-01-01

    When positioned into the integrin ?-6 gene, an Hoxd9lacZ reporter transgene displayed parental imprinting in mouse embryos. While the expression from the paternal allele was comparable with patterns seen for the same transgene when present at the neighboring HoxD locus, almost no signal was scored at this integration site when the transgene was inherited from the mother, although the Itga6 locus itself is not imprinted. The transgene exhibited maternal allele-specific DNA hypermethylation acquired during oogenesis, and its expression silencing was reversible on passage through the male germ line. Histone modifications also corresponded to profiles described at known imprinted loci. Chromosome conformation analyses revealed distinct chromatin microarchitectures, with a more compact structure characterizing the maternally inherited repressed allele. Such genetic analyses of well-characterized transgene insertions associated with a de novo-induced parental imprint may help us understand the molecular determinants of imprinting. PMID:23818637

  11. Analysis of novel sph (spherocytosis) alleles in mice reveals allele-specific loss of band 3 and adducin in ?-spectrin–deficient red cells

    PubMed Central

    Robledo, Raymond F.; Lambert, Amy J.; Birkenmeier, Connie S.; Cirlan, Marius V.; Cirlan, Andreea Flavia M.; Campagna, Dean R.; Lux, Samuel E.

    2010-01-01

    Five spontaneous, allelic mutations in the ?-spectrin gene, Spna1, have been identified in mice (spherocytosis [sph], sph1J, sph2J, sph2BC, sphDem). All cause severe hemolytic anemia. Here, analysis of 3 new alleles reveals previously unknown consequences of red blood cell (RBC) spectrin deficiency. In sph3J, a missense mutation (H2012Y) in repeat 19 introduces a cryptic splice site resulting in premature termination of translation. In sphIhj, a premature stop codon occurs (Q1853Stop) in repeat 18. Both mutations result in markedly reduced RBC membrane spectrin content, decreased band 3, and absent ?-adducin. Reevaluation of available, previously described sph alleles reveals band 3 and adducin deficiency as well. In sph4J, a missense mutation occurs in the C-terminal EF hand domain (C2384Y). Notably, an equally severe hemolytic anemia occurs despite minimally decreased membrane spectrin with normal band 3 levels and present, although reduced, ?-adducin. The severity of anemia in sph4J indicates that the highly conserved cysteine residue at the C-terminus of ?-spectrin participates in interactions critical to membrane stability. The data reinforce the notion that a membrane bridge in addition to the classic protein 4.1-p55-glycophorin C linkage exists at the RBC junctional complex that involves interactions between spectrin, adducin, and band 3. PMID:20056793

  12. Germ line transmission of an inactive N-myc allele generated by homologous recombination in mouse embryonic stem cells.

    PubMed Central

    Stanton, B R; Reid, S W; Parada, L F

    1990-01-01

    We have disrupted one allele of the N-myc locus in mouse embryonic stem (ES) cells by using homologous recombination techniques and have obtained germ line transmission of null N-myc ES cell lines with transmission of the null N-myc allele to the offspring. The creation of mice with a deficient N-myc allele will allow the generation of offspring bearing null N-myc alleles in both chromosomes and permit study of the role that this proto-oncogene plays in embryonic development. Images PMID:1701023

  13. Genetic Exchange of Fimbrial Alleles Exemplifies the Adaptive Virulence Strategy of Porphyromonas gingivalis

    PubMed Central

    Kerr, Jennifer E.; Abramian, Jared R.; Dao, Doan-Hieu V.; Rigney, Todd W.; Fritz, Jamie; Pham, Tan; Gay, Isabel; Parthasarathy, Kavitha; Wang, Bing-yan; Zhang, Wenjian; Tribble, Gena D.

    2014-01-01

    Porphyromonas gingivalis is a gram–negative anaerobic bacterium, a member of the human oral microbiome, and a proposed “keystone” pathogen in the development of chronic periodontitis, an inflammatory disease of the gingiva. P. gingivalis is a genetically diverse species, and is able to exchange chromosomal DNA between strains by natural competence and conjugation. In this study, we investigate the role of horizontal DNA transfer as an adaptive process to modify behavior, using the major fimbriae as our model system, due to their critical role in mediating interactions with the host environment. We show that P. gingivalis is able to exchange fimbrial allele types I and IV into four distinct strain backgrounds via natural competence. In all recombinants, we detected a complete exchange of the entire fimA allele, and the rate of exchange varies between the different strain backgrounds. In addition, gene exchange within other regions of the fimbrial genetic locus was identified. To measure the biological implications of these allele swaps we compared three genotypes of fimA in an isogenic background, strain ATCC 33277. We demonstrate that exchange of fimbrial allele type results in profound phenotypic changes, including the quantity of fimbriae elaborated, membrane blebbing, auto-aggregation and other virulence-associated phenotypes. Replacement of the type I allele with either the type III or IV allele resulted in increased invasion of gingival fibroblast cells relative to the isogenic parent strain. While genetic variability is known to impact host-microbiome interactions, this is the first study to quantitatively assess the adaptive effect of exchanging genes within the pan genome cloud. This is significant as it presents a potential mechanism by which opportunistic pathogens may acquire the traits necessary to modify host-microbial interactions. PMID:24626479

  14. Meta-analysis of APOE4 allele and outcome after traumatic brain injury.

    PubMed

    Zhou, Weidong; Xu, Di; Peng, Xiaoxia; Zhang, Qiuhong; Jia, Jianping; Crutcher, Keith A

    2008-04-01

    There is conflicting evidence regarding a possible association between the apolipoprotein E4 (APOE4) allele and the consequences of traumatic brain injury (TBI). Our aim was to carry out a meta-analysis of cohort studies of sufficient rigor to determine whether the presence of the APOE4 allele contributes to initial injury severity and/or poor outcome following TBI. MEDLINE, EMBase, CBMdisc, and CNKI databases were searched for literature published from January 1993 to October 2007. Of the 100 identified studies, 14 cohort studies were selected for analysis based on comprehensive quality assessment using a standardized scale. Data from the 14 eligible cohort studies included a total of 2527 participants, 736 with and 1791 without the APOE4 allele. The APOE4 allele was not associated with initial injury severity of TBI. The pooled RR were 1.11 (95% confidence interval [CI], 0.91 to 1.35) for severe injury, 1.06 (95% CI, 0.86-1.31) for moderate injury and 0.93 (95% CI, 0.81-1.06) for mild injury. However, the APOE4 allele was significantly associated with a poor outcome of TBI at 6 months after injury (RR = 1.36; 95% CI, 1.04-1.78). The association remained significant in sensitivity tests. This meta-analysis indicates that the presence of the APOE4 allele is not associated with the initial severity of brain injury following TBI but is associated with increased risk of poor long-term outcome at 6 months after injury. PMID:18373478

  15. Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy

    PubMed Central

    Zeng, R; Coates, JR; Johnson, GC; Hansen, L; Awano, T; Kolicheski, A; Ivansson, E; Perloski, M; Lindblad-Toh, K; O'Brien, DP; Guo, J; Katz, ML; Johnson, GS

    2014-01-01

    Background Previous reports associated 2 mutant SOD1 alleles (SOD1:c.118A and SOD1:c.52T) with degenerative myelopathy in 6 canine breeds. The distribution of these alleles in other breeds has not been reported. Objective To describe the distribution of SOD1:c.118A and SOD1:c.52T in 222 breeds. Animals DNA from 33,747 dogs was genotyped at SOD1:c.118, SOD1:c.52, or both. Spinal cord sections from 249 of these dogs were examined. Methods Retrospective analysis of 35,359 previously determined genotypes at SOD1:c.118G>A or SOD1:c.52A>T and prospective survey to update the clinical status of a subset of dogs from which samples were obtained with a relatively low ascertainment bias. Results The SOD1:c.118A allele was found in cross-bred dogs and in 124 different canine breeds whereas the SOD1:c.52T allele was only found in Bernese Mountain Dogs. Most of the dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A homozygotes, but 8 dogs with histopathologically confirmed degenerative myelopathy were SOD1:c.118A/G heterozygotes and had no other sequence variants in their SOD1 amino acid coding regions. The updated clinical conditions of dogs from which samples were obtained with a relatively low ascertainment bias suggest that SOD1:c.118A homozygotes are at a much higher risk of developing degenerative myelopathy than are SOD1:c.118A/G heterozygotes. Conclusions and Clinical Importance We conclude that the SOD1:c.118A allele is widespread and common among privately owned dogs whereas the SOD1:c.52T allele is rare and appears to be limited to Bernese Mountain Dogs. We also conclude that breeding to avoid the production of SOD1:c.118A homozygotes is a rational strategy. PMID:24524809

  16. Imputation of TPMT defective alleles for the identification of patients with high-risk phenotypes

    PubMed Central

    Almoguera, Berta; Vazquez, Lyam; Connolly, John J.; Bradfield, Jonathan; Sleiman, Patrick; Keating, Brendan; Hakonarson, Hakon

    2014-01-01

    Background: The activity of thiopurine methyltransferase (TPMT) is subject to genetic variation. Loss-of-function alleles are associated with various degrees of myelosuppression after treatment with thiopurine drugs, thus genotype-based dosing recommendations currently exist. The aim of this study was to evaluate the potential utility of leveraging genomic data from large biorepositories in the identification of individuals with TPMT defective alleles. Material and methods: TPMT variants were imputed using the 1000 Genomes Project reference panel in 87,979 samples from the biobank at The Children's Hospital of Philadelphia. Population ancestry was determined by principal component analysis using HapMap3 samples as reference. Frequencies of the TPMT imputed alleles, genotypes and the associated phenotype were determined across the different populations. A sample of 630 subjects with genotype data from Sanger sequencing (N = 59) and direct genotyping (N = 583) (12 samples overlapping in the two groups) was used to check the concordance between the imputed and observed genotypes, as well as the sensitivity, specificity and positive and negative predictive values of the imputation. Results: Two SNPs (rs1800460 and rs1142345) that represent three TPMT alleles (*3A, *3B, and *3C) were imputed with adequate quality. Frequency for the associated enzyme activity varied across populations and 89.36–94.58% were predicted to have normal TPMT activity, 5.3–10.31% intermediate and 0.12–0.34% poor activities. Overall, 98.88% of individuals (623/630) were correctly imputed into carrying no risk alleles (553/553), heterozygous (45/46) and homozygous (25/31). Sensitivity, specificity and predictive values of imputation were over 90% in all cases except for the sensitivity of imputing homozygous subjects that was 80.64%. Conclusion: Imputation of TPMT alleles from existing genomic data can be used as a first step in the screening of individuals at risk of developing serious adverse events secondary to thiopurine drugs. PMID:24860591

  17. Genetic exchange of fimbrial alleles exemplifies the adaptive virulence strategy of Porphyromonas gingivalis.

    PubMed

    Kerr, Jennifer E; Abramian, Jared R; Dao, Doan-Hieu V; Rigney, Todd W; Fritz, Jamie; Pham, Tan; Gay, Isabel; Parthasarathy, Kavitha; Wang, Bing-yan; Zhang, Wenjian; Tribble, Gena D

    2014-01-01

    Porphyromonas gingivalis is a gram-negative anaerobic bacterium, a member of the human oral microbiome, and a proposed "keystone" pathogen in the development of chronic periodontitis, an inflammatory disease of the gingiva. P. gingivalis is a genetically diverse species, and is able to exchange chromosomal DNA between strains by natural competence and conjugation. In this study, we investigate the role of horizontal DNA transfer as an adaptive process to modify behavior, using the major fimbriae as our model system, due to their critical role in mediating interactions with the host environment. We show that P. gingivalis is able to exchange fimbrial allele types I and IV into four distinct strain backgrounds via natural competence. In all recombinants, we detected a complete exchange of the entire fimA allele, and the rate of exchange varies between the different strain backgrounds. In addition, gene exchange within other regions of the fimbrial genetic locus was identified. To measure the biological implications of these allele swaps we compared three genotypes of fimA in an isogenic background, strain ATCC 33277. We demonstrate that exchange of fimbrial allele type results in profound phenotypic changes, including the quantity of fimbriae elaborated, membrane blebbing, auto-aggregation and other virulence-associated phenotypes. Replacement of the type I allele with either the type III or IV allele resulted in increased invasion of gingival fibroblast cells relative to the isogenic parent strain. While genetic variability is known to impact host-microbiome interactions, this is the first study to quantitatively assess the adaptive effect of exchanging genes within the pan genome cloud. This is significant as it presents a potential mechanism by which opportunistic pathogens may acquire the traits necessary to modify host-microbial interactions. PMID:24626479

  18. Quantifying Selection Acting on a Complex Trait Using Allele Frequency Time Series Data

    PubMed Central

    Illingworth, Christopher J.R.; Parts, Leopold; Schiffels, Stephan; Liti, Gianni; Mustonen, Ville

    2012-01-01

    When selection is acting on a large genetically diverse population, beneficial alleles increase in frequency. This fact can be used to map quantitative trait loci by sequencing the pooled DNA from the population at consecutive time points and observing allele frequency changes. Here, we present a population genetic method to analyze time series data of allele frequencies from such an experiment. Beginning with a range of proposed evolutionary scenarios, the method measures the consistency of each with the observed frequency changes. Evolutionary theory is utilized to formulate equations of motion for the allele frequencies, following which likelihoods for having observed the sequencing data under each scenario are derived. Comparison of these likelihoods gives an insight into the prevailing dynamics of the system under study. We illustrate the method by quantifying selective effects from an experiment, in which two phenotypically different yeast strains were first crossed and then propagated under heat stress (Parts L, Cubillos FA, Warringer J, et al. [14 co-authors]. 2011. Revealing the genetic structure of a trait by sequencing a population under selection. Genome Res). From these data, we discover that about 6% of polymorphic sites evolve nonneutrally under heat stress conditions, either because of their linkage to beneficial (driver) alleles or because they are drivers themselves. We further identify 44 genomic regions containing one or more candidate driver alleles, quantify their apparent selective advantage, obtain estimates of recombination rates within the regions, and show that the dynamics of the drivers display a strong signature of selection going beyond additive models. Our approach is applicable to study adaptation in a range of systems under different evolutionary pressures. PMID:22114362

  19. HLA-DR2-associated DRB1 and DRB5 alleles and haplotypes in Koreans.

    PubMed

    Song, E Y; Kang, S J; Lee, Y J; Park, M H

    2000-09-01

    There are considerable racial differences in the distribution of HLA-DR2-associated DRB1 and DRB5 alleles and the characteristics of linkage disequilibrium between these alleles. In this study, the frequencies of DR2-associated DRB1 and DRB5 alleles and related haplotypes were analyzed in 186 DR2-positive individuals out of 800 normal Koreans registered for unrelated bone marrow donors. HLA class I antigen typing was performed by the serological method and DRB1 and DRB5 genotyping by the PCR-single strand conformational polymorphism method. Only 3 alleles were detected for DR2-associated DRB1 and DRB5 genes, respectively: DRB1(*)1501 (gene frequency 8.0%), (*)1502 (3.2%), (*)1602 (0.9%); DRB5(*)0101 (8.0%), (*)0102 (3.2%), and (*)0202 (0.9%). DRB1-DRB5 haplotype analysis showed an exclusive association between these alleles: DRB1*1501-DRB5*0101 (haplotype frequency 8.0%), DRB1(*)1502-DRB5(*)0102 (3.2%), and DRB1(*)1602-DRB5(*)0202 (0.9%). The 5 most common DR2-associated A-B-DRB1 haplotypes occurring at frequencies of > or = 0.5% were A24-B52-DRB1(*)1502 (1.8%), A2-B62-DRB1(*)1501, A2-B54-DRB1(*)1501, A26-B61-DRB1(*)1501, and A24-B51-DRB1(*)1501. The remarkable homogeneity in the haplotypic associations between DR2-associated DRB1 and DRB5 alleles in Koreans would be advantageous for organ transplantation compared with other ethnic groups showing considerable heterogeneity in the distribution of DRB1-DRB5 haplotypes. PMID:11053638

  20. Catalogue of alleles of gliadin-coding loci in durum wheat (Triticum durum Desf.).

    PubMed

    Melnikova, N V; Kudryavtseva, A V; Kudryavtsev, A M

    2012-02-01

    Gliadins are seed storage proteins which are characterized by high intervarietal polymorphism and can be used as genetic markers. As a result of our work, a considerably extended catalogue of allelic variants of gliadin component blocks was compiled for durum wheat; 74 allelic variants for four gliadin-coding loci were identified for the first time. The extended catalogue includes a total of 131 allelic variants: 16 for locus Gli-A1(d), 19 for locus Gli-B1(d), 41 for locus Gli-A2(d), and 55 for locus Gli-B2(d). The electrophoretic pattern of the standard cultivar and a diagram are provided for every block identified. The number of alleles per family is quite small for loci Gli-A1(d) and Gli-B1(d) of durum wheat, as contrasted to loci Gli-A2(d) and Gli-B2(d) that are characterized by large families including many alleles. The presence of large block families determines a higher diversity of durum wheat for loci Gli-A2(d) and Gli-B2(d) as compared to Gli-A1(d) and Gli-B1(d). The catalogue of allelic variants of gliadin component blocks can be used by seed farmers to identify durum wheat cultivars and evaluate their purity; by breeders, to obtain homogenous cultivars and control the initial stages of selection; by gene bank experts, to preserve native varieties and the original biotypic composition of cultivars. PMID:21946233

  1. The heterogeneous allelic repertoire of human toll-like receptor (TLR) genes.

    PubMed

    Georgel, Philippe; Macquin, Cécile; Bahram, Seiamak

    2009-01-01

    Toll-Like Receptors (TLR) are critical elements of the innate arm of the vertebrate immune system. They constitute a multigenic family of receptors which collectively bind a diverse array of--exogeneous as well as endogeneous--ligands. An exponential burst of knowledge has defined their biological role in fight against infections and generation/modulation of auto-immune disorders. Hence, they could at least be conceptually recognized--despite being structurally unrelated - as innate counterparts to Major Histocompatibility Complex (MHC) molecules--equally recognizing antigenic ligands (albeit structurally more homogeneous i.e., peptides), again derived from self and/or non-self sources--preeminent this time in adaptive immunity. Our great disparities in face of infections and/or susceptibility to auto-immune diseases have provoked an intense search for genetic explanations, in part satisfied by the extraordinary MHC allelic repertoire. An equally in-depth and systematic analysis of TLR diversity is lacking despite numerous independent reports of a growing number of SNPs within these loci. The work described here aims at providing a preliminary picture of the allelic repertoire--and not purely SNPs--of all 10 human TLR coding sequences (with exception of TLR3) within a single cohort of up to 100 individuals. It appears from our work that TLR are unequally polymorphic: TLR2 (DNA alleles: 7/protein alleles: 3), 4 (4/3), 7 (6/3), 8 (9/2) and 9 (8/3) being comparatively least diverse whereas TLR1 (11/10), 5 (14/12), 6 (10/8) and 10 (15/10) show a substantial number of alleles. In addition to allelic assignment of a large number of SNPs, 10 new polymorphic positions were hereby identified. Hence this work depicts a first overview of the diversity of almost all human TLR genes, a prelude for large-scale population genetics as well as genetic association studies. PMID:19924287

  2. Mining the human phenome using allelic scores that index biological intermediates.

    PubMed

    Evans, David M; Brion, Marie Jo A; Paternoster, Lavinia; Kemp, John P; McMahon, George; Munafò, Marcus; Whitfield, John B; Medland, Sarah E; Montgomery, Grant W; Timpson, Nicholas J; St Pourcain, Beate; Lawlor, Debbie A; Martin, Nicholas G; Dehghan, Abbas; Hirschhorn, Joel; Davey Smith, George

    2013-10-01

    It is common practice in genome-wide association studies (GWAS) to focus on the relationship between disease risk and genetic variants one marker at a time. When relevant genes are identified it is often possible to implicate biological intermediates and pathways likely to be involved in disease aetiology. However, single genetic variants typically explain small amounts of disease risk. Our idea is to construct allelic scores that explain greater proportions of the variance in biological intermediates, and subsequently use these scores to data mine GWAS. To investigate the approach's properties, we indexed three biological intermediates where the results of large GWAS meta-analyses were available: body mass index, C-reactive protein and low density lipoprotein levels. We generated allelic scores in the Avon Longitudinal Study of Parents and Children, and in publicly available data from the first Wellcome Trust Case Control Consortium. We compared the explanatory ability of allelic scores in terms of their capacity to proxy for the intermediate of interest, and the extent to which they associated with disease. We found that allelic scores derived from known variants and allelic scores derived from hundreds of thousands of genetic markers explained significant portions of the variance in biological intermediates of interest, and many of these scores showed expected correlations with disease. Genome-wide allelic scores however tended to lack specificity suggesting that they should be used with caution and perhaps only to proxy biological intermediates for which there are no known individual variants. Power calculations confirm the feasibility of extending our strategy to the analysis of tens of thousands of molecular phenotypes in large genome-wide meta-analyses. We conclude that our method represents a simple way in which potentially tens of thousands of molecular phenotypes could be screened for causal relationships with disease without having to expensively measure these variables in individual disease collections. PMID:24204319

  3. Y-chromosome Short Tandem Repeat Intermediate Variant Alleles DYS392.2, DYS449.2, and DYS385.2 Delineate New Phylogenetic Substructure in Human Y-chromosome Haplogroup Tree

    PubMed Central

    Myres, Natalie M.; Ritchie, Kathleen H.; Lin, Alice A.; Hughes, Robert H.; Woodward, Scott R.; Underhill, Peter A.

    2009-01-01

    Aim To determine the human Y-chromosome haplogroup backgrounds of intermediate-sized variant alleles displayed by short tandem repeat (STR) loci DYS392, DYS449, and DYS385, and to evaluate the potential of each intermediate variant to elucidate new phylogenetic substructure within the human Y-chromosome haplogroup tree. Methods Molecular characterization of lineages was achieved using a combination of Y-chromosome haplogroup defining binary polymorphisms and up to 37 short tandem repeat loci. DNA sequencing and median-joining network analyses were used to evaluate Y-chromosome lineages displaying intermediate variant alleles. Results We show that DYS392.2 occurs on a single haplogroup background, specifically I1*-M253, and likely represents a new phylogenetic subdivision in this European haplogroup. Intermediate variants DYS449.2 and DYS385.2 both occur on multiple haplogroup backgrounds, and when evaluated within specific haplogroup contexts, delineate new phylogenetic substructure, with DYS449.2 being informative within haplogroup A-P97 and DYS385.2 in haplogroups D-M145, E1b1a-M2, and R1b*-M343. Sequence analysis of variant alleles observed within the various haplogroup backgrounds showed that the nature of the intermediate variant differed, confirming the mutations arose independently. Conclusions Y-chromosome short tandem repeat intermediate variant alleles, while relatively rare, typically occur on multiple haplogroup backgrounds. This distribution indicates that such mutations arise at a rate generally intermediate to those of binary markers and Y-STR loci. As a result, intermediate-sized Y-STR variants can reveal phylogenetic substructure within the Y-chromosome phylogeny not currently detected by either binary or Y-STR markers alone, but only when such variants are evaluated within a haplogroup context. PMID:19480020

  4. Alleles of the fibroin gene coding for proteins of different lengths.

    PubMed

    Sprague, K U; Roth, M B; Manning, R F; Gage, L P

    1979-06-01

    Bombyx mori silkworms producing fibroin proteins of different lengths have been analyzed genetically and shown to possess variant alleles of a single fibroin gene. The structures of two alleles have been compared by using restriction endonuclease sites inside and outsite the fibroin gene as physical markers. We find that fibroins distinguishable on the basis of length are encoded by genes with different internal structures and overall lengths. Our results strongly support the idea that rearrangements within the highly repetitive sequences of the fibroin gene are the result of unequal recombination, and can give rise to variant fibroin genes with altered coding lengths. PMID:455471

  5. Allele frequencies of six miniSTR loci of three ethnic populations in Singapore.

    PubMed

    Yong, R Y Y; Gan, L S H; Coble, M D; Yap, E P H

    2007-03-01

    MiniSTR loci has demonstrated to be an effective approach to recover genetic information from degraded sample, due to the improved PCR efficiency of their reduced PCR product sizes. This study investigated the allele frequency of six miniSTR loci, D1S1677, D2S441, D4S2364, D10S1248, D14S1434 and D22S1045, in three Singapore populations. All loci showed a moderate degree of polymorphism with observed heterozygosity >0.6 for all three populations. The allele frequencies, forensic parameters and heterozygosity comparison with other CODIS STR in similar populations are presented. PMID:16431057

  6. An allele-specific gene expression assay to test the functional basis of genetic associations.

    PubMed

    Paracchini, Silvia; Monaco, Anthony P; Knight, Julian C

    2010-01-01

    The number of significant genetic associations with common complex traits is constantly increasing. However, most of these associations have not been understood at molecular level. One of the mechanisms mediating the effect of DNA variants on phenotypes is gene expression, which has been shown to be particularly relevant for complex traits. This method tests in a cellular context the effect of specific DNA sequences on gene expression. The principle is to measure the relative abundance of transcripts arising from the two alleles of a gene, analysing cells which carry one copy of the DNA sequences associated with disease (the risk variants). Therefore, the cells used for this method should meet two fundamental genotypic requirements: they have to be heterozygous both for DNA risk variants and for DNA markers, typically coding polymorphisms, which can distinguish transcripts based on their chromosomal origin. DNA risk variants and DNA markers do not need to have the same allele frequency but the phase (haplotypic) relationship of the genetic markers needs to be understood. It is also important to choose cell types which express the gene of interest. This protocol refers specifically to the procedure adopted to extract nucleic acids from fibroblasts but the method is equally applicable to other cells types including primary cells. DNA and RNA are extracted from the selected cell lines and cDNA is generated. DNA and cDNA are analysed with a primer extension assay, designed to target the coding DNA markers. The primer extension assay is carried out using the MassARRAY (Sequenom) platform according to the manufacturer's specifications. Primer extension products are then analysed by matrix-assisted laser desorption/ionization time of-flight mass spectrometry (MALDI-TOF/MS). Because the selected markers are heterozygous they will generate two peaks on the MS profiles. The area of each peak is proportional to the transcript abundance and can be measured with a function of the MassARRAY Typer software to generate an allelic ratio (allele 1: allele 2) calculation. The allelic ratio obtained for cDNA is normalized using that measured from genomic DNA, where the allelic ratio is expected to be 1:1 to correct for technical artifacts. Markers with a normalised allelic ratio significantly different to 1 indicate that the amount of transcript generated from the two chromosomes in the same cell is different, suggesting that the DNA variants associated with the phenotype have an effect on gene expression. Experimental controls should be used to confirm the results. PMID:21085102

  7. CARD15 and HLA DRB1 Alleles Influence Susceptibility and Disease Localization in Crohn's Disease

    Microsoft Academic Search

    Bill Newman; Mark S. Silverberg; Xiangjun Gu; Qing Zhang; Ana Lazaro; A. Hillary Steinhart; Gordon R. Greenberg; Anne M. Griffiths; Robin S. McLeod; Zane Cohen; Marcelo Fernández-Viña; Christopher I. Amos; Katherine Siminovitch

    2004-01-01

    OBJECTIVES:Crohn's disease (CD) is a chronic inflammatory disease of the gut associated with allelic variants of CARD15 and HLA-DRB1 genes. We investigated the prevalence and effects of these variants in a Canadian CD cohort.METHODS:507 unrelated CD patients were genotyped for the three major CD-associated variants (Arg702Trp, Gly908Arg, and Leu1007fsinsC) and for thirteen HLA-DRB1 alleles.RESULTS:At least one CARD15 variant was present

  8. Genetic Variation in the Strongly Canalized Sex Pheromone Communication System of the European Corn Borer, Ostrinia Nubilalis Hubner (Lepidoptera; Pyralidae)

    PubMed Central

    Zhu, J.; Lofstedt, C.; Bengtsson, B. O.

    1996-01-01

    The major difference in pheromone production between the so-called E and Z strains of the European corn borer Ostrinia nubilalis is controlled by two alleles at a single autosomal locus. E-strain females produce an (E)-11-tetradecenyl acetate pheromone with 1-3% of the Z isomer, whereas Z-strain females produce the opposite blend. In laboratory-reared insects we found that F(1) females produced, on average, a 71:29 E/Z ratio, but the distribution was clearly bimodal. The variability in pheromone blend produced by heterozygous females could be explained by the existence of two different alleles in the Z strain which in combination with the E-strain allele for the major production locus cause the production of a component mixture either high or low in the E isomer. In addition, evidence was found for an independently inherited factor, existing in the E strain, with a dominant effect on the amount of E isomer produced by females homozygous for Z-alleles at the major production locus. Thus, the low variability normally found in the pheromone mixture produced by O. nubilalis and other moth females may, by canalization, hide a considerable amount of underlying genetic variation. PMID:8889536

  9. Implication of European-derived adiposity loci in African Americans

    PubMed Central

    Hester, JM; Wing, MR; Li, J; Palmer, ND; Xu, J; Hicks, PJ; Roh, BH; Norris, JM; Wagenknecht, LE; Langefeld, CD; Freedman, BI; Bowden, DW; Ng, MCY

    2012-01-01

    Objective Recent genome-wide association studies (GWAS) have identified multiple novel loci associated with adiposity in European-derived study populations. Limited study of these loci has been reported in African Americans. Here we examined the effects of these previously identified adiposity loci in African Americans. Methods A total of 46 representative single-nucleotide polymorphisms (SNPs) in 19 loci that were previously reported in GWAS in Europeans (including FTO and MC4R) were genotyped in 4992 subjects from six African-American cohorts. These SNPs were tested for association with body mass index (BMI) after adjustment for age, gender, disease status and population structure in each cohort. Meta-analysis was conducted to combine the results. Results Meta-analysis of 4992 subjects revealed seven SNPs near four loci, including NEGR1, TMEM18, SH2B1/ATP2A1 and MC4R, showing significant association at 0.005allele. The most significantly associated SNPs (rs9424977, rs3101336 and rs2568958) are located in the NEGR1 gene (P = 0.005, 0.020 and 0.019, respectively). Conclusion We replicated the association of variants at four loci in six African-American cohorts that demonstrated a consistent direction of association with previous studies of adiposity in Europeans. These loci are all highly expressed in the brain, consistent with an important role for central nervous system processes in weight regulation. However, further comprehensive examination of these regions may be necessary to fine map and elucidate for possible genetic differences between these two populations. PMID:21750520

  10. Identification of repeat sequence heterogeneity at the polymorphic short tandem repeat locus HUMTH01[AATG][sub n] and reassignment of alleles in population analysis by using a locus-specific allelic ladder

    SciTech Connect

    Puers, C. (Institute for Forensic Medicine, Muenster (Germany)); Schumm, J.W. (Promega Corp., Madison, WI (United States)); Hammond, H.A.; Caskey, C.T.; Jin, L.

    1993-10-01

    An allelic ladder containing amplified sequences of seven alleles of the polymorphic human tyrosine hydroxylase locus, HUMTH01, was constructed and employed as a standard marker. Sequence analysis of each ladder component indicates that fragments differ by integral multiples of the AATG core repeat sequence characteristic of this locus. Individual alles are designated [open quotes]5[close quotes] through [open quotes]11,[close quotes] according to the number of complete reiterations of the core repeat contained within them. Comparison of the HUMTH01 allelic ladder with DNA samples amplified at this locus revealed core repeat length heterogeneity (i.e., deletions or insertions shorter than one core repeat) within the human population. In particular, a common allele was identified which migrates more quickly than allele 10, but more slowly than allele 9, on electrophoresis through a denaturing polyacrylamide gel. Sequence analysis of this allele, designated [open quotes]10-1,[close quotes] reveals lack of a single adenine normally present in the seventh copy of the AATG. The allelic ladder was used to reevaluate previously published population data. Results of testing for Hardy-Weinberg equilibrium and population substructure were not altered significantly by these modifications. 29 refs., 1 fig., 3 tabs.

  11. Conservation genetics and population history of the threatened European mink Mustela lutreola, with an emphasis on the west European population.

    PubMed

    Michaux, J R; Hardy, O J; Justy, F; Fournier, P; Kranz, A; Cabria, M; Davison, A; Rosoux, R; Libois, R

    2005-07-01

    In species of great conservation concern, special attention must be paid to their phylogeography, in particular the origin of animals for captive breeding and reintroduction. The endangered European mink lives now in at least three well-separated populations in northeast, southeast and west Europe. Our aim is to assess the genetic structure of these populations to identify 'distinct population segments' (DPS) and advise captive breeding programmes. First, the mtDNA control region was completely sequenced in 176 minks and 10 polecats. The analysis revealed that the western population is characterized by a single mtDNA haplotype that is closely related to those in eastern regions but nevertheless, not found there to date. The northeast European animals are much more variable (pi = 0.012, h = 0.939), with the southeast samples intermediate (pi = 0.0012, h = 0.469). Second, 155 European mink were genotyped using six microsatellites. The latter display the same trends of genetic diversity among regions as mtDNA [gene diversity and allelic richness highest in northeast Europe (H(E) = 0.539, R(S) = 3.76), lowest in west Europe (H(E) = 0.379, R(S) = 2.12)], and provide evidences that the southeast and possibly the west populations have undergone a recent bottleneck. Our results indicate that the western population derives from a few animals which recently colonized this region, possibly after a human introduction. Microsatellite data also reveal that isolation by distance occurs in the western population, causing some inbreeding because related individuals mate. As genetic data indicate that the three populations have not undergone independent evolutionary histories for long (no phylogeographical structure), they should not be considered as distinct DPS. In conclusion, the captive breeding programme should use animals from different parts of the species' present distribution area. PMID:15969721

  12. European Southern Observatory

    NSDL National Science Digital Library

    The European Southern Observatory (ESO) is an intergovernmental organization comprised of 14 member countries. Its headquarters are in Germany, but they have three observatories in Chile as well. Their website is loaded with information and visitors shouldn't miss going on the "Virtual Tours", on the far right side of the homepage. The tours are of the three observatories in Chile, and offer almost 360 degree views of beautiful, yet sparse landscapes. The tour of La Silla has two particularly beautiful views, "La Silla Moonlight" and "La Silla Sunset". Visitors interested in seeing a panning of an artist's 3D rendering of the Orion Nebula must go to the "Video" link on the left hand menu on the homepage. There are over 1400 videos to choose from, so for those not into the Orion Nebula, never fear, there are plenty of other video choices. Finally, visitors must go to the "Top 100 Images" link on the right side of the homepage to see amazing and gorgeous images taken from the ESO's various observatories.

  13. European Solar Engineering School Homepage

    NSDL National Science Digital Library

    The European Solar Engineering School (ESES) provides courses in advanced solar energy engineering for well qualified master's level engineering students. The following are offered: advanced solar thermal engineering, advanced photovoltaic engineering, applied solar energy engineering, and utilization of solar energy.

  14. Whither Europeanization? Concept Stretching and Substantive Change

    Microsoft Academic Search

    Claudio M. Radaelli

    2002-01-01

    This paper discusses the concept of Europeanization in the light of recent research on the impact of the European Union politics and policy. Conceptual analysis is preliminary to empirical analysis. Accordingly, I examine the risk of 'concept stretching', discuss extension and intension of Europeanization, and propose a taxonomy to 'unpack' the concept and organize empirical research. The explanation of Europeanization

  15. information & research skills programme European Union Resources

    E-print Network

    Hickman, Mark

    informED information & research skills programme European Union Resources © European Community and politics 4 The Budget - Financing the European Union 5 Economic and monetary policy 6 Single market. Culture 18 External Relations 19 Law EUROPA ­ Gateway to the European Union http

  16. Collyriclosis in Central European hirundines

    Microsoft Academic Search

    Petr Heneberg; Tibor Szép; Tomasz Iciek; Ivan Literák

    Cutaneous monostome trematode Collyriclum faba (Bremser in Schmalz 1831) is a digenetic flatworm with unknown life cycle. Here, we provide the first compelling evidence\\u000a that despite low prevalence of the parasite, European hirundines are parasitized by this species. First host record for sand\\u000a martin (Riparia riparia) and first European host record for barn swallow (Hirundo rustica) is provided. The birds

  17. Derivative Alleles of the Arabidopsis Gibberellin-Insensitive (gai) Mutation Confer a Wild-Type Phenotype.

    PubMed Central

    Peng, J; Harberd, NP

    1993-01-01

    The gai mutation of Arabidopsis confers a dwarf phenotype resembling that of mutants defective in gibberellin (GA) biosynthesis. However, gai mutant plants differ from GA biosynthesis mutants because they fail to respond to exogenous GAs and accumulate endogenous GA species to higher (rather than lower) levels than found in wild-type controls. The gai mutation, therefore, identifies a gene that modulates the response of plant cells to GA. We have mapped gai with respect to visible and restriction fragment length polymorphism (RFLP) markers from chromosome 1. To observe the phenotype exhibited by individuals potentially lacking wild-type (GAI) function, we have also isolated novel irradiation-induced derivative alleles of gai. When homozygous, these alleles confer a revertant phenotype that is indistinguishable from the wild type. gai is a semidominant mutation that exerts its effects either because it is a gain-of-function mutation or because it is a loss-of-function or reduced-function mutation. The genetic and physiological properties of the derivative alleles are considered with reference to these alternative modes of dominance of gai. Because these alleles are potential deletion or rearrangement mutations, together with the closely linked RFLP markers identified in the linkage mapping experiments, they provide useful resources for the isolation of the gai locus via a map-based cloning approach. PMID:12271067

  18. Alleles conferring improved fiber quality from EMS mutagenesis of elite cotton genotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The elite gene pool of cotton (Gossypium spp.) has less diversity than those of most other major crops, making identification of novel alleles important to ongoing crop improvement. A total of 3,164 M5 lines resulting from ethyl methanesulfonate mutagenesis of two G. hirsutum breeding lines, TAM 94L...

  19. Selection for Antimicrobial Peptide Diversity in Frogs Leads to Gene Duplication and Low Allelic Variation

    E-print Network

    Blouin, Michael S.

    Selection for Antimicrobial Peptide Diversity in Frogs Leads to Gene Duplication and Low Allelic Springer Science+Business Media, LLC 2007 Abstract Antimicrobial peptides are highly diverse pathogen duplication. It has been proposed that genes encoding antimicrobial peptides might be subject to balancing

  20. Estimating copy numbers of alleles from population-scale high-throughput sequencing data

    PubMed Central

    2015-01-01

    Background With the recent development of microarray and high-throughput sequencing (HTS) technologies, a number of studies have revealed catalogs of copy number variants (CNVs) and their association with phenotypes and complex traits. In parallel, a number of approaches to predict CNV regions and genotypes are proposed for both microarray and HTS data. However, only a few approaches focus on haplotyping of CNV loci. Results We propose a novel approach to infer copy unit alleles and their numbers in each sample simultaneously from population-scale HTS data by variational Bayesian inference on a generative probabilistic model inspired by latent Dirichlet allocation, which is a well studied model for document classification problems. In simulation studies, we evaluated concordance between inferred and true copy unit alleles for lower-, middle-, and higher-copy number dataset, in which precision and recall were ? 0.9 for data with mean coverage ? 10× per copy unit. We also applied the approach to HTS data of 1123 samples at highly variable salivary amylase gene locus and a pseudogene locus, and confirmed consistency of the estimated alleles within samples belonging to a trio of CEPH/Utah pedigree 1463 with 11 offspring. Conclusions Our proposed approach enables detailed analysis of copy number variations, such as association study between copy unit alleles and phenotypes or biological features including human diseases. PMID:25707811

  1. Efficient Simulation and Likelihood Methods for Non-neutral Multi-allele Models

    E-print Network

    Buzbas, Erkan

    of chromosomes in the population. Alleles are subject to a random parent-independent mutation process, in which numerous significant contributions to population genetics theory. As genetic data, in particular DNA to develop a likelihood method to estimate the population-genetic parameters using full DNA sequences. Now

  2. Epistasis in allelic expression at upper temperature tolerance QTL in rainbow trout

    Microsoft Academic Search

    Roy G. Danzmann; Timothy R. Jackson; Moira M. Ferguson

    1999-01-01

    We have mapped the location of QTL affecting upper temperature tolerance in three backcross families of rainbow trout (Oncorhynchus mykiss) derived from matings between an F1 male (high (H)×low (L) temperature tolerance selected lines) and two H and one L line females using variation at 61 microsatellite loci. Physiological epistasis was observed among paternally inherited QTL alleles and this depended

  3. Diversity of benzimidazole-resistance alleles in populations of small ruminant parasites

    E-print Network

    Jacquet, Stéphan

    Diversity of benzimidazole-resistance alleles in populations of small ruminant parasites A-intestinal nematodes of small ruminants (sheep and goat) to benzimidazole anthelmintic drugs seems to be linked of the benzimidazole-resistance in small ruminant trichostrongylid parasites is now well under- stood, but no data

  4. INTRODUCTION The epsilon 4 allele of the ApolipoproteinE gene (APOE4) is a prevalent

    E-print Network

    Thompson, Paul

    INTRODUCTION The epsilon 4 allele of the ApolipoproteinE gene (APOE4) is a prevalent risk factor atrophy3. However, so far, it is not known how APOE4 and TOMM40 SNPs might interact to influence regional brain volumes; interactions are likely as TOMM40 lies close to APOE4 gene on chromosome 19 and the two

  5. Allele-Specific Silencing of Mutant Huntingtin in Rodent Brain and Human Stem Cells

    PubMed Central

    Zala, Diana; Feyeux, Maxime; Auregan, Gwennaëlle; Cambon, Karine; Troquier, Laetitia; Carpentier, Johann; Aubert, Sophie; Merienne, Nicolas; Bourgois-Rocha, Fany; Hassig, Raymonde; Rey, Maria; Dufour, Noëlle; Saudou, Frédéric; Perrier, Anselme L.; Hantraye, Philippe; Déglon, Nicole

    2014-01-01

    Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder resulting from polyglutamine expansion in the huntingtin (HTT) protein and for which there is no cure. Although suppression of both wild type and mutant HTT expression by RNA interference is a promising therapeutic strategy, a selective silencing of mutant HTT represents the safest approach preserving WT HTT expression and functions. We developed small hairpin RNAs (shRNAs) targeting single nucleotide polymorphisms (SNP) present in the HTT gene to selectively target the disease HTT isoform. Most of these shRNAs silenced, efficiently and selectively, mutant HTT in vitro. Lentiviral-mediated infection with the shRNAs led to selective degradation of mutant HTT mRNA and prevented the apparition of neuropathology in HD rat's striatum expressing mutant HTT containing the various SNPs. In transgenic BACHD mice, the mutant HTT allele was also silenced by this approach, further demonstrating the potential for allele-specific silencing. Finally, the allele-specific silencing of mutant HTT in human embryonic stem cells was accompanied by functional recovery of the vesicular transport of BDNF along microtubules. These findings provide evidence of the therapeutic potential of allele-specific RNA interference for HD. PMID:24926995

  6. Allele loss in colorectal cancer at the Cowden disease/juvenile polyposis locus on 10q.

    PubMed

    Frayling, I M; Bodmer, W F; Tomlinson, I P

    1997-08-01

    The genes that are mutated in inherited cancer syndromes are often involved in the pathogenesis of sporadic cancers of the types that characterize those syndromes. In colorectal cancer such loci include the familial adenomatous polyposis (APC) gene and the hereditary nonpolyposis colorectal cancer (DNA mismatch repair) genes. Juvenile hamartomatous polyposis syndromes, which include Juvenile Polyposis and Cowden disease, also predispose to colorectal cancer. The gene for Cowden disease has recently been localized to chromosome 10q22-q23, and a juvenile polyposis locus, JP1, has been reported as mapping to the same location. We have studied up to 70 cases of sporadic colorectal cancer for allele loss at markers predominantly on the long arm of chromosome 10, including loci flanking the putative Cowden Disease/JP1 locus. Frequencies of allele loss of about 35% were found close to this locus, whereas low frequencies of allele loss were found elsewhere on 10q. Mutations at the putative Cowden Disease/JP1 locus may therefore be important in sporadic colorectal cancer and fine mapping of allele loss on 10q in sporadic colon cancers may help to refine the position of this gene. PMID:9242220

  7. Extent of differential allelic expression of candidate breast cancer genes is similar in blood and breast

    E-print Network

    Maia, Ana-Teresa; Spiteri, Inmaculada; Lee, Alvin J X; O'Reilly, Martin; Jones, Linda; Caldas, Carlos; Ponder, Bruce A J

    2009-12-10

    suitable surrogate test tissue must be identified for future studies. Methods We measured differential allelic expression of 12 candidate genes possibly related to breast cancer susceptibility (BRCA1, BRCA2, C1qA, CCND3, EMSY, GPX1, GPX4, MLH3, MTHFR, NBS1...

  8. mStruct: Inference of Population Structure in Light of Both Genetic Admixing and Allele

    E-print Network

    Xing, Eric P.

    accurate association studies and other population genetics problems. Various methods have been proposed) in a structural map over the study population sample. Figure 1 shows an example of a structural map of four modernmStruct: Inference of Population Structure in Light of Both Genetic Admixing and Allele Mutations

  9. mStruct: Inference of Population Structure in Light of both Genetic Admixing and Allele

    E-print Network

    accurate association studies and other population genetics problems. Various methods have been proposed) in a structural map over the study population sample. Figure 1 shows an example of a structural map of four modernmStruct: Inference of Population Structure in Light of both Genetic Admixing and Allele Mutations

  10. theoretical population biology 50, 91 104 (1996) The Sampling Theory of Neutral Alleles in an

    E-print Network

    1996-01-01

    island populations, is studied by analytical methods. A new result is presented for the distribution further studies the mathematical properties of the con- tinuous-generation island model of population population size. In this paper, the distribution of alleles on islands under a haploid BDI process is studied

  11. Association of the Apolipoprotein E 2 Allele with Concurrent Occurrence of Endometrial Hyperplasia and Endometrial Carcinoma

    PubMed Central

    Ivanova, Tatiana I.; Krikunova, Ludmila I.; Ryabchenko, Nikolay I.; Mkrtchyan, Liana S.; Khorokhorina, Vera A.; Salnikova, Lyubov E.

    2015-01-01

    Genes encoding proteins with antioxidant properties may influence susceptibility to endometrial hyperplasia (EH) and endometrial carcinoma (ECa). Patients with EH (n = 89), EH concurrent with ECa (n = 76), ECa (n = 186), and healthy controls (n = 1110) were genotyped for five polymorphic variants in the genes involved in metabolism of lipoproteins (APOE Cys112Arg and Arg158Cys), iron (HFE Cys282Tyr and His63Asp), and catecholamines (COMT Val158Met). Patients and controls were matched by ethnicity (all Caucasians), age, body mass index (BMI), and incidence of hypertension and diabetes. The frequency of the APOE E 2 allele (158Cys) was higher in patients with EH + ECa than in controls (P = 0.0012, PBonferroni = 0.018, OR = 2.58, 95% CI 1.49–4.45). The APOE E 4 allele (112Arg) was more frequently found in patients with EH than in controls and HFE minor allele G (63Asp) had a protective effect in the ECa group, though these results appeared to be nonsignificant after correction for multiple comparisons. The results of the study indicate that E 2 allele might be associated with concurrent occurrence of EH and ECa. PMID:25741405

  12. Estimating Allele Age and Selection Coefficient from Time-Serial Data

    PubMed Central

    Malaspinas, Anna-Sapfo; Malaspinas, Orestis; Evans, Steven N.; Slatkin, Montgomery

    2012-01-01

    Recent advances in sequencing technologies have made available an ever-increasing amount of ancient genomic data. In particular, it is now possible to target specific single nucleotide polymorphisms in several samples at different time points. Such time-series data are also available in the context of experimental or viral evolution. Time-series data should allow for a more precise inference of population genetic parameters and to test hypotheses about the recent action of natural selection. In this manuscript, we develop a likelihood method to jointly estimate the selection coefficient and the age of an allele from time-serial data. Our method can be used for allele frequencies sampled from a single diallelic locus. The transition probabilities are calculated by approximating the standard diffusion equation of the Wright–Fisher model with a one-step process. We show that our method produces unbiased estimates. The accuracy of the method is tested via simulations. Finally, the utility of the method is illustrated with an application to several loci encoding coat color in horses, a pattern that has previously been linked with domestication. Importantly, given our ability to estimate the age of the allele, it is possible to gain traction on the important problem of distinguishing selection on new mutations from selection on standing variation. In this coat color example for instance, we estimate the age of this allele, which is found to predate domestication. PMID:22851647

  13. RESEARCH ARTICLE Open Access Sequence analysis of two alleles reveals that

    E-print Network

    Boyer, Edmond

    , Eric Rivals2 , Hakim Mireau1 , Françoise Budar1* Abstract Background: Land plant genomes contain fragment, likely originating from another part of the radish genome, inserted into the L7rfo sequenceRESEARCH ARTICLE Open Access Sequence analysis of two alleles reveals that intra-and intergenic

  14. Rapid Screening for Temperature-Sensitive Alleles in Plants1[W][OA

    PubMed Central

    Vidali, Luis; Augustine, Robert C.; Fay, Scotty N.; Franco, Paula; Pattavina, Kelli A.; Bezanilla, Magdalena

    2009-01-01

    We developed a simple and fast method to identify temperature-sensitive alleles of essential plant genes. We used primary and tertiary structure information to identify residues in the core of the protein of interest. These residues were mutated and tested for temperature sensitivity, taking advantage of the exceptionally rapid 1-week complementation assay in the moss Physcomitrella patens. As test molecules, we selected the actin-binding proteins profilin and actin-depolymerizing factor, because they are essential and their loss-of-function phenotype can be fully rescued. Screening a small number of candidate mutants, we successfully identified temperature-sensitive alleles of both profilin and actin-depolymerizing factor. Plants harboring these alleles grew well at the permissive temperature of 20°C to 25°C but showed a complete loss of function at the restrictive temperature of 32°C. Notably, the profilin mutation identified in the moss gene can be transferred to profilins from other plant species, also rendering them temperature sensitive. The ability to routinely generate temperature-sensitive alleles of essential plant proteins provides a powerful tool for the study of gene function in plants. PMID:19666707

  15. Preferential loss of a polymorphic RIZ allele in human hepatocellular carcinoma

    PubMed Central

    Fang, W; Piao, Z; Buyse, I M; Simon, D; Sheu, J C; Perucho, M; Huang, S

    2001-01-01

    The RIZ (PRDM2) locus commonly undergoes loss of heterozygosity (LOH) and maps within the minimal deleted region on 1p36 in hepatocellular carcinoma (HCC). Although peptide-altering mutations of RIZ are rare in HCC, the RIZ1 product is commonly lost in HCC and has tumour suppressive activities. Here, we analysed RIZ gene mutations and LOH in HCC, breast cancer, familial melanoma, colon cancer, and stomach cancer. We found 7 polymorphisms but no mutations. By analysing the Pro704-deletion polymorphism, we detected LOH of RIZ in 31 of 79 (39%) informative HCC cases, 11 of 47 (23%) colon cancer cases, 8 of 43 (19%) breast cancer cases, 8 of 66 (12%) stomach cancer cases. Importantly, loss of the Pro704+allele was found in 74% of the 31 LOH positive HCC cases (P< 0.01), indicating a preferential loss and hence a stronger tumour suppressor role for this allele compared to the P704?allele. In addition, the Pro704+allele was found to be more common in Asians (0.61) than Caucasians (0.42) (P = 0.0000), suggesting an interesting link between gene polymorphisms and potential differences in tumour incidence between racial groups. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11259086

  16. Registration of hard kernel puroindoline allele nearisogenic line hexaploid wheat genetic stocks.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seven puroindoline allele near-isogenic line (NIL) hexaploid wheat (Triticum aestivum L.) genetic stocks (GS-xxxx – GS-xxxx; PI 644080 – PI 644086) were developed by Dr. Craig F. Morris at the USDA-ARS Western Wheat Quality Laboratory, Pullman, Washington. As they incorporate the first seven known ...

  17. NOTICE OF RELEASE OF HARD KERNEL PUROINDOLINE ALLELE NEAR-ISOGENIC LINE HEXAPLOID WHEAT GENETIC STOCKS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Agricultural Research Service, U.S. Department of Agriculture announces the release of seven hard kernel puroindoline allele near-isogenic line (NIL) hexaploid wheat (Triticum aestivum L.) genetic stocks (PI xxxxxx – PI xxxxxx) developed by Dr. Craig F. Morris at the USDA-ARS Western Wheat Quali...

  18. HLA-class II alleles in patients with drug-resistant pulmonary tuberculosis in Kazakhstan.

    PubMed

    Kuranov, A B; Kozhamkulov, U A; Vavilov, M N; Belova, E S; Bismilda, V L; Alenova, A H; Ismailov, S S; Momynaliev, K T

    2014-02-01

    The human leukocyte antigen (HLA) system has a major role in the regulation of the immune response as it is involved in the defense against pathogens. Some studies have reported that HLA class II genes play a strong role in severe cases of pulmonary tuberculosis (PTB) in several populations. Thus the aim of the study was to compare the HLA-class II alleles of patients with drug resistant tuberculosis with those of healthy controls from the same ethnic group in Kazakhstan. The aim of the present study was to evaluate the correlation of HLA-class II alleles by patients with drug resistant tuberculosis and the healthy controls of the same ethnic group in Kazakhstan. The HLA-class II alleles of 76 patients with tuberculosis (TB) and 157 healthy volunteers were investigated using sequence-based typing (SBT)-method. HLA-DQA1*03:02 HLA-DRB1*08:01 and DRB1*08:03 occurred more frequently (P?=?0.05) in patients with drug resistant tuberculosis than in controls. We observed a possible association between certain HLA alleles and TB that are specific for the Kazakh population. Further studies are needed to confirm our findings using a larger number of patients with drug resistant tuberculosis. PMID:24397488

  19. Common Risk Alleles for Inflammatory Diseases Are Targets of Recent Positive Selection

    E-print Network

    Raychaudhuri, Soumya

    .16,17 Similarly, it was shown that the positively selected celiac disease (MIM 212750) risk variantARTICLE Common Risk Alleles for Inflammatory Diseases Are Targets of Recent Positive Selection identified hundreds of loci harboring genetic variation influencing inflammatory- disease susceptibility

  20. Molecular mapping of the mutant fap4(A24) allele for elevated palmitate concentration in soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soybean [Glycine max L. Merr.] oil with an elevated palmitate concentration is useful for some food and industrial applications. The objective of this study was to map the genetic location of the fap4(A24) allele that controls an increase in palmitate concentration and to identify molecular marker...

  1. What phylogeny and gene genealogy analyses reveal about homoplasy in citrus microsatellite alleles

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sixty-five microsatellite alleles from three Simple Sequence Repeat (SSR) loci (cAGG9, CCT01 and GT03) of various Citrus, Fortunella or Poncirus accessions were cloned and sequenced to determine their mode of evolution. This data was used to assess sequence variation by calculating the average numb...

  2. Distribution of MICA alleles and haplotypes associated with HLA in the Korean population

    Microsoft Academic Search

    Chul-Woo Pyo; Seong-Suk Hur; Yang-Kyum Kim; Hee-Baeg Choi; Tae-Yoon Kim; Tai-Gyu Kim

    2003-01-01

    The MICA (MHC class I chain-related gene A) is a polymorphic gene located 46 kb centromeric of the HLA-B gene, and is preferentially expressed in epithelial cells and intestinal mucosa. The MICA gene, similar to human leukocyte antigen (HLA) class I, displays a high degree of genetic polymorphism in exons 2, 3, 4, and 5, amounting to 54 alleles. In

  3. Neuronal Polymorphism among Natural Alleles of a cGMP-Dependent Kinase Gene, foraging, in Drosophila

    E-print Network

    Sokolowski, Marla

    Neuronal Polymorphism among Natural Alleles of a cGMP-Dependent Kinase Gene, foraging, Ontario, M3J 1P3, Canada Natural variation in neuronal excitability and connectivity has not been- rons. Voltage-clamp examination demonstrated reduced voltage-dependent K currents in sitter neurons

  4. Identifying neutral allele Sb at pollen-sterility loci in cultivated rice with Oryza rufipogon origin

    Microsoft Academic Search

    LeiGang Shi; XiangDong Liu; Bo Liu; XingJuan Zhao; Lan Wang; JinQuan Li; YongGen Lu

    2009-01-01

    Pollen sterility is commonly found in the intra-specific hybrids of indica and japonica rice, which is one of the main constrains for the utilization of heterosis between indica and japonica. Six loci controlling the pollen sterility of F1 between indica and japonica have been identified from previous studies. Neutral alleles at each locus are potential to overcome the F1 pollen

  5. Power of Genetic Association Studies in the Presence of Linkage Disequilibrium and Allelic Heterogeneity

    PubMed Central

    Fisher, Sheila A.; Lewis, Cathryn M.

    2008-01-01

    Objectives The calculation of the power and sample size required for association studies is essential, particularly for follow-up of genome-wide association studies, where much genotyping is required to replicate the original finding and identify the true disease susceptibility mutation. Methods In this paper, we derive equations for estimation of sample sizes for the transmission disequilibrium test (TDT) and for case-control studies, in the presence of allelic heterogeneity and indirect association – where the genotyped tagging SNP is in linkage disequilibrium (LD) with the true mutation. Using data from NOD2 and PTPN22, we show that the true sample sizes required to detect association may be incorrect when calculated under the assumption of a single mutation and complete LD with the genotyped marker. Results The true sample sizes may be lower when allelic heterogeneity acts in a recessive model across mutations, or increased when mutations lie on different alleles of a common tagging SNP. Conclusion Calculating power and sample size under a range of realistic models of LD and allelic heterogeneity is essential to ensure that association studies have sufficient power to detect mutations. PMID:18612206

  6. Cloning of the Zea mays controlling element Ac from the wx-m7 allele

    Microsoft Academic Search

    U. Behrens; N. Fedoroff; A. Laird; M. Miiller-Neumann; P. Starlinger; J. Yoder

    1984-01-01

    The cloning of the controlling element Ac from the wx-m7 allele of Zea mays is described. The cloned fragment carries a 4.3 kb insertion that by restriction analysis is indistinguishable from the Ac insertion in Ac wx-m9. It is located approximately 2.5 kb upstream of the Ac wx-m9 insertion.

  7. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism

    SciTech Connect

    Noble, E.P.; Blum, K.; Ritchie, T.; Montgomery, A.; Sheridan, P.J. (Neuropsychiatric Institute, UCLA (USA))

    1991-07-01

    The allelic association of the human D2 dopamine receptor gene with the binding characteristics of the D2 dopamine receptor was determined in 66 brains of alcoholic and non-alcoholic subjects. In a blinded experiment, DNA from the cerebral cortex was treated with the restriction endonuclease Taql and probed with a 1.5-kilobase (kb) digest of a clone (lambda hD2G1) of the human D2 dopamine receptor gene. The binding characteristics (Kd (binding affinity) and Bmax (number of binding sites)) of the D2 dopamine receptor were determined in the caudate nuclei of these brains using tritiated spiperone as the ligand. The adjusted Kd was significantly lower in alcoholic than in nonalcoholic subjects. In subjects with the A1 allele, in whom a high association with alcoholism was found, the Bmax was significantly reduced compared with the Bmax of subjects with the A2 allele. Moreover, a progressively reduced Bmax was found in subjects with A2/A2, A1/A2, and A1/A1 alleles, with subjects with A2/A2 having the highest mean values, and subjects with A1/A1, the lowest. The polymorphic pattern of the D2 dopamine receptor gene and its differential expression of receptors suggests the involvement of the dopaminergic system in conferring susceptibility to at least one subtype of severe alcoholism.

  8. A novel hypomorphic Looptail allele at the planar cell polarity Vangl2 gene

    PubMed Central

    Guyot, Marie-Claude; Bosoi, Ciprian M.; Kharfallah, Fares; Reynolds, Annie; Drapeau, Pierre; Justice, Monica; Gros, Philippe; Kibar, Zoha

    2013-01-01

    Vangl2 forms part of the planar cell polarity signalling pathway and is the gene defective in the Looptail (Lp) mouse mutant. Two previously described alleles, Lp and Lpm1Jus, segregate in a semi-dominant fashion, with heterozygotes displaying the looped-tail appearance, while homozygotes show the neural tube defect called craniorachischisis. Here, we report a novel experimentally-induced allele, Lpm2Jus, that carries a missense mutation, R259L, in Vangl2. This mutation was specific to the Lp phenotype and absent from both parental strains and 28 other inbred strains. Notably, this mutation segregates in a recessive manner with all heterozygotes appearing normal and 47% of homozygotes showing a looped-tail. Homozygous Lpm2Jus embryos showed spina bifida in 12%. Lpm2Jus genetically interacts with Lp with 77% of compound heterozygotes displaying craniorachischisis. Vangl2R259L behaved like the wild-type allele in overexpression and morpholino knockdown/rescue assays in zebrafish embryos. These data suggest that Lpm2Jus represents a new hypomorphic allele of Lp. PMID:21404367

  9. Rapid Publication A Mouse Model for the AF508 Allele of Cystic Fibrosis

    E-print Network

    Capecchi, Mario R.

    Rapid Publication A Mouse Model for the AF508 Allele of Cystic Fibrosis Bernhardt G. Zeiher,* Ernst College ofMedicine, Salt Lake City, Utah 84112 Abstract The most common cause of cystic fibrosis is a mutation that deletes phenylalanine 508 in cystic fibrosis transmembrane conductance regulator (CFTR

  10. AlleleCoder: a PERL script for coding codominant polymorphism data for PCA analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A useful biological interpretation of diploid heterozygotes is in terms of the dose of the common allele (0, 1 or 2 copies). We have developed a PERL script that converts FASTA files into coded spreadsheets suitable for Principal Component Analysis (PCA). In combination with R and R Commander, two- ...

  11. Single-Stranded RNAs Use RNAi to Potently and Allele-Selectively Inhibit Mutant Huntingtin Expression

    PubMed Central

    Yu, Dongbo; Pendergraff, Hannah; Liu, Jing; Kordasiewicz, Holly B.; Cleveland, Don W.; Swayze, Eric E.; Lima, Walt F.; Crooke, Stanley T.; Prakash, Thazha P.; Corey, David R.

    2012-01-01

    Mutant huntingtin (HTT) protein causes Huntington’s Disease (HD), an incurable neurological disorder. Silencing mutant HTT using nucleic acids would eliminate the root cause of HD. Developing nucleic acid drugs is challenging, and an ideal clinical approach to gene silencing would combine the simplicity of single-stranded antisense oligonucleotides with the efficiency of RNAi. Here we describe RNAi by single-stranded silencing RNAs (ss-siRNAs). ss-siRNAs are potent (>100-fold more than unmodified RNA) and allele-selective (>30-fold) inhibitors of mutant HTT expression in cells derived from HD patients. Strategic placement of mismatched bases mimics micro-RNA recognition and optimizes discrimination between mutant and wild-type alleles. ss-siRNAs require argonaute protein and function through the RNAi pathway. Intraventricular infusion of ss-siRNA produced selective silencing of the mutant HTT allele throughout the brain in a mouse HD model. These data demonstrate that chemically modified ss-siRNAs function through the RNAi pathway and provide allele-selective compounds for clinical development. PMID:22939619

  12. Allele identification for transcriptome-based population genomics in the invasive plant Centaurea solstitialis.

    PubMed

    Dlugosch, Katrina M; Lai, Zhao; Bonin, Aurélie; Hierro, José; Rieseberg, Loren H

    2013-02-01

    Transcriptome sequences are becoming more broadly available for multiple individuals of the same species, providing opportunities to derive population genomic information from these datasets. Using the 454 Life Science Genome Sequencer FLX and FLX-Titanium next-generation platforms, we generated 11-430 Mbp of sequence for normalized cDNA for 40 wild genotypes of the invasive plant Centaurea solstitialis, yellow starthistle, from across its worldwide distribution. We examined the impact of sequencing effort on transcriptome recovery and overlap among individuals. To do this, we developed two novel publicly available software pipelines: SnoWhite for read cleaning before assembly, and AllelePipe for clustering of loci and allele identification in assembled datasets with or without a reference genome. AllelePipe is designed specifically for cases in which read depth information is not appropriate or available to assist with disentangling closely related paralogs from allelic variation, as in transcriptome or previously assembled libraries. We find that modest applications of sequencing effort recover most of the novel sequences present in the transcriptome of this species, including single-copy loci and a representative distribution of functional groups. In contrast, the coverage of variable sites, observation of heterozygosity, and overlap among different libraries are all highly dependent on sequencing effort. Nevertheless, the information gained from overlapping regions was informative regarding coarse population structure and variation across our small number of population samples, providing the first genetic evidence in support of hypothesized invasion scenarios. PMID:23390612

  13. Allele Identification for Transcriptome-Based Population Genomics in the Invasive Plant Centaurea solstitialis

    PubMed Central

    Dlugosch, Katrina M.; Lai, Zhao; Bonin, Aurélie; Hierro, José; Rieseberg, Loren H.

    2013-01-01

    Transcriptome sequences are becoming more broadly available for multiple individuals of the same species, providing opportunities to derive population genomic information from these datasets. Using the 454 Life Science Genome Sequencer FLX and FLX-Titanium next-generation platforms, we generated 11?430 Mbp of sequence for normalized cDNA for 40 wild genotypes of the invasive plant Centaurea solstitialis, yellow starthistle, from across its worldwide distribution. We examined the impact of sequencing effort on transcriptome recovery and overlap among individuals. To do this, we developed two novel publicly available software pipelines: SnoWhite for read cleaning before assembly, and AllelePipe for clustering of loci and allele identification in assembled datasets with or without a reference genome. AllelePipe is designed specifically for cases in which read depth information is not appropriate or available to assist with disentangling closely related paralogs from allelic variation, as in transcriptome or previously assembled libraries. We find that modest applications of sequencing effort recover most of the novel sequences present in the transcriptome of this species, including single-copy loci and a representative distribution of functional groups. In contrast, the coverage of variable sites, observation of heterozygosity, and overlap among different libraries are all highly dependent on sequencing effort. Nevertheless, the information gained from overlapping regions was informative regarding coarse population structure and variation across our small number of population samples, providing the first genetic evidence in support of hypothesized invasion scenarios. PMID:23390612

  14. Two steps forward, one step back: the pleiotropic effects of favoured alleles

    Microsoft Academic Search

    Sarah P. Otto

    2004-01-01

    Pleiotropy is one of the most commonly observed attributes of genes. Yet the extent and influence of pleiotropy have been underexplored in population genetics models. In this paper, I quantify the extent to which pleiotropy inhibits the spread of alleles in response to directional selection on a focal trait. Under the assumption that pleiotropic effects are extensive and deleterious, the

  15. Illegitimate recombination leading to allelic loss and unbalanced translocation in p53-mutated human lymphoblastoid cells.

    PubMed Central

    Honma, M; Zhang, L S; Hayashi, M; Takeshita, K; Nakagawa, Y; Tanaka, N; Sofuni, T

    1997-01-01

    Allelic loss and translocation are critical mutational events in human tumorigenesis. Allelic loss, which is usually identified as loss of heterozygosity (LOH), is frequently observed at tumor suppressor loci in various kinds of human tumors. It is generally thought to result from deletion or mitotic recombination between homologous chromosomes. In this report, we demonstrate that illegitimate (nonhomologous) recombination strongly contributes to the generation of allelic loss in p53-mutated cells. Spontaneous and X-ray-induced LOH mutations at the heterozygous thymidine kinase (tk) gene, which is located on the long arm of chromosome 17, from normal (TK6) and p53-mutated (WTK-1) human lymphoblastoid cells were cytogenetically analyzed by chromosome 17 painting. We observed unbalanced translocations in 53% of LOH mutants spontaneously arising from WTK-1 cells but none spontaneously arising from TK6 cells. We postulate that illegitimate recombination was occurring between nonhomologous chromosomes after DNA replication, leading to allelic loss and unbalanced translocations in p53-mutated WTK-1 cells. X-ray irradiation, which induces DNA double-strand breaks (DSBs), enhanced the generation of unbalanced translocation more efficiently in WTK-1 than in TK6 cells. This observation implicates the wild-type p53 protein in the regulation of homologous recombination and recombinational DNA repair of DSBs and suggests a possible mechanism by which loss of p53 function may cause genomic instability. PMID:9234733

  16. Synchronous allelic expression at the glucosephosphate isomerase A and B loci in interspecific sunfish hybrids.

    PubMed

    Champion, M J; Whitt, G S

    1976-10-01

    Allelic isozymes of glucosephosphate isomerase at the Gpi-A and -B loci were separated by starch gel electrophoresis in the warmouth (Lepomis gulosus) and green sunfish (L. cyanellus). The specific tissue distributions and developmental expressions of the GPI-A2, -AB, and -B2 isozymes were not different between these two species. The synchrony of allelic expression in normal intraspecific sunfish crosses was demonstrated by means of an electrophoretic variant at the Gpi-B locus. In embryos formed from warmouth x green sunfish hybrid crosses, the paternal GPI-A2 isozymes were first expressed at the same time in both reciprocal hybrids, at 21-25 hr after fertilization. The maternal and paternal GPI-B subunits were synchronously expressed in reciprocal hybrids just for prior to hatching. The parental allelic isozymes at both loci shoed codominant expression in all tissues of the mature F1 hybrids. These results are consistent with the absence of allelic asynchrony and inhibition in interspecific hybrids formed from more evolutionarily related species. PMID:1008802

  17. MHC class I allele frequencies in pigtail macaques of diverse origin

    Microsoft Academic Search

    Bridget F. Pratt; David H. O’Connor; Bernard A. P. Lafont; Joseph L. Mankowski; Caroline S. Fernandez; Retno Triastuti; Andrew G. Brooks; Stephen J. Kent; Miranda Z. Smith

    2006-01-01

    Pigtail macaques (Macaca nemestrina) are an increasingly common primate model for the study of human AIDS. Major Histocompatibility complex (MHC) class I-restricted CD8+ T cell responses are a critical part of the adaptive immune response to HIV-1 in humans and simian immunodeficiency virus (SIV) in macaques; however, MHC class I alleles have not yet been comprehensively characterized in pigtail macaques.

  18. Phenotype determining alleles in GM1 gangliosidosis patients bearing novel GLB1 mutations

    Microsoft Academic Search

    D. Hofer; K. Paul; K. Fantur; M. Beck; A. Roubergue; A. Vellodi; B. J. Poorthuis; H. Michelakakis; B. Plecko; E. Paschke

    2010-01-01

    GM1 gangliosidosis manifests with progressive psychomotor deterioration and dysostosis of infantile, juvenile, or adult onset, caused by alterations in the structural gene coding for lysosomal acid ?-galactosidase (GLB1). In addition allelic variants of this gene can result in Morquio B disease, a phenotype with dysostosis multiplex and entire lack of neurologic involvement. More than 100 sequence alterations in the GLB1

  19. Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele.

    PubMed

    Bange, Johannes; Prechtl, Dieter; Cheburkin, Yuri; Specht, Katja; Harbeck, Nadia; Schmitt, Manfred; Knyazeva, Tatjana; Müller, Susanne; Gärtner, Silvia; Sures, Irmi; Wang, Hongyang; Imyanitov, Evgeny; Häring, Hans-Ulrich; Knayzev, Pjotr; Iacobelli, Stefano; Höfler, Heinz; Ullrich, Axel

    2002-02-01

    Expression analysis of genes encoding components of the phosphotyrosine signaling system by cDNA array hybridization revealed elevated levels of FGFR4 transcripts in several mammary carcinoma cell lines. In the FGFR4 gene transcript from MDA-MB-453 mammary carcinoma cells, a G to A conversion was discovered that results in the substitution of glycine by arginine at position 388 in the transmembrane domain of the receptor. The Arg(388) allele was also found in cell lines derived from a variety of other tumor types as well as in the germ-line of cancer patients and healthy individuals. Analysis of three geographically separated groups indicated that it occurs in approximately 50% of the human population. Investigation of the clinical data of 84 breast cancer patients revealed that homo- or heterozygous carriers of the Arg(388) allele had a significantly reduced disease-free survival time (P = 0.01) within a median follow-up of 62 months. Moreover, the FGFR4 Arg(388) allele was associated with early lymph node metastasis and advanced tumor-node-metastasis (TNM) stage in 82 colon cancer patients. Consistent with this finding, MDA-MB-231 mammary tumor cells expressing FGFR4 Arg(388) exhibited increased motility relative to cells expressing the FGFR4 Gly(388) isotype. Our results support the conclusion that the FGFR4 Arg(388) allele represents a determinant that is innocuous in healthy individuals but predisposes cancer patients for significantly accelerated disease progression. PMID:11830541

  20. Haplotype-based profiling of subtle allelic imbalance with SNP arrays.

    PubMed

    Vattathil, Selina; Scheet, Paul

    2013-01-01

    Due to limitations of surgical dissection and tumor heterogeneity, tumor samples collected for cancer genomics studies are often heavily diluted with normal tissue or contain subpopulations of cells harboring important aberrations. Methods for profiling tumor-associated allelic imbalance in such scenarios break down at aberrant cell proportions of 10%-15% and below. Here, we present an approach that offers a vast improvement for detection of subtle allelic imbalance, or low proportions of cells harboring aberrant allelic ratio among nonaberrant cells, in unpaired tumor samples using SNP microarrays. We leverage the expected pattern of allele-specific intensity ratios determined by an individual's germline haplotypes, information that has been ignored in existing approaches. We demonstrate our method on real and simulated data from the CRL-2324 breast cancer cell line genotyped on the Illumina 370K array. Assuming a 5 million SNP array, we can detect the presence of aberrant cells in proportions lower than 0.25% in the breast cancer sample, approaching the sensitivity of some minimal residual disease assays. Further, we apply a hidden Markov model to identify copy-neutral LOH (loss of heterozygosity) events as short as 11 Mb in mixtures of only 4% tumor using 370K data. We anticipate our approach will offer a new paradigm for genomic profiling of heterogeneous samples. PMID:23028187

  1. A-Elute alleles of the ABO blood group system in Japanese

    Microsoft Academic Search

    Tatsuyuki Okiura; Yasuo Fukumori; Koji Nishimura; Chitoshi Orimoto; Kenji Fujii; Hiroaki Nishimukai

    2003-01-01

    The ABO blood group system is important in forensic genetics, as well as transfusion medicine. Since the elucidation of the molecular basis of ABO gene regulation, nucleotides of variant alleles or suballeles have been analyzed by polymerase chain reaction (PCR)-based methods and sequencing. Ael (A-elute) is one of the subgroups of A in the ABO system. By analyzing the suballeles

  2. Polymorphisms of the HTR1a Allele are linked to Frontal Brain Electrical Asymmetry

    PubMed Central

    Bismark, Andrew W.; Moreno, Francisco A.; Stewart, Jennifer L.; Towers, David N.; Coan, James A.; Oas, Jennifer; Erickson, Robert P.; Allen, John J.B.

    2010-01-01

    Polymorphic variations in genes related to serotonin synthesis, transport, recognition, or degradation may convey subtle changes in serotonin system architecture that may place an individual at risk for psychopathology when faced with life stressors. The relationship between three key serotonin alleles and frontal brain electrical asymmetry, a putative endophenotype of depression, was examined. Risk alleles were hypothesized to predict relatively greater right frontal brain activity regardless of current clinical state. A sample of 313 college-age individuals, spanning a range of depressive severity from no symptomotology to clinically meaningful levels, participated. Resting encephalographic (EEG) activity was recorded from 64 scalp sites on four occasions separated by at least 24 hours (two 8-min recording sessions occurring at each occasion). Alpha power asymmetry scores between homologous sites were calculated for each session and then averaged to form a trait metric of asymmetry for each pair. PCR based genotyping was conducted for the HTR1A, HTR2A, and HTTLPR genes. Variations in the HTR1A gene were related to trait EEG asymmetry, regardless of any history of depression. Compared to subjects with at least one non-risk allele, subjects with homozygous HTR1A risk alleles had significantly greater relative right frontal activity at sites F7/F8, F5/F6, & F1/F2. In conclusion, variation in HTR1A can influence trait level brain activity, which may ultimately be indicative of risk for psychopathology. PMID:20025927

  3. Allelic configuration and polysomic inheritance of highly variable microsatellites in tetraploid gynodioecious Thymus praecox agg

    Microsoft Academic Search

    Urs Landergott; Yamama Naciri; J. Jakob Schneller; Rolf Holderegger

    2006-01-01

    Polyploidy plays a pivotal role in plant evolution. However, polyploids with polysomic inheritance have hitherto been severely underrepresented in plant population genetic studies, mainly due to a lack of appropriate molecular genetic markers. Here we report the establishment and experimental validation of six fully informative microsatellite markers in tetraploid gynodioecious Thymus praecox agg. Sequence data of 150 microsatellite alleles and

  4. Association between AgI-CA alleles and severity of autosomal recessive proximal spina lmuscular atrophy

    SciTech Connect

    DiDonato, C.J.; Carpten, J.D.; Fuerst, P.; Ingraham, S.E.; Mendell, J.R.; Burghes, A.H.M. [Ohio State Univ., Columbus, OH (United States); Morgan, K. [McGill Univ. (Canada); Prescott, G.; Simard, L.R. [Hopital Sainte-Justine, Montreal (Canada); McPherson, J.D. [Univ. of California, Irvine, CA (United States)] [and others

    1994-12-01

    The gene for autosomal recessive proximal spinal muscular atrophy (SMA) has been mapped to an 850-kb interval on 5q11.2-q13.3, between the centromeric D5S823 and telomeric D5S557 markers. We report a new complex marker, Ag1-CA, that lies in this interval, whose primers produce one, two, or rarely three amplification-fragment-length variants (AFLVs) per allele. Class I chromosomes are those which amplify a single AFLV allele, and class II chromosomes are those which amplify an allele with two or three AFLVs. Ag1-CA shows highly significant allelic association with type I SMA in both the French Canadian (Hopital Sainte-Justine (HSJ)) and American (Ohio State University (OSU)) populations (P < .0001). Significant association between the Ag1-CA genotype and disease severity was also observed. Type I patients were predominantly homozygous for class I chromosomes (P = .0003 OSU; P = 0.0012 HSJ), whereas the majority of type II patients were heterozygous for class I and II chromosomes (P = .0014 OSU; P = .001 HSJ). There was no significant difference in Ag1-CA genotype frequencies between type III patients (P = .5 OSU; P = .25 HSJ) and the paired normal chromosomes from both carrier parents. Our results indicate that Ag1-CA is the most closely linked marker to SMA and defines the critical candidate-gene region. Finally, we have proposed a model that should be taken into consideration when screening candidates SMA genes.

  5. Msx1 is close but not allelic to either Hm or Hx on mouse Chromosome 5

    Microsoft Academic Search

    B. Robert; X. Montagutelli; D. Houzelstein; L. Ferland; A. Cohen; M. Buckingham; J.-L. Guénet

    1994-01-01

    The Msx1 homeobox locus has been mapped in relation to the mutations hammer-toe (Hm) and hemimelic extra toes (Hx). Msx1 is expressed in the developing limb, while limb development is affected by the Hm and Hx mutations. Hm and Hx are very tightly linked loci. In interspecific crosses, the segregation of either mutation was followed in relation to polymorphic alleles

  6. Direct micro-haplotyping by multiple double PCR amplifications of specific alleles (MD-PASA)

    PubMed Central

    Eitan, Yuval; Kashi, Yechezkel

    2002-01-01

    Analysis of haplotypes is an important tool in population genetics, familial heredity and gene mapping. Determination of haplotypes of multiple single nucleotide polymorphisms (SNPs) or other simple mutations is time consuming and expensive when analyzing large populations, and often requires the help of computational and statistical procedures. Based on double PCR amplification of specific alleles, described previously, we have developed a simple, rapid and low-cost method for direct haplotyping of multiple SNPs and simple mutations found within relatively short specific regions or genes (micro-haplotypes). Using this method, it is possible to directly determine the physical linkage of multiple heterozygous alleles, by conducting a series of double allele-specific PCR amplification sets with simple analysis by gel electrophoresis. Application of the method requires prior information as to the sequence of the segment to be haplotyped, including the polymorphic sites. We applied the method to haplotyping of nine sites in the chicken HSP108 gene. One of the haplotypes in the population apparently arose by recombination between two existing haplotypes, and we were able to locate the point of recombination within a segment of 19 bp. We anticipate rapidly growing needs for SNP haplotyping in human (medical and pharmacogenetics), animal and plant genetics; in this context, the multiple double PCR amplifications of specific alleles (MD-PASA) method offers a useful haplotyping tool. PMID:12060700

  7. Maximum likelihood estimation of the frequency of null alleles at microsatellite loci

    E-print Network

    Kalinowski, Steven T

    Maximum likelihood estimation of the frequency of null alleles at microsatellite loci Steven T Microsatellite loci are the markers of choice for estimating evolutionary relationships between populations and genealogical relationships between individuals. When using microsatellite loci, however, care must be taken

  8. Always look on both sides: Phylogenetic information conveyed by simple sequence repeat allele sequences

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Simple sequence repeat (SSR) markers are widely used tools for inferences about genetic diversity, phylogeography and spatial genetic structure. Their applications assume that variation among alleles is essentially caused by an expansion or contraction of the number of repeats and that, accessorily,...

  9. Functionality of Native Tetraploid Wheat Starches: Effects of Waxy Loci Alleles and Amylose Concentration in Blends

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Partial waxy (reduced-amylose) and fully waxy (amylose-free) tetraploid durum wheats (Triticum turgidum L. var. durum) were developed by introgression of null alleles at the Wx-A1 and Wx-B1 loci from common hexaploid wheat (T. aestivum L.). These genotypes were used to investigate the relationships...

  10. Evidence of HIV-1 adaptation to host HLA alleles following chimp-to-human transmission

    PubMed Central

    Ngandu, Nobubelo K; Seoighe, Cathal; Scheffler, Konrad

    2009-01-01

    Background The cytotoxic T-lymphocyte immune response is important in controlling HIV-1 replication in infected humans. In this immune pathway, viral peptides within infected cells are presented to T-lymphocytes by the polymorphic human leukocyte antigens (HLA). HLA alleles exert selective pressure on the peptide regions and immune escape mutations that occur at some of the targeted sites can enable the virus to adapt to the infected host. The pattern of ongoing immune escape and reversion associated with several human HLA alleles has been studied extensively. Such mutations revert upon transmission to a host without the HLA allele because the escape mutation incurs a fitness cost. However, to-date there has been little attempt to study permanent loss of CTL epitopes due to escape mutations without an effect on fitness. Results Here, we set out to determine the extent of adaptation of HIV-1 to three well-characterized HLA alleles during the initial exposure of the virus to the human cytotoxic immune responses following transmission from chimpanzee. We generated a chimpanzee consensus sequence to approximate the virus sequence that was initially transmitted to the human host and used a method based on peptide binding affinity to HLA crystal structures to predict peptides that were potentially targeted by the HLA alleles on this sequence. Next, we used codon-based phylogenetic models to quantify the average selective pressure that acted on these regions during the period immediately following the zoonosis event, corresponding to the branch of the phylogenetic tree leading to the common ancestor of all of the HIV-1 sequences. Evidence for adaptive evolution during this period was observed at regions recognised by HLA A*6801 and A*0201, both of which are common in African populations. No evidence of adaptive evolution was observed at sites targeted by HLA-B*2705, which is a rare allele in African populations. Conclusion Our results suggest that the ancestral HIV-1 virus experienced a period of positive selective pressure due to immune responses associated with HLA alleles that were common in the infected human population. We propose that this resulted in permanent escape from immune responses targeting unconstrained regions of the virus. PMID:19818146

  11. HLA class II alleles in Romanian patients with chronic hepatitis C

    PubMed Central

    Gheorghe, Loredana; Rugin?, Sorin; Dumitru, Irina Magdalena; Franciuc, Irina; Martinescu, Alina; Bala?, Iulia

    2015-01-01

    Introduction The objective of the study was to determine the association of host human leukocyte antigen (HLA) class II genotype DRB1 alleles with the response to interferon therapy, viral loads and extent of liver fibrosis in a group of Romanian patients diagnosed with chronic hepatitis C, with different clinical outcomes. Class II HLA genes, particularly the HLA-DRB1 and DQB1 genes, have been shown to have an important role in self-limiting or persistent viral infection, in different genetic populations. In chronic hepatitis C both susceptible and protective alleles have been described, influencing the development of autoimmunity and progression to cirrhosis and hepatocellular carcinoma. Methods The study included 54 patients diagnosed with chronic hepatitis C, registered and monitored from January 2014 to January 2015 at the Clinical Hospital of Infectious Diseases, Constan?a, Romania. The selected patients were positive for anti-HCV antibodies and HCV-RNA, with screening laboratory results indicating HCV genotype 1b. The method used for the assignment of alleles at HLA-DRB1 and DQB1 loci was molecular genotyping, by the sequence specific oligonucleotide (SSO) hybridization method, and when required, by the sequence specific primers method (SSP). The presence of different alleles in patients has been analyzed for statistical significance. Results The presence of HLA-DRB1*0301 had a high frequency (14.8%) in null-responders (NR) while alleles DRB1*0701 (11.1%), DRB1*11# (22.2%) and DRB1*0101 (16.7%) were prevalent in sustained virologic responders (SVR). No significant correlation was found between the presence of HLA-DRB1* alleles and viral loads or liver fibrosis with p values not statistically significant after the Bonferroni correction. Conclusion The presented data suggest that in this group of Romanian patients, certain HLA alleles influence the therapeutic response in HCV infection and genetic predisposition may play a role in hepatitis C virus infection in those patients. PMID:26097834

  12. What can I do with a degree in European and European Union Studies?

    E-print Network

    Hickman, Mark

    What can I do with a degree in European and European Union Studies? ARTS Planning your career to www.canterbury.ac.nz/liaison/best_prep.shtml What is European and European Union Studies? The European Union (EU) is New Zealand's most significant bilateral partner after Australia and is one of the world

  13. OCCURRENCE OF THE WAXY ALLELES WXA AND WXB IN WAXY SORGHUM PLANT INTRODUCTIONS AND THEIR EFFECT ON GRAIN THERMAL PROPERTIES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The existence of two waxy alleles, wxa associated with no detectable Granule Bound Starch Synthase (GBSS), and wxb associated with apparently inactive GBSS was recently reported in sorghum (Sorghum bicolor L. Moench). In this paper, the occurrence of the wxa and wxb alleles in the USDA-ARS photoperi...

  14. Allelic exclusion of the immunoglobulin heavy chain locus is independent of its nuclear localization in mature B cells

    PubMed Central

    Holwerda, Sjoerd J. B.; van de Werken, Harmen J. G.; Ribeiro de Almeida, Claudia; Bergen, Ingrid M.; de Bruijn, Marjolein J. W.; Verstegen, Marjon J. A. M.; Simonis, Marieke; Splinter, Erik; Wijchers, Patrick J.; Hendriks, Rudi W.; de Laat, Wouter

    2013-01-01

    In developing B cells, the immunoglobulin heavy chain (IgH) locus is thought to move from repressive to permissive chromatin compartments to facilitate its scheduled rearrangement. In mature B cells, maintenance of allelic exclusion has been proposed to involve recruitment of the non-productive IgH allele to pericentromeric heterochromatin. Here, we used an allele-specific chromosome conformation capture combined with sequencing (4C-seq) approach to unambigously follow the individual IgH alleles in mature B lymphocytes. Despite their physical and functional difference, productive and non-productive IgH alleles in B cells and unrearranged IgH alleles in T cells share many chromosomal contacts and largely reside in active chromatin. In brain, however, the locus resides in a different repressive environment. We conclude that IgH adopts a lymphoid-specific nuclear location that is, however, unrelated to maintenance of allelic exclusion. We additionally find that in mature B cells—but not in T cells—the distal VH regions of both IgH alleles position themselves away from active chromatin. This, we speculate, may help to restrict enhancer activity to the productively rearranged VH promoter element. PMID:23748562

  15. The CFTR Met 470 Allele Is Associated with Lower Birth Rates in Fertile Men from a Population Isolate

    E-print Network

    Abney, Mark

    470 allele was associated with lower birth rates, defined as the number of births per year of marriage homozygous for the Met470 allele had 0.56 fewer children on average compared to Val470 carrier men systems. The clinical manifestations of CF in affected individuals vary widely, with both age at diagnosis

  16. S-allele diversity in a natural population of Physalis crassifolia (Solanaceae) (ground cherry) assessed by RT-PCR

    Microsoft Academic Search

    Adam D Richman; Marcy K Uyenoyama; Joshua R Kohn

    1996-01-01

    Allelic diversity at the self-incompatibility (S-) locus in the ground cherry, Physalis crassifolia (Solanaceae), was surveyed in a natural population occurring in Deep Canyon, CA, using a molecular assay to determine the genotype of individual plants. A total of 28 different S-alleles were identified and sequenced from a sample of 22 plants. All plants examined were heterozygous, as expected under

  17. [CANCER RESEARCH 63, 58085812, September 15, 2003] Congenic Rats Reveal Three Independent Copenhagen Alleles within the Mcs1

    E-print Network

    Gould, Michael N.

    Copenhagen Alleles within the Mcs1 Quantitative Trait Locus That Confer Resistance to Mammary Cancer1 Jill D susceptibility 1 (Mcs1), is located on the centromeric end of chromosome 2 and appears to act in a semidom- inant of the physical location of the Mcs1 gene, congenic lines were generated by transferring the Mcs1 COP allele onto

  18. Competition-based cellular peptide binding assays for 13 prevalent HLA class I alleles using fluorescein-labeled synthetic peptides

    Microsoft Academic Search

    Jan H Kessler; Bregje Mommaas; Tuna Mutis; Ivo Huijbers; Debby Vissers; Willemien E Benckhuijsen; Geziena M. Th Schreuder; Rienk Offringa; Els Goulmy; Cornelis J. M Melief; Sjoerd H van der Burg; Jan W Drijfhout

    2003-01-01

    We report the development, validation, and application of competition-based peptide binding assays for 13 prevalent human leukocyte antigen (HLA) class I alleles. The assays are based on peptide binding to HLA molecules on living cells carrying the particular allele. Competition for binding between the test peptide of interest and a fluorescein-labeled HLA class I binding peptide is used as read

  19. Individual-based genotype analysis in studies of parentage and population assignment: how many loci, how many alleles?

    Microsoft Academic Search

    Louis Bernatchez; Pierre Duchesne

    2000-01-01

    We developed multivatiate analytical models to predict the probability of assigning offspring to parental cou- ples as a function of population size, number of loci, and allelic diversity and the relationships between the probability of allocating individuals to their population of origin as a function of number of loci and allelic diversity. The parent- age model predicts that the number

  20. Am. J. Hum. Genet. 60:447-458, 1997 Estimating the Age of Alleles by Use of Intraallelic Variability

    E-print Network

    over the coalescence times. The method is applied to two alleles at the cystic fibrosis (CFTR) locus of mutation and treats the age of an allele as a random variable (Watterson 1976; Sawyer Received August 6 in the past; its age is then a fixed parameter, rather than a random variable. Thompson used the theory

  1. Snapshots of Selection: Changes in SNP Allele Frequencies during Phenotypic, Marker-Assisted, and Genomewide Selection in Maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Changes in allele frequencies underlie improvements in mean performance for quantitative traits. Limited published information is available on how genomewide marker-allele frequencies change during phenotypic and marker-based selection for multiple traits in applied breeding programs. Here we descri...

  2. Global phylogeography of the avian malaria pathogen Plasmodium relictum based on MSP1 allelic diversity

    USGS Publications Warehouse

    Hellgren, Olof; Atkinson, Carter T.; Bensch, Staffan; Albayrak, Tamer; Dimitrov, Dimitar; Ewen, John G.; Kim, Kyeong Soon; Lima, Marcos R.; Martin, Lynn; Palinauskas, Vaidas; Ricklefs, Robert; Sehgal, Ravinder N. M.; Gediminas, Valkiunas; Tsuda, Yoshio; Marzal, Alfonso

    2015-01-01

    Knowing the genetic variation that occurs in pathogen populations and how it is distributed across geographical areas is essential to understand parasite epidemiology, local patterns of virulence, and evolution of host-resistance. In addition, it is important to identify populations of pathogens that are evolutionarily independent and thus ‘free’ to adapt to hosts and environments. Here, we investigated genetic variation in the globally distributed, highly invasive avian malaria parasite Plasmodium relictum, which has several distinctive mitochondrial haplotyps (cyt b lineages, SGS1, GRW11 and GRW4). The phylogeography of P. relictum was accessed using the highly variable nuclear gene merozoite surface protein 1 (MSP1), a gene linked to the invasion biology of the parasite. We show that the lineage GRW4 is evolutionarily independent of GRW11 and SGS1 whereas GRW11 and SGS1 share MSP1 alleles and thus suggesting the presence of two distinct species (GRW4 versus SGS1 and GRW11). Further, there were significant differences in the global distribution of MSP1 alleles with differences between GRW4 alleles in the New and the Old World. For SGS1, a lineage formerly believed to have both tropical and temperate transmission, there were clear differences in MSP1 alleles transmitted in tropical Africa compared to the temperate regions of Europe and Asia. Further, we highlight the occurrence of multiple MSP1 alleles in GRW4 isolates from the Hawaiian Islands, where the parasite has contributed to declines and extinctions of endemic forest birds since it was introduced. This study stresses the importance of multiple independent loci for understanding patterns of transmission and evolutionary independence across avian malaria parasites.

  3. Variant RH alleles and Rh immunisation in patients with sickle cell disease

    PubMed Central

    Sippert, Emilia; Fujita, Claudia R.; Machado, Debora; Guelsin, Glaucia; Gaspardi, Ane C.; Pellegrino, Jordão; Gilli, Simone; Saad, Sara S.T.O.; Castilho, Lilian

    2015-01-01

    Background Alloimmunisation is a major complication in patients with sickle cell disease (SCD) receiving red blood cell (RBC) transfusions and despite provision of Rh phenotyped RBC units, Rh antibodies still occur. These antibodies in patients positive for the corresponding Rh antigen are considered autoantibodies in many cases but variant RH alleles found in SCD patients can also contribute to Rh alloimmunisation. In this study, we characterised variant RH alleles in 31 SCD patients who made antibodies to Rh antigens despite antigen-positive status and evaluated the clinical significance of the antibodies produced. Materials and methods RHD and RHCE BeadChip™ from BioArray Solutions and/or amplification and sequencing of exons were used to identify the RH variants. The serological features of all Rh antibodies in antigen-positive patients were analysed and the clinical significance of the antibodies was evaluated by retrospective analysis of the haemoglobin (Hb) levels before and after transfusion; the change from baseline pre-transfusion Hb and the percentage of HbS were also determined. Results We identified variant RH alleles in 31/48 (65%) of SCD patients with Rh antibodies. Molecular analyses revealed the presence of partial RHD alleles and variant RHCE alleles associated with altered C and e antigens. Five patients were compound heterozygotes for RHD and RHCE variants. Retrospective analysis showed that 42% of antibodies produced by the patients with RH variants were involved in delayed haemolytic transfusion reactions or decreased survival of transfused RBC. Discussion In this study, we found that Rh antibodies in SCD patients with RH variants can be clinically significant and, therefore, matching patients based on RH variants should be considered. PMID:24960646

  4. Two Novel ? 1,2-Fucosyltransferase Alleles in an H-Deficient Phenotype Individual

    PubMed Central

    He, Ziyi; Liu, Fuping

    2014-01-01

    Summary Background: Abnormal ?1,2-fucosyltransferase activity due to gene mutation results in decreased synthesis of H antigen and leads to an H-deficient phenotype. Here we studied the underlying molecular mechanisms in 7 Chinese blood donors with the H-deficient phenotype. Methods: Red blood cell typing was performed using standard serologic tests, and ABO genotype was analyzed using ABO polymerase chain reaction with sequence-specific primer tests. The coding sequence of the FUT1 gene was amplified using the specific primers. The FUT1 alleles were identified by a pCRII-TOPO carrier for TOPO TA cloning sequencing. Results: The H-deficient phenotype frequency was estimated to be approximately 1/30,000 (6/159,515) in the Chinese Han population. The FUT1 gene mutation was demonstrated in 6 Chinese blood donors with the H-deficient phenotype. In only 1 case, no mutation was detected. Novel FUT1 alleles were found in 1 donor. One of these novel FUT1 alleles showed nucleotide 35C>T and 748C>T site mutations that resulted in amino acid substitution of Ala to Val and Trp to Arg at positions 11 and 250, respectively. Another novel FUT1 allele had a nucleotide 655G>C site mutation, causing amino acid substitution of Leu to Val at position 219. Conclusions: Two novel FUT1 alleles, 35T+748T and 655C, were identified that may greatly diminish the activity of ?1,2-fucosyltransferase and result in the H-deficient phenotype. PMID:25538540

  5. Functionally compromised CHD7 alleles in patients with isolated GnRH deficiency

    PubMed Central

    Balasubramanian, Ravikumar; Choi, Jin-Ho; Francescatto, Ludmila; Willer, Jason; Horton, Edward R.; Asimacopoulos, Eleni P.; Stankovic, Konstantina M.; Plummer, Lacey; Buck, Cassandra L.; Quinton, Richard; Nebesio, Todd D.; Mericq, Veronica; Meyer, Brian F.; Monies, Dorota; Gusella, James F.; Al Tassan, Nada; Katsanis, Nicholas; Crowley, William F.

    2014-01-01

    Inactivating mutations in chromodomain helicase DNA binding protein 7 (CHD7) cause CHARGE syndrome, a severe multiorgan system disorder of which Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is a minor feature. Recent reports have described predominantly missense CHD7 alleles in IGD patients, but it is unclear if these alleles are relevant to causality or overall genetic burden of Kallmann syndrome (KS) and normosmic form of IGD. To address this question, we sequenced CHD7 in 783 well-phenotyped IGD patients lacking full CHARGE features; we identified nonsynonymous rare sequence variants in 5.2% of the IGD cohort (73% missense and 27% splice variants). Functional analyses in zebrafish using a surrogate otolith assay of a representative set of these CHD7 alleles showed that rare sequence variants observed in controls showed no altered function. In contrast, 75% of the IGD-associated alleles were deleterious and resulted in both KS and normosmic IGD. In two families, pathogenic mutations in CHD7 coexisted with mutations in other known IGD genes. Taken together, our data suggest that rare deleterious CHD7 alleles contribute to the mutational burden of patients with both KS and normosmic forms of IGD in the absence of full CHARGE syndrome. These findings (i) implicate a unique role or preferential sensitivity for CHD7 in the ontogeny of GnRH neurons, (ii) reiterate the emerging genetic complexity of this family of IGD disorders, and (iii) demonstrate how the coordinated use of well-phenotyped cohorts, families, and functional studies can inform genetic architecture and provide insights into the developmental biology of cellular systems. PMID:25472840

  6. Detection of Ancestry Informative HLA Alleles Confirms the Admixed Origins of Japanese Population

    PubMed Central

    Nakaoka, Hirofumi; Mitsunaga, Shigeki; Hosomichi, Kazuyoshi; Shyh-Yuh, Liou; Sawamoto, Taiji; Fujiwara, Tsutomu; Tsutsui, Naohisa; Suematsu, Koji; Shinagawa, Akira; Inoko, Hidetoshi; Inoue, Ituro

    2013-01-01

    The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD) between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago. PMID:23577161

  7. Detection of ancestry informative HLA alleles confirms the admixed origins of Japanese population.

    PubMed

    Nakaoka, Hirofumi; Mitsunaga, Shigeki; Hosomichi, Kazuyoshi; Shyh-Yuh, Liou; Sawamoto, Taiji; Fujiwara, Tsutomu; Tsutsui, Naohisa; Suematsu, Koji; Shinagawa, Akira; Inoko, Hidetoshi; Inoue, Ituro

    2013-01-01

    The polymorphisms in the human leukocyte antigen (HLA) region are powerful tool for studying human evolutionary processes. We investigated genetic structure of Japanese by using five-locus HLA genotypes (HLA-A, -B, -C, -DRB1, and -DPB1) of 2,005 individuals from 10 regions of Japan. We found a significant level of population substructure in Japanese; particularly the differentiation between Okinawa Island and mainland Japanese. By using a plot of the principal component scores, we identified ancestry informative alleles associated with the underlying population substructure. We examined extent of linkage disequilibrium (LD) between pairs of HLA alleles on the haplotypes that were differentiated among regions. The LDs were strong and weak for pairs of HLA alleles characterized by low and high frequencies in Okinawa Island, respectively. The five-locus haplotypes whose alleles exhibit strong LD were unique to Japanese and South Korean, suggesting that these haplotypes had been recently derived from the Korean Peninsula. The alleles characterized by high frequency in Japanese compared to South Korean formed segmented three-locus haplotype that was commonly found in Aleuts, Eskimos, and North- and Meso-Americans but not observed in Korean and Chinese. The serologically equivalent haplotype was found in Orchid Island in Taiwan, Mongol, Siberia, and Arctic regions. It suggests that early Japanese who existed prior to the migration wave from the Korean Peninsula shared ancestry with northern Asian who moved to the New World via the Bering Strait land bridge. These results may support the admixture model for peopling of Japanese Archipelago. PMID:23577161

  8. Always Look on Both Sides: Phylogenetic Information Conveyed by Simple Sequence Repeat Allele Sequences

    PubMed Central

    Barthe, Stéphanie; Gugerli, Felix; Barkley, Noelle A.; Maggia, Laurent; Cardi, Céline; Scotti, Ivan

    2012-01-01

    Simple sequence repeat (SSR) markers are widely used tools for inferences about genetic diversity, phylogeography and spatial genetic structure. Their applications assume that variation among alleles is essentially caused by an expansion or contraction of the number of repeats and that, accessorily, mutations in the target sequences follow the stepwise mutation model (SMM). Generally speaking, PCR amplicon sizes are used as direct indicators of the number of SSR repeats composing an allele with the data analysis either ignoring the extent of allele size differences or assuming that there is a direct correlation between differences in amplicon size and evolutionary distance. However, without precisely knowing the kind and distribution of polymorphism within an allele (SSR and the associated flanking region (FR) sequences), it is hard to say what kind of evolutionary message is conveyed by such a synthetic descriptor of polymorphism as DNA amplicon size. In this study, we sequenced several SSR alleles in multiple populations of three divergent tree genera and disentangled the types of polymorphisms contained in each portion of the DNA amplicon containing an SSR. The patterns of diversity provided by amplicon size variation, SSR variation itself, insertions/deletions (indels), and single nucleotide polymorphisms (SNPs) observed in the FRs were compared. Amplicon size variation largely reflected SSR repeat number. The amount of variation was as large in FRs as in the SSR itself. The former contributed significantly to the phylogenetic information and sometimes was the main source of differentiation among individuals and populations contained by FR and SSR regions of SSR markers. The presence of mutations occurring at different rates within a marker’s sequence offers the opportunity to analyse evolutionary events occurring on various timescales, but at the same time calls for caution in the interpretation of SSR marker data when the distribution of within-locus polymorphism is not known. PMID:22808236

  9. The characteristic trajectory of a fixing allele: a consequence of fictitious selection that arises from conditioning.

    PubMed

    Zhao, Lei; Lascoux, Martin; Overall, Andrew D J; Waxman, David

    2013-11-01

    This work is concerned with the historical progression, to fixation, of an allele in a finite population. This progression is characterized by the average frequency trajectory of alleles that achieve fixation before a given time, T. Under a diffusion analysis, the average trajectory, conditional on fixation by time T, is shown to be equivalent to the average trajectory in an unconditioned problem involving additional selection. We call this additional selection "fictitious selection"; it plays the role of a selective force in the unconditioned problem but does not exist in reality. It is a consequence of conditioning on fixation. The fictitious selection is frequency dependent and can be very large compared with any real selection that is acting. We derive an approximation for the characteristic trajectory of a fixing allele, when subject to real additive selection, from an unconditioned problem, where the total selection is a combination of real and fictitious selection. Trying to reproduce the characteristic trajectory from the action of additive selection, in an infinite population, can lead to estimates of the strength of the selection that deviate from the real selection by >1000% or have the opposite sign. Strong evolutionary forces may be invoked in problems where conditioning has been carried out, but these forces may largely be an outcome of the conditioning and hence may not have a real existence. The work presented here clarifies these issues and provides two useful tools for future analyses: the characteristic trajectory of a fixing allele and the force that primarily drives this, namely fictitious selection. These should prove useful in a number of areas of interest including coalescence with selection, experimental evolution, time series analyses of ancient DNA, game theory in finite populations, and the historical dynamics of selected alleles in wild populations. PMID:24002647

  10. Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE) gene

    SciTech Connect

    Primo-Parmo, S.L.; Wiersema, B.; Spek, A.F.L. van der [Univ. of Michigan Medical School, Ann Arbor, MI (United States)] [and others

    1996-01-01

    The silent phenotype of human butyrylcholinesterase (BChE), present in most human populations in frequencies of {approximately}1/100,000, is characterized by the complete absence of BChE activity or by activity < 10 % of the average levels of the usual phenotype. Heterogeneity in this phenotype has been well established at the phenotypic level, but only a few silent BCHE alleles have been characterized at the DNA level. Twelve silent alleles of the human butyrylcholinesterase gene (BCHE) have been identified in 17 apparently unrelated patients who were selected by their increased sensitivity to the muscle relaxant succinylcholine. All of these alleles are characterized by single nucleotide substitutions or deletions leading to distinct changes in the structure of the BChE enzyme molecule. Nine of the nucleotide substitutions result in the replacement of single amino acid residues. Three of these variants, BCHE*33C, BCHE*198G, and BCHE*201T, produce normal amounts of immunoreactive but enzymatically inactive BChE protein in the plasma. The other six amino acid substitutions, encoded by BCHE*37S, BCHE*125F, BCHE*170E, BCHE-471R, and BCHE*518L, seem to cause reduced expression of BChE protein, and their role in determining the silent phenotype was confirmed by expression in cell culture. The other four silent alleles, BCHE*271STOP, BCHE*500STOP, BCHE*FS6, and BCHE*I2E3-8G, encode BChEs truncated at their C-terminus because of premature stop codons caused by nucleotide substitutions, a frame shift, or altered splicing. The large number of different silent BCHE alleles found within a relatively small number of patients shows that the heterogeneity of the silent BChE phenotype is high. The characterization of silent BChE variants will be useful in the study of the structure/function relationship for this and other closely related enzymes. 83 refs., 3 figs., 4 tabs.

  11. Quantification of the paternal allele bias for new germline mutations in the retinoblastoma gene

    SciTech Connect

    Morrow, J.F.; Rapaport, J.M.; Dryia, T.P. [Massachusetts Eye & Ear Infirmary, Boston, MA (United States)

    1994-09-01

    New germline mutations in the human retinoblastoma gene preferentially arise on a paternally derived allele. In nonhereditary retinoblastoma, the initial somatic mutation seems to have no such bias. The few previous reports of these phenomena included relatively few cases (less than a dozen new germline or initial somatic mutations), so that the magnitude of the paternal allele bias for new germline mutations is not known. Knowledge of the magnitude of the bias is valuable for genetic counseling, since, for example, patients with new germline mutations who reproduce transmit risk for retinoblastoma according to the risk that the transmitted allele has a germline mutation. We sought to quantitate the paternal allele bias and to determine whether paternal age is a factor possibly accounting for it. We studied 311 families with retinoblastoma (261 simplex, 50 multiplex) that underwent clinical genetic testing and 5 informative families recruited from earlier research. Using RFLPs and polymorphic microsatellites in the retinoblastoma gene, we could determine the parental origin of 45 new germline mutations and 44 probable initial somatic mutations. Thirty-seven of the 45 new germline mutations, or 82%, arose on a paternal allele while only 24 of the 44 initial somatic mutations (55%) did so. Increased paternal age does not appear to account for the excess of new paternal germline mutations, since the average age of fathers of children with new germline mutations (29.4 years, n=26, incomplete records on 11) was not significantly different from the average age of fathers of children with maternal germline mutations or somatic initial mutations (29.8 years, n=35, incomplete records on 17).

  12. Functionally compromised CHD7 alleles in patients with isolated GnRH deficiency.

    PubMed

    Balasubramanian, Ravikumar; Choi, Jin-Ho; Francescatto, Ludmila; Willer, Jason; Horton, Edward R; Asimacopoulos, Eleni P; Stankovic, Konstantina M; Plummer, Lacey; Buck, Cassandra L; Quinton, Richard; Nebesio, Todd D; Mericq, Veronica; Merino, Paulina M; Meyer, Brian F; Monies, Dorota; Gusella, James F; Al Tassan, Nada; Katsanis, Nicholas; Crowley, William F

    2014-12-16

    Inactivating mutations in chromodomain helicase DNA binding protein 7 (CHD7) cause CHARGE syndrome, a severe multiorgan system disorder of which Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is a minor feature. Recent reports have described predominantly missense CHD7 alleles in IGD patients, but it is unclear if these alleles are relevant to causality or overall genetic burden of Kallmann syndrome (KS) and normosmic form of IGD. To address this question, we sequenced CHD7 in 783 well-phenotyped IGD patients lacking full CHARGE features; we identified nonsynonymous rare sequence variants in 5.2% of the IGD cohort (73% missense and 27% splice variants). Functional analyses in zebrafish using a surrogate otolith assay of a representative set of these CHD7 alleles showed that rare sequence variants observed in controls showed no altered function. In contrast, 75% of the IGD-associated alleles were deleterious and resulted in both KS and normosmic IGD. In two families, pathogenic mutations in CHD7 coexisted with mutations in other known IGD genes. Taken together, our data suggest that rare deleterious CHD7 alleles contribute to the mutational burden of patients with both KS and normosmic forms of IGD in the absence of full CHARGE syndrome. These findings (i) implicate a unique role or preferential sensitivity for CHD7 in the ontogeny of GnRH neurons, (ii) reiterate the emerging genetic complexity of this family of IGD disorders, and (iii) demonstrate how the coordinated use of well-phenotyped cohorts, families, and functional studies can inform genetic architecture and provide insights into the developmental biology of cellular systems. PMID:25472840

  13. Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE) gene.

    PubMed Central

    Primo-Parmo, S. L.; Bartels, C. F.; Wiersema, B.; van der Spek, A. F.; Innis, J. W.; La Du, B. N.

    1996-01-01

    The silent phenotype of human butyrylcholinesterase (BChE), present in most human populations in frequencies of approximately 1/100,000, is characterized by the complete absence of BChE activity or by activity <10% of the average levels of the usual phenotype. Heterogeneity in this phenotype has been well established at the phenotypic level, but only a few silent BCHE alleles have been characterized at the DNA level. Twelve silent alleles of the human butyrylcholinesterase gene (BCHE) have been identified in 17 apparently unrelated patients who were selected by their increased sensitivity to the muscle relaxant succinylcholine. All of these alleles are characterized by single nucleotide substitutions or deletions leading to distinct changes in the structure of the BChE enzyme molecule. Nine of the nucleotide substitutions result in the replacement of single amino acid residues. Three of these variants, BCHE*33C, BCHE*198G, and BCHE*201T, produce normal amounts of immunoreactive but enzymatically inactive BChE protein in the plasma. The other six amino acid substitutions, encoded by BCHE*37S, BCHE*125F, BCHE*170E, BCHE*471R, and BCHE*518L, seem to cause reduced expression of BChE protein, and their role in determining the silent phenotype was confirmed by expression in cell culture. The other four silent alleles, BCHE*271STOP, BCHE*500STOP, BCHE*FS6, and BCHE*I2E3-8G, encode BChES truncated at their C-terminus because of premature stop codons caused by nucleotide substitutions, a frame shift, or altered splicing. The large number of different silent BCHE alleles found within a relatively small number of patients shows that the heterogeneity of the silent BChE phenotype is high. The characterization of silent BChE variants will be useful in the study of the structure/function relationship for this and other closely related enzymes. Images Figure 2 PMID:8554068

  14. Whole Genome Association Mapping of Fusarium Head Blight Resistance in European Winter Wheat (Triticum aestivum L.)

    PubMed Central

    Kollers, Sonja; Rodemann, Bernd; Ling, Jie; Korzun, Viktor; Ebmeyer, Erhard; Argillier, Odile; Hinze, Maike; Plieske, Jörg; Kulosa, Dagmar; Ganal, Martin W.; Röder, Marion S.

    2013-01-01

    A total of 358 recent European winter wheat varieties plus 14 spring wheat varieties were evaluated for resistance to Fusarium head blight (FHB) caused by Fusarium graminearum and Fusarium culmorum in four separate environments. The FHB scores based on FHB incidence (Type I resistance)×FHB severity (Type II resistance) indicated a wide phenotypic variation of the varieties with BLUE (best linear unbiased estimation) values ranging from 0.07 to 33.67. Genotyping with 732 microsatellite markers resulted in 782 loci of which 620 were placed on the ITMI map. The resulting average marker distance of 6.8 cM allowed genome wide association mapping employing a mixed model. Though no clear population structure was discovered, a kinship matrix was used for stratification. A total of 794 significant (?log10(p)-value?3.0) associations between SSR-loci and environment-specific FHB scores or BLUE values were detected, which included 323 SSR alleles. For FHB incidence and FHB severity a total of 861 and 877 individual marker-trait associations (MTA) were detected, respectively. Associations for both traits co-located with FHB score in most cases. Consistent associations detected in three or more environments were found on all chromosomes except chromosome 6B, and with the highest number of MTA on chromosome 5B. The dependence of the number of favourable and unfavourable alleles within a variety to the respective FHB scores indicated an additive effect of favourable and unfavourable alleles, i.e. genotypes with more favourable or less unfavourable alleles tended to show greater resistance to FHB. Assessment of a marker specific for the dwarfing gene Rht-D1 resulted in strong effects. The results provide a prerequisite for designing genome wide breeding strategies for FHB resistance. PMID:23451238

  15. Slight instability of a FMR-1 allele over three generations in a family from the general population

    SciTech Connect

    Abramowicz, M.J.; Parma, J.; Cochaux, P. [Brussels Univ. Clinic-Erasme Hospital, Brussels (Belgium)] [Brussels Univ. Clinic-Erasme Hospital, Brussels (Belgium)

    1996-08-09

    We report on a family segregating a FMR-1 allele within the {open_quotes}grey zone{close_quotes} of triplet repeat length (n = 51). The allele showed a 1-unit increment when transmitted through a female meiosis and a 1-unit increment when transmitted through a male of the next generation. At the following generation, a pregnant woman had amniocentesis performed. The latter showed she transmitted the allele unchanged (n = 53) to her male fetus. This family was not ascertained through an affected subject, and there was no family history of mental retardation. Thus our observation reflects the natural history of an unstable allele in the general population. Systematic analysis of such alleles may help refine our understanding of the grey zone of triplet repeat length. 5 refs., 1 fig.

  16. FISH-detected delay in replication timing of mutated FMR1 alleles on both active and inactive X-chromosomes.

    PubMed

    Yeshaya, J; Shalgi, R; Shohat, M; Avivi, L

    1999-01-01

    X-chromosome inactivation and the size of the CGG repeat number are assumed to play a role in the clinical, physical, and behavioral phenotype of female carriers of a mutated FMR1 allele. In view of the tight relationship between replication timing and the expression of a given DNA sequence, we have examined the replication timing of FMR1 alleles on active and inactive X-chromosomes in cell samples (lymphocytes or amniocytes) of 25 females: 17 heterozygous for a mutated FMR1 allele with a trinucleotide repeat number varying from 58 to a few hundred, and eight homozygous for a wild-type allele. We have applied two-color fluorescence in situ hybridization (FISH) with FMR1 and X-chromosome alpha-satellite probes to interphase cells of the various genotypes: the alpha-satellite probe was used to distinguish between early replicating (active) and late replicating (inactive) X-chromosomes, and the FMR1 probe revealed the replication pattern of this locus. All samples, except one with a large trinucleotide expansion, showed an early replicating FMR1 allele on the active X-chromosome and a late replicating allele on the inactive X-chromosome. In samples of mutation carriers, both the early and the late alleles showed delayed replication compared with normal alleles, regardless of repeat size. We conclude therefore that: (1) the FMR1 locus is subjected to X-inactivation; (2) mutated FMR1 alleles, regardless of repeat size, replicate later than wild-type alleles on both the active and inactive X-chromosomes; and (3) the delaying effect of the trinucleotide expansion, even with a low repeat size, is superimposed on the delay in replication associated with X-inactivation. PMID:10480360

  17. Restrictive flamenco alleles are maintained in Drosophila melanogaster population cages, despite the absence of their endogenous gypsy retroviral targets.

    PubMed

    Pélisson, Alain; Payen-Groschêne, Geneviève; Terzian, Christophe; Bucheton, Alain

    2007-02-01

    The flamenco (flam) locus, located at 20A1-3 in the centromeric heterochromatin of the Drosophila melanogaster X chromosome, is a major regulator of the gypsy/mdg4 endogenous retrovirus. In restrictive strains, functional flam alleles maintain gypsy proviruses in a repressed state. By contrast, in permissive strains, proviral amplification results from infection of the female germ line and subsequent insertions into the chromosomes of the progeny. A restrictive/permissive polymorphism prevails in natural and laboratory populations. This polymorphism was assumed to be maintained by the interplay of opposite selective forces; on one hand, the increase of genetic load caused by proviral insertions would favor restrictive flam alleles because they make flies resistant to these gypsy replicative transpositions and, on the other, a hypothetical resistance cost would select against such alleles in the absence of the retrovirus. However, the population cage data presented in this paper do not fit with this simple resistance cost hypothesis because restrictive alleles were not eliminated in the absence of functional gypsy proviruses; on the contrary, using 2 independent flam allelic pairs, the restrictive frequency rose to about 90% in every experimental population, whatever the pair of alleles and the allelic proportions in the initial inoculum. These data suggest that the flam polymorphism is maintained by some strong balancing selection, which would act either on flam itself, independently of the deleterious effect of gypsy, or on a hypothetical flanking gene, in linkage disequilibrium with flam. Alternatively, restrictive flam alleles might also be resistant to some other retroelements that would be still present in the cage populations, causing a positive selection for these alleles. Whatever selective forces that maintain high levels of restrictive alleles independently of gypsy, this unknown mechanism can set up an interesting kind of antiviral innate immunity, at the population level. PMID:17119009

  18. German and British labour law in a European context following European Union enlargement 

    E-print Network

    Zahn, Rebecca Lisa

    2011-07-01

    This thesis examines and compares German and British trade union responses in a European context following the recent European enlargements which are unprecedented in the history of the European Union. In terms of labour ...

  19. Duponchelia fovealisDuponchelia fovealis (Zeller)(Zeller) European Pepper MothEuropean Pepper Moth

    E-print Network

    Watson, Craig A.

    Duponchelia fovealisDuponchelia fovealis (Zeller)(Zeller) European Pepper MothEuropean Pepper Moth Agriculture Pest Survey program). The photographs of the European pepper moth were used with permission from

  20. Using haplotypes for the prediction of allelic identity to fine-map QTL: characterization and properties

    PubMed Central

    2014-01-01

    Background Numerous methods have been developed over the last decade to predict allelic identity at unobserved loci between pairs of chromosome segments along the genome. These loci are often unobserved positions tested for the presence of quantitative trait loci (QTL). The main objective of this study was to understand from a theoretical standpoint the relation between linkage disequilibrium (LD) and allelic identity prediction when using haplotypes for fine mapping of QTL. In addition, six allelic identity predictors (AIP) were also compared in this study to determine which one performed best in theory and application. Results A criterion based on a simple measure of matrix distance was used to study the relation between LD and allelic identity prediction when using haplotypes. The consistency of this criterion with the accuracy of QTL localization, another criterion commonly used to compare AIP, was evaluated on a set of real chromosomes. For this set of chromosomes, the criterion was consistent with the mapping accuracy of a simulated QTL with either low or high effect. As measured by the matrix distance, the best AIP for QTL mapping were those that best captured LD between a tested position and a QTL. Moreover the matrix distance between a tested position and a QTL was shown to decrease for some AIP when LD increased. However, the matrix distance for AIP with continuous predictions in the [0,1] interval was algebraically proven to decrease less rapidly up to a lower bound with increasing LD in the simplest situations, than the discrete predictor based on identity by state between haplotypes (IBS hap), for which there was no lower bound. The expected LD between haplotypes at a tested position and alleles at a QTL is a quantity that increases naturally when the tested position gets closer to the QTL. This behavior was demonstrated with pig and unrelated human chromosomes. Conclusions When the density of markers is high, and therefore LD between adjacent loci can be assumed to be high, the discrete predictor IBS hap is recommended since it predicts allele identity correctly when taking LD into account. PMID:25022866