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1

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

PubMed Central

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

Faure, Eric

2008-01-01

2

Distribution of the CCR5delta32 allele (gene variant CCR5) in Rondônia, Western Amazonian region, Brazil  

PubMed Central

Since around 1723, on the occasion of its initial colonization by Europeans, Rondonia has received successive waves of immigrants. This has been further swelled by individuals from northeastern Brazil, who began entering at the beginning of the twentieth century. The ethnic composition varies across the state according to the various sites of settlement of each wave of immigrants. We analyzed the frequency of the CCR5?32 allele of the CCR5 chemokine receptor, which is considered a Caucasian marker, in five sample sets from the population. Four were collected in Porto Velho, the state capital and the site of several waves of migration. Of these, two, from the Hospital de Base were comprised of HB Mothers and HB Newborns presenting allele frequencies of 3.5% and 3.1%, respectively, a third from the peri-urban neighborhoods of Candelária/Bate-Estaca (1.8%), whereas a fourth, from the Research Center on Tropical Medicine/CEPEM (0.6%), was composed of malaria patients under treament. The fifth sample (3.4%) came from the inland Quilombola village of Pedras Negras. Two homozygous individuals (CCR5?32/CCR5?32) were detected among the HB Mother samples. The frequency of this allele was heterogeneous and higher where the European inflow was more pronounced. The presence of the allele in Pedras Negras revealed European miscegenation in a community largely comprising Quilombolas. PMID:22481870

de Farias, Josileide Duarte; Santos, Marlene Guimarães; de França, Andonai Krauze; Delani, Daniel; Tada, Mauro Shugiro; Casseb, Almeida Andrade; Simões, Aguinaldo Luiz; Engracia, Vera

2012-01-01

3

Distribution of the HIV1 Resistance-Conferring Alleles (CCR5delta32, CCR2-64I, and SDF1-3?A) in Russian, Ukrainian, and Belarusian Populations  

Microsoft Academic Search

The frequencies of three alleles, CCR5delta32, CCR2-64I, and SDF1-3'A, known to decrease the risk of AIDS onset and the rate of the disease progression in HIV-infected individuals were determined in three native population samples from Russia, Ukraine, and Belarus. The frequencies of the alleles were 0.15, 0.12, 0.21; 0.12, 0.07, 0.20; and 0.12, 0.08, 0.26 for Russians, Ukrainians, and Belarussians,

Zh. M. Kozhekbaeva; T. A. Borodina; S. A. Borinskaya; V. A. Gusar; S. P. Feschenko; V. L. Akhmetova; R. I. Khusainova; E. Yu. Gupalo; V. A. Spitsyn; E. J. Grechanina; E. K. Khusnutdinova; N. K. Yankovsky

2004-01-01

4

High prevalence of the CCR5Delta32 HIV-resistance mutation among Estonian HIV type 1-infected individuals.  

PubMed

The aim of this survey was to investigate human immunodeficiency virus type 1 (HIV-1) coreceptor, chemokine receptor 5 (CCR5), polymorphism among Estonian HIV-1-infected individuals. Homozygous CCR5Delta32 genotypes have been associated with resistance to HIV-1 infection; however, inconsistent evidence exists as to whether a single copy of a mutant allele among heterozygotes confers protection from HIV-1 infection. In an Estonian population the frequency of the CCR5Delta32 allele has been found to be among the greatest observed to date. Ironically, Estonia is concomitantly characterized by a very high HIV-1 prevalence. We compared the allele frequencies in a healthy control population to the HIV-positive group. The frequency of heterozygous individuals did not differ significantly between the HIV-positive group and the control population. Allele frequencies were analyzed among different risk groups as well as groups with different HIV genetic backgrounds. We did not find a difference between CCR5Delta32 allele frequencies among intravenous drug users (IDUs) and sexually infected persons. Likewise, the distribution of CCR5Delta32 allele frequencies among patients infected with different subtypes did not differ while data from "pure" subtypes A, B, and CRF06_cpx were pooled and evaluated against unique recombinant forms. PMID:17331026

Adojaan, Maarja; Mölder, Tarmo; Männik, Andres; Kivisild, Toomas; Villems, Richard; Krispin, Tõnu; Ustav, Mart

2007-02-01

5

Frequency of the CCR5-delta32 mutation in the Atlantic island populations of Madeira, the Azores, Cabo Verde, and São Tomé e Príncipe.  

PubMed

There is evidence that the CCR5-delta32 mutation confers protection against HIV-1 infection to homozygous individuals. It is believed that this mutation spread through Europe with the Vikings and that it has been subjected to positive selection, leading to a high frequency in Europe (approximately 10%). We carried out the present study to determine the 32-bp deletion allele and genotype frequencies of the CCR5 gene (CCR5-delta32) in the Atlantic island populations of Madeira, the Azores, Cabo Verde, and São Tomé e Principe. These Atlantic archipelagos were all colonized by the Portuguese in the 15th and 16th centuries, but the latter two received most of their settlers from the West African coast. The frequency of the CCR5-delta32 mutation varies between 0% in São Tomé e Príncipe and 16.5% in the Azores. The Azores Islands have one of the highest frequencies of homozygotes found in Europe (4.8%). There are significant differences (P < 0.05) between some of these populations, for example, between São Tomé e Príncipe and Cabo Verde, and even within populations (e.g., Portugal, Madeira, and the Azores). PMID:17564248

Freitas, Tamira; Brehm, António; Fernandes, Ana Teresa

2006-12-01

6

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

PubMed Central

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

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

2015-01-01

7

A comparison of type 2 diabetes risk allele load between African Americans and European Americans.  

PubMed

The prevalence of type 2 diabetes (T2D) is greater in populations of African descent compared to European-descent populations. Genetic risk factors may underlie the disparity in disease prevalence. Genome-wide association studies (GWAS) have identified >60 common genetic variants that contribute to T2D risk in populations of European, Asian, African and Hispanic descent. These studies have not comprehensively examined population differences in cumulative risk allele load. To investigate the relationship between risk allele load and T2D risk, 46 T2D single nucleotide polymorphisms (SNPs) in 43 loci from GWAS in European, Asian, and African-derived populations were genotyped in 1,990 African Americans (n = 963 T2D cases, n = 1,027 controls) and 1,644 European Americans (n = 719 T2D cases, n = 925 controls) ascertained and recruited using a common protocol in the southeast United States. A genetic risk score (GRS) was constructed from the cumulative risk alleles for each individual. In African American subjects, risk allele frequencies ranged from 0.024 to 0.964. Risk alleles from 26 SNPs demonstrated directional consistency with previous studies, and 3 SNPs from ADAMTS9, TCF7L2, and ZFAND6 showed nominal evidence of association (p < 0.05). African American individuals carried 38-67 (53.7 ± 4.0, mean ± SD) risk alleles. In European American subjects, risk allele frequencies ranged from 0.084 to 0.996. Risk alleles from 36 SNPs demonstrated directional consistency, and 10 SNPs from BCL11A, PSMD6, ADAMTS9, ZFAND3, ANK1, CDKN2A/B, TCF7L2, PRC1, FTO, and BCAR1 showed evidence of association (p < 0.05). European American individuals carried 38-65 (50.9 ± 4.4) risk alleles. African Americans have a significantly greater burden of 2.8 risk alleles (p = 3.97 × 10(-89)) compared to European Americans. However, GRS modeling showed that cumulative risk allele load was associated with risk of T2D in European Americans, but only marginally in African Americans. This result suggests that there are ethnic-specific differences in genetic architecture underlying T2D, and that these differences complicate our understanding of how risk allele load impacts disease susceptibility. PMID:25273842

Keaton, Jacob M; Cooke Bailey, Jessica N; Palmer, Nicholette D; Freedman, Barry I; Langefeld, Carl D; Ng, Maggie C Y; Bowden, Donald W

2014-12-01

8

Impact of CCR5delta32 host genetic background and disease progression on HIV-1 intrahost evolutionary processes: efficient hypothesis testing through hierarchical phylogenetic models.  

PubMed

The interplay between C-C chemokine receptor type 5 (CCR5) host genetic background, disease progression, and intrahost HIV-1 evolutionary dynamics remains unclear because differences in viral evolution between hosts limit the ability to draw conclusions across hosts stratified into clinically relevant populations. Similar inference problems are proliferating across many measurably evolving pathogens for which intrahost sequence samples are readily available. To this end, we propose novel hierarchical phylogenetic models (HPMs) that incorporate fixed effects to test for differences in dynamics across host populations in a formal statistical framework employing stochastic search variable selection and model averaging. To clarify the role of CCR5 host genetic background and disease progression on viral evolutionary patterns, we obtain gp120 envelope sequences from clonal HIV-1 variants isolated at multiple time points in the course of infection from populations of HIV-1-infected individuals who only harbored CCR5-using HIV-1 variants at all time points. Presence or absence of a CCR5 wt/?32 genotype and progressive or long-term nonprogressive course of infection stratify the clinical populations in a two-way design. As compared with the standard approach of analyzing sequences from each patient independently, the HPM provides more efficient estimation of evolutionary parameters such as nucleotide substitution rates and d(N)/d(S) rate ratios, as shown by significant shrinkage of the estimator variance. The fixed effects also correct for nonindependence of data between populations and results in even further shrinkage of individual patient estimates. Model selection suggests an association between nucleotide substitution rate and disease progression, but a role for CCR5 genotype remains elusive. Given the absence of clear d(N)/d(S) differences between patient groups, delayed onset of AIDS symptoms appears to be solely associated with lower viral replication rates rather than with differences in selection on amino acid fixation. PMID:21135151

Edo-Matas, Diana; Lemey, Philippe; Tom, Jennifer A; Serna-Bolea, Cèlia; van den Blink, Agnes E; van 't Wout, Angélique B; Schuitemaker, Hanneke; Suchard, Marc A

2011-05-01

9

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

PubMed Central

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

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

2015-01-01

10

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

PubMed

The human angiotensin converting enzyme (ACE) gene is one of the most investigated candidate genes for cardiovascular diseases (CVD), but the understanding of its role among the elderly is vague. Therefore, this study focuses at: (a) testing the association of ACE polymorphism with CVD risk factors among the elderly, and (b) detecting the possible unequal distribution of ACE genotypes between senescent and younger segments of the European populations. The association of ACE I/D polymorphism with CVD health status [hypertension (HT), obesity, dislypidemia] in 301 very old subjects (88.2 ± 5 years; F/M = 221/80) was tested by means of logistic regression analysis. The meta-analysis of D allele frequency in general vs. elderly (80+ years) groups was conducted using all publicly available data for European populations comprising both age cohorts. Multiple multinomial logistic regression revealed that within this elderly sample, age (younger olds, 80-90 years), female sex (OR = 3.13, 95% CI = 1.59-6.19), and elevated triglycerides (OR = 2.53, 95% CI = 1.29-4.95) were positively associated with HT, while ACE polymorphism was not. It was also established that the DD genotype was twice as high in 80+ cohort compared to general population of Croatia (p < 0.00001). This trend was confirmed by the meta-analysis that showed higher D allele frequencies in olds from nine of ten considered European populations (OR = 1.19, 95% CI = 1.08-1.31). The data in elderly cohort do not confirm previously reported role of ACE DD genotype to the development of HT. Moreover, meta-analysis indicated that ACE D allele has some selective advantage that contributes to longevity in majority of European populations. PMID:21614448

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

2012-06-01

11

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

PubMed Central

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

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

2007-01-01

12

Diverging trends between heterozygosity and allelic richness during postglacial colonization in the European beech.  

PubMed

Variation at 12 polymorphic isozyme loci was studied in the European beech on the basis of an extensive sample of 389 populations distributed throughout the species range. Special emphasis was given to the analysis of the pattern of geographic variation on the basis of two contrasting measures of genetic diversity, gene diversity (H) and allelic richness, and to their relationship. Measures of allelic richness were corrected for variation in sample size by using the rarefaction method. As expected, maximum allelic richness was found in the southeastern part of the range (southern Italy and the Balkans), where beech was confined during the last ice age. Surprisingly, H was lower in refugia than in recently colonized regions, resulting in a negative correlation between the two diversity measures. The decrease of allelic richness and the simultaneous increase of H during postglacial recolonization was attributed to several processes that differentially affect the two diversity parameters, such as bottlenecks due to long-distance founding events, selection during population establishment, and increased gene flow at low population densities. PMID:11139519

Comps, B; Gömöry, D; Letouzey, J; Thiébaut, B; Petit, R J

2001-01-01

13

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

PubMed

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

Sala, A; Penacino, G; Corach, D

1998-10-01

14

A deletion in the chemokine receptor 5 (CCR5) gene is associated with tickborne encephalitis.  

PubMed

Tickborne encephalitis (TBE) virus infections can be asymptomatic or cause moderate to severe injuries of the central nervous system. Why some individuals develop severe disease is unknown, but a role for host genetic factors has been suggested. To investigate whether chemokine receptor CCR5 is associated with TBE, CCR5Delta32 genotyping was performed among Lithuanian patients with TBE (n=129) or with aseptic meningoencephalitis (n=76) as well as among control subjects (n=134). We found individuals homozygous for CCR5Delta32 (P= .026) only among patients with TBE and a higher allele prevalence among patients with TBE compared with the other groups studied. CCR5Delta32 allele prevalence also increased with the clinical severity of disease. PMID:18179389

Kindberg, Elin; Mickiene, Aukse; Ax, Cecilia; Akerlind, Britt; Vene, Sirkka; Lindquist, Lars; Lundkvist, Ake; Svensson, Lennart

2008-01-15

15

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

PubMed Central

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

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

16

Association of Autoimmune Addison's Disease with Alleles of STAT4 and GATA3 in European Cohorts  

PubMed Central

Background Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for. Aim To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts. Methods A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity. Results We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P?=?0.00016; rs10931481: P?=?0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-?B1 and IL23A genes in the UK and Italian cohorts respectively. Conclusions Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis. PMID:24614117

Mitchell, Anna L.; Macarthur, Katie D. R.; Gan, Earn H.; Baggott, Lucy E.; Wolff, Anette S. B.; Skinningsrud, Beate; Platt, Hazel; Short, Andrea; Lobell, Anna; Kämpe, Olle; Bensing, Sophie; Betterle, Corrado; Kasperlik-Zaluska, Anna; Zurawek, Magdalena; Fichna, Marta; Kockum, Ingrid; Nordling Eriksson, Gabriel; Ekwall, Olov; Wahlberg, Jeanette; Dahlqvist, Per; Hulting, Anna-Lena; Penna-Martinez, Marissa; Meyer, Gesine; Kahles, Heinrich; Badenhoop, Klaus; Hahner, Stephanie; Quinkler, Marcus; Falorni, Alberto; Phipps-Green, Amanda; Merriman, Tony R.; Ollier, William; Cordell, Heather J.; Undlien, Dag; Czarnocka, Barbara; Husebye, Eystein; Pearce, Simon H. S.

2014-01-01

17

HMW and LMW glutenin alleles among putative tetraploid and hexaploid European spelt wheat (Triticum spelta L.) progenitors.  

PubMed

The allelic compositions of high- and low-molecular-weight subunits of glutenins (HMW-GS and LMW-GS) among European spelt ( Triticum spelta L.) and related hexaploid and tetraploid Triticum species were investigated by one- and two-dimensional polyacrylamide-gel electrophoresis (PAGE) and capillary electrophoresis (CE). A total of seven novel glutenin alleles (designated A1a*, B1d*, B1g*, B1f*, B1j*, D1a* at Glu-1 and A3h at the Glu-3 loci, respectively) in European spelt wheat were detected by SDS-PAGE, which were confirmed further by employing A-PAGE and CE methods. Particularly, two HMW-GS alleles, Glu-B1d* coding the subunits 6.1 and 22.1, and Glu-B1f* coding the subunits 13 and 22*, were found to occur in European spelt with frequencies of 32.34% and 5.11%, respectively. These two alleles were present in cultivated emmer (Triticum dicoccum), but they were not observed in bread wheat (Triticum aestivum L.). The allele Glu-B1g* coding for 13* and 19* subunits found in spelt wheat was also detected in club wheat (Triticum compactum L.). Additionally, two alleles coding for LMW-GS, Glu-A3h and Glu-B3d, occurred with high frequencies in spelt, club and cultivated emmer wheat, whereas these were not found or present with very low frequencies in bread wheat. Our results strongly support the secondary origin hypothesis, namely European spelt wheat originated from hybridization between cultivated emmer and club wheat. This is also confirmed experimentally by the artificial synthesis of spelt through crossing between old European emmer wheat, T. dicoccum and club wheat, T. compactum. PMID:13679994

Yan, Y; Hsam, S L K; Yu, J Z; Jiang, Y; Ohtsuka, I; Zeller, F J

2003-11-01

18

HMW and LMW glutenin alleles among putative tetraploid and hexaploid European spelt wheat ( Triticum spelta L.) progenitors  

Microsoft Academic Search

The allelic compositions of high- and low-molecular-weight subunits of glutenins (HMW-GS and LMW-GS) among European spelt ( Triticum spelta L.) and related hexaploid and tetraploid Triticum species were investigated by one- and two-dimensional polyacrylamide-gel electrophoresis (PAGE) and capillary electrophoresis (CE). A total of seven novel glutenin alleles (designated A1a*, B1d*, B1g*, B1f*, B1j*, D1a* at Glu-1 and A3h at the

Y. Yan; S. L. K. Hsam; J. Z. Yu; Y. Jiang; I. Ohtsuka; F. J. Zeller

2003-01-01

19

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

PubMed Central

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

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

20

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

Microsoft Academic Search

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

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

21

The ITGAV rs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study  

PubMed Central

The integrin ?v?3, whose ?v subunit is encoded by the ITGAV gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the ITGAV gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the ITGAV gene for association and linkage to RA in a family-based study from the European Caucasian population. Two single nucleotide polymorphisms were genotyped by PCR-restriction fragment length polymorphism in 100 French Caucasian RA trio families (one RA patient and both parents), 100 other French families and 265 European families available for replication. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies (affected family-based controls), the transmission disequilibrium test, and the genotype relative risk. We observed a significant RA association for the C allele of rs3738919 in the first sample (affected family-based controls, RA index cases 66.5% versus controls 56.7%; P = 0.04). The second sample showed the same trend, and the third sample again showed a significant RA association. When all sets were combined, the association was confirmed (affected family-based controls, RA index cases 64.6% versus controls 58.1%; P = 0.005). The rs3738919-C allele was also linked to RA (transmission disequilibrium test, 56.5% versus50% of transmission; P = 0.009) and the C-allele-containing genotype was more frequent in RA index cases than in controls (RA index cases 372 versus controls 339; P = 0.002, odds ratio = 1.94, 95% confidence interval = 1.3–2.9). The rs3738919-C allele of the ITGAV gene is associated with RA in the European Caucasian population, suggesting ITGAV as a new minor RA susceptibility gene. PMID:17615072

Jacq, Laurent; Garnier, Sophie; Dieudé, Philippe; Michou, Laëtitia; Pierlot, Céline; Migliorini, Paola; Balsa, Alejandro; Westhovens, René; Barrera, Pilar; Alves, Helena; Vaz, Carlos; Fernandes, Manuela; Pascual-Salcedo, Dora; Bombardieri, Stefano; Dequeker, Jan; Radstake, Timothy R; Van Riel, Piet; van de Putte, Leo; Lopes-Vaz, Antonio; Glikmans, Elodie; Barbet, Sandra; Lasbleiz, Sandra; Lemaire, Isabelle; Quillet, Patrick; Hilliquin, Pascal; Teixeira, Vitor Hugo; Petit-Teixeira, Elisabeth; Mbarek, Hamdi; Prum, Bernard; Bardin, Thomas; Cornélis, François

2007-01-01

22

Unraveling Multiple MHC Gene Associations with Systemic Lupus Erythematosus: Model Choice Indicates a Role for HLA Alleles and Non-HLA Genes in Europeans  

PubMed Central

We have performed a meta-analysis of the major-histocompatibility-complex (MHC) region in systemic lupus erythematosus (SLE) to determine the association with both SNPs and classical human-leukocyte-antigen (HLA) alleles. More specifically, we combined results from six studies and well-known out-of-study control data sets, providing us with 3,701 independent SLE cases and 12,110 independent controls of European ancestry. This study used genotypes for 7,199 SNPs within the MHC region and for classical HLA alleles (typed and imputed). Our results from conditional analysis and model choice with the use of the Bayesian information criterion show that the best model for SLE association includes both classical loci (HLA-DRB1?03:01, HLA-DRB1?08:01, and HLA-DQA1?01:02) and two SNPs, rs8192591 (in class III and upstream of NOTCH4) and rs2246618 (MICB in class I). Our approach was to perform a stepwise search from multiple baseline models deduced from a priori evidence on HLA-DRB1 lupus-associated alleles, a stepwise regression on SNPs alone, and a stepwise regression on HLA alleles. With this approach, we were able to identify a model that was an overwhelmingly better fit to the data than one identified by simple stepwise regression either on SNPs alone (Bayes factor [BF] > 50) or on classical HLA alleles alone (BF > 1,000). PMID:23084292

Morris, David L.; Taylor, Kimberly E.; Fernando, Michelle M.A.; Nititham, Joanne; Alarcón-Riquelme, Marta E.; Barcellos, Lisa F.; Behrens, Timothy W.; Cotsapas, Chris; Gaffney, Patrick M.; Graham, Robert R.; Pons-Estel, Bernardo A.; Gregersen, Peter K.; Harley, John B.; Hauser, Stephen L.; Hom, Geoffrey; Langefeld, Carl D.; Noble, Janelle A.; Rioux, John D.; Seldin, Michael F.; Criswell, Lindsey A.; Vyse, Timothy J.

2012-01-01

23

Unraveling multiple MHC gene associations with systemic lupus erythematosus: model choice indicates a role for HLA alleles and non-HLA genes in Europeans.  

PubMed

We have performed a meta-analysis of the major-histocompatibility-complex (MHC) region in systemic lupus erythematosus (SLE) to determine the association with both SNPs and classical human-leukocyte-antigen (HLA) alleles. More specifically, we combined results from six studies and well-known out-of-study control data sets, providing us with 3,701 independent SLE cases and 12,110 independent controls of European ancestry. This study used genotypes for 7,199 SNPs within the MHC region and for classical HLA alleles (typed and imputed). Our results from conditional analysis and model choice with the use of the Bayesian information criterion show that the best model for SLE association includes both classical loci (HLA-DRB1(?)03:01, HLA-DRB1(?)08:01, and HLA-DQA1(?)01:02) and two SNPs, rs8192591 (in class III and upstream of NOTCH4) and rs2246618 (MICB in class I). Our approach was to perform a stepwise search from multiple baseline models deduced from a priori evidence on HLA-DRB1 lupus-associated alleles, a stepwise regression on SNPs alone, and a stepwise regression on HLA alleles. With this approach, we were able to identify a model that was an overwhelmingly better fit to the data than one identified by simple stepwise regression either on SNPs alone (Bayes factor [BF] > 50) or on classical HLA alleles alone (BF > 1,000). PMID:23084292

Morris, David L; Taylor, Kimberly E; Fernando, Michelle M A; Nititham, Joanne; Alarcón-Riquelme, Marta E; Barcellos, Lisa F; Behrens, Timothy W; Cotsapas, Chris; Gaffney, Patrick M; Graham, Robert R; Pons-Estel, Bernardo A; Gregersen, Peter K; Harley, John B; Hauser, Stephen L; Hom, Geoffrey; Langefeld, Carl D; Noble, Janelle A; Rioux, John D; Seldin, Michael F; Criswell, Lindsey A; Vyse, Timothy J

2012-11-01

24

Allelic differences between Europeans and Chinese for CREB1 SNPs and their implications in gene expression regulation, hippocampal structure and function, and bipolar disorder susceptibility.  

PubMed

Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64,888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P=6.32 × 10(-5), odds ratio (OR)=1.090). Risk SNPs were then subjected to further analyses in healthy Europeans for intermediate phenotypes of BD, including hippocampal volume, hippocampal function and cognitive performance. Our results showed that the risk SNPs were significantly associated with hippocampal volume and hippocampal function, with the risk alleles showing a decreased hippocampal volume and diminished activation of the left hippocampus, adding further evidence for their involvement in BD susceptibility. We also found the risk SNPs were strongly associated with CREB1 expression in lymphoblastoid cells (P<0.005) and the prefrontal cortex (P<1.0 × 10(-6)). Remarkably, population genetic analysis indicated that CREB1 displayed striking differences in allele frequencies between continental populations, and the risk alleles were completely absent in East Asian populations. We demonstrated that the regional prevalence of the CREB1 risk alleles in Europeans is likely caused by genetic hitchhiking due to natural selection acting on a nearby gene. Our results suggest that differential population histories due to natural selection on regional populations may lead to genetic heterogeneity of susceptibility to complex diseases, such as BD, and explain inconsistencies in detecting the genetic markers of these diseases among different ethnic populations. PMID:23568192

Li, M; Luo, X-J; Rietschel, M; Lewis, C M; Mattheisen, M; Müller-Myhsok, B; Jamain, S; Leboyer, M; Landén, M; Thompson, P M; Cichon, S; Nöthen, M M; Schulze, T G; Sullivan, P F; Bergen, S E; Donohoe, G; Morris, D W; Hargreaves, A; Gill, M; Corvin, A; Hultman, C; Toga, A W; Shi, L; Lin, Q; Shi, H; Gan, L; Meyer-Lindenberg, A; Czamara, D; Henry, C; Etain, B; Bis, J C; Ikram, M A; Fornage, M; Debette, S; Launer, L J; Seshadri, S; Erk, S; Walter, H; Heinz, A; Bellivier, F; Stein, J L; Medland, S E; Arias Vasquez, A; Hibar, D P; Franke, B; Martin, N G; Wright, M J; Su, B

2014-04-01

25

Allele-Level Haplotype Frequencies and Pairwise Linkage Disequilibrium for 14 KIR Loci in 506 European-American Individuals  

PubMed Central

The immune responses of natural killer cells are regulated, in part, by killer cell immunoglobulin-like receptors (KIR). The 16 closely-related genes in the KIR gene system have been diversified by gene duplication and unequal crossing over, thereby generating haplotypes with variation in gene copy number. Allelic variation also contributes to diversity within the complex. In this study, we estimated allele-level haplotype frequencies and pairwise linkage disequilibrium statistics for 14 KIR loci. The typing utilized multiple methodologies by four laboratories to provide at least 2x coverage for each allele. The computational methods generated maximum-likelihood estimates of allele-level haplotypes. Our results indicate the most extensive allele diversity was observed for the KIR framework genes and for the genes localized to the telomeric region of the KIR A haplotype. Particular alleles of the stimulatory loci appear to be nearly fixed on specific, common haplotypes while many of the less frequent alleles of the inhibitory loci appeared on multiple haplotypes, some with common haplotype structures. Haplotype structures cA01 and/or tA01 predominate in this cohort, as has been observed in most populations worldwide. Linkage disequilibrium is high within the centromeric and telomeric haplotype regions but not between them and is particularly strong between centromeric gene pairs KIR2DL5?KIR2DS3S5 and KIR2DS3S5?KIR2DL1, and telomeric KIR3DL1?KIR2DS4. Although 93% of the individuals have unique pairs of full-length allelic haplotypes, large genomic blocks sharing specific sets of alleles are seen in the most frequent haplotypes. These high-resolution, high-quality haplotypes extend our basic knowledge of the KIR gene system and may be used to support clinical studies beyond single gene analysis. PMID:23139747

Vierra-Green, Cynthia; Roe, David; Hou, Lihua; Hurley, Carolyn Katovich; Rajalingam, Raja; Reed, Elaine; Lebedeva, Tatiana; Yu, Neng; Stewart, Mary; Noreen, Harriet; Hollenbach, Jill A.; Guethlein, Lisbeth A.; Wang, Tao; Spellman, Stephen; Maiers, Martin

2012-01-01

26

Spelt-specific alleles in HMW glutenin genes from modern and historical European spelt ( Triticum spelta L.)  

Microsoft Academic Search

A partial promoter region of the high-molecular weight (HMW) glutenin genes was studied in two wheat specimens, a 300 year-old\\u000a spelt (Triticum spelta L.) and an approximately 250 year-old bread wheat (Triticum aestivum L.) from Switzerland. Sequences were compared to a recent Swiss landrace T. spelta ’Oberkulmer.’ The alleles from the historical bread wheat were most similar to those of

Robert H. E. Blatter; Stefanie Jacomet; Angela Schlumbaum

2002-01-01

27

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

PubMed Central

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

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

28

Ancient DNA analysis reveals high frequency of European lactase persistence allele (T-13910) in medieval central europe.  

PubMed

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

Krüttli, Annina; Bouwman, Abigail; Akgül, Gülfirde; Della Casa, Philippe; Rühli, Frank; Warinner, Christina

2014-01-01

29

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

PubMed Central

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

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

2014-01-01

30

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

was adopted in populations with preadaptive high LP allele frequencies. Analysis based on the conservation this experimental strategy, we have ob- tained high-confidence LP-associated genotypes from eight Neo- lithic

31

Analysis of FMR1 (CGG)(n) alleles and DXS548-FRAXAC1 haplotypes in three European circumpolar populations: traces of genetic relationship with Asia.  

PubMed

Fragile X syndrome, the most common form of inherited mental retardation, is caused by expansion of a (CGG)(n) repeat located in the FMR1 gene. The molecular factors involved in the mutation process from stable (CGG)(n) alleles towards unstable alleles are largely unknown, although family transmission studies and population studies have suggested that loss of AGG interruptions in the (CGG)(n) repeat is essential. We have analysed the AGG interspersion pattern of the FMR1 (CGG)(n) repeat and the haplotype distribution of closely located microsatellite markers DXS548 and FRAXAC1, in three circumarctic populations: Norwegians, Nenets and Saami. The data confirm the conservation, reported in all human populations studied so far, of an AGG interruption for each 9-10 CGG and support the stabilising effect of AGG interruptions. The data also indicate the existence of chromosomes of Asian origin in the Saami and Nenets population, thereby confirming a genetic relationship between Northern Europe and Asia. DXS548-FRAXAC1 haplotype frequencies were compared between 24 Norwegian fragile X males and 119 normal males. Significant linkage disequilibrium were found between the fragile X mutation and haplotype 6-4 and between normal (CGG)(n) alleles and haplotype 7-3. PMID:11571563

Larsen, L A; Vuust, J; Nystad, M; Evseeva, I; Van Ghelue, M; Tranebjaerg, L

2001-09-01

32

About the origin of European spelt ( Triticum spelta L.): allelic differentiation of the HMW Glutenin B1-1 and A1-2 subunit genes  

Microsoft Academic Search

To investigate the origin of European spelt (Triticum spelta L., genome AABBDD) and its relation to bread wheat (Triticum aestivum L., AABBDD), we analysed an approximately 1-kb sequence, including a part of the promoter and the coding region, of the high-molecular-weight (HMW) glutenin B1-1 and A1-2 subunit genes in 58 accessions of hexa- and tetraploid wheat from different geographical regions.

R. H. E. Blatter; S. Jacomet; A. Schlumbaum

2004-01-01

33

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

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

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

2013-01-01

34

Resolution of HLA-B*44:02:01G, -DRB1*14:01:01G and -DQB1*03:01:01G reveals a high allelic variability among 12 European populations.  

PubMed

Within the framework of the EU-funded HLA-NET action, an analysis of three G-group alleles, HLA-B*44:02:01G, DRB1*14:01:01G and DQB1*03:01:01G, was undertaken in 12 European populations. Ambiguities were resolved by polymerase chain reaction-sequence-specific amplification (PCR-SSP) or PCR-sequence-based typing (PCR-SBT) in a total of 5095 individuals. The results of the DRB1*14:01/14:54 ambiguity showed high relative ratios (24-53%) of DRB1*14:01 in Bulgarians, Croatians, Greeks, Italians and Slovenians, contrasting with low ratios (6-13%) in Austrians, Finnish, French, Hungarians, Norwegians and Swiss. Resolution of the B*44:02/44:27 ambiguity showed that B*44:27 had a high relative ratio in Slovenians (25.5%) and Bulgarians (37%) and low in French and Swiss (0.02-1%), and was not observed in Greeks and Italians. The highest relative ratio of DQB1*03:19 was found in Portuguese (11%), by contrast with low ratios (0-3%) in the other five populations. Analysis of the A, B, DRB1 phenotypes and family-derived haplotypes in 1719 and 403 individuals positive for either HLA-B*44:02G or DRB1*14:01G ambiguities, respectively, showed some preferential associations, such as A*26?DRB1*14:01, B*35?DRB1*14:01, B*38?DRB1*14:01 and B*44:27?DRB1*16. Because these ambiguities are located outside the peptide-binding site, they may not be recognized by alloreactive T-cells. However, because of strong linkage disequilibrium (LD), the DRB1*14:01 vs DRB1*14:54 and the B*44:02 vs B*44:27 mismatches are associated to DRB3-, and C-mismatches, respectively. These results are informative for algorithms searching unrelated hematopoietic stem cell donors. For B*44:27-positive patients, searches are expected to be more successful when requesting donors from Southeastern-European ancestry. Furthermore, the introduction of human leukocyte antigen (HLA)-typing strategies that allow resolving exon 4 (for class I) and exon 3 (for class II) polymorphisms can be expected to contribute significantly to population genetics studies. PMID:25209151

Vidan-Jeras, B; Buhler, S; Dubois, V; Grubic, Z; Ivanova, M; Jaatinen, T; Ligeiro, D; Lokki, M-L; Papasteriades, C; Poli, F; Spyropoulou-Vlachou, M; Tordai, A; Viken, M K; Wenda, S; Nunes, J M; Sanchez-Mazas, A; Tiercy, J-M

2014-11-01

35

Allelic loss in colorectal carcinoma  

SciTech Connect

Clinical and pathological associations with molecular genetic alterations were studied in colorectal carcinomas from 83 patients. Fractional allelic loss, a measure of allelic deletions throughout the genome, and allelic deletions of specific chromosomal arms (the short arm of 17 and long arm of 18) each provided independent prognostic information by multivariate analysis when considered individually with Dukes' classification. Distant metastasis was significantly associated with high fractional allelic loss and with deletions of 17p and 18q. Mutations of ras proto-oncogenes and deletions of 5q had no prognostic importance. Statistically significant associations were also found between allelic losses and a family history of cancer, left-sided tumor location, and absence of extracellular tumor mucin. Allelic deletion analysis thus identified subsets of colorectal carcinoma with increased predilection for distant metastasis and cancer-related death. Further studies may define a subset of genetic alterations that can be used clinically to help assess prognosis.

Kern, S.E.; Fearon, E.R.; Tersmette, K.W.F.; Enterline, J.P.; Vogelstein, B.; Hamilton, S.R. (Johns Hopkins Medical Institutions, Baltimore, MD (USA)); Leppert, M.; Nakamura, Yusuke; White, R. (Univ. of Utah School of Medicine, Salt Lake City (USA))

1989-06-02

36

[Alleles at storage protein loci in Triticum spelta L. accessions and their occurrence in related wheats].  

PubMed

Variation at eight storage protein loci was analyzed in the collection of T. spelta accessions from the National Centre of Plant Genetic Resources of Ukraine, most of which are European spelts. The analysis allowed identification of seven alleles at the Gli-B1 locus, five alleles at the Gli-A1 and Glu-B1 loci, three alleles at the Gli-A3 locus, two at the Gli-D1, Gli-B5, Glu-A1, and Glu-D1 loci. The majority of alleles are encountered among common wheat cultivars, only five alleles were specific for spelts. The high frequency of the alleles Gli-B1hs* and h encoding the 45-type gamma-gliadin in European spelts and durum wheat cultivars, as well as the occurrence of these alleles in T. dicoccum, in particular, in accessions from Switzerland and Germany, supports von Büren's hypothesis that European spelt resulted from hybridization between a tetraploid wheat with the 45-type y-gliadin and a hexaploid wheat. Analysis of genetic distances based on the genotypes at eight storage protein loci permitted differentiation of the Asian spelt accession from European spelts. PMID:24791472

Kozub, N A; Boguslavski?, R L; Sozinov, I A; Tverdokhleb, E V; Ksinias, I N; Blium, Ia B; Sozinov, A A

2014-01-01

37

Break zones in the distributions of alleles and species in alpine plants  

E-print Network

plants and species-based break zones in the silicicolous flora of the European Alps. We also ask whether such break zones coincide with areas of large elevational variation. Location The European Alps. Methods On a regular grid laid across the entire Alps, we determined areas of allele- and species-based break zones

38

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

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,

Lionel Garnery; Michel Solignac; Jean-Marie Cornuett

39

What Is a Recessive Allele?  

ERIC Educational Resources Information Center

Presents four misconceptions students have concerning the concepts of recessive and dominant alleles. Discusses the spectrum of dominant-recessive relationships, different levels of analysis between phenotype and genotype, possible causes of dominance, and an example involving wrinkled peas. (MDH)

American Biology Teacher, 1991

1991-01-01

40

?-5/?-3 nicotinic receptor subunit alleles increase risk for heavy smoking  

PubMed Central

Twin studies indicate that additive genetic effects explain most of the variance in nicotine dependence (ND), a construct emphasizing habitual heavy smoking despite adverse consequences, tolerance and withdrawal. To detect ND alleles, we assessed cigarettes per day (CPD) regularly smoked, in two European populations via whole genome association techniques. In these ?7500 persons, a common haplotype in the CHRNA3–CHRNA5 nicotinic receptor subunit gene cluster was associated with CPD (nominal P = 6.9 × 10?5). In a third set of European populations (n = ?7500) which had been genotyped for ?6000 SNPs in ?2000 genes, an allele in the same haplotype was associated with CPD (nominal P = 2.6 × 10?6). These results (in three independent populations of European origin, totaling ?15 000 individuals) suggest that a common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to ND. PMID:18227835

Berrettini, W; Yuan, X; Tozzi, F; Song, K; Francks, C; Chilcoat, H; Waterworth, D; Muglia, P; Mooser, V

2008-01-01

41

Evidence of Still-Ongoing Convergence Evolution of the Lactase Persistence T-13910 Alleles in Humans  

PubMed Central

A single-nucleotide variant, C/T-13910, located 14 kb upstream of the lactase gene (LCT), has been shown to be completely correlated with lactase persistence (LP) in northern Europeans. Here, we analyzed the background of the alleles carrying the critical variant in 1,611 DNA samples from 37 populations. Our data show that the T-13910 variant is found on two different, highly divergent haplotype backgrounds in the global populations. The first is the most common LP haplotype (LP H98) present in all populations analyzed, whereas the others (LP H8–H12), which originate from the same ancestral allelic haplotype, are found in geographically restricted populations living west of the Urals and north of the Caucasus. The global distribution pattern of LP T-13910 H98 supports the Caucasian origin of this allele. Age estimates based on different mathematical models show that the common LP T-13910 H98 allele (?5,000–12,000 years old) is relatively older than the other geographically restricted LP alleles (?1,400–3,000 years old). Our data about global allelic haplotypes of the lactose-tolerance variant imply that the T-13910 allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans. PMID:17701907

Enattah, Nabil Sabri ; Trudeau, Aimee ; Pimenoff, Ville ; Maiuri, Luigi ; Auricchio, Salvatore ; Greco, Luigi ; Rossi, Mauro ; Lentze, Michael ; Seo, J. K. ; Rahgozar, Soheila ; Khalil, Insaf ; Alifrangis, Michael ; Natah, Sirajedin ; Groop, Leif ; Shaat, Nael ; Kozlov, Andrew ; Verschubskaya, Galina ; Comas, David ; Bulayeva, Kazima ; Mehdi, S. Qasim ; Terwilliger, Joseph D. ; Sahi, Timo ; Savilahti, Erkki ; Perola, Markus ; Sajantila, Antti ; Järvelä, Irma ; Peltonen, Leena 

2007-01-01

42

Human acetylator polymorphism: estimate of allele frequency in Libya and details of global distribution.  

PubMed Central

Acetylator phenotyping by means of a sulphadimidine tests revealed 65% of Libyan Arabs to be slow acetylators. Hence the frequency of the allele controlling slow acetylation (As) is estimated as q = 0.81 +/- 0.05. This estimate is similar to those previously recorded in European and adjacent Middle Eastern populations. PMID:7328611

Karim, A K; Elfellah, M S; Evans, D A

1981-01-01

43

An historical perspective on "The world-wide distribution of allele frequencies at the human dopamine D4 receptor locus".  

PubMed

Human population genetics is a completely different science today compared to two decades ago, at least at the empiric level. Our paper [Chang (Hum Genet 98:91-101, 1996a)] demonstrated that three different alleles were common when one considered many populations although other low frequency alleles occurred. Because previous work had been largely done on European subjects, our findings involved 36 distinct populations and showed that East Asian populations had nearly lost the 7-repeat allele, and that Native American populations had the highest frequencies of that allele globally, was a significant early empiric demonstration of the potential magnitude of population variation at important genes. There are thousands of loci tested on many of the same populations and the gene frequency pattern seen for the DRD4 7-repeat allele is seen at other loci, arguing that this pattern commonly reflects the pattern of divergence of populations and accumulated random genetic drift. PMID:24162668

Kidd, Kenneth K; Pakstis, Andrew J; Yun, Libing

2014-04-01

44

Prevalence of HLA-DQA1 alleles and haplotypes in blood donors resident in Wales.  

PubMed

Two hundred and fifty-four normal blood donors, from a largely UK European population, were sequence-based typed for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1 and HLA-DQB1. The fit to Hardy-Weinberg expectations was good for all loci (all P values >0.5). Fifteen DQA1 alleles were identified to the second field. DQA1 carriage, allele and DQA1-DQB1 and DRB1-DQA1-DQB1 haplotype frequencies, linkage disequilibria and related values are presented. PMID:25345618

Lemin, A J; Darke, C

2014-12-01

45

Characterization of the treefrog null allele, 1991  

SciTech Connect

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.

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

1992-04-01

46

Characterization of the treefrog null allele  

SciTech Connect

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.

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

1990-12-01

47

Interethnic differences of CYP2C9 alleles in healthy Hungarian and Roma population samples: relationship to worldwide allelic frequencies.  

PubMed

CYP2C9 gene polymorphisms are widely studied in several ethnic groups, however they are less known in the Roma population. The aim of this work was to study the ethnic differences of the CYP2C9 allele distribution in a healthy Roma population in order to compare them with a healthy Hungarian population. A total of 535 Hungarian and 465 Roma volunteers were genotyped for the CYP2C9*2 (Arg144Cys) and CYP2C9*3 (Ile359Leu) allelic variants by PCR-RFLP assay. The frequencies of the CYP2C9*1, *2 and *3 alleles in the Hungarian population were 0.787, 0.125, and 0.088 and in Roma 0.727, 0.118, and 0.155, respectively. We found a significant difference in CYP2C9*3 prevalence between the Hungarian and Roma populations, which have therapeutic consequences (p<0.005). The distribution of *1/*1, *1/*2, *1/*3, *2/*2, *2/*3, and *3/*3 genotypes in Hungarians were 0.620, 0.195, 0.139, 0.021, 0.015, and 0.011, while in Roma were 0.533, 0.168, 0.219, 0.011, 0.047, and 0.022, respectively. A significant difference was found between the Hungarian and Roma populations regarding the *1/*1, *1/*3 and the *2/*3 (p<0.005) genotypes. This is the first study to investigate the polymorphisms of CYP2C9 gene in the two largest populations in Hungary, healthy Hungarians and Roma. The prevalence of variant CYP2C9 alleles in the Hungarian population is similar to that observed in other European populations. In contrast, the Roma population differs from Hungarians, from most of other Caucasian groups, and from Indians in the incidence of CYP2C9 common variants. The difference in allele distribution patterns between the two populations studied has therapeutic implications as it influences the optimization of therapies. PMID:19541511

Sipeky, Csilla; Lakner, Lilla; Szabo, Melinda; Takacs, Istvan; Tamasi, Viola; Polgar, Noemi; Falus, Andras; Melegh, Bela

2009-01-01

48

Are common disease susceptibility alleles the same in outbred and founder populations?  

PubMed

Founder populations have been the subjects of complex disease studies because of their decreased genetic heterogeneity, increased linkage disequilibrium and more homogeneous environmental exposures. However, it is possible that disease alleles identified in founder populations may not contribute significantly to susceptibility in outbred populations. In this study we examine the Hutterites, a founder population of European descent, for 103 polymorphisms in 66 genes that are candidates for cardiovascular or inflammatory diseases. We compare the frequencies of alleles at these loci in the Hutterites to their frequencies in outbred European-American populations and test for associations with cardiovascular disease-associated phenotypes in the Hutterites. We show that alleles at these loci are found at similar frequencies in the Hutterites and in outbred populations. In addition, we report associations between 39 alleles or haplotypes and cardiovascular disease phenotypes (P<0.05), with five loci remaining significant after adjusting for multiple comparisons. These data indicate that this founder population is informative and offers considerable advantages for genetic studies of common complex diseases. PMID:15100713

Newman, Dina L; Hoffjan, Sabine; Bourgain, Catherine; Abney, Mark; Nicolae, Raluca I; Profits, Elle T; Grow, Michael A; Walker, Karen; Steiner, Lori; Parry, Rodney; Reynolds, Rebecca; McPeek, Mary Sara; Cheng, Suzanne; Ober, Carole

2004-07-01

49

Alleles of keratin 1 in families and populations.  

PubMed

Keratin 1 is found in the upper layers of the epidermis, on the surface of endothelial cells and in the membrane of the neuroblastoma NMB7. It is important for the structural integrity of the skin, has been found to regulate the activity of kinases, such as protein kinase C (PKC) and SRC, to participate in complement activation by the lectin pathway and to be involved in fibrinolysis, angiogenesis and the response to oxidative stress. Studies of the polymorphisms of the Keratin 1 (KRT1) gene have been driven mostly by interest in its role in skin diseases. However, much of the KRT1 variation occurs in normal populations and is not associated with dermal pathology. In the present experiments, we have investigated the polymorphism of KRT1 genes by nucleotide sequencing in normal families and normal populations of European, African, Hispanic and Asian background. The frequencies of the KRT1 alleles were strikingly different in the four ethnic groups and most of the mutations resulted in amino acid substitutions, with only 3 out of 19 being synonymous. Analysis of selective neutrality by the Ewens-Watterson and Tajima D statistics showed that KRT1 allele homozygosity was decreased in three of the populations suggesting that KRT1 genes may be under the influence of balancing selection. It is possible that the role of KRT1 as a receptor, rather than its structural function in the epidermis, is what drives the selective forces that are apparent in the inheritance of this gene. PMID:23707441

Han, Mei; Fan, Lin; Qin, Zhiqiang; Lavingia, Bhavna; Stastny, Peter

2013-11-01

50

Initiation of allelic exclusion by stochastic interaction of Tcrb alleles with repressive nuclear compartments  

PubMed Central

Earlier studies of antigen-receptor loci implicated directed monoallelic association with peri-centromeric heterochromatin in the initiation or maintenance of allelic exclusion. Here we provide evidence for a fundamentally different basis for Tcrb allelic exclusion. Using 3D Immuno-FISH we found that germline Tcrb alleles associated stochastically and at high frequency with the nuclear lamina or with peri-centromeric heterochromatin in developing thymocytes, and that such interactions inhibited V?-to-D?J? recombination prior to ?-selection. Introduction of an ectopic enhancer into Tcrb reduced these interactions and impaired allelic exclusion. We propose that initial V?-to-D?J? recombination events are generally monoallelic in developing thymocytes due to frequent stochastic, rather than directed, interactions of Tcrb alleles with repressive nuclear compartments. Such interactions may be essential for Tcrb allelic exclusion. PMID:18536719

Schlimgen, Ryan J; Reddy, Karen L; Singh, Harinder; Krangel, Michael S

2008-01-01

51

Complex arylsulfatase A alleles causing metachromatic leukodystrophy.  

PubMed

Metachromatic leukodystrophy is a lysosomal storage disorder caused by the deficiency of arylsulfatase A. Sequencing of the arylsulfatase A genes of a patient affected with late infantile metachromatic leukodystrophy revealed that the patient is a compound heterozygote of two alleles carrying two deleterious mutation each. One allele bears a splice donor site mutation together with two polymorphisms and an additional missense mutation (Gly122 > Ser). The splice donor site mutation and the Gly122 > Ser substitution have been described recently but on different alleles. The other allele carries two missense mutations causing a Gly154 > Asp and a Pro167 > Arg substitution. When arylsulfatase A cDNAs carrying these mutations separately or in combination were transfected into baby hamster kidney cells expression of arylsulfatase A activity could not be detected. Linkage of mutations was verified by sequencing of the parental DNAs. Biosynthesis studies performed with the patients' fibroblasts show that the enzyme carrying both mutations is synthesized in almost normal amounts but is rapidly degraded in an early biosynthetic compartment. The occurence of two disease causing mutations on the same allele is a novel phenomenon in metachromatic leukodystrophy and as far as lysosomal storage diseases are concerned have so far only been described in Fabry disease and in the complex glucocerebrosidase alleles associated with Gaucher disease. PMID:7981715

Kappler, J; Sommerlade, H J; von Figura, K; Gieselmann, V

1994-01-01

52

Most parsimonious haplotype allele sharing determination  

PubMed Central

Background The "common disease – common variant" hypothesis and genome-wide association studies have achieved numerous successes in the last three years, particularly in genetic mapping in human diseases. Nevertheless, the power of the association study methods are still low, in particular on quantitative traits, and the description of the full allelic spectrum is deemed still far from reach. Given increasing density of single nucleotide polymorphisms available and suggested by the block-like structure of the human genome, a popular and prosperous strategy is to use haplotypes to try to capture the correlation structure of SNPs in regions of little recombination. The key to the success of this strategy is thus the ability to unambiguously determine the haplotype allele sharing status among the members. The association studies based on haplotype sharing status would have significantly reduced degrees of freedom and be able to capture the combined effects of tightly linked causal variants. Results For pedigree genotype datasets of medium density of SNPs, we present two methods for haplotype allele sharing status determination among the pedigree members. Extensive simulation study showed that both methods performed nearly perfectly on breakpoint discovery, mutation haplotype allele discovery, and shared chromosomal region discovery. Conclusion For pedigree genotype datasets, the haplotype allele sharing status among the members can be deterministically, efficiently, and accurately determined, even for very small pedigrees. Given their excellent performance, the presented haplotype allele sharing status determination programs can be useful in many downstream applications including haplotype based association studies. PMID:19379528

Cai, Zhipeng; Sabaa, Hadi; Wang, Yining; Goebel, Randy; Wang, Zhiquan; Xu, Jiaofen; Stothard, Paul; Lin, Guohui

2009-01-01

53

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

PubMed

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

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

2014-01-01

54

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

PubMed Central

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

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

2014-01-01

55

Description of a novel HLA-B35 (B*3514) allele found in a Mexican family of Nahua Aztec descent.  

PubMed

A new allele, HLA-B*3514, has been found in a Mexican family from Nahua descent. Its exon 2 is identical to that of B*3501 allele, but exon 3 bears a 3-base difference at codons 152 and 156, which results in Val-->Glu and Leu-->Trp changes, respectively, in the corresponding HLA molecule at the peptide-binding site. These substitutions may have originated from a DNA stretch donation from an allele belonging to the B15 group, enabling HLA-B*3514 to cope with the presentation of a new set of antigenic peptides. The high frequency of serologic B35 in Amerindians, together with the variety of B35 alleles detected by DNA sequencing in these populations, suggest that a frequent B35 subtype was present in the founder population and that several B35 subtypes may have been recently generated, probably due to the abrupt arrival of new pathogens following European invasions. PMID:8882414

Vargas-Alarcon, G; Martinez-Laso, J; Granados, J; Diaz-Campos, N; Alvarez, M; Gomez-Casado, E; Alcocer-Varela, J; Arnaiz-Villena, A

1996-02-01

56

Latitudinal variability of Drosophila melanogaster: Allozyme frequencies divergence between European and Afrotropical populations  

Microsoft Academic Search

Allelic frequencies at five polymorphic loci were determined in seven European and six Afrotropical populations of Drosophila melanogaster. African populations, which may be considered as ancestral for the species, showed a greater genetic diversity as measured by the number of alleles found. Within each geographic group (Europe or tropical Africa) genetic distances between local populations were very small (D=0.027). By

Jean R. David

1982-01-01

57

Functional analysis of 11 novel GBA alleles.  

PubMed

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

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

2014-04-01

58

Functional analysis of 11 novel GBA alleles  

PubMed Central

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

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

59

European Mistletoe  

MedlinePLUS

... for more information. European mistletoe is a semiparasitic plant that grows on several types of trees in ... and even death. American mistletoe is unsafe for medicinal use. In countries where commercial mistletoe is available ...

60

Demographic history and rare allele sharing among human populations.  

PubMed

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

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

61

Demographic history and rare allele sharing among human populations  

PubMed Central

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

Gravel, Simon; Henn, Brenna M.; Gutenkunst, Ryan N.; Indap, Amit R.; Marth, Gabor T.; Clark, Andrew G.; Yu, Fuli; Gibbs, Richard A.; Bustamante, Carlos D.; Altshuler, David L.; Durbin, Richard M.; Abecasis, Gonçalo R.; Bentley, David R.; Chakravarti, Aravinda; Clark, Andrew G.; Collins, Francis S.; De La Vega, Francisco M.; Donnelly, Peter; Egholm, Michael; Flicek, Paul; Gabriel, Stacey B.; Gibbs, Richard A.; Knoppers, Bartha M.; Lander, Eric S.; Lehrach, Hans; Mardis, Elaine R.; McVean, Gil A.; Nickerson, Debbie A.; Peltonen, Leena; Schafer, Alan J.; Sherry, Stephen T.; Wang, Jun; Wilson, Richard K.; Gibbs, Richard A.; Deiros, David; Metzker, Mike; Muzny, Donna; Reid, Jeff; Wheeler, David; Wang, Jun; Li, Jingxiang; Jian, Min; Li, Guoqing; Li, Ruiqiang; Liang, Huiqing; Tian, Geng; Wang, Bo; Wang, Jian; Wang, Wei; Yang, Huanming; Zhang, Xiuqing; Zheng, Huisong; Lander, Eric S.; Altshuler, David L.; Ambrogio, Lauren; Bloom, Toby; Cibulskis, Kristian; Fennell, Tim J.; Gabriel, Stacey B.; Jaffe, David B.; Shefler, Erica; Sougnez, Carrie L.; Bentley, David R.; Gormley, Niall; Humphray, Sean; Kingsbury, Zoya; Koko-Gonzales, Paula; Stone, Jennifer; McKernan, Kevin J.; Costa, Gina L.; Ichikawa, Jeffry K.; Lee, Clarence C.; Sudbrak, Ralf; Lehrach, Hans; Borodina, Tatiana A.; Dahl, Andreas; Davydov, Alexey N.; Marquardt, Peter; Mertes, Florian; Nietfeld, Wilfiried; Rosenstiel, Philip; Schreiber, Stefan; Soldatov, Aleksey V.; Timmermann, Bernd; Tolzmann, Marius; Egholm, Michael; Affourtit, Jason; Ashworth, Dana; Attiya, Said; Bachorski, Melissa; Buglione, Eli; Burke, Adam; Caprio, Amanda; Celone, Christopher; Clark, Shauna; Conners, David; Desany, Brian; Gu, Lisa; Guccione, Lorri; Kao, Kalvin; Kebbel, Andrew; Knowlton, Jennifer; Labrecque, Matthew; McDade, Louise; Mealmaker, Craig; Minderman, Melissa; Nawrocki, Anne; Niazi, Faheem; Pareja, Kristen; Ramenani, Ravi; Riches, David; Song, Wanmin; Turcotte, Cynthia; Wang, Shally; Mardis, Elaine R.; Wilson, Richard K.; Dooling, David; Fulton, Lucinda; Fulton, Robert; Weinstock, George; Durbin, Richard M.; Burton, John; Carter, David M.; Churcher, Carol; Coffey, Alison; Cox, Anthony; Palotie, Aarno; Quail, Michael; Skelly, Tom; Stalker, James; Swerdlow, Harold P.; Turner, Daniel; De Witte, Anniek; Giles, Shane; Gibbs, Richard A.; Wheeler, David; Bainbridge, Matthew; Challis, Danny; Sabo, Aniko; Yu, Fuli; Yu, Jin; Wang, Jun; Fang, Xiaodong; Guo, Xiaosen; Li, Ruiqiang; Li, Yingrui; Luo, Ruibang; Tai, Shuaishuai; Wu, Honglong; Zheng, Hancheng; Zheng, Xiaole; Zhou, Yan; Li, Guoqing; Wang, Jian; Yang, Huanming; Marth, Gabor T.; Garrison, Erik P.; Huang, Weichun; Indap, Amit; Kural, Deniz; Lee, Wan-Ping; Leong, Wen Fung; Quinlan, Aaron R.; Stewart, Chip; Stromberg, Michael P.; Ward, Alistair N.; Wu, Jiantao; Lee, Charles; Mills, Ryan E.; Shi, Xinghua; Daly, Mark J.; DePristo, Mark A.; Altshuler, David L.; Ball, Aaron D.; Banks, Eric; Bloom, Toby; Browning, Brian L.; Cibulskis, Kristian; Fennell, Tim J.; Garimella, Kiran V.; Grossman, Sharon R.; Handsaker, Robert E.; Hanna, Matt; Hartl, Chris; Jaffe, David B.; Kernytsky, Andrew M.; Korn, Joshua M.; Li, Heng; Maguire, Jared R.; McCarroll, Steven A.; McKenna, Aaron; Nemesh, James C.; Philippakis, Anthony A.; Poplin, Ryan E.; Price, Alkes; Rivas, Manuel A.; Sabeti, Pardis C.; Schaffner, Stephen F.; Shefler, Erica; Shlyakhter, Ilya A.; Cooper, David N.; Ball, Edward V.; Mort, Matthew; Phillips, Andrew D.; Stenson, Peter D.; Sebat, Jonathan; Makarov, Vladimir; Ye, Kenny; Yoon, Seungtai C.; Bustamante, Carlos D.; Clark, Andrew G.; Boyko, Adam; Degenhardt, Jeremiah; Gravel, Simon; Gutenkunst, Ryan N.; Kaganovich, Mark; Keinan, Alon; Lacroute, Phil; Ma, Xin; Reynolds, Andy; Clarke, Laura; Flicek, Paul; Cunningham, Fiona; Herrero, Javier; Keenen, Stephen; Kulesha, Eugene; Leinonen, Rasko; McLaren, William M.; Radhakrishnan, Rajesh; Smith, Richard E.; Zalunin, Vadim; Zheng-Bradley, Xiangqun; Korbel, Jan O.; Stütz, Adrian M.; Humphray, Sean; Bauer, Markus; Cheetham, R. Keira; Cox, Tony; Eberle, Michael; James, Terena; Kahn, Scott; Murray, Lisa; Chakravarti, Aravinda; Ye, Kai; De La Vega, Francisco M.; Fu, Yutao; Hyland, Fiona C. L.; Manning, Jonathan M.; McLaughlin, Stephen F.; Peckham, Heather E.; Sakarya, Onur; Sun, Yongming A.; Tsung, Eric F.; Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.; Sudbrak, Ralf; Albrecht, Marcus W.; Amstislavskiy, Vyacheslav S.; Herwig, Ralf; Parkhomchuk, Dimitri V.; Sherry, Stephen T.; Agarwala, Richa; Khouri, Hoda M.; Morgulis, Aleksandr O.; Paschall, Justin E.; Phan, Lon D.; Rotmistrovsky, Kirill E.; Sanders, Robert D.

2011-01-01

62

European Community.  

PubMed

The European Community was established in 1951 to reconcile France and Germany after World War II and to make possible the eventual federation of Europe. By 1986, there were 12 member countries: France, Italy, Belgium, the Federal Republic of Germany, Luxembourg, the Netherlands, Denmark, Ireland, the United Kingdom, Greece, Spain, and Portugal. Principal areas of concern are internal and external trade, agriculture, monetary coordination, fisheries, common industrial and commercial policies, assistance, science and research, and common social and regional policies. The European Community has a budget of US$34.035 billion/year, funded by customs duties and 1.4% of each member's value-added tax. The treaties establishing the European Community call for members to form a common market, a common customs tariff, and common agricultural, transport, economic, and nuclear policies. Major European Community institutions include the Commission, Council of Ministers, European Parliament, Court of Justice, and Economic and Social Committee. The Community is the world's largest trading unit, accounting for 15% of world trade. The 2 main goals of the Community's industrial policy are to create an open internal market and to promote technological innovation in order to improve international competitiveness. The European Community aims to contribute to the economic and social development of Third World countries as well. PMID:12177941

1987-05-01

63

Three allele combinations associated with Multiple Sclerosis  

PubMed Central

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

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

64

Evolutionary Dynamics of Sporophytic Self-Incompatibility Alleles in Plants  

PubMed Central

The stationary frequency distribution and allelic dynamics in finite populations are analyzed through stochastic simulations in three models of single-locus, multi-allelic sporophytic self-incompatibility. The models differ in the dominance relationships among alleles. In one model, alleles act codominantly in both pollen and style (SSIcod), in the second, alleles form a dominance hierarchy in pollen and style (SSIdom). In the third model, alleles interact codominantly in the style and form a dominance hierarchy in the pollen (SSIdomcod). The SSIcod model behaves similarly to the model of gametophytic self-incompatibility, but the selection intensity is stronger. With dominance, dominant alleles invade the population more easily than recessive alleles and have a lower frequency at equilibrium. In the SSIdom model, recessive alleles have both a higher allele frequency and higher expected life span. In the SSIdomcod model, however, loss due to drift occurs more easily for pollen-recessive than for pollen-dominant alleles, and therefore, dominant alleles have a higher expected life span than the more recessive alleles. The process of allelic turnover in the SSIdomcod and SSIdom models is closely approximated by a random walk on a dominance ladder. Implications of the results for experimental studies of sporophytic self-incompatibility in natural populations are discussed. PMID:9335618

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

1997-01-01

65

A SERIES OF FIVE MULTIPLE ALLELES1  

Microsoft Academic Search

In 1937 Boye and Rife (1) reported a single pair of alleles as being responsible for a solid purple leaf color versus pattern (brown or red area in central portion of upper epidermis of otherwise green leaves). Purple (P) is dominant to pattern (p). The difference between the solid green of the Golden Bedder variety and. pattern was likewise shown

DAVID C. RIFE

66

Tetrasomic segregation for multiple alleles in alfalfa.  

PubMed

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

Quiros, C F

1982-05-01

67

Estimation of Allele Frequencies at Isoloci  

PubMed Central

In some polyploid animals and plants, pairs of duplicated loci occur that share alleles encoding proteins with identical electrophoretic mobilities. Except in cases where these ``isoloci'' are known to be inherited tetrasomically, individual genotypes cannot be determined unambiguously, and there is no direct way to assign observed variation to a particular locus of the pair. For a pair of diallelic isoloci, nine genotypes are possible but only five phenotypes can be identified, corresponding to individuals with 0-4 doses of the variant allele. A maximum likelihood (ML) approach is used here to identify the set of allele frequencies (p, q) at the individual gene loci with the highest probability of producing the observed phenotypic distribution. A likelihood ratio test is used to generate the asymmetrical confidence intervals around ML estimates. Simulations indicate that the standard error of p is typically about twice the binomial sampling error associated with single locus allele frequency estimates. ML estimates can be used in standard indices of genetic diversity and differentiation and in goodness-of-fit tests of genetic hypotheses. The noncentral ?(2) distribution is used to evaluate the power of a test of apparent heterozygote deficiency that results from attributing all variation to one locus when both loci are polymorphic. PMID:3360307

Waples, R. S.

1988-01-01

68

Non-random Allelic Variation Natural Selection  

E-print Network

Non-random Allelic Variation AKA Natural Selection #12;Adaptation!Adaptation! #12;#12;Venus comb or ­ a feature that is maintained because of natural selection for its function preadaptation ­ a trait history #12;Natural Selection Evolution evolution is a two step process 1) origin of genetic variation 2

Houde, Peter

69

Comparing alleles between wild and domesticated tomato  

Technology Transfer Automated Retrieval System (TEKTRAN)

At the USDA, ARS Plant Genetic Resources Unit (PGRU), we conserve approximately 6,000 accessions of tomato (Solanum lycopersicum L.) and several hundred accessions of wild tomato species. Characterizing alleles in our collection will aid breeders and other researchers in using the germplasm. Domesti...

70

Development of microsatellite loci in the European Dipper, Cinclus cinclus  

Microsoft Academic Search

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.

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

2009-01-01

71

The Genetic Legacy of Paleolithic Homo sapiens sapiens in Extant Europeans: A Y Chromosome Perspective  

Microsoft Academic Search

A genetic perspective of human history in Europe was derived from 22 binary markers of the nonrecombining Y chromosome (NRY). Ten lineages account for >95% of the 1007 European Y chromosomes studied. Geographic distribution and age estimates of alleles are compatible with two Paleolithic and one Neolithic migratory episode that have contributed to the modern European gene pool. A significant

Ornella Semino; Giuseppe Passarino; Peter J. Oefner; Alice A. Lin; Svetlana Arbuzova; Lars E. Beckman; Giovanna De Benedictis; Paolo Francalacci; Anastasia Kouvatsi; Svetlana Limborska; Mladen Marcikiæ; Anna Mika; Barbara Mika; Dragan Primorac; A. Silvana Santachiara-Benerecetti; L. Luca Cavalli-Sforza; Peter A. Underhill

2000-01-01

72

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

PubMed Central

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

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

2015-01-01

73

Identification of the haplotype pattern associated with the mutant PKU allele in the Gypsy population of Wales.  

PubMed Central

Using the full length cDNA probe, the RFLP haplotype patterns at the phenylalanine hydroxylase locus have been studied in the extensive and highly consanguineous Welsh Gypsy population. The pattern associated with the mutant PKU allele is identical to haplotype 4 in the northern European population. Two children with classical PKU are homozygous for this haplotype. We have tracked the mutant allele through four generations to a great grandfather who died 22 years ago. Both affected children almost certainly have inherited a double dose of the same mutant PKU allele from one common ancestor. It should be possible to identify the specific mutation that is associated with haplotype 4 which results in the more serious form of PKU. PMID:2570158

Tyfield, L A; Meredith, A L; Osborn, M J; Harper, P S

1989-01-01

74

Role of GBSS allelic diversity in rice grain quality  

E-print Network

protein than those with the Wxb allele (Villareal and Juliano 1989). The Wxb allele is often found in the japonica subspecies of O. sativa, while Wxa is primarily found in the indica subspecies (Hirano and Sano 1991). Genotypes with the wx allele have...

Dobo, Macaire

2009-05-15

75

Mutant maize variety containing the glt1-1 allele  

DOEpatents

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.

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

1994-01-01

76

Mutant maize variety containing the glt1-1 allele  

DOEpatents

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.

Nelson, O.E.; Pan, D.

1994-07-19

77

Increasing long term response by selecting for favorable minor alleles  

Technology Transfer Automated Retrieval System (TEKTRAN)

Long-term response of genomic selection can be improved by considering allele frequencies of selected markers or quantitative trait loci (QTLs). A previous formula to weight allele frequency of favorable minor alleles was tested, and 2 new formulas were developed. The previous formula used nonlinear...

78

HLA-DRB1 Alleles Are Associated with the Susceptibility to Sporadic Parkinson’s Disease in Chinese Han Population  

PubMed Central

Immune disorders may play an important role in the pathogenesis of Parkinson's disease (PD). Recently, polymorphisms in the HLA-DR region have been found to be associated with sporadic PD in European ancestry populations. However, polymorphisms in the HLA complex are highly variable with ethnic and geographic origin. To explore the relationships between polymorphisms of the HLA-DR region and sporadic PD in Chinese Han population, we genotyped 567 sporadic PD patients and 746 healthy controls in two independent series for the HLA-DRB1 locus with Polymerase chain reaction-sequence based typing(PCR-SBT). The ?2 test was used to evaluate the distribution of allele frequencies between the patients and healthy controls. The impact of HLA-DRB1 alleles on PD risk was estimated by unconditional logistic regression. We found a significant higher frequency of HLA-DRB1*0301 in sporadic PD patients than in healthy controls and a positive association, which was independent of onset age, between HLA-DRB1*0301 and PD risk. Conversely, a lower frequency of HLA-DRB1*0406 was found in sporadic PD patients than in healthy controls, with a negative association between HLA-DRB1*0406 and PD risk. Furthermore, a meta-analysis involving 195205 individuals was conducted to summarize the frequencies of these two alleles in populations from various ethnic regions, we found a higher frequency of HLA-DRB1*0301, but a lower frequency of HLA-DRB1*0406 in European ancestry populations than that in Asians, this was consistent with the higher prevalence of sporadic PD in European ancestry populations. Based on these results, we speculate that HLA-DRB1 alleles are associated with the susceptibility to sporadic PD in Chinese Han population, among them HLA-DRB1*0301 is a risk allele while the effect of HLA-DRB1*0406 deserves debate. PMID:23139797

Sun, Congcong; Wei, Lei; Luo, Feifei; Li, Yi; Li, Jiaobiao; Zhu, Feiqi; Kang, Ping; Xu, Rensi; Xiao, LuLu; Liu, Zhuolin; Xu, Pingyi

2012-01-01

79

Allele frequencies of gene polymorphisms related to economic traits in Bos taurus and Bos indicus cattle breeds.  

PubMed

Allele frequencies of 10 representative polymorphisms for beef and milk traits were investigated for a total of 240 animals from Bos taurus and Bos indicus breeds, including two Japanese groups (Japanese Black and Japanese Brown), two East Asian groups (Korean and Mongolian), three European groups (Holstein, Angus and Hereford) and a Bos indicus group in South Asia (Myanmar, Laos and Cambodia). The Japanese Black revealed unique genetic construction in GH, FASN and SREBP-1 and the other Asian populations show intermediate frequencies between European and Japanese populations. The Bos indicus group showed low favorable allele frequencies in most of the genes. The study showed the variability and distribution of 10 genes affecting economic traits among world representative cattle breeds. The genetic information would contribute to elucidating the genetic background for worldwide cattle breeds and the possibility of improvement using the markers. PMID:22111625

Kaneda, Makoto; Lin, Bang Zhong; Sasazaki, Shinji; Oyama, Kenji; Mannen, Hideyuki

2011-12-01

80

Distribution of CYP2D6 Alleles and Phenotypes in the Brazilian Population  

PubMed Central

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

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

81

SIBLING family genes and bone mineral density: association and allele-specific expression in humans.  

PubMed

Osteoporosis is a common complex disorder with reduced bone mineral density (BMD) and increased susceptibility to fracture. Peak BMD is one of the primary determinants of osteoporotic fracture risk, and is under substantial genetic control. Extracellular matrix, a major component of the bone, influences BMD by regulating mineral deposition and maintaining cellular activity. It contains several SIBLING family proteins, null mutations of which cause mineralization defects in humans. In this study, we tested 59 single-nucleotide polymorphisms (SNPs) located in the 5 SIBLING family genes (DSPP, DMP1, IBSP, MEPE and SPP1) for association with normal variation in peak BMD in healthy men and women. We measured femoral neck (FN) and lumbar spine (LS) areal BMD by dual energy x-ray absorptiometry (DXA) in 1692 premenopausal European-American women, 512 premenopausal African-American women and 715 European-American men. SNPs were tested for association with FN and LS-BMD in the 3 subsamples. In the European-American women, we observed association (p?0.005) with LS-BMD for SNPs in DSPP, IBSP and MEPE, and for FN-BMD with SNPs in DMP1 and IBSP. Allele-specific regulation of gene expression (ASE) is an important mechanism in which an allele giving rise to modest influence in transcript abundance might result in a predisposition to disease. To identify whether there was ASE of SIBLING family genes at these SNPs, we examined 52 human bone samples obtained from the femoral neck during surgical hip replacement (27 female, 25 male; 44 European-American and 8 African-American). We observed unidirectional ASE for the IBSP gene, with lower expression of the G allele compared to the A allele for SNP rs17013181. Our data suggest that SNPs within the SIBLING genes may contribute to normal variation of peak BMD. Further studies are necessary to identify the functional variants and to determine the mechanisms underlying the differences in ASE and how these differences relate to the pathophysiology of osteoporosis. PMID:24747200

Alam, Imranul; Padgett, Leah R; Ichikawa, Shoji; Alkhouli, Mohammed; Koller, Daniel L; Lai, Dongbing; Peacock, Munro; Xuei, Xiaoling; Foroud, Tatiana; Edenberg, Howard J; Econs, Michael J

2014-07-01

82

Assignment of allelic configuration in polyploids using the MAC-PR (microsatellite DNA allele counting—peak ratios) method  

Microsoft Academic Search

Polysomic inheritance frequently results in the simultaneous occurrence of several microsatellite DNA alleles on a single locus. The MAC-PR (microsatellite DNA allele counting—peak ratios) method was recently developed for the analysis of polyploid plants and makes use of the quantitative values for microsatellite allele peak areas. To date, this approach has only been used in plants with known genetic relationships.

G. D. Esselink; H. Nybom; B. J. Vosman

2004-01-01

83

Allele frequencies of a SNP and a 27-bp deletion that are the determinant of earwax type in the ABCC11 gene  

Microsoft Academic Search

Allele frequencies for a SNP (rs17822931) and a 27-bp deletion that are the determinant of earwax type in the ABCC11 gene were investigated in seven Japanese, one Korean, and one German populations. The SNP will be useful as one of ancestry information markers, because it showed marked difference in frequencies between Asian and European populations.

Takashi Kitano; Isao Yuasa; Kentaro Yamazaki; Nori Nakayashiki; Aya Miyoshi; Kyung Sook Park; Kazuo Umetsu

2008-01-01

84

Allelic genealogies in sporophytic self-incompatibility systems in plants.  

PubMed Central

Expectations for the time scale and structure of allelic genealogies in finite populations are formed under three models of sporophytic self-incompatibility. The models differ in the dominance interactions among the alleles that determine the self-incompatibility phenotype: In the SSIcod model, alleles act codominantly in both pollen and style, in the SSIdom model, alleles form a dominance hierarchy, and in SSIdomcod, alleles are codominant in the style and show a dominance hierarchy in the pollen. Coalescence times of alleles rarely differ more than threefold from those under gametophytic self-incompatibility, and transspecific polymorphism is therefore expected to be equally common. The previously reported directional turnover process of alleles in the SSIdomcod model results in coalescence times lower and substitution rates higher than those in the other models. The SSIdom model assumes strong asymmetries in allelic action, and the most recessive extant allele is likely to be the most recent common ancestor. Despite these asymmetries, the expected shape of the allele genealogies does not deviate markedly from the shape of a neutral gene genealogy. The application of the results to sequence surveys of alleles, including interspecific comparisons, is discussed. PMID:9799270

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

1998-01-01

85

Several different lactase persistence associated alleles and high diversity of the lactase gene in the admixed Brazilian population.  

PubMed

Adult-type hypolactasia is a common phenotype caused by the lactase enzyme deficiency. The -13910 C>T polymorphism, located 14 Kb upstream of the lactase gene (LCT) in the MCM6 gene was associated with lactase persistence (LP) in Europeans. This polymorphism is rare in Africa but several other variants associated with lactase persistence were observed in Africans. The aims of this study were to identify polymorphisms in the MCM6 region associated with the lactase persistence phenotype and to determine the distribution of LCT gene haplotypes in 981 individuals from North, Northeast and South Brazil. These polymorphisms were genotyped by PCR based methods and sequencing. The -13779*C,-13910*T, -13937*A, -14010*C, -14011*T LP alleles previously described in the MCM6 gene region that acts as an enhancer for the LCT gene were identified in Brazilians. The most common LP allele was -13910*T. Its frequency was highly correlated with European ancestry in the Brazilian populations investigated. The -13910*T was higher (0.295) in southern Brazilians of European ancestry and lower (0.175) in the Northern admixed population. LCT haplotypes were derived from the 10 LCT SNPs genotyped. Overall twenty six haplotypes previously described were identified in the four Brazilian populations studied. The Multidimensional Scaling analysis showed that Belém, in the north, was closer to Amerindians. Northeastern and southern Afro-descendants were more related with Bantu-speaking South Africans whereas the Southern population with European ancestry grouped with Southern and Northern Europeans. This study shows a high variability considering the number of LCT haplotypes observed. Due to the highly admixed nature of the Brazilian populations, the diagnosis of hypolactasia in Brazil, based only in the investigation of the -13910*T allele is an oversimplification. PMID:23029545

Friedrich, Deise C; Santos, Sidney E B; Ribeiro-dos-Santos, Ândrea K C; Hutz, Mara H

2012-01-01

86

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).

87

Exquisite allele discrimination by toehold hairpin primers  

PubMed Central

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

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

2014-01-01

88

Cellular Adhesion Gene SELP Is Associated with Rheumatoid Arthritis and Displays Differential Allelic Expression  

PubMed Central

In rheumatoid arthritis (RA), a key event is infiltration of inflammatory immune cells into the synovial lining, possibly aggravated by dysregulation of cellular adhesion molecules. Therefore, single nucleotide polymorphisms of 14 genes involved in cellular adhesion processes (CAST, ITGA4, ITGB1, ITGB2, PECAM1, PTEN, PTPN11, PTPRC, PXN, SELE, SELP, SRC, TYK2, and VCAM1) were analyzed for association with RA. Association analysis was performed consecutively in three European RA family sample groups (Nfamilies?=?407). Additionally, we investigated differential allelic expression, a possible functional consequence of genetic variants. SELP (selectin P, CD62P) SNP-allele rs6136-T was associated with risk for RA in two RA family sample groups as well as in global analysis of all three groups (ptotal?=?0.003). This allele was also expressed preferentially (p<10?6) with a two- fold average increase in regulated samples. Differential expression is supported by data from Genevar MuTHER (p1?=?0.004; p2?=?0.0177). Evidence for influence of rs6136 on transcription factor binding was also found in silico and in public datasets reporting in vitro data. In summary, we found SELP rs6136-T to be associated with RA and with increased expression of SELP mRNA. SELP is located on the surface of endothelial cells and crucial for recruitment, adhesion, and migration of inflammatory cells into the joint. Genetically determined increased SELP expression levels might thus be a novel additional risk factor for RA. PMID:25147926

Petit-Teixeira, Elisabeth; Hugo Teixeira, Vitor; Steiner, Anke; Quente, Elfi; Wolfram, Grit; Scholz, Markus; Pierlot, Céline; Migliorini, Paola; Bombardieri, Stefano; Balsa, Alejandro; Westhovens, René; Barrera, Pilar; Radstake, Timothy R. D. J.; Alves, Helena; Bardin, Thomas; Prum, Bernard; Emmrich, Frank; Cornelis, François

2014-01-01

89

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

PubMed

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

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

2014-10-01

90

Frequencies of allele groups HLA-A, HLA-B and HLA-DRB1 in a population from the northwestern region of São Paulo State, Brazil.  

PubMed

The aim of this study was to estimate the HLA-A, HLA-B and HLA-DRB1 allele groups frequencies in a population of 1559 volunteer bone marrow donors from the northwestern region of São Paulo State grouped according to ethnicity. An additional objective was to compare the allele frequencies of the current study with data published for other Brazilian populations. The allele groups were characterized by the PCR-rSSO method using Luminex(®) technology. Twenty HLA-A, 32 HLA-B and 13 HLA-DRB1 allele groups were identified. The most common allele groups in European descent and mixed African and European descent samples were HLA-A*02, HLA-B*35 and HLA-DRB1*13, while HLA-A*02, HLA-B*35 and HLA-DRB1*11 were more common in African descent samples. The HLA-A*23, HLA-A*36, HLA-B*58 and HLA-B*81 allele groups were more common in sample from African descent than European descent, and the HLA-DRB1*08 was more common in mixed African and European descent than in European descent. Allele group frequencies were compared with samples from other Brazilian regions. The HLA-A*30 and HLA-A*23 were more common in this study than in the populations of Rio Grande do Sul and Paraná; and the HLA-A*01, HLA-B*18, HLA-B*57 and HLA-DRB1*11 were more common in this study than in the population of Piauí. The least frequent allele groups were HLA-A*31, HLA-B*15, HLA-B*40 and HLA-DRB1*08 for the population of Piauí, HLA-A*01 and HLA-A*11 for Parana, HLA-A*02 and -A*03 for Rio Grande do Sul and HLA-DRB1*04 for Paraná, Rio Grande do Sul and Piauí. These data provide an overview on the knowledge on HLA diversity in the population of the northwestern region of São Paulo State and show that the genes of this system are useful to distinguish different ethnic groups. PMID:25418108

Ayo, C M; da Silveira Camargo, A V; Xavier, D H; Batista, M F; Carneiro, O A; Brandão de Mattos, C C; Ricci, O; de Mattos, L C

2015-02-01

91

Black Europeans  

NSDL National Science Digital Library

The British Library has been producing quality online features for close to a decade now, and this latest offering is worth a close look. This particular feature offers some insights and commentary on five prominent black Europeans. It may even come as a surprise to some visitors that several of the individuals profiled were black, such as Alexandre Dumas, the celebrated author of The Three Musketeers. These profiles are supplemented with essays by Dr. Mike Phillips, a writer, scholar, and journalist. The essays are accompanied by a series of images, including engravings, portraits, and illustrations. Visitors may also want to view and print out extended versions of Phillipsâ?? essays, which are available here in the pdf format.

92

Allele-specific disparity in breast cancer  

PubMed Central

Background In a cancer cell the number of copies of a locus may vary due to amplification and deletion and these variations are denoted as copy number alterations (CNAs). We focus on the disparity of CNAs in tumour samples, which were compared to those in blood in order to identify the directional loss of heterozygosity. Methods We propose a numerical algorithm and apply it to data from the Illumina 109K-SNP array on 112 samples from breast cancer patients. B-allele frequency (BAF) and log R ratio (LRR) of Illumina were used to estimate Euclidian distances. For each locus, we compared genotypes in blood and tumour for subset of samples being heterozygous in blood. We identified loci showing preferential disparity from heterozygous toward either the A/B-allele homozygous (allelic disparity). The chi-squared and Cochran-Armitage trend tests were used to examine whether there is an association between high levels of disparity in single nucleotide polymorphisms (SNPs) and molecular, clinical and tumour-related parameters. To identify pathways and network functions over-represented within the resulting gene sets, we used Ingenuity Pathway Analysis (IPA). Results To identify loci with a high level of disparity, we selected SNPs 1) with a substantial degree of disparity and 2) with substantial frequency (at least 50% of the samples heterozygous for the respective locus). We report the overall difference in disparity in high-grade tumours compared to low-grade tumours (p-value < 0.001) and significant associations between disparity in multiple single loci and clinical parameters. The most significantly associated network functions within the genes represented in the loci of disparity were identified, including lipid metabolism, small-molecule biochemistry, and nervous system development and function. No evidence for over-representation of directional disparity in a list of stem cell genes was obtained, however genes appeared to be more often altered by deletion than by amplification. Conclusions Our data suggest that directional loss and amplification exist in breast cancer. These are highly associated with grade, which may indicate that they are enforced with increasing number of cell divisions. Whether there is selective pressure for some loci to be preferentially amplified or deleted remains to be confirmed. PMID:22188678

2011-01-01

93

Detection of Borrelia burgdorferi Sensu Stricto ospC Alleles Associated with Human Lyme Borreliosis Worldwide in Non-Human-Biting Tick Ixodes affinis and Rodent Hosts in Southeastern United States  

PubMed Central

Comparative analysis of ospC genes from 127 Borrelia burgdorferi sensu stricto strains collected in European and North American regions where Lyme disease is endemic and where it is not endemic revealed a close relatedness of geographically distinct populations. ospC alleles A, B, and L were detected on both continents in vectors and hosts, including humans. Six ospC alleles, A, B, L, Q, R, and V, were prevalent in Europe; 4 of them were detected in samples of human origin. Ten ospC alleles, A, B, D, E3, F, G, H, H3, I3, and M, were identified in the far-western United States. Four ospC alleles, B, G, H, and L, were abundant in the southeastern United States. Here we present the first expanded analysis of ospC alleles of B. burgdorferi strains from the southeastern United States with respect to their relatedness to strains from other North American and European localities. We demonstrate that ospC genotypes commonly associated with human Lyme disease in European and North American regions where the disease is endemic were detected in B. burgdorferi strains isolated from the non-human-biting tick Ixodes affinis and rodent hosts in the southeastern United States. We discovered that some ospC alleles previously known only from Europe are widely distributed in the southeastern United States, a finding that confirms the hypothesis of transoceanic migration of Borrelia species. PMID:23263953

Golovchenko, Maryna; Hönig, Václav; Mallátová, Nadja; Krbková, Lenka; Mikulášek, Peter; Fedorova, Natalia; Belfiore, Natalia M.; Grubhoffer, Libor; Lane, Robert S.; Oliver, James H.

2013-01-01

94

Allele Interaction – Single Locus Genetics Meets Regulatory Biology  

PubMed Central

Background Since the dawn of genetics, additive and dominant gene action in diploids have been defined by comparison of heterozygote and homozygote phenotypes. However, these definitions provide little insight into the underlying intralocus allelic functional dependency and thus cannot serve directly as a mediator between genetics theory and regulatory biology, a link that is sorely needed. Methodology/Principal Findings We provide such a link by distinguishing between positive, negative and zero allele interaction at the genotype level. First, these distinctions disclose that a biallelic locus can display 18 qualitatively different allele interaction sign motifs (triplets of +, – and 0). Second, we show that for a single locus, Mendelian dominance is not related to heterozygote allele interaction alone, but is actually a function of the degrees of allele interaction in all the three genotypes. Third, we demonstrate how the allele interaction in each genotype is directly quantifiable in gene regulatory models, and that there is a unique, one-to-one correspondence between the sign of autoregulatory feedback loops and the sign of the allele interactions. Conclusion/Significance The concept of allele interaction refines single locus genetics substantially, and it provides a direct link between classical models of gene action and gene regulatory biology. Together with available empirical data, our results indicate that allele interaction can be exploited experimentally to identify and explain intricate intra- and inter-locus feedback relationships in eukaryotes. PMID:20186347

Gjuvsland, Arne B.; Plahte, Erik; Ådnøy, Tormod; Omholt, Stig W.

2010-01-01

95

Nomenclature for human CYP2D6 alleles.  

PubMed

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

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

96

Predicting HLA alleles from high-resolution SNP data in three Southeast Asian populations.  

PubMed

The major histocompatibility complex (MHC) containing the classical human leukocyte antigen (HLA) Class I and Class II genes is among the most polymorphic and diverse regions in the human genome. Despite the clinical importance of identifying the HLA types, very few databases jointly characterize densely genotyped single nucleotide polymorphisms (SNPs) and HLA alleles in the same samples. To date, the HapMap presents the only public resource that provides a SNP reference panel for predicting HLA alleles, constructed with four collections of individuals of north-western European, northern Han Chinese, cosmopolitan Japanese and Yoruba Nigerian ancestry. Owing to complex patterns of linkage disequilibrium in this region, it is unclear whether the HapMap reference panels can be appropriately utilized for other populations. Here, we describe a public resource for the Singapore Genome Variation Project with: (i) dense genotyping across ? 9000 SNPs in the MHC; (ii) four-digit HLA typing for eight Class I and Class II loci, in 96 southern Han Chinese, 89 Southeast Asian Malays and 83 Tamil Indians. This resource provides population estimates of the frequencies of HLA alleles at these eight loci in the three population groups, particularly for HLA-DPA1 and HLA-DPB1 that were not assayed in HapMap. Comparing between population-specific reference panels and a cosmopolitan panel created from all four HapMap populations, we demonstrate that more accurate imputation is obtained with population-specific panels than with the cosmopolitan panel, especially for the Malays and Indians but even when imputing between northern and southern Han Chinese. As with SNP imputation, common HLA alleles were imputed with greater accuracy than low-frequency variants. PMID:24698974

Pillai, Nisha Esakimuthu; Okada, Yukinori; Saw, Woei-Yuh; Ong, Rick Twee-Hee; Wang, Xu; Tantoso, Erwin; Xu, Wenting; Peterson, Trevor A; Bielawny, Thomas; Ali, Mohammad; Tay, Koon-Yong; Poh, Wan-Ting; Tan, Linda Wei-Lin; Koo, Seok-Hwee; Lim, Wei-Yen; Soong, Richie; Wenk, Markus; Raychaudhuri, Soumya; Little, Peter; Plummer, Francis A; Lee, Edmund J D; Chia, Kee-Seng; Luo, Ma; De Bakker, Paul I W; Teo, Yik-Ying

2014-08-15

97

Four novel PEPD alleles causing prolidase deficiency  

SciTech Connect

Mutations at the PEPD locus cause prolidase (an enzyme specific for proline- and hydroxyproline-terminated dipeptides) deficiency (McKusick 170100), a rare autosomal recessive disorder characterized by iminodipeptiduria, skin ulcers, mental retardation, and recurrent infections. Four PEPD mutations from five severely affected individuals were characterized by analysis of reverse-transcribed, PCR-amplified (RT-PCR) cDNA. The authors used SSCP analysis on four overlapping cDNA fragments covering the entire coding region of the PEPD gene and detected abnormal SSCP bands for the fragments spanning all or part of exons 13-15 in three of the probands. Direct sequencing of the mutant cDNAs showed a G[yields]A, 1342 substitution (G448R) in two patients and a 3-bp deletion ([Delta]E452 or [Delta]E453) in another. In the other two probands the amplified products were of reduced size. Direct sequencing of these mutant cDNAs revealed a deletion of exon 5 in one patient and of exon 7 in the other. Intronic sequences flanking exons 5 and 7 were identified using inverse PCR followed by direct sequencing. Conventional PCR and direct sequencing then established the intron-exon borders of the mutant genomic DNA revealing two splice acceptor mutations: a G[yields]C substitution at position -1 of intron 4 and an A[yields]G substitution at position -2 of intron 6. The results indicate that the severe form of prolidase deficiency is caused by multiple PEPD alleles. In this report the authors attempt to begin the process of describing these alleles and cataloging their phenotype expression. 31 refs., 8 figs., 2 tabs.

Ledoux, P.; Scriver, C.; Hechtman, P. (McGill Univ., Montreal (Canada))

1994-06-01

98

European Space Agency European Space Exploration  

E-print Network

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

Crawford, Ian

99

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.

100

Polymorphic microsatellites identified by cross-species amplifications in the European Coot Fulica atra  

Microsoft Academic Search

We tested the cross-amplification of 26 microsatellites developed for passerines and an additional three developed for Gallinula species in eight European Coots from two populations. Sixteen microsatellite markers successfully amplified, of which nine\\u000a were polymorphic with 2–6 alleles (mean 3.7 alleles) and an expected heterozygosity (H\\u000a e) ranging from 0.375 to 0.805 (mean H\\u000a e = 0.589). On average, we found 2.22 alleles\\/locus

Adeline Loyau; Dirk S. Schmeller

2009-01-01

101

POPULATION DYNAMICS OF SEX-DETERMINING ALLELES IN HONEY BEES AND SELF-INCOMPATIBILITY ALLELES IN PLANTS  

Microsoft Academic Search

Mathematical theories of the population dynamics of sex-determining alleles in honey bees are developed. It is shown that in an infinitely large population the equilibrium frequency of a sex allele is l\\/n, where n is the number of alleles in the population, and the asymptotic rate of approach to this equilibrium is 2\\/(3n) per generation. Formulae for the distribution of

SHOZO YOKOYAMA; MASATOSHI NET

102

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

PubMed

Genotyping of polymorphic short tandem repeats (STRs) loci is widely used in forensic DNA analysis. STR loci eventually present tri-allelic pattern as a genotyping irregularity and, in that situation, the doubt about the tri-allele locus frequency calculation can reduce the analysis strength. In the TPOX human STR locus, tri-allelic genotypes have been reported with a widely varied frequency among human populations. We investigate whether there is a single extra allele (the third allele) in the TPOX tri-allelic pattern, what it is, and where it is, aiming to understand its genomic anatomy and to propose the knowledge of this TPOX extra allele from genetic profile, thus preserving the two standard TPOX alleles in forensic analyses. We looked for TPOX tri-allelic subjects in 75,113 Brazilian families. Considering only the parental generation (mother+father) we had 150,226 unrelated subjects evaluated. From this total, we found 88 unrelated subjects with tri-allelic pattern in the TPOX locus (0.06%; 88/150,226). Seventy three of these 88 subjects (73/88; 83%) had the Clayton's original Type 2 tri-allelic pattern (three peaks of even intensity). The remaining 17% (15/88) show a new Type 2 derived category with heterozygote peak imbalance (one double dose peak plus one regular sized peak). In this paper we present detailed data from 66 trios (mother+father+child) with true biological relationships. In 39 of these families (39/66; 59%) the extra TPOX allele was transmitted either from the mother or from the father to the child. Evidences indicated the allele 10 as the extra TPOX allele, and it is on the X chromosome. The present data, which support the previous Lane hypothesis, improve the knowledge about tri-allelic pattern of TPOX CODIS' locus allowing the use of TPOX profile in forensic analyses even when with tri-allelic pattern. This evaluation is now available for different forensic applications. PMID:25549886

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

2015-05-01

103

B-Complex Alleles Immunity to Salmonella enteritidis in Chickens  

Microsoft Academic Search

Six experiments were conducted during which a total of 12 congenic lines homozygous for various B-complex alleles, were challenged by intraperitone al injection with either of two isolates of Salmonella enteritidis. Because these B alleles were expressed on a common genetic background and mortality differences among lines were statistically significant in three of the six trials and morbidity (body weight)

E. S. Soliman; P. G. Reddy; R. Nimmanapel; E. M. Abouelhass

2009-01-01

104

Rescue of Progeria in Trichothiodystrophy by Homozygous Lethal Xpd Alleles  

PubMed Central

Although compound heterozygosity, or the presence of two different mutant alleles of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been well documented. This is most likely because of the inherent difficulty in distinguishing specific biallelic effects from differences in environment or genetic background. We addressed the potential of different recessive alleles to contribute to the enigmatic pleiotropy associated with XPD recessive disorders in compound heterozygous mouse models. Alterations in this essential helicase, with functions in both DNA repair and basal transcription, result in diverse pathologies ranging from elevated UV sensitivity and cancer predisposition to accelerated segmental progeria. We report a variety of biallelic effects on organismal phenotype attributable to combinations of recessive Xpd alleles, including the following: (i) the ability of homozygous lethal Xpd alleles to ameliorate a variety of disease symptoms when their essential basal transcription function is supplied by a different disease-causing allele, (ii) differential developmental and tissue-specific functions of distinct Xpd allele products, and (iii) interallelic complementation, a phenomenon rarely reported at clinically relevant loci in mammals. Our data suggest a re-evaluation of the contribution of “null” alleles to XPD disorders and highlight the potential of combinations of recessive alleles to affect both normal and pathological phenotypic plasticity in mammals. PMID:17020410

Andressoo, Jaan-Olle; Jans, Judith; de Wit, Jan; Coin, Frederic; Hoogstraten, Deborah; van de Ven, Marieke; Toussaint, Wendy; Huijmans, Jan; Thio, H. Bing; van Leeuwen, Wibeke J; de Boer, Jan; Egly, Jean-Marc; Hoeijmakers, Jan H. J; van der Horst, Gijsbertus T. J; Mitchell, James R

2006-01-01

105

Substitution Processes in Molecular Evolution. 111. Deleterious Alleles  

Microsoft Academic Search

The substitution processes for various models of deleterious alleles are examined using computer simulations and mathematical analyses. Most of the work focuses on the house-ofcards model, which is a popular model of deleterious allele evolution. The rate of substitution is shown to be a concave function of the strength of selection as measured by a = 2Nu, where N is

John H. Gillespie

1994-01-01

106

Rescue of Progeria in Trichothiodystrophy by Homozygous Lethal Xpd Alleles  

E-print Network

of the same gene, is common in human recessive disease, its potential to impact disease outcome has not been of different recessive alleles to contribute to the enigmatic pleiotropy associated with XPD recessive effects on organismal phenotype attributable to combinations of recessive Xpd alleles, including

Boyer, Edmond

107

Allele diversity and germline mutation at the insulin minisatellite  

Microsoft Academic Search

Previous analysis of germline mutation at highly unstable GC-rich minisatellites with continuous allele size distributions revealed similar meiotic recombinational mechanisms operating at all loci investigated. The insulin minisatellite has been studied intensively due to its associations with diabetes, polycystic ovary syn- drome, obesity and birth size. Its bimodal allele size distribution in Caucasians suggests a much lower muta- tion rate

John D. H. Stead; Alec J. Jeffreys

2000-01-01

108

Molecular inversion probe assay for allelic quantitation  

PubMed Central

Molecular inversion probe (MIP) technology has been demonstrated to be a robust platform for large-scale dual genotyping and copy number analysis. Applications in human genomic and genetic studies include the possibility of running dual germline genotyping and combined copy number variation ascertainment. MIPs analyze large numbers of specific genetic target sequences in parallel, relying on interrogation of a barcode tag, rather than direct hybridization of genomic DNA to an array. The MIP approach does not replace, but is complementary to many of the copy number technologies being performed today. Some specific advantages of MIP technology include: Less DNA required (37 ng vs. 250 ng), DNA quality less important, more dynamic range (amplifications detected up to copy number 60), allele specific information “cleaner” (less SNP crosstalk/contamination), and quality of markers better (fewer individual MIPs versus SNPs needed to identify copy number changes). MIPs can be considered a candidate gene (targeted whole genome) approach and can find specific areas of interest that otherwise may be missed with other methods. PMID:19488872

Ji, Hanlee; Welch, Katrina

2010-01-01

109

MicroRNA-3148 modulates allelic expression of toll-like receptor 7 variant associated with systemic lupus erythematosus.  

PubMed

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 (R(2)?=?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

Deng, Yun; Zhao, Jian; 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

110

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

PubMed Central

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

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

111

CGG allele size somatic mosaicism and methylation in FMR1 premutation alleles  

PubMed Central

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

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

112

Heteroduplex molecules formed between allelic sequences cause nonparental RAPD bands.  

PubMed Central

Primers (10-mers) of random sequence were used to amplify RAPD bands from genomic DNA of an F1 strain of flax rust (Melampsora lini) and its two parent strains. One primer out of 160 tested was unusual in that it amplified a product from F1 DNA that was not amplified from either parental DNAs. The same primer also generated two RAPD bands that segregated as codominant alleles amongst F2 progeny. The nonparental band was only generated from DNAs of F2 individuals that were heterozygous for these two allelic sequences. Sequence analysis of the two RAPD alleles demonstrated greater than 99% sequence identity, although the larger allele possessed an additional 38bp relative to the smaller. Mixing of the two allelic sequences followed by denaturation and annealing in the absence of polymerase activity resulted in the formation of the nonparental band. Thus the nonparental band present in some RAPD reactions consisted of a heteroduplex molecule formed between two allelic sequences of different size. These data demonstrate that heteroduplex molecules formed between allelic RAPD products are a potential source of artifactual polymorphism that can arise during RAPD analysis. Images PMID:8202363

Ayliffe, M A; Lawrence, G J; Ellis, J G; Pryor, A J

1994-01-01

113

Allelic Diversity and Its Implications for the Rate of Adaptation  

PubMed Central

Genetic variation is usually estimated empirically from statistics based on population gene frequencies, but alternative statistics based on allelic diversity (number of allelic types) can provide complementary information. There is a lack of knowledge, however, on the evolutionary implications attached to allelic-diversity measures, particularly in structured populations. In this article we simulated multiple scenarios of single and structured populations in which a quantitative trait subject to stabilizing selection is adapted to different fitness optima. By forcing a global change in the optima we evaluated which diversity variables are more strongly correlated with both short- and long-term adaptation to the new optima. We found that quantitative genetic variance components for the trait and gene-frequency-diversity measures are generally more strongly correlated with short-term response to selection, whereas allelic-diversity measures are more correlated with long-term and total response to selection. Thus, allelic-diversity variables are better predictors of long-term adaptation than gene-frequency variables. This observation is also extended to unlinked neutral markers as a result of the information they convey on the demographic population history. Diffusion approximations for the allelic-diversity measures in a finite island model under the infinite-allele neutral mutation model are also provided. PMID:24121776

Caballero, Armando; García-Dorado, Aurora

2013-01-01

114

Allelic variation and environmental lead exposure in urban children.  

PubMed

The advent of the Human Genome Project has allowed for increased understanding and sophistication in diagnosis, treatment methods, and overall care planning on the part of healthcare providers for children with genetic disorders. Genetics research dealing with polymorphic changes within a genome has opened the door to awareness of how dormant genetic alleles may become active when coupled with certain environmental insults. Such genetic aberrations may place a child at a higher risk for health disparities when exposed to environmental toxins. It has been posited that such exposure in children with an arylsulfatase-A (ASA) allelic variation is associated with increased risk for neurodevelopmental damage. This initial study contributes to this new field and supports development of finer-tuned methods to prevent ominous outcomes of lead exposure. The purpose of this study was to explore the incidence of children in a representative sample from a Midwest metropolitan city with positive test results for the ASA allelic variation who have been exposed to the environmental toxin lead. In this corollary study of 107 children, part of a parent study on the behavior of African American children prenatally exposed to cocaine, 45% were found to be heterozygous, 11% mutant homozygous, and 44% normal in terms of ASA allele or alleles. Further studies on neurodeficiencies, low-level exposure to environmental toxins, and allelic variations must be conducted before a relation between ASA allelic variance and environmental lead can be determined. PMID:12473917

Long, Jacquelyn; Covington, Chandice; Delaney-Black, Virginia; Nordstrom, Beth

2002-11-01

115

Allele frequencies of six STR loci in Argentine populations.  

PubMed

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

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

1999-11-01

116

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

PubMed

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

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

117

[Polymorphism of human HLA-DRB1 leukocyte antigen alleles and its association to juvenile rheumatoid arthritis in a sample of Colombian mestizo children].  

PubMed

Oligotypes of the human leukocyte antigen HLA Class II, DRB1 alleles were characterized at the molecular level in a group of Colombian children suffering juvenile rheumatoid arthritis (JRA). The distribution of these alleles was examined in a group of Colombian mestizo children (genetic admixture of Amerindians, Europeans and Africans) suffering from clinically distinct JRA subsets in order to detect HLA allele frequency differences in patients with different JRA subsets. A group of 65 patients with JRA and 65 controls were characterized for the subtypes of the HLA-DRB1 alleles using polymerase chain reaction with sequence-specific oligonucleotide probes (PCR-SSOP). The oligotyping protocol recommended by the 12th International Histocompatibility Workshop held in St. Malo, Paris, in 1996, was used. Subtype HLA-DRB1*1104 was the allele most strongly associated with susceptibility to JRA (Fisher's p = 0.013, odds ratio (OR) = 16.79, etiologic fraction (EF) = 0.93). HLA-DRB1*1602 was also associated with susceptibility to a lesser degree (Fisher's p = 0.016, OR = 8.98, EF = 0.88). HLA-DRB1 alleles participating in JRA protection were HLA-DRB1*1501 (preventive fraction (PF) = 0.466, p = 0.005) and HLA DRB1*1402 (PF = 0.49, p = 0.009). The relationship between some HLA-DRB1 alleles and clinical features was also compared. The presence of rheumatic factor was associated with the alleles HLA-DRB1*0407 (p = 0.05, OR = 11.2, EF = 0.45) and HLA-DRB1*1302 (p = 0.02, OR = 22.8, EF = 0.63). There was also an association between HLA-DRB1*0701 (p = 0.001, OR = 58, EF = 0.73) with expressing ANA +. We found that in the oligoarticular subset, the allele HLA-DRB1*1104 (p = 0.0034, OR = 41.53, EF = 0.97) was the one expressed most commonly. In the poliarticular group, the alleles most frequently expressed were HLA-DRB1*0404 (Fisher's p = 0.012, OR = 8.75, EF = 0.88). In patients with systemic JRA, the HLA-DRB1*1602 allele (p = 0.005, OR = 21.33, EF = 0.95) was most frequent. These results suggested that the MHC genes of mestizo children influence not only the clinical expression of the disease, but also the susceptibility to its development. PMID:14582328

Garavito, Gloria; Malagón, Clara; Ramírez, Luis A; De La Cruz, Oscar F; Uribe, Oscar; Navarro, Edgar; Iglesias, Antonio; Martínez, Paz; Jaraquemada, Dolores; Egea, Eduardo

2003-09-01

118

Uneven segregation of sporophytic self-incompatibility alleles in Arabidopsis lyrata  

Microsoft Academic Search

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.

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

2004-01-01

119

Hidden Alleles at the ?-Glycerophosphate Dehydrogenase Locus in Colias Butterflies  

PubMed Central

By varying polyacrylamide gel pore size, the ?-glycerophosphate dehydrogenase locus of Colias butterflies is shown to contain at least five alleles, rather than the two which had been reported previously. Two of the alleles have the same apparent net charge, and presumably are detected electrophoretically because of conformational differences. Additional variation occurs in the isoelectric points of the proteins. It is suggested that electrophoresis employing a single gel of intermediate pore size will fail to discriminate between many alleles, and that the concept of electrophoretic alleles as differing simply in charge may not always be appropriate. "How does one know what it is one believes When it's so difficult to know what it is one knows?" —Jumpers (Stoppard, 1972) PMID:1269917

Johnson, George B.

1976-01-01

120

Numerical and exact solutions for continuum of alleles models.  

PubMed

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

Waxman, D

2003-03-01

121

Allelic exclusion of immunoglobulin genes: models and mechanisms  

PubMed Central

Summary The allelic exclusion of immunoglobulin (Ig) genes is one of the most evolutionarily conserved features of the adaptive immune system and underlies the monospecificity of B cells. While much has been learned about how Ig allelic exclusion is established during B-cell development, the relevance of monospecificity to B-cell function remains enigmatic. Here, we review the theoretical models that have been proposed to explain the establishment of Ig allelic exclusion and focus on the molecular mechanisms utilized by developing B cells to ensure the monoallelic expression of Ig? and Ig? light chain genes. We also discuss the physiological consequences of Ig allelic exclusion and speculate on the importance of monospecificity of B cells for immune recognition. PMID:20727027

Vettermann, Christian; Schlissel, Mark S.

2010-01-01

122

Differential and limited expression of mutant alleles in multiple myeloma.  

PubMed

Recent work has delineated mutational profiles in multiple myeloma and reported a median of 52 mutations per patient, as well as a set of commonly mutated genes across multiple patients. In this study, we have used deep sequencing of RNA from a subset of these patients to evaluate the proportion of expressed mutations. We find that the majority of previously identified mutations occur within genes with very low or no detectable expression. On average, 27% (range, 11% to 47%) of mutated alleles are found to be expressed, and among mutated genes that are expressed, there often is allele-specific expression where either the mutant or wild-type allele is suppressed. Even in the absence of an overall change in gene expression, the presence of differential allelic expression within malignant cells highlights the important contribution of RNA-sequencing in identifying clinically significant mutational changes relevant to our understanding of myeloma biology and also for therapeutic applications. PMID:25237203

Rashid, Naim U; Sperling, Adam S; Bolli, Niccolo; Wedge, David C; Van Loo, Peter; Tai, Yu-Tzu; Shammas, Masood A; Fulciniti, Mariateresa; Samur, Mehmet K; Richardson, Paul G; Magrangeas, Florence; Minvielle, Stephane; Futreal, P Andrew; Anderson, Kenneth C; Avet-Loiseau, Herve; Campbell, Peter J; Parmigiani, Giovanni; Munshi, Nikhil C

2014-11-13

123

Identification of incompatibility alleles in the tetraploid species sour cherry.  

PubMed

The incompatibility genetics of sour cherry ( Prunus cerasus), an allotetraploid species thought to be derived from sweet cherry (diploid) and ground cherry (tetraploid), were investigated by test crossing and by analysis of stylar ribonucleases which are known to be the products of incompatibility alleles in sweet cherry. Stylar extracts of 36 accessions of sour cherry were separated electrophoretically and stained for ribonuclease activity. The zymograms of most accessions showed three bands, some two or four. Of the ten bands seen, six co-migrated with bands that in sweet cherry are attributed to the incompatibility alleles S(1), S(3), S(4), S(6, ) S(9) and S(13). 'Cacanski Rubin', 'Erdi Botermo B', 'Koros' and 'Ujfehertoi Furtos', which showed bands apparently corresponding to S(1) and S(4), were test pollinated with the sweet cherry 'Merton Late' ( S(1) S(4)). Monitoring pollen tube growth, and, in one case, fruit set, showed that these crosses were incompatible and that the four sour cherries indeed have the alleles S(1) and S(4). Likewise, test pollination of 'Marasca Piemonte', 'Marasca Savena' and 'Morello, Dutch' with 'Noble' ( S(6) S(13)) showed that these three sour cherries have the alleles S(6) and S(13). S(13) was very frequent in sour cherry cultivars, but is rare in sweet cherry cultivars, whereas with S(3) the situation is reversed. It was suggested that the other four bands are derived from ground cherry and one of these, provisionally attributed to S(B), occurred frequently in a small set of ground cherry accessions surveyed. Analysing some progenies from sour by sweet crosses by S allele-specific PCR and monitoring the success of some sweet by sour crosses were informative. They indicated mostly disomic inheritance, with sweet cherry S alleles belonging to one locus and, presumably, the ground cherry alleles to the other, and helped clarify the genomic arrangement of the alleles and the interactions in heteroallelic pollen. PMID:14689184

Tobutt, K R; Boskovi?, R; Cerovi?, R; Sonneveld, T; Ruzi?, D

2004-03-01

124

Robust identification of local adaptation from allele frequencies.  

PubMed

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

Günther, Torsten; Coop, Graham

2013-09-01

125

Robust Identification of Local Adaptation from Allele Frequencies  

PubMed Central

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

Günther, Torsten; Coop, Graham

2013-01-01

126

DRD4 dopamine receptor allelic diversity in various primate species  

SciTech Connect

The DRD4 dopamine receptor is uniquely characterized by a 48 bp repeating segment within the coding region, located in exon III. Different DRD4 alleles are produced by the presence of additional 48 bp repeats, each of which adds 16 amino acids to the length of the 3rd intracytoplasmic loop of the receptor. The DRD4 receptor is therefore an intriguing candidate gene for behaviors which are influenced by dopamine function. In several human populations, DRD4 alleles with 2-8 and 10 repeats have previously been identified, and the 4 and 7 repeat alleles are the most abundant. We have determined DRD4 genotypes in the following nonhuman primate species: chimpanzee N=2, pygmy chimpanzee N=2, gorilla N=4, siamang N=2, Gelada baboon N=1, gibbon N=1, orangutan (Bornean and Sumatran) N=62, spider monkey N=4, owl monkey N=1, Colobus monkey N=1, Patas monkey N=1, ruffed lemur N=1, rhesus macaque N=8, and vervet monkey N=28. The degree of DRD4 polymorphism and which DRD4 alleles were present both showed considerable variation across primate species. In contrast to the human, rhesus macaque monkeys were monomorphic. The 4 and 7 repeat allels, highly abundant in the human, may not be present in certain other primates. For example, the four spider monkeys we studied showed the 7, 8 and 9 repeat length alleles and the only gibbon we analyzed was homozygous for the 9 repeat allele (thus far not observed in the human). Genotyping of other primate species and sequencing of the individual DRD4 repeat alleles in different species may help us determine the ancestral DRD4 repeat length and identify connections between DRD4 genotype and phenotype.

Adamson, M.; Higley, D. [NIAAA, Rockville, MD (United States); O`Brien, S. [NCI, Frederick, MD (United States)] [and others

1994-09-01

127

Numerical and exact solutions for continuum of alleles models  

Microsoft Academic Search

Two results are presented for problems involving alleles with a continuous range of effects. The first result is a simple\\u000a yet highly accurate numerical method that determines the equilibrium distribution of allelic effects, moments of this distribution,\\u000a and the mutational load. The numerical method is explicitly applied to the mutation-selection balance problem of stabilising\\u000a selection. The second result is an

D. Waxman

2003-01-01

128

Allele diversity for the apoplastic invertase inhibitor gene from potato.  

PubMed

In planta the enzymatic activity of apoplastic and vacuolar invertases is controlled by inhibitory proteins. Although these invertase inhibitors (apoplastic and vacuolar forms) have been implicated as contributing to resistance to cold-induced sweetening (CIS) in tubers of potato (Solanum tuberosum L.), there is a lack of information on the structure and allelic diversity of the apoplastic invertase inhibitor genes. We have PCR-isolated and sequenced the alleles of the apoplastic invertase inhibitor gene (Stinh1) from three tetraploid potato genotypes: 1021/1 (a genotype with very high tolerance to CIS), 'Karaka' and 'Summer Delight' (two cultivars that are highly susceptible to CIS). In total, five alleles were identified in these genotypes, of which four (Stinh1-c, Stinh1-d, Stinh1-e, Stinh1-f) were novel. An analysis of allele diversity was conducted by incorporating previously published sequences of apoplastic invertase inhibitors from potato. Eight alleles were assessed for sequence polymorphism in the two exons and the single hypervariable intron. Contrary to the hypervariable intron, only 65 single nucleotide polymorphisms were observed in the exons, of which 42 confer amino acid substitutions. Phylogenetic analysis of amino acid sequences indicates that the alleles of the invertase inhibitor are highly conserved amongst members of the Solanaceae family. PMID:22526372

Datir, Sagar S; Latimer, Julie M; Thomson, Susan J; Ridgway, Hayley J; Conner, Anthony J; Jacobs, Jeanne M E

2012-06-01

129

ALEA: a toolbox for allele-specific epigenomics analysis.  

PubMed

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

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

130

Single European Sky and Single European Railway Area  

E-print Network

Single European Sky and Single European Railway Area: A System Level Analysis of Air and Rail; Single European Railway Area; system capacity management. 1 Introduction Air and rail are two extremely Commission, 1999) and the Single European Railway Area (European Commission, 2010a). The Single European Sky

Paris-Sud XI, Université de

131

Whole-exome imputation of sequence variants identified two novel alleles associated with adult body height in African Americans.  

PubMed

Adult body height is a quantitative trait for which genome-wide association studies (GWAS) have identified numerous loci, primarily in European populations. These loci, comprising common variants, explain <10% of the phenotypic variance in height. We searched for novel associations between height and common (minor allele frequency, MAF ?5%) or infrequent (0.5% < MAF < 5%) variants across the exome in African Americans. Using a reference panel of 1692 African Americans and 471 Europeans from the National Heart, Lung, and Blood Institute's (NHLBI) Exome Sequencing Project (ESP), we imputed whole-exome sequence data into 13 719 African Americans with existing array-based GWAS data (discovery). Variants achieving a height-association threshold of P < 5E-06 in the imputed dataset were followed up in an independent sample of 1989 African Americans with whole-exome sequence data (replication). We used P < 2.5E-07 (=0.05/196 779 variants) to define statistically significant associations in meta-analyses combining the discovery and replication sets (N = 15 708). We discovered and replicated three independent loci for association: 5p13.3/C5orf22/rs17410035 (MAF = 0.10, ? = 0.64 cm, P = 8.3E-08), 13q14.2/SPRYD7/rs114089985 (MAF = 0.03, ? = 1.46 cm, P = 4.8E-10) and 17q23.3/GH2/rs2006123 (MAF = 0.30; ? = 0.47 cm; P = 4.7E-09). Conditional analyses suggested 5p13.3 (C5orf22/rs17410035) and 13q14.2 (SPRYD7/rs114089985) may harbor novel height alleles independent of previous GWAS-identified variants (r(2) with GWAS loci <0.01); whereas 17q23.3/GH2/rs2006123 was correlated with GWAS-identified variants in European and African populations. Notably, 13q14.2/rs114089985 is infrequent in African Americans (MAF = 3%), extremely rare in European Americans (MAF = 0.03%), and monomorphic in Asian populations, suggesting it may be an African-American-specific height allele. Our findings demonstrate that whole-exome imputation of sequence variants can identify low-frequency variants and discover novel variants in non-European populations. PMID:25027330

Du, Mengmeng; Auer, Paul L; Jiao, Shuo; Haessler, Jeffrey; Altshuler, David; Boerwinkle, Eric; Carlson, Christopher S; Carty, Cara L; Chen, Yii-Der Ida; Curtis, Keith; Franceschini, Nora; Hsu, Li; Jackson, Rebecca; Lange, Leslie A; Lettre, Guillaume; Monda, Keri L; Nickerson, Deborah A; Reiner, Alex P; Rich, Stephen S; Rosse, Stephanie A; Rotter, Jerome I; Willer, Cristen J; Wilson, James G; North, Kari; Kooperberg, Charles; Heard-Costa, Nancy; Peters, Ulrike

2014-12-15

132

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

PubMed Central

The role of the major histocompatibility complex (MHC) in the immune response makes it an attractive candidate gene for associations with disease resistance and susceptibility. This study describes genetic variability in the BoLA-DRB3 in Iranian buffaloes. Heminested PCR-RFLP method was used to identify the frequency of BoLA-DRB3 alleles. The BoLA-DRB3 locus is highly polymorphic in the study herd (12 alleles). Almost 63.50% of the alleles were accounted for by four alleles (BoLA-DRB3.2 ?48, ?20, ?21, and obe) in Iranian buffalo. The DRB3.2 ?48 allele frequency (24.20%) was higher than the others. The frequencies of the DRB3.2 ?20 and DRB3.2 ?21 are 14.52 and 14.00, respectively, and obe and gbb have a new pattern. Significant distinctions have been found between Iranian buffalo and other cattle breed studied. In the Iranian buffaloes studied alleles associated with resistance to various diseases are found. PMID:22454612

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

2012-01-01

133

Parental Analysis of Introgressive Hybridization between African and European Honeybees Using Nuclear DNA Rflps  

PubMed Central

African honeybees, introduced into Brazil 33 years ago, have spread through most of South and Central America and have largely replaced the extant European bees. Due to a paucity of genetic markers, genetic interactions between European and African bees are not well understood. Three restriction fragment length polymorphisms (RFLPs), detected with random, nuclear DNA probes, are described. The polymorphisms are specific to bees of European descent, possibly specific to certain European races. Each European marker was found present at a high frequency in U.S. colonies but absent in South African bees. Previous mitochondrial DNA studies of neotropical bees have revealed negligible maternal gene flow from managed European apiaries into feral African populations. The findings reported here with nuclear DNA show paternal gene flow between the two but suggest asymmetries in levels of introgressive hybridization. Managed colonies in southern Mexico, derived from European maternal lines, showed diminished levels of the European nuclear markers, reflecting significant hybridization with African drones. The European alleles were present only at low frequencies in feral swarms from the same area. The swarms were of African maternal descent. In Venezuelan colonies, also derived from African maternal lines, the European markers were almost totally absent. The results point to limited paternal introgression from European colonies into the African honeybee populations. These findings dispute other views regarding modes of Africanization. PMID:1974226

Hall, H. G.

1990-01-01

134

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

PubMed

Short tandem repeat (STR) genotyping methods are widely used for human identity testing applications, including forensic DNA analysis. Samples of DNA containing the length-variant STR alleles are typically separated and genotyped by comparison to an allelic ladder. Here, we describe a newly devised library of cloned STR alleles. The library covers alleles X and Y for the sex-determining locus Amelogenin and 259 other alleles for 22 autosomal STR loci (TPOX, D3S1358, FGA, D5S818, CSF1PO, D7S820, D8S1179, TH01, vWA, D13S317, D16S539, D18S51, D21S11, D2S1338, D6S1043, D12S391, Penta E, D19S433, D11S4463, D17S974, D3S4529 and D12ATA63). New primers were designed for all these loci to construct recombinant plasmids so that the library retains core repeat elements of STR as well as 5'- and 3'-flanking sequences of ?500 base pairs. Since amplicons of commercial STR genotyping kits and systems developed in laboratories are usually distributed from 50 to <500 base pairs, this library could provide universal templates for allelic ladder preparation. We prepared three different sets of allelic ladders for this locus TH01 and an updated version of an allelic ladder for the DNATyper(®)19 multiplex system using these plasmids to confirm the suitability of the library as a good source for allelic ladder preparation. Importantly, the authenticity of each construct was confirmed by bidirectional nucleotide sequencing and we report the repeat structures of the 259 STR alleles. The sequencing results showed all repeat structures we obtained for TPOX, CSF1PO, D7S820, TH01, D16S539, D18S51 and Penta E were the same as reported. However, we identified 102 unreported repeat structures from the other 15 STR loci, supplementing our current knowledge of repeat structures and leading to further understanding of these widely used loci. PMID:24997318

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

2014-09-01

135

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

PubMed Central

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

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

2008-01-01

136

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

PubMed

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

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

2014-09-10

137

Further Evidence for an Association of ABCR Alleles with Age-Related Macular Degeneration  

PubMed Central

Age-related macular degeneration (AMD) accounts for >50% of the registered visual disability among North American and Western European populations and has been associated both with environmental factors, such as smoking, and with genetic factors. Previously we have reported disease-associated variants in the ABCR (also called ABCA4) gene in a subset of patients affected with this complex disorder. We have now tested our original hypothesis, that ABCR is a dominant susceptibility locus for AMD, by screening 1,218 unrelated AMD patients of North American and Western European origin and 1,258 comparison individuals from 15 centers in North America and Europe for the two most frequent AMD-associated variants found in ABCR. These two sequence changes, G1961E and D2177N, were found in one allele of ABCR in 40 patients (?3.4%), and in 13 control subjects (?0.95%). Fisher’s two-sided exact test confirmed that these two variants are associated with AMD at a statistically significant level (P<.0001). The risk of AMD is elevated approximately threefold in D2177N carriers and approximately fivefold in G1961E carriers. The identification of a gene that confers risk of AMD is an important step in unraveling this complex disorder. PMID:10880298

Allikmets, Rando

2000-01-01

138

Molecular evolution of alleles of the glycophorin A gene.  

PubMed

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

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

2002-03-01

139

HLA class II allelic variation and susceptibility to pemphigus vulgaris.  

PubMed Central

The autoimmune dermatologic disease pemphigus vulgaris (PV) is associated with the HLA serotypes DR4 and DRw6. Susceptibility to PV could be conferred either by sequences shared between the DR4 and DRw6 haplotypes or by different sequences in these haplotypes. We have examined the distribution of DR and DQ beta-chain and DQ alpha-chain alleles in PV patients and in control subjects by hybridization with oligonucleotide probes and sequence analysis of in vitro amplified DNA. Ninety percent (34/38) of the DR4 haplotypes in patients contain a specific DR beta I sequence present in 36% (16 of 44) of DR4 controls (P = 0.001). This sequence is also found in DRw6 haplotypes. However, it is present in only 25% (6 of 24) of DRw6 patients. The results of our analysis indicate that predisposition to PV is conferred by different sequences in DR4 and DRw6 haplotypes. The DR4 susceptibility is highly associated with the Dw10 DR beta I allele, implicating the polymorphic residues in the third hypervariable region. The DRw6 susceptibility is strongly associated with a rare DQ beta allele (DQB1.3). This allele differs from a common DQ beta allele (DQB1.1) only by a valine----aspartic acid substitution at position 57. Images PMID:3368460

Scharf, S J; Friedmann, A; Brautbar, C; Szafer, F; Steinman, L; Horn, G; Gyllensten, U; Erlich, H A

1988-01-01

140

Allele-sharing statistics using information on family history.  

PubMed

When conducting genetic studies for complex traits, large samples are commonly required to detect new genetic factors. A possible strategy to decrease the sample size is to reduce heterogeneity using available information. In this paper we propose a new class of model-free linkage analysis statistics which takes into account the information given by the ungenotyped affected relatives (positive family history). This information is included into the scoring function of classical allele-sharing statistics. We studied pedigrees of affected sibling pairs with one ungenotyped affected relative. We show that, for rare allele common complex diseases, the proposed method increases the expected power to detect linkage. Allele-sharing methods were applied to the symptomatic osteoarthritis GARP study where taking into account the family-history increased considerably the evidence of linkage in the region of the DIO2 susceptibility locus. PMID:20707788

Callegaro, A; Meulenbelt, I; Kloppenburg, M; Slagboom, P E; Houwing-Duistermaat, J J

2010-11-01

141

Generation and characterization of an analog-sensitive PERK allele.  

PubMed

Restriction of nutrients and oxygen in the tumor microenvironment disrupts ER homeostasis and adaptation to such stress is mediated by the key UPR effector PERK. Given its pro-tumorigenic activity, significant efforts have been made to elucidate the molecular mechanisms that underlie PERK function. Chemical-genetic approaches have recently proven instrumental in pathway mapping and interrogating kinase function. To enable a detailed study of PERK signaling we have generated an analog-sensitive PERK allele that accepts N(6)-alkylated ATP analogs. We find that this allele can be regulated by bulky ATP-competitive inhibitors, confirming the identity of the PERK gatekeeper residue as methionine 886. Furthermore, this analog-sensitive allele can be used to specifically label substrates with thiophosphate both in vitro and in cells. These data highlight the potential for using chemical-genetic techniques to identify novel PERK substrates, thereby providing an expanded view of PERK function and further definition of its signaling networks. PMID:24846185

Maas, Nancy L; Singh, Nickpreet; Diehl, J Alan

2014-08-01

142

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

PubMed Central

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

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

2010-01-01

143

European Union Center of Excellence European Studies Center  

E-print Network

the Arab perspective on the European Neighborhood Policy. 4 Fellowships, Grants, and Opportunities. 5 into the following categories: Muslim/Turkish, East European/Russian, and West European. Clearly, there was reasonNEWSLETTER European Union Center of Excellence European Studies Center URAL Continued on page 6

Sibille, Etienne

144

Distribution of a pseudodeficiency allele among Tay-Sachs carriers  

SciTech Connect

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.

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

1993-08-01

145

European utility fuel procurement  

SciTech Connect

The article describes the major factors affecting the procurement strategies of European nuclear utilities for purchasing natural uranium, conversion services, and enrichment services. The role of the EURATOM Supply Agency in negotiating contracts for nuclear materials for the European Union is described. Bilateral agreements between the United States and EURATOM, and between the European Union and Russia are briefly outlined. National procurement strategies of Belgium, France, Germany, and Sweden are also discussed.

NONE

1995-04-01

146

Haplotype analysis of the apolipoprotein E and apolipoprotein C1 loci in Portugal and São Tomé e Príncipe (Gulf of Guinea): linkage disequilibrium evidence that APOE*4 is the ancestral APOE allele.  

PubMed

The joint distributions of phenotypes from the apolipoprotein E gene (APOE) and from a closely linked restriction site polymorphism at the apolipoprotein C1 locus (APOC1) were studied in population samples from Portugal and São Tomé e Príncipe (Gulf of Guinea), a former Portuguese colony that was originally populated by slaves imported from the African mainland. The frequencies of the APOE alleles (*2, *3, and *4) in Portugal and São Tomé fitted the ranges of variation generally observed in European and African populations, respectively. Haplotype analysis showed that in both populations the strength of linkage disequilibrium was highest for the APOE*2 allele and lowest for the APOE*4 allele, suggesting that the origin of the APOE alleles followed a 4-->3-->2 pathway and thus providing independent confirmation of the results from sequence homology studies with nonhuman primates. In accordance with global trends in the distribution of human genetic variation, the European sample from Portugal presented more intense linkage disequilibrium between APOE and APOC1 than the African sample from São Tomé where, despite the short 4-kb distance that separates the 2 loci, the level of association between the APOC1 alleles and APOE*4 was nonsignificant. PMID:10592690

Seixas, S; Trovoada, M J; Rocha, J

1999-12-01

147

Alternative Fitness Models with the Same Allele Frequency Dynamics  

PubMed Central

For any set of one- or two-locus genotypic fitnesses there are alternative sets, usually frequency-dependent and often with quite different biological meanings, that give rise to the same equations for change of allele or haplotype frequencies. Therefore, it is not possible to distinguish among alternative fitness models from allele or haplotype frequency trajectories or equilibrium distributions. For a single locus and for two loci when linkage equilibrium can be assumed, a simple procedure generates some of the alternative fitness sets. PMID:2341032

Denniston, C.; Crow, J. F.

1990-01-01

148

A common allele on chromosome 9 associated with coronary heartdisease  

SciTech Connect

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.

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

149

ADH1B is associated with alcohol dependence and alcohol consumption in populations of European and African ancestry  

Microsoft Academic Search

A coding variant in alcohol dehydrogenase 1B (ADH1B) (rs1229984) that leads to the replacement of Arg48 with His48 is common in Asian populations and reduces their risk for alcoholism, but because of very low allele frequencies the effects in European or African populations have been difficult to detect. We genotyped and analyzed this variant in three large European and African-American

L J Bierut; A M Goate; N Breslau; E O Johnson; S Bertelsen; L Fox; A Agrawal; K K Bucholz; R Grucza; V Hesselbrock; J Kramer; S Kuperman; J Nurnberger; B Porjesz; N L Saccone; M Schuckit; J Tischfield; J C Wang; T Foroud; J P Rice; H J Edenberg

2012-01-01

150

Assessment of biodiversity in Chilean cattle using the distribution of major histocompatibility complex class II BoLA-DRB3 allele.  

PubMed

Bovine leukocyte antigens (BoLAs) are used extensively as markers for bovine disease and immunological traits. In this study, we estimated BoLA-DRB3 allele frequencies using 888 cattle from 10 groups, including seven cattle breeds and three crossbreeds: 99 Red Angus, 100 Black Angus, 81 Chilean Wagyu, 49 Hereford, 95 Hereford × Angus, 71 Hereford × Jersey, 20 Hereford × Overo Colorado, 113 Holstein, 136 Overo Colorado, and 124 Overo Negro cattle. Forty-six BoLA-DRB3 alleles were identified, and each group had between 12 and 29 different BoLA-DRB3 alleles. Overo Negro had the highest number of alleles (29); this breed is considered in Chile to be an 'Old type' European Holstein Friesian descendant. By contrast, we detected 21 alleles in Holstein cattle, which are considered to be a 'Present type' Holstein Friesian cattle. Chilean cattle groups and four Japanese breeds were compared by neighbor-joining trees and a principal component analysis (PCA). The phylogenetic tree showed that Red Angus and Black Angus cattle were in the same clade, crossbreeds were closely related to their parent breeds, and Holstein cattle from Chile were closely related to Holstein cattle in Japan. Overall, the tree provided a thorough description of breed history. It also showed that the Overo Negro breed was closely related to the Holstein breed, consistent with historical data indicating that Overo Negro is an 'Old type' Holstein Friesian cattle. This allelic information will be important for investigating the relationship between major histocompatibility complex (MHC) and disease. PMID:25430590

Takeshima, S-N; Miyasaka, T; Matsumoto, Y; Xue, G; Diaz, V de la Barra; Rogberg-Muñoz, A; Giovambattista, G; Ortiz, M; Oltra, J; Kanemaki, M; Onuma, M; Aida, Y

2015-01-01

151

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

PubMed

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

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

2014-02-10

152

Nonfrequent but well-documented, rare and very rare HLA alleles observed in the Croatian population.  

PubMed

The aim of the study was to evaluate the presence of nonfrequent, rare and very rare alleles among Croats and to estimate whether they are associated with specific alleles at other human leukocyte antigen (HLA) loci. This retrospective study included the typing results from the last 10?years; total number of individuals included was approximately 45,000. Among 17 alleles so far observed only once in our population, 6 (A*24:41, B*07:02:28, B*35:03:03, B*39:40N, DRB1*13:23 and DRB1*14:111) belong to very rare alleles, 2 (B*44:16 and DRB1*01:31) belong to rare alleles according to the 'Rare Alleles Detector' tool ( www.allelefrequencies.net), while for the B*35:101:01 allele published data exist only in the IMGT/HLA database. The remaining eight HLA alleles observed only once among Croats are considered as frequent according to the 'Rare Alleles Detector'. Those 17 HLA alleles are not declared as common well defined (CWD) alleles in the CWD allele catalogue 2.0.0. Haplotype analysis of nonfrequent alleles detected in our sample supports the idea that different populations, although similar in some aspects regarding HLA allele and haplotype distribution, still have some unique characteristics. This is the case for A*01:02, B*39:10 and DRB1*13:32 which form haplotypes unreported to date among our subjects. PMID:25413106

Grubic, Z; Burek Kamenaric, M; Maskalan, M; Stingl Jankovic, K; Zunec, R

2014-12-01

153

Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study  

Microsoft Academic Search

Background Multiple sclerosis has a clinically significant heritable component. We conducted a ge- nomewide association study to identify alleles associated with the risk of multiple sclerosis. Methods We used DNA microarray technology to identify common DNA sequence variants in 931 family trios (consisting of an affected child and both parents) and tested them for association. For replication, we genotyped another

David A. Hafler; Alastair Compston; Stephen Sawcer; Eric S. Lander; Mark J. Daly; Philip L. De Jager; Paul I. W. de Bakker; Stacey B. Gabriel; Daniel B. Mirel; Adrian J. Ivinson; Margaret A. Pericak-Vance; Simon G. Gregory; John D. Rioux; Jacob L. McCauley; Jonathan L. Haines; Lisa F. Barcellos; Bruce Cree; Jorge R. Oksen-berg; Stephen L. Hauser

2010-01-01

154

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...

155

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...

156

Powerful Allele Sharing Statistics for Nonparametric Linkage Analysis  

Microsoft Academic Search

Nonparametric linkage analysis is widely used to map susceptibility genes for complex diseases. This paper introduces six nonparametric statistics for measuring marker allele sharing among the affected members of a pedigree. We compare the power of these new statistics and three previous statistics to detect linkage with Mendelian diseases having recessive, additive, and dominant modes of inheritance. The nine statistics

Ethan M. Lange; Kenneth Lange

2004-01-01

157

A measure of population subdivision based on microsatellite allele frequencies  

Microsoft Academic Search

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

Montgomery Slatkin

1995-01-01

158

cause of mortality. However, another hemoglobin allele C  

E-print Network

to have even higher fitness, and now appears to be replacing allele S, suggesting that the sickle nucleotide polymorphism (SNP) density. These studies suggest either that a low proportion of loci detecting such loci. Future genomic studies in humans and similar studies with other species should help

Morgan, David

159

Estimating the age of alleles by use of intraallelic variability  

SciTech Connect

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.

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

1997-02-01

160

Allelic Loss and the Progression of Breast Cancer  

Microsoft Academic Search

To study geneticchangesand the evolutionof breastcancer,we assayed for loss of heterozygosity(LOH) in 12 sets of synchronouscarcinomain situ (CIS) and invasive cancer, compared to normal control DNA. Micro satellite markers were used, which map to each nonacrocentric autosomal arm. Eight tumor sets demonstrated LOH of the same allele in both concurrent invasive cancer and ductal OS, for a total of 18

Diane M. Radford; Nancy J. Phillips; Ken L. Fair; Jon H. Ritter; Matthew Holt; Helen Donis-Keller

161

Disease-causing allele-specific silencing by RNA interference.  

PubMed

Small double-stranded RNAs (dsRNAs) of approximately 21-nucleotides in size, referred to as small interfering RNA (siRNA) duplexes, can induce sequence-specific posttranscriptional gene silencing, or RNA interference (RNAi). Since chemically synthesized siRNA duplexes were found to induce RNAi in mammalian cells, RNAi has become a powerful reverse genetic tool for suppressing the expression of a gene of interest in mammals, including human, and its application has been expanding to various fields. Recent studies further suggest that synthetic siRNA duplexes have the potential for specifically inhibiting the expression of an allele of interest without suppressing the expression of other alleles, i.e., siRNA duplexes likely confer allele-specific silencing. Such gene silencing by RNAi is an advanced technique with very promising applications. In this review, I would like to discuss the potential utility of allele-specific silencing by RNAi as a therapeutic method for dominantly inherited diseases, and describe possible improvements in siRNA duplexes for enhancing their efficacy. PMID:24276122

Hohjoh, Hirohiko

2013-01-01

162

MHC class II DR allelic diversity in bighorn sheep  

Technology Transfer Automated Retrieval System (TEKTRAN)

We hypothesized that decreased diversity and/or unique polymorphisms in MHC class II alleles of bighorn sheep (BHS, Ovis canadensis) are responsible for lower titer of antibodies against Mannheimia haemolytica leukotoxin, in comparison to domestic sheep (DS, Ovis aries). To test this hypothesis, DRA...

163

Functional Allelic Variation at Key Photoperiod Response QTL in Maize  

Technology Transfer Automated Retrieval System (TEKTRAN)

Tropical maize represents a valuable genetic resource containing unique alleles not present in elite temperate maize. The strong delay in flowering in response to long daylength photoperiods exhibited by most tropical maize hinders its incorporation into temperate maize breeding programs. We tested ...

164

A genotype probability index for multiple alleles and haplotypes.  

PubMed

We use linear algebra to calculate an index of information content in genotype probabilities which has previously been calculated using trigonometry. The new method can be generalized allowing the index to be calculated for loci with more than two alleles. Applications of this index include its use in genotyping strategies, strategies to manage genetic disorders and in estimation of genotype effects. PMID:16274422

Percy, A; Kinghorn, B P

2005-12-01

165

Concerted Nonsyntenic Allelic Loss in Human Colorectal Carcinoma  

Microsoft Academic Search

Familial polyposis coli (FPC) is caused by an autosomal dominant gene on chromosome 5, and it has been proposed that colorectal cancer in the general population arises from loss or inactivation of the FPC gene, analogous to recessive tumor genes in retinoblastoma and Wilms' tumor. Since allelic loss can be erroneously scored in nonhomogeneous samples, tumor cell populations were first

David J. Law; Sylviane Olschwang; Jean-Philippe Monpezat; Danielle Lefrancois; David Jagelman; Nicholas J. Petrelli; Gilles Thomas; Andrew P. Feinberg

1988-01-01

166

Multifragment alleles in DNA fingerprints of the parrot, Amazona ventralis  

USGS Publications Warehouse

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.

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

1991-01-01

167

Tyrosinase and Tyrosinase Related Protein 1 Alleles Specify Domestic Cat  

E-print Network

Tyrosinase and Tyrosinase Related Protein 1 Alleles Specify Domestic Cat Coat Color Phenotypes address above, or e-mail: aschmidt@ncifcrf.gov. Abstract The genes encoding enzymes of the tyrosinase tyrosinase (TYR)--a plausible candidate gene for the albino (C) locus, and tyrosinase related protein 1 (TYRP

Eizirik, Eduardo

168

Experimental evolution of a novel sexually antagonistic allele.  

PubMed

Evolutionary conflict permeates biological systems. In sexually reproducing organisms, sex-specific optima mean that the same allele can have sexually antagonistic expression, i.e. beneficial in one sex and detrimental in the other, a phenomenon known as intralocus sexual conflict. Intralocus sexual conflict is emerging as a potentially fundamental factor for the genetic architecture of fitness, with important consequences for evolutionary processes. However, no study to date has directly experimentally tested the evolutionary fate of a sexually antagonistic allele. Using genetic constructs to manipulate female fecundity and male mating success, we engineered a novel sexually antagonistic allele (SAA) in Drosophila melanogaster. The SAA is nearly twice as costly to females as it is beneficial to males, but the harmful effects to females are recessive and X-linked, and thus are rarely expressed when SAA occurs at low frequency. We experimentally show how the evolutionary dynamics of the novel SAA are qualitatively consistent with the predictions of population genetic models: SAA frequency decreases when common, but increases when rare, converging toward an equilibrium frequency of ?8%. Furthermore, we show that persistence of the SAA requires the mating advantage it provides to males: the SAA frequency declines towards extinction when the male advantage is experimentally abolished. Our results empirically demonstrate the dynamics underlying the evolutionary fate of a sexually antagonistic allele, validating a central assumption of intralocus sexual conflict theory: that variation in fitness-related traits within populations can be maintained via sex-linked sexually antagonistic loci. PMID:22956914

Dean, Rebecca; Perry, Jennifer C; Pizzari, Tommaso; Mank, Judith E; Wigby, Stuart

2012-01-01

169

Towards European urinalysis guidelines  

Microsoft Academic Search

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

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

2000-01-01

170

European Commission Agriculture and  

E-print Network

European Commission Agriculture and Rural Development Good practice guidance on the sustainable 64 94 89 39 E-mail: liaison.unit.oslo@foresteurope.org Web: https://www.foresteurope.org European Commission (EC) DG Agriculture and Rural Development 130, Rue de la Loi B ­ 1049 Brussels, Belgium Phone: +32

171

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.

172

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

PubMed Central

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

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

1995-01-01

173

Frequency and allele burden of CALR mutations in Chinese with essential thrombocythemia and primary myelofibrosis without JAK2(V617F) or MPL mutations.  

PubMed

CALR mutations are detected in about 50% of persons of predominately European descent with essential thrombocythemia (ET) or primary myelofibrosis (PMF) with wild-type alleles of JAK2 and MPL. We studied 1088 Chinese with diverse myeloproliferative neoplasms including ET (N=234) and PMF (N=50) without JAK2(V617F) or MPL exon 10 mutations. CALR mutation was detected in 53% (95% CI, 46-60%) of subjects with ET and 56% (95% CI, 41-70%) of subjects with PMF. 152 CALR mutations were identified clustering into 15 types including deletions (N=8), insertions (N=3) and complex indels (N=4). We also identified 9 new mutations. Mean (±SD) mutant allele burden was 31±12% (range, 0.5-69%). Persons with PMF had higher CALR mutant allele burdens than those with ET (38±8% vs. 29±12%; P<0.001). Amongst persons with CALR mutations, those with PMF had different clinical features from those with ET. These data may be useful for diagnosing ET and PMF in Chinese who are about 40% of all persons with ET and PMF and for monitoring therapy-response. They also highlight similarities and differences in CALR mutations between Chinese and persons of predominately European descent with these diseases. PMID:25746303

Li, Ning; Yao, Qiu-Mei; Gale, Robert Peter; Li, Jin-Lan; Li, Ling-Di; Zhao, Xiao-Su; Jiang, Hao; Jiang, Qian; Jiang, Bin; Shi, Hong-Xia; Chen, Shan-Shan; Liu, Kai-Yan; Huang, Xiao-Jun; Ruan, Guo-Rui

2015-05-01

174

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.

175

European Geography Test  

NSDL National Science Digital Library

European Geography Test is a collection of challenging Web-based geography exams that survey students' knowledge of European topography, European urban geography, and general map skills. Currently, this site hosts seven tests, which are available in English, Swedish, Spanish, and Dutch. Tests are divided into three different learning levels, and the focus and objectives for each test are clearly stated. The tests employ interactive maps, photographic images, pull-down menus, radio buttons, and fill-in forms to ask students a series of multiple choice, true or false, and matching questions. The questions included in European Geography Test were developed as part of an inter-university project for DGXXII of the European Commission by a consortium of instructors in the UK, Sweden, Belgium, Spain, and The Netherlands. Note: users must register at the site to take the free tests; registration requires name, email address, age, and country of residence.

176

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

PubMed

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

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

177

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

PubMed Central

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

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

178

A comparison of adjustment methods to test the robustness of an STR DNA database comprised of 24 European populations  

Microsoft Academic Search

An aim of the European Network of Forensic Science Institutes (ENFSI) is to produce a DNA database of second generation multiplex (SGM) STR profiles that is representative of the resident cosmopolitan populations. To achieve this, data were collected from 24 different populations. All of the data were combined to form one database of 5700 profiles from which allele proportions were

Peter Gill; Lindsey Foreman; John S Buckleton; Christopher M Triggs; Heather Allen

2003-01-01

179

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

180

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

PubMed

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

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

2014-06-01

181

The European Spallation Source  

NASA Astrophysics Data System (ADS)

In 2003 the joint European effort to design a European Spallation Source (ESS) resulted in a set of reports, and in May 2009 Lund was agreed to be the ESS site. The ESS Scandinavia office has since then worked on setting all the necessary legal and organizational matters in place so that the Design Update and construction can be started in January 2011, in collaboration with European partners. The Design Update phase is expected to end in 2012, to be followed by a construction phase, with first neutrons expected in 2018-2019.

Lindroos, M.; Bousson, S.; Calaga, R.; Danared, H.; Devanz, G.; Duperrier, R.; Eguia, J.; Eshraqi, M.; Gammino, S.; Hahn, H.; Jansson, A.; Oyon, C.; Pape-Møller, S.; Peggs, S.; Ponton, A.; Rathsman, K.; Ruber, R.; Satogata, T.; Trahern, G.

2011-12-01

182

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.

183

CCR5 as a natural and modulated target for inhibition of HIV.  

PubMed

Human immunodeficiency virus type 1 (HIV-1) infection of target cells requires CD4 and a co-receptor, predominantly the chemokine receptor CCR5. CCR5-delta32 homozygosity results in a truncated protein providing natural protection against HIV infection-this without detrimental effects to the host-and transplantation of CCR5-delta32 stem cells in a patient with HIV ("Berlin patient") achieved viral eradication. As a more feasible approach gene-modification strategies are being developed to engineer cellular resistance to HIV using autologous cells. We have developed a dual therapeutic anti-HIV lentiviral vector (LVsh5/C46) that down-regulates CCR5 and inhibits HIV-1 fusion via cell surface expression of the gp41-derived peptide, C46. This construct, effective against multiple strains of both R5- and X4-tropic HIV-1, is being tested in Phase I/II trials by engineering HIV-resistant hematopoietic cells. PMID:24381033

Burke, Bryan P; Boyd, Maureen P; Impey, Helen; Breton, Louis R; Bartlett, Jeffrey S; Symonds, Geoff P; Hütter, Gero

2014-01-01

184

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

E-print Network

, invasive species, parallelism, recessive allele, threespine stickleback. INTRODUCTION Charles Darwin (1859 not attempt to study natural selection and evolution in contemporary natural populations. Darwin's successorsContemporary evolution, allelic recycling, and adaptive radiation of the threespine stickleback

Aguirre, Windsor E.

185

The Characteristics of Allelic Polymorphism in Killer Immunoglobulin-Like Receptor Framework Genes in African Americans  

PubMed Central

The frequencies of alleles of killer cell immunoglobulin like receptor genes, KIR3DL3 and KIR3DL2, and the carrier frequency of KIR2DL4 alleles have been determined from a population of African Americans (n=100) by DNA sequencing of the coding regions. Fifty alleles of KIR3DL3 were observed with the most frequent, KIR3DL3*00901 (13%). KIR3DL2 was also diverse, 32 alleles with KIR3DL2*00103 the most frequent (17%). For KIR2DL4, of the 18 alleles observed, one allele, KIR2DL4*00103 was found in 64 of the 100 individuals. Thirty six novel alleles encoding a total of 28 unique receptors are described. Pairwise comparisons among all of the alleles at each locus suggest a predominance of synonymous substitutions. The variation at all three framework loci fits a neutral model of evolution. PMID:21607693

Hou, LiHua; Jiang, Bo; Chen, Minghua; Ng, Jennifer; Hurley, Carolyn Katovich

2012-01-01

186

A natural allele of Nxf1 suppresses retrovirus insertional mutations.  

PubMed

Endogenous retroviruses have shaped the evolution of mammalian genomes. Host genes that control the effects of retrovirus insertions are therefore of great interest. The modifier-of-vibrator-1 locus (Mvb1) controls levels of correctly processed mRNA from genes mutated by endogenous retrovirus insertions into introns, including the Pitpn(vb) tremor mutation and the Eya1(BOR) model of human branchiootorenal syndrome. Positional complementation cloning identifies Mvb1 as the nuclear export factor Nxf1, providing an unexpected link between the mRNA export receptor and pre-mRNA processing. Population structure of the suppressive allele in wild Mus musculus castaneus suggests selective advantage. A congenic Mvb1(CAST) allele is a useful tool for modifying gene expression from existing mutations and could be used to manipulate engineered mutations containing retroviral elements. PMID:14517553

Floyd, Jennifer A; Gold, David A; Concepcion, Dorothy; Poon, Tiffany H; Wang, Xiaobo; Keithley, Elizabeth; Chen, Dan; Ward, Erica J; Chinn, Steven B; Friedman, Rick A; Yu, Hon-Tsen; Moriwaki, Kazuo; Shiroishi, Toshihiko; Hamilton, Bruce A

2003-11-01

187

S-allele diversity in Sorbus aucuparia and Crataegus monogyna (Rosaceae: Maloideae)  

Microsoft Academic Search

RT-PCR was used to obtain the first estimates from natural populations of allelic diversity at the RNase-based gametophytic self-incompatibility locus in the Rosaceae. A total of 20 alleles were retrieved from 20 Sorbus aucuparia individuals, whereas 17 alleles were found in 13 Crataegus monogyna samples. Estimates of population-level allele numbers fall within the range observed in the Solanaceae, the only

O Raspé; J R Kohn

2002-01-01

188

European Molecular Biology Laboratory  

E-print Network

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.

1973-01-01

189

European Elder (Elderberry)  

MedlinePLUS

... Names: European elder, black elder, elder, elderberry, elder flower, sambucus Latin Name: Sambucus nigra elder_foster.jpg © ... the elder tree—such as the berries and flowers—have historically been used for pain, swelling, infections, ...

190

European Economic Integration  

ERIC Educational Resources Information Center

Recounts the history and problems of European Economic Integration from the first post World War II organization, the OEEC, to the EEC (Common Market) and the EFTA. Suggestions for further reading are included. (JB)

Huston, James A.

1971-01-01

191

European space programme  

NASA Astrophysics Data System (ADS)

Successful European Space Agency (ESA) programs include the Ariane launcher development, the Meteosat meteorological satellites and the Intelsat 6, ECS (European Communications Satellite) series of communications satellites. The ESA's policy of placing contracts with industrial companies in its 13 member countries has contributed to the strategic development of European high technology in the world market. The ESA's long-term programs, in addition to the Ariane launcher and Columbus/Hermes space-station/spaceplane programs, include participation in the International Space Station program, the Data Relay Satellite system and a variety of space applications programs. Two high-performance satellites to be placed in polar orbits will contribute to European environmental and climate variation studies and, together with the Polar Platform sector of the Columbus program, will drive the establishment and development of new institutions, industrial structures and infrastructure.

Luton, J.-M.

1992-02-01

192

European psychotraumatology – alongside the recent European history  

PubMed Central

This article outlines a personal reflection of experiences within the field of traumatic stress, especially in relation to specific events, which affected the author's professional life. Conclusions for further challenges for European Society for Traumatic Stress Studies (ESTSS) are delineated. ESTSS's role in the global network of traumatic stress societies is discussed. This is a personal view of Brigitte Lueger-Schuster, president of ESTSS on behalf of the 20th birthday of ESTSS. PMID:23755321

Lueger-Schuster, Brigitte

2013-01-01

193

SSR allelic variation in almond ( Prunus dulcis Mill.)  

Microsoft Academic Search

Sixteen SSR markers including eight EST-SSR and eight genomic SSRs were used for genetic diversity analysis of 23 Chinese\\u000a and 15 international almond cultivars. EST- and genomic SSR markers previously reported in species of Prunus, mainly peach, proved to be useful for almond genetic analysis. DNA sequences of 117 alleles of six of the 16 SSR loci were\\u000a analysed to

Hua Xie; Yi Sui; Feng-Qi Chang; Yong Xu; Rong-Cai Ma

2006-01-01

194

Teratogenic Alleles in Autism and Other Neurodevelopmental Disorders  

Microsoft Academic Search

\\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

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

195

Expanding Allelic Diversity of Helicobacter pylori vacA  

Microsoft Academic Search

The diversity of the gene encoding the vacuolating cytotoxin (vacA )o fHelicobacter pylori was analyzed in 98 isolates obtained from different geographic locations. The studies focused on variation in the previously defined s and m regions of vacA, as determined by PCR and direct sequencing. Phylogenetic analysis revealed the existence of four distinct types of s-region alleles: aside from the

LEEN-JAN VAN DOORN; C EU FIGUEIREDO; RICARDO SANNA; SALVADOR PENA; PETER MIDOLO; ENDERS K. W. NG; JOHN C. ATHERTON; MARTIN J. BLASER; WIM G. V. QUINT

1998-01-01

196

Capillary electrophoresis for the detection of Fragile X expanded alleles.  

PubMed

Capillary electrophoresis is an analytical technique that separates ions based on their electrophoresis mobility with the use of an applied voltage. Capillary electrophoresis is used most predominantly in nuclear acid fragment analysis as well as DNA sequencing because it gives faster results and provides high resolution separation. Here we describe an application using capillary electrophoreses for screening the Fragile X expanded alleles to demonstrate the application. PMID:22976108

Mao, Rong; Bayrak-Toydemir, Pinar; Lyon, Elaine

2013-01-01

197

TETRASOMIC SEGREGATION FOR MULTIPLE ALLELES IN ALFALFA1  

Microsoft Academic Search

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

CARLOS F. QUIROSZ

198

The Rh allele frequencies in Gaza city in Palestine  

PubMed Central

Background: The Rh blood group system is the second most clinically significant blood group system. It includes 49 antigens, but only five (D, C, E, c and e) are the most routinely identified due to their unique relation to hemolytic disease of the newborn (HDN) and transfusion reactions. Frequency of the Rh alleles showed variation, with regard to race and ethnic. Objectives: The purpose of the study was to document the Rh alleles’ frequencies amongst males (M) and females (F) in Gaza city in Palestine. Materials and Methods: Two hundred and thirty-two blood samples (110 M and 122 F) were tested against monoclonal IgM anti-C,anti-c, anti-E, anti-e and a blend of monoclonal/polyclonal IgM/IgG anti-D. The expected Rh phenotypes were calculated using gene counting method. Results: The most frequent Rh antigen in the total sample was e, while the least frequent was E.The order of the combined Rh allele frequencies in both M and F was CDe > cDe > cde > CdE > cDE > Cde > CDE. A significant difference was reported between M and F regarding the phenotypic frequencies (P < 0.05). However, no significance (P > 0.05) was reported with reference to the observed and expected Rh phenotypic frequencies in either M or F students. Conclusion: It was concluded that the Rh antigens, alleles and phenotypes in Gaza city have unique frequencies, which may be of importance to the Blood Transfusion Center in Gaza city and anthropology. PMID:21897594

EL-Wahhab Skaik, Younis Abed

2011-01-01

199

[Phenotypic effects of puroindoline gene alleles of bread wheat].  

PubMed

85 winter bread wheat varieties and lines that have been developed mostly in Ukraine were analyzed with NIR for parameters of hardness and protein content. The hardness data were compared with the data of puroindoline gene alleles analysis done earlier and the published data. Significant variation of parameters of hardness was revealed when there was low polymorphism of puroindoline genes indicating the presence of additional genes that influence the hardness parameters. PMID:23074957

Chebotar, S V; Kurakina, K O; Khokhlov, O M; Chebotar, H O; Syvolap, Iu M

2012-01-01

200

Beta 2-glycoprotein I--a Bi-Allelic polymorphism.  

PubMed

Population samples from Hungary and India have been typed for beta 2-glycoprotein I concentrations. Whereas the Hungarian sample is in fairly good accord with the genetic model set up by Cleve2-beta 2-glycoprotein I concentrations are controlled by two autosomal codominant alleles BgN and BgD-the Indian samples do not fit this model. Thus the Indian data favour the assumption of a more complex genetic mechanism controlling the serum concentration of this protein. PMID:7272000

Walter, H; Schliwa, R; Lankenau, H; Singh, I P; Bhasin, M K; Veerraju, P; Goud, J D; Nemeskeri, J

1981-01-01

201

Inferring Selection Intensity and Allele Age from Multilocus Haplotype Structure  

PubMed Central

It is a challenging task to infer selection intensity and allele age from population genetic data. Here we present a method that can efficiently estimate selection intensity and allele age from the multilocus haplotype structure in the vicinity of a segregating mutant under positive selection. We use a structured-coalescent approach to model the effect of directional selection on the gene genealogies of neutral markers linked to the selected mutant. The frequency trajectory of the selected allele follows the Wright-Fisher model. Given the position of the selected mutant, we propose a simplified multilocus haplotype model that can efficiently model the dynamics of the ancestral haplotypes under the joint influence of selection and recombination. This model approximates the ancestral genealogies of the sample, which reduces the number of states from an exponential function of the number of single-nucleotide polymorphism loci to a quadratic function. That allows parameter inference from data covering DNA regions as large as several hundred kilo-bases. Importance sampling algorithms are adopted to evaluate the probability of a sample by exploring the space of both allele frequency trajectories of the selected mutation and gene genealogies of the linked sites. We demonstrate by simulation that the method can accurately estimate selection intensity for moderate and strong positive selection. We apply the method to a data set of the G6PD gene in an African population and obtain an estimate of 0.0456 (95% confidence interval 0.0144?0.0769) for the selection intensity. The proposed method is novel in jointly modeling the multilocus haplotype pattern caused by recombination and mutation, allowing the analysis of haplotype data in recombining regions. Moreover, the method is applicable to data from populations under exponential growth and a variety of other demographic histories. PMID:23797107

Chen, Hua; Slatkin, Montgomery

2013-01-01

202

European PTTI report  

NASA Technical Reports Server (NTRS)

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.

Cordara, Franco; Grimaldi, Sabrina; Leschiutta, Sigfrido

1994-01-01

203

Generation of a Magoh conditional allele in mice.  

PubMed

Magoh encodes a core component of the exon junction complex (EJC), which binds mRNA and regulates mRNA metabolism. Magoh is highly expressed in proliferative tissues during development. EJC components have been implicated in several developmental disorders including TAR syndrome, Richieri-Costa-Pereira syndrome, and intellectual disability. Existing germline null Magoh mice are embryonic lethal as homozygotes and perinatal lethal as heterozygotes, precluding detailed analysis of embryonic and postnatal functions. Here, we report the generation of a new genetic tool to dissect temporal and tissue-specific roles for Magoh in development and adult homeostasis. This Magoh conditional allele has two loxP sites flanking the second exon. Ubiquitous Cre-mediated deletion of the floxed allele in a heterozygous mouse (Magoh(del/+) ) causes 50% reduction of both Magoh mRNA and protein. Magoh(del/+) mice exhibit both microcephaly and hypopigmentation, thus phenocopying germline haploinsufficient Magoh mice. Using Emx1-Cre, we further show that conditional Magoh deletion in neural progenitors during embryonic development also causes microcephaly. We anticipate this novel conditional allele will be a valuable tool for assessing tissue-specific roles for Magoh in mammalian development and postnatal processes. PMID:24771530

McMahon, John J; Shi, Lei; Silver, Debra L

2014-08-01

204

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

PubMed

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

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

1998-08-01

205

Allele-Specific Enzymatic Amplification of beta -globin Genomic DNA for Diagnosis of Sickle Cell Anemia  

Microsoft Academic Search

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

Dan Y. Wu; Luis Ugozzoli; Bijay K. Pal; R. Bruce Wallace

1989-01-01

206

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

Microsoft Academic Search

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

G. L. Chandler; T. C. Bjornn

1989-01-01

207

Effect of Total Allelic Relationship on Accuracy of Evaluation and Response to Selection  

Microsoft Academic Search

Total allelic relationship (TA) as a possible alternative to the pedigree-derived additive genetic relationship (RA) is defined. The TA meas- ures the actual allelic identity between individuals for loci segregating for the trait concerned. Its value was studied by simulation in populations of different family structure, different numbers of loci, different numbers of alleles per locus, and different heritability levels.

A. Nejati-Javaremi; C. Smith; J. P. Gibson

2010-01-01

208

Identification of alleles of carotenoid pathway genes important for zeaxanthin accumulation in potato tubers.  

PubMed

We have investigated the genetics and molecular biology of orange flesh colour in potato (Solanum tuberosum L.). To this end the natural diversity in three genes of the carotenoid pathway was assessed by SNP analyses. Association analysis was performed between SNP haplotypes and flesh colour phenotypes in diploid and tetraploid potato genotypes. We observed that among eleven beta-carotene hydroxylase 2 (Chy2) alleles only one dominant allele has a major effect, changing white into yellow flesh colour. In contrast, none of the lycopene epsilon cyclase (Lcye) alleles seemed to have a large effect on flesh colour. Analysis of zeaxanthin epoxidase (Zep) alleles showed that all (diploid) genotypes with orange tuber flesh were homozygous for one specific Zep allele. This Zep allele showed a reduced level of expression. The complete genomic sequence of the recessive Zep allele, including the promoter, was determined, and compared with the sequence of other Zep alleles. The most striking difference was the presence of a non-LTR retrotransposon sequence in intron 1 of the recessive Zep allele, which was absent in all other Zep alleles investigated. We hypothesise that the presence of this large sequence in intron 1 caused the lower expression level, resulting in reduced Zep activity and accumulation of zeaxanthin. Only genotypes combining presence of the dominant Chy2 allele with homozygosity for the recessive Zep allele produced orange-fleshed tubers that accumulated large amounts of zeaxanthin. PMID:20490894

Wolters, Anne-Marie A; Uitdewilligen, Jan G A M L; Kloosterman, Bjorn A; Hutten, Ronald C B; Visser, Richard G F; van Eck, Herman J

2010-08-01

209

Increasing long-term response by selecting for favorable minor alleles  

Technology Transfer Automated Retrieval System (TEKTRAN)

Long-term response of genomic selection can be improved by considering allele frequencies of selected markers or quantitative trait loci (QTLs). A previous formula to weight allele frequency of favorable minor alleles was tested, and 2 new formulas were developed. The previous formula used nonlinear...

210

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.

211

High prevalence of CYP2C19*2 allele in Roma samples: study on Roma and Hungarian population samples with review of the literature.  

PubMed

The purpose of our study was to characterise the CYP2C19*2 and CYP2C19*3 alleles in healthy Roma and Hungarian populations. DNA of 500 Roma and 370 Hungarian subjects were genotyped for CYP2C19*2 (G681A, rs4244285) and CYP2C19*3 (G636A, rs4986893) by PCR-RFLP assay and direct sequencing. Significant differences were found comparing the Roma and Hungarian populations in CYP2C19 681 GG (63.6 vs. 75.9%), GA (31.8 vs. 23.0%), AA (4.6 vs. 1.1%), GA+AA (36.4 vs. 24.1%) and A allele frequencies (0.205 vs. 0.125) (p<0.004). Striking differences were found between Roma and Hungarian samples in CYP2C19*1 (79.5 vs. 87.4%) and CYP2C19*2 (20.5 vs. 12.6%) alleles, respectively (p<0.001). None of the subjects was found to carry the CYP2C19*3 allele. Frequencies of the intermedier metabolizer phenotype defined by the *1/*2 genotype (0.318 vs. 0.230, p<0.005) and poor metabolizer predicted by the *2/*2 genotype (0.046 vs. 0.011, p<0.005) was significantly higher in Roma than in Hungarians, respectively. Genotype distribution of the Roma population was similar to those of the population of North India, however, a major difference was found in the frequency of the CYP2C19*2 allele, which is likely a result of admixture with European lineages. In conclusion, the frequencies of the CYP2C19 alleles, genotypes and corresponding extensive, intermediate and poor metabolizer phenotypes studied here in the Hungarian population are similar to those of other European Caucasian populations, but display clear differences when compared to the Roma population. PMID:23645039

Sipeky, Csilla; Weber, Agnes; Szabo, Melinda; Melegh, Bela I; Janicsek, Ingrid; Tarlos, Greta; Szabo, Istvan; Sumegi, Katalin; Melegh, Bela

2013-08-01

212

Novel Method for Analysis of Allele Specific Expression in Triploid Oryzias latipes Reveals Consistent Pattern of Allele Exclusion  

PubMed Central

Assessing allele-specific gene expression (ASE) on a large scale continues to be a technically challenging problem. Certain biological phenomena, such as X chromosome inactivation and parental imprinting, affect ASE most drastically by completely shutting down the expression of a whole set of alleles. Other more subtle effects on ASE are likely to be much more complex and dependent on the genetic environment and are perhaps more important to understand since they may be responsible for a significant amount of biological diversity. Tools to assess ASE in a diploid biological system are becoming more reliable. Non-diploid systems are, however, not uncommon. In humans full or partial polyploid states are regularly found in both healthy (meiotic cells, polynucleated cell types) and diseased tissues (trisomies, non-disjunction events, cancerous tissues). In this work we have studied ASE in the medaka fish model system. We have developed a method for determining ASE in polyploid organisms from RNAseq data and we have implemented this method in a software tool set. As a biological model system we have used nuclear transplantation to experimentally produce artificial triploid medaka composed of three different haplomes. We measured ASE in RNA isolated from the livers of two adult, triploid medaka fish that showed a high degree of similarity. The majority of genes examined (82%) shared expression more or less evenly among the three alleles in both triploids. The rest of the genes (18%) displayed a wide range of ASE levels. Interestingly the majority of genes (78%) displayed generally consistent ASE levels in both triploid individuals. A large contingent of these genes had the same allele entirely suppressed in both triploids. When viewed in a chromosomal context, it is revealed that these genes are from large sections of 4 chromosomes and may be indicative of some broad scale suppression of gene expression. PMID:24945156

Garcia, Tzintzuni I.; Matos, Isa; Shen, Yingjia; Pabuwal, Vagmita; Coelho, Maria Manuela; Wakamatsu, Yuko; Schartl, Manfred; Walter, Ronald B.

2014-01-01

213

Characterization of 38 microsatellite loci in the European blackbird, Turdus merula (Turdidae, AVES).  

PubMed

We characterized 38 microsatellite loci in the European blackbird, Turdus merula. Thirty-seven loci were identified by testing 242 loci that had been originally isolated in other avian species. One additional locus was isolated from a European blackbird genomic library. All loci were characterized in 20-29 blackbirds from a population in the Czech Republic and displayed between two and 16 alleles, with observed heterozygosity ranging from 0.04 to 1.00. Thirty-seven loci could be assigned a chromosome location in the zebra finch (Taeniopygia guttata) genome based on sequence homology. PMID:21564948

Simeoni, Michelle; Dawson, Deborah A; Gentle, Louise K; Coiffait, Lisette; Wolff, Kirsten; Evans, Karl L; Gaston, Kevin J; Hatchwell, Ben J

2009-11-01

214

Application of bovine microsatellite markers for genetic diversity analysis of European bison (Bison bonasus).  

PubMed

In this study, the cross-amplification of a commercial multiplex set of 11 cattle (Bos taurus) microsatellites was tested on a panel of 35 European bison (Bison bonasus) individuals. After polymerase chain reaction optimization, all loci cross-amplified successfully in investigated bisons. Number of alleles and observed and expected heterozygosity per locus are in the range of 2-4, 0.086-0.629 and 0.288-0.621 respectively. The availability of a heterologous set of multiplexed microsatellite markers derived from cattle opens an avenue for collecting profound genetic data for efficient conservation management strategies of the European bison. PMID:17177698

Roth, T; Pfeiffer, I; Weising, K; Brenig, B

2006-12-01

215

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

PubMed

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

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

2004-02-01

216

European Union Scandal  

NSDL National Science Digital Library

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.

Osmond, Andrew.

217

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

Microsoft Academic Search

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

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

2010-01-01

218

A family with two female siblings with compound heterozygous FMR1 premutation alleles.  

PubMed

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, seven 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

Basuta, K; Lozano, R; Schneider, A; Yrigollen, C M; Hessl, D; Hagerman, R J; Tassone, F

2014-05-01

219

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

PubMed Central

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

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

2014-01-01

220

Polymorphism of Mhc-DRB alleles in Cercopithecus aethiops (green monkey): generation and functionality.  

PubMed

DRB genes have been studied for the first time in green monkeys (Cercopithecus aethiops). Eleven new DRB alleles (exon 2, exon 3) have been obtained and sequenced from cDNA. A limited number of lineages have been identified: DRB1*03 (4 alleles), DRB1*07 (3 alleles), DRB5 (1 allele), DRB*w6 (1 allele), and DRB*w7 (2 alleles). The existence of Ceae-DRB1 duplications is supported by the finding of 3 DRB1 alleles in 3 different individuals. Ceae-DRB1*0701 may be non-functional because it bears serine at position 82, which hinders molecule surface expression in mice; the allele is only found in Ceae-DRB duplicated haplotypes. Base changes in cDNA Ceae-DRB alleles are consistent with the generation of polymorphism by point mutations or short segment exchanges between alleles. The eleven green monkey DRB alleles meet the requirements for functionality as antigen-presenting molecules (perhaps, excluding DRB1*0701), since: 1) they have been isolated from cDNA and do not present deletions, insertions or stop codons: 2) structural motifs necessary for a correct folding of the molecule, for the formation of DR/DR dimers and for CD4 interactions are conserved, and 3) the number of non-synonymous substitutions is higher than the number of synonymous substitutions in the peptide binding region (PBR), while the contrary holds true for the non-PBR region. PMID:9672153

Rosal-Sánchez, M; Paz-Artal, E; Moreno-Pelayo, M A; Martínez-Quiles, N; Martínez-Laso, J; Martín-Villa, J M; Arnaiz-Villena, A

1998-05-01

221

Alcohol and European transformation.  

PubMed

Against the background of papers and discussions from the East-West seminar at the European Conference on Health, Society and Alcohol, the differences and similarities in eastern and western European transformation processes are discussed. After some remarks on the general nature of eastern transition and western integration, the two sides of Europe are compared with respect to various alcohol-specific issues. It will be shown that the ongoing transition touches alcohol-related phenomena on a broad spectrum, and no single characterization (e.g. commercialization and the rise of market interests) is sufficient alone. The changing balance between state, markets and civil society provides, however, an interesting perspective for comparing alcohol-related changes in various European societies. Finally, the prospects for a common European alcohol agenda are discussed briefly from the point of view of international mobilization on the dimensions of state, markets and civil society. There are signs of increased cooperation along all dimensions, but an all-European alcohol agenda seems unlikely. PMID:9167285

Simpura, J

1997-03-01

222

European Monetary Institute (EMI)  

NSDL National Science Digital Library

The European Monetary Institute was established in 1994 to oversee the implementation of a single currency for Europe. The EMI site contains information on its staff, organization, structure, and financial resources, and outlines the process of entering the third and final phase of the European Monetary Union. 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.

223

Systematic classification of alleles of the glycophorin A (MN blood group) gene.  

PubMed

Ten alleles (five M and five N alleles) of the MN blood group system with normal antigenicity were found by sequencing the glycophorin A (GPA) gene. This study demonstrates the systematic classification of these alleles to major or minor variations of the standard alleles. GPA-specific fragments ranging from 150 to 3.8 kb in length were amplified from the templates, and exons 1-7 and introns 1-6 were sequenced. The data were analyzed phylogenetically to classify these alleles into major groups or clusters. The ten alleles were grouped into four major clusters M10X (M101-M103), M20X (M201 and M202), N10X (N101-N104) and N20X (N201), where 'X' represents a digit indicating minor variations. This grouping was supported by phylogenetic analysis. The cluster system of GPA alleles is highly informative for genetic screening. PMID:16205834

Mizukami, Hajime; Akane, Atsushi; Nakayashiki, Nori; Aoki, Yasuhiro; Shiono, Hiroshi

2005-01-01

224

Analysis of elite variety tag SNPs reveals an important allele in upland rice  

PubMed Central

Elite crop varieties usually fix alleles that occur at low frequencies within non-elite gene pools. Dissecting these alleles for desirable agronomic traits can be accomplished by comparing the genomes of elite varieties with those from non-elite populations. Here we deep-sequence six elite rice varieties and use two large control panels to identify elite variety tag single-nucleotide polymorphism alleles (ETASs). Guided by this preliminary analysis, we comprehensively characterize one protein-altering ETAS in the 9-cis-epoxycarotenoid dioxygenase gene of the IRAT104 upland rice variety. This allele displays a drastic frequency difference between upland and irrigated rice, and a selective sweep is observed around this allele. Functional analysis indicates that in upland rice, this allele is associated with significantly higher abscisic acid levels and denser lateral roots, suggesting its association with upland rice suitability. This report provides a potential strategy to mine rare, agronomically important alleles. PMID:23828614

Lyu, Jun; Zhang, Shilai; Dong, Yang; He, Weiming; Zhang, Jing; Deng, Xianneng; Zhang, Yesheng; Li, Xin; Li, Baoye; Huang, Wangqi; Wan, Wenting; Yu, Yang; Li, Qiong; Li, Jun; Liu, Xin; Wang, Bo; Tao, Dayun; Zhang, Gengyun; Wang, Jun; Xu, Xun; Hu, Fengyi; Wang, Wen

2013-01-01

225

Allele-specific MVR-PCR analysis at minisatellite D1S8.  

PubMed

Minisatellite variant repeat mapping by the polymerase chain reaction (MVR-PCR) provides a digital approach to DNA typing of great potential use both in forensic medicine and, by mapping single alleles, for exploring allelic variability and mutation processes at minisatellites. The MVR haplotypes of single alleles can be determined either from physically separated alleles or by pedigree analysis of digital diploid codes generated from both alleles simultaneously. We now show that single alleles can be rapidly mapped from total genomic DNA using allele-specific PCR primers directed to polymorphic sites in the DNA flanking the minisatellite. This approach can also be used to dissect mixed DNA samples such as those often encountered in forensic DNA analysis. PMID:8518788

Monckton, D G; Tamaki, K; MacLeod, A; Neil, D L; Jeffreys, A J

1993-05-01

226

Report of the European DNA profiling group (EDNAP): an investigation of the complex STR loci D21S11 and HUMFIBRA (FGA)  

Microsoft Academic Search

This paper describes a collaborative exercise which was intended to demonstrate whether uniformity of DNA profiling results could be achieved between European laboratories using two complex short tandem repeat (STR) loci. The loci D21S11 and HUMFIBRA (FGA) were chosen because they are commonly used by different European laboratories. D21S11 has approximately 14 common alleles (f>0.001), whereas HUMFIBRA has 19 common

Peter Gill; E d'Aloja; J Andersen; B Dupuy; M Jangblad; V Johnsson; A. D Kloosterman; A Kratzer; M. V Lareu; M Meldegaard; C Phillips; H Pfitzinger; S Rand; M Sabatier; R Scheithauer; H Schmitter; P Schneider; M. C Vide

1997-01-01

227

European Universe Awareness  

NASA Astrophysics Data System (ADS)

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.

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

2011-10-01

228

The European nitrogen case.  

PubMed

The N budget for Europe (excluding the former Soviet Union) indicates that the 3 principal driving forces of the acceleration of the European N cycle are fertilizer production (14 Mt (mill. tonnes) N yr-1), fossil fuel combustion and other industry (3.3 Mt N yr-1) and import of N in various products (7.6 Mt N yr-1). The various leaks of reactive N species from European food, energy and industrial production systems are estimated and their effects on human health and terrestrial and aquatic ecosystems are assessed. Future European environmental policy measures to close the N cycle and to reduce leaks of reactive N can best focus on the three major driving forces, taking into consideration the possible consequences in the N cascade. Critical loads may be useful tools in determining N-emission ceilings and developing integrated policies for regulating N flows such as fertilizer use and imports and N levels. PMID:12078012

van Egmond, Klaas; Bresser, Ton; Bouwman, Lex

2002-03-01

229

Bi-allelic gene targeting in mouse embryonic stem cells.  

PubMed

The EUCOMM and KOMP programs have generated targeted conditional alleles in mouse embryonic stem cells for nearly 10,000 genes. The availability of these stem cell resources will greatly accelerate the functional analysis of genes in mice and in cultured cells. We present a method for conditional ablation of genes in ES cells using vectors and targeted clones from the EUCOMM and KOMP conditional resources. Inducible homozygous cells described here provide a precisely controlled experimental system to study gene function in a model cell. PMID:21288739

Tate, Peri H; Skarnes, William C

2011-04-01

230

A study of an allele sharing statistic on extended pedigrees  

Microsoft Academic Search

Abstract Linkage analysis using allele-sharing methods,is a trait-model free approach,to test for the location of a disease gene by studying,the joint inheritance pattern of genes at different loci. For large pedigrees, the space of inheritance vectors becomes large and unavailability of data on individuals makes,the probability computation,of multilocus inheritance,pattern almost,infeasible. MCMC techniques,provide a solution to this problem,as they produce,in real

S. Basu; E. A. Thompson

231

Allele typing of short tandem repeats by capillary electrophoresis  

Microsoft Academic Search

Capillary electrophoresis with laser-induced fluorescence was applied to the analysis of six STRs and the amelogenin sex\\u000a test with the purpose of verifying accuracy and precision of the sizing method with the GS500 internal standard. Sequenced\\u000a dye-labeled, PCR-amplified alleles from amelogenin, HumVWA31, HumTH01, HumF13A01, HumFIBRA, D21S11 and HumCSF1PO loci were\\u000a run several times on the same capillary and on multiple

Adriano Tagliabracci; Loredana Buscemi; Corrado Sassaroli; Massimo Paoli; Daniele Rodriguez

1999-01-01

232

European Forest Institute: Research  

NSDL National Science Digital Library

This European Forest Institute (EFI) is "An independent non-governmental organization conducting European forest research." This website provides information about EFI's mission, research goals, strategies and programs. Site users can view information about on-going and completed projects in any of the four EFI research programs which include: Forest Ecology and Management, Forest Products Markets and Socio-Economics, Policy Analysis, and Forest Resources and Information. EFI also provides a search engine for locating specific research projects as well as information about how to propose an EFI project.

233

Preferential Binding to Elk-1 by SLE-Associated IL10 Risk Allele Upregulates IL10 Expression  

PubMed Central

Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P?=?2.7×10?8, OR?=?1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans. PMID:24130510

Kelly, Jennifer A.; Brown, Elizabeth E.; Harley, John B.; Bae, Sang-Cheol; Alarc?n-Riquelme, Marta E.; Edberg, Jeffrey C.; Kimberly, Robert P.; Ramsey-Goldman, Rosalind; Petri, Michelle A.; Reveille, John D.; Vilá, Luis M.; Alarcón, Graciela S.; Kaufman, Kenneth M.; Vyse, Timothy J.; Jacob, Chaim O.; Gaffney, Patrick M.; Sivils, Kathy Moser; James, Judith A.; Kamen, Diane L.; Gilkeson, Gary S.; Niewold, Timothy B.; Merrill, Joan T.; Scofield, R. Hal; Criswell, Lindsey A.; Stevens, Anne M.; Boackle, Susan A.; Kim, Jae-Hoon; Choi, Jiyoung; Pons-Estel, Bernardo A.; Freedman, Barry I.; Anaya, Juan-Manuel; Martin, Javier; Yu, C. Yung; Chang, Deh-Ming; Song, Yeong Wook; Langefeld, Carl D.; Chen, Weiling; Grossman, Jennifer M.; Cantor, Rita M.; Hahn, Bevra H.; Tsao, Betty P.

2013-01-01

234

Preferential binding to Elk-1 by SLE-associated IL10 risk allele upregulates IL10 expression.  

PubMed

Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P?=?2.7×10??, OR?=?1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans. PMID:24130510

Sakurai, Daisuke; Zhao, Jian; Deng, Yun; Kelly, Jennifer A; Brown, Elizabeth E; Harley, John B; Bae, Sang-Cheol; Alarc?n-Riquelme, Marta E; Edberg, Jeffrey C; Kimberly, Robert P; Ramsey-Goldman, Rosalind; Petri, Michelle A; Reveille, John D; Vilá, Luis M; Alarcón, Graciela S; Kaufman, Kenneth M; Vyse, Timothy J; Jacob, Chaim O; Gaffney, Patrick M; Sivils, Kathy Moser; James, Judith A; Kamen, Diane L; Gilkeson, Gary S; Niewold, Timothy B; Merrill, Joan T; Scofield, R Hal; Criswell, Lindsey A; Stevens, Anne M; Boackle, Susan A; Kim, Jae-Hoon; Choi, Jiyoung; Pons-Estel, Bernardo A; Freedman, Barry I; Anaya, Juan-Manuel; Martin, Javier; Yu, C Yung; Chang, Deh-Ming; Song, Yeong Wook; Langefeld, Carl D; Chen, Weiling; Grossman, Jennifer M; Cantor, Rita M; Hahn, Bevra H; Tsao, Betty P

2013-01-01

235

Waxy genes from spelt wheat: new alleles for modern wheat breeding and new phylogenetic inferences about the origin of this species  

PubMed Central

Background and Aims Waxy proteins are responsible for amylose synthesis in wheat seeds, being encoded by three waxy genes (Wx-A1, Wx-B1 and Wx-D1) in hexaploid wheat. In addition to their role in starch quality, waxy loci have been used to study the phylogeny of wheat. The origin of European spelt (Triticum aestivum ssp. spelta) is not clear. This study compared waxy gene sequences of a Spanish spelt collection with their homologous genes in emmer (T. turgidum ssp. dicoccum), durum (T. turgidum ssp. durum) and common wheat (T. aestivum ssp. aestivum), together with other Asian and European spelt that could be used to determine the origin of European spelt. Methods waxy genes were amplified and sequenced. Geneious Pro software, DNAsp and MEGA5 were used for sequence, nucleotide diversity and phylogenetic analysis, respectively. Key Results Three, four and three new alleles were described for the Wx-A1, Wx-B1 and Wx-D1 loci, respectively. Spelt accessions were classified into two groups based on the variation in Wx-B1, which suggests that there were two different origins for the emmer wheat that has been found to be part of the spelt genetic make-up. One of these groups was only detected in Iberian material. No differences were found between the rest of the European spelt and the Asiatic spelt, which suggested that the Iberian material had a different origin from the other spelt sources. Conclusions The results suggested that the waxy gene variability present in wheat is undervalued. The evaluation of this variability has permitted the detection of ten new waxy alleles that could affect starch quality and thus could be used in modern wheat breeding. In addition, two different classes of Wx-B1 were detected that could be used for evaluating the phylogenetic relationships and the origins of different types of wheat. PMID:22984164

Guzmán, Carlos; Caballero, Leonor; Martín, Luis M.; Alvarez, Juan B.

2012-01-01

236

Characterization of Mhc-DRB allelic diversity in white-tailed deer (Odocoileus virginianus) provides insight into Mhc-DRB allelic evolution within Cervidae.  

PubMed

Although white-tailed deer (Odocoileus virginianus) are one of North America's best studied mammals, no information is available concerning allelic diversity at any locus of the major histocompatibility complex in this taxon. Using the polymerase chain reaction, single-stranded conformation polymorphism analysis, and DNA sequencing techniques, 15 DRB exon 2 alleles were identified among 150 white-tailed deer from a single population in southeastern Oklahoma. These alleles represent a single locus and exhibit a high degree of nucleotide and amino acid polymorphism, with most amino acid variation occurring at positions forming the peptide binding sites. Furthermore, twenty-seven amino acid residues unique to white-tailed deer DRB alleles were detected, with 19 of these occurring at residues forming contact points of the peptide binding region. Significantly higher rates of nonsynonymous than synonymous substitutions were detected among these DRB alleles. In contrast to other studies of Artiodactyla DRB sequences, interallelic recombination does not appear to be playing a significant role in the generation of allelic diversity at this locus in white-tailed deer. To examine evolution of white-tailed deer (Odvi-DRB) alleles within Cervidae, we performed a phylogenetic analysis of all published red deer (Ceel-DRB), roe deer (Caca-DRB), and moose (Alal-DRB) DRB alleles. The phylogenetic tree clearly shows a trans-species persistence of DRB lineages among these taxa. Moreover, this phylogenetic tree provides insight into evolution of DRB allelic lineages within Cervidae and may aid in assignment of red deer DRB alleles to specific loci. PMID:10199919

Van Den Bussche, R A; Hoofer, S R; Lochmiller, R L

1999-05-01

237

Null allele, allelic dropouts or rare sex detection in clonal organisms: simulations and application to real data sets of pathogenic microbes  

PubMed Central

Background Pathogens and their vectors are organisms whose ecology is often only accessible through population genetics tools based on spatio-temporal variability of molecular markers. However, molecular tools may present technical difficulties due to the masking of some alleles (allelic dropouts and/or null alleles), which tends to bias the estimation of heterozygosity and thus the inferences concerning the breeding system of the organism under study. This is especially critical in clonal organisms in which deviation from panmixia, as measured by Wright’s FIS, can, in principle, be used to infer both the extent of clonality and structure in a given population. In particular, null alleles and allelic dropouts are locus specific and likely produce high variance of Wright’s FIS across loci, as rare sex is expected to do. In this paper we propose a tool enabling to discriminate between consequences of these technical problems and those of rare sex. Methods We have performed various simulations of clonal and partially clonal populations. We introduce allelic dropouts and null alleles in clonal data sets and compare the results with those that exhibit increasing rates of sexual recombination. We use the narrow relationship that links Wright’s FIS to genetic diversity in purely clonal populations as assessment criterion, since this relationship disappears faster with sexual recombination than with amplification problems of certain alleles. Results We show that the relevance of our criterion for detecting poorly amplified alleles depends partly on the population structure, the level of homoplasy and/or mutation rate. However, the interpretation of data becomes difficult when the number of poorly amplified alleles is above 50%. The application of this method to reinterpret published data sets of pathogenic clonal microbes (yeast and trypanosomes) confirms its usefulness and allows refining previous estimates concerning important pathogenic agents. Conclusion Our criterion of superimposing between the FIS expected under clonality and the observed FIS, is effective when amplification difficulties occur in low to moderate frequencies (20-30%). PMID:25027508

2014-01-01

238

A collaborative European search for non- DQA1*05-DQB1*02 celiac disease loci on HLA-DR3 haplotypes: analysis of transmission from homozygous parents  

Microsoft Academic Search

The HLA-DQA1*05 with DQB1*02 alleles are a major risk factor for celiac disease (CD). To search for additional human leukocyte antigen (HLA) risk factors, we looked on the DR3-DQ2 risk haplotype, selected because it carries both DQ risk alleles in cis and is the more represented among CD patients. In a European consortium, we identified 109 families with a parent

Andrew S Louka; Simon J Moodie; Kati Karell; Elisabetta Bolognesi; Henry Ascher; Luigi Greco; Patricia Momigliano-Richiardi; Jukka Partanen; Paul J Ciclitira; Ludvig M Sollid

2003-01-01

239

The European Parliament and the Europeanization of Green Parties  

Microsoft Academic Search

‘Europeanization’, or the adaptation of national political actors to European integration, has increased the professionalization of European Green parties. Previous studies of this phenomenon’s effects on the Greens have not fully accounted for the processes behind this form of party development. Using a qualitative adaptation of Harmel and Janda’s (1994) model of party change as a foundation, this article develops

Eric H. Hines

2003-01-01

240

Maize ARGOS1 (ZAR1) transgenic alleles increase hybrid maize yield  

PubMed Central

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

Guo, Mei

2014-01-01

241

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

SciTech Connect

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.

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

242

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

PubMed

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 AR GOS1 (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

Guo, Mei; Rupe, Mary A; Wei, Jun; Winkler, Chris; Goncalves-Butruille, Marymar; Weers, Ben P; Cerwick, Sharon F; Dieter, Jo Ann; Duncan, Keith E; Howard, Richard J; Hou, Zhenglin; Löffler, Carlos M; Cooper, Mark; Simmons, Carl R

2014-01-01

243

Inference on Population Histories by Approximating Infinite Alleles Diffusion  

PubMed Central

Reconstruction of the past is an important task of evolutionary biology. It takes place at different points in a hierarchy of molecular variation, including genes, individuals, populations, and species. Statistical inference about population histories has recently received considerable attention, following the development of computational tools to provide tractable approaches to this very challenging problem. Here, we introduce a likelihood-based approach which generalizes a recently developed model for random fluctuations in allele frequencies based on an approximation to the neutral Wright–Fisher diffusion. Our new framework approximates the infinite alleles Wright–Fisher model and uses an implementation with an adaptive Markov chain Monte Carlo algorithm. The method is especially well suited to data sets harboring large population samples and relatively few loci for which other likelihood-based models are currently computationally intractable. Using our model, we reconstruct the global population history of a major human pathogen, Streptococcus pneumoniae. The results illustrate the potential to reach important biological insights to an evolutionary process by a population genetics approach, which can appropriately accommodate very large population samples. PMID:22993237

Sirén, Jukka; Hanage, William P.; Corander, Jukka

2013-01-01

244

Substitution processes in molecular evolution. III. Deleterious alleles.  

PubMed

The substitution processes for various models of deleterious alleles are examined using computer simulations and mathematical analyses. Most of the work focuses on the house-of-cards model, which is a popular model of deleterious allele evolution. The rate of substitution is shown to be a concave function of the strength of selection as measured by alpha = 2N sigma, where N is the population size and sigma is the standard deviation of fitness. For alpha < 1, the house-of-cards model is essentially a neutral model; for alpha > 4, the model ceases to evolve. The stagnation for large alpha may be understood by appealing to the theory of records. The house-of-cards model evolves to a state where the vast majority of all mutations are deleterious, but precisely one-half of those mutations that fix are deleterious (the other half are advantageous). Thus, the model is not a model of exclusively deleterious evolution as is frequently claimed. It is argued that there are no biologically reasonable models of molecular evolution where the vast majority of all substitutions are deleterious. Other models examined include the exponential and gamma shift models, the Hartl-Dykhuizen-Dean (HDD) model, and the optimum model. Of all those examined, only the optimum and HDD models appear to be reasonable candidates for silent evolution. None of the models are viewed as good candidates for protein evolution, as none are both biologically reasonable and exhibit the variability in substitutions commonly observed in protein sequence data. PMID:7851786

Gillespie, J H

1994-11-01

245

Alzheimer pathology of patients carrying apolipoprotein E epsilon 4 allele.  

PubMed

A recent report suggested that brains of Alzheimer patients homozygous for APOE epsilon 4 show increased amyloid pathology compared to APOE epsilon 3 homozygotes. We studied APOE allele frequencies in 73 AD patients and 38 controls. We also investigated relation of APOE genotypes to beta/A4 immunopositive plaques, cerebrovascular beta/A4 deposition, neurons expressing paired helical filaments (PHFs), and synaptophysin-like immunopositivity in 22 neuropathologically verified AD patients. We also correlated APOE genotypes of definite AD patients to beta/A4 immunoreactivity in dermal vessel walls detected in lifetime skin biopsy samples. APOE allele epsilon 4 frequency was increased in AD compared to nondemented controls (0.37 vs. 0.11; p = 0.006). The number of beta/A4 immunoreactive plaques, PHFs-containing neurons, the degree of cerebrovascular beta/A4 deposition or synaptophysin-like immunoreactivity did not differ significantly in AD patients with or without epsilon 4. beta/A4 deposition in dermal vessel walls was more frequent in definite AD patients with epsilon 4 (43%) than in patients without epsilon 4 (22%). However, the difference did not reach the statistical significance. PMID:8544899

Heinonen, O; Lehtovirta, M; Soininen, H; Helisalmi, S; Mannermaa, A; Sorvari, H; Kosunen, O; Paljärvi, L; Ryynänen, M; Riekkinen, P J

1995-01-01

246

Gluten-dependent enteropathy and atypical human leukocyte antigen alleles.  

PubMed

The risk for developing celiac disease is associated with the major histocompatibility complex class II human leukocyte antigen DQ2 and DQ8. We retrospectively reviewed the medical records of 127 consecutive cases of adult-onset celiac disease evaluated at a single United States center to determine the distribution of the associated human leukocyte antigen DQA1 and DQB1 alleles. The median patient age of diagnosis was 41 (range, 16-81) years. Ninety-five adults underwent human leukocyte antigen DQ typing. Eighty patients were DQ2 positive, 24 were DQ8 positive, and 11 were DQ2 and DQ8 positive. Four patients carried the uncommon, low-risk haplotype DQ2.2 (DQA1*02 and DQB1*02) without DQA1*05. Two patients did not carry human leukocyte antigen DQ2 or DQ8. All of the patients with atypical human leukocyte antigen DQ responded to a gluten-free diet. Although the majority of patients carry the human leukocyte antigen DQ2 or DQ8, gluten-dependent enteropathy periodically presents in adults with low-risk alleles. PMID:21292306

Harmon, Gregory S; Lebeck, Lauralynn K; Weidner, Noel

2011-08-01

247

Russian and East European Studies  

E-print Network

service and government work, business, advertising, finance, foreign trade, and teaching. A languageRussian and East European Studies Certificate About Us The Russian and East European Studies (REES see your future in international business? Many international corporations have interests

Saldin, Dilano

248

Cybergeo : European Journal of Geography  

E-print Network

Cybergeo : European Journal of Geography Systèmes, Modélisation, Géostatistiques context », Cybergeo : European Journal of Geography [En ligne], Systèmes, Modélisation, Géostatistiques of Geography Mehdi Saqalli, Charles L. Bielders, Pierre Defourny et Bruno Gérard Reconstituting family

Paris-Sud XI, Université de

249

Cybergeo : European Journal of Geography  

E-print Network

Cybergeo : European Journal of Geography Systèmes, Modélisation, Géostatistiques of Geography [En ligne], Systèmes, Modélisation, Géostatistiques, document 413, mis en ligne le 25 février 2008 environment at a regional level 2 Cybergeo : European Journal of Geography Isabelle Thomas, Cécile Tannier et

Paris-Sud XI, Université de

250

Eastern European Cinema.  

ERIC Educational Resources Information Center

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…

Iordanova, Dina

1999-01-01

251

European Green Crab  

USGS Multimedia Gallery

The European green crab (Carcinus maenas), has invaded fisheries in Northern California and in British Columbia, where it may compete with the much more valuable Dungeness crab. The CD it holds in its claws is a database for the USGS Pacific Coast Estuarine Information System, just one source used t...

252

European Space Agency (ESA)  

NSDL National Science Digital Library

The European Space Agency's homepage provides information on the ESA's telecommunications, navigations, Earth observations, human spaceflight missions, launches, space science, technology, industry, space operations, technical and quality management and television broadcasting. The site also contains a multimedia gallery, press releases, and an educational page for kids.

253

Trends in European English.  

ERIC Educational Resources Information Center

It is proposed that a European variety of English without native speakers is emerging as a language of international communication in Europe. This is a consequence of many factors, including the strength of the American economy, the breadth and depth of American research in science and technology, the pervasive influence of American-style popular…

Wilkinson, Robert

254

European cities: Towards a \\  

Microsoft Academic Search

The article puts forth the thesis that European cities are increasingly influenced by recreation, changing the essential quality of the urban space. I begin by setting out a theoretical framework in which cities are seen as specific places used as a resource by mobile individuals in a specific \\

Mathis Stock

2006-01-01

255

European inflation dynamics  

Microsoft Academic Search

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

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

2001-01-01

256

European Bioinformatics Institute  

NSDL National Science Digital Library

Some interesting research projects are described on this website from the European Bioinformatics Institute. The site offers a number of data resources on topics such as genomes, macromolecular structures, protein families, and structure analysis. Taxonomy and ontology databases are also linked here, as well as databases of research literature.

257

European leadership in globalization  

Microsoft Academic Search

Examines characteristics of successful organizations in the year 2000, and contributions of European leaders to the process. Compares different competencies of business leaders who merely travel abroad with those who settle there as expatriates for a time. Considers the environmental forces and other factors which require organizations to be globally transformed if they are to survive and prosper in the

Philip R. Harris; Robert T. Moran

1996-01-01

258

Multilingualism in European Workplaces  

ERIC Educational Resources Information Center

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…

Gunnarsson, Britt-Louise

2014-01-01

259

Efficiency in European banking  

Microsoft Academic Search

This paper extends the established literature on modelling the cost characteristics of banking markets by applying the flexible Fourier functional form and stochastic cost frontier methodologies to estimate scale economies, X-inefficiencies and technical change for a large sample of European banks between 1989 and 1997. The results reveal that scale economies are widespread for smallest banks and those in the

Y. Altunba?; E. P. M. Gardener; P. Molyneux; B. Moore

2001-01-01

260

Prevalence of CYP2C9 and VKORC1 alleles in the Argentine population and implications for prescribing dosages of anticoagulants.  

PubMed

Dicumarinic oral anticoagulants have a narrow therapeutic range and a great individual variability in response, which makes calculation of the correct dose difficult and critical. Genetic factors involved in this variability include polymorphisms of genes that encode the metabolic enzyme CYP2C9 and the target enzyme vitamin K epoxide reductase complex 1 (VKORC1); these polymorphisms can be associated with reduced enzymatic expression. We examined the frequency of the most relevant variants encoding CYP2C9 (alleles *1, *2 and *3) and VKORC1 (SNP -1639A>G) in the Argentinian population. Molecular typing was performed by PCR-RFLP on a randomly selected sample of 101 healthy volunteers from the Hospital Italiano de Buenos Aires gene bank. Fifty-seven subjects were identified as homozygous for CYP2C9*1 and 14 for *2, while 24 and 5 were heterozygous for *2 and *3 alleles; one individual was a composite heterozygote (*2/*3). When we examined VKORC1, 21 subjects were AA homozygous, 60 were AG heterozygotes and 20 were GG homozygotes. This is the first analysis of genotypic frequencies for CYP2C9 and VKORC1 performed in an Argentinian population. These allele prevalences are similar to what is known for Caucasian population, reflecting the European ancestor of our patient population, coming mostly from Buenos Aires city and surroundings. Knowledge of this prevalence information is instrumental for cost-effective pharmacogenomic testing in patients undergoing oral anticoagulation treatment. PMID:22290467

Scibona, P; Redal, M A; Garfi, L G; Arbelbide, J; Argibay, P F; Belloso, W H

2012-01-01

261

European Biodiversity Observation Network – EBONE  

Microsoft Academic Search

EBONE (European Biodiversity Observation Network) is a project developing a system of biodiversity observation at regional, national and European levels as a contribution to European reporting on biodiversity. The project focuses on GEO (Group of Earth Observations) task BI 07-01 to unify many of the disparate biodiversity observing systems and creates a platform to integrate biodiversity data with other types

R. H. G. Jongmanb; R. H. G. Jongman; F. Gerard; L. Whittaker; R. G. H. Bunce; B. Bauch; D. S. Schmeller

2009-01-01

262

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

PubMed

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

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

2007-10-01

263

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

PubMed Central

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

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

264

A Novel Dominant Transformer Allele of the Sex-Determining Gene Her-1 of Caenorhabditis Elegans  

PubMed Central

We have characterized a novel dominant allele of the sex-determining gene her-1 of Caenorhabditis elegans. This allele, called n695, results in the incomplete transformation of XX animals into phenotypic males. Previously characterized recessive her-1 alleles transform XO animals into phenotypic hermaphrodites. We have identified five new recessive her-1 mutations as intragenic suppressors of n695. Three of these suppressors are weak, temperature-sensitive alleles. We show that the recessive her-1 mutations are loss-of-function alleles, and that the her-1(n695) mutation results in a gain-of-function at the her-1 locus. The existence of dominant and recessive alleles that cause opposite phenotypic transformations demonstrates that the her-1 gene acts to control sexual identity in C. elegans. PMID:3220248

Trent, C.; Wood, W. B.; Horvitz, H. R.

1988-01-01

265

Molecular definition of an allelic series of mutations disrupting the mouse Lmx1a (dreher) gene.  

PubMed

Mice homozygous for the dreher (dr) mutation are characterized by pigmentation and skeletal abnormalities and striking behavioral phenotypes, including ataxia, vestibular deficits, and hyperactivity. The ataxia is associated with a cerebellar malformation that is remarkably similar to human Dandy-Walker malformation. Previously, positional cloning identified mutations in LIM homeobox transcription factor 1 alpha gene (Lmx1a) in three dr alleles. Two of these alleles, however, are extinct and unavailable for further analysis. In this article we report a new spontaneous dr allele and describe the Lmx1a mutations in this and six additional dr alleles. Strikingly, deletion null, missense, and frameshift mutations in these alleles all cause similar cerebellar malformations, suggesting that all dr mutations analyzed to date are null alleles. PMID:17019651

Chizhikov, Victor; Steshina, Ekaterina; Roberts, Richard; Ilkin, Yesim; Washburn, Linda; Millen, Kathleen J

2006-10-01

266

DEMETER DNA Glycosylase Establishes MEDEA Polycomb Gene Self-Imprinting by Allele-Specific Demethylation  

PubMed Central

SUMMARY MEDEA (MEA) is an Arabidopsis Polycomb group gene that is imprinted in the endosperm. The maternal allele is expressed and the paternal allele is silent. MEA is controlled by DEMETER (DME), a DNA glycosylase required to activate MEA expression, and METHYLTRANSFERASE I (MET1), which maintains CG methylation at the MEA locus. Here we show that DME is responsible for endosperm maternal-allele-specific hypomethylation at the MEA gene. DME can excise 5-methylcytosine in vitro and when expressed in E. coli. Abasic sites opposite 5-methylcytosine inhibit DME activity and might prevent DME from generating double-stranded DNA breaks. Unexpectedly, paternal-allele silencing is not controlled by DNA methylation. Rather, Polycomb group proteins that are expressed from the maternal genome, including MEA, control paternal MEA silencing. Thus, DME establishes MEA imprinting by removing 5-methylcytosine to activate the maternal allele. MEA imprinting is subsequently maintained in the endosperm by maternal MEA silencing the paternal allele. PMID:16469697

Gehring, Mary; Huh, Jin Hoe; Hsieh, Tzung-Fu; Penterman, Jon; Choi, Yeonhee; Harada, John J.; Goldberg, Robert B.; Fischer, Robert L.

2014-01-01

267

De novo mutations and allelic diversity at minisatellite locus D7S22 investigated by allele-specific four-state MVR-PCR analysis.  

PubMed

We have studied the allelic diversity and de novo mutations at the hypervariable minisatellite locus D7S22. A four-state minisatellite variant repeat unit mapping by PCR (MVR-PCR) method was developed for this purpose, and a substitution polymorphism close to the repeat array was used to design allele-specific flanking primers to study individual haplotypes in genomic DNA. A total of 150 alleles from different allele size groups and flanking haplotypes were mapped. On average, MVR-codes extending 65 repeats (2.4 kb) into the repeat array were obtained. The interspersion patterns of variant repeats were highly polymorphic. However, subgroups of alleles close in size and with identical flanking haplotype revealed common MVR-code characteristics indicating a close evolutionary relationship. Unlike the situation in many other hypervariable minisatellites, no polarized variability was revealed at this minisatellite locus. Fifty four small families with D7S22 de novo mutations were analysed by MVR-PCR. The sites where the length change occurred were revealed in 22 cases, while in 32 cases the mutation obviously occurred further into the repeat array. In agreement with a non-polar distribution of the allelic variation, there was no evidence for a hypermutable hot spot for mutation within the repeat array. Comparison of MVR-codes in the mutant and progenitor in gain mutations indicated that at least one, possibly four cases, reflected inter-allelic events. Together with evidence from DNA sequencing of alleles of <2 kb, this indicates that as many as half of the gain mutations might be inter-allelic events in D7S22. Based on these results, different factors which might affect the mutation rate are discussed. PMID:9817929

Andreassen, R; Olaisen, B

1998-12-01

268

Variation in optineurin (OPTN) allele frequencies between and within populations  

PubMed Central

Purpose To evaluate the extent to which mutations in the optineurin (OPTN) glaucoma gene play a role in glaucoma in different populations. Methods Case-controlled study of OPTN sequence variants in individuals with or without glaucoma in populations of different ancestral origins and evaluate previous OPTN reports. We analyzed 314 subjects with African, Asian, Caucasian and Hispanic ancestries included 229 cases of primary open-angle glaucoma, 51 cases of juvenile-onset open-angle glaucoma, 33 cases of normal tension glaucoma, and 371 controls. Polymerase chain reaction-amplified OPTN coding exons were resequenced and case frequencies were compared to frequencies in controls matched for ancestry. Results The E50K sequence variant was identified in one individual from Chile with normal tension glaucoma, and the 691_692insAG variant was found in one Ashkenazi Jewish individual from Russia. The R545Q variant was found in two Asian individuals with primary open-angle glaucoma; one of Filipino ancestry and one of Korean ancestry. In addition to presenting OPTN allele frequencies for Caucasian and Asian populations that have been the subject of previous reports, we also present information for populations of Hispanic and black African ancestries. Conclusions Our study contributes additional evidence to support the previously reported association of the OPTN E50K mutation with glaucoma. After finding an additional 691_692insAG OPTN variant, we can still only conclude that this variant is rare. Combined analysis of our data with data from more than a dozen other studies indicates no association of R545Q with glaucoma in most populations. Those same studies disagree in their conclusions regarding the role of M98K in glaucoma. Our analysis of the combined data provides statistically significant evidence of association of M98K with normal tension glaucoma in Asian populations, but not in Caucasian populations; however, the validity of this conclusion is questionable because of large differences in allele frequencies between and within populations. It is currently not possible to tell how much of the underlying cause of the allele frequency difference is attributable to demographic, technical, or ascertainment differences among the studies. PMID:17293779

Ayala-Lugo, Rosa M.; Pawar, Hemant; Reed, David M.; Lichter, Paul R.; Moroi, Sayoko E.; Page, Michael; Eadie, James; Azocar, Veronica; Maul, Eugenio; Ntim-Amponsah, Christine; Bromley, William; Obeng-Nyarkoh, Ebenezer; Johnson, A. Tim; Kijek, Theresa Guckian; Downs, Catherine A.; Johnson, Jenae M.; Perez-Grossmann, Rodolfo A.; Guevara-Fujita, Maria-Luisa; Fujita, Ricardo; Wallace, Margaret R.

2007-01-01

269

Attention-deficit\\/hyperactivity disorder (ADHD) association with the DAT1 core promoter ?67 T allele  

Microsoft Academic Search

Association between attention deficit hyperactivity disorder (ADHD) and the 10-repeat allele of a polymorphism (a 40 bp variable number of tandem repeats) in the dopamine transporter gene (DAT1) has been reported by several groups. In this study, we examined whether either allele of the DAT1 core promoter ?67 functional polymorphism is associated with ADHD in a case\\/control study. The allele

Mina Ohadi; Elham Shirazi; Mehdi Tehranidoosti; Narges Moghimi; Mohammad R. Keikhaee; Sima Ehssani; Ali Aghajani; Hossein Najmabadi

2006-01-01

270

Correlation in chicken between the marker LEI0258 alleles and Major Histocompatibility Complex sequences  

Microsoft Academic Search

Background  The LEI0258 marker is located within the B region of the chicken Major Histocompatibility Complex (MHC), and is surprisingly\\u000a well associated with serology. Therefore, the correlation between the LEI0258 alleles and the MHC class I and the class II\\u000a alleles at the level of sequences is worth investigating in chickens. Here we describe to which extent the LEI0258 alleles\\u000a are

Olympe Chazara; Helle Risdahl Juul-Madsen; Chi-Sheng Chang; Michele Tixier-Boichard; Bertrand Bed’hom

2011-01-01

271

Dynamics of insecticide resistance alleles in house fly populations from New York and Florida  

Microsoft Academic Search

The frequency of insecticide-resistance alleles for two genes (Vssc1 and CYP6D1) was studied in field collected populations of house flies from two different climates. While the frequency of these resistance alleles in flies at dairies from four states has recently been reported, there is no information on the relative change of these allele frequencies over time. House flies were collected

Frank D. Rinkevich; Ronda L. Hamma; Christopher J. Geden; Jeffrey G. Scott

2007-01-01

272

Identification of a novel HLA-A allele HLA-A*2451 in a Chinese donor.  

PubMed

A novel human leucocyte antigen-A (HLA-A) allele, A*2451, has been identified during routine sequence-specific oligonucleotide typing and sequence-based typing of a sample from a registered donor of the Chinese Marrow Donor Program. The A*2451 allele differs from the closest matching allele A*2415 by one nucleotide substitution in exon 3, nt 363 G-->A, resulting in an amino acid change from M ATG to I ATA at codon 121. PMID:15982259

Li, J-P; Liu, X-Z; Gao, H-F; Liu, X; Chen, Y; Li, X-F; Zhe, Q; Gao, J-B; Zhang, X; Lv, Y-Z; Yang, L-Y; Huang, X-Y; Yu, Y-Y; Yu, F-Q; Chi, L-P

2005-07-01

273

Association of apolipoprotein E allele {epsilon}4 with late-onset sporadic Alzheimer`s disease  

SciTech Connect

Apolipoprotein E, type {epsilon}4 allele (ApoE {epsilon}4), is associated with late-onset sporadic Alzheimer`s disease (AD) in French patients. The association is highly significant (0.45 AD versus 0.12 controls for {epsilon}4 allele frequencies). These data support the involvement of ApoE {epsilon}4 allele as a very important risk factor for the clinical expression of AD. 22 refs., 1 fig., 3 tabs.

Lucotte, G.; David, F.; Berriche, S. [Regional Center of Neurogenetics, Reims (France)] [and others

1994-09-15

274

Apolipoprotein E polymorphism in Southern Iran: E4 allele in the lowest reported amounts  

Microsoft Academic Search

Background: Apolipoprotein E (apoE) with three major alleles E2, E3 and E4 is one of the critical genes in lipid metabolism. Common\\u000a apoE alleles are in association with an increase in risk for central nervous and cardiovascular diseases such as Alzheimer’s\\u000a disease, dementia, multiple sclerosis, atherosclerosis, coronary heart disease, hyperlipoproteinemia and stroke. ApoE3 is\\u000a known as the most frequent allele

Masood Bazrgar; Mehran Karimi; Mohsen Fathzadeh; Sara Senemar; Farah Peiravian; Ashraf Shojaee; Mostafa Saadat

2008-01-01

275

Association between clozapine response and allelic variation in 5HT 2A receptor gene  

Microsoft Academic Search

We report allelic association between a polymorphism (T102C) within the coding region of the 5-HT2A gene (HTR2A, 13q14-21) and response to clozapine in schizophrenic patients. Homozygosity for the C102 allele was more frequent (30\\/57, 53%) among patients who did not respond to clozapine than in those who responded (23\\/92, 25%). This finding is evidence that allelic variation of genes which

M. J. Arranz; D. A. Collier; M. Sodhi; D. Ball; G. W. Roberts; P. Sham; R. Kerwin; J. Price

1995-01-01

276

ERPA: European Research Papers Archive  

NSDL National Science Digital Library

ERPA, the European Research Papers Archive, provides a common interface for searching a database of online working papers relevant to European integration. Contributors to the archive include the Robert Schuman Centre of the Academy of European Law at the European University Institute, the Max Planck Institute for the Study of Societies, the Jean Monnet Working Papers Series at Harvard Law School, and the European Communities Studies Association-Austria. Users can select either a short form to search recent additions to the archive or a long form to either or to also access the many advanced search options, including full-text searches.

277

Only three mutations account for almost all defective alleles causing adenine phosphoribosyltransferase deficiency in Japanese patients.  

PubMed

We analyzed mutant alleles of adenine phosphoribosyltransferase (APRT) deficiency in Japanese patients. Among 141 defective APRT alleles from 72 different families, 96 (68%), 30 (21%), and 10 (7%) had an ATG to ACG missense mutation at codon 136 (APRT*J allele), TGG to TGA nonsense mutation at codon 98, and duplication of a 4-bp sequence in exon 3, respectively. The disease-causing mutations of only four (3%) of all the alleles among Japanese remain to be elucidated. Thus, a diagnosis can be made for most of the Japanese APRT-deficient patients by identifying only three disease-causing mutations. All of the different alleles with the same mutation had the same haplotype, except for APRT*J alleles, thereby suggesting that alleles with the same mutation in different families were derived from the same ancestral gene. Evidence for a crossover or gene conversion event within the APRT gene was observed in an APRT*J mutant allele. Distribution of mutant alleles encoding APRT deficiency among the Japanese was similar to that seen in cystic fibrosis genes among Caucasians and Tay-Sachs genes among the Ashkenazi Jews. PMID:1353080

Kamatani, N; Hakoda, M; Otsuka, S; Yoshikawa, H; Kashiwazaki, S

1992-07-01

278

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

SciTech Connect

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.

Wu, D.Y.; Ugozzoli, L.; Pal, B.K.; Wallace, B. (Beckman Research Institute of the City of Hope, Duarte, CA (USA))

1989-04-01

279

Haptoglobin genotyping of Vietnamese: global distribution of HP del, complete deletion allele of the HP gene.  

PubMed

The haptoglobin (HP) gene deletion allele (HP(del)) is responsible for anhaptoglobinemia and a genetic risk factor for anaphylaxis reaction after transfusion due to production of the anti-HP antibody. The distribution of this allele has been explored by several groups including ours. Here, we studied the frequency of HP(del) in addition to the distribution of common HP genotypes in 293 Vietnamese. The HP(del) was encountered with the frequency of 0.020. The present result suggested that this deletion allele is restricted to East and Southeast Asians. Thus, this allele seems to be a potential ancestry informative marker for these populations. PMID:25212669

Soejima, Mikiko; Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Lan, Vi Thi Mai; Minh, Tu Binh; Takahashi, Shin; Trang, Pham Thi Kim; Viet, Pham Hung; Tanabe, Shinsuke; Koda, Yoshiro

2015-01-01

280

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

ERIC Educational Resources Information Center

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)

Nussbaum, Francis, Jr.

1988-01-01

281

Allelic Variation in KIR2DL3 Generates a KIR2DL2-like Receptor with Increased Binding to Its HLA-C Ligand12  

PubMed Central

Although extensive homology exists between their extracellular domains, natural killer cell inhibitory receptors KIR2DL2*001 and KIR2DL3*001 have previously been shown to differ substantially in their HLA-C binding avidity. To explore the largely uncharacterized impact of allelic diversity, the most common KIR2DL2/3 allelic products in European American and African American populations were evaluated for surface expression and binding affinity to their HLA-C group 1 and 2 ligands. Although no significant differences in the degree of cell membrane localization were detected in a transfected human NKL cell line by flow cytometry, surface plasmon resonance and KIR binding to a panel of HLA allotypes demonstrated that KIR2DL3*005 differed significantly from other KIR2DL3 allelic products in its ability to bind HLA-C. The increased affinity and avidity of KIR2DL3*005 for its ligand was also demonstrated to have a larger impact on the inhibition of IFN-? production by the human KHYG-1 NK cell line compared to KIR2DL3*001, a low affinity allelic product. Site-directed mutagenesis established that the combination of arginine at residue 11 and glutamic acid at residue 35 in KIR2DL3*005 were critical to the observed phenotype. Although these residues are distal to the KIR/HLA-C interface, molecular modeling suggests that alteration in the interdomain hinge angle of KIR2DL3*005 towards that found in KIR2DL2*001, another strong receptor of the KIR2DL2/3 family, may be the cause of this increased affinity. The regain of inhibitory capacity by KIR2DL3*005 suggests that the rapidly evolving KIR locus may be responding to relatively recent selective pressures placed upon certain human populations. PMID:23686481

Frazier, William R.; Steiner, Noriko; Hou, Lihua; Dakshanamurthy, Sivanesan; Hurley, Carolyn Katovich

2013-01-01

282

Haplotype Variation of Glu-D1 Locus and the Origin of Glu-D1d Allele Conferring Superior End-Use Qualities in Common Wheat  

PubMed Central

In higher plants, seed storage proteins (SSPs) are frequently expressed from complex gene families, and allelic variation of SSP genes often affects the quality traits of crops. In common wheat, the Glu-D1 locus, encoding 1Dx and 1Dy SSPs, has multiple alleles. The Glu-D1d allele frequently confers superior end-use qualities to commercial wheat varieties. Here, we studied the haplotype structure of Glu-D1 genomic region and the origin of Glu-D1d. Using seven diagnostic DNA markers, 12 Glu-D1 haplotypes were detected among common wheat, European spelt wheat (T. spelta, a primitive hexaploid relative of common wheat), and Aegilops tauschii (the D genome donor of hexaploid wheat). By comparatively analyzing Glu-D1 haplotypes and their associated 1Dx and 1Dy genes, we deduce that the haplotype carrying Glu-D1d was likely differentiated in the ancestral hexaploid wheat around 10,000 years ago, and was subsequently transmitted to domesticated common wheat and T. spelta. A group of relatively ancient Glu-D1 haplotypes was discovered in Ae. tauschii, which may serve for the evolution of other haplotypes. Moreover, a number of new Glu-D1d variants were found in T. spelta. The main steps in Glu-D1d differentiation are proposed. The implications of our work for enhancing the utility of Glu-D1d in wheat quality improvement and studying the SSP alleles in other crop species are discussed. PMID:24098671

Li, Yiwen; Zhang, Kunpu; Lou, Haijuan; An, Xueli; Dong, Lingli; Gu, Yong Qiang; Anderson, Olin D.; Liu, Xin; Qin, Huanju; Wang, Daowen

2013-01-01

283

Population structure at different minor allele frequency levels.  

PubMed

Inferring population genetic structure from large-scale genotyping of single-nucleotide polymorphisms or variants is an important technique for studying the history and distribution of extant human populations, but it is also a very important tool for adjusting tests of association. However, the structures inferred depend on the minor allele frequency of the variants; this is very important when considering the phenotypic association of rare variants. Using the Genetic Analysis Workshop 18 data set for 142 unrelated individuals, which includes genotypes for many rare variants, we study the following hypothesis: the difference in detected structure is the result of a "scale" effect; that is, rare variants are likely to be shared only locally (smaller scale), while common variants can be spread over longer distances. The result is similar to that of using kernel principal component analysis, as the bandwidth of the kernel is changed. We show how different structures become evident as we consider rare or common variants. PMID:25519390

De la Cruz, Omar; Raska, Paola

2014-01-01

284

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

PubMed Central

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

Schiffers, Katja H; Travis, Justin MJ

2014-01-01

285

New York State TrueAllele® Casework Validation Study*  

PubMed Central

DNA evidence can pose interpretation challenges, particularly with low-level or mixed samples. It would be desirable to make full use of the quantitative data, consider every genotype possibility, and objectively produce accurate and reproducible DNA match results. Probabilistic genotype computing is designed to achieve these goals. This validation study assessed TrueAllele® probabilistic computer interpretation on 368 evidence items in 41 test cases and compared the results with human review of the same data. Whenever there was a human result, the computer's genotype was concordant. Further, the computer produced a match statistic on 81 mixture items (for 87 inferred matching genotypes) in the test cases, while human review reported a statistic on 25 of these items (30.9%). Using match statistics to quantify information, probabilistic genotyping was shown to be sensitive, specific, and reproducible. These results demonstrate that objective probabilistic genotyping of biological evidence can reliably preserve DNA identification information. PMID:23865896

Perlin, Mark W; Belrose, Jamie L; Duceman, Barry W

2013-01-01

286

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

PubMed

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

Qiu, Shuhao; Fedorov, Alexei

2015-05-01

287

Fine-mapping natural alleles: quantitative complementation to the rescue  

PubMed Central

Mapping the genes responsible for natural variation and divergence is a challenging task. Many studies have mapped genes to genomic regions, or generated lists of candidates, but few studies have implicated specific genes with a high standard of evidence. I propose that combining recent advances in genomic engineering with a modified version of the quantitative complementation test will help turn candidate genes into causal genes. By creating loss-of-function mutations in natural strains, and using these mutations to quantitatively fail-to-complement natural alleles, fine mapping should be greatly facilitated. As an example, I propose that the CRISPR/Cas9 system could be combined with the FLP/FRT system to fine-map genes in the numerous systems where inversions have frustrated these efforts. PMID:24628660

Turner, Thomas L.

2014-01-01

288

Early detrimental metabolic outcomes of rs17300539-A allele of ADIPOQ gene despite higher adiponectinemia.  

PubMed

Minor allele A of single-nucleotide polymorphism (SNP) 11391 G/A of ADIPOQ gene (rs17300539) has been consistently associated with higher adiponectin levels in adults and children. The aim of this study was to investigate the metabolic role of this variant in a large cohort of children of European origin. A total of 1,852 children from two general populations in Verona and in Fleurbaix-Laventie and from the Lille childhood obesity cohort, were genotyped and pooled together after checking for the absence of genetic heterogeneity for rs17300539 between Italian and French children. The genotype of rs17300539 was studied in relation to circulating adiponectin levels, BMI, fasting plasma glucose, fasting serum insulin (FSI), insulin resistance index (homeostasis model assessment of insulin resistance (HOMA(IR))), high-density lipoprotein cholesterol, and triglycerides. After adjustment for known confounders, rs17300539 GA+AA carriers had 1.6 microg/ml higher adiponectin levels (P = 6 x 10(-8)) than GG carriers. They also showed higher BMI (B = 0.97, P = 0.015) and higher prevalence of obesity (OR = 1.35 (1.06-1.85), P = 0.015) than GG carriers. Before adjusting for obesity status, GA+AA carriers had higher FSI (B = 1.10, P = 0.040) and higher HOMA(IR) (B = 0.31, P = 0.020) than GG carriers. After adjustment for obesity status, they did not differ from GG carriers for any metabolic parameter, either among obese or nonobese children. The rs17300539-A variant, though consistently associated with higher adiponectin levels, does not exert any appreciable protective metabolic effect in children, either in the presence or absence of obesity. In contrast, this SNP may increase the risk for childhood obesity and related insulin resistance. PMID:19893502

Morandi, Anita; Maffeis, Claudio; Lobbens, Stéphane; Bouatia-Naji, Nabila; Heude, Barbara; Pinelli, Leonardo; Meyre, David; Froguel, Philippe

2010-07-01

289

Identification of Allelic Heterogeneity at Type-2 Diabetes Loci and Impact on Prediction  

PubMed Central

Although over 60 single nucleotide polymorphisms (SNPs) have been identified by meta-analysis of genome-wide association studies for type-2 diabetes (T2D) among individuals of European descent, much of the genetic variation remains unexplained. There are likely many more SNPs that contribute to variation in T2D risk, some of which may lie in the regions surrounding established SNPs - a phenomenon often referred to as allelic heterogeneity. Here, we use the summary statistics from the DIAGRAM consortium meta-analysis of T2D genome-wide association studies along with linkage disequilibrium patterns inferred from a large reference sample to identify novel SNPs associated with T2D surrounding each of the previously established risk loci. We then examine the extent to which the use of these additional SNPs improves prediction of T2D risk in an independent validation dataset. Our results suggest that multiple SNPs at each of 3 loci contribute to T2D susceptibility (TCF7L2, CDKN2A/B, and KCNQ1; p<5×10?8). Using a less stringent threshold (p<5×10?4), we identify 34 additional loci with multiple associated SNPs. The addition of these SNPs slightly improves T2D prediction compared to the use of only the respective lead SNPs, when assessed using an independent validation cohort. Our findings suggest that some currently established T2D risk loci likely harbor multiple polymorphisms which contribute independently and collectively to T2D risk. This opens a promising avenue for improving prediction of T2D, and for a better understanding of the genetic architecture of T2D. PMID:25393876

Klimentidis, Yann C.; Zhou, Jin; Wineinger, Nathan E.

2014-01-01

290

Burden of risk alleles for Hypertension Increases Risk of Intracerebral Hemorrhage  

PubMed Central

SUMMARY Background and Purpose Genetic variation influences risk of intracerebral hemorrhage (ICH). Hypertension (HTN) is a potent risk factor for ICH and several common genetic variants (SNPs) associated with blood pressure (BP) levels have been identified. We sought to determine whether the cumulative burden of BP-related SNPs is associated with risk of ICH and pre-ICH diagnosis of HTN. Methods Prospective multicenter case-control study in 2272 subjects of European descent (1025 cases and 1247 controls). Thirty-nine SNPs reported to be associated with BP levels were identified from the National Human Genome Research Institute GWAS catalog. Single-SNP association analyses were performed for the outcomes ICH and pre-ICH HTN. Subsequently, weighted and unweighted genetic risk scores were constructed using these SNPs and entered as the independent variable in logistic regression models with ICH and pre-ICH HTN as the dependent variables. Results No single SNP was associated with either ICH or pre-ICH HTN. The BP-based unweighted genetic risk score was associated with risk of ICH (odds ratio [OR] = 1.11, 95% confidence interval [CI] 1.02–1.21, p=0.01) and the subset of ICH in deep regions (OR=1.18, 95%CI 1.07–1.30, p=0.001), but not with the subset of lobar ICH. The score was associated with a history of HTN among controls (OR=1.17, 95%CI 1.04–1.31, p=0.009) and ICH cases (OR=1.15, 95%CI 1.01–1.31, p=0.04). Similar results were obtained when using a weighted score. Conclusion Increasing numbers of high blood pressure-related alleles are associated with increased risk of deep ICH as well as with clinically identified HTN. PMID:22933587

Falcone, Guido J.; Biffi, Alessandro; Devan, William; Jagiella, Jeremiasz M.; Schmidt, Helena; Kissela, Brett; Hansen, Björn M.; Jimenez-Conde, Jordi; Giralt-Steinhauer, Eva; Elosua, Roberto; Cuadrado-Godia, Elisa; Soriano, Carolina; Ayres, Alison M.; Schwab, Kristin; Pera, Joanna; Urbanik, Andrzej; Rost, Natalia S.; Goldstein, Joshua N.; Viswanathan, Anand; Pichler, Alexander; Enzinger, Christian; Norrving, Bo; Tirschwell, David L.; Selim, Magdy; Brown, Devin L.; Silliman, Scott L.; Worrall, Bradford B.; Meschia, James F.; Kidwell, Chelsea S.; Montaner, Joan; Fernandez-Cadenas, Israel; Delgado, Pilar; Broderick, Joseph P.; Greenberg, Steven M.; Roquer, Jaume; Lindgren, Arne; Slowik, Agnieszka; Schmidt, Reinhold; Flaherty, Matthew L.; Kleindorfer, Dawn O.; Langefeld, Carl D.; Woo, Daniel; Rosand, Jonathan

2012-01-01

291

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.

292

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.

293

A Melanocortin 1 Receptor Allele Suggests Varying Pigmentation Among Neanderthals  

Microsoft Academic Search

The melanocortin 1 receptor (MC1R) regulates pigmentation in humans and other vertebrates. Variants of MC1R with reduced function are associated with pale skin color and red hair in humans of primarily European origin. We amplified and sequenced a fragment of the MC1R gene (mc1r) from two Neanderthal remains. Both specimens have a mutation that was not found in ~3700 modern

Carles Lalueza-Fox; Holger Römpler; David Caramelli; Claudia Stäubert; Giulio Catalano; David Hughes; Nadin Rohland; Elena Pilli; Laura Longo; Silvana Condemi; Marco de la Rasilla; Javier Fortea; Antonio Rosas; Mark Stoneking; Torsten Schöneberg; Jaume Bertranpetit; Michael Hofreiter

2007-01-01

294

Fibroblast phenotype in male carriers of FMR1 premutation alleles  

PubMed Central

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an adult-onset neurodegenerative disorder among carriers of premutation expansions (55–200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. The clinical features of FXTAS, as well as various forms of clinical involvement in carriers without FXTAS, are thought to arise through a direct toxic gain of function of high levels of FMR1 mRNA containing the expanded CGG repeat. Here we report a cellular endophenotype involving increased stress response (HSP27, HSP70 and CRYAB) and altered lamin A/C expression/organization in cultured skin fibroblasts from 11 male carriers of premutation alleles of the FMR1 gene, including six patients with FXTAS and five premutation carriers with no clinical evidence of FXTAS, compared with six controls. A similar abnormal cellular phenotype was found in CNS tissue from 10 patients with FXTAS. Finally, there is an analogous abnormal cellular distribution of lamin A/C isoforms in knock-in mice bearing the expanded CGG repeat in the murine Fmr1 gene. These alterations are evident even in mouse embryonic fibroblasts, raising the possibility that, in humans, the expanded-repeat mRNA triggers pathogenic mechanisms early in development, thus providing a molecular basis for the neurodevelopmental abnormalities observed in some children and clinical symptoms in some adults who are carriers of premutation FMR1 alleles. Cellular dysregulation in fibroblasts represents a novel and highly advantageous model for investigating disease pathogenesis in premutation carriers and for quantifying and monitoring disease progression. Fibroblast studies may also prove useful in screening and testing the efficacy of therapeutic interventions. PMID:19864489

Garcia-Arocena, Dolores; Yang, Jane E.; Brouwer, Judith R.; Tassone, Flora; Iwahashi, Christine; Berry-Kravis, Elizabeth M.; Goetz, Christopher G.; Sumis, Allison M.; Zhou, Lili; Nguyen, Danh V.; Campos, Luis; Howell, Erin; Ludwig, Anna; Greco, Claudia; Willemsen, Rob; Hagerman, Randi J.; Hagerman, Paul J.

2010-01-01

295

Introgressive hybridization: brown bears as vectors for polar bear alleles.  

PubMed

The dynamics and consequences of introgression can inform about numerous evolutionary processes. Biologists have therefore long been interested in hybridization. One challenge, however, lies in the identification of nonadmixed genotypes that can serve as a baseline for accurate quantification of admixture. In this issue of Molecular Ecology, Cahill et al. (2015) analyse a genomic data set of 28 polar bears, eight brown bears and one American black bear. Polar bear alleles are found to be introgressed into brown bears not only near a previously identified admixture zone on the Alaskan Admiralty, Baranof and Chichagof (ABC) Islands, but also far into the North American mainland. Elegantly contrasting admixture levels at autosomal and X chromosomal markers, Cahill and colleagues infer that male-biased dispersal has spread these introgressed alleles away from the Late Pleistocene contact zone. Compared to a previous study on the ABC Island population in which an Alaskan brown bear served as a putatively admixture-free reference, Cahill et al. (2015) utilize a newly sequenced Swedish brown bear as admixture baseline. This approach reveals that brown bears have been impacted by introgression from polar bears to a larger extent (up to 8.8% of their genome), than previously known, including the bear that had previously served as admixture baseline. No evidence for introgression of brown bear into polar bear is found, which the authors argue could be a consequence of selection. Besides adding new exciting pieces to the puzzle of polar/brown bear evolutionary history, the study by Cahill and colleagues highlights that wildlife genomics is moving from analysing single genomes towards a landscape genomics approach. PMID:25775930

Hailer, Frank

2015-03-01

296

Genetic Tools for Allelic Replacement in Burkholderia Species? †  

PubMed Central

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 ?-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 (Telr) and trimethoprim (Tpr) 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 Telr-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 (Tpr), which is one of two constructed flp-containing plasmids, pFLP-AB4 (Telr) and pFLP-AB5 (Tpr). 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 ?betBA::Telr-FRT and ?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

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

2008-01-01

297

Associations of HLA alleles with specific language impairment  

PubMed Central

Background Human leukocyte antigen (HLA) loci have been implicated in several neurodevelopmental disorders in which language is affected. However, to date, no studies have investigated the possible involvement of HLA loci in specific language impairment (SLI), a disorder that is defined primarily upon unexpected language impairment. We report association analyses of single-nucleotide polymorphisms (SNPs) and HLA types in a cohort of individuals affected by language impairment. Methods We perform quantitative association analyses of three linguistic measures and case-control association analyses using both SNP data and imputed HLA types. Results Quantitative association analyses of imputed HLA types suggested a role for the HLA-A locus in susceptibility to SLI. HLA-A A1 was associated with a measure of short-term memory (P = 0.004) and A3 with expressive language ability (P = 0.006). Parent-of-origin effects were found between HLA-B B8 and HLA-DQA1*0501 and receptive language. These alleles have a negative correlation with receptive language ability when inherited from the mother (P = 0.021, P = 0.034, respectively) but are positively correlated with the same trait when paternally inherited (P = 0.013, P = 0.029, respectively). Finally, case control analyses using imputed HLA types indicated that the DR10 allele of HLA-DRB1 was more frequent in individuals with SLI than population controls (P = 0.004, relative risk = 2.575), as has been reported for individuals with attention deficit hyperactivity disorder (ADHD). Conclusion These preliminary data provide an intriguing link to those described by previous studies of other neurodevelopmental disorders and suggest a possible role for HLA loci in language disorders. PMID:24433325

2014-01-01

298

Telemedicine and European law.  

PubMed

A Directive of the European Union was first published in 2000, which dealt with telemedicine as part of its provisions. This E-Commerce Directive, as it became known, was subjected to further study which revealed some problems relative to the practice of telemedicine. Among the subjects discussed in this paper are those of privacy, data protection, free movement of services, the impact of electronic communication and ethical issues. PMID:15074761

Callens, Stefaan

2003-01-01

299

The European Spallation Source  

SciTech Connect

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.

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

300

European Environmental Education Newsletter  

NSDL National Science Digital Library

Written by professionals at the Technical University of Hamburg-Harburg (Germany), the European Environmental Education Newsletter strives "to provide further insights into the subject matter of environmental education and on matters related to sustainability, with an international flavor." To that end, the newsletter provides updates of current events as well as announcements of upcoming meetings, educational materials, and publications, with an emphasis on Europe.

301

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.

302

Apolipoprotein E alleles in Alzheimer`s and Parkinson`s patients  

SciTech Connect

A number of investigators have found an association between the apolipoprotein E4 allele and Alzheimer`s disease. The E4 allele appears at a higher frequency in late onset familial Alzheimer`s patients. In our studies we obtained blood samples from early and late onset familial and sporadic Alzheimer`s patients and spouses, as well as from Parkinson`s patients. The patients were diagnosed as probable Alzheimer`s patients after a neurological examination, extensive blood work, and a CAT scan. The diagnosis was made according to the NINCDS-ADRDA criteria. The apolipoprotein E4 polymorphism was detected after PCR amplification of genomic DNA, restriction enzyme digestion with Hhal, and polyacrylamide gel electrophoresis. Ethidium bromide-stained bands at 91 bp were designated as allele 3, at 83 bp as allele 2, and at 72 bp as allele 4. Of the 84 probable Alzheimer`s patients (all of whom were Caucasian), 47 were heterozygous and 13 were homozygous for the E4 allele. There were 26 early onset patients; 13 were heterozygous and 7 homozygous for the E4 allele. The frequencies for the E4 allele for late onset familial patients was 0.45 and for sporadic patients was 0.37. We analyzed 77 spouses with an average age of 71.9 {plus_minus} 7.4 years as controls, and 15 were heterozygous for the E4 allele for an E4 frequency of 0.097. Of the 53 Parkinson`s patients, 11 had the E4 allele for a frequency of 0.113. Thus our findings support the association of the ApoE4 allele with Alzheimer`s disease.

Poduslo, S.E. [Texas Tech Univ., Lubbock, TX (United States); Schwankhaus, J.D. [Department of Veterans Affairs, Lubbock, TX (United States)

1994-09-01

303

AGG interruptions and maternal age affect FMR1 CGG repeat allele stability during transmission  

PubMed Central

Background The presence of AGG interruptions in the CGG repeat locus of the fragile X mental retardation 1 (FMR1) gene decreases the instability of the allele during transmission from parent to child, and decreases the risk of expansion of a premutation allele to a full mutation allele (the predominant cause of fragile X syndrome) during maternal transmission. Methods To strengthen recent findings on the utility of AGG interruptions in predicting instability or expansion to a full mutation of FMR1 CGG repeat alleles, we assessed the outcomes of 108 intermediate (also named gray zone) and 710 premutation alleles that were transmitted from parent to child, and collected from four international clinical sites. We have used the results to revise our initial model that predicted the risk of a maternal premutation allele expanding to a full mutation during transmission and to test the effect of AGG interruptions on the magnitude of expanded allele instability of intermediate or premutation alleles that did not expand to a full mutation. Results Consistent with previous studies, the number of AGG triplets that interrupts the CGG repeat locus was found to influence the risk of allele instability, including expansion to a full mutation. The total length of the CGG repeat allele remains the best predictor of instability or expansion to a full mutation, but the number of AGG interruptions and, to a much lesser degree, maternal age are also factors when considering the risk of transmission of the premutation allele to a full mutation. Conclusions Our findings demonstrate that a model with total CGG length, number of AGG interruptions, and maternal age is recommended for calculating the risk of expansion to a full mutation during maternal transmission. Taken together, the results of this study provide relevant information for the genetic counseling of female premutation carriers, and improve the current predictive models which calculate risk of expansion to a full mutation using only total CGG repeat length. PMID:25110527

2014-01-01

304

Generation of Humoral Immune Responses to Multi-Allele PfAMA1 Vaccines; Effect of Adjuvant and Number of Component Alleles on the Breadth of Response  

Microsoft Academic Search

There is increasing interest in multi-allele vaccines to overcome strain-specificity against polymorphic vaccine targets such as Apical Membrane Antigen 1 (AMA1). These have been shown to induce broad inhibitory antibodies in vitro and formed the basis for the design of three Diversity-Covering (DiCo) proteins with similar immunological effects. The antibodies produced are to epitopes that are shared between vaccine alleles

Kwadwo A. Kusi; Bart W. Faber; Vanessa Riasat; Alan W. Thomas; Clemens H. M. Kocken; Edmond J. Remarque; Mauricio Martins Rodrigues

2010-01-01

305

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

PubMed Central

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

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

2015-01-01

306

Molecular-genetic characterization of CMS-S restorer-of-fertility alleles identified in Mexican maize and teosinte.  

PubMed Central

Restorer-of-fertility (Rf) alleles for S-type cytoplasmic male sterility (CMS-S) are prevalent in Mexican races of maize and teosinte. Forty-five Rf alleles from 26 races of maize and 6 Rf alleles from different accessions of teosinte were found to be homozygous viable, consistent with the hypothesis that they are naturally occurring Rf alleles. Mapping and allelism studies were performed to assess the number of genes represented by these 51 alleles. Forty-two of the Rf alleles mapped to the long arm of chromosome 2 (2L), and 5 of these were further mapped to the whp1-rf3 region. The Rf3 restoring allele, found in some U.S. maize inbred lines, cosegregates with internal processing of CMS-S mitochondrial transcripts. Three of the 5 mapped Rf alleles were associated with a similar RNA processing event. Allelism or tight linkage was confirmed between Rf3 and 2 teosinte alleles (Rf K-69-6 and Rf 9477) and between Rf3 and the Cónico Norteño allele Rf C-N (GTO 22). The rf3 region of 2L potentially encodes a complex of linked rf genes. The prevalence of restoring alleles in this chromosomal region, among normal-cytoplasm accessions of Mexican maize and teosinte, supports the conclusion that these alleles have functions in normal mitochondrial gene expression that by chance allow them to restore male fertility in S cytoplasm. PMID:15020480

Gabay-Laughnan, Susan; Chase, Christine D; Ortega, Victor M; Zhao, Liming

2004-01-01

307

Identification and DNA sequence analysis of 15 new {alpha}{sub 1}-antitrypsin variants, including two PI*QO alleles and one deficient PI*M allele  

SciTech Connect

The authors have investigated the molecular basis of 15 new {alpha}{sub 1}-antitrypsin ({alpha}1AT) variants. Phenotyping by isoelectric focusing (IEF) was used as a screening method to detect {alpha}1AT variants at the protein level. Genotyping was then performed by sequence analysis of all coding exons, exon-intron junctions, and the hepatocyte-specific promotor region including exon Ic. Three of these rare variants are alleles of clinical relevance, associated with undetectable or very low serum levels of {alpha}1AT: the PI*Q0saarbruecken allele generated by a 1-bp C-nucleotide insertion within a stretch of seven cytosines spanning residues 360-362, resulting in a 3{prime} frameshift and the acquisition of a stop codon at residue 376; a point mutation in the PI*Q0lisbon allele, resulting in a single amino acid substitution Thr{sup 68}(ACC){yields}Ile(ATC); and an in-frame trinucleotide deletion {Delta}Phe{sup 51} (TTC) in the highly deficient PI*Mpalermo allele. The remaining 12 alleles are associated with normal {alpha}1AT serum levels and are characterized by point mutations causing single amino acid substitutions in all but one case. This exception is a silent mutation, which does not affect the amino acid sequence. The limitation of IEF compared with DNA sequence analysis, for identification of new variants, their generation by mutagenesis, and the clinical relevance of the three deficiency alleles are discussed.

Faber, J.P.; Kirchgesser, M.; Schwaab, R.; Bidlingmaier, F. [Universitaet Bonn (Germany); Poller, W. [Universitaet Wuerzburg (Germany); Weidinger, S. [Medizinische Immunologische Laboratorien, Munich (Germany); Olek, K. [Universitaet Bonn (Germany)]|[Institut fuer Molekularbiologische Diagnostik, Bornheim-Hersel (Germany)

1994-12-01

308

Seven novel HLA alleles reflect different mechanisms involved in the evolution of HLA diversity: description of the new alleles and review of the literature.  

PubMed

The human leukocyte antigen (HLA) loci are among the most polymorphic genes in the human genome. The diversity of these genes is thought to be generated by different mechanisms including point mutation, gene conversion and crossing-over. During routine HLA typing, we discovered seven novel HLA alleles which were probably generated by different evolutionary mechanisms. HLA-B*41:21, HLA-DQB1*02:10 and HLA-DQA1*01:12 likely emerged from the common alleles of their groups by point mutations, all of which caused non-synonymous amino acid substitutions. In contrast, a deletion of one nucleotide leading to a frame shift with subsequent generation of a stop codon is responsible for the appearance of a null allele, HLA-A*01:123N. Whereas HLA-B*35:231 and HLA-B*53:31 were probably products of intralocus gene conversion between HLA-B alleles, HLA-C*07:294 presumably evolved by interlocus gene conversion between an HLA-C and an HLA-B allele. Our analysis of these novel alleles illustrates the different mechanisms which may have contributed to the evolution of HLA polymorphism. PMID:25500251

Adamek, Martina; Klages, Cornelia; Bauer, Manuela; Kudlek, Evelina; Drechsler, Alina; Leuser, Birte; Scherer, Sabine; Opelz, Gerhard; Tran, Thuong Hien

2015-01-01

309

Cognitive and neural correlates of the 5-repeat allele of the dopamine D4 receptor gene in a population lacking the 7-repeat allele.  

PubMed

The 5-repeat allele of a common length polymorphism in the gene that encodes the dopamine D4 receptor (DRD4) is robustly associated with the risk of attention deficit hyperactivity disorder (ADHD) and substantially exists in Asian populations, which have a lower ADHD prevalence. In this study, we investigated the effect of this allele on microstructural properties of the brain and on its functional activity during externally directed attention-demanding tasks and creative performance in the 765 Asian subjects. For this purpose, we employed diffusion tensor imaging, N-back functional magnetic resonance imaging paradigms, and a test to measure creativity by divergent thinking. The 5-repeat allele was significantly associated with increased originality in the creative performance, increased mean diffusivity (the measure of how the tissue includes water molecules instead of neural and vessel components) in the widespread gray and white matter areas of extensive areas, particularly those where DRD4 is expressed, and reduced task-induced deactivation in the areas that are deactivated during the tasks in the course of both the attention-demanding working memory task and simple sensorimotor task. The observed neural characteristics of 5-repeat allele carriers may lead to an increased risk of ADHD and behavioral deficits. Furthermore, the increased originality of creative thinking observed in the 5-repeat allele carriers may support the notion of the side of adaptivity of the widespread risk allele of psychiatric diseases. PMID:25659462

Takeuchi, Hikaru; Tomita, Hiroaki; Taki, Yasuyuki; Kikuchi, Yoshie; Ono, Chiaki; Yu, Zhiqian; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

2015-04-15

310

The European Social Contract and the European Public Sphere  

Microsoft Academic Search

Abstract:?The possible existence of a European democracy does not depend on the prerequisite of a homogeneous public sphere but on the understanding of the relationship between the normative basis of a European democracy—here a social contract—the structure of the European public sphere and the corresponding institutions. The normative concept of democracy as expressed in social contract theory is neither bound

Stephan Bredt

2006-01-01

311

Global diversity and genetic contributions of chicken populations from African, Asian and European regions.  

PubMed

Genetic diversity and population structure of 113 chicken populations from Africa, Asia and Europe were studied using 29 microsatellite markers. Among these, three populations of wild chickens and nine commercial purebreds were used as reference populations for comparison. Compared to commercial lines and chickens sampled from the European region, high mean numbers of alleles and a high degree of heterozygosity were found in Asian and African chickens as well as in Red Junglefowl. Population differentiation (FST ) was higher among European breeds and commercial lines than among African, Asian and Red Junglefowl populations. Neighbour-Net genetic clustering and structure analysis revealed two main groups of Asian and north-west European breeds, whereas African populations overlap with other breeds from Eastern Europe and the Mediterranean region. Broilers and brown egg layers were situated between the Asian and north-west European clusters. structure analysis confirmed a lower degree of population stratification in African and Asian chickens than in European breeds. High genetic differentiation and low genetic contributions to global diversity have been observed for single European breeds. Populations with low genetic variability have also shown a low genetic contribution to a core set of diversity in attaining maximum genetic variation present from the total populations. This may indicate that conservation measures in Europe should pay special attention to preserving as many single chicken breeds as possible to maintain maximum genetic diversity given that higher genetic variations come from differentiation between breeds. PMID:25315897

Lyimo, C M; Weigend, A; Msoffe, P L; Eding, H; Simianer, H; Weigend, S

2014-12-01

312

Allelic Expression Changes in Medaka (Oryzias latipes) Hybrids between Inbred Strains Derived from Genetically Distant Populations  

Microsoft Academic Search

Variations in allele expressions between genetically distant populations are one of the most important factors which affects their morphological and physiological variations. These variations are caused by natural mutations accumulated in their habitats. It has been reported that allelic expression differences in the hybrids of genetically distant populations are different from parental strains. In that case, there is a possibility

Yasuhiko Murata; Shoji Oda; Hiroshi Mitani

2012-01-01

313

Maximum likelihood estimation of the frequency of null alleles at microsatellite loci  

E-print Network

, null Abstract We review three methods for estimating the frequency of null alleles at codominant loci of its actual sire. There are currently three methods for estimat- ing the frequency of null alleles from co-dominant genotypes, such as those at microsatellite loci (Chakraborty et al. 1992; Brookfield 1996

Kalinowski, Steven T

314

A Preliminary Report on the Frequency of Scrapie Susceptibility Alleles in Hampshire Sheep  

Microsoft Academic Search

Blood samples were collected from a total of 201 animals in five purebred Hampshire sheep flocks. DNA was isolated from the samples, and the protein-coding region of the prion protein gene was amplified using the polymerase chain reaction. The allelic frequencies of the prion protein codons 171 and 136 were determined. Results revealed that the codon 171 alleles Q, R,

Curtis R. Youngs; Amanda K. Purdy; James R. Mickelson

1997-01-01

315

DNAs of the Two Mating-Type Alleles of Neurospora crassa are Highly Dissimilar  

Microsoft Academic Search

The mating-type alleles A and a of Neurospora crassa control mating in the sexual cycle and function in establishing heterokaryon incompatibility in the vegetative cycle. The A and a alleles were cloned, and they were shown to encode both the sexual functions and vegetative incompatibility. The mating-type clones contain nonhomologous DNA segments that are flanked by common DNA sequences. Neurospora

N. Louise Glass; Steven J. Vollmer; Chuck Staben; Jeff Grotelueschen; Robert L. Metzenberg; Charles Yanofsky

1988-01-01

316

A new model for the origins of allelic dimorphism in Plasmodium falciparum.  

PubMed

In his landmark 1987 study of the merozoite surface protein-1 locus in Plasmodium falciparum, Kazuyuki Tanabe and coauthors introduced the phenomenon of allelic dimorphism, in which antigenic diversity is arranged into two maximally diverged haplotypes. Further work has extended this finding to other loci in P. falciparum. Each of the loci at which allelic dimorphism is observed encodes major surface antigens of blood-stage malaria parasites, and is consequently a major vaccine target, thus understanding the origins and implications of allelic dimorphism is of crucial importance. Here we examine the essential features of allelic dimorphism in dimorphic malarial surface antigens. From sequence analysis, we conclude that the ancestral population may have been recombining/multimorphic rather than dimorphic. We hypothesize a pathway to allelic dimorphism in which an ancestral allele-rich recombining population could have undergone a severe population bottleneck, putatively caused by the lateral transfer of P. falciparum from apes to humans. This bottleneck produced a reduction in allelic diversity, favoring the survival of the most divergent alleles, which in turn led to recombination suppression by strong natural selection against recombinants. PMID:25251164

Roy, Scott W; Ferreira, Marcelo U

2015-06-01

317

Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues  

PubMed Central

Personal exome and genome sequencing provides access to loss-of-function and rare deleterious alleles whose interpretation is expected to provide insight into individual disease burden. However, for each allele, accurate interpretation of its effect will depend on both its penetrance and the trait's expressivity. In this regard, an important factor that can modify the effect of a pathogenic coding allele is its level of expression; a factor which itself characteristically changes across tissues. To better inform the degree to which pathogenic alleles can be modified by expression level across multiple tissues, we have conducted exome, RNA and deep, targeted allele-specific expression (ASE) sequencing in ten tissues obtained from a single individual. By combining such data, we report the impact of rare and common loss-of-function variants on allelic expression exposing stronger allelic bias for rare stop-gain variants and informing the extent to which rare deleterious coding alleles are consistently expressed across tissues. This study demonstrates the potential importance of transcriptome data to the interpretation of pathogenic protein-coding variants. PMID:24786518

Kukurba, Kimberly R.; Zhang, Rui; Li, Xin; Smith, Kevin S.; Knowles, David A.; How Tan, Meng; Piskol, Robert; Lek, Monkol; Snyder, Michael; MacArthur, Daniel G.; Li, Jin Billy; Montgomery, Stephen B.

2014-01-01

318

Biased Tests of Association: Comparisons of Allele Frequencies when Departing from Hardy-Weinberg Proportions  

Microsoft Academic Search

Association studies of genetic markers or candidate genes with disease are often conducted using the traditional case-control design. Cases and controls are sampled from genetically unrelated subjects, and allele frequencies compared between cases and controls using Pearson's chi-square statistic. An assumption of this analysis method is that the two alleles within each subject are statistically independent, at least when no

Daniel J. Schaid; Steven J. Jacobsen

319

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

PubMed

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

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

2014-11-01

320

Adaptive Mutation with Fitness and Allele Distribution Correlation for Genetic Algorithms  

E-print Network

Adaptive Mutation with Fitness and Allele Distribution Correlation for Genetic Algorithms 34469 Istanbul, Turkey etaner@cs.itu.edu.tr ABSTRACT In this paper, a new gene based adaptive mutation and on gene based allele distribution statistics are correlated to explicitly adapt the mutation probability

Yang, Shengxiang

321

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...

322

The effect of wild card designations and rare alleles in forensic DNA database searches.  

PubMed

Forensic DNA databases are powerful tools used for the identification of persons of interest in criminal investigations. Typically, they consist of two parts: (1) a database containing DNA profiles of known individuals and (2) a database of DNA profiles associated with crime scenes. The risk of adventitious or chance matches between crimes and innocent people increases as the number of profiles within a database grows and more data is shared between various forensic DNA databases, e.g. from different jurisdictions. The DNA profiles obtained from crime scenes are often partial because crime samples may be compromised in quantity or quality. When an individual's profile cannot be resolved from a DNA mixture, ambiguity is introduced. A wild card, F, may be used in place of an allele that has dropped out or when an ambiguous profile is resolved from a DNA mixture. Variant alleles that do not correspond to any marker in the allelic ladder or appear above or below the extent of the allelic ladder range are assigned the allele designation R for rare allele. R alleles are position specific with respect to the observed/unambiguous allele. The F and R designations are made when the exact genotype has not been determined. The F and R designation are treated as wild cards for searching, which results in increased chance of adventitious matches. We investigated the probability of adventitious matches given these two types of wild cards. PMID:25576850

Tvedebrink, Torben; Bright, Jo-Anne; Buckleton, John S; Curran, James M; Morling, Niels

2015-05-01

323

Apolipoprotein E ε4 Allele Frequency and Age at Onset of Alzheimer’s Disease  

Microsoft Academic Search

The age distribution of the ε4 allelic form of the apolipoprotein E gene (APOE) was investigated in 630 patients with Alzheimer’s disease (AD) with onset age ranging from 35 to 90 years. Overall, mean age at onset in APOE ε4 allele bearers was significantly later than that in nonbearers. However, when stratified into early onset AD (EOAD) and late onset

Yvonne Davidson; Linda Gibbons; Antonia Pritchard; Jayne Hardicre; Joanne Wren; Cheryl Stopford; Camille Julien; Jennifer Thompson; Antony Payton; Stuart M. Pickering-Brown; Neil Pendleton; Michael A. Horan; Alistair Burns; Nitin Purandare; Corinne L. Lendon; David Neary; Julie S. Snowden; David M. A. Mann

2007-01-01

324

Estimating minimum allele frequencies for DNA profile frequency estimates for PCR-based loci  

Microsoft Academic Search

In order that there can be confidence that DNA profile frequency estimates will not place undue bias against a defendant, 2 methods are described for estimating minimum allele frequency bounds for PCR-based loci. One approach estimates minimum allele frequencies for VNTR and STR loci using sample size and the observed heterozygosity at a locus, while the second approach, appropriate for

B. Budowle; K. L. Monson; R. Chakraborty

1996-01-01

325

METHODOLOGY ARTICLE Open Access Sources of bias in measures of allele-specific  

E-print Network

from RNA-seq data aligned to a single reference genome Kraig R Stevenson1 , Joseph D Coolon2 and Patricia J Wittkopp1,2,3* Abstract Background: RNA-seq can be used to measure allele-specific expression, Allelic imbalance, Genomics, Gene expression, Illumina Background During the last five years, massively

Gruber, Jonathan

326

SNPs in Transcripts In our analysis, 30% of the aligned reads are allele-specific.  

E-print Network

SNPs in Transcripts In our analysis, 30% of the aligned reads are allele-specific. The figure below of the transcriptomes. 2. Transcript level analysis reveals strong evidence for allele-specific differential expressions shows that 85% of transcripts have at least one SNP between 129 and PWK, which makes the F1 cross- es

Whitton, Mary C.

327

A Novel Allele of Hap1 Causes Uninducible Expression of Hem13 in Saccharomyces Cerevisiae  

PubMed Central

Transcription of HEM13 in Saccharomyces cerevisiae is repressed by heme and oxygen. We have isolated two mutants in which expression of HEM13 is aberrant. The mutant alleles in these strains represent two different alleles of HAP1. HAP1 encodes an activator protein whose DNA binding activity is stimulated by heme, and is required for the transcription of CYC1, ROX1 and a number of other heme-dependent genes. One of our mutant alleles confers a phenotype much like that of the hap1::LEU2 allele. Expression of HEM13 in a strain with this mutation is elevated under repressing conditions and not fully inducible in the absence of heme. The other mutant allele of HAP1 we uncovered confers a novel phenotype. A strain containing this allele exhibits heme-independent expression of CYC1 and ROX1 and uninducible expression of HEM13 and ANB1. The mutation associated with this novel allele of HAP1 was localized to a glycine to aspartate change in amino acid 235 of HAP1, between the DNA binding and heme responsive domains. DNA binding assays demonstrated that the protein made from this HAP1 allele retains the ability to bind DNA, but that unlike wild-type HAP1 protein, this binding is not stimulated by heme. PMID:8005437

Ushinsky, S. C.; Keng, T.

1994-01-01

328

Surrogate genetics and metabolic profiling for characterization of human disease alleles.  

PubMed

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

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

2012-04-01

329

Surrogate Genetics and Metabolic Profiling for Characterization of Human Disease Alleles  

PubMed Central

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

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

330

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

E-print Network

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

Jensen, Shane T.

331

Allele frequencies for STR loci in a Sicilian population: Genetic prevalence and disequilibrium  

Microsoft Academic Search

The aim of our work was to study the allelic frequencies and distribution within the 15 forensic STR loci in a group of 440 unrelated Sicilian subjects. Afterwards we have evaluated the genetic equilibrium among the most recurrent allele loci and have compared our data to those already published by other authors referring to different populations.

I. Ciuna; M. Guarnaccia; E. Ginestra; A. Agodi; D. Piscitello; S. Spitaleri; G. Marcì; G. Paravizzini; C. Trapani; S. Travali; L. Saravo

2006-01-01

332

An autosomal locus that controls chromosome-wide replication timing and mono-allelic expression  

PubMed Central

Mammalian DNA replication initiates at multiple sites along chromosomes at different times, following a temporal replication program. Homologous alleles typically replicate synchronously; however, mono-allelically expressed genes such as imprinted genes, allelically excluded genes and genes on the female X chromosome replicate asynchronously. We have used a chromosome engineering strategy to identify a human autosomal locus that controls this replication timing program in cis. We show that Cre/loxP-mediated rearrangements at a discrete locus at 6q16.1 result in delayed replication of the entire chromosome. This locus displays asynchronous replication timing that is coordinated with other mono-allelically expressed genes on chromosome 6. Characterization of this locus revealed mono-allelic expression of a large intergenic non-coding RNA, which we have named asynchronous replication and autosomal RNA on chromosome 6, ASAR6. Finally, disruption of this locus results in the activation of the previously silent alleles of linked mono-allelically expressed genes. We previously found that chromosome rearrangements involving eight different autosomes display delayed replication timing, and that cells containing chromosomes with delayed replication timing have a 30–80-fold increase in the rate at which new gross chromosomal rearrangements occurred. Taken together, these observations indicate that human autosomes contain discrete cis-acting loci that control chromosome-wide replication timing, mono-allelic expression and the stability of entire chromosomes. PMID:21459774

Stoffregen, Eric P.; Donley, Nathan; Stauffer, Daniel; Smith, Leslie; Thayer, Mathew J.

2011-01-01

333

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

PubMed Central

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

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

2014-01-01

334

PGI*3(Israel), a new, unstable allele in the phosphoglucose isomerase system.  

PubMed

Phosphoglucose isomerase (PGI) and 16 other biochemical genetic markers were studied in an Israeli-Arab family previously described for hereditary deficiency of adenylate kinase (AK) and glucose 6-phosphate dehydrogenase (G6PD). In this inbred family a rare PGI*3 allele was observed in 11 of 32 members tested, indicating an autosomal codominant inheritance. The electrophoretic mobility of this allele is similar to that of the PGI*3 allele found in Indian populations, but unlike the Indian allele, it has a very low specific activity and heat stability. This PGI*3 allele, designated PGI*3 (Israel), seems to be a different unstable mutation and along with AK and G6PD deficiencies seems to be associated with severe anaemia. PMID:3476458

Bonné-Tamir, B; Papiha, S S; Ashbel, S; Brok-Simoni, F; Kende, G; Ramot, B

1987-09-01

335

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

SciTech Connect

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).

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

336

Biophotonics: a European perspective  

NASA Astrophysics Data System (ADS)

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.

Robin, Thierry; Cochard, Jacques; Breussin, Frédéric

2013-03-01

337

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.

338

European Environmental Law Homepage  

NSDL National Science Digital Library

The European Environmental Law Homepage provides access to the full text of treaties, legislation, case law, scholarly legal articles, and EU and NGO documents relevant to environmental law in Europe. In addition, the site has compiled a directory of important governmental Websites for most nations in Europe and maintains a list of pointers to other legal sites with environmental information. The site is edited by Wybe Th. Douma of the T.M.C. Asser Institute, and Jurgen G.J. Lefevere of both the Foundation for International Environmental Law and Development, and the METRO Institute, Maastricht University.

339

Allelic Prevalence of ABO Blood Group Genes in Iranian Azari Population  

PubMed Central

Introduction ABO blood group system is the most important blood group in transfusion and has been widely used in population studies. Several molecular techniques for ABO allele’s detection are widely used for distinguishing various alleles of glycosyl transferase locus on chromosome 9. Methods 744 randomly selected samples from Azari donors of East Azerbaijan province (Iran) were examined using well-adjusted multiplex allele- specific PCR ABO genotyping technique. Results The results were consistent for all individuals. The ABO blood group genotype of 744 healthy Azari blood donors was: 25.8% AA/AO (2), 7.6% AO (1), 1.6% BB, 11.3% B0 (1), 10% AB, 9.3% 0(1)0(1) and 15.3%0(1)0(2). The highest genotype frequency belonged to O01/O02 genotype (15.3%) and the lowest frequency belonged to A101/A102 genotype (0.4%). Conclusions: The frequencies of ABO alleles didn’t show significant differences between East Azerbaijan province population and that of other areas of the country. Meanwhile, statistical analysis of frequencies of A and B alleles between East Azerbaijan province population and neighbor countries showed significant differences whereas the frequency of allele O between them did not show significant difference (P>0.05). Conclusions The frequencies of ABO alleles didn’t show significant differences between East Azerbaijan province population and that of other areas of the country. Meanwhile, statistical analysis of frequencies of A and B alleles between East Azerbaijan province population and neighbor countries showed significant differences whereas the frequency of allele O between them did not show significant difference (P>0.05). PMID:23678461

Nojavan, Mohammad; Shamsasenjan, Karrim; Movassaghpour, Ali Akbar; Akbarzadehlaleh, Parvin; Torabi, Seyd Esmail; Ghojazadeh, Morteza

2012-01-01

340

Distinct Allelic Patterns of Nanog Expression Impart Embryonic Stem Cell Population Heterogeneity  

PubMed Central

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

Wu, Jincheng; Tzanakakis, Emmanuel S.

2013-01-01

341

Co-Operative Additive Effects between HLA Alleles in Control of HIV-1  

PubMed Central

Background HLA class I genotype is a major determinant of the outcome of HIV infection, and the impact of certain alleles on HIV disease outcome is well studied. Recent studies have demonstrated that certain HLA class I alleles that are in linkage disequilibrium, such as HLA-A*74 and HLA-B*57, appear to function co-operatively to result in greater immune control of HIV than mediated by either single allele alone. We here investigate the extent to which HLA alleles - irrespective of linkage disequilibrium - function co-operatively. Methodology/Principal Findings We here refined a computational approach to the analysis of >2000 subjects infected with C-clade HIV first to discern the individual effect of each allele on disease control, and second to identify pairs of alleles that mediate ‘co-operative additive’ effects, either to improve disease suppression or to contribute to immunological failure. We identified six pairs of HLA class I alleles that have a co-operative additive effect in mediating HIV disease control and four hazardous pairs of alleles that, occurring together, are predictive of worse disease outcomes (q<0.05 in each case). We developed a novel ‘sharing score’ to quantify the breadth of CD8+ T cell responses made by pairs of HLA alleles across the HIV proteome, and used this to demonstrate that successful viraemic suppression correlates with breadth of unique CD8+ T cell responses (p?=?0.03). Conclusions/Significance These results identify co-operative effects between HLA Class I alleles in the control of HIV-1 in an extended Southern African cohort, and underline complementarity and breadth of the CD8+ T cell targeting as one potential mechanism for this effect. PMID:23094091

Carlson, Jonathan M.; Payne, Rebecca; Huang, Kuan-Hsiang Gary; Frater, John; Goedhals, Dominique; Steyn, Dewald; van Vuuren, Cloete; Paioni, Paolo; Jooste, Pieter; Ogwu, Anthony; Shapiro, Roger; Mncube, Zenele; Ndung'u, Thumbi; Walker, Bruce D.; Heckerman, David; Goulder, Philip J. R.

2012-01-01

342

European Anti Poverty Network (EAPN)  

NSDL National Science Digital Library

European Anti Poverty Network was created in 1989 "to put the fight against poverty and social exclusion on the political agenda of the European Union." The Network consists of 25 European organizations that work to alleviate poverty and 15 national networks that fight poverty specifically inside the EU. EAPN offers a nice collection of position papers and reports analyzing the ongoings of the European Union, its member countries and their policies, as well as news releases and news flashes. The site gives general information about the EAPN including its mission, members, and activities, as well as providing a tightly organized set of links.

343

European Conference on Health Economics.  

PubMed

The biennial European Conference on Health Economics was held in Finland this year, at the Finlandia Hall in the centre of Helsinki. The European conferences rotate among European countries and fall between the biennial world congresses organized by the International Health Economics Association (iHEA). A record attendance of approximately 800 delegates from 50 countries around the world were present at the Helsinki conference. The theme of the conference was 'Connecting Health and Economics'. All major topics of health economics were covered in the sessions. For the first time, social care economics was included in the agenda of the European Conference as a session of its own. PMID:21155696

Malmivaara, Antti

2010-12-01

344

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.

345

EIOP: European Integration Online Papers  

NSDL National Science Digital Library

The European Community Studies Association Austria provides this new working paper archive to house peer-reviewed, interdisciplinary working papers in the field of European integration research, including legal studies, political science, economics, and history. At present eleven papers are available, including "Democracy and Governance in the European Union," "The Economic Consequences of a Large EMU--Results of Macroeconomic Model Simulations," and "The Making of a Polity: The Struggle Over European Integration." Though English is the preferred language for papers, papers in German may also be included; abstracts are presented in both languages. A mailing list is available for those wishing to be informed when new papers are posted.

346

Hypomorphic Temperature-Sensitive Alleles of NSDHL Cause CK Syndrome  

PubMed Central

CK syndrome (CKS) is an X-linked recessive intellectual disability syndrome characterized by dysmorphism, cortical brain malformations, and an asthenic build. Through an X chromosome single-nucleotide variant scan in the first reported family, we identified linkage to a 5 Mb region on Xq28. Sequencing of this region detected a segregating 3 bp deletion (c.696_698del [p.Lys232del]) in exon 7 of NAD(P) dependent steroid dehydrogenase-like (NSDHL), a gene that encodes an enzyme in the cholesterol biosynthesis pathway. We also found that males with intellectual disability in another reported family with an NSDHL mutation (c.1098 dup [p.Arg367SerfsX33]) have CKS. These two mutations, which alter protein folding, show temperature-sensitive protein stability and complementation in Erg26-deficient yeast. As described for the allelic disorder CHILD syndrome, cells and cerebrospinal fluid from CKS patients have increased methyl sterol levels. We hypothesize that methyl sterol accumulation, not only cholesterol deficiency, causes CKS, given that cerebrospinal fluid cholesterol, plasma cholesterol, and plasma 24S-hydroxycholesterol levels are normal in males with CKS. In summary, CKS expands the spectrum of cholesterol-related disorders and insight into the role of cholesterol in human development. PMID:21129721

McLarren, Keith W.; Severson, Tesa M.; du Souich, Christèle; Stockton, David W.; Kratz, Lisa E.; Cunningham, David; Hendson, Glenda; Morin, Ryan D.; Wu, Diane; Paul, Jessica E.; An, Jianghong; Nelson, Tanya N.; Chou, Athena; DeBarber, Andrea E.; Merkens, Louise S.; Michaud, Jacques L.; Waters, Paula J.; Yin, Jingyi; McGillivray, Barbara; Demos, Michelle; Rouleau, Guy A.; Grzeschik, Karl-Heinz; Smith, Raffaella; Tarpey, Patrick S.; Shears, Debbie; Schwartz, Charles E.; Gecz, Jozef; Stratton, Michael R.; Arbour, Laura; Hurlburt, Jane; Van Allen, Margot I.; Herman, Gail E.; Zhao, Yongjun; Moore, Richard; Kelley, Richard I.; Jones, Steven J.M.; Steiner, Robert D.; Raymond, F. Lucy; Marra, Marco A.; Boerkoel, Cornelius F.

2010-01-01

347

Allele-specific chemical genetics: concept, strategies, and applications.  

PubMed

The relationship between DNA and protein sequences is well understood, yet because the members of a protein family/subfamily often carry out the same biochemical reaction, elucidating their individual role in cellular processes presents a challenge. Forward and reverse genetics have traditionally been employed to understand protein functions with considerable success. A fundamentally different approach that has gained widespread application is the use of small organic molecules, known as chemical genetics. However, the slow time-scale of genetics and inherent lack of specificity of small molecules used in chemical genetics have limited the applicability of these methods in deconvoluting the role of individual proteins involved in fast, dynamic biological events. Combining the advantages of both the techniques, the specificity achieved with genetics along with the reversibility and tunability of chemical genetics, has led to the development of a powerful approach to uncover protein functions in complex biological processes. This technique is known as allele-specific chemical genetics and is rapidly becoming an essential toolkit to shed light on proteins and their mechanism of action. The current review attempts to provide a comprehensive description of this approach by discussing the underlying principles, strategies, and successful case studies. Potential future implications of this technology in expanding the frontiers of modern biology are discussed. PMID:25436868

Islam, Kabirul

2015-02-20

348

The first modern Europeans.  

PubMed

The discovery of new human fossil remains is one of the most obvious ways to improve our understanding of the dynamics of human evolution. The reanalysis of existing fossils using newer methods is also crucial, and may lead to a reconsideration of the biological and taxonomical status of some specimens, and improve our understanding of highly debated periods in human prehistory. This is particularly true for those remains that have previously been studied using traditional approaches, with only morphological descriptions and standard calliper measurements available. My own interest in the Uluzzian, and its associated human remains grew from my interest in applying recently developed analytical techniques to quantify morphological variation. Discovered more than 40 years ago, the two deciduous molars from Grotta del Cavallo (Apulia, Italy) are the only human remains associated with the Uluzzian culture (one of the main three European "transitional" cultures). These teeth were previously attributed to Neanderthals. This attribution contributed to a consensus view that the Uluzzian, with its associated ornament and tool complexes, was produced by Neanderthals. A reassessment of these deciduous teeth by means of digital morphometric analysis revealed that these remains belong to anatomically modern humans (AMHs). This finding contradicts previous assumptions and suggests that modern humans, and not Neanderthals, created the Uluzzian culture. Of equal importance, new chronometric analyses date these dental remains to 43,000-45,000 cal BP. Thus, the teeth from Grotta del Cavallo represent the oldest European AMH currently known. PMID:22781582

Benazzi, Stefano

2012-01-01

349

An American Construction of European Education Space  

ERIC Educational Resources Information Center

The construction of the European education space has typically been attributed to European education policy makers, institutions, and networks. Rarely do scholars consider the role of outside, non-European actors in shaping the terrain of European education thought and practice. This article considers the construction of the European education…

Silova, Iveta; Brehm, William C.

2010-01-01

350

New European Programmes for the New European College.  

ERIC Educational Resources Information Center

This document, which is designed for further education (FE) college managers and program teams throughout the United Kingdom (UK), provides guidance for conducting the following activities: incorporating new European Union (EU) policies/programs into FE college curricula; ensuring maximum access to the full range of European curriculum activities…

Murray, Alan

351

MHC associations with clinical and autoantibody manifestations in European SLE.  

PubMed

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies. PMID:24598797

Morris, D L; Fernando, M M A; Taylor, K E; Chung, S A; Nititham, J; Alarcón-Riquelme, M E; Barcellos, L F; Behrens, T W; Cotsapas, C; Gaffney, P M; Graham, R R; Pons-Estel, B A; Gregersen, P K; Harley, J B; Hauser, S L; Hom, G; Langefeld, C D; Noble, J A; Rioux, J D; Seldin, M F; Vyse, T J; Criswell, L A

2014-04-01

352

MHC associations with clinical and autoantibody manifestations in European SLE  

PubMed Central

Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease affecting multiple organ systems and characterized by autoantibody formation to nuclear components. Although genetic variation within the major histocompatibility complex (MHC) is associated with SLE, its role in the development of clinical manifestations and autoantibody production is not well defined. We conducted a meta-analysis of four independent European SLE case collections for associations between SLE sub-phenotypes and MHC single-nucleotide polymorphism genotypes, human leukocyte antigen (HLA) alleles and variant HLA amino acids. Of the 11 American College of Rheumatology criteria and 7 autoantibody sub-phenotypes examined, anti-Ro/SSA and anti-La/SSB antibody subsets exhibited the highest number and most statistically significant associations. HLA-DRB1*03:01 was significantly associated with both sub-phenotypes. We found evidence of associations independent of MHC class II variants in the anti-Ro subset alone. Conditional analyses showed that anti-Ro and anti-La subsets are independently associated with HLA-DRB1*0301, and that the HLA-DRB1*03:01 association with SLE is largely but not completely driven by the association of this allele with these sub-phenotypes. Our results provide strong evidence for a multilevel risk model for HLA-DRB1*03:01 in SLE, where the association with anti-Ro and anti-La antibody-positive SLE is much stronger than SLE without these autoantibodies. PMID:24598797

Morris, DL; Fernando, MMA; Taylor, KE; Chung, SA; Nititham, J; Alarcón-Riquelme, ME; Barcellos, LF; Behrens, TW; Cotsapas, C; Gaffney, PM; Graham, RR; Pons-Estel, BA; Gregersen, PK; Harley, JB; Hauser, SL; Hom, G; Langefeld, CD; Noble, JA; Rioux, JD; Seldin, MF; Vyse, TJ; Criswell, LA

2014-01-01

353

Geographical structure and differential natural selection among North European populations  

PubMed Central

Population structure can provide novel insight into the human past, and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and European-American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogeneous region. There is evidence from FST-based analysis of genic and nongenic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to the HLA-G gene on chromosome 6. Evidence of the sweep extends over a 8-Mb/3.5-cM region. Overall, the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it, and their implications in both explaining disease prevalence and mapping these genes by association. PMID:19265028

McEvoy, Brian P.; Montgomery, Grant W.; McRae, Allan F.; Ripatti, Samuli; Perola, Markus; Spector, Tim D.; Cherkas, Lynn; Ahmadi, Kourosh R.; Boomsma, Dorret; Willemsen, Gonneke; Hottenga, Jouke J.; Pedersen, Nancy L.; Magnusson, Patrik K.E.; Kyvik, Kirsten Ohm; Christensen, Kaare; Kaprio, Jaakko; Heikkilä, Kauko; Palotie, Aarno; Widen, Elisabeth; Muilu, Juha; Syvänen, Ann-Christine; Liljedahl, Ulrika; Hardiman, Orla; Cronin, Simon; Peltonen, Leena; Martin, Nicholas G.; Visscher, Peter M.

2009-01-01

354

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

E-print Network

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 ...

Thormaehlen, Aenne S.

355

S-allele diversity in Sorbus aucuparia and Crataegus monogyna (Rosaceae: Maloideae).  

PubMed

RT-PCR was used to obtain the first estimates from natural populations of allelic diversity at the RNase-based gametophytic self-incompatibility locus in the Rosaceae. A total of 20 alleles were retrieved from 20 Sorbus aucuparia individuals, whereas 17 alleles were found in 13 Crataegus monogyna samples. Estimates of population-level allele numbers fall within the range observed in the Solanaceae, the only other family with RNase-based incompatibility for which estimates are available. The nucleotide diversity of S-allele sequences was found to be much lower in the two Rosaceae species as compared with the Solanaceae. This was not due to a lower sequence divergence among most closely related alleles. Rather, it is the depth of the entire genealogy that differs markedly in the two families, with Rosaceae S-alleles exhibiting more recent apparent coalescence. We also investigated patterns of selection at the molecular level by comparing nucleotide diversity at synonymous and nonsynonymous sites. Stabilizing selection was inferred for the 5' region of the molecule, while evidence of diversifying selection was present elsewhere. PMID:12180088

Raspé, O; Kohn, J R

2002-06-01

356

Characterization of missense alleles of the glial cells missing gene of Drosophila.  

PubMed

Glial cells missing (Gcm) is the primary regulator of glial cell fate in Drosophila. Gcm belongs to a small family of transcriptional regulators involved in fundamental developmental processes found in diverse animal phyla including vertebrates. Gcm proteins contain the highly conserved DNA-binding GCM domain, which recognizes an octamer DNA sequence. To date, studies in Drosophila have primarily relied on gcm alleles caused by P-element induced DNA deletions at the gcm locus, as well as a null allele caused by a single base pair substitution in the GCM domain that completely abolishes DNA binding. Here I characterize two hypomorphic missense alleles of gcm with intermediate glial cells missing phenotypes. In embryos homozygous for either of these gcm alleles the number of glial cells in the central nervous cystem (CNS) is reduced approximately in half. Both alleles have single amino acid changes in the GCM domain. These results suggest that Gcm protein activities in these mutant alleles have been attenuated such that they are operating at threshold levels, and trigger glial cell differentiation in neural precursors in the CNS in a stochastic fashion. These hypomorphic alleles provide additional genetic resources for understanding Gcm functions and structure in Drosophila and other species. PMID:25044731

Jones, Bradley W

2014-10-01

357

Distinct physiological and behavioural functions for parental alleles of imprinted Grb10  

PubMed Central

Imprinted genes, defined by their preferential expression of a single parental allele, represent a subset of the mammalian genome and often have key roles in embryonic development1, but also post-natal functions including energy homeostasis2 and behaviour3, 4. When the two parental alleles are unequally represented within a social group (when there is sex-bias in dispersal and/or variance in reproductive success)5, 6, imprinted genes may evolve to modulate social behaviour, although to date no such instance is known. Predominantly expressed from the maternal allele during embryogenesis, Grb10 encodes an intracellular adapter protein that can interact with a number of receptor tyrosine kinases and downstream signalling molecules7. Here we demonstrate that within the brain Grb10 is expressed from the paternal allele from fetal life into adulthood and that ablation of this expression engenders increased social dominance specifically among other aspects of social behaviour, a finding supported by the observed increase in allogrooming by paternal Grb10 deficient animals. Grb10 is, therefore, the first example of an imprinted gene that regulates social behaviour. It is also currently alone in exhibiting imprinted expression from each of the parental alleles in a tissue specific manner, as loss of the peripherally expressed maternal allele leads to significant fetal and placental overgrowth. Thus, Grb10 is to date a unique imprinted gene, able to influence distinct physiological processes, fetal growth and adult behaviour, due to actions of the two parental alleles in different tissues. PMID:21270893

Garfield, Alastair S.; Cowley, Michael; Smith, Florentia M.; Moorwood, Kim; Stewart-Cox, Joanne E.; Gilroy, Kerry; Baker, Sian; Xia, Jing; Dalley, Jeffrey W.; Hurst, Laurence D.; Wilkinson, Lawrence S.; Isles, Anthony R.; Ward, Andrew

2010-01-01

358

Prolonged P300 latency in children with the D2 dopamine receptor A1 allele.  

PubMed Central

Previous studies have indicated the presence of a hereditary component in the generation of the P300, or P3, a late positive component of the event-related potential. Moreover, the dopaminergic system has been implicated in the P3. In the present study, 98 healthy Caucasian boys, mean age of 12.5 years and of above-average intelligence, were studied. The sample was composed of 32 sons of active alcoholic (SAA) fathers, 36 sons of recovering alcoholic (SRA) fathers, and 30 sons of social drinker (SSD) fathers, with none of them having yet begun to consume alcohol or other drugs. TaqI A D2 dopamine receptor alleles (A1 and A2) were determined. A significant difference in the frequency of the A1 allele was found among these three groups of boys, with the SAA group having the highest A1 allele frequency (.313), followed by the SRA (.139) and the SSD (.133) groups. The relationship of the A1 and A2 alleles to P3 amplitude and latency was also determined. The results showed no significant difference in P3 amplitude between boys with the A1 and A2 allele. However, P3 latency was significantly longer in the total sample of boys with the A1 allele compared with those carrying the A2 allele. These findings suggest that polymorphism of the D2 dopamine receptor gene is an important determinant of P3 latency. PMID:8128963

Noble, E. P.; Berman, S. M.; Ozkaragoz, T. Z.; Ritchie, T.

1994-01-01

359

Maximum likelihood estimation of individual inbreeding coefficients and null allele frequencies.  

PubMed

In this paper, we developed and compared several expectation-maximization (EM) algorithms to find maximum likelihood estimates of individual inbreeding coefficients using molecular marker information. The first method estimates the inbreeding coefficient for a single individual and assumes that allele frequencies are known without error. The second method jointly estimates inbreeding coefficients and allele frequencies for a set of individuals that have been genotyped at several loci. The third method generalizes the second method to include the case in which null alleles may be present. In particular, it is able to jointly estimate individual inbreeding coefficients and allele frequencies, including the frequencies of null alleles, and accounts for missing data. We compared our methods with several other estimation procedures using simulated data and found that our methods perform well. The maximum likelihood estimators consistently gave among the lowest root-mean-square-error (RMSE) of all the estimators that were compared. Our estimator that accounts for null alleles performed particularly well and was able to tease apart the effects of null alleles, randomly missing genotypes and differing degrees of inbreeding among members of the datasets we analysed. To illustrate the performance of our estimators, we analysed previously published datasets on mice (Mus musculus) and white-tailed deer (Odocoileus virginianus). PMID:22805896

Hall, Nathan; Mercer, Laina; Phillips, Daisy; Shaw, Jonathan; Anderson, Amy D

2012-06-01

360

Genetic Dissection of the Drosophila melanogaster Female Head Transcriptome Reveals Widespread Allelic Heterogeneity  

PubMed Central

Modern genetic mapping is plagued by the “missing heritability” problem, which refers to the discordance between the estimated heritabilities of quantitative traits and the variance accounted for by mapped causative variants. One major potential explanation for the missing heritability is allelic heterogeneity, in which there are multiple causative variants at each causative gene with only a fraction having been identified. The majority of genome-wide association studies (GWAS) implicitly assume that a single SNP can explain all the variance for a causative locus. However, if allelic heterogeneity is prevalent, a substantial amount of genetic variance will remain unexplained. In this paper, we take a haplotype-based mapping approach and quantify the number of alleles segregating at each locus using a large set of 7922 eQTL contributing to regulatory variation in the Drosophila melanogaster female head. Not only does this study provide a comprehensive eQTL map for a major community genetic resource, the Drosophila Synthetic Population Resource, but it also provides a direct test of the allelic heterogeneity hypothesis. We find that 95% of cis-eQTLs and 78% of trans-eQTLs are due to multiple alleles, demonstrating that allelic heterogeneity is widespread in Drosophila eQTL. Allelic heterogeneity likely contributes significantly to the missing heritability problem common in GWAS studies. PMID:24810915

King, Elizabeth G.; Sanderson, Brian J.; McNeil, Casey L.; Long, Anthony D.; Macdonald, Stuart J.

2014-01-01

361

Yy1 Gene Dosage Effect and Bi-Allelic Expression of Peg3  

PubMed Central

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

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

2015-01-01

362

Origins of the Recent Emergence of Plasmodium falciparum Pyrimethamine Resistance Alleles in Madagascar? †  

PubMed Central

The combination of sulfadoxine-pyrimethamine is recommended for use as intermittent preventive treatment of malaria during pregnancy and is deployed in Africa. The emergence and the spread of resistant parasites are major threats to such an intervention. We have characterized the Plasmodium falciparum dhfr (pfdhfr) haplotypes and flanking microsatellites in 322 P. falciparum isolates collected from the Comoros Islands and Madagascar. One hundred fifty-six (48.4%) carried the wild-type pfdhfr allele, 19 (5.9%) carried the S108N single-mutation allele, 30 (9.3%) carried the I164L single-mutation allele, 114 (35.4%) carried the N51I/C59R/S108N triple-mutation allele, and 3 (1.0%) carried the N51I/C59R/S108N/I164L quadruple-mutation allele. Microsatellite analysis showed the introduction from the Comoros Islands of the ancestral pfdhfr triple mutant allele of Asian origin and its spread in Madagascar. Evidence for the emergence on multiple occasions of the I164L single-mutation pfdhfr allele in Madagascar was also obtained. Thus, the conditions required to generate mutants with quadruple mutations are met in Madagascar, representing a serious threat to current drug policy. PMID:20308388

Andriantsoanirina, Valérie; Bouchier, Christiane; Tichit, Magali; Jahevitra, Martial; Rabearimanana, Stéphane; Randrianjafy, Rogelin; Ratsimbasoa, Arsène; Mercereau-Puijalon, Odile; Durand, Rémy; Ménard, Didier

2010-01-01

363

Diversity of sequences and expression patterns among alleles of a sugarcane loading stem gene.  

PubMed

Modern sugarcane cultivars are highly polyploid and aneuploid hybrids, which are propagated as clones. Their complex genome structure comprises 100-130 chromosomes and 10-13 hom(e)ologous copies of most loci. There is preliminary evidence of very high heterozygosity, with implications for genetic improvement approaches ranging from marker-assisted selection to transgenics. Here, we report that sugarcane cultivar Q200 has at least nine alleles at the Loading Stem Gene (ScLSG) locus. Exon-intron structure is identical and the predicted protein products show at least 92 % identity, across sugarcane alleles and the Sorghum homologue Sb07g027880. There is substantial variation in the 5' UTR and promoter regions including numerous allele-specific nucleotide polymorphisms, insertions and deletions. We developed an allele-specific qRT-PCR method to undertake the first compelling test of allele-specific expression in polyploid sugarcane. Seven alleles distinguished by this method all showed peak expression in the sucrose-loading zone of the stem, but there was apparent variability in expression patterns across other tissues. The ScLSG2 and ScLSG5 alleles appear promising for specificity of expression in stems, relative to leaf, meristem, emerging shoot and root tissues. Within the stem, there was activity in parenchyma, vascular and rind tissues. This expression pattern is of interest in basic research and biotechnology aimed at enhanced sucrose content, engineering value-added products, and manipulation of stem biomass composition. PMID:23546592

Moyle, Richard L; Birch, Robert G

2013-07-01

364

Quantifying the transcriptional output of single alleles in single living mammalian cells  

PubMed Central

Transcription kinetics of actively transcribing genes in vivo have generally been measured using tandem gene arrays. However, tandem arrays do not reflect the endogenous state of genome organization where genes appear as single alleles. We present here a robust technique for the quantification of mRNA synthesis from a single allele in real-time, in single living mammalian cells. The protocol describes how to generate cell clones harboring a tagged allele and how to detect in vivo transcription from this tagged allele at high spatial and temporal resolution throughout the cell cycle. Quantification of nascent mRNAs produced from the single tagged allele is performed using RNA fluorescence in situ hybridization (FISH) and live-cell imaging. Subsequent analyses and data modeling detailed in the protocol include measurements of: transcription rates of RNA polymerase II; determining the number of polymerases recruited to the tagged allele; and measuring the spacing between polymerases. Generating the cells containing the single tagged alleles should take up to a month; RNA FISH or live-cell imaging will require an additional week. PMID:23424748

Yunger, Sharon; Rosenfeld, Liat; Garini, Yuval; Shav-Tal, Yaron

2013-01-01

365

Brazilian Portuguese Ethnonymy and Europeanisms.  

ERIC Educational Resources Information Center

Delineates the incorporation and analyzes the impact of European borrowings in Brazilian racio-ethnic terminology. This overview covers French, Italian, Spanish, and English influences. Borrowings from European languages have had a small impact on the calculus of Brazilian racio-ethnic terms. (43 references) (Author/CK)

Stephens, Thomas M.

1994-01-01

366

Adult Education and European Identity  

ERIC Educational Resources Information Center

Europe is coming together. This is a historic project; for the first time in modern history, will and consciousness are used for bringing political, social and cultural unity to the European continent. In this process lifelong learning and hence adult education are gaining in importance. The European project takes place in an age characterised by…

Negt, Oskar

2008-01-01

367

Integrating European security through space  

Microsoft Academic Search

For decades, Western European nations have been comparatively uninterested in the military use of space, largely content to rely on the far greater resources of the USA in this area. Today, however, the traditional belief that the security requirements of ‘the West’ are synonymous with those of the USA is increasingly open to challenge. A new European defence identity is

Alasdair McLean

1995-01-01

368

European hair and eye color  

Microsoft Academic Search

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

Peter Frost

2006-01-01

369

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

Microsoft Academic Search

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

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

2007-01-01

370

Prospective identification of high-risk polycythemia vera patients based on JAK2V617F allele burden  

Microsoft Academic Search

The aim of this study was to determine whether the burden of JAK2V617F allele correlated with major clinical outcomes in patients with polycythemia vera (PV). To this end, we determined JAK2 mutant allele levels in granulocytes of 173 PV patients at diagnosis. The mean (±s.d.) mutant allele burden was 52% (±29); 32 patients (18%) had greater than 75% mutant allele.

A M Vannucchi; E Antonioli; P Guglielmelli; G Longo; A Pancrazzi; V Ponziani; C Bogani; P R Ferrini; A Rambaldi; V Guerini; A Bosi; T Barbui

2007-01-01

371

Multiple Origins of Plasmodium falciparum Dihydropteroate Synthetase Mutant Alleles Associated with Sulfadoxine Resistance in India?†  

PubMed Central

With the spread of chloroquine (CQ)-resistant malaria in India, sulfadoxine-pyrimethamine (SP) alone or in combination with artesunate is used as an alternative antimalarial drug. Due to continuous drug pressure, the Plasmodium falciparum parasite is exhibiting resistance to antifolates because of mutations in candidate genes dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps). Our earlier study on flanking microsatellite markers of dhfr mutant alleles from India had shown a single origin of the pyrimethamine resistance and some minor haplotypes which shared haplotypes with Southeast Asian (Thailand) strains. In the present study, we have analyzed 193 of these Indian P. falciparum isolates for 15 microsatellite loci around dhps to investigate the genetic lineages of the mutant dhps alleles in different parts of the country. Eighty-one of these samples had mutant dhps alleles, of which 62 were from Andaman and Nicobar Islands and the remaining 19 were from mainland India. Of 112 isolates with a wild-type dhps allele, 109 were from mainland India and only 3 were from Andaman and Nicobar Islands. Consistent with the model of selection, the mean expected heterozygosity (He) around mutant dhps alleles (He = 0.55; n = 81) associated with sulfadoxine resistance was lower (P ? 0.05) than the mean He around the wild-type dhps allele (He = 0.80; n = 112). There was more genetic diversity in flanking microsatellites of dhps than dhfr among these isolates, which confirms the assertion that dhps mutations are at a very early stage of fixation in the parasite population. Microsatellite haplotypes around various mutant dhps alleles suggest that the resistant dhps alleles have multiple independent origins in India, especially in Andaman and Nicobar Islands. Determining the genetic lineages of the resistant dhps alleles on Andaman and Nicobar Islands and mainland India is significant, given the role of Asia in the intercontinental spread of chloroquine- and pyrimethamine-resistant parasites in the past. PMID:21422213

Lumb, Vanshika; Das, Manoj K.; Singh, Neeru; Dev, Vas; Khan, Wajihullah; Sharma, Yagya D.

2011-01-01

372

Allelic variation in the squirrel monkey x-linked color vision gene: biogeographical and behavioral correlates.  

PubMed

Most Neotropical primate species possess a polymorphic X-linked and a monomorphic autosomal color vision gene. Consequently, populations are composed of both dichromatics and trichromatics. Most theories on the maintenance of this genetic system revolve around possible advantages for foraging ecology. To examine the issue from a different angle, we compared the numbers and relative frequencies of alleles at the X-linked locus among three species of Saimiri representing a wide range of geographical and behavioral variation in the genus. Exons 3, 4, and 5 of the X-linked opsin gene were sequenced for a large number of X chromosomes for all three species. Several synonymous mutations were detected in exons 4 and 5 for the originally reported alleles but only a single nonsynonymous change was detected. Two alleles were found that appeared to be the result of recombination events. The low occurrence of recombinant alleles and absence of mutations in the amino acids critical for spectral tuning indicates that stabilizing selection acts to maintain the combinations of critical sites specific to each allele. Allele frequencies were approximately the same for all Saimiri species, with a slight but significant difference between S. boliviensis and S. oerstedii. No apparent correlation exists between allele frequencies and behavioral or biogeographical differences between species, casting doubt on the speculation that the spectral sensitivities of the alleles have been maintained because they are specifically well-tuned to Saimiri visual ecology. Rather, the spectral tuning peaks might have been maintained because they are as widely spaced as possible within the limited range of middlewave to longwave spectra useful to all primates. This arrangement creates a balance between maximizing the distance between spectral tuning peaks (allowing the color opponency of the visual system to distinguish between peaks) and maximizing the number of alleles within a limited range (yielding the greatest possible frequency of heterozygotes). PMID:12029355

Cropp, Susan; Boinski, Sue; Li, Wen-Hsiung

2002-06-01

373

HLA-DRB1*13:01 allele in the genetic susceptibility to colorectal carcinoma.  

PubMed

Increasing evidence suggests that HLA-DRB1 alleles reduce or increase the risk of developing ulcerative colitis-associated colorectal carcinoma (CRC) tumors. However, the role of HLA-DRB1 locus on the susceptibility to develop CRC tumor, in the absence of a history of inflammatory bowel diseases (IBDs), is unclear. The aim of our study was to determine whether HLA-DRB1 alleles are associated with IBD-independent CRC tumor. HLA-DRB1 allele polymorphisms were identified by sequence-based typing method in 53 CRC patients and 57 sex- and age-matched healthy Caucasian controls. Pearson's chi-squared analysis with Yate's correction or Fisher's exact test with Bonferroni's correction, as appropriate, were used to compare the allele frequency (AF) differences of HLA-DRB1 in patients and controls. A total of 29 HLA-DRB1 alleles were recognized. A detailed study of these alleles allowed to identify DRB1*13:01 and DRB1*11:01 alleles that were significantly associated with an increased and reduced risk to develop CRC tumor, respectively. AF of DRB1*13:01, in CRC patients, was significantly higher than that of healthy controls, even following Bonferroni's correction (p?=?0.029). In contrast, the presence of the DRB1*11:01 allele was negatively associated with CRC tumor as evidenced by the significantly lower AF in CRC patients than that of healthy controls (p?=?0.005). However, following Bonferroni's correction, the AF of DRB*11:01 lost its statistical significance. These results suggest that HLA-DRB1*13:01 allele could be a potential marker for predicting genetic susceptibility to CRC tumor. In contrast, the protective role of DRB1*11:01 remains unclear. PMID:25346274

Aureli, Anna; Canossi, Angelica; Del Beato, Tiziana; Franceschilli, Luana; Buonomo, Oreste; Papola, Franco; De Sanctis, Flavio; Lanzilli, Giulia; Sileri, Pierpaolo; Coppola, Andrea; Caratelli, Sara; Arriga, Roberto; Orlandi, Augusto; Lauro, Davide; Rossi, Piero; Sconocchia, Giuseppe

2015-05-15

374

European Training Foundation  

NSDL National Science Digital Library

Working in conjunction with a host of other inter-governmental agencies, the European Training Foundation (ETF) is committed to "developing a range of quality of education and training systems" across Europe and into Asia. First-time visitors to the site will want to take a look at their "About the ETF" area to learn more about their mission, and then proceed to the "Themes" area, which contains basic information about their work in such areas as adult learning and online education. As might be expected from such an organization, their publications area is a real treasure-trove for policy analysts and others, as it contains works on "best practices" and overviews of educational systems throughout the region. In keeping with the strong emphasis place on vocational education, the site also contains a number of related events and conferences that will be of great interest as well.

375

Detection and inheritance of stylar ribonucleases associated with incompatibility alleles in apricot  

Microsoft Academic Search

Stylar proteins were surveyed by non-equilibrium pH gradient electrofocusing to identify S-RNases associated with gametophytic\\u000a self-incompatibility in nine apricot cultivars. RNase activities associated with the alleles of incompatibility S\\u000a \\u000a 1\\u000a , S\\u000a \\u000a 2\\u000a , S\\u000a \\u000a 5\\u000a , and S\\u000a \\u000a 6\\u000a and with the allele of compatibility Sc were clearly identified. Two other bands that we considered related to the alleles

L. Burgos; O. Pérez-Tornero; J. Ballester; E. Olmos

1998-01-01

376

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

SciTech Connect

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.

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

377

The relative quantities and catalytic activities of enzymes produced by alleles at the alcohol dehydrogenase locus in Drosophila melanogaster  

Microsoft Academic Search

We have examined the kinetic properties of enzymes produced by the electrophoretically fast (F) and slow (S) alleles at the alcohol dehydrogenase locus in a polymorphic laboratory population of Drosophila melanogaster. The product of the F allele has approximately twice the specific activity of the product of the S allele. We have estimated four Michaelis constants (Kethanol, KNAD, K'ethanol, and

Thomas H. Day; P. C. Hillier; Bryan Clarke

1974-01-01

378

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

PubMed Central

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

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

379

Genome-wide Ancestry Association Testing Identifies a Common European Variant on 6q14.1 as a Risk Factor for Asthma in African Americans  

PubMed Central

Background Genetic variants that contribute to asthma susceptibility may be present at varying frequencies in different populations, which is an important consideration and advantage for performing genetic association studies in admixed populations. Objective To identify asthma-associated loci in African Americans. Methods We compared local African and European ancestry estimated from dense single nucleotide polymorphism (SNP) genotype data in African American adults with asthma and non-asthmatic controls. Allelic tests of association were performed within the candidate regions identified, correcting for local European admixture. Results We identified a significant ancestry association peak on chromosomes 6q. Allelic tests for association within this region identified a SNP (rs1361549) on 6q14.1 that was associated with asthma exclusively in African Americans with local European admixture (OR=2.2). The risk allele is common in Europe (42% in the HapMap CEU) but absent in West Africa (0% in the HapMap YRI), suggesting the allele is present in African Americans due to recent European admixture. We replicated our findings in Puerto Ricans and similarly found that the signal of association is largely specific to individuals who are heterozygous for African and non-African ancestry at 6q14.1. However, we found no evidence for association in European Americans or in Puerto Ricans in the absence of local African ancestry, suggesting that the association with asthma at rs1361549 is due to an environmental or genetic interaction. Conclusion We identified a novel asthma-associated locus that is relevant to admixed populations with African ancestry, and highlight the importance of considering local ancestry in genetic association studies of admixed populations. PMID:22607992

Torgerson, Dara G.; Capurso, Daniel; Ampleford, Elizabeth J.; Li, Xingnan; Moore, Wendy C.; Gignoux, Christopher R.; Hu, Donglei; Eng, Celeste; Mathias, Rasika A.; Busse, William W.; Castro, Mario; Erzurum, Serpil C.; Fitzpatrick, Anne M.; Gaston, Benjamin; Israel, Elliot; Jarjour, Nizar N.; Teague, W. Gerald; Wenzel, Sally E.; Rodríguez-Santana, José R.; Rodríguez-Cintrón, William; Avila, Pedro C.; Ford, Jean G.; Barnes, Kathleen C.; Burchard, Esteban G.; Howard, Timothy D.; Bleecker, Eugene R.; Meyers, Deborah A.; Cox, Nancy J.; Ober, Carole; Nicolae, Dan L.

2012-01-01

380

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

PubMed Central

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

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

2015-01-01

381

Null alleles of ABCG2 encoding the breast cancer resistance protein define the new blood group system Junior.  

PubMed

The breast cancer resistance protein, also known as ABCG2, is one of the most highly studied ATP-binding cassette (ABC) transporters because of its ability to confer multidrug resistance. The lack of information on the physiological role of ABCG2 in humans severely limits cancer chemotherapeutic approaches targeting this transporter. We report here that ABCG2 comprises the molecular basis of a new blood group system (Junior, Jr) and that individuals of the Jr(a-) blood type have inherited two null alleles of ABCG2. We identified five frameshift and three nonsense mutations in ABCG2. We also show that the prevalence of the Jr(a-) blood type in the Japanese and European Gypsy populations is related to the p.Gln126* and p.Arg236* protein alterations, respectively. The identification of ABCG2(-/-) (Jr(a-)) individuals who appear phenotypically normal is an essential step toward targeting ABCG2 in cancer and also in understanding the physiological and pharmacological roles of this promiscuous transporter in humans. PMID:22246505

Saison, Carole; Helias, Virginie; Ballif, Bryan A; Peyrard, Thierry; Puy, Hervé; Miyazaki, Toru; Perrot, Sébastien; Vayssier-Taussat, Muriel; Waldner, Mauro; Le Pennec, Pierre-Yves; Cartron, Jean-Pierre; Arnaud, Lionel

2012-02-01

382

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

NASA Astrophysics Data System (ADS)

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.

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

2012-08-01

383

Reevaluation of the relative risk for susceptibility to celiac disease of HLA-DRB1, -DQA1, -DQB1, -DPB1, and TAP2 alleles in a French population  

Microsoft Academic Search

In a population of 46 children with CD recruited in the Paris area of France, an excess of DRB1?03 and DRB1?07 alleles and of DR3\\/DR7, DR3\\/ DR3, and DR11(or12)\\/DR7 phenotypes was found (RRs of 6.3, 9.3, 24.6,15, and15.1, respectively), which is reminiscent of the markers of susceptibility observed in southern rather than in northern European celiac patients. More importantly, the

A. Meddeb-Garnaoui; D. Zeliszewski; J. F. Mougenot; I. Djilali-Saiah; S. Caillat-Zucman; A. Dormoy; C. Gaudebout; M. M. Tongio; J. J. Baudon; G. Sterkers

1995-01-01

384

NKX2-3 and IRGM variants are associated with disease susceptibility to IBD in Eastern European patients  

PubMed Central

AIM: To investigate variants of immunity-related GTPase family M (IRGM) and NKX2-3 genes and genotype-phenotype in Eastern European patients with inflammatory bowel disease (IBD). METHODS: We analyzed 1707 Hungarian and Czech subjects with Crohn’s disease (CD) (n = 810, age: 37.1 ± 12.6 years, duration: 10.7 ± 8.4 years) and ulcerative colitis (UC) (n = 428, age: 43.7 ± 15.0 years, duration: 12.6 ± 9.9 years), as well as 469 healthy controls. IRGM rs13361189, NKX2-3 rs10883365 and ECM1 rs13294 polymorphisms were tested by LightCycler allele discrimination. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: NKX2-3 rs10883365 variant allele was associated with increased risk for CD (P = 0.009, OR = 1.24, 95% CI = 1.06-1.48) and UC (P = 0.001, OR = 1.36, 95% CI = 1.13-1.63), whereas variant IRGM allele increased risk for CD (P = 0.029, OR = 1.36, 95% CI = 1.03-1.79). In contrast, ECM1 rs13294 was not associated with either CD or UC. In CD, the variant IRGM allele was associated with a colon-only location (P = 0.02, OR = 1.62, 95% CI = 1.07-2.44), whereas in UC, the ECM1 variant was associated with cutaneous manifestations (P = 0.002, OR = 3.36, 95% CI = 1.48-7.63). Variant alleles did not predict resistance to steroids or azathioprine, efficacy of infliximab, or need for surgery. CONCLUSION: NKX2-3 and IRGM are susceptibility loci for IBD in Eastern European patients. Further studies are needed to confirm the reported phenotype-genotype associations. PMID:21049557

Meggyesi, Nora; Kiss, Lajos S; Koszarska, Magdalena; Bortlik, Martin; Duricova, Dana; Lakatos, Laszlo; Molnar, Tamas; Leni?ek, Martin; Vítek, Libor; Altorjay, Istvan; Papp, Maria; Tulassay, Zsolt; Miheller, Pal; Papp, Janos; Tordai, Attila; Andrikovics, Hajnalka; Lukas, Milan; Lakatos, Peter Laszlo

2010-01-01

385

Distribution of CC-chemokine receptor-5-?32 allele among the tribal and caste population of Vidarbha region of Maharashtra state  

PubMed Central

BACKGROUND: Genetic relationships among the ethnic groups are not uniform across the geographical region. Considering this assumption, we analyzed the frequency of the CC-chemokine receptor-5 (CCR5)-?32 allele of the CCR5 chemokine receptor, which is considered a Caucasian marker, in Bhil tribal and Brahmin caste sample sets from the population. MATERIALS AND METHODS: 108 blood samples were collected from 6 tribe's populations and a caste population from the district of Vidarbha region. RESULTS AND DISCUSSION: The presence of low frequencies of CCR5-?32 in an individual of Bhil tribe (0.034, ?2 value 0.017) in the present study implies that these communities may have a better resistance toward human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) than the other studied tribe sample, as non-show such mutation. CONCLUSION: The marginal presence of the allele seen in the studied tribal population could be due to gene flow from the people of European descent. However, lack of the homozygous CCR5-?32 mutation and the low prevalence of heterozygous CCR5-?32 mutations suggest that the Indians are highly susceptible to HIV/AIDS, and this correlates with the highest number of HIV/AIDS infected individuals in India. PMID:23901195

Chavhan, Arvind B.; Pawar, Santosh S.; Jadhao, Rajusing G.; Patil, Kishor G.

2013-01-01

386

Modified bases enable high-efficiency oligonucleotide-mediated allelic replacement via mismatch repair evasion  

E-print Network

Genome engineering using single-stranded oligonucleotides is an efficient method for generating small chromosomal and episomal modifications in a variety of host organisms. The efficiency of this allelic replacement strategy ...

Wang, Harris H.

387

Dopamine receptor D4 allele distribution in Amerindians: a reflection of past behavior differences?  

PubMed

The DRD4 variable number of tandem repeats (VNTR) allele distribution of 172 Guarani (Kaiowá and Ñandeva subgroups) and Kaingang Brazilian Amerindians is reported. These results are integrated with those previously obtained for this ethnic group. Allele frequencies for the three populations are within the interval observed for 15 other Native American populations and show intermediate values between those observed in Amazonia and Patagonia. Significant differences in allele distribution between recent past hunter-gatherer and agriculturalist populations are observed, with an increase of the 7R allele among hunter-gatherers (P < 0.001). Analysis of molecular variance (AMOVA) and pairwise F(ST) data suggest three distinct sectors for the genetic landscape of Native South America: Andes, Center/Southeast region, and Amazonia. Common traits among hunter-gatherers such as novelty-seeking temperament, hyperactivity, and impulsivity could have been important and advantageous in new environments during America's prehistoric colonization. PMID:20623607

Tovo-Rodrigues, Luciana; Callegari-Jacques, Sidia M; Petzl-Erler, M Luiza; Tsuneto, Luiza; Salzano, Francisco M; Hutz, Mara H

2010-11-01

388

MicroDrop: a program for estimating and correcting for allelic dropout in nonreplicated microsatellite genotypes  

E-print Network

microsatellite genotypes version 1.01 Chaolong Wang1 Department of Computational Medicine and Bioinformatics estimation . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.3 Genotype imputation for allelic dropout in microsatellite genotype data from diploid organisms. The code is written in C

Rosenberg, Noah

389

A new high-frequency allele of the BM2113 locus in the Yunnan mithun population.  

PubMed

The BM2113 locus was amplified in Yunnan mithun (Bos frontalis) from the southwest mountains of China. It showed a high degree of polymorphism with a total of 12 alleles. The 121-bp polymorphic allele of the BM2113 locus that accounted for 37.1% of homozygotes was the predominant allele with a frequency of 58.57%, identified as mithun-specific for Bos species in Yunnan mithun. The polymorphism information content value was high with a mean of 0.6170, the expected and observed heterozygosity was moderate with values of 0.6427 and 0.6000, respectively, and the BM2113 locus was under Hardy-Weinberg equilibrium (P = 0.2897) in the Yunnan mithun population. This study elucidated the genetic diversity, multi-origin, specific alleles, and characterization of mithun. PMID:24737440

Qu, K-X; He, Z-X; Hao, R-J; Zhang, J-C; Huang, B-Z; Zan, L-S; Zhang, Y-P

2014-01-01

390

Identification of low penetrance alleles for lung cancer: The GEnetic Lung CAncer Predisposition Study (GELCAPS)  

E-print Network

Abstract Background Part of the inherited risk to lung cancer is likely to include common, low risk alleles. The identification of this class of susceptibility is contingent on association-based analyses. We established GEnetic Lung CAncer...

Eisen, Tim; Matakidou, Athena; Consortium, Gelcaps; Houlston, Richard

2008-08-20

391

SNP-specific array-based allele-specific expression analysis  

PubMed Central

We have developed an optimized array-based approach for customizable allele-specific gene expression (ASE) analysis. The central features of the approach are the ability to select SNPs at will for detection, and the absence of need to PCR amplify the target. A surprisingly long probe length (39–49 nt) was needed for allelic discrimination. Reconstitution experiments demonstrate linearity of ASE over a broad range. Using this approach, we have discovered at least two novel imprinted genes, NLRP2, which encodes a member of the inflammasome, and OSBPL1A, which encodes a presumed oxysterol-binding protein, were both preferentially expressed from the maternal allele. In contrast, ERAP2, which encodes an aminopeptidase, did not show preferential parent-of-origin expression, but rather, cis-acting nonimprinted differential allelic control. The approach is scalable to the whole genome and can be used for discovery of functional epigenetic modifications in patient samples. PMID:18369178

Bjornsson, Hans T.; Albert, Thomas J.; Ladd-Acosta, Christine M.; Green, Roland D.; Rongione, Michael A.; Middle, Christina M.; Irizarry, Rafael A.; Broman, Karl W.; Feinberg, Andrew P.

2008-01-01

392

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

PubMed Central

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

Shahin, Arwa; Smulders, Marinus J. M.; van Tuyl, Jaap M.; Arens, Paul; Bakker, Freek T.

2014-01-01

393

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

PubMed

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

Shahin, Arwa; Smulders, Marinus J M; van Tuyl, Jaap M; Arens, Paul; Bakker, Freek T

2014-01-01

394

Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder  

SciTech Connect

We present evidence of a genetic association between bipolar disorder and alleles at 3 monoamine oxidase A (MAOA) markers, but not with alleles of a monoamine oxidase B (MAOB) polymorphism. The 3 MAOA markers, including one associated with low MAOA activity, show strong allelic association with each other but surprisingly not with MAOB. Our results are significantly only for females, though the number of males in our sample is too small to draw any definite conclusions. Our data is consistent with recent reports of reduced MAOA activity in patients with abnormal behavioral phenotypes. The strength of the association is weak, but significant, which suggests that alleles at the MAOA locus contribute to susceptibility to bipolar disorder rather than being a major determinant. 58 refs., 1 fig., 3 tabs.

Lim, L.C.C.; Sham, P.; Castle, D. [Institute of Psychiatry, London (United Kingdom)] [and others

1995-08-14

395

Known unknowns for allele-specific expression and genomic imprinting effects  

PubMed Central

Recent studies have provided evidence for non-canonical imprinting effects that are associated with allele-specific expression biases at the tissue level in mice. These imprinting effects have features that are distinct from canonical imprinting effects that involve allele silencing. Here, I discuss some of the evidence for non-canonical imprinting effects in the context of random X-inactivation and epigenetic allele-specific expression effects on the autosomes. I propose several mechanisms that may underlie non-canonical imprinting effects and outline future directions and approaches to study these effects at the cellular level in vivo. The growing evidence for complex allele-specific expression effects that are cell- and developmental stage-specific has opened a new frontier for study. Currently, the function of these effects and the underlying regulatory mechanisms are largely unknown. PMID:25343032

2014-01-01

396

Risk for ACPA-positive rheumatoid arthritis is driven by shared HLA amino acid polymorphisms in Asian and European populations.  

PubMed

Previous studies have emphasized ethnically heterogeneous human leukocyte antigen (HLA) classical allele associations to rheumatoid arthritis (RA) risk. We fine-mapped RA risk alleles within the major histocompatibility complex (MHC) in 2782 seropositive RA cases and 4315 controls of Asian descent. We applied imputation to determine genotypes for eight class I and II HLA genes to Asian populations for the first time using a newly constructed pan-Asian reference panel. First, we empirically measured high imputation accuracy in Asian samples. Then we observed the most significant association in HLA-DR?1 at amino acid position 13, located outside the classical shared epitope (Pomnibus = 6.9 × 10(-135)). The individual residues at position 13 have relative effects that are consistent with published effects in European populations (His > Phe > Arg > Tyr ? Gly > Ser)--but the observed effects in Asians are generally smaller. Applying stepwise conditional analysis, we identified additional independent associations at positions 57 (conditional Pomnibus = 2.2 × 10(-33)) and 74 (conditional Pomnibus = 1.1 × 10(-8)). Outside of HLA-DR?1, we observed independent effects for amino acid polymorphisms within HLA-B (Asp9, conditional P = 3.8 × 10(-6)) and HLA-DP?1 (Phe9, conditional P = 3.0 × 10(-5)) concordant with European populations. Our trans-ethnic HLA fine-mapping study reveals that (i) a common set of amino acid residues confer shared effects in European and Asian populations and (ii) these same effects can explain ethnically heterogeneous classical allelic associations (e.g. HLA-DRB1*09:01) due to allele frequency differences between populations. Our study illustrates the value of high-resolution imputation for fine-mapping causal variants in the MHC. PMID:25070946

Okada, Yukinori; Kim, Kwangwoo; Han, Buhm; Pillai, Nisha E; Ong, Rick T-H; Saw, Woei-Yuh; Luo, Ma; Jiang, Lei; Yin, Jian; Bang, So-Young; Lee, Hye-Soon; Brown, Matthew A; Bae, Sang-Cheol; Xu, Huji; Teo, Yik-Ying; de Bakker, Paul I W; Raychaudhuri, Soumya

2014-12-20

397

Interrogation of allelic chromatin states in human cells by high-density ChIP-genotyping.  

PubMed

Allele-specific (AS) assessment of chromatin has the potential to elucidate specific cis-regulatory mechanisms, which are predicted to underlie the majority of the known genetic associations to complex disease. However, development of chromatin landscapes at allelic resolution has been challenging since sites of variable signal strength require substantial read depths not commonly applied in sequencing based approaches. In this study, we addressed this by performing parallel analyses of input DNA and chromatin immunoprecipitates (ChIP) on high-density Illumina genotyping arrays. Allele-specificity for the histone modifications H3K4me1, H3K4me3, H3K27ac, H3K27me3, and H3K36me3 was assessed using ChIP samples generated from 14 lymphoblast and 6 fibroblast cell lines. AS-ChIP SNPs were combined into domains and validated using high-confidence ChIP-seq sites. We observed characteristic patterns of allelic-imbalance for each histone-modification around allele-specifically expressed transcripts. Notably, we found H3K4me1 to be significantly anti-correlated with allelic expression (AE) at transcription start sites, indicating H3K4me1 allelic imbalance as a marker of AE. We also found that allelic chromatin domains exhibit population and cell-type specificity as well as heritability within trios. Finally, we observed that a subset of allelic chromatin domains is regulated by DNase I-sensitive quantitative trait loci and that these domains are significantly enriched for genome-wide association studies hits, with autoimmune disease associated SNPs specifically enriched in lymphoblasts. This study provides the first genome-wide maps of allelic-imbalance for five histone marks. Our results provide new insights into the role of chromatin in cis-regulation and highlight the need for high-depth sequencing in ChIP-seq studies along with the need to improve allele-specificity of ChIP-enrichment. PMID:25055051

Light, Nicholas; Adoue, Véronique; Ge, Bing; Chen, Shu-Huang; Kwan, Tony; Pastinen, Tomi

2014-09-01

398

Europlanet in the European Parliament  

NASA Astrophysics Data System (ADS)

Europlanet RI has as one of its deliverables "dissemination" to policy makers. To this end, it started a project in May 2010 to contact Members of the European Parliament to discuss Europlanet goals. Between June and December 2010, Europlanet key members held meetings with 16 MEPs or their assistants. Europlanet organised a Dinner Debate at the Brussels Parliament on February 2nd, hosted by MEPs Britta Thomsen and Teresa Riera Madurell. Seven MEPs attended, along with representatives from the European Commission, Industry, the European Space Policy Institute and members of the Europlanet Research Infrastructure.

Raszler, V.; Miller, S.; Heward, A.

2011-10-01

399

No evidence for allelic association between bipolar disorder and monoamine oxidase A gene polymorphisms  

SciTech Connect

We have tested the hypothesis that DNA markers in the MAOA gene show allelic association with bipolar affective disorder. Eighty-four unrelated Caucasian patients with DSM III-R bipolar disorder and 84 Caucasian controls were typed for three markers in MAOA: a dinucleotide repeat in intron 2, a VNTR in intron 1, and an Fnu4HI RFLP in exon 8. No evidence for allelic association was observed between any of the markers and bipolar disorder. 9 refs., 1 tab.

Craddock, N.; Daniels, J.; Roberts, E. [Univ. of Wales, College of Medicine, Cardiff (United Kingdom)] [and others

1995-08-14

400

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

Microsoft Academic Search

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

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

401

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

Microsoft Academic Search

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

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

402

HLA-DMA allele polymorphism: no impact on kidney allograft outcome  

Microsoft Academic Search

The purpose of this study was to analyze the association of HLA-DMA alleles with rejection episodes and early graft loss (EGL) in renal transplant recipients. One hundred and eighty four HLA-DMA alleles were retrospectively analyzed by DNA sequence analysis in 92 kidney transplant recipients. The gene frequencies of HLA-DMA ?0101, ?0102, ?0103 and ?0104 were found to be similar in

Elia Saadeh; Michael Szatkowski; Calvin P. H Vary; Joshua D Smith; Jonathan Himmelfarb; Richard J Mahoney

2000-01-01

403

Allelic association between the D10S1423 marker and Alzheimer's disease in a German population  

Microsoft Academic Search

Recently a full genome survey detected an allelic association between Alzheimer's disease (AD) and the D10S1423 marker on chromosome 10p12-14 (40 cM from the telomere). In this study we examined the D10S1423 marker in an ethnically homogeneous German population of 80 AD patients and two groups of controls, 168 healthy subjects and 149 depressed patients. The 234-bp allele of the

Michael Majores; Metin Bagli; Andreas Papassotiropoulos; Sybille G Schwab; Frank Jessen; Marie Luise Rao; Wolfgang Maier; Reinhard Heun

2000-01-01

404

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

Microsoft Academic Search

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

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

1998-01-01

405

CYPalleles: a web page for nomenclature of human cytochrome P450 alleles.  

PubMed

Genetic variations in the genes encoding the cytochrome P450s (CYPs) are important determinants for interindividual differences in sensitivity to drugs and environmental chemicals as well as for the pathogenesis of several human diseases. In order to standardise the nomenclature of the rapidly increasing number of alleles described, a web page was established a few years ago. Here, we describe the present status of the web page and summarise the principles used for CYP allele nomenclature. PMID:15618703

Oscarson, Mikael; Ingelman-Sundberg, Magnus

2002-01-01

406

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

Microsoft Academic Search

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

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

1995-01-01

407

Apolipoprotein E ε4 Allele in Alzheimer's Disease and Vascular Dementia  

Microsoft Academic Search

The frequency of the ε4 allele of the apolipoprotein E (apoE) is increased in familial and sporadic late-onset Alzheimer's disease, but its prevalence in non-Alzheimer dementias in Caucasian populations is unknown. We found that the frequency of the apoE ε4 allele was 0.45 in 93 Alzheimer's disease patients, 0.46 in 23 vascular dementia patients, 0.31 in 13 dementia of the

Giovanni B. Frisoni; Laura Calabresi; Cristina Geroldi; Angelo Bianchetti; Antonio L. DAcquarica; Stefano Govoni; Cesare R. Sirtori; Marco Trabucchi; Guido Franceschini

1994-01-01

408

A new DRB1 allele ( DRB1 * 0811 ) identified in Native Americans  

Microsoft Academic Search

A novel DRB1 allele was identified in a potential bone marrow transplantation recipient and her father. Both are Native Americans of Navajo descent. Class II serologic typing of the patient demonstrated the presence of DR8, DR14, DR52, and DQ3. Sequence specific polymerase chain reaction (PCR) amplification of genomic DNA was consistent with the DRB1 alleles *08 and *14. Direct DNA

Thomas M. Williams; Jin Wu; Terry Foutz; Joan D. McAuley; Gary M. Troup

1994-01-01

409

Extensive interbreed, but minimal intrabreed, variation of DLA class II alleles and haplotypes in dogs.  

PubMed

The DLA class II genes in the dog major histocompatibility complex are highly polymorphic. To date, 52 DLA-DRB1, 16 DLA-DQA1 and 41 DLA-DQB1 allelic sequences have been assigned. The aim of this study was to examine the intrabreed and interbreed variation of DLA allele and haplotype frequencies in dogs, and to ascertain whether conserved DLA class II haplotypes occur within and between different breeds. One thousand and 25 DNA samples from over 80 different breeds were DLA class II genotyped, the number of dogs per breed ranging from 1 to 61. DNA sequence based typing and sequence specific oligonucleotide probing were used to characterize dogs for their DLA-DRB1, DQA1 and DQB1 alleles. The high frequency of DLA class II homozygous animals (35%), allowed the assignment of many haplotypes despite the absence of family data. Four new DLA alleles were identified during the course of this study. Analysis of the data revealed considerable interbreed variation, not only in allele frequency, but also in the numbers of alleles found per breed. There was also considerable variation in the number of breeds in which particular alleles were found. These interbreed variations were found in all three DLA class II loci tested, and also applied to the three-locus haplotypes identified. Within this data set, 58 different DLA-DRB1/DQA1/DQB1 three-locus haplotypes were identified, which were all found in at least two different animals. Some of the haplotypes appeared to be characteristic of certain breeds. The high interbreed, and relatively low intrabreed, variation of MHC alleles and haplotypes found in this study could provide an explanation for reports of interbreed variation of immune responses to vaccines, viruses and other infections. PMID:12074709

Kennedy, Lorna J; Barnes, A; Happ, G M; Quinnell, R J; Bennett, D; Angles, J M; Day, M J; Carmichael, N; Innes, J F; Isherwood, D; Carter, S D; Thomson, W; Ollier, W E R

2002-03-01

410

Distribution of HLA Class I Alleles Differs in Celiac Disease Patients According to Age of Onset  

Microsoft Academic Search

Celiac disease (CD) or gluten-sensitive enteropathy is strongly associated with HLA-DQ alleles; more than 95% of patients are DQB1?02. However, the uniform association with HLA-DQ alleles does not explain the clinical heterogeneity, especially the wide range in the age of onset of CD. We asked whether the age of onset of CD is also influenced by class I genes of

Harald Vogelsang; Simon Panzer; Wolfgang R. Mayr; Gerhard Granditsch; Gottfried F. Fischer

2003-01-01

411

HLA-DQ? allele and genotype frequencies in a native Kuwaiti population  

Microsoft Academic Search

We report the allele and genotype frequencies in a sample of an unrelated native Kuwaiti population determined by the use of polymerase chain reaction (PCR) and reverse dot-blot analysis. This technique, involving the use of commercially available AmpliType HLA-DQ? forensic DNA amplification and typing kit, has permitted the definition of six alleles and 21 genotypes in a sample of 220

Khaled E. Al-Nassar; Jancy Mathew; Nancy Thomas; Hasmukh R. Fatania

1995-01-01

412

Increased frequency of specific alleles of the cHa ras gene in Japanese cancer patients  

Microsoft Academic Search

We have examined the c-Ha-ras locus in 145 cancer patients of a mixed group and 164 normal individuals in Japan for restriction fragment length polymorphisms and compared the allele distributions in normal and cancer populations. The c-Ha-ras gene is highly polymorphic in Japanese as previously reported in Caucasians. Two rare alleles were found to be present with increased frequencies in

Kazuo Honda; Kanji Ishizaki; Mituo Ikenaga; Junya Toguchida; Takashi Inamoto; Kouichi Tanaka; Kazue Ozawa

1988-01-01

413

Science, technology and European foreign policy: European integration, global interaction  

Microsoft Academic Search

Co-operation in science and technology is a significant component of European integration and of the European Community\\/Union's relations with the rest of the world. Science and technology are themselves becoming ever more relevant to global issues and to international interactions that together exercise the world of diplomacy. However, linkages between international S&T co-operation and foreign policy in Europe are rarely

Josephine Anne Stein

2002-01-01

414

Fragile X AGG Analysis Provides New Risk Predictions for 45–69 Repeat Alleles  

PubMed Central

We investigated the effect of AGG interruptions on fragile X repeat instability upon transmission of fragile X intermediate and small premutation alleles with 45–69 CGG repeats. The FMR1 repeat structure was determined for 375 mothers, 48 fathers, and 538 offspring (457 maternal and 81 paternal transmissions) using a novel PCR assay to determine repeat length and AGG interruptions. The number of AGG interruptions and the length of uninterrupted CGG repeats at the 3? end were correlated with repeat instability on transmission. Maternal alleles with no AGGs conferred the greatest risk for unstable transmissions. All nine full mutation expansions were inherited from maternal alleles with no AGGs. Furthermore, the magnitude of repeat expansion was larger for alleles lacking AGG interruptions. Transmissions from paternal alleles with no AGGs also exhibited greater instability than those with one or more AGGs. Our results demonstrate that characterization of the AGG structure within the FMR1 repeat allows more accurate risk estimates of repeat instability and expansion to full mutations for intermediate and small premutation alleles. PMID:23444167

Nolin, Sarah L.; Sah, Sachin; Glicksman, Anne; Sherman, Stephanie L.; Allen, Emily; Berry-Kravis, Elizabeth; Tassone, Flora; Yrigollen, Carolyn; Cronister, Amy; Jodah, Marcia; Ersalesi, Nicole; Dobkin, Carl; Brown, W. Ted; Shroff, Raghav; Latham, Gary J.; Hadd, Andrew G.

2015-01-01

415

How Old Is the Most Recent Ancestor of Two Copies of an Allele?  

PubMed Central

An important clue to the evolutionary history of an allele is the structure of the neighboring region of the genome, which we term the genomic background of the allele. Consider two copies of the allele. How similar we expect their genomic background to be is strongly influenced by the age of their most recent common ancestor (MRCA). We apply diffusion theory, first used by Motoo Kimura as a tool for predicting the changes in allele frequencies over time and developed by him in many articles in this journal, to prove a variety of new results on the age of the MRCA under the simplest demographic assumptions. In particular, we show that the expected age of the MRCA of two copies of an allele with population frequency f is just 2Nf generations, where N is the effective population size. Our results are a first step in running exact coalescent simulations, where we also simulate the history of the population frequency of an allele. PMID:15520271

Patterson, Nick J.

2005-01-01

416

Balancing Selection at a Frog Antimicrobial Peptide Locus: Fluctuating Immune Effector Alleles?  

PubMed Central

Balancing selection is common on many defense genes, but it has rarely been reported for immune effector proteins such as antimicrobial peptides (AMPs). We describe genetic diversity at a brevinin-1 AMP locus in three species of leopard frogs (Rana pipiens, Rana blairi, and Rana palustris). Several highly divergent allelic lineages are segregating at this locus. That this unusual pattern results from balancing selection is demonstrated by multiple lines of evidence, including a ratio of nonsynonymous/synonymous polymorphism significantly higher than 1, the ZnS test, incongruence between the number of segregating sites and haplotype diversity, and significant Tajima's D values. Our data are more consistent with a model of fluctuating selection in which alleles change frequencies over time than with a model of stable balancing selection such as overdominance. Evidence for fluctuating selection includes skewed allele frequencies, low levels of synonymous variation, nonneutral values of Tajima's D within allelic lineages, an inverse relationship between the frequency of an allelic lineage and its degree of polymorphism, and divergent allele frequencies among populations. AMP loci could be important sites of adaptive genetic diversity, with consequences for host–pathogen coevolution and the ability of species to resist disease epidemics. PMID:18799711

Blouin, Michael S.

2008-01-01

417

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

PubMed Central

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

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

2014-01-01

418

Is the Ala12 variant of the PPARG gene an "unthrifty allele"?  

PubMed Central

Background: The thrifty genotype hypothesis proposes that genetic susceptibility to type 2 diabetes results from the positive selection of "thrifty" alleles in the past. A corollary of this hypothesis is that genetic variants protecting against the development of diabetes are "unthrifty" and thus subject to negative selection during human evolution. Methods: It was assessed whether age estimates of the diabetes protective PPARG Ala12 allele indicate effects of natural selection. Based on published data from four populations, the date of origin of the diabetes protective PPARG Ala12 variant was estimated using both allele frequency and linkage disequilibrium (LD) with the C1431T single nucleotide polymorphism in exon 6 of the PPARG gene. Results: The best LD based estimate of the age of the Ala12 allele gave an average of ?32 000 years with a maximum upper bound of ?58 000 years. Assuming a population with a growth rate of r = 0.01 per generation, the frequency based estimate of the age of the Ala12 variant gave an average of ?27 000 years with a maximum upper bound of ?42 000 years. Discussion: The similarity of both time estimates is consistent with selective equivalence of the diabetes protective PPARG Ala12 allele and the diabetes susceptible PPARG Pro12 allele. PMID:15994875

Ruiz-Narvaez, E

2005-01-01

419

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

PubMed

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

Kangueane, Pandjassarame; Sakharkar, Meena Kishore

2007-01-01

420

Validation of statistical imputation of allele-level multilocus phased genotypes from ambiguous HLA assignments.  

PubMed

Genetic matching for loci in the human leukocyte antigen (HLA) region between a donor and a patient in hematopoietic stem cell transplantation (HSCT) is critical to outcome; however, methods for HLA genotyping of donors in unrelated stem cell registries often yield results with allelic and phase ambiguity and/or do not query all clinically relevant loci. We present and evaluate a statistical method for in silico imputation of HLA alleles and haplotypes in large ambiguous population data from the Be The Match(®) Registry. Our method builds on haplotype frequencies estimated from registry populations and exploits patterns of linkage disequilibrium (LD) across HLA haplotypes to infer high resolution HLA assignments. We performed validation on simulated and real population data from the Registry with non-trivial ambiguity content. While real population datasets caused some predictions to deviate from expectation, validations still showed high percent recall for imputed results with average recall >76% when imputing HLA alleles from registry data. We simulated ambiguity generated by several HLA genotyping methods to evaluate the imputation performance on several levels of typing resolution. On average, imputation percent recall of allele-level HLA haplotypes was >95% for allele-level typing, >92% for intermediate resolution typing and >58% for serology (low-resolution) typing. Thus, allele-level HLA assignments can be imputed through the application of a set of statistical and population genetics inferences and with knowledge of haplotype frequencies and self-identified race and ethnicities. PMID:25040134

Madbouly, A; Gragert, L; Freeman, J; Leahy, N; Gourraud, P-A; Hollenbach, J A; Kamoun, M; Fernandez-Vina, M; Maiers, M

2014-09-01

421

Allelic diversity and molecular characterization of puroindoline genes in five diploid species of the Aegilops genus.  

PubMed

Grain hardness is an important quality trait in wheat. This trait is related to the variation in, and the presence of, puroindolines (PINA and PINB). This variation can be increased by the allelic polymorphism present in the Aegilops species that are related to wheat. This study evaluated allelic Pina and Pinb gene variability in five diploid species of the Aegilops genus, along with the molecular characterization of the main allelic variants found in each species. This polymorphism resulted in 16 alleles for the Pina gene and 24 alleles for the Pinb gene, of which 10 and 17, respectively, were novel. Diverse mutations were detected in the deduced mature proteins of these alleles, which could influence the hardness characteristics of these proteins. This study shows that the diploid species of the Aegilops genus could be a good source of genetic variability for both Pina and Pinb genes, which could be used in breeding programmes to extend the range of different textures in wheat. PMID:24058161

Cuesta, Susana; Guzmán, Carlos; Alvarez, Juan B

2013-11-01

422

ACE-II genotype and I allele predicts ischemic stroke among males in south India.  

PubMed

Two hundred ischemic stroke patients and 193 age and sex matched healthy controls were studied for the presence of Angiotensin Converting Enzyme Insertion/Deletion (ACE I/D) gene polymorphism. The PCR studies revealed that ACE 'II' (OR = 2.055; p = 0.004) genotype and 'I' (OR = 1.411; p = 0.018) alleles were significantly associated with IS patients. Gender specific analysis revealed a strong association of 'II' (OR = 2.044; p = 0.014) genotype and 'I' (OR = 1.531; p = 0.011) allele with male sex. Classification of patients based on TOAST criteria, revealed a significant association for 'II' genotype (OR = 1.713; p = 0.043) and 'I' (OR = 1.382; p = 0.039) allele in LVD patients only. When the data was stratified based on age and sex, a statistically significant association was observed for ACE 'II' genotype (OR = 2.288; p = 0.006) and 'I' allele (OR = 1.395; p = 0.054) in IS male patients of > 50 years of age. The ACE 'D' allele was found to be increased in controls (OR = 0.709; p = 0.018) than IS patients. Multivariate logistic regression analysis showed that smoking and diabetes were the most powerful independent risk factor in LVD type of stroke. Thus, we presented here an evidence for a strong association of ACE 'II' genotype and 'I' allele compounded by factors such as smoking and diabetes among south Indian IS patients. PMID:25606450

Vijayan, Murali; Chinniah, Rathika; Ravi, Padma Malini; Mosses Joseph, Arun Kumar; Vellaiappan, Neethi Arasu; Krishnan, Jeyaram Illiayaraja; Karuppiah, Balakrishnan

2014-12-01