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1

Is the European spatial distribution of the HIV-1-resistant CCR5-Delta32 allele formed by a breakdown of the pathocenosis due to the historical Roman expansion?  

PubMed

We studied the possible effects of the expansion of ancient Mediterranean civilizations during the five centuries before and after Christ on the European distribution of the mutant allele for the chemokine receptor gene CCR5 which has a 32-bp deletion (CCR5-Delta32). There is a strong evidence for the unitary origin of the CCR5-Delta32 mutation, this it is found principally in Europe and Western Asia, with generally a north-south downhill cline frequency. Homozygous carriers of this mutation show a resistance to HIV-1 infection and a slower progression towards AIDS. However, HIV has clearly emerged too recently to have been the selective force on CCR5. Our analyses showed strong negative correlations in Europe between the allele frequency and two historical parameters, i.e. the first colonization dates by the great ancient Mediterranean civilizations, and the distances from the Northern frontiers of the Roman Empire in its greatest expansion. Moreover, other studies have shown that the deletion frequencies in both German Bronze Age and Swedish Neolithic populations were similar to those found in the corresponding modern populations, and this deletion has been found in ancient DNA of around 7000 years ago, suggesting that in the past, the deletion frequency could have been relatively high in European populations. In addition, in West Nile virus pathogenesis, CCR5 plays an antimicrobial role showing that host genetic factors are highly pathogen-specific. Our results added to all these previous data suggest that the actual European allele frequency distribution might not be due to genes spreading, but to a negative selection resulting in the spread of pathogens principally during Roman expansion. Indeed, as gene flows from colonizers to European native populations were extremely low, the mutational changes might be associated with vulnerability to imported infections. To date, the nature of the parasites remains unknown; however, zoonoses could be incriminated. PMID:18790087

Faure, Eric; Royer-Carenzi, Manuela

2008-08-27

2

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

PubMed

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

2012-01-06

3

Distribution of the CCR5delta32 allele (gene variant CCR5) in Rond?nia, 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.

de Farias, Josileide Duarte; Santos, Marlene Guimaraes; de Franca, Andonai Krauze; Delani, Daniel; Tada, Mauro Shugiro; Casseb, Almeida Andrade; Simoes, Aguinaldo Luiz; Engracia, Vera

2012-01-01

4

Evolution of the CCR5 Delta32 mutation based on haplotype variation in Jewish and Northern European population samples.  

PubMed

The chemokine receptor 5 (CCR5) serves as a fusion cofactor for macrophage-tropic strains of HIV-1. In addition, CCR5 has been shown to mediate the entry of poxviruses into target cells. Individuals homozygous for the Delta32 deletion-mutation have no surface expression of CCR5 and are highly protected against HIV-1 infection. To gain insights into the evolution of the mutation in modern populations, the relatively high frequency of the Delta32-ccr5 allele in some European and Jewish populations is explored here by examining haplotypes of 3p21.3 constructed of five polymorphic marker loci surrounding CCR5. By sampling Ashkenazi, non-Ashkenazi and non-Jewish populations, we utilize the natural experiment that occurred as a consequence of the Jewish Diaspora, and demonstrate that a single mutation was responsible for all copies of Delta32. This mutation must have moved from Northern European populations to the Ashkenazi Jews where evidence suggests that Delta32 carriers of both groups were favored by repeated occurrence of epidemic small pox beginning in the 8th century AD. PMID:11334678

Klitz, W; Brautbar, C; Schito, A M; Barcellos, L F; Oksenberg, J R

2001-05-01

5

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

PubMed Central

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

2013-01-01

6

The Black Death and AIDS: CCR5-Delta32 in genetics and history.  

PubMed

Black Death and AIDS are global pandemics that have captured the popular imagination, both attracting extravagant hypotheses to account for their origins and geographical distributions. Medical scientists have recently attempted to connect these two great pandemics. Some argue that the Black Death of 1346-52 was responsible for a genetic shift that conferred a degree of resistance to HIV 1 infection, that this shift was almost unique to European descendents, and that it mirrors the intensity of Black Death mortality within Europe. Such a hypothesis is not supported by the historical evidence: the Black Death did not strike Europe alone but spread from the east, devastating regions such as China, North Africa, and the Middle East as much or even more than Europe. Further, in Europe its levels of mortality do not correspond with the geographic distribution of the proportion of descendents with this CCR5 gene. If anything, the gradient of Black Death mortality sloped in the opposite direction from that of present-day genotypes: the heaviest casualties were in the Mediterranean, the very regions whose descendents account for the lowest incidences of the HIV-1 resistant allele. We argue that closer collaboration between historians and scientists is needed to understand the selective pressures on genetic mutation, and the possible triggers for changes in genetic spatial frequencies over the past millennia. This requires care and respect for each other's methods of evaluating data. PMID:16880184

Cohn, S K; Weaver, L T

2006-08-01

7

Lack of association between the chemokine receptor 5 polymorphism CCR5delta32 in rheumatoid arthritis and juvenile idiopathic arthritis  

Microsoft Academic Search

BACKGROUND: The chemokine receptor CCR5 has been detected at elevated levels on synovial T cells, and a 32 bp deletion in the CCR5 gene leads to a non-functional receptor. A negative association between the CCR5?32 and rheumatoid arthritis (RA) has been reported, although with conflicting results. In juvenile idiopathic arthritis (JIA), an association with CCR5 was recently reported. The purpose

Ewald Lindner; Gry BN Nordang; Espen Melum; Berit Flatø; Anne Marit Selvaag; Erik Thorsby; Tore K Kvien; Øystein T Førre; Benedicte A Lie

2007-01-01

8

Development of a CAPS marker system for genotyping European pear cultivars harboring 17 S alleles.  

PubMed

The full-length cDNAs of eight S ribonucleases (S-RNases) were cloned from stylar RNA of European pear cultivars that could not be characterized by the cleaved amplified polymorphic sequences (CAPS) marker system for genotyping European pear cultivars harboring nine S alleles Sa, Sb, Sd, Se, Sh, Sk, Sl, Sq, and Sr. Comparison of the nucleotide sequences between these cDNAs and six putative S-RNase alleles previously amplified by genomic PCR revealed that five corresponded to the putative Sc-, Si-, Sm-, Sn-, and Sp-RNase alleles and the other three corresponded new S-RNase alleles (designated as putative Sg-, Ss-, and St-RNase alleles). Genomic PCR with a new set of primers was used to amplify 17 S-RNase alleles: 1906 bp (Sg), 1642 bp (St), 1414 bp (Sl), ca. 1.3 kb (Sk and Sq), 998 bp (Se), 440 bp (Sb), and ca. 350 bp (Sa, Sc, Sd, Sh, Si, Sm, Sn, Sp, Sr, and Ss). Among them, S-RNase alleles of similar size were discriminated by digestion with 11 restriction endo-nucleases. The PCR amplification of 17 S-RNase alleles following digestion with the restriction endonucleases provided a new CAPS marker system for rapid S-genotyping of European pear cultivars harboring 17 S alleles. Using the CAPS analysis, Sc, Sg, Si, Sm, Sn, Sp, Ss, and St alleles were found in 32 cultivars, which were classified into 23 S-genotypes. PMID:17061100

Moriya, Yuki; Yamamoto, Kentaro; Okada, Kazuma; Iwanami, Hiroshi; Bessho, Hideo; Nakanishi, Tetsu; Takasaki, Takeshi

2006-10-24

9

A European allele map of the C282Y mutation of hemochromatosis: Celtic versus Viking origin of the mutation?  

Microsoft Academic Search

The aim of this new meta-analysis (to the end of 2002) is to compile the Y allele frequencies of the C282Y mutation of hereditary hemochromatosis (HFE gene) for 63 European populations, representing a total of 10,708 unrelated people concerning control samples. A new allele map of C282Y frequencies in Europe was constructed. The highest European frequencies are observed in the

Gérard Lucotte; Florent Dieterlen

2003-01-01

10

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

11

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

PubMed Central

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.

Comps, B; Gomory, D; Letouzey, J; Thiebaut, B; Petit, R J

2001-01-01

12

HLA-A, -B, -C, -DRB1 Allele and Haplotype Frequencies Distinguish Eastern European Americans from the General European American Population  

PubMed Central

Sequence based typing was used to identify HLA-A,B,C,DRB1 alleles from 558 consecutively recruited U.S. volunteers with Eastern European ancestry for an unrelated hematopoietic stem cell registry. Four of the 31 HLA-A alleles, 29 -C alleles, 59 -B alleles, and 42 -DRB1 alleles identified (A*0325, B*440204, Cw*0332, and *0732N) are novel. The HLA-A*02010101g allele was observed at a frequency of 0.28. Two-, three- and four-locus haplotypes were estimated using the expectation maximization algorithm. The highest-frequency extended haplotypes (A*010101g-Cw*070101g-B*0801g-DRB1*0301 and A*03010101g-Cw*0702-B*0702-DRB1*1501) were observed at frequencies of 0.04 and 0.03, respectively. Linkage disequilibrium values (D’ij) of the constituent 2-locus haplotypes were highly significant for both extended haplotypes (p-values were less than 8 × 10?10), but were consistently higher for the more frequent haplotype. Balancing selection was inferred to be acting on all four loci, with the strongest evidence of balancing selection observed for the HLA-C locus. Comparisons of the A-C-B haplotype and DRB1 frequencies in this population to those for African, European and western Asian populations revealed high degrees of identity with Czech, Polish, and Slovenian populations and significant differences from the general European American population.

Mack, Steven J.; Tu, Bin; Lazaro, Ana; Yang, Ruyan; Lancaster, Alex K.; Cao, Kai; Ng, Jennifer; Hurley, Carolyn Katovich

2012-01-01

13

Pistil-function breakdown in a new S-allele of European pear, S21*, confers self-compatibility.  

PubMed

European pear exhibits RNase-based gametophytic self-incompatibility controlled by the polymorphic S-locus. S-allele diversity of cultivars has been extensively investigated; however, no mutant alleles conferring self-compatibility have been reported. In this study, two European pear cultivars, 'Abugo' and 'Ceremeño', were classified as self-compatible after fruit/seed setting and pollen tube growth examination. S-genotyping through S-PCR and sequencing identified a new S-RNase allele in the two cultivars, with identical deduced amino acid sequence as S(21), but differing at the nucleotide level. Test-pollinations and analysis of descendants suggested that the new allele is a self-compatible pistil-mutated variant of S(21), so it was named S(21)*. S-genotypes assigned to 'Abugo' and 'Ceremeño' were S(10)S(21)* and S(21)*S(25) respectively, of which S(25) is a new functional S-allele of European pear. Reciprocal crosses between cultivars bearing S(21) and S(21)* indicated that both alleles exhibit the same pollen function; however, cultivars bearing S(21)* had impaired pistil-S function as they failed to reject either S(21) or S (21)* pollen. RT-PCR analysis showed absence of S(21)* -RNase gene expression in styles of 'Abugo' and 'Ceremeño', suggesting a possible origin for S(21)* pistil dysfunction. Two polymorphisms found within the S-RNase genomic region (a retrotransposon insertion within the intron of S(21)* and indels at the 3'UTR) might explain the different pattern of expression between S(21) and S(21)*. Evaluation of cultivars with unknown S-genotype identified another cultivar 'Azucar Verde' bearing S(21)*, and pollen tube growth examination confirmed self-compatibility for this cultivar as well. This is the first report of a mutated S-allele conferring self-compatibility in European pear. PMID:19096853

Sanzol, Javier

2008-12-19

14

Temporal evolution of the ABO allele frequencies in the Canary Islands: the impact of the European colonization  

Microsoft Academic Search

The indigenous Canary Islands population suffered a strong cultural and genetic impact when they were colonized by Europeans\\u000a in the fifteenth century. The molecular analysis of the ABO blood group gene on aboriginal and seventeenth to eighteenth century\\u000a remains confirms the demographic history of the islands depicted by previous archaeological, anthropological, and genetic\\u000a studies. ABO allele frequencies clearly related Canarian

Rosa Fregel; Eva Betancor; Nicolás M. Suárez; Vicente M. Cabrera; Jose Pestano; Jose M. Larruga; Ana M. González

2009-01-01

15

Analysis of Allele and Haplotype Diversity Across 25 Genomic Regions in Three Eastern European Populations  

Microsoft Academic Search

Objective: Individual population history is the main reason for the variability of linkage disequilibrium (LD) patterns and haplotype frequencies among populations. Such diversity may influence the transferability of tag SNPs from one population to another. Our goal was to compare patterns of pairwise LD and allele and haplotype frequencies in Estonian and Russian populations, to estimate the genetic variation between

Andrey Khrunin; Evelin Mihailov; Tiit Nikopensius; Kaarel Krjutškov; Svetlana Limborska; Andres Metspalu

2009-01-01

16

cDNA cloning of nine S alleles and establishment of a PCR-RFLP system for genotyping European pear cultivars.  

PubMed

Nine full-length cDNAs of S ribonucleases (S-RNases) were cloned from stylar RNA of European pear cultivars by RT-PCR and 3' and 5' RACE. Comparison of the nucleotide sequences between the nine S-RNases cloned and 13 putative S alleles previously amplified by genomic PCRs revealed that seven corresponded to Sa, Sb, Sd, Se, Sh, Sk and Sl alleles, and the other two were new S alleles (designated as Sq and Sr alleles). Genomic PCR with a set of a8FTQQYQa9 and a8EP-anti-IIWPNVa9 primers was used to amplify nine S alleles; 1,414 bp (Sl), ca. 1.3 kb (Sk and Sq), 998 bp (Se), 440 bp (Sb) and ca. 350 bp (Sa, Sd, Sh and Sr). Among these, S alleles of similar size were discriminated by digestion with BaeI, BglII, BssHII, HindIII, EcoO109I and SphI. The PCR amplification of S allele following digestion with the restriction enzymes provided a PCR-RFLP system for rapid S-genotyping European pear cultivars harboring nine S alleles. The PCR-RFLP system assigned a total of 63 European pear cultivars to 25 genotypes. Among these, 14 genotypes were shared by two or more cultivars, which were cross-incompatible. These results suggested that the genes cloned represented the S-RNases from European pear, and that there were many cross-incompatible combinations among European pear varieties. PMID:16565843

Takasaki, T; Moriya, Y; Okada, K; Yamamoto, K; Iwanami, H; Bessho, H; Nakanishi, T

2006-03-25

17

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

PubMed

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

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

2012-11-03

18

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

Microsoft Academic Search

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

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

2004-01-01

19

Haplotype block structure study of the CFTR gene. Most variants are associated with the M470 allele in several European populations  

Microsoft Academic Search

An average of about 1700 CFTR (cystic fibrosis transmembrane conductance regulator) alleles from normal individuals from different European populations were extensively screened for DNA sequence variation. A total of 80 variants were observed: 61 coding SNSs (results already published), 13 noncoding SNSs, three STRs, two short deletions, and one nucleotide insertion. Eight DNA variants were classified as non-CF causing due

Fiorenza Pompei; Bianca Maria Ciminelli; Cristina Bombieri; Cinzia Ciccacci; Monika Koudova; Silvia Giorgi; Francesca Belpinati; Angela Begnini; Milos Cerny; Marie Des Georges; Mireille Claustres; Claude Ferec; Milan Macek; Guido Modiano; Pier Franco Pignatti

2006-01-01

20

Is the European spatial distribution of the HIV1-resistant CCR5-?32 allele formed by a breakdown of the pathocenosis due to the historical Roman expansion?  

Microsoft Academic Search

We studied the possible effects of the expansion of ancient Mediterranean civilizations during the five centuries before and after Christ on the European distribution of the mutant allele for the chemokine receptor gene CCR5 which has a 32-bp deletion (CCR5-?32). There is a strong evidence for the unitary origin of the CCR5-?32 mutation, this it is found principally in Europe

Eric Faure; Manuela Royer-Carenzi

2008-01-01

21

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

2012-10-18

22

One mutation in the galactocerebrosidase gene is responsible for a majority of mutant alleles in Northern European patients with infantile Krabbe disease  

SciTech Connect

Globoid cell leukodystrophy (GCL) or Krabbe disease is an autosomal recessive disorder resulting from a deficiency of galactocerebrosidase (GALC) activity. The typical human patient presents with symptoms of spasticity, developmental delay and irritability by 6 months of age. Older patients, including adults, are also diagnosed with this disorder. While patients from all ethnic groups are included within the more than 230 patients diagnosed in this laboratory, many trace their ancestry to Northern Europe. Patients are easy to diagnose by their low GALC activity. However, carriers are difficult to identify due to a large overlap in the {open_quotes}control{close_quotes} and carrier ranges. With our cloning of the GALC gene we have undertaken a study to identify mutations causing GCL in some of our families. We have identified a C to T transition at position {open_quotes}502{close_quotes} (counting form the A of the initiation codon) in about 65% of the mutant alleles in patients with Northern European ancestry. Identification of an intron 32 nucleotides downstream from the site of the mutation permits amplification of genomic DNA samples and rapid cycle sequencing. This mutation was found primarily in classic infantile patients, however it was found in the heterozygous state in a juvenile patient and in an African-American patient. This mutation changes the codon for arginine to one for cysteine, and computer analysis predicts a significant change in the secondary structure of this multi-subunit enzyme. A G to A transition at position {open_quotes}694{close_quotes} was found in the homozygous state in another infantile patient from a consanguineous mating. We are in the process of looking for this mutation in other patients. It is hoped that a few mutations will be found to be responsible for infantile Krabbe disease so that carrier identification can be improved for some families.

Rafi, M.A.; Luzi, P.; Hershberger, M. [Jefferson Medical College, Philadelphia, PA (United States)] [and others

1994-09-01

23

CCR5 deletion protects against inflammation-associated mortality in dialysis patients.  

PubMed

The CC-chemokine receptor 5 (CCR5) is a receptor for various proinflammatory chemokines, and a deletion variant of the CCR5 gene (CCR5 Delta 32) leads to deficiency of the receptor. We hypothesized that CCR5 Delta 32 modulates inflammation-driven mortality in patients with ESRD. We studied the interaction between CCR5 genotype and levels of high-sensitivity C-reactive protein (hsCRP) in 603 incident dialysis patients from the multicenter, prospective NEtherlands COoperative Study on the Adequacy of Dialysis (NECOSAD) cohort. CCR5 genotype and hsCRP levels were both available for 413 patients. During 5 yr of follow-up, 170 patients died; 87 from cardiovascular causes. Compared with the reference group of patients who had the wild-type CCR5 genotype and hsCRP allele with hsCRP 10 mg/L (n = 108) had an increased risk for mortality (HR: 1.82; 95% CI: 1.29 to 2.58). However, those carrying the deletion allele with hsCRP > 10 mg/L (n = 25) had a mortality rate similar to the reference group; this seemingly protective effect of the CCR5 deletion was even more pronounced for cardiovascular mortality. We replicated these findings in an independent Swedish cohort of 302 ESRD patients. In conclusion, the CCR5 Delta 32 polymorphism attenuates the adverse effects of inflammation on overall and cardiovascular mortality in ESRD. PMID:19389855

Muntinghe, Friso L H; Verduijn, Marion; Zuurman, Mike W; Grootendorst, Diana C; Carrero, Juan Jesus; Qureshi, Abdul Rashid; Luttropp, Karin; Nordfors, Louise; Lindholm, Bengt; Brandenburg, Vincent; Schalling, Martin; Stenvinkel, Peter; Boeschoten, Elisabeth W; Krediet, Raymond T; Navis, Gerjan; Dekker, Friedo W

2009-04-23

24

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.

Stanciu, Florin; Vladu, Simona; Cutar, Veronica; Cocioaba, Daniela; Iancu, Florentina; Cotolea, Adnana; Stoian, Ionel Marius

2013-01-01

25

CCR5 expression influences the progression of human breast cancer in a p53-dependent manner.  

PubMed

Chemokines are implicated in tumor pathogenesis, although it is unclear whether they affect human cancer progression positively or negatively. We found that activation of the chemokine receptor CCR5 regulates p53 transcriptional activity in breast cancer cells through pertussis toxin-, JAK2-, and p38 mitogen-activated protein kinase-dependent mechanisms. CCR5 blockade significantly enhanced proliferation of xenografts from tumor cells bearing wild-type p53, but did not affect proliferation of tumor xenografts bearing a p53 mutation. In parallel, data obtained in a primary breast cancer clinical series showed that disease-free survival was shorter in individuals bearing the CCR5Delta32 allele than in CCR5 wild-type patients, but only for those whose tumors expressed wild-type p53. These findings suggest that CCR5 activity influences human breast cancer progression in a p53-dependent manner. PMID:14597737

Mañes, Santos; Mira, Emilia; Colomer, Ramón; Montero, Sagrario; Real, Luis M; Gómez-Moutón, Concepción; Jiménez-Baranda, Sonia; Garzón, Alfredo; Lacalle, Rosa Ana; Harshman, Keith; Ruíz, Agustín; Martínez-A, Carlos

2003-11-01

26

A novel allelic variant of the human serotonin transporter gene regulatory polymorphism.  

PubMed

Allelic variation of the human serotonin transporter gene (SLC6A4) has recently been shown to modulate anxiety-related traits. A tandemly repeated sequence in close proximity to the promoter was found to be represented by a long (L) and short (S) variant, differentially modulating gene expression in vitro. Specifically, allele S, generated by a deletion of 44 bp involving repeats VI to VIII, reduced transcriptional efficiency, gene expression, and 5-hydroxytryptamine uptake and was associated with increased neuroticism scores. We have now identified a novel allelic variant of this promoter-linked polymorphism that is significantly larger than the L allele and which we have designated allele XL (for "extra large"). Sequence analysis revealed that XL arose through duplication of an internal segment composed of repeat elements VI to IX, comprising 85 bp in total, and, most notably, including the segments deleted in the S allele. Additional allelic variants larger than human allele L were observed predominantly in various nonhuman primates. Preliminary data indicated that these variable allelic extensions similarly originate from this specific repeat region. These allelic variants may serve as a valuable model system to further elucidate the relationship between repeat structure, regulatory properties, and behavioral correlates. Finally, allelic variants were found to vary significantly among different human populations, with allele XL being uniquely present in individuals of African origin, allele L most frequent in Africans and Caucasians of Western European descent, and allele S most abundant in East Asians. PMID:9605856

Delbrück, S J; Wendel, B; Grunewald, I; Sander, T; Morris-Rosendahl, D; Crocq, M A; Berrettini, W H; Hoehe, M R

1997-01-01

27

Allelic discrimination, three-dimensional analysis and gene expression of multiple transferrin alleles of common carp (Cyprinus carpio L.).  

PubMed

We cloned and sequenced four different transferrin (Tf) alleles (C, D, F and G) of European common carp (Cyprinus carpio carpio L.) and studied allelic diversity with respect to differences in sequence, constitutive transcription and three-dimensional structure. Most of the disulfide bonds were conserved between human and carp Tf, and modeling confirmed the overall conservation of the three-dimensional structure of carp Tf. While the iron-binding sites in the C-lobe of carp Tf were completely conserved, in the N-lobe the majority of iron-coordinating residues were not conserved. This may have a serious impact on the ability of carp Tf to bind iron with both the C- and N-lobe. In contrast to human Tf, we could not detect potential N-glycosylation sites in carp Tf, which does not seem to be a glycoprotein. Comparison of the cDNA of the four Tf alleles of carp indicated 21 polymorphic sites of which 13 resulted in non-synonymous changes. Allelic diversity did not seem to influence the overall conservation of carp Tf. Neither the iron binding sites nor the receptor binding of carp Tf seemed influenced by allelic diversity. Possibly, interaction with pathogen-associated receptors for Tf could be influenced by allelic diversity. Basal gene expression of Tf alleles D and G was especially high in carp liver. Although we could detect a higher transcription level of allele D than of Tf allele G in head kidney, thymus and spleen, the differences seem minor with respect to the very high transcription level in liver. Preliminary results with Tf-typed serum suggest a difference in the ability of Tf alleles D and G to modulate LPS-induced NO production in carp macrophages. PMID:18824109

Jurecka, Patrycja; Irnazarow, Ilgiz; Westphal, Adrie H; Forlenza, Maria; Arts, Joop A J; Savelkoul, Huub F J; Wiegertjes, Geert F

2008-09-12

28

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

29

Bisulfite sequencing of cloned alleles.  

PubMed

Bisulfite sequencing of cloned alleles is a widely used method for capturing the methylation profiles of single alleles. This method combines PCR amplification of the bisulfite-modified DNA with the subcloning of the amplicons into plasmids followed by transformation into bacteria and plating on selective media. The resulting colony forming units are each comprised of bacterial clones containing the same plasmid reflecting a single allele in the original PCR reaction. Following whole cell PCR and sequencing, the results provide highly detailed information about the status of each CG site within an allele. Sequencing of a large number of individual clones can provide quantitative information, assuming unbiased PCR, subcloning and clone selection. The proportion of methylated cytosine at a particular position within the sequenced alleles can be determined by counting the number of alleles showing methylation at the position of interest and dividing this by the total number of clones sequenced. PMID:23913211

Huang, Zhiqing; Bassil, Christopher F; Murphy, Susan K

2013-01-01

30

Allele coding in genomic evaluation  

PubMed Central

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

2011-01-01

31

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

32

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

33

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

Microsoft Academic Search

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

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

2007-01-01

34

Chemokine coreceptor usage by diverse primary isolates of human immunodeficiency virus type 1.  

PubMed

We tested chemokine receptor subset usage by diverse, well-characterized primary viruses isolated from peripheral blood by monitoring viral replication with CCR1, CCR2b, CCR3, CCR5, and CXCR4 U87MG.CD4 transformed cell lines and STRL33/BONZO/TYMSTR and GPR15/BOB HOS.CD4 transformed cell lines. Primary viruses were isolated from 79 men with confirmed human immunodeficiency virus type 1 (HIV-1) infection from the Chicago component of the Multicenter AIDS Cohort Study at interval time points. Thirty-five additional well-characterized primary viruses representing HIV-1 group M subtypes A, B, C, D, and E and group O and three primary simian immunodeficiency virus (SIV) isolates were also used for these studies. The restricted use of the CCR5 chemokine receptor for viral entry was associated with infection by a virus having a non-syncytium-inducing phenotype and correlated with a reduced rate of disease progression and a prolonged disease-free interval. Conversely, broadening chemokine receptor usage from CCR5 to both CCR5 and CXCR4 was associated with infection by a virus having a syncytium-inducing phenotype and correlated with a faster rate of CD4 T-cell decline and progression of disease. We also observed a greater tendency for infection with a virus having a syncytium-inducing phenotype in men heterozygous for the defective CCR5 Delta32 allele (25%) than in those men homozygous for the wild-type CCR5 allele (6%) (P = 0.03). The propensity for infection with a virus having a syncytium-inducing phenotype provides a partial explanation for the rapid disease progression among some men heterozygous for the defective CCR5 Delta32 allele. Furthermore, we did not identify any primary viruses that used CCR3 as an entry cofactor, despite this CC chemokine receptor being expressed on the cell surface at a level commensurate with or higher than that observed for primary peripheral blood mononuclear cells. Whereas isolates of primary viruses of SIV also used STRL33/BONZO/TYMSTR and GPR15/BOB, no primary isolates of HIV-1 used these particular chemokine receptor-like orphan molecules as entry cofactors, suggesting a limited contribution of these other chemokine receptors to viral evolution. Thus, despite the number of chemokine receptors implicated in viral entry, CCR5 and CXCR4 are likely to be the physiologically relevant chemokine receptors used as entry cofactors in vivo by diverse strains of primary viruses isolated from blood. PMID:9765480

Zhang, L; He, T; Huang, Y; Chen, Z; Guo, Y; Wu, S; Kunstman, K J; Brown, R C; Phair, J P; Neumann, A U; Ho, D D; Wolinsky, S M

1998-11-01

35

The distribution of MICA alleles in an Austrian population: Evidence for increasing polymorphism.  

PubMed

The Major Histocompatibility Complex Class I Chain-Related Gene A (MICA) is located 46.4Kb centromeric to HLA-B locus on chromosome 6; 84 alleles have been described so far. To assess the distribution of MICA alleles in an Austrian population, 322 unrelated Austrian blood donors have been typed for MICA by direct sequencing of amplified exons 2-5; sequencing of exon 6 and separating alleles by haplotype specific primers or by cloning was performed to resolve ambiguities. HLA-B was typed at low level resolution and linkage disequilibrium was determined. We observed 20 already known and four novel MICA alleles. MICA(?)008:01/04 was the most frequent allele (42%), followed by MICA(?)002:01 (11%) and MICA(?)009:01 (9%), three alleles (MICA(?)029, (?)067 and (?)068) were observed only once. No deviation from the Hardy Weinberg equilibrium was observed. Linkage disequilibrium between MICA and HLA-B alleles was observed, most extensively between MICA(?)008:01/04 and HLA-B(?)07. Our population data are in agreement with other European populations. The fact that four novel alleles have been observed indicates that the polymorphism of MICA is larger than currently estimated. PMID:23777932

Wenda, Sabine; Faé, Ingrid; Sanchez-Mazas, Alicia; Nunes, José M; Mayr, Wolfgang R; Fischer, Gottfried F

2013-06-15

36

Type 2 Diabetes Risk Alleles Demonstrate Extreme Directional Differentiation among Human Populations, Compared to Other Diseases  

PubMed Central

Many disease-susceptible SNPs exhibit significant disparity in ancestral and derived allele frequencies across worldwide populations. While previous studies have examined population differentiation of alleles at specific SNPs, global ethnic patterns of ensembles of disease risk alleles across human diseases are unexamined. To examine these patterns, we manually curated ethnic disease association data from 5,065 papers on human genetic studies representing 1,495 diseases, recording the precise risk alleles and their measured population frequencies and estimated effect sizes. We systematically compared the population frequencies of cross-ethnic risk alleles for each disease across 1,397 individuals from 11 HapMap populations, 1,064 individuals from 53 HGDP populations, and 49 individuals with whole-genome sequences from 10 populations. Type 2 diabetes (T2D) demonstrated extreme directional differentiation of risk allele frequencies across human populations, compared with null distributions of European-frequency matched control genomic alleles and risk alleles for other diseases. Most T2D risk alleles share a consistent pattern of decreasing frequencies along human migration into East Asia. Furthermore, we show that these patterns contribute to disparities in predicted genetic risk across 1,397 HapMap individuals, T2D genetic risk being consistently higher for individuals in the African populations and lower in the Asian populations, irrespective of the ethnicity considered in the initial discovery of risk alleles. We observed a similar pattern in the distribution of T2D Genetic Risk Scores, which are associated with an increased risk of developing diabetes in the Diabetes Prevention Program cohort, for the same individuals. This disparity may be attributable to the promotion of energy storage and usage appropriate to environments and inconsistent energy intake. Our results indicate that the differential frequencies of T2D risk alleles may contribute to the observed disparity in T2D incidence rates across ethnic populations.

Chen, Rong; Corona, Erik; Sikora, Martin; Dudley, Joel T.; Morgan, Alex A.; Moreno-Estrada, Andres; Nilsen, Geoffrey B.; Ruau, David; Lincoln, Stephen E.; Bustamante, Carlos D.; Butte, Atul J.

2012-01-01

37

KIR allele and gene polymorphism group (KAG).  

PubMed

Recent research presented at this meeting verifies the extent of the polymorphism of KIR genes and their alleles and shows their association with various diseases. Methods were described for the determination of alleles of several of the KIR genes in different populations including a novel allele formed by an unequal recombination event. Associations of KIR genes were found with several diseases: type I diabetes; psoriatic arthritis; and hepatitis C infection. Discussion took place on nomenclature issues of the KIR genes and their alleles, and a website has been developed to collect frequencies of KIR genes and alleles in various diverse populations. PMID:15607798

Middleton, D

2005-02-01

38

Molecular background of novel silent RHCE alleles.  

PubMed

BACKGROUND: The absence of expression of C/c and E/e antigens has been associated with rare variant RHCE alleles, referred to as silent RHCE alleles, classically identified among individuals with a rare D-?- or Rh(null) phenotype. This work reports on different molecular mechanisms identified in three novel silent RHCE alleles. STUDY DESIGN AND METHODS: Samples from D-?- or Rh(null) individuals and their family members, from families for whom Rh phenotype and/or serologic data were unexplained by inheritance of conventional RH alleles, were analyzed. Genomic DNA and transcripts were tested by sequencing analysis. RESULTS: The first silent allele was a RHCE*cE allele carrying an intronic IVS3+5G>A mutation. The second was a RHCE*ce allele carrying an intronic IVS7-2A>G mutation, whereas the third was a silent RHCE*ce allele carrying a 5-bp deletion (Nucleotides 679-683) in Exon?5. CONCLUSION: In addition to hybrid alleles and nucleotide deletion, intronic mutations may be associated with the nonexpression of RhCE antigens. Regarding the RH system, silent alleles may not be investigated among D-?- or Rh(null) individuals only. Rh phenotype and/or serologic data unexplained by inheritance of conventional RH alleles should lead to molecular investigations. PMID:23252593

Pham, Bach-Nga; Ramelet, Stéphanie; Wibaut, Bénédicte; Juszczak, Genevieve; Loukil, Chawki; Dubeaux, Isabelle; Gien, Dominique; Kappler-Gratias, Sandrine; Rouger, Philippe; Le Pennec, Pierre-Yves

2012-12-17

39

Prediction of deleterious human alleles.  

PubMed

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

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

2001-03-15

40

Comparative analysis of Hoxa5 allelic series.  

PubMed

Analysis of the Hoxa5(-/-) mutants has revealed the critical role of Hoxa5 in survival, specification of axial identity, and ontogeny of organs, including the respiratory tract. The presence of the selection cassette in the original Hoxa5(-/-) mutation may interfere with the interpretation of the phenotypes. To circumvent this aspect and to bypass the lethality of the Hoxa5 mutation, we have designed a conditional approach and generated Hoxa5 allelic variants. The conditional allele (Hoxa5(floxed)) behaves as a wild-type allele. In contrast, both the Hoxa5(Delta) and the Hoxa5(floxneo) alleles are characterized by the loss of the functional transcript and protein, the lethality due to lung defects and the skeletal homeotic transformations similar to those of the Hoxa5(-/-) mutants. Analysis of neighboring Hox gene expression patterns in the Hoxa5 mutants produced further confirmed that the Hoxa5 allelic variants are true null alleles. PMID:17417799

Tabariès, Sébastien; Lemieux, Margot; Aubin, Josée; Jeannotte, Lucie

2007-04-01

41

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

PubMed Central

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

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

2011-01-01

42

Recovery of CD4+ T Cells in HIV patients with a stable virologic response to antiretroviral therapy is associated with polymorphisms of interleukin-6 and central major histocompatibility complex genes.  

PubMed

We investigated whether polymorphisms in genes associated with HIV disease progression and/or immune activation affect CD4+ T-cell recovery in HIV patients who began combination antiretroviral therapy (ART) with advanced immunodeficiency and achieved stable control of plasma viremia. Patients with CD4 T-cell counts <300 cells/microL (n = 33) and >400 cells/microL (n = 37) on ART were compared. A multiple case-control logistic regression associated carriage of BAT1(1,2) or interleukin (IL)6-174(2,2) with low CD4 T-cell counts (P = 0.012). BAT1*2 uniquely marks the central major histocompatibility complex region of a conserved haplotype (HLA-A1,B8,BAT1*2,TNFA-308*2,DR3,DQ2). There was no association between alleles carried at CCR5Delta32, CCR5 59029, CCR5 59353, CCR2+190 (V64I), SDF1 3'UTR, IL1A+4845, IL1B+3953, IL4-589, IL10-592, IL10-R1+536, IL10-R1+1112, IL12B 3'UTR, TNFA-308, or TNFA-1031 and CD4 T-cell counts. We suggest that immune activation and/or CD4 T-cell apoptosis in HIV patients on effective ART is influenced by genetic factors. PMID:16340466

Fernandez, Sonia; Rosenow, Ann A; James, Ian R; Roberts, Steven G; Nolan, Richard C; French, Martyn A; Price, Patricia

2006-01-01

43

Genetic Differences between Five European Populations  

Microsoft Academic Search

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

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

2010-01-01

44

Frequency Analysis and Allele Map in Favor of the Celtic Origin of the C282Y Mutation of Hemochromatosis  

Microsoft Academic Search

ABSTRACTAfter the main hereditary hemochromatosis mutation C282Y in the HFE gene was described, we report here the C282Y frequencies for various European populations. The aim of this meta-analysis is to compile the Y allele frequencies of the C282Y mutation for 53 European populations, representing a total of 9265 unrelated people representing control samples. The most elevated values are observed in

Gérard Lucotte

2001-01-01

45

Caution! Analyze transcripts from conditional knockout alleles.  

PubMed

A common strategy for conditional knockout alleles is to "flox" (flank with loxP sites) a 5' exon within the target gene. Typically, the floxed exon does not contain a unit number of codons so that the Cre-mediated recombination event yields a frameshift and a null allele. Documenting recombination within the genomic DNA is often regarded as sufficient proof of a frameshift, and the analysis of transcripts is neglected. We evaluated a previously reported conditional knockout allele for the beta-subunit of protein farnesyltransferase. The recombination event in that allele-the excision of exon 3-was predicted to yield a frameshift. However, following the excision of exon 3, exon 4 was skipped by the mRNA splicing machinery, and the predominant transcript from the mutant allele lacked exon 3 and exon 4 sequences. The "Deltaexon 3-4 transcript" does not contain a frameshift but rather is predicted to encode a protein with a short in-frame deletion. This represents a significant concern when studying an enzyme, since an enzyme with partial function could lead to erroneous conclusions. With thousands of new conditional knockout alleles under construction within mouse mutagenesis consortiums, the protein farnesyltransferase allele holds an important lesson-to characterize knockout alleles at both the DNA and RNA levels. PMID:19093225

Yang, Shao H; Bergo, Martin O; Farber, Emily; Qiao, Xin; Fong, Loren G; Young, Stephen G

2008-12-18

46

Caution! Analyze transcripts from conditional knockout alleles  

PubMed Central

A common strategy for conditional knockout alleles is to “flox” (flank with loxP sites) a 5? exon within the target gene. Typically, the floxed exon does not contain a unit number of codons so that the Cre-mediated recombination event yields a frameshift and a null allele. Documenting recombination within the genomic DNA is often regarded as sufficient proof of a frameshift, and the analysis of transcripts is neglected. We evaluated a previously reported conditional knockout allele for the ?-subunit of protein farnesyltransferase. The recombination event in that allele—the excision of exon 3—was predicted to yield a frameshift. However, following the excision of exon 3, exon 4 was skipped by the mRNA splicing machinery, and the predominant transcript from the mutant allele lacked exon 3 and exon 4 sequences. The “?exon 3–4 transcript” does not contain a frameshift but rather is predicted to encode a protein with a short in-frame deletion. This represents a significant concern when studying an enzyme, since an enzyme with partial function could lead to erroneous conclusions. With thousands of new conditional knockout alleles under construction within mouse mutagenesis consortiums, the protein farnesyltransferase allele holds an important lesson—to characterize knockout alleles at both the DNA and RNA levels.

Yang, Shao H.; Bergo, Martin O.; Farber, Emily; Qiao, Xin; Fong, Loren G.; Young, Stephen G.

2008-01-01

47

Generation of new Notch2 mutant alleles  

Microsoft Academic Search

The Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism, and mutations in its components disrupt embryonic development in many organisms and cause inherited diseases in humans. We previously described construction and analysis of a hypomorphic allele of the Notch2 gene. Homozygosity for this allele leads to embryonic and perinatal lethality due to cardiovascular and kidney defects. We report

B McCright; J Lozier; T Gridley

2006-01-01

48

Generation of new Notch2 mutant alleles.  

PubMed

The Notch signaling pathway is an evolutionarily conserved intercellular signaling mechanism, and mutations in its components disrupt embryonic development in many organisms and cause inherited diseases in humans. We previously described construction and analysis of a hypomorphic allele of the Notch2 gene. Homozygosity for this allele leads to embryonic and perinatal lethality due to cardiovascular and kidney defects. We report here novel Notch2 mutant alleles generated by gene targeting in embryonic stem cells, including a conditional null allele in which exon 3 of the Notch2 gene is flanked by loxP sequences. These new Notch2 mutant alleles expand the set of tools available for studying the myriad roles of the Notch pathway during mammalian development and will enable analysis of Notch2 function at additional stages of embryogenesis and in adult mice. PMID:16397869

McCright, Brent; Lozier, Julie; Gridley, Thomas

2006-01-01

49

EUROPEAN AUSTERITY WITHOUT GROWTH? EUROPEAN GROWTH WITHOUT EUROPEAN DEMOCRACY?  

Microsoft Academic Search

The European project is facing a crisis. Citizens no longer understand what the EU is about. Young people and the new ruling class have forgotten the clear message of the European project launched just after the Second World War \\

Montani Guido

2011-01-01

50

European solar thermal market  

Microsoft Academic Search

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

Gerhard Stryi-Hipp

2001-01-01

51

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).

52

Identification of HLA alleles with low or no cell surface expression in the Czech population.  

PubMed

The presence of the A*24020102L allele is implicated in one donor from the CBMD who serologically was typed as A2; B44, B55; Cwl, Cw7. The DRB4*01030102N allele was identified in one healthy donor and in one patient with MDS during routine HLA class II DNA typing. The DRB4*01030102N allele was identified in the patient's father, who had CML, and was associated with the HLA-A3-B7-Cw7-DRB1*0701-DQB1*0303 haplotype, which is common for European populations. In order to avoid mistyping, both techniques, serology and molecular biology must be used for HLA typing, especially for cases where just one antigen appeared to be present using serological methods. PMID:14748437

Bendukidze, N; Ivasková, E; Zahlavová, L; Slavcev, A; Kupková, L; Sajdlová, H; Day, S; Dunn, P P J

2003-01-01

53

Survey of allelic expression using EST mining  

PubMed Central

Cis-acting allelic variation in gene regulation is a source of phenotypic variation. Consequently, recent studies have experimentally screened human genes in an attempt to initiate a catalog of genes possessing cis-acting variants. In this study, we use human EST data in dbEST as the source of allelic expression data, and the HapMap database to provide expected allele frequencies in human populations. We demonstrate a greater concordance of allele frequencies estimated from human ESTs in dbEST with those derived from the CEPH HapMap sample representing Caucasians from northern and western Europe, than population samples obtained in Asia and Africa. Deviations between allele frequencies observed in EST databases and the ones obtained from the CEPH HapMap samples may result from common heritable cis-acting variants altering the relative allele distribution in RNA. We provide in silico as well as experimental evidence that this strategy does allow significant enrichment of genes harboring common heritable cis-acting polymorphisms in linkage disequilibrium with expressed alleles.

Ge, Bing; Gurd, Scott; Gaudin, Tiffany; Dore, Carole; Lepage, Pierre; Harmsen, Eef; Hudson, Thomas J.; Pastinen, Tomi

2005-01-01

54

OCA2*481Thr , a hypofunctional allele in pigmentation, is characteristic of northeastern Asian populations  

Microsoft Academic Search

Asians as well as Europeans have light skin, for which no genes to date are known to be responsible. A mutation, Ala481Thr\\u000a (c.G1559A), in the oculocutaneous albinism type II (OCA2) gene has approximately 70% function of the wild type allele in melanogenesis. In this study, the distribution of the mutation\\u000a was investigated in a total of 2,615 individuals in 20

Isao Yuasa; Kazuo Umetsu; Shinji Harihara; Aya Miyoshi; Naruya Saitou; Kyung Sook Park; Bumbein Dashnyam; Feng Jin; Gérard Lucotte; Prasanta K. Chattopadhyay; Lotte Henke; Jürgen Henke

2007-01-01

55

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

56

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

2013-05-23

57

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

58

Allelic diagnosis of susceptibility to compulsive disorder  

US Patent & Trademark Office Database

In an important embodiment, the present invention concerns a method for diagnosing and detecting compulsive disorder susceptibility of an individual. The method comprises initially obtaining a DNA sample of said individual and then determining the presence or absence of particular human D.sub.2 receptor gene alleles in said sample. Detection of said alleles in the sample are indicative of predilection to compulsive disorder. A most preferred embodiment is to detect predisposition to impulsive, addictive, and compulsive disorders such as, but not limited to, alcoholism, obesity, smoking, polysubstance abuse and drug addiction, particularly because said alleles have been found to be present in a majority of individuals clinically diagnosed with these compulsive disorders. The human D.sub.2 receptor gene A1, B1, and .sup.In6-Ex7 haplotype I alleles are most preferably detected in said sample.

1996-08-27

59

Characterization of the treefrog null allele, 1991.  

National Technical Information Service (NTIS)

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 fou...

S. I. Guttman

1992-01-01

60

Haplotype study of intermediate-length alleles at the fragile X (FMR1) gene: ATL1, FMRb, and microsatellite haplotypes differ from those found in common-size FMR1 alleles.  

PubMed

The CGG repeat within the X-chromosome-linked FMR1 gene, which in hyperexpansion (> 200 copies) results in fragile X syndrome, is highly polymorphic. The mechanism of expansion is not well understood, but CGG repeats called intermediate-length or gray zone alleles (approximately equal 35-60 repeats) are thought to make up the FMR1 alleles showing initial steps in this expansion process. It has been hypothesized that the background haplotype of these alleles plays a role in their susceptibility to expansion. In this study we investigate whether or not the frequencies of alleles and haplotypes at four marker loci in the FMR1 gene region (microsatellites DXS548 and FRAXAC1 and SNPs ATL1 and FMRb) in 84 intermediate-length male chromosomes differ from those in 94 common-size male alleles. The ATL1*G and FMRB*A alleles were more frequent among intermediate-length alleles than among common alleles. In addition, the DXS548-FRAXAC1 T50-T42 and T40-T42 haplotypes were strongly associated with intermediate-length alleles between 41 and 60 CGG repeats (p < 0.001). Two extended haplotypes, DXS548-FRAXAC1-ATL1-FMRb T50-T42-G-A and T40-T42-G-A, are strongly associated (p < 0.001) with intermediate-length alleles between 41 and 60 CGG repeats, and these haplotypes have also been reported as fragile X associated haplotypes in European populations. These data suggest that these haplotypes are among the most susceptible to further expansion among the intermediate-length alleles. T50-T42-G-A was also much more prevalent in males with 35-40 CGG repeats than in males with common-size alleles. ATL1 did not increase discrimination among intermediate-length alleles beyond that detected by DXS548-FRAXAC1 haplotypes, but the FMRb locus did, particularly for the DXS548-FRAXAC1-ATL1 T50-T42-G and T40-T42-G haplotypes. Comparison with fragile X associated haplotypes, from the literature, suggests that repeat hyperexpansion occurs most frequently on chromosomes carrying FMRB*A. Within the intermediate-length allele category, however, there were some significant differences in haplotype frequencies between smaller and larger alleles, and this finding has implications for future studies. PMID:16114822

Curlis, Yvette; Zhang, Cuiling; Holden, Jeanette J A; Loesch, P Ken Kirkby Danuta; Mitchell, R John

2005-02-01

61

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.

1997-01-01

62

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

63

Abnormal segregation of alleles in CEPH pedigree DNAs arising from allele loss in lymphoblastoid DNA  

SciTech Connect

Somatic events that result in the reduction to hemior homozygosity at all loci affected by the event have been identified in lymphoblastoid DNA from mothers of two CEPH families. Using suitably informative probes, the allele deficiencies were detected by the abnormal transmission of alleles from grandparents to grandchildren, with the apparent absence of the alleles from the parent. Undetected somatic deficiencies in family DNAs could result in misscoring of recombination events and consequently introduce errors into linkage analysis. 15 refs., 2 figs.

Royle, N.J.; Armour, J.A.L.; Crosier, M.; Jeffreys, A.J. (Univ. of Leicester (United Kingdom))

1993-01-01

64

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

Microsoft Academic Search

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

H. Sert; F. Suchentrunk; A. Erdo?an

2005-01-01

65

Allele-specific DNA methylation: beyond imprinting  

PubMed Central

Allele-specific DNA methylation (ASM) and allele-specific gene expression (ASE) have long been studied in genomic imprinting and X chromosome inactivation. But these types of allelic asymmetries, along with allele-specific transcription factor binding (ASTF), have turned out to be far more pervasive—affecting many non-imprinted autosomal genes in normal human tissues. ASM, ASE and ASTF have now been mapped genome-wide by microarray-based methods and NextGen sequencing. Multiple studies agree that all three types of allelic asymmetries, as well as the related phenomena of expression and methylation quantitative trait loci, are mostly accounted for by cis-acting regulatory polymorphisms. The precise mechanisms by which this occurs are not yet understood, but there are some testable hypotheses and already a few direct clues. Future challenges include achieving higher resolution maps to locate the epicenters of cis-regulated ASM, using this information to test mechanistic models, and applying genome-wide maps of ASE/ASM/ASTF to pinpoint functional regulatory polymorphisms influencing disease susceptibility.

Tycko, Benjamin

2010-01-01

66

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.

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

67

Phylogenetic relationship analysis of Iranians and other world populations using allele frequencies at 12 polymorphic markers.  

PubMed

The estimation of genetic distance between populations could improve our viewpoint about human migration and its genetic origin. In this study, we used allele frequency data of 12 polymorphic markers on 250 individuals (500 alleles) from the Iranian population to estimate genetic distance between the Iranians and other world populations. The phylogenetic trees for three different sets of allele frequency data were constructed. Our results revealed the genetic similarity between the Iranians and European populations. The lowest genetic distance was observed between the Iranians and some populations reside in Russia. Furthermore, the high genetic distance was observed between the Iranians and East Asian populations. The data suggested that the Iranians might have relatively close evolutionary history with Europeans, but historically independent from East Asian populations. The evaluation of genetic distance between Indians populations and Iranians was also performed. The Indian groups showed low genetic distance with others, but high genetic distance with the Iranians. This study could provide a new insight into the evolutionary history of the Iranian population. PMID:23065267

Fazeli, Zahra; Vallian, Sadeq

2012-10-14

68

Allelic expression analysis of the osteoarthritis susceptibility locus that maps to MICAL3  

PubMed Central

Background A genome-wide association scan with subsequent replication study that involved over 67,000 individuals of European ancestry has produced evidence of association of single nucleotide polymorphism rs2277831 to primary osteoarthritis (OA) with a P-value of 2.9 × 10-5. rs2277831, an A/G transition, is located in an intron of MICAL3. This gene is located on chromosome 22q11.21 and the association signal encompasses two additional genes, BCL2L13 and BID. It is becoming increasingly apparent that many common complex traits are mediated by cis-acting regulatory polymorphisms that influence, in a tissue-specific manner, gene expression or transcript stability. Methods We used total and allelic expression analysis to assess whether the OA association to rs2277831 is mediated by an influence on MICAL3, BCL2L13 or BID expression. Using RNA extracted from joint tissues of 60 patients who had undergone elective joint replacement surgery, we assessed whether rs2277831 correlated with allelic expression of either of the three genes by: 1) measuring the expression of each gene by quantitative PCR and then stratifying the data by genotype at rs2277831 and 2) accurately discriminating and quantifying the mRNA synthesised from the alleles of OA patients using allelic-quantitative PCR. Results We found no evidence for a correlation between gene expression and genotype at rs2277831, with P-values of 0.09 for BCL2L13, 0.07 for BID and 0.33 for MICAL3. In the allelic expression analysis we observed several examples of significant (p < 0.05) allelic imbalances, with an allelic expression ratio of 2.82 observed in BCL2L13 (P = 0.004), 2.09 at BID (P = 0.001) and the most extreme case being at MICAL3, with an allelic expression ratio of 5.47 (P = 0.001). However, there was no correlation observed between the pattern of allelic expression and the genotype at rs2277831. Conclusions In the tissues that we have studied, our data do not support our hypothesis that the association between rs2277831 and OA is due to the effect this SNP has on MICAL3, BCL2L13 or BID gene expression. Instead, our data point towards other functional effects accounting for the OA associated signal.

2012-01-01

69

Molecular analysis of human leukocyte antigen class I and class II allele frequencies and haplotype distribution in Pakistani population  

PubMed Central

AIM: Distribution of HLA class I and II alleles and haplotype was studied in Pakistani population and compared with the data reported for Caucasoid, Africans, Orientals and Arab populations. MATERIALS AND METHODS: HLA class I and II polymorphisms in 1000 unrelated Pakistani individuals was studied using sequence-specific primers and polymerase chain reaction and assay. RESULTS: The most frequent class I alleles observed were A*02, B*35 and CW*07, with frequencies of 19.2, 13.7 and 20%, respectively. Fifteen distinct HLA-DRB1 alleles and eight HLA-DQB1 alleles were recognized. The most frequently observed DRB1 alleles which represented more than 60% of the subjects were DRB1 *03, *07, *11 and *15. The rare DRB1 alleles detected in this study were HLADRB1 *08 and *09, having frequencies of 0.9 and 1.7%, respectively. In addition, at DRB1-DQB1 loci there were 179 different haplotypes and 285 unique genotypes and the most common haplotype was DRB1*15-DQB1*06 which represented 17% of the total DRB1-DQB1 haplotypes. In our population, haplotype A*33-B*58-Cw*03 comprised 2.8% of the total class I haplotypes observed. This haplotype was seen only in the oriental populations and has not been reported in the African or European Caucasoid. CONCLUSION: Our study showed a close similarity of HLA class I and II alleles with that of European Caucasoid and Orientals. In Pakistani population, two rare loci and three haplotypes were identified, whereas haplotypes characteristic of Caucasians, Africans and Orientals were also found, suggesting an admixture of different races due to migration to and from this region.

Moatter, T.; Aban, M.; Tabassum, S.; Shaikh, U.; Pervez, S.

2010-01-01

70

Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture.  

PubMed

The T(-13910) variant located in the enhancer element of the lactase (LCT) gene correlates perfectly with lactase persistence (LP) in Eurasian populations whereas the variant is almost nonexistent among Sub-Saharan African populations, showing high prevalence of LP. Here, we report identification of two new mutations among Saudis, also known for the high prevalence of LP. We confirmed the absence of the European T(-13910) and established two new mutations found as a compound allele: T/G(-13915) within the -13910 enhancer region and a synonymous SNP in the exon 17 of the MCM6 gene T/C(-3712), -3712 bp from the LCT gene. The compound allele is driven to a high prevalence among Middle East population(s). Our functional analyses in vitro showed that both SNPs of the compound allele, located 10 kb apart, are required for the enhancer effect, most probably mediated through the binding of the hepatic nuclear factor 1 alpha (HNF1 alpha). High selection coefficient (s) approximately 0.04 for LP phenotype was found for both T(-13910) and the compound allele. The European T(-13910) and the earlier identified East African G(-13907) LP allele share the same ancestral background and most likely the same history, probably related to the same cattle domestication event. In contrast, the compound Arab allele shows a different, highly divergent ancestral haplotype, suggesting that these two major global LP alleles have arisen independently, the latter perhaps in response to camel milk consumption. These results support the convergent evolution of the LP in diverse populations, most probably reflecting different histories of adaptation to milk culture. PMID:18179885

Enattah, Nabil Sabri; Jensen, Tine G K; Nielsen, Mette; Lewinski, Rikke; Kuokkanen, Mikko; Rasinpera, Heli; El-Shanti, Hatem; Seo, Jeong Kee; Alifrangis, Michael; Khalil, Insaf F; Natah, Abdrazak; Ali, Ahmed; Natah, Sirajedin; Comas, David; Mehdi, S Qasim; Groop, Leif; Vestergaard, Else Marie; Imtiaz, Faiqa; Rashed, Mohamed S; Meyer, Brian; Troelsen, Jesper; Peltonen, Leena

2008-01-01

71

Apolipoprotein ?3 allele is associated with persistent hepatitis C virus infection  

PubMed Central

Background Host genetic factors may significantly influence the ability to clear hepatitis C virus (HCV) following infection. HCV is associated with very low density lipoproteins (VLDL) and low density lipoproteins (LDL) in the host's circulation. Apolipoprotein E (APOE) is found in VLDL and binds to potential receptors involved in HCV entry into cells, the LDL receptor, and the scavenger receptor protein SR?B1. The APOE gene is polymorphic with three alleles coding for three isoforms: Apo??2, Apo??3, and Apo??4. The aim of this study was to assess if these functional polymorphisms determine disease outcome in HCV infected individuals. Methods The APOE genotype was determined in 420 Northern European patients with evidence of exposure to HCV. Genotype and allele distribution were compared with those of 288 healthy controls and progression of liver disease and viral clearance were analysed according to APOE allele status. Results The APOE*E2 and APOE*E4 alleles were both associated with a reduced likelihood of chronic infection (odds ratio (OR) 0.39 (95% confidence interval (CI) 0.211–0.728), p?=?0.003; and OR 0.6 (95% CI 0.38–0.96), p?=?0.032) and there was a notable absence of the E2E2 genotype in the HCV antibody positive group compared with the control population (p?=?0.0067). Overall the genotypes carrying the E2 allele (E2,E3 and E2,E4) were associated with the equivalent of a 3–5?fold reduction in the risk of chronic HCV infection (genotype relative risk 0.36 and 0.20, respectively). Conclusion This study indicates that functional APOE gene polymorphisms may be a determinant of outcome in HCV infection. We hypothesise that the E2 allele may protect against viral persistence via defective binding of HCV lipoviral particles to the cellular receptors involved in entry of these infectious particles.

Price, D A; Bassendine, M F; Norris, S M; Golding, C; Toms, G L; Schmid, M L; Morris, C M; Burt, A D; Donaldson, P T

2006-01-01

72

Estimation of allele frequencies at isoloci.  

PubMed

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 chi 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

1988-02-01

73

Selection Against Recessive Deleterious and Lethal Alleles  

Microsoft Academic Search

For a fully recessive allele with mutation rate to it ?, from it v and complete selection against homozygous recessives, the equilibrium frequency is approximately ?1\\/2. It is possible to reduce the equilibrium by eliminating from the breeding population all homozygous recessives and all individuals identified as heterozygous on the basis of having produced one or more homozygous progeny. The

J. F. Kidwell; G. W. Hagy

1971-01-01

74

Overcoming allelic specificity by immunization with five allelic forms of Plasmodium falciparum apical membrane antigen 1.  

PubMed

Apical membrane antigen 1 (AMA1) is a leading vaccine candidate, but the allelic polymorphism is a stumbling block for vaccine development. We previously showed that a global set of AMA1 haplotypes could be grouped into six genetic populations. Using this information, six recombinant AMA1 proteins representing each population were produced. Rabbits were immunized with either a single recombinant AMA1 protein or mixtures of recombinant AMA1 proteins (mixtures of 4, 5, or 6 AMA1 proteins). Antibody levels were measured by enzyme-linked immunosorbent assay (ELISA), and purified IgG from each rabbit was used for growth inhibition assay (GIA) with 12 different clones of parasites (a total of 108 immunogen-parasite combinations). Levels of antibodies to all six AMA1 proteins were similar when the antibodies were tested against homologous antigens. When the percent inhibitions in GIA were plotted against the number of ELISA units measured with homologous AMA1, all data points followed a sigmoid curve, regardless of the immunogen. In homologous combinations, there were no differences in the percent inhibition between the single-allele and allele mixture groups. However, all allele mixture groups showed significantly higher percent inhibition than the single-allele groups in heterologous combinations. The 5-allele-mixture group showed significantly higher inhibition to heterologous parasites than the 4-allele-mixture group. On the other hand, there was no difference between the 5- and 6-allele-mixture groups. These data indicate that mixtures with a limited number of alleles may cover a majority of the parasite population. In addition, using the data from 72 immunogen-parasite combinations, we mathematically identified 13 amino acid polymorphic sites which significantly impact GIA activities. These results could be a foundation for the rational design of a future AMA1 vaccine. PMID:23429537

Miura, Kazutoyo; Herrera, Raul; Diouf, Ababacar; Zhou, Hong; Mu, Jianbing; Hu, Zonghui; MacDonald, Nicholas J; Reiter, Karine; Nguyen, Vu; Shimp, Richard L; Singh, Kavita; Narum, David L; Long, Carole A; Miller, Louis H

2013-02-19

75

S -allele Diversity in Lycium andersonii: Implications for the Evolution of S Allele Age in the Solanaceae  

Microsoft Academic Search

We evaluate competing explanations for striking differences in the average age of self-incompatibility (S -) alleles in population samples. The age of alleles is inferred from evidence for trans-generic evolution (TGE), in which an allele sampled from one species is more closely related to an allele found in another genus than any con-generic allele, as determined by phylogenetic analysis. Whereas

Adam D. Richman

2000-01-01

76

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

PubMed

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

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

2011-05-19

77

Allelic Variation of Gene Expression in Maize HybridsW?  

PubMed Central

Allelic expression variation of nonimprinted autosomal genes has recently been uncovered in mouse hybrids and humans. The allelic expression variation is attributed to differences in noncoding DNA sequences and does not involve epigenetic regulation or gene imprinting. This expression variation is suggested to play important roles in determining phenotypic diversity. Virtually nothing is known about such allele-specific expression variation in a hybrid plant where two alleles are compared in the same genetic context. We examined parental transcript accumulation in maize (Zea mays) hybrids using allele-specific RT-PCR analysis. Among 15 genes analyzed, 11 showed differences at the RNA level, ranging from unequal expression of the two alleles (biallelic) to expression of a single allele (monoallelic). Maternal or paternal transmission had little effect on the allele-specific transcript ratio of nearly all genes analyzed, suggesting that parent-of-origin effect was minimal. We analyzed the allelic difference in genetically contrasting hybrids and hybrids under high planting density and drought stress. Whereas a genetically improved modern hybrid expressed both alleles, a less improved old hybrid frequently showed mono-allelic expression. Furthermore, the two alleles in the hybrid responded differentially to abiotic stresses. The results of allele-specific regulation in different tissues in responding to environment and stress suggest an unequivalent function of the parental alleles in the hybrid, which may have an impact on heterosis.

Guo, Mei; Rupe, Mary A.; Zinselmeier, Christopher; Habben, Jeffrey; Bowen, Benjamin A.; Smith, Oscar S.

2004-01-01

78

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.

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

1997-01-01

79

Modulation of JAK2 V617F allele burden dynamics by hydroxycarbamide in polycythaemia vera and essential thrombocythaemia patients.  

PubMed

The modulation of JAK2 V617F allele burden dynamics was prospectively analysed in 47 patients (26 polycythaemia vera [PV] and 21 essential thrombocythaemia [ET]) treated with first-line hydroxyurea (HU) and compared with the JAK2 V617F dynamics of a control group of 45 PV and ET patients. A partial molecular response (PMR), according to European Leukaemia Net criteria, was observed in 27/47 (57%) patients. Median time to PMR was 14?months (3-66) with a probability of PMR at 3?years of 57%. A significant decrease in JAK2 V617F allele load was observed at 36?months both in PV and ET patients, being the reduction in PV higher than in ET patients (P?=?0·01). A haematocrit ?0·45?L/L was associated with a higher probability of attaining a PMR (HR:3·4; 95%CI:1·02-11·6, P?=?0·04). Control group showed a slight increase of JAK2 V617F allele burden over time. The reduction in the mutated allele load comparing treated patients versus controls was highly significant both in PV and ET, demonstrating a clear effect of HU on the JAK2 V617F allele burden. In conclusion, first-line HU can attain PMR in more than 50% of newly diagnosed PV and ET patients, with a continuous decrease of the JAK2 V617F allele burden in PV patients during treatment. PMID:21219298

Besses, Carlos; Alvarez-Larrán, Alberto; Martínez-Avilés, Luz; Mojal, Sergi; Longarón, Raquel; Salar, Antonio; Florensa, Lourdes; Serrano, Sergi; Bellosillo, Beatriz

2011-01-10

80

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

SciTech Connect

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

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

1995-05-01

81

Use of allele scores as instrumental variables for Mendelian randomization  

PubMed Central

Background An allele score is a single variable summarizing multiple genetic variants associated with a risk factor. It is calculated as the total number of risk factor-increasing alleles for an individual (unweighted score), or the sum of weights for each allele corresponding to estimated genetic effect sizes (weighted score). An allele score can be used in a Mendelian randomization analysis to estimate the causal effect of the risk factor on an outcome. Methods Data were simulated to investigate the use of allele scores in Mendelian randomization where conventional instrumental variable techniques using multiple genetic variants demonstrate ‘weak instrument’ bias. The robustness of estimates using the allele score to misspecification (for example non-linearity, effect modification) and to violations of the instrumental variable assumptions was assessed. Results Causal estimates using a correctly specified allele score were unbiased with appropriate coverage levels. The estimates were generally robust to misspecification of the allele score, but not to instrumental variable violations, even if the majority of variants in the allele score were valid instruments. Using a weighted rather than an unweighted allele score increased power, but the increase was small when genetic variants had similar effect sizes. Naive use of the data under analysis to choose which variants to include in an allele score, or for deriving weights, resulted in substantial biases. Conclusions Allele scores enable valid causal estimates with large numbers of genetic variants. The stringency of criteria for genetic variants in Mendelian randomization should be maintained for all variants in an allele score.

Burgess, Stephen; Thompson, Simon G

2013-01-01

82

Near Fixation of 374l Allele Frequencies of the Skin Pigmentation Gene SLC45A2 in Africa.  

PubMed

The L374F polymorphism of the SLC45A2 gene, encoding the membrane-associated transporter protein that plays an important role in melanin synthesis, has been suggested to be associated with skin color in human populations. In this study, the detailed distribution of the 374f and 374l alleles has been investigated in 2,581 unrelated subjects from 36 North, East, West, and Central African populations. We found once more the highly significant (p < 0.001) correlation coefficient (r = 0.957) cline of 374f frequencies with degrees of latitude in European and North African populations. Almost all the African populations located below 16° of latitude are fixed for the 374l allele. Peul, Toucouleur, and Soninké populations have 374l allele frequencies of 0.06, 0.03, and 0.03, respectively. PMID:23660638

Lucotte, Gérard; Yuasa, Isao

2013-05-10

83

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

PubMed

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

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

2002-02-01

84

Linker histone subtypes and their allelic variants.  

PubMed

Members of histone H1 family bind to nucleosomal and linker DNA to assist in stabilization of higher-order chromatin structures. Moreover, histone H1 is involved in regulation of a variety of cellular processes by interactions with cytosolic and nuclear proteins. Histone H1, composed of a series of subtypes encoded by distinct genes, is usually differentially expressed in specialized cells and frequently non-randomly distributed in different chromatin regions. Moreover, a role of specific histone H1 subtype might be also modulated by post-translational modifications and/or presence of polymorphic isoforms. While the significance of covalently modified histone H1 subtypes has been partially recognized, much less is known about the importance of histone H1 polymorphic variants identified in various plant and animal species, and human cells as well. Recent progress in elucidating amino acid composition-dependent functioning and interactions of the histone H1 with a variety of molecular partners indicates a potential role of histone H1 polymorphic variation in adopting specific protein conformations essential for chromatin function. The histone H1 allelic variants might affect chromatin in order to modulate gene expression underlying some physiological traits and, therefore could modify the course of diverse histone H1-dependent biological processes. This review focuses on the histone H1 allelic variability, and biochemical and genetic aspects of linker histone allelic isoforms to emphasize their likely biological relevance. PMID:23075301

Kowalski, Andrzej; Pa?yga, Jan

2012-11-01

85

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

PubMed Central

The relative frequency of the common phenylalanine hydroxylase (PAH) mutation R408W and its associations with polymorphic RFLP, VNTR, and short-tandem-repeat (STR) sites in the PAH gene were examined in many European populations and one representative North American population of defined European descent. This mutation was found to cluster in two regions: in northwest Europe among Irish and Scottish peoples, and in eastern Europe, including the Commonwealth of Independent States. This allele was significantly less frequent in intervening populations. In eastern European populations, the R408W mutation is strongly associated with RFLP haplotype 2, the three-copy VNTR allele (VNTR 3), and the 240-bp STR allele. In northwestern European populations, it is strongly associated with RFLP haplotype 1, the VNTR allele containing eight repeats (VNTR 8), and the 244-bp STR allele. An examination of the linkage between the R408W mutation and highly polymorphic RFLP, VNTR, and STR haplotypes suggests that recurrence is the most likely mechanism to account for the two different major haplotype associations of R408W in Europe. ImagesFigure 1Figure 2

Eisensmith, Randy C.; Goltsov, Alexei A.; O'Neill, Charles; Tyfield, Linda A.; Schwartz, Eugene I.; Kuzmin, Alexei I.; Baranovskaya, Svetlana S.; Tsukerman, Gennady L.; Treacy, Eileen; Scriver, Charles R.; Guttler, Flemming; Guldberg, Per; Eiken, Hans G.; Apold, Jaran; Svensson, Elisabeth; Naughten, Eileen; Cahalane, Seamus F.; Croke, David T.; Cockburn, Forrester; Woo, Savio L. C.

1995-01-01

86

Comprehensive Phenotype of the p.Arg420his Allelic Form of Spinocerebellar Ataxia Type 13.  

PubMed

The p.Arg420His allelic form of spinocerebellar ataxia type 13 has been reported in a large Filipino kindred, as well as three European index cases, one with an affected offspring. Haplotype analysis has confirmed independent mutational events. All individuals share adult-onset, predominantly cerebellar signs and a slowly progressive course. However, a comprehensive phenotypic description has yet to be published on SCA13(p.Arg420His). In this study, we present the results of a detailed neurological clinical and diagnostic testing on 21 mutation-positive members of a four-generation Filipino family to further define this disease, aiding diagnosis and prognosis. PMID:23912307

Subramony, Sh; Advincula, Joel; Perlman, Susan; Rosales, Raymond L; Lee, Lillian V; Ashizawa, Tetsuo; Waters, Michael F

2013-12-01

87

Worldwide Distribution of the MYH9 Kidney Disease Susceptibility Alleles and Haplotypes: Evidence of Historical Selection in Africa  

Microsoft Academic Search

MYH9 was recently identified as renal susceptibility gene (OR 3–8, p<10?8) for major forms of kidney disease disproportionately affecting individuals of African descent. The risk haplotype (E-1) occurs at much higher frequencies in African Americans (?60%) than in European Americans (<4%), revealing a genetic basis for a major health disparity. The population distributions of MYH9 risk alleles and the E-1

Taras K. Oleksyk; George W. Nelson; Ping An; Jeffrey B. Kopp; Cheryl A. Winkler; Henry Harpending

2010-01-01

88

Apolipoprotein E (APOE) allele distribution in the world. Is APOE*4 a 'thrifty' allele?  

PubMed

Apolipoprotein E (APOE = gene, apoE = protein) plays a central role in plasma lipoprotein metabolism and in lipid transport within tissues. The APOE shows a genetic polymorphism determined by three common alleles, APOE*2, APOE*3, APOE*4 and the product of the three alleles differs in several functional properties. APOE is involved in the development of certain pathological conditions. In particular, the APOE*4 allele is a risk factor for susceptibility to coronary artery disease (CAD) and Alzheimer's Disease (AD). In the present study we analyzed the APOE allele distribution in the world. The APOE*3 is the most frequent in all the human groups, especially in populations with a long-established agricultural economy like those of the Mediterranean basin (0.849-0.898). The frequency of APOE*4, the ancestral allele, remains higher in populations like Pygmies (0.407) and Khoi San (0.370), aborigines of Malaysia (0.240) and Australia (0.260), Papuans (0.368), some Native Americans (0.280), and Lapps (0.310) where an economy of foraging still exists, or food supply is (or was until the recent past) scarce and sporadically available. The APOE*2 frequency fluctuates with no apparent trend (0.145-0.02) and is absent in Native Americans. We suggest that the APOE*4, based on some functional properties it has and on its distribution among human populations, could be identified as a 'thrifty' allele. The exposure of APOE*4 to the contemporary environmental conditions (Western diet, longer lifespans) could have rendered it a susceptibility allele for CAD and AD. The absence of the association of APOE*4 with CAD and AD in Sub-Saharan Africans, and its presence in African Americans, seems to confirm this hypothesis. PMID:10738542

Corbo, R M; Scacchi, R

1999-07-01

89

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

90

Patterns of hemoglobin polymorphism [?-globin (HBA) and ?-globin (HBB)] across the contact zone of two distinct phylogeographic lineages of the European rabbit ( Oryctolagus cuniculus )  

Microsoft Academic Search

Two loci, HBA and HBB, were studied for protein polymorphism across the contact zone of the European rabbit (Oryctolagus cuniculus). Six alleles were identified in HBA and two in HBB. Three alleles at the HBA locus were found to be restricted to some populations,\\u000a while the other three revealed more broad geographic structure. An apparent substitution of the three major

Rita Campos; Madalena Branco; Steven Weiss; Nuno Ferrand

91

[Selective elimination of alleles in rice anther cultures].  

PubMed

The nature of heterosis is discussed and selective elimination of alleles (introduced in the hybrid genotype by the parental forms) in anther culture is shown. This supports the possibility of removing viability-reducing alleles (lethal, semilethal, and less effective alleles) from the genotypes of heterotic hybrids in anther culture. PMID:23668085

Goncharova, Iu K

2013-02-01

92

MHC class II genes in European wolves: a comparison with dogs.  

PubMed

The genome of the grey wolf, one of the most widely distributed land mammal species, has been subjected to both stochastic factors, including biogeographical subdivision and population fragmentation, and strong selection during the domestication of the dog. To explore the effects of drift and selection on the partitioning of MHC variation in the diversification of species, we present nine DQA, 10 DQB, and 17 DRB1 sequences of the second exon for European wolves and compare them with sequences of North American wolves and dogs. The relatively large number of class II alleles present in both European and North American wolves attests to their large historical population sizes, yet there are few alleles shared between these regions at DQB and DRB1. Similarly, the dog has an extensive array of class II MHC alleles, a consequence of a genetically diverse origin, but allelic overlap with wolves only at DQA. Although we might expect a progression from shared alleles to shared allelic lineages during differentiation, the partitioning of diversity between wolves and dogs at DQB and DRB1 differs from that at DQA. Furthermore, an extensive region of nucleotide sequence shared between DRB1 and DQB alleles and a shared motif suggests intergenic recombination may have contributed to MHC diversity in the Canidae. PMID:12389097

Seddon, Jennifer M; Ellegren, Hans

2002-08-29

93

Fragile X full mutation alleles composed of few alleles: implications for CGG repeat expansion.  

PubMed

Southern analysis of the FMR1 repeat region has suggested that individuals with the full mutation usually carry a heterogeneous array of FMR1 alleles in somatic tissue that can range from 200 to more than 1,000 repeats. Our studies indicate that this heterogeneity is an artifact generated by ethidium bromide commonly used in Southern analysis. When analyzed in the absence of ethidium bromide, nearly all full mutation individuals carried only one to four major alleles and did not exhibit the heterogeneity often referred to as a "smear" in the literature. Full mutations in chorionic villi, however, exhibited much greater heterogeneity. Nine transmissions from mothers with full mutation alleles to offspring indicated that the full mutations continued to expand in transmission to the next generation. In contrast, analysis of leukocyte DNA from three full mutation males revealed no change in somatic full mutation alleles over many years. Our studies support the hypothesis that the FMR1 CGG repeat instability is limited to very early embryogenesis in the soma. These studies also have clinical importance because the omission of ethidium bromide will facilitate the diagnosis of females with full mutation alleles. PMID:18074381

Nolin, Sarah L; Ding, Xiao-hua; Houck, George E; Brown, W Ted; Dobkin, Carl

2008-01-01

94

Several Different Lactase Persistence Associated Alleles and High Diversity of the Lactase Gene in the Admixed Brazilian Population  

PubMed Central

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.

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

2012-01-01

95

European space transport systems  

NASA Astrophysics Data System (ADS)

Present and future European space transport systems are discussed. The development of the ARIANE 1-4 family is briefly reviewed, and the space transport competition between Europe and the United States is described. The HM60 and European propulsion technology are discussed, giving the characteristics of various engines. The features of the future European cargo rocket ARIANE 5P are outlined, and the need for orbital maneuvering vehicles in low earth orbit is discussed.

Lo, R. E.

96

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.

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

1998-01-01

97

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

PubMed Central

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

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

2009-01-01

98

Allele Frequencies at Microsatellite Loci: The Stepwise Mutation Model Revisited  

PubMed Central

We summarize available data on the frequencies of alleles at microsatellite loci in human populations and compare observed distributions of allele frequencies to those generated by a simulation of the stepwise mutation model. We show that observed frequency distributions at 108 loci are consistent with the results of the model under the assumption that mutations cause an increase or decrease in repeat number by one and under the condition that the product Nu, where N is the effective population size and u is the mutation rate, is larger than one. We show that the variance of the distribution of allele sizes is a useful estimator of Nu and performs much better than previously suggested estimators for the stepwise mutation model. In the data, there is no correlation between the mean and variance in allele size at a locus or between the number of alleles and mean allele size, which suggests that the mutation rate at these loci is independent of allele size.

Valdes, A. M.; Slatkin, M.; Freimer, N. B.

1993-01-01

99

Allele-Specific KRT1 Expression Is a Complex Trait  

PubMed Central

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

Tao, Heng; Cox, David R; Frazer, Kelly A

2006-01-01

100

A novel polymorphic allele of human arylacetamide deacetylase leads to decreased enzyme activity.  

PubMed

Human arylacetamide deacetylase (AADAC) is responsible for the hydrolysis of clinically used drugs such as flutamide, phenacetin, and rifamycins. Our recent studies suggested that human AADAC is a relevant enzyme pharmacologically and toxicologically. To date, the genetic polymorphisms that affect enzyme activity in AADAC have been unknown. In this study, we found single-nucleotide polymorphisms in the human AADAC gene in a liver sample that showed remarkably low flutamide hydrolase activity. Among them, g.13651G > A (V281I) and g.14008T > C (X400Q) were nonsynonymous. The latter would be predicted to cause a C-terminal one-amino acid (glutamine) extension. The AADAC*2 allele (g.13651G > A) was found in all populations investigated in this study (European American, African American, Korean, and Japanese), at allelic frequencies of 52.6 to 63.5%, whereas the AADAC*3 allele (g.13651G > A/g.14008T > C) was found in European American (1.3%) and African American (2.0%) samples. COS7 cells expressing AADAC.1 (wild-type) exhibited flutamide, phenacetin, and rifampicin hydrolase activities with intrinsic clearance (CLint) values of 1.31 ± 0.06, 1.00 ± 0.02, and 0.39 ± 0.02 ?l x min(-1) x unit(-1), respectively. AADAC.2, which is a protein produced from the AADAC*2 allele, showed moderately lower or similar CLint values, compared with AADAC.1, but AADAC.3 showed substantially lower CLint values (flutamide hydrolase, 0.21 ± 0.02 ?l x min(-1) x unit(-1); phenacetin hydrolase, 0.12 ± 0.00 ?l x min(-1) x unit(-1); rifampicin hydrolase, 0.03 ± 0.01 ?l x min(-1) x unit(-1), respectively). Microsomes from a liver sample genotyped as AADAC*3/AADAC*3 showed decreased enzyme activities, compared with those genotyped as AADAC*1/AADAC*1, AADAC*1/AADAC*2, and AADAC*2/AADAC*2. In conclusion, we found an AADAC allele that yielded decreased enzyme activity. This study should provide useful information on interindividual variations in AADAC enzyme activity. PMID:22415931

Shimizu, Mai; Fukami, Tatsuki; Kobayashi, Yuki; Takamiya, Masataka; Aoki, Yasuhiro; Nakajima, Miki; Yokoi, Tsuyoshi

2012-03-13

101

Allele-specific gene targeting in Candida albicans results from heterology between alleles  

Microsoft Academic Search

The opportunistic fungal pathogen Candida albicans is asexual and diploid. Thus, introduction of recessive mutations requires targeted gene replacement of two alleles to effect expression of a recessive phenotype. This is often performed by recycling of a URA3 marker gene that is flanked by direct repeats of hisG. After targeting to a locus, recombination between the repeats excises URA3 leaving

Kyle Yesland; William A. Fonzi

2000-01-01

102

Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain  

Microsoft Academic Search

It is widely thought that alleles that influence susceptibility to common diseases, including schizophrenia, will frequently do so through effects on gene expression. As only a small proportion of the genetic variance for schizophrenia has been attributed to specific loci, this remains an unproven hypothesis. The International Schizophrenia Consortium (ISC) recently reported a substantial polygenic contribution to that disorder, and

A L Richards; L Jones; V Moskvina; G Kirov; P V Gejman; D F Levinson; A R Sanders; S Purcell; P M Visscher; N Craddock; M J Owen; P Holmans; M C O'Donovan

2012-01-01

103

Ten Novel HLA-DRB1 Alleles and One Novel DRB3 Allele.  

National Technical Information Service (NTIS)

Ten novel HLA-DRB1 and one DRB3 alleles are described. Eight of the variants are single-nucleotide substitutions, four resulting in an amino acid change (DRB1*1145, *1148, *0828 and *1514) and four with silent substitutions (DRB1*040504, *130103, *160502 ...

A. M. Lazaro J. Ng J. R. Moraes M. E. Moraes N. K. Steiner

2006-01-01

104

Education and European Integration.  

ERIC Educational Resources Information Center

|Reviews implications for education and training of the movement toward integration among European Community nations and the end of Communist governments. Discusses common concerns for new Europe, including data sharing, teacher training, educational quality, disadvantaged learners, demographic and employment trends, European Studies curricula,…

Lowe, John

1992-01-01

105

European Hemp Industry 2002  

Microsoft Academic Search

This paper presents results from market surveys conducted by the European Industrial Hemp Association (EIHA) in 2001, 2002 and 2003 on hemp production, processing and products. In 2003, the area under hemp cultivation in the European Union (EU) has reached 18,000 ha. The average yield of dry hemp stalks was 6 t\\/ha in 2001 and 2002. Seventy percent to 80%

Michael Karus

2004-01-01

106

THEORIES OF EUROPEAN INTEGRATION  

Microsoft Academic Search

Summary This course provides an introduction to leading theories of regional integration. The theories covered include classics such as neofunctionalism and (liberal) inter- governmentalism but constructivist as well as comparative perspectives on the European Union will also be treated. The theories will be applied to cases of horizontal, vertical and sectoral integration in the European Union. Objectives Students will gain

Dirk Leuffen

107

European media law  

Microsoft Academic Search

European Union legislation concerning electronic communications media is firmly established as an essential part of the law in the field in Europe. From relevant provisions of the European Convention of Human Rights and the EC Treaty to numerous directives, the most recent being the Audiovisual Media Services Directive 2007, a supranational and interrelated regime lays an extensive groundwork on which

O. Castendyk; E. Dommering; A. Scheuer

2008-01-01

108

European Network of Forensic Science Institutes (ENFSI): Evaluation of new commercial STR multiplexes that include the European Standard Set (ESS) of markers.  

PubMed

To support and to underpin the European initiative to increase the European set of standard markers (ESS), by the addition of five new loci, a collaborative project was organised by the European Network of Forensic Science Institutes (ENFSI) DNA working group in order to assess the new multiplex kits available. We have prepared allele frequency databases from 26 EU populations. Concordance studies were carried out to verify that genotyping results were consistent between kits. Population genetics studies were conducted and it was estimated that F(ST)<0.001. The results showed that the kits were comparable to each other in terms of performance and major discrepancy issues were highlighted. We provide details of allele frequencies for each of the populations analysed per laboratory. PMID:22658771

Welch, L A; Gill, P; Phillips, C; Ansell, R; Morling, N; Parson, W; Palo, J U; Bastisch, I

2012-05-31

109

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.

110

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.

111

Naturally occurring allele diversity allows potato cultivation in northern latitudes.  

PubMed

Potato (Solanum tuberosum L.) originates from the Andes and evolved short-day-dependent tuber formation as a vegetative propagation strategy. Here we describe the identification of a central regulator underlying a major-effect quantitative trait locus for plant maturity and initiation of tuber development. We show that this gene belongs to the family of DOF (DNA-binding with one finger) transcription factors and regulates tuberization and plant life cycle length, by acting as a mediator between the circadian clock and the StSP6A mobile tuberization signal. We also show that natural allelic variants evade post-translational light regulation, allowing cultivation outside the geographical centre of origin of potato. Potato is a member of the Solanaceae family and is one of the world's most important food crops. This annual plant originates from the Andean regions of South America. Potato develops tubers from underground stems called stolons. Its equatorial origin makes potato essentially short-day dependent for tuberization and potato will not make tubers in the long-day conditions of spring and summer in the northern latitudes. When introduced in temperate zones, wild material will form tubers in the course of the autumnal shortening of day-length. Thus, one of the first selected traits in potato leading to a European potato type is likely to have been long-day acclimation for tuberization. Potato breeders can exploit the naturally occurring variation in tuberization onset and life cycle length, allowing varietal breeding for different latitudes, harvest times and markets. PMID:23467094

Kloosterman, Bjorn; Abelenda, José A; Gomez, María del Mar Carretero; Oortwijn, Marian; de Boer, Jan M; Kowitwanich, Krissana; Horvath, Beatrix M; van Eck, Herman J; Smaczniak, Cezary; Prat, Salomé; Visser, Richard G F; Bachem, Christian W B

2013-03-06

112

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

Microsoft Academic Search

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

Manali Patel

2012-01-01

113

Mutations in the arylsulfatase A pseudodeficiency allele causing metachromatic leukodystrophy.  

PubMed Central

We identified a patient suffering from late infantile metachromatic leukodystrophy who genetically seemed to be homozygous for the mutations signifying the arylsulfatase A pseudodeficiency allele. Homozygosity for the pseudodeficiency allele is associated with low arylsulfatase A activity but does not cause a disease. Analysis of the arylsulfatase A gene in this patient revealed a C----T transition in exon 2, causing a Ser 96----Phe substitution in addition to the sequence alterations causing arylsulfatase A pseudodeficiency. Although this mutation was found only in 1 of 78 metachromatic leukodystrophy patients tested, five more patients were identified who seemed hetero- or homozygous for the pseudodeficiency allele. The existence of nonfunctional arylsulfatase A alleles derived from the pseudodeficiency allele calls for caution when the diagnosis of arylsulfatase A pseudodeficiency is based solely on the identification of the mutations characterizing the pseudodeficiency allele. Images Figure 1 Figure 2 Figure 3

Gieselmann, V; Fluharty, A L; T?nnesen, T; Von Figura, K

1991-01-01

114

Association between ACE D allele and elite short distance swimming  

Microsoft Academic Search

The influence of ACE gene on athletic performance has been widely explored, and most of the published data refers to an I\\/D\\u000a polymorphism leading to the presence (I allele) or absence (D allele) of a 287-bp sequence in intron 16, determining ACE activity\\u000a in serum and tissues. A higher I allele frequency has been reported among elite endurance athletes, while

Aldo Matos Costa; António José Silva; Nuno Domingos Garrido; Hugo Louro; Ricardo Jacó de Oliveira; Luiza Breitenfeld

2009-01-01

115

Molecular mechanisms of alpha 1-antitrypsin null alleles  

Microsoft Academic Search

Alpha1-antitrypsin (?1-AT) is the most abundant circulating inhibitor of serine proteases and therefore is essential to normal protease–anti-protease homeostasis. Inheritance of two parental ?1-AT deficiency alleles is associated with a substantially increased risk for development of emphysema and liver disease. In very rare circumstances individuals may inherit ?1-AT null alleles. Null?1 -AT alleles are characterized by the total absence of

J. H LEE; M BRANTLY

2000-01-01

116

Synergy between the C2 allele of transferrin and the C282Y allele of the haemochromatosis gene (HFE) as risk factors for developing Alzheimer's disease  

PubMed Central

Background: There is evidence that iron may play a role in the pathology of Alzheimer's disease (AD). There may be genetic factors that contribute to iron deposition resulting in tissue damage thus exacerbating AD. Methods: We have genotyped 269 healthy elderly controls, 191 cases with definite or probable AD, and 69 with mild cognitive impairment (MCI) from the OPTIMA cohort. Results: We have examined the interaction between the C2 variant of the transferrin (TF) gene and the C282Y allele of the haemochromatosis (HFE) gene as risk factors for developing AD. Our results showed that each of the two variants was associated with an increased risk of AD only in the presence of the other. Neither allele alone had any effect. Carriers of both variants were at 5 times greater risk of AD compared with all others. The interaction was significant by logistic regression (p = 0.014) and by synergy factor analysis (p = 0.015, synergy factor = 5.1). Further, carriers of these two alleles plus apolipoprotein E ?4 (APOE4) were at still higher risk of AD: of the 14 tri-carriers of the three variants, identified in this study, 12 had AD and two MCI. Conclusion: We suggest that the combination of TF C2 and HFE C282Y may lead to an excess of redox-active iron and the induction of oxidative stress in neurones, which is exacerbated in carriers of APOE4. Since 4% of Northern Europeans carry the two iron-related variants and since iron overload is a treatable condition, these results merit replication.

Robson, K; Lehmann, D; Wimhurst, V; Livesey, K; Combrinck, M; Merryweather-Clar..., A; Warden, D; Smith, A

2004-01-01

117

The European Spallation Source  

SciTech Connect

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.; Calaga R.; Bousson S.; Danared H.; Devanz G. et al

2011-04-20

118

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.

119

A novel HLA-A allele: A*0257.  

PubMed

A novel human leucocyte antigen-A*02 (HLA-A*02) allele was detected by reference strand-mediated conformation analysis (RSCA) of a DNA sample from a Tarahumara individual. Direct sequencing of HLA-A locus polymerase chain reaction products identified a mutation in one of the alleles. Cloning and sequencing confirmed the presence of a new allele, A*0257 which differed from A*0206 by two nucleotides at positions 355 and 362, inducing changes in residues 95 and 97, respectively, within the peptide-binding site. Those changes suggest that allele A*0257 may have resulted from an intralocus recombination event. PMID:14651529

García-Ortiz, J E; Cox, S T; Sandoval-Ramirez, L; Little, A M; Marsh, S G E; Madrigal, J A; Argüello, J R

2004-01-01

120

Genome-wide allele- and strand-specific expression profiling  

PubMed Central

Recent reports have shown that most of the genome is transcribed and that transcription frequently occurs concurrently on both DNA strands. In diploid genomes, the expression level of each allele conditions the degree to which sequence polymorphisms affect the phenotype. It is thus essential to quantify expression in an allele- and strand-specific manner. Using a custom-designed tiling array and a new computational approach, we piloted measuring allele- and strand-specific expression in yeast. Confident quantitative estimates of allele-specific expression were obtained for about half of the coding and non-coding transcripts of a heterozygous yeast strain, of which 371 transcripts (13%) showed significant allelic differential expression greater than 1.5-fold. The data revealed complex allelic differential expression on opposite strands. Furthermore, combining allele-specific expression with linkage mapping enabled identifying allelic variants that act in cis and in trans to regulate allelic expression in the heterozygous strain. Our results provide the first high-resolution analysis of differential expression on all four strands of an eukaryotic genome.

Gagneur, Julien; Sinha, Himanshu; Perocchi, Fabiana; Bourgon, Richard; Huber, Wolfgang; Steinmetz, Lars M

2009-01-01

121

Genome-wide allele- and strand-specific expression profiling.  

PubMed

Recent reports have shown that most of the genome is transcribed and that transcription frequently occurs concurrently on both DNA strands. In diploid genomes, the expression level of each allele conditions the degree to which sequence polymorphisms affect the phenotype. It is thus essential to quantify expression in an allele- and strand-specific manner. Using a custom-designed tiling array and a new computational approach, we piloted measuring allele- and strand-specific expression in yeast. Confident quantitative estimates of allele-specific expression were obtained for about half of the coding and non-coding transcripts of a heterozygous yeast strain, of which 371 transcripts (13%) showed significant allelic differential expression greater than 1.5-fold. The data revealed complex allelic differential expression on opposite strands. Furthermore, combining allele-specific expression with linkage mapping enabled identifying allelic variants that act in cis and in trans to regulate allelic expression in the heterozygous strain. Our results provide the first high-resolution analysis of differential expression on all four strands of an eukaryotic genome. PMID:19536197

Gagneur, Julien; Sinha, Himanshu; Perocchi, Fabiana; Bourgon, Richard; Huber, Wolfgang; Steinmetz, Lars M

2009-06-16

122

The effect of deleterious alleles on adaptation in asexual populations.  

PubMed Central

We calculate the fixation probability of a beneficial allele that arises as the result of a unique mutation in an asexual population that is subject to recurrent deleterious mutation at rate U. Our analysis is an extension of previous works, which make a biologically restrictive assumption that selection against deleterious alleles is stronger than that on the beneficial allele of interest. We show that when selection against deleterious alleles is weak, beneficial alleles that confer a selective advantage that is small relative to U have greatly reduced probabilities of fixation. We discuss the consequences of this effect for the distribution of effects of alleles fixed during adaptation. We show that a selective sweep will increase the fixation probabilities of other beneficial mutations arising during some short interval afterward. We use the calculated fixation probabilities to estimate the expected rate of fitness improvement in an asexual population when beneficial alleles arise continually at some low rate proportional to U. We estimate the rate of mutation that is optimal in the sense that it maximizes this rate of fitness improvement. Again, this analysis relaxes the assumption made previously that selection against deleterious alleles is stronger than on beneficial alleles.

Johnson, Toby; Barton, Nick H

2002-01-01

123

A noncomplementation screen for quantitative trait alleles in saccharomyces cerevisiae.  

PubMed

Both linkage and linkage disequilibrium mapping provide well-defined approaches to mapping quantitative trait alleles. However, alleles of small effect are particularly difficult to refine to individual genes and causative mutations. Quantitative noncomplementation provides a means of directly testing individual genes for quantitative trait alleles in a fixed genetic background. Here, we implement a genome-wide noncomplementation screen for quantitative trait alleles that affect colony color or size by using the yeast deletion collection. As proof of principle, we find a previously known allele of CYS4 that affects colony color and a novel allele of CTT1 that affects resistance to hydrogen peroxide. To screen nearly 4700 genes in nine diverse yeast strains, we developed a high-throughput robotic plating assay to quantify colony color and size. Although we found hundreds of candidate alleles, reciprocal hemizygosity analysis of a select subset revealed that many of the candidates were false positives, in part the result of background-dependent haploinsufficiency or second-site mutations within the yeast deletion collection. Our results highlight the difficulty of identifying small-effect alleles but support the use of noncomplementation as a rapid means of identifying quantitative trait alleles of large effect. PMID:22870398

Kim, Hyun Seok; Huh, Juyoung; Riles, Linda; Reyes, Alejandro; Fay, Justin C

2012-07-01

124

European Population Genetic Substructure: Further Definition of Ancestry Informative Markers for Distinguishing among Diverse European Ethnic Groups  

PubMed Central

The definition of European population genetic substructure and its application to understanding complex phenotypes is becoming increasingly important. In the current study using over 4,000 subjects genotyped for 300,000 single-nucleotide polymorphisms (SNPs), we provide further insight into relationships among European population groups and identify sets of SNP ancestry informative markers (AIMs) for application in genetic studies. In general, the graphical description of these principal components analyses (PCA) of diverse European subjects showed a strong correspondence to the geographical relationships of specific countries or regions of origin. Clearer separation of different ethnic and regional populations was observed when northern and southern European groups were considered separately and the PCA results were influenced by the inclusion or exclusion of different self-identified population groups including Ashkenazi Jewish, Sardinian, and Orcadian ethnic groups. SNP AIM sets were identified that could distinguish the regional and ethnic population groups. Moreover, the studies demonstrated that most allele frequency differences between different European groups could be controlled effectively in analyses using these AIM sets. The European substructure AIMs should be widely applicable to ongoing studies to confirm and delineate specific disease susceptibility candidate regions without the necessity of performing additional genome-wide SNP studies in additional subject sets.

Tian, Chao; Kosoy, Roman; Nassir, Rami; Lee, Annette; Villoslada, Pablo; Klareskog, Lars; Hammarstrom, Lennart; Garchon, Henri-Jean; Pulver, Ann E; Ransom, Michael; Gregersen, Peter K; Seldin, Michael F

2009-01-01

125

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

PubMed Central

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

McCormack, Mark; Alfirevic, Ana; Bourgeois, Stephane; Farrell, John J.; Kasperaviciute, Dalia; Carrington, Mary; Sills, Graeme J.; Marson, Tony; Jia, Xiaoming; de Bakker, Paul I.W.; Chinthapalli, Krishna; Molokhia, Mariam; Johnson, Michael R.; O'Connor, Gerard D.; Chaila, Elijah; Alhusaini, Saud; Shianna, Kevin V.; Radtke, Rodney A.; Heinzen, Erin L.; Walley, Nicole; Pandolfo, Massimo; Pichler, Werner; Park, B. Kevin; Depondt, Chantal; Sisodiya, Sanjay M.; Goldstein, David B.; Deloukas, Panos; Delanty, Norman; Cavalleri, Gianpiero L.; Pirmohamed, Munir

2011-01-01

126

Evolutionary history of an MHC gene in two leporid species: characterisation of Mhc-DQA in the European brown hare and comparison with the European rabbit.  

PubMed

We surveyed the genetic diversity of the expressed major histocompatibility complex class II DQA locus in natural populations of European brown hares, Lepus europaeus, from Austria and Belgium (267 individuals in total). Based on cDNA sequences, we designed hare-specific primers to amplify the highly variable second exon of the DQA gene. Using cloning-sequencing methodology and capillary electrophoresis single-strand conformation polymorphism, we found ten alleles of the DQA exon 2 locus across these two European regions, of which eight are described for the first time. To search for signals of selection and recombination in the evolution of the DQA gene within the leporids, we augmented our sample with orthologous DQA alleles from the European rabbit, Oryctolagus cuniculus, in order to carry out a species level, species pairwise comparison. We found evidence of recombination in the history of the DQA sequences in leporids with some recombinant alleles bridging the species divide. In both species, selection on peptide binding site codons can be detected, though stronger for the rabbit. This result suggests that there may be a differential selection pressure in the deeper evolutionary history of these two species due to differences in several demographic and ecological traits likely subjecting them to differential selection by parasites. Finally, evolutionary relationships show a widespread and statistically significant intermingling of alleles from the two species. The many macroparasites shared between hares and rabbits may explain this pattern of trans-species polymorphism. PMID:19104797

Goüy de Bellocq, Joëlle; Suchentrunk, Franz; Baird, Stuart J E; Schaschl, Helmut

2008-12-23

127

CD80 and CD86 polymorphisms in populations of various ancestries: 5 new CD80 promoter alleles.  

PubMed

CD80 and CD86 are closely linked genes on chromosome 3 that code for glycoproteins of the immunoglobulin superfamily, expressed on the surface of antigen-presenting cells. These costimulatory molecules play essential roles for stimulation and inhibition of T cells through binding to CD28 and CTLA-4 receptors. In this study, CD80 promoter and CD86 exon 8 polymorphisms were analyzed to investigate the genetic diversity and microevolution of the 2 genes. We genotyped 1,124 individuals, including Brazilians of predominantly European, mixed African and European, and Japanese ancestry, 5 Amerindian populations, and an African sample. All variants were observed in Africans, which suggests their origin in Africa before the human migrations out of that continent. Five new CD80 promoter alleles were identified and confirmed by cloning and sequencing, and promoter 2 is most likely the ancestral allele. Nucleotide -79 is monomorphic in 4 Amerindian populations, where the presence of the -79 G allele is probably the result of gene flow from non-Amerindians. PMID:22074996

Beltrame, Márcia Holsbach; Pincerati, Márcia Regina; Dalla-Costa, Ricardo; Wassem, Roseli; Köhler, Karen Francine; Chautard-Freire-Maia, Eleidi Alice; Tsuneto, Luiza Tamie; Petzl-Erler, Maria Luiza

2011-10-23

128

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.

Lueger-Schuster, Brigitte

2013-01-01

129

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

Microsoft Academic Search

Recent data suggest that HLA-B locus alleles can evolve quickly in native South American populations. To investigate further this phenomenon of new HLA-B variants among Amerindians, we studied samples from another South American tribe, the Cayapa from Ecuador. We selected individuals for HLA-B molecular typing based upon their HLA class II typing results. Three new variants of HLA-B39 and one

Theodore L. Garber; Lesley M. Butler; Elizabeth A. Trachtenberg; Henry A. Erlich; Olga Rickards; Gianfranco Stefano; David I. Watkins

1995-01-01

130

European Navy: Can it Complete European Political and Economic Integration.  

National Technical Information Service (NTIS)

With the euro-crisis of the year 2011 threatening to fracture the European Union, the timing may seem wrong for makers of policy and sailors to imagine a unitary European Navy within a comprehensive European defense policy. But as Europeans explore the li...

I. P. Tranbarger

2012-01-01

131

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

132

The European Solar Telescope  

NASA Astrophysics Data System (ADS)

The European Solar Telescope (EST) is a project to design, build and operate an European Solar 4-meter class telescope to be located in the Canary Islands, with the participation of institutions from fifteen European countries gathered around the consortium EAST (European Association for Solar Telescopes). The project main objective up to the present has been the development of the conceptual design study (DS) of a large aperture Solar Telescope. The study has demonstrated the scientific, technical and financial feasibility of EST. The DS has been possible thanks to the co-financing allocated specifically by the EU and the combined efforts of all the participant institutions. Different existing alternatives have been analysed for all telescope systems and subsystems, and decisions have been taken on the ones that are most compatible with the scientific goals and the technical strategies. The present status of some subsystems is reviewed in this paper.

Collados, M.; Bettonvil, F.; Cavaller, L.; Ermolli, I.; Gelly, B.; Pérez, A.; Socas-Navarro, H.; Soltau, D.; Volkmer, R.; EST Team

133

European Space Agency (ESA)  

NASA Astrophysics Data System (ADS)

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

Murdin, P.

2000-11-01

134

Ethics and European security  

SciTech Connect

The alliance between the United States and her NATO partners has been strained severely in the last few years. American perceptions of European disloyalty and European impressions of American assertiveness and lack of judgment have played a large part in generating tensions between the allies and emphasising the new peace movements. This book is an attempt to develop a broader understanding of the problem of European security based on Christian ethics. There are disagreements and differences of emphasis among the contributors but they have in common the view that an exclusive preoccupation with the military dimension is damagingly one-sided. Instead the contributors argue that moral and theological concerns are a vital part of the politics and mechanics of European security and must be incorporated in any effort to devise new policies for security in Europe and the West.

Paskins, B.

1986-01-01

135

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

136

STR data for the AmpFlSTR Identifiler loci from Swedish population in comparison to European, as well as with non-European population.  

PubMed

The modern Swedish population is a mixture of people that originate from different parts of the world. This is also the truth for the clients participating in the paternity cases investigated at the department. Calculations based on a Swedish frequency database only, could give us overestimated figures of probability and power of exclusion in cases including clients with a genetic background other than Swedish. Here, we describe allele frequencies regarding the markers in the Identifiler-kit. We have compared three sets of population samples; Swedish, European and non-European to investigate how these three groups of population samples differ. Also, all three population sets were compared to data reported from other European and non-European populations. Swedish allele frequencies for the 15 autosomal STRs included in the Identifiler kit were obtained from unrelated blood donors with Swedish names. The European and non-European frequencies were based on DNA-profiles of alleged fathers from our paternity cases in 2005 and 2006. PMID:19083816

Montelius, Kerstin; Karlsson, Andreas O; Holmlund, Gunilla

2008-02-14

137

THE EUROPEAN XFEL PROJECT  

Microsoft Academic Search

The European XFEL will be a free electron laser based on self amplified spontaneous emission in the X-ray regime. The FEL\\u000a is driven by a superconducting 17.5 GeV linear accelerator, followed by 5 separate undulators both for SASE FEL radiation\\u000a and incoherent radiation. Start of operation is foreseen for 2013. This paper presents the layout of the European XFEL, with

W. Decking

138

Evolution of allelic dimorphism in malarial surface antigens  

Microsoft Academic Search

The extensive sequence variation in most surface antigens of Plasmodium falciparum is one of the major factors why clinical immunity to malaria develops only after repeated infections with the same species over several years. For some P. falciparum surface antigens, all observed alleles clearly fall into two allelic classes, with divergence between classes dwarfing divergence within classes. We discuss the

SW Roy; MU Ferreira; DL Hartl

2006-01-01

139

Asynchronous replication and allelic exclusion in the immune system  

Microsoft Academic Search

The development of mature B cells involves a series of molecular decisions which culminate in the expression of a single light-chain and heavy-chain antigen receptor on the cell surface. There are two alleles for each receptor locus, so the ultimate choice of one receptor type must involve a process of allelic exclusion. One way to do this is with a

Raul Mostoslavsky; Nandita Singh; Toyoaki Tenzen; Maya Goldmit; Chana Gabay; Sharon Elizur; Peimin Qi; Benjamin E. Reubinoff; Andrew Chess; Howard Cedar; Yehudit Bergman

2001-01-01

140

No association between apolipoprotein E alleles and olivopontocerebellar atrophy  

Microsoft Academic Search

Apolipoprotein E (apo E) ?4 is a risk factor for sporadic and late-onset familial Alzheimer's disease, but it is not well known whether the apo E is associated with spinocerebellar degeneration. We studied the frequency of apo E allele in 59 olivopontocerebellar atrophy (OPCA) patients, including 13 pathologically confirmed cases. The distribution of the apo E allele frequency did not

Hiromasa Toji; Hideshi Kawakami; Toshitaka Kawarai; Takayasu Nakayama; Osamu Komure; Sadako Kuno; Shigenobu Nakamura

1998-01-01

141

Genome-wide allele- and strand-specific expression profiling  

Microsoft Academic Search

Recent reports have shown that most of the genome is transcribed and that transcription frequently occurs concurrently on both DNA strands. In diploid genomes, the expression level of each allele conditions the degree to which sequence polymorphisms affect the phenotype. It is thus essential to quantify expression in an allele- and strand-specific manner. Using a custom-designed tiling array and a

Julien Gagneur; Himanshu Sinha; Fabiana Perocchi; Richard Bourgon; Wolfgang Huber; Lars M Steinmetz

2009-01-01

142

Tests and Estimates of Allelic Association in Complex Inheritance  

Microsoft Academic Search

Family-based procedures such as the transmission disequilibrium test (TDT) were motivated by concern that sample-based methods to map disease genes by allelic association are not robust to population stratification, migration, and admixture. Other factors to consider in designing a study of allelic association are specification of gene action in a weakly parametric model, efficiency, diagnostic reliability for hypernormal individuals, interest

N. E. Morton; A. Collins

1998-01-01

143

Allelism of genes controlling resistance to TMV in Capsicum L  

Microsoft Academic Search

The genes for resistance to pepper strains of TMV in five C. chinenseJacq. accessions, the PI numbers 152225, 159236, 315008, 315023 and 315024, were investigated for allelism. The resistance of these five C. chinense accessions was found to be inherited monogenically and to be partially dominant. The resistance genes in these accessions appeared to be allelic and were also found

Ietje W. Boukema

1980-01-01

144

Identification of the MICA*070 allele by sequencing and phasing.  

PubMed

A novel MICA allele, MICA*070, was defined by sequencing. The new allele differs from the MICA*008:04 sequence in exon 2, encoding a C instead of G corresponding to cDNA nucleotide position 183. This nucleotide substitution is predicted to encode serine instead of arginine at residue 38 of the ?1 domain of the MICA molecule. PMID:23200759

Moran, D; Morishima, S; Malkki, M; Petersdorf, E W

2012-11-29

145

Allelic exchange in Francisella tularensis using PCR products  

Microsoft Academic Search

We describe here a technique for allelic exchange in Francisella tularensis subsp. novicida utilizing polymerase chain reaction (PCR) products. Linear PCR fragments containing gene deletions with an erythromycin resistance cassette insertion were transformed into F. tularensis. The subsequent ErmR progeny were found to have undergone allelic exchange at the correct location in the genome; the minimum flanking homology necessary was

Crystal M. Lauriano; Jeffrey R. Barker; Francis E. Nano; Bernard P. Arulanandam; Karl E. Klose

2003-01-01

146

Interpreting simple STR mixtures using allele peak areas  

Microsoft Academic Search

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

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

1998-01-01

147

Heterogeneity of alleles encoding high- and low-prevalence red blood cell antigens across Africa: useful data to facilitate transfusion in African patients.  

PubMed

Ethnic variations in red blood cell (RBC) antigens can be a source of alloimmunization, especially in migrant populations. To improve transfusion safety in continental Africa and countries with African migrants, we performed RBC genotyping to determine allele frequencies coding for high- and low-prevalence antigens. A total of 481 blood samples were collected in ethnic groups from West, Central and East Africa. Molecular typing was performed using a polymerase chain reaction - reverse sequence specific oligonucleotide method. Results demonstrated no DI*1, DI*3, YT*2, SC*2, LW*7, KN*2 alleles in any sample and the CO*2 allele was rare. The frequency of LU*1 was comparable to that of European-Caucasians (2%) except in Biaka pygmies (8%). The frequency of CROM*-1 was high in Mbuti pygmies (13%). High frequency of KN*7 and KN*6 may reflect selection pressure in the countries investigated. Analysis of Dombrock allele patterns confirmed uneven distribution of the DO*1 and DO*2 alleles with high frequencies of DO*-4 and DO*-5 in all groups. Altogether, findings demonstrated extensive allele-frequency heterogeneity across Africa and suggested that knowledge of patient ethnicity gives information about the high-prevalence antigens that may be lacking. These data are medically useful to support transfusion care of African migrants living in countries where the majority of the population is from a different ethnical background. PMID:24032660

Silvy, Monique; Beley, Sophie; Granier, Thomas; Ba, Alhassane; Chiaroni, Jacques; Bailly, Pascal

2013-08-29

148

ALFRED: an allele frequency resource for research and teaching  

PubMed Central

ALFRED (http://alfred.med.yale.edu) is a free, web accessible, curated compilation of allele frequency data on DNA sequence polymorphisms in anthropologically defined human populations. Currently, ALFRED has allele frequency tables on over 663?400 polymorphic sites; 170 of them have frequency tables for more than 100 different population samples. In ALFRED, a population may have multiple samples with each ‘sample’ consisting of many individuals on which an allele frequency is based. There are 3566 population samples from 710 different populations with allele frequency tables on at least one polymorphism. Fifty of those population samples have allele frequency data for over 650?000 polymorphisms. Records also have active links to relevant resources (dbSNP, PharmGKB, OMIM, Ethnologue, etc.). The flexible search options and data display and download capabilities available through the web interface allow easy access to the large quantity of high-quality data in ALFRED.

Rajeevan, Haseena; Soundararajan, Usha; Kidd, Judith R.; Pakstis, Andrew J.; Kidd, Kenneth K.

2012-01-01

149

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.

150

Genome-wide identification of allelic expression in hypertensive rats  

PubMed Central

Background Identification of genes involved in complex cardiovascular disease traits has proven challenging. Inbred animal models can facilitate genetic studies of disease traits. The spontaneously hypertensive rat (SHR) is an inbred model of hypertension that exists in several closely related, but genetically distinct lines. Methods and Results We used renal gene expression profiling across 3 distinct SHR lines to identify genes that show different expression in SHR than in the genetically related normotensive control strain, WKY. In order to ensure robust discovery of genes showing SHR-specific expression differences we considered only those genes in which differential expression is replicated in multiple animals of each of multiple hypertensive rat lines at multiple time points during the ontogeny of hypertension. Mutation analysis was performed on the identified genes to uncover allelic variation. We identified those genes where all SHR lines share a single allele of the gene while normotensive controls (WKY) have fixed the alternative allele. We then identified which of the differentially expressed genes show expression that is controlled by the alleleic variation present in and around the gene. Allelic expression was demonstrated by observing the effect on gene expression of alleles inherited in the freely segregating F2 progeny of a cross between SHR and WKY animals. Conclusions The result of these studies is the identification of several genes (Ptprj, Ela1, Dapk-2, Gstt2) in which each of 4 SHR lines examined have fixed the same allele and in which each of 2 WKY lines have a contrasting allele for which the inherited allele influences the level of gene expression. We further show that alleles of these genes lie in extensive haplotype blocks that have been inherited identical by descent in the hypertensive lines.

Dmitrieva, Renata I.; Hinojos, Cruz A.; Grove, Megan L.; Bell, Rebecca J.; Boerwinkle, Eric; Fornage, Myriam; Doris, Peter A.

2009-01-01

151

Whole transcriptome RNA-Seq allelic expression in human brain  

PubMed Central

Background Measuring allelic RNA expression ratios is a powerful approach for detecting cis-acting regulatory variants, RNA editing, loss of heterozygosity in cancer, copy number variation, and allele-specific epigenetic gene silencing. Whole transcriptome RNA sequencing (RNA-Seq) has emerged as a genome-wide tool for identifying allelic expression imbalance (AEI), but numerous factors bias allelic RNA ratio measurements. Here, we compare RNA-Seq allelic ratios measured in nine different human brain regions with a highly sensitive and accurate SNaPshot measure of allelic RNA ratios, identifying factors affecting reliable allelic ratio measurement. Accounting for these factors, we subsequently surveyed the variability of RNA editing across brain regions and across individuals. Results We find that RNA-Seq allelic ratios from standard alignment methods correlate poorly with SNaPshot, but applying alternative alignment strategies and correcting for observed biases significantly improves correlations. Deploying these methods on a transcriptome-wide basis in nine brain regions from a single individual, we identified genes with AEI across all regions (SLC1A3, NHP2L1) and many others with region-specific AEI. In dorsolateral prefrontal cortex (DLPFC) tissues from 14 individuals, we found evidence for frequent regulatory variants affecting RNA expression in tens to hundreds of genes, depending on stringency for assigning AEI. Further, we find that the extent and variability of RNA editing is similar across brain regions and across individuals. Conclusions These results identify critical factors affecting allelic ratios measured by RNA-Seq and provide a foundation for using this technology to screen allelic RNA expression on a transcriptome-wide basis. Using this technology as a screening tool reveals tens to hundreds of genes harboring frequent functional variants affecting RNA expression in the human brain. With respect to RNA editing, the similarities within and between individuals leads us to conclude that this post-transcriptional process is under heavy regulatory influence to maintain an optimal degree of editing for normal biological function.

2013-01-01

152

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

153

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.

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.; Vila, Luis M.; Alarcon, 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

154

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

155

WFPDB: European Plate Archives  

NASA Astrophysics Data System (ADS)

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

Tsvetkov, Milcho

2007-08-01

156

The nature of tri-allelic TPOX genotypes in African populations  

Microsoft Academic Search

Approximately 2.4% of indigenous South Africans have three rather than two TPOX alleles. Data collected during routine paternity testing revealed that the extra allele is almost always allele 10 and that it segregates independently of those at the main TPOX locus. Approximately twice as many females as males have tri-allelic genotypes which suggested that the extra allele is on an

2008-01-01

157

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.

158

HLA class II allele frequencies in the Lebanese population.  

PubMed

Human leukocyte antigens (HLA) allele determination is becoming an increasingly important aspect in the field of transplantation as well as in the area of HLA association with a number of diseases. Through Lebanon's history, this country, situated at a crossroads between Europe, Asia and Africa, has been a host for various populations of different ethnicities. The aim of our study is to determine whether allele polymorphisms in the Lebanese population present a distinguishing feature. Although data on HLA phenotypic polymorphisms in Lebanon have been reported in the literature, our study is the first to examine frequencies of HLA polymorphisms in the country at the molecular level. Allele frequencies of the Lebanese population were analyzed and compared with those of other populations. HLA class II genotyping of DRB1* and DQB1* loci by PCR-sequence-specific primer (SSP) was performed on 191 unrelated Lebanese subjects of both sexes and of different regions and sects in Lebanon. The study revealed that DRB1*1101, DRB1*0401 and DRB1*0301 were the three most common DRB1* alleles observed (respective allele frequencies of 0.302, 0.164 and 0.096). In the DQB locus allele group, DQB1*0301 (allele frequency of 0.384) was highly predominant followed by the DQB1* 0501, DQB1*0201 and DQB1*0302 with respective allele frequencies of 0.199, 0.195 and 0.103. These results confirm previous serological studies and show the high prevalence of DRB1*1101 and DQB1*0301 in Lebanon, which could be explained by the high frequency of consanguineous marriages in the population. The presence of other common alleles is consistent with historical data showing that the Lebanese population is an admixture of various ethnicities. PMID:12835080

Samaha, Hanady; Rahal, Elias A; Abou-Jaoude, Maroun; Younes, Mazen; Dacchache, Jocelyn; Hakime, Noha

2003-07-01

159

A risk allele for focal segmental glomerulosclerosis in African Americans is located within a region containing APOL1 and MYH9  

Microsoft Academic Search

Genetic variation at the MYH9 locus is linked to the high incidence of focal segmental glomerulosclerosis (FSGS) and non-diabetic end-stage renal disease among African Americans. To further define risk alleles with FSGS we performed a genome-wide association analysis using more than one million single-nucleotide polymorphisms in 56 African-American and 61 European-American patients with biopsy-confirmed FSGS. Results were compared to 1641

Giulio Genovese; Stephen J Tonna; Andrea U Knob; Gerald B Appel; Avi Katz; Andrea J Bernhardy; Alexander W Needham; Ross Lazarus; Martin R Pollak

2010-01-01

160

Differences in allele frequencies of autosomal dominant hypercholesterolemia SNPs in the Malaysian population.  

PubMed

Hypercholesterolemia is caused by different interactions of lifestyle and genetic determinants. At the genetic level, it can be attributed to the interactions of multiple polymorphisms, or as in the example of familial hypercholesterolemia (FH), it can be the result of a single mutation. A large number of genetic markers, mostly single nucleotide polymorphisms (SNP) or mutations in three genes, implicated in autosomal dominant hypercholesterolemia (ADH), viz APOB (apolipoprotein B), LDLR (low density lipoprotein receptor) and PCSK9 (proprotein convertase subtilisin/kexin type-9), have been identified and characterized. However, such studies have been insufficiently undertaken specifically in Malaysia and Southeast Asia in general. The main objective of this study was to identify ADH variants, specifically ADH-causing mutations and hypercholesterolemia-associated polymorphisms in multiethnic Malaysian population. We aimed to evaluate published SNPs in ADH causing genes, in this population and to report any unusual trends. We examined a large number of selected SNPs from previous studies of APOB, LDLR, PCSK9 and other genes, in clinically diagnosed ADH patients (n=141) and healthy control subjects (n=111). Selection of SNPs was initiated by searching within genes reported to be associated with ADH from known databases. The important finding was 137 mono-allelic markers (44.1%) and 173 polymorphic markers (55.8%) in both subject groups. By comparing to publicly available data, out of the 137 mono-allelic markers, 23 markers showed significant differences in allele frequency among Malaysians, European Whites, Han Chinese, Yoruba and Gujarati Indians. Our data can serve as reference for others in related fields of study during the planning of their experiments. PMID:22534770

Alex, Livy; Chahil, Jagdish Kaur; Lye, Say Hean; Bagali, Pramod; Ler, Lian Wee

2012-04-26

161

Genetic Differences between Five European Populations.  

PubMed

Aims: We sought to examine the magnitude of the differences in SNP allele frequencies between five European populations (Scotland, Ireland, Sweden, Bulgaria and Portugal) and to identify the loci with the greatest differences. Methods: We performed a population-based genome-wide association analysis with Affymetrix 6.0 and 5.0 arrays. We used a 4 degrees of freedom chi(2) test to determine the magnitude of stratification for each SNP. We then examined the genes within the most stratified regions, using a highly conservative cutoff of p < 10(-45). Results: We found 40,593 SNPs which are genome-wide significantly (p European populations, indicating that they might also have provided selective advantages: several zinc finger genes, two genes involved in glutathione synthesis or function, and most intriguingly, FOXP2, implicated in speech development. Conclusion: Our analysis demonstrates that many SNPs show genome-wide significant differences within European populations and the magnitude of the differences correlate with the geographical distance. At least some of these differences are due to the selective advantage of polymorphisms within these loci. PMID:20616560

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

2010-07-08

162

Human Leukocyte Antigens-A, -B, -C, -DRB1 allele and haplotype frequencies in Americans originating from Southern Europe: Contrasting patterns of population differentiation between Italian and Spanish Americans  

PubMed Central

High resolution DNA sequencing was used to identify the HLA-A, -B, -C, and -DRB1 alleles found in 552 individuals from the United States indicating Southern European (Italian or Spanish) heritage. A total of 46 HLA-A, 80 HLA-B, 32 HLA-C, and 50 DRB1 alleles were identified. Frequent alleles included A*02:01:01G (allele frequency = 0.26 in Italian Americans; 0.22 in Spanish Americans); B*07:02:01G (Italian Americans allele frequency = 0.11); B*44:03 (Spanish Americans allele frequency = 0.07); C*04:01:01G and C*07:01:01G (allele frequency = 0.13 and 0.16, respectively, in Italian Americans; 0.15 and 0.12, respectively, in Spanish Americans); and DRB1*07:01:01 (allele frequency = 0.12 in each population). The action of balancing selection was inferred at the HLA-B and -C loci in both populations. The A*01:01:01G-C*07:01:01G-B*08:01:01G-DRB1*03:01:01 haplotype was the most frequent A-C-B-DRB1 haplotype in Italian Americans (haplotype frequency = 0.049), and was the second most frequent haplotype in Spanish Americans (haplotype frequency = 0.021). A*29:02:01-C*16:01:01-B*44:03-DRB1*07:01:01 was the most frequent A-C-B-DRB1 haplotype in Spanish Americans (haplotype frequency = 0.023), and was observed at a frequency of 0.015 in Italian Americans. Pairwise F’st values measuring the degree of differentiation between these Southern European-American populations and European and European-American populations suggest that Spanish Americans constitute a distinct subset of the European-American population, most similar to Mexican Americans, whereas Italian Americans cannot be distinguished from the larger European-American population.

Mack, Steven J.; Tu, Bin; Yang, Ruyan; Masaberg, Carly; Ng, Jennifer; Hurley, Carolyn Katovich

2010-01-01

163

Genetic Epidemiology of Glioblastoma Multiforme: Confirmatory and New Findings from Analyses of Human Leukocyte Antigen Alleles and Motifs  

PubMed Central

Background Human leukocyte antigen (HLA) class I genes mediate cytotoxic T-lymphocyte responses and natural killer cell function. In a previous study, several HLA-B and HLA-C alleles and haplotypes were positively or negatively associated with the occurrence and prognosis of glioblastoma multiforme (GBM). Methodology/Principal Findings As an extension of the Upper Midwest Health Study, we have performed HLA genotyping for 149 GBM patients and 149 healthy control subjects from a non-metropolitan population consisting almost exclusively of European Americans. Conditional logistic regression models did not reproduce the association of HLA-B*07 or the B*07-Cw*07 haplotype with GBM. Nonetheless, HLA-A*32, which has previously been shown to predispose GBM patients to a favorable prognosis, was negatively associated with occurrence of GBM (odds ratio?=?0.41, p?=?0.04 by univariate analysis). Other alleles (A*29, A*30, A*31 and A*33) within the A19 serology group to which A*32 belongs showed inconsistent trends. Sequencing-based HLA-A genotyping established that A*3201 was the single A*32 allele underlying the observed association. Additional evaluation of HLA-A promoter and exon 1 sequences did not detect any unexpected single nucleotide polymorphisms that could suggest differential allelic expression. Further analyses restricted to female GBM cases and controls revealed a second association with a specific HLA-B sequence motif corresponding to Bw4-80Ile (odds ratio?=?2.71, p?=?0.02). Conclusions/Significance HLA-A allelic product encoded by A*3201 is likely to be functionally important to GBM. The novel, sex-specific association will require further confirmation in other representative study populations.

Song, Wei; Ruder, Avima M.; Hu, Liangyuan; Li, Yufeng; Ni, Rong; Shao, Wenshuo; Kaslow, Richard A.; Butler, MaryAnn; Tang, Jianming

2009-01-01

164

Paternally transmitted FMR1 alleles are less stable than maternally transmitted alleles in the common and intermediate size range.  

PubMed

Fragile X syndrome, a form of X-linked mental retardation, results from the hyperexpansion of a CGG trinucleotide repeat located in the 5' untranslated region of the fragile X mental retardation (FMR1) gene. Relatively little is known about the initial mutation that causes a stable allele to become unstable and, eventually, to expand to the full mutation. In the present study, we have examined 1,452 parent-child transmissions of alleles of common (< or =39 repeats) or intermediate (40-59 repeats) sizes to study the initial mutation events. Of these, 201 have been sequenced and haplotyped. Using logistic regression analysis, we found that parental origin of transmission, repeat size (for unsequenced alleles), and number of the 3' CGGs (for sequenced alleles) were significant risk factors for repeat instability. Interestingly, transmission of the repeat through males was less stable than that through females, at the common- and intermediate-size level. This pattern differs from that seen for premutation-size alleles: paternally transmitted alleles are far more stable than maternally transmitted alleles. This difference that depends on repeat size suggests either a different mutational mechanism of instability or an increase in selection against sperm as their repeat size increases. PMID:11992259

Sullivan, Amy K; Crawford, Dana C; Scott, Elizabeth H; Leslie, Mary L; Sherman, Stephanie L

2002-05-03

165

Duffy blood group genotyping in French Basques using polymerase chain reaction with allele-specific primers (PCR-ASP).  

PubMed

Blood group antigens such as Duffy represent interesting models for population genetics studies. The distribution of the Duffy blood group was determined using PCR in a sample of Basque (n = 126) and non-Basque (n = 110) patients from the general hospital of the French Basque Country. The frequency of FY*A allele was significantly lower among autochthonous French Basques (P < 0.001). This result, obtained for the first time by PCR analysis in this population, was within the range of previous historical studies in various Basque subpopulations using traditional hemagglutination methods. When compared with European data, our Basque sample demonstrated the lowest FY*A/FY*B ratio, this fact confirming hemotypology data published before the molecular biology era. Our results with FY*X were quite similar to those reported in European populations. PMID:14689518

Bauduer, Frédéric; Touinssi, Mhammed; Degioanni, Anna; Leroux, Stéphane; Dutour, Olivier; Ducout, Louis; De Micco, Philippe; Chiaroni, Jacques

166

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

167

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

168

European Televised Women  

Microsoft Academic Search

This study is based on the analysis of a week of programmes on European television channels. In the news programmes an under-representation of women among the journalists as well as in the news items themselves may be observed. If women are predominant in commercials, they appear there mainly as housewives, whose decisions to purchase a product need to be guided

Gabriel Thoveron

1986-01-01

169

European Polistes venom allergy.  

PubMed

The American Polistes species venom mixture--that of P. annularis, P. fuscatus, P. metricus and P. exclamans--was the only commercially available mixture for diagnosis and therapy until 1996. However, these species of Polistes are not present in Europe, where P. dominulus and P. gallicus and to a lesser extent P. nimphus are widespread. The aim of this study was to assess the allergenic differences among the commercial American mix, P. dominulus and P. gallicus venom in European patients and therefore to verify if this mixture is suitable for diagnosis in these patients. We carried out skin tests, radioallergosorbent tests (RAST) and RAST inhibition in Italian patients with adverse reactions to Polistes stings. RAST inhibition results demonstrated that cross-reactivity between the American and European species is only partial and that P. dominulus and P. gallicus venoms have exclusive allergens. Skin tests and direct RAST confirmed these results and also showed that European Polistes venom is more suitable than the American mix in Italian patients. Moreover, we found a high rate of cross-reactivity between P. dominulus and P. gallicus. To conclude, P. dominulus and/or P. gallicus venoms are necessary for diagnosis and therefore in the therapy of European patients. PMID:16792585

Severino, M G; Campi, P; Macchia, D; Manfredi, M; Turillazzi, S; Spadolini, I; Bilò, M B; Bonifazi, F

2006-07-01

170

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

171

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

172

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.

Vettermann, Christian; Schlissel, Mark S.

2010-01-01

173

Natural allelic variation of duck erythrocyte histone H1b  

Microsoft Academic Search

In our previous work (J. Pa?yga, Genetic polymorphisms of histone H1.b in duck erythrocytes. Hereditas114, 85–89, 1991) we reported a genetic polymorphism of duck erythrocyte histone H1.b. Here, we screened H1 preparations in a two-dimensional polyacrylamide gel to refine the distribution of allelic forms of H1.b in fifteen duck populations. We have revealed that the frequency of H1.b allelic variants

Jan Pa?yga; Ewa Górnicka-Michalska; Andrzej Kowalski; Juliusz Ksi??kiewicz

2000-01-01

174

Analysis of allelic differential expression in human white blood cells  

PubMed Central

Allelic variation of gene expression is common in humans, and is of interest because of its potential contribution to variation in heritable traits. To identify human genes with allelic expression differences, we genotype DNA and examine mRNA isolated from the white blood cells of 12 unrelated individuals using oligonucleotide arrays containing 8406 exonic SNPs. Of the exonic SNPs, 1983, located in 1389 genes, are both expressed in the white blood cells and heterozygous in at least one of the 12 individuals, and thus can be examined for differential allelic expression. Of the 1389 genes, 731 (53%) show allele expression differences in at least one individual. To gain insight into the regulatory mechanisms governing allelic expression differences, we analyze a set of 60 genes containing exonic SNPs that are heterozygous in three or more samples, and for which all heterozygotes display differential expression. We find three patterns of allelic expression, suggesting different underlying regulatory mechanisms. Exonic SNPs in three of the 60 genes are monoallelically expressed in the human white blood cells, and when examined in families show expression of only the maternal copy, consistent with regulation by imprinting. Approximately one-third of the genes have the same allele expressed more highly in all heterozygotes, suggesting that their regulation is predominantly influenced by cis-elements in strong linkage disequilibrium with the assayed exonic SNP. The remaining two-thirds of the genes have different alleles expressed more highly in different heterozygotes, suggesting that their expression differences are influenced by factors not in strong linkage disequilibrium with the assayed exonic SNP.

Pant, P.V. Krishna; Tao, Heng; Beilharz, Erica J.; Ballinger, Dennis G.; Cox, David R.; Frazer, Kelly A.

2006-01-01

175

Allele-specific copy number analysis of tumors  

PubMed Central

We present an allele-specific copy number analysis of the in vivo breast cancer genome. We describe a unique bioinformatics approach, ASCAT (allele-specific copy number analysis of tumors), to accurately dissect the allele-specific copy number of solid tumors, simultaneously estimating and adjusting for both tumor ploidy and nonaberrant cell admixture. This allows calculation of “ASCAT profiles” (genome-wide allele-specific copy-number profiles) from which gains, losses, copy number-neutral events, and loss of heterozygosity (LOH) can accurately be determined. In an early-stage breast carcinoma series, we observe aneuploidy (>2.7n) in 45% of the cases and an average nonaberrant cell admixture of 49%. By aggregation of ASCAT profiles across our series, we obtain genomic frequency distributions of gains and losses, as well as genome-wide views of LOH and copy number-neutral events in breast cancer. In addition, the ASCAT profiles reveal differences in aberrant tumor cell fraction, ploidy, gains, losses, LOH, and copy number-neutral events between the five previously identified molecular breast cancer subtypes. Basal-like breast carcinomas have a significantly higher frequency of LOH compared with other subtypes, and their ASCAT profiles show large-scale loss of genomic material during tumor development, followed by a whole-genome duplication, resulting in near-triploid genomes. Finally, from the ASCAT profiles, we construct a genome-wide map of allelic skewness in breast cancer, indicating loci where one allele is preferentially lost, whereas the other allele is preferentially gained. We hypothesize that these alternative alleles have a different influence on breast carcinoma development.

Van Loo, Peter; Nordgard, Silje H.; Lingjaerde, Ole Christian; Russnes, Hege G.; Rye, Inga H.; Sun, Wei; Weigman, Victor J.; Marynen, Peter; Zetterberg, Anders; Naume, Bj?rn; Perou, Charles M.; Kristensen, Vessela N.

2010-01-01

176

Allele-specific copy number analysis of tumors.  

PubMed

We present an allele-specific copy number analysis of the in vivo breast cancer genome. We describe a unique bioinformatics approach, ASCAT (allele-specific copy number analysis of tumors), to accurately dissect the allele-specific copy number of solid tumors, simultaneously estimating and adjusting for both tumor ploidy and nonaberrant cell admixture. This allows calculation of "ASCAT profiles" (genome-wide allele-specific copy-number profiles) from which gains, losses, copy number-neutral events, and loss of heterozygosity (LOH) can accurately be determined. In an early-stage breast carcinoma series, we observe aneuploidy (>2.7n) in 45% of the cases and an average nonaberrant cell admixture of 49%. By aggregation of ASCAT profiles across our series, we obtain genomic frequency distributions of gains and losses, as well as genome-wide views of LOH and copy number-neutral events in breast cancer. In addition, the ASCAT profiles reveal differences in aberrant tumor cell fraction, ploidy, gains, losses, LOH, and copy number-neutral events between the five previously identified molecular breast cancer subtypes. Basal-like breast carcinomas have a significantly higher frequency of LOH compared with other subtypes, and their ASCAT profiles show large-scale loss of genomic material during tumor development, followed by a whole-genome duplication, resulting in near-triploid genomes. Finally, from the ASCAT profiles, we construct a genome-wide map of allelic skewness in breast cancer, indicating loci where one allele is preferentially lost, whereas the other allele is preferentially gained. We hypothesize that these alternative alleles have a different influence on breast carcinoma development. PMID:20837533

Van Loo, Peter; Nordgard, Silje H; Lingjærde, Ole Christian; Russnes, Hege G; Rye, Inga H; Sun, Wei; Weigman, Victor J; Marynen, Peter; Zetterberg, Anders; Naume, Bjørn; Perou, Charles M; Børresen-Dale, Anne-Lise; Kristensen, Vessela N

2010-09-13

177

Allelic Gene Structure Variations in Anopheles gambiae Mosquitoes  

Microsoft Academic Search

BackgroundAllelic gene structure variations and alternative splicing are responsible for transcript structure variations. More than 75% of human genes have structural isoforms of transcripts, but to date few studies have been conducted to verify the alternative splicing systematically.Methodology\\/Principal FindingsThe present study used expressed sequence tags (ESTs) and EST tagged SNP patterns to examine the transcript structure variations resulting from allelic

Jun Li; Jose M. C. Ribeiro; Guiyun Yan; Juan Valcarcel

2010-01-01

178

Allelic dropout from a high-quality DNA source  

Microsoft Academic Search

Allelic dropouts are an important source of genotyping error, particularly in studies using non-invasive sampling techniques.\\u000a This has important implications for conservation biology, as an increasing number of studies are now using non-invasive techniques\\u000a to study rare species or endangered populations. Previously, allelic dropout has typically been associated with PCR amplification\\u000a of low quality\\/quantity template DNA. However, in this study

Carl D. Soulsbury; Graziella Iossa; Keith J. Edwards; Philip J. Baker; Stephen Harris

2007-01-01

179

Origin of allelic diversity in antirrhinum S locus RNases.  

PubMed Central

In many plant species, self-incompatibility (SI) is genetically controlled by a single multiallelic S locus. Previous analysis of S alleles in the Solanaceae, in which S locus ribonucleases (S RNases) are responsible for stylar expression of SI, has demonstrated that allelic diversity predated speciation within this family. To understand how allelic diversity has evolved, we investigated the molecular basis of gametophytic SI in Antirrhinum, a member of the Scrophulariaceae, which is closely related to the Solanaceae. We have characterized three Antirrhinum cDNAs encoding polypeptides homologous to S RNases and shown that they are encoded by genes at the S locus. RNA in situ hybridization revealed that the Antirrhinum S RNase are primarily expressed in the stylar transmitting tissue. This expression is consistent with their proposed role in arresting the growth of self-pollen tubes. S alleles from the Scrophulariaceae form a separate group from those of the Solanaceae, indicating that new S alleles have been generated since these families separated (approximately 40 million years). We propose that the recruitment of an ancestral RNase gene into SI occurred during an early stage of angiosperm evolution and that, since that time, new alleles subsequently have arisen at a low rate.

Xue, Y; Carpenter, R; Dickinson, H G; Coen, E S

1996-01-01

180

Allele-specific MMP-3 transcription under in vivo conditions  

SciTech Connect

A common matrix metalloproteinases-3 (MMP-3) -1612 5A/6A promoter polymorphism is associated with risk for cardiovascular disease, rheumatoid arthritis, and other diseases. Here we used the haplotype chromatin immunoprecipitation method to study allele-specific MMP-3 expression under in vivo conditions in heterozygous THP-1 cells. Pyrosequencing was used to analyse the ratio of 5A-allele to 6A-allele after chromatin immunoprecipitation using an antibody against phosphorylated active RNA polymerase II. There was no allele-specific difference in transcriptional activity during basal conditions, i.e., in unstimulated monocytic THP-1 cells. However, after stimulation of MMP-3 expression by monocyte differentiation or incubation with IL-1{beta}, the haplotype containing the 5A-allele was associated with higher transcriptional activity compared with the 6A-containing haplotype. Electromobility shift assay demonstrated increased binding of nuclear proteins to the 5A-allele after monocyte differentiation. In conclusion, the common MMP-3 5A/6A promoter polymorphism appears to be functional only during specific environmental conditions involving inflammation.

Zhu Chaoyong [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Odeberg, Jacob [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Department of Biotechnology, AlbaNova University Center, Royal Institute of Technology, Stockholm (Sweden); Hamsten, Anders [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Eriksson, Per [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden)]. E-mail: Per.Eriksson@ki.se

2006-09-29

181

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

Technology Transfer Automated Retrieval System (TEKTRAN)

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

182

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

183

Towards the European Education Metathesaurus.  

ERIC Educational Resources Information Center

Designed to offer a "common language" to all of the parties involved in European cooperation in education, the European Education Metathesaurus is the set made up of the European Education Thesaurus (the third edition of the EUDISED Thesaurus) and the indexing languages that will be attached to it, whether sub-thesauri, specialized vocabularies,…

Roulin, Corentin

184

High allelic heterogeneity between Afro-Brazilians and Euro-Brazilians impacts cystic fibrosis genetic testing.  

PubMed

Cystic fibrosis (CF) is an autosomal recessive disease caused by at least 1,000 different mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR). To determine the frequency of 70 common worldwide CFTR mutations in 155 Euro-Brazilian CF patients and in 38 Afro-Brazilian CF patients, we used direct PCR amplification of DNA from a total of 386 chromosomes from CF patients born in three different states of Brazil. The results show that screening for seventy mutations accounts for 81% of the CF alleles in Euro-Brazilians, but only 21% in the Afro-Brazilian group. We found 21 different mutations in Euro-Brazilians and only 7 mutations in Afro-Brazilians. The frequency of mutations and the number of different mutations detected in Euro-Brazilians are different from Northern European and North American populations, but similar to Southern European populations; in Afro-Brazilians, the mix of CF-mutations is different from those reported in Afro-American CF patients. We also found significant differences in detection rates between Euro-Brazilian (75%) and Afro-Brazilian CF patients (21%) living in the same state, Minas Gerais. These results, therefore, have implications for the use of DNA-based tests for risk assessment in heterogeneous populations like the Brazilians. Further studies are needed to identify the remaining CF mutations in the different populations and regions of Brazil. PMID:14641997

Raskin, Salmo; Pereira, Lilian; Reis, Francisco; Rosario, Nelson A; Ludwig, Norberto; Valentim, Lairton; Phillips, John A; Allito, Bernice; Heim, Ruth A; Sugarman, Elaine A; Probst, Christian M; Faucz, Fabio; Culpi, Lodercio

2003-01-01

185

A study of a single variant allele (rs1426654) of the pigmentation-related gene SLC24A5 in Greek subjects.  

PubMed

The SLC24A5 gene, the human orthologue of the zebrafish golden gene, has been shown to play a key role in human pigmentation. In this study, we investigate the prevalence of the variant allele rs1426654 in a selected sample of Greek subjects. Allele-specific polymerase chain reaction was performed in peripheral blood samples from 158 attendants of a dermatology outpatient service. The results were correlated with pigmentary traits and MC1R genotype. The vast majority of subjects (99%) were homozygous for the Thr(111) allele. Only two subjects from the control group (1.26%) were heterozygous for the alanine and threonine allele. Both of these Thr(111)/Ala(111) heterozygotes carried a single polymorphism of MC1R (one with the V92M variant and another with the V60L variant). Following reports of the rs1426654 polymorphism reaching fixation in the European population, our study of Greek subjects showed a prevalence of the Thr(111) allele, even among subjects with darker skin pigmentation or phototype. PMID:18637132

Dimisianos, Gerasimos; Stefanaki, Irene; Nicolaou, Vicky; Sypsa, Vana; Antoniou, Christina; Poulou, Myrto; Papadopoulos, Othon; Gogas, Helen; Kanavakis, Emmanouel; Nicolaidou, Electra; Katsambas, Andreas D; Stratigos, Alexander J

2008-07-07

186

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.

187

The European Nucleotide Archive  

PubMed Central

The European Nucleotide Archive (ENA; http://www.ebi.ac.uk/ena) is Europe’s primary nucleotide-sequence repository. The ENA consists of three main databases: the Sequence Read Archive (SRA), the Trace Archive and EMBL-Bank. The objective of ENA is to support and promote the use of nucleotide sequencing as an experimental research platform by providing data submission, archive, search and download services. In this article, we outline these services and describe major changes and improvements introduced during 2010. These include extended EMBL-Bank and SRA-data submission services, extended ENA Browser functionality, support for submitting data to the European Genome-phenome Archive (EGA) through SRA, and the launch of a new sequence similarity search service.

Leinonen, Rasko; Akhtar, Ruth; Birney, Ewan; Bower, Lawrence; Cerdeno-Tarraga, Ana; Cheng, Ying; Cleland, Iain; Faruque, Nadeem; Goodgame, Neil; Gibson, Richard; Hoad, Gemma; Jang, Mikyung; Pakseresht, Nima; Plaister, Sheila; Radhakrishnan, Rajesh; Reddy, Kethi; Sobhany, Siamak; Ten Hoopen, Petra; Vaughan, Robert; Zalunin, Vadim; Cochrane, Guy

2011-01-01

188

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.

189

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

190

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

191

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.

1999-01-01

192

THE EUROPEAN XFEL PROJECT  

Microsoft Academic Search

The European X-ray Free Electron Laser XFEL is a 4th generation synchrotron radiation facility based on the SASE FEL concept and the superconducting TESLA technology for the linear accelerator. This multi-user facility will provide photon beams in a wavelength regime from 0.1nm to 5nm in three FEL beam lines and hard X-rays in two spontaneous radiation beam lines, serving in

R. Brinkmann

193

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.

194

Expanding Allelic Diversity of Helicobacter pylori vacA  

PubMed Central

The diversity of the gene encoding the vacuolating cytotoxin (vacA) of Helicobacter 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 previously described s1a, s1b, and s2 allelic types, a novel subtype, designated s1c, was found. Subtype s1c was observed exclusively in isolates from East Asia and appears to be the major s1 allele in that part of the world. Three different allelic forms (m1, m2a, and m2b) were detected in the m region. On the basis of sequence alignments, universal PCR primers that allow effective amplification of the s and m regions from H. pylori isolates from all over the world were defined. Amplimers were subsequently analyzed by reverse hybridization onto a line probe assay (LiPA) that allows the simultaneous and highly specific hybridization of the different vacA s- and m-region alleles and tests for the presence of the cytotoxin-associated gene (cagA). This PCR-LiPA method permits rapid analysis of the vacA and cagA status of H. pylori strains for clinical and epidemiological studies and will facilitate identification of any further variations.

van Doorn, Leen-Jan; Figueiredo, Ceu; Sanna, Ricardo; Pena, Salvador; Midolo, Peter; Ng, Enders K. W.; Atherton, John C.; Blaser, Martin J.; Quint, Wim G. V.

1998-01-01

195

Evaluation of Allele Frequency Estimation Using Pooled Sequencing Data Simulation  

PubMed Central

Next-generation sequencing (NGS) technology has provided researchers with opportunities to study the genome in unprecedented detail. In particular, NGS is applied to disease association studies. Unlike genotyping chips, NGS is not limited to a fixed set of SNPs. Prices for NGS are now comparable to the SNP chip, although for large studies the cost can be substantial. Pooling techniques are often used to reduce the overall cost of large-scale studies. In this study, we designed a rigorous simulation model to test the practicability of estimating allele frequency from pooled sequencing data. We took crucial factors into consideration, including pool size, overall depth, average depth per sample, pooling variation, and sampling variation. We used real data to demonstrate and measure reference allele preference in DNAseq data and implemented this bias in our simulation model. We found that pooled sequencing data can introduce high levels of relative error rate (defined as error rate divided by targeted allele frequency) and that the error rate is more severe for low minor allele frequency SNPs than for high minor allele frequency SNPs. In order to overcome the error introduced by pooling, we recommend a large pool size and high average depth per sample.

Guo, Yan; Samuels, David C.; Li, Jiang; Clark, Travis; Li, Chung-I; Shyr, Yu

2013-01-01

196

Rare allelic forms of PRDM9 associated with childhood leukemogenesis  

PubMed Central

One of the most rapidly evolving genes in humans, PRDM9, is a key determinant of the distribution of meiotic recombination events. Mutations in this meiotic-specific gene have previously been associated with male infertility in humans and recent studies suggest that PRDM9 may be involved in pathological genomic rearrangements. In studying genomes from families with children affected by B-cell precursor acute lymphoblastic leukemia (B-ALL), we characterized meiotic recombination patterns within a family with two siblings having hyperdiploid childhood B-ALL and observed unusual localization of maternal recombination events. The mother of the family carries a rare PRDM9 allele, potentially explaining the unusual patterns found. From exomes sequenced in 44 additional parents of children affected with B-ALL, we discovered a substantial and significant excess of rare allelic forms of PRDM9. The rare PRDM9 alleles are transmitted to the affected children in half the cases; nonetheless there remains a significant excess of rare alleles among patients relative to controls. We successfully replicated this latter observation in an independent cohort of 50 children with B-ALL, where we found an excess of rare PRDM9 alleles in aneuploid and infant B-ALL patients. PRDM9 variability in humans is thought to influence genomic instability, and these data support a potential role for PRDM9 variation in risk of acquiring aneuploidies or genomic rearrangements associated with childhood leukemogenesis.

Hussin, Julie; Sinnett, Daniel; Casals, Ferran; Idaghdour, Youssef; Bruat, Vanessa; Saillour, Virginie; Healy, Jasmine; Grenier, Jean-Christophe; de Malliard, Thibault; Busche, Stephan; Spinella, Jean-Francois; Lariviere, Mathieu; Gibson, Greg; Andersson, Anna; Holmfeldt, Linda; Ma, Jing; Wei, Lei; Zhang, Jinghui; Andelfinger, Gregor; Downing, James R.; Mullighan, Charles G.; Awadalla, Philip

2013-01-01

197

Allele-dependent barley grain beta-amylase activity.  

PubMed

The wild ancestor of cultivated barley, Hordeum vulgare subsp. spontaneum (K. Koch) A. & Gr. (H. spontaneum), is a source of wide genetic diversity, including traits that are important for malting quality. A high beta-amylase trait was previously identified in H. spontaneum strains from Israel, and transferred into the backcross progeny of a cross with the domesticated barley cv Adorra. We have used Southern-blot analysis and beta-amy1 gene characterization to demonstrate that the high beta-amylase trait in the backcross line is co-inherited with the beta-amy1 gene from the H. spontaneum parent. We have analyzed the beta-amy1 gene organization in various domesticated and wild-type barley strains and identified three distinct beta-amy1 alleles. Two of these beta-amy1 alleles were present in modern barley, one of which was specifically found in good malting barley cultivars. The third allele, linked with high grain beta-amylase activity, was found only in a H. spontaneum strain from the Judean foothills in Israel. The sequences of three isolated beta-amy1 alleles are compared. The involvement of specific intron III sequences, in particular a 126-bp palindromic insertion, in the allele-dependent expression of beta-amylase activity in barley grain is proposed. PMID:9625721

Erkkilä, M J; Leah, R; Ahokas, H; Cameron-Mills, V

1998-06-01

198

Evaluation of allele frequency estimation using pooled sequencing data simulation.  

PubMed

Next-generation sequencing (NGS) technology has provided researchers with opportunities to study the genome in unprecedented detail. In particular, NGS is applied to disease association studies. Unlike genotyping chips, NGS is not limited to a fixed set of SNPs. Prices for NGS are now comparable to the SNP chip, although for large studies the cost can be substantial. Pooling techniques are often used to reduce the overall cost of large-scale studies. In this study, we designed a rigorous simulation model to test the practicability of estimating allele frequency from pooled sequencing data. We took crucial factors into consideration, including pool size, overall depth, average depth per sample, pooling variation, and sampling variation. We used real data to demonstrate and measure reference allele preference in DNAseq data and implemented this bias in our simulation model. We found that pooled sequencing data can introduce high levels of relative error rate (defined as error rate divided by targeted allele frequency) and that the error rate is more severe for low minor allele frequency SNPs than for high minor allele frequency SNPs. In order to overcome the error introduced by pooling, we recommend a large pool size and high average depth per sample. PMID:23476151

Guo, Yan; Samuels, David C; Li, Jiang; Clark, Travis; Li, Chung-I; Shyr, Yu

2013-02-07

199

An African Ancestry-Specific Allele of CTLA4 Confers Protection against Rheumatoid Arthritis in African Americans  

PubMed Central

Cytotoxic T-lymphocyte associated protein 4 (CTLA4) is a negative regulator of T-cell proliferation. Polymorphisms in CTLA4 have been inconsistently associated with susceptibility to rheumatoid arthritis (RA) in populations of European ancestry but have not been examined in African Americans. The prevalence of RA in most populations of European and Asian ancestry is ?1.0%; RA is purportedly less common in black Africans, with little known about its prevalence in African Americans. We sought to determine if CTLA4 polymorphisms are associated with RA in African Americans. We performed a 2-stage analysis of 12 haplotype tagging single nucleotide polymorphisms (SNPs) across CTLA4 in a total of 505 African American RA patients and 712 African American controls using Illumina and TaqMan platforms. The minor allele (G) of the rs231778 SNP was 0.054 in RA patients, compared to 0.209 in controls (4.462×10?26, Fisher's exact). The presence of the G allele was associated with a substantially reduced odds ratio (OR) of having RA (AG+GG genotypes vs. AA genotype, OR 0.19, 95% CI: 0.13–0.26, p?=?2.4×10?28, Fisher's exact), suggesting a protective effect. This SNP is polymorphic in the African population (minor allele frequency [MAF] 0.09 in the Yoruba population), but is very rare in other groups (MAF?=?0.002 in 530 Caucasians genotyped for this study). Markers associated with RA in populations of European ancestry (rs3087243 [+60C/T] and rs231775 [+49A/G]) were not replicated in African Americans. We found no confounding of association for rs231778 after stratifying for the HLA-DRB1 shared epitope, presence of anti-cyclic citrullinated peptide antibody, or degree of admixture from the European population. An African ancestry-specific genetic variant of CTLA4 appears to be associated with protection from RA in African Americans. This finding may explain, in part, the relatively low prevalence of RA in black African populations.

Kelley, James M.; Hughes, Laura B.; Faggard, Jeffrey D.; Danila, Maria I.; Crawford, Monica H.; Edberg, Yuanqing; Padilla, Miguel A.; Tiwari, Hemant K.; Westfall, Andrew O.; Alarcon, Graciela S.; Conn, Doyt L.; Jonas, Beth L.; Callahan, Leigh F.; Smith, Edwin A.; Brasington, Richard D.; Allison, David B.; Kimberly, Robert P.; Moreland, Larry W.; Edberg, Jeffrey C.; Bridges, S. Louis

2009-01-01

200

Glutathione-S-transferase gene polymorphism in Russian populations of European part of Russia  

Microsoft Academic Search

Distribution of several widespread, extensively studied polymorphic variants of genes of the cytosol glutathione-S-transferase\\u000a subfamily (GSTA1, GSTM1, GSTM3, GSTP1, and GSTT1) has been studied in samples from Russian populations of European Russia, as well as Komi and Yakut populations used for\\u000a comparison. Analysis of the GSTP1 and GSTM3 polymorphisms has not revealed significant differences in the distribution of alleles of

A. V. Khrunin; D. V. Khokhrin; S. A. Limborska

2008-01-01

201

FRAXE intermediate alleles are associated with Parkinson's disease.  

PubMed

There is evidence that male subjects with a clinical picture of action tremor, Parkinsonism, and cerebellar ataxia may have Fragile X premutations (FRAXA). We analyzed FRAXA and FRAXE triplet repeats in 203 male subjects with Parkinson's disease (PD) and 370 healthy controls. No full mutations or premutations at the FRAXA and FRAXE loci were found in the subjects with PD or in the controls. FRAXA allele distribution was similar in patients and controls. FRAXE intermediate alleles (31-60 repeats CCG) were found in 13 of 203 (6.4%) subjects with PD and in only one of the 370 (0.27%) healthy controls (P < 0.001), thus indicating that these relatively large alleles may be associated with PD. PMID:15342126

Annesi, Grazia; Nicoletti, Giuseppe; Tarantino, Patrizia; Cutuli, Nunzio; Annesi, Ferdinanda; Marco, Elvira Valeria De; Zappia, Mario; Morgante, Letterio; Arabia, Gennarina; Pugliese, Pierfrancesco; Condino, Francesca; Carrideo, Sara; Civitelli, Donatella; Caracciolo, Manuela; Romeo, Nelide; Spadafora, Patrizia; Candiano, Innocenza Cirò; Quattrone, Aldo

2004-09-16

202

Extensive HLA class I allele promiscuity among viral CTL epitopes.  

PubMed

Promiscuous binding of T helper epitopes to MHC class II molecules has been well established, but few examples of promiscuous class I-restricted epitopes exist. To address the extent of promiscuity of HLA class I peptides, responses to 242 well-defined viral epitopes were tested in 100 subjects regardless of the individuals' HLA type. Surprisingly, half of all detected responses were seen in the absence of the originally reported restricting HLA class I allele, and only 3% of epitopes were recognized exclusively in the presence of their original allele. Functional assays confirmed the frequent recognition of HLA class I-restricted T cell epitopes on several alternative alleles across HLA class I supertypes and encoded on different class I loci. These data have significant implications for the understanding of MHC class I-restricted antigen presentation and vaccine development. PMID:17705138

Frahm, Nicole; Yusim, Karina; Suscovich, Todd J; Adams, Sharon; Sidney, John; Hraber, Peter; Hewitt, Hannah S; Linde, Caitlyn H; Kavanagh, Daniel G; Woodberry, Tonia; Henry, Leah M; Faircloth, Kellie; Listgarten, Jennifer; Kadie, Carl; Jojic, Nebojsa; Sango, Kaori; Brown, Nancy V; Pae, Eunice; Zaman, M Tauheed; Bihl, Florian; Khatri, Ashok; John, Mina; Mallal, Simon; Marincola, Francesco M; Walker, Bruce D; Sette, Alessandro; Heckerman, David; Korber, Bette T; Brander, Christian

2007-09-01

203

Researching the European Union  

NSDL National Science Digital Library

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

1997-01-01

204

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.

205

Eastern European risk management  

SciTech Connect

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

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

1992-01-01

206

Characterization of Allozyme Null and Low Activity Alleles from Two Natural Populations of DROSOPHILA MELANOGASTER  

PubMed Central

Null and low enzyme activity alleles recovered from two natural populations were analyzed for a number of genetic and biochemical properties. Analysis of 58 mutations at 14 loci showed that all but one allele were genetically viable and fertile, four alleles were associated with chromosome rearrangements, 28 alleles retained some enzyme activity, 13 alleles formed an active heterodimer with active alleles and five alleles showed partial interallelic complementation. Available evidence indicates that this sample includes mutations resulting from lesions in both coding and regulatory sequences. Certain mutations may be caused by transposable element insertions.

Burkhart, Barbara Dickson; Montgomery, Elizabeth; Langley, Charles H.; Voelker, Robert A.

1984-01-01

207

Increased transmission of intermediate alleles of the FMR1 gene compared with normal alleles among female heterozygotes.  

PubMed

Fragile X syndrome (Fra X) is the most common heritable disease accounting for mental retardation and is caused by an expanded CGG repeat in the first exon of the FMR1gene. Previous studies have shown an increased fertility rate among fragile X carrier mothers and a preponderance of mentally retarded boys among the male offspring. In this study, we examined the transmission of the intermediate allele in the lower range of CGG repeats in carrier mothers found randomly in a screening program of the normal population. We tested 10,587 healthy women with no family history of mental retardation and identified 138 (1.3%) who were carriers of the intermediate allele (51-200 CGG repeats). Of these, 107 underwent prenatal testing during 108 pregnancies for Fra X in the fetus. Of the 108 pregnancies, the abnormal allele was transmitted in 67 (segregation ratio = 0.62, P < 0.012). We found a significant increase in the transmission of the abnormal allele by mothers who had between 51 and 60 repeats (segregation ratio = 0.69 [P < 0.007] for the group with 51-55 repeats, and 0.74 [P < 0.04] for the group with 56-60 repeats), but no increase by mothers who had more than 61 repeats. This suggests a genetic advantage for the abnormal allele in the 51- to 60-repeat range. PMID:10869119

Drasinover, V; Ehrlich, S; Magal, N; Taub, E; Libman, V; Shohat, T; Halpern, G J; Shohat, M

2000-07-17

208

The CFTR Met 470 Allele Is Associated with Lower Birth Rates in Fertile Men from a Population Isolate  

PubMed Central

Although little is known about the role of the cystic fibrosis transmembrane regulator (CFTR) gene in reproductive physiology, numerous variants in this gene have been implicated in etiology of male infertility due to congenital bilateral absence of the vas deferens (CBAVD). Here, we studied the fertility effects of three CBAVD–associated CFTR polymorphisms, the (TG)m and polyT repeat polymorphisms in intron 8 and Met470Val in exon 10, in healthy men of European descent. Homozygosity for the Met470 allele was associated with lower birth rates, defined as the number of births per year of marriage (P?=?0.0029). The Met470Val locus explained 4.36% of the phenotypic variance in birth rate, and men homozygous for the Met470 allele had 0.56 fewer children on average compared to Val470 carrier men. The derived Val470 allele occurs at high frequencies in non-African populations (allele frequency ?=?0.51 in HapMap CEU), whereas it is very rare in African population (Fst ?=?0.43 between HapMap CEU and YRI). In addition, haplotypes bearing Val470 show a lack of genetic diversity and are thus longer than haplotypes bearing Met470 (measured by an integrated haplotype score [iHS] of ?1.93 in HapMap CEU). The fraction of SNPs in the HapMap Phase2 data set with more extreme Fst and iHS measures is 0.003, consistent with a selective sweep outside of Africa. The fertility advantage conferred by Val470 relative to Met470 may provide a selective mechanism for these population genetic observations.

Kosova, Gulum; Pickrell, Joseph K.; Kelley, Joanna L.; McArdle, Patrick F.; Shuldiner, Alan R.; Abney, Mark; Ober, Carole

2010-01-01

209

A common mutation associated with the Duarte galactosemia allele  

SciTech Connect

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

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

1994-06-01

210

A common mutation associated with the Duarte galactosemia allele.  

PubMed Central

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

Elsas, L. J.; Dembure, P. P.; Langley, S.; Paulk, E. M.; Hjelm, L. N.; Fridovich-Keil, J.

1994-01-01

211

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

212

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

PubMed

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

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

2012-02-12

213

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

214

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.

1997-01-01

215

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

216

Clonal Ordering of 17p and 5q Allelic Losses in Barrett Dysplasia and Adenocarcinoma  

NASA Astrophysics Data System (ADS)

Both 17p and 5q allelic losses appear to be involved in the pathogenesis or progression of many human solid tumors. In colon carcinogenesis, there is strong evidence that the targets of the 17p and 5q allelic losses are TP53, the gene encoding p53, and APC, respectively. It is widely accepted that 5q allelic losses precede 17p allelic losses in the progression to colonic carcinoma. The data, however, supporting this proposed order are largely based on the prevalence of 17p and 5q allelic losses in adenomas and unrelated adenocarcinomas from different patients. We investigated the order in which 17p and 5q allelic losses developed during neoplastic progression in Barrett esophagus by evaluating multiple aneuploid cell populations from the same patient. Using DNA content flow cytometric cell sorting and polymerase chain reaction, 38 aneuploid cell populations from 14 patients with Barrett esophagus who had high grade dysplasia, cancer or both were evaluated for 17p and 5q allelic losses. 17p allelic losses preceded 5q allelic losses in 7 patients, both 17p and 5q allelic losses were present in all aneuploid populations of 4 patients, and only 17p (without 5q) allelic losses were present in the aneuploid populations of 3 patients. In no patient did we find that a 5q allelic loss preceded a 17p allelic loss. Our data suggest that 17p allelic losses typically occur before 5q allelic losses during neoplastic progression in Barrett esophagus.

Blount, Patricia L.; Meltzer, Stephen J.; Yin, Jing; Huang, Ying; Krasna, Mark J.; Reid, Brian J.

1993-04-01

217

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

218

European television: politics and broadcasting in the European Community  

Microsoft Academic Search

The paper takes the European media revolution as its starting point and traces the history of the European Community's (EC's) first major legislation on audiovisual internationalization and deregulation-the `television without frontiers' directive on broadcasting. Specifically, the aims of the EC's audiovisual policy are characterized as tenuously resolving two conflicting models of broadcast regulation-the trusteeship model and the marketplace model. An

Mitch Baranowski

1993-01-01

219

A commonly carried allele of the obesity-related FTO gene is associated with reduced brain volume in the healthy elderly  

PubMed Central

A recently identified variant within the fat mass and obesity-associated (FTO) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

Stein, Jason L.; Hua, Xue; Lee, Suh; Hibar, Derrek P.; Leow, Alex D.; Dinov, Ivo D.; Toga, Arthur W.; Saykin, Andrew J.; Shen, Li; Foroud, Tatiana; Pankratz, Nathan; Huentelman, Matthew J.; Craig, David W.; Gerber, Jill D.; Allen, April N.; Corneveaux, Jason J.; Stephan, Dietrich A.; DeCarli, Charles S.; DeChairo, Bryan M.; Potkin, Steven G.; Jack, Clifford R.; Weiner, Michael W.; Raji, Cyrus A.; Lopez, Oscar L.; Becker, James T.; Carmichael, Owen T.; Thompson, Paul M.; Weiner, Michael; Thal, Leon; Petersen, Ronald; Jack, Clifford R.; Jagust, William; Trojanowki, John; Toga, Arthur W.; Beckett, Laurel; Green, Robert C.; Gamst, Anthony; Potter, William Z.; Montine, Tom; Anders, Dale; Bernstein, Matthew; Felmlee, Joel; Fox, Nick; Thompson, Paul; Schuff, Norbert; Alexander, Gene; Bandy, Dan; Koeppe, Robert A.; Foster, Norm; Reiman, Eric M.; Chen, Kewei; Trojanowki, John; Shaw, Les; Lee, Virginia M.-Y.; Korecka, Magdalena; Toga, Arthur W.; Crawford, Karen; Neu, Scott; Harvey, Danielle; Gamst, Anthony; Kornak, John; Kachaturian, Zaven; Frank, Richard; Snyder, Peter J.; Molchan, Susan; Kaye, Jeffrey; Vorobik, Remi; Quinn, Joseph; Schneider, Lon; Pawluczyk, Sonia; Spann, Bryan; Fleisher, Adam S.; Vanderswag, Helen; Heidebrink, Judith L.; Lord, Joanne L.; Johnson, Kris; Doody, Rachelle S.; Villanueva-Meyer, Javier; Chowdhury, Munir; Stern, Yaakov; Honig, Lawrence S.; Bell, Karen L.; Morris, John C.; Mintun, Mark A.; Schneider, Stacy; Marson, Daniel; Griffith, Randall; Badger, Beverly; Grossman, Hillel; Tang, Cheuk; Stern, Jessica; deToledo-Morrell, Leyla; Shah, Raj C.; Bach, Julie; Duara, Ranjan; Isaacson, Richard; Strauman, Silvia; Albert, Marilyn S.; Pedroso, Julia; Toroney, Jaimie; Rusinek, Henry; de Leon, Mony J; De Santi, Susan M; Doraiswamy, P. Murali; Petrella, Jeffrey R.; Aiello, Marilyn; Clark, Christopher M.; Pham, Cassie; Nunez, Jessica; Smith, Charles D.; Given II, Curtis A.; Hardy, Peter; DeKosky, Steven T.; Oakley, MaryAnn; Simpson, Donna M.; Ismail, M. Saleem; Porsteinsson, Anton; McCallum, Colleen; Cramer, Steven C.; Mulnard, Ruth A.; McAdams-Ortiz, Catherine; Diaz-Arrastia, Ramon; Martin-Cook, Kristen; DeVous, Michael; Levey, Allan I.; Lah, James J.; Cellar, Janet S.; Burns, Jeffrey M.; Anderson, Heather S.; Laubinger, Mary M.; Bartzokis, George; Silverman, Daniel H.S.; Lu, Po H.; Fletcher, Rita; Parfitt, Francine; Johnson, Heather; Farlow, Martin; Herring, Scott; Hake, Ann M.; van Dyck, Christopher H.; MacAvoy, Martha G.; Bifano, Laurel A.; Chertkow, Howard; Bergman, Howard; Hosein, Chris; Black, Sandra; Graham, Simon; Caldwell, Curtis; Feldman, Howard; Assaly, Michele; Hsiung, Ging-Yuek R.; Kertesz, Andrew; Rogers, John; Trost, Dick; Bernick, Charles; Gitelman, Darren; Johnson, Nancy; Mesulam, Marsel; Sadowsky, Carl; Villena, Teresa; Mesner, Scott; Aisen, Paul S.; Johnson, Kathleen B.; Behan, Kelly E.; Sperling, Reisa A.; Rentz, Dorene M.; Johnson, Keith A.; Rosen, Allyson; Tinklenberg, Jared; Ashford, Wes; Sabbagh, Marwan; Connor, Donald; Obradov, Sanja; Killiany, Ron; Norbash, Alex; Obisesan, Thomas O.; Jayam-Trouth, Annapurni; Wang, Paul; Auchus, Alexander P.; Huang, Juebin; Friedland, Robert P.; DeCarli, Charles; Fletcher, Evan; Carmichael, Owen; Kittur, Smita; Mirje, Seema; Johnson, Sterling C.; Borrie, Michael; Lee, T-Y; Asthana, Sanjay; Carlsson, Cynthia M.; Potkin, Steven G.; Highum, Diane; Preda, Adrian; Nguyen, Dana; Tariot, Pierre N.; Hendin, Barry A.; Scharre, Douglas W.; Kataki, Maria; Beversdorf, David Q.; Zimmerman, Earl A.; Celmins, Dzintra; Brown, Alice D.; Gandy, Sam; Marenberg, Marjorie E.; Rovner, Barry W.; Pearlson, Godfrey; Blank, Karen; Anderson, Karen; Saykin, Andrew J.; Santulli, Robert B.; Pare, Nadia; Williamson, Jeff D.; Sink, Kaycee M.; Potter, Huntington; Ashok Raj, B.; Giordano, Amy; Ott, Brian R.; Wu, Chuang-Kuo; Cohen, Ronald; Wilks, Kerri L.

2010-01-01

220

The clinical spectrum of complete FBN1 allele deletions  

Microsoft Academic Search

The most common mutations found in FBN1 are missense mutations (56%), mainly substituting or creating a cysteine in a cbEGF domain. Other mutations are frameshift, splice and nonsense mutations. There are only a few reports of patients with marfanoid features and a molecularly proven complete deletion of a FBN1 allele. We describe the clinical features of 10 patients with a

Yvonne Hilhorst-Hofstee; Ben CJ Hamel; Joke BGM Verheij; Marry EB Rijlaarsdam; Jan M Cobben; Cindy Giroth; Claudia AL Ruivenkamp; Kerstin BM Hansson; Janneke Timmermans; Henriette A Moll; Martijn H Breuning; Gerard Pals

2011-01-01

221

Efficient nonmeiotic allele introgression in livestock using custom endonucleases  

PubMed Central

We have expanded the livestock gene editing toolbox to include transcription activator-like (TAL) effector nuclease (TALEN)- and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-stimulated homology-directed repair (HDR) using plasmid, rAAV, and oligonucleotide templates. Toward the genetic dehorning of dairy cattle, we introgressed a bovine POLLED allele into horned bull fibroblasts. Single nucleotide alterations or small indels were introduced into 14 additional genes in pig, goat, and cattle fibroblasts using TALEN mRNA and oligonucleotide transfection with efficiencies of 10–50% in populations. Several of the chosen edits mimic naturally occurring performance-enhancing or disease- resistance alleles, including alteration of single base pairs. Up to 70% of the fibroblast colonies propagated without selection harbored the intended edits, of which more than one-half were homozygous. Edited fibroblasts were used to generate pigs with knockout alleles in the DAZL and APC genes to model infertility and colon cancer. Our methods enable unprecedented meiosis-free intraspecific and interspecific introgression of select alleles in livestock for agricultural and biomedical applications.

Tan, Wenfang; Carlson, Daniel F.; Lancto, Cheryl A.; Garbe, John R.; Webster, Dennis A.; Hackett, Perry B.; Fahrenkrug, Scott C.

2013-01-01

222

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

223

Allelism and Molecular Mapping of Soybean Necrotic Root Mutants  

Technology Transfer Automated Retrieval System (TEKTRAN)

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

224

Natural allelic variation of duck erythrocyte histone H1b.  

PubMed

In our previous work (J. Palyga, Genetic polymorphisms of histone H1. b in duck erythrocytes. Hereditas 114, 85-89, 1991) we reported a genetic polymorphism of duck erythrocyte histone H1.b. Here, we screened H1 preparations in a two-dimensional polyacrylamide gel to refine the distribution of allelic forms of H1.b in fifteen duck populations. We have revealed that the frequency of H1.b allelic variants was significantly different among many conservative and breeding duck groups. While b(1) and b(3) were common in all populations screened, the allele b(2), with a slightly lower apparent molecular weight, was confined mainly to brown-feathered ducks (Khaki Campbell and Orpington) and descendent lines. The C- and N-terminal peptides released upon cleavage with N-bromosuccinimide and Staphylococcus aureus protease V8 from duck allelic histones H1. b2 and H1.b3, respectively, migrated differently in the gel, probably as a result of potential amino acid variation in a C-terminal domain. PMID:10785363

Pa?yga, J; Górnicka-Michalska, E; Kowalski, A; Ksiazkiewicz, J

2000-06-01

225

Rescue of Progeria in Trichothiodystrophy by Homozygous Lethal Xpd Alleles  

Microsoft Academic Search

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

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

2006-01-01

226

Haplotype allelic classes for detecting ongoing positive selection  

PubMed Central

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

2010-01-01

227

Chromosome 11 allele imbalance and clinicopathological correlates in ovarian tumours.  

PubMed Central

Allele imbalance on chromosome 11 loci in ovarian cancer is a frequent event, suggesting the presence of tumour-suppressor genes for ovarian carcinogenesis on this chromosome. Ten highly polymorphic (CA) repeat microsatellites were used to determine allele imbalance in 60 primary ovarian tumours, including 47 epithelial ovarian cancers (EOCs). Forty EOCs (85%) showed allele imbalance at one or more loci, and in 39 of these (83%) the data suggested subchromosomal deletions: eight of 11p only; six of 11q only; and 25 of both 11p and 11q. Three consensus regions of deletion were indicated at 11p15.5-p15.3, 11q12-q22 and 11q23.3-q24.1. Allele imbalance at the 11q subtelomeric region (D11S912) correlated significantly with adverse survival, while imbalance at 11q14.3 and retention of heterozygosity at 11q22 (close to the site of the progesterone receptor gene) were associated with favourable clinicopathological features. The findings allow development of a preliminary model for the molecular evolution of epithelial ovarian cancer. Images Figure 1

Gabra, H.; Taylor, L.; Cohen, B. B.; Lessels, A.; Eccles, D. M.; Leonard, R. C.; Smyth, J. F.; Steel, C. M.

1995-01-01

228

Systematic underestimation of the age of selected alleles  

PubMed Central

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

Kelley, Joanna L.

2012-01-01

229

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...

230

Allele frequency distribution for 21 autosomal STR loci in Bhutan  

Microsoft Academic Search

We studied the allele frequency distribution of 21 autosomal STR loci contained in the AmpFlSTR® Identifiler™ (Applied Biosystems), the Powerplex®16 (Promega) and the FFFL (Promega) multiplex PCR kits among 936 individuals from the Royal Kingdom of Bhutan. As such these are the first published autosomal DNA results from this country.

Thirsa Kraaijenbrink; George L. van Driem; Peter de Knijff

2007-01-01

231

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 ...

232

Associations between HLA-C alleles and definite Meniere's disease.  

PubMed

Both genetic and environmental factors seem to play role in the etiology of Meniere's disease (MD). Several genes may be involved in susceptibility of MD including Human Leukocyte Antigens (HLA). The associations between MD and HLA alleles have been previously studied in other populations and certain HLA alleles were shown to be predisposing. The aim of this study was to determine the association between HLA-C allele frequencies and definite MD in patients who refer to Amir-Alam otolaryngology tertiary referral center in Tehran. Patients with definite MD (N=22) enrolled according to the diagnostic criteria of American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS). Cases with all 3 symptoms of MD (Vertigo, Tinnitus and lower frequency of sensory-neural hearing loss) were included and those with suspected MD were excluded from study. HLA-Cw allele frequencies were determined in patients non-related healthy controls (N=91) using PCR -SSP. We found that the frequency of HLACw*04 was significantly higher in patients compared to the controls [P = 0.0015, OR; 20, 95% CI (3.7-196.9)]. Our results revealed that HLA-C is a genetic predisposing factor in definite MD in patients who refer to Amir-Alam otolaryngology tertiary referral center. PMID:21625020

Khorsandi, Mohammad-Taghi; Amoli, Mahsa M; Borghei, Hebatodin; Emami, Hamed; Amiri, Parvin; Amirzargar, Ali; Yazdani, Nasrin

2011-06-01

233

Generation of conditional knockout alleles for PDGF-C.  

PubMed

PDGF-C is a newly identified member of the platelet-derived growth factor (PDGF) family, which is involved in multiple cellular functions by signaling through PDGF receptor (PDGFR)-alphaalpha and alphabeta dimers. PDGF-C deficiency is perinatal lethal due to the formation of cleft palate. To further characterize the cellular function of PDGF-C during both embryonic and postnatal development, we have generated two conditional alleles of the Pdgf-c gene in which two loxP sites flank exon 5. Global Cre-mediated excision of the floxed exon 5 in these alleles resulted in a complete loss of PDGF-C expression and caused embryonic defects identical to those previously described for the PDGF-C null embryos. These conditional alleles will therefore be the important genetic tools for dissecting the spatial and temporal roles of PDGF-C during development and in adult tissues. Furthermore, from this work, we have also described a simple approach for creating mouse conditional alleles in an efficient manner. PMID:17941048

Wu, Xiaoli; Ding, Hao

2007-10-01

234

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

235

Efficient nonmeiotic allele introgression in livestock using custom endonucleases.  

PubMed

We have expanded the livestock gene editing toolbox to include transcription activator-like (TAL) effector nuclease (TALEN)- and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-stimulated homology-directed repair (HDR) using plasmid, rAAV, and oligonucleotide templates. Toward the genetic dehorning of dairy cattle, we introgressed a bovine POLLED allele into horned bull fibroblasts. Single nucleotide alterations or small indels were introduced into 14 additional genes in pig, goat, and cattle fibroblasts using TALEN mRNA and oligonucleotide transfection with efficiencies of 10-50% in populations. Several of the chosen edits mimic naturally occurring performance-enhancing or disease- resistance alleles, including alteration of single base pairs. Up to 70% of the fibroblast colonies propagated without selection harbored the intended edits, of which more than one-half were homozygous. Edited fibroblasts were used to generate pigs with knockout alleles in the DAZL and APC genes to model infertility and colon cancer. Our methods enable unprecedented meiosis-free intraspecific and interspecific introgression of select alleles in livestock for agricultural and biomedical applications. PMID:24014591

Tan, Wenfang; Carlson, Daniel F; Lancto, Cheryl A; Garbe, John R; Webster, Dennis A; Hackett, Perry B; Fahrenkrug, Scott C

2013-09-06

236

The origin of sickle cell alleles in Israel  

Microsoft Academic Search

Molecular genetic studies were undertaken to determine the source of chromosomes carrying the sickle cell allele in Israeli patients. Analysis of restriction fragment length polymorphism (RFLP) patterns (haplotypes) along the ß-globin gene cluster was performed on 31 sickle chromosomes obtained from 10 unrelated families living in Israel. One is a Caucasian Jewish family, recently found to be carrying the sickle

Deborah Rund; Naomi Kornhendler; Oded Shalev; Ariella Oppenheim

1990-01-01

237

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

238

Biochemical genetic relationships among Tunisian hares (Lepus sp.), South African cape hares (L. capensis), and European brown hares (L. europaeus).  

PubMed

Tunisian hares (n = 45), currently assigned to Lepus capensis, were assayed for allelic variation at 40 allozyme loci, and allele frequencies at 32 loci were directly compared with earlier data of South African cape hares (L. capensis, n = 9) and European brown hares (L. europaeus, n = 244) to reveal genetic relationships among them. European mountain hares (L. timidus, n = 200) were used for outgroup comparison. In the Tunisian hares 27.5% of the loci were polymorphic with 2-4 alleles. Among all alleles at polymorphic loci, 15.1% occurred exclusively in Tunisian hares, 5.7% exclusively in cape hares, and 7.5% exclusively in brown hares at low frequencies. Not a single locus showed alternately fixed alleles between the samples of the L. capensis/L. europaeus complex. Levels of absolute and relative genetic differentiation among the samples of the L. capensis/L. europaeus complex were low, relative to pairwise comparisons involving mountain hares. Diverse cluster analyses and multidimensional scaling of various pairwise genetic distance matrices concordantly grouped Tunisian hares with brown hares, and South African cape hares clustered only slightly farther apart, whereas mountain hares were distinctly separate. These results suggest regionally distinct phylogenetic units within an overall cohesive gene pool in the L. capensis/L. europaeus complex, supporting Petter's view that all North African hares belong to L. capensis except for one local population of savanna hares, and that cape hares and brown hares are conspecific. PMID:16382363

Ben Slimen, Hichem; Suchentrunk, Franz; Memmi, Abdelmajid; Ben Ammar Elgaaied, Amel

2005-12-01

239

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

240

Testing allele homogeneity: the problem of nested hypotheses  

PubMed Central

Background The evaluation of associations between genotypes and diseases in a case-control framework plays an important role in genetic epidemiology. This paper focuses on the evaluation of the homogeneity of both genotypic and allelic frequencies. The traditional test that is used to check allelic homogeneity is known to be valid only under Hardy-Weinberg equilibrium, a property that may not hold in practice. Results We first describe the flaws of the traditional (chi-squared) tests for both allelic and genotypic homogeneity. Besides the known problem of the allelic procedure, we show that whenever these tests are used, an incoherence may arise: sometimes the genotypic homogeneity hypothesis is not rejected, but the allelic hypothesis is. As we argue, this is logically impossible. Some methods that were recently proposed implicitly rely on the idea that this does not happen. In an attempt to correct this incoherence, we describe an alternative frequentist approach that is appropriate even when Hardy-Weinberg equilibrium does not hold. It is then shown that the problem remains and is intrinsic of frequentist procedures. Finally, we introduce the Full Bayesian Significance Test to test both hypotheses and prove that the incoherence cannot happen with these new tests. To illustrate this, all five tests are applied to real and simulated datasets. Using the celebrated power analysis, we show that the Bayesian method is comparable to the frequentist one and has the advantage of being coherent. Conclusions Contrary to more traditional approaches, the Full Bayesian Significance Test for association studies provides a simple, coherent and powerful tool for detecting associations.

2012-01-01

241

Bipolar disorder risk alleles in children with ADHD.  

PubMed

Bipolar disorder (BD) and attention deficit/hyperactivity disorder (ADHD) may share common genetic risk factors as indicated by the high co-morbidity of BD and ADHD, their phenotypic overlap especially in pediatric populations, the high heritability of both disorders, and the co-occurrence in families. We therefore examined whether known polygenic BD risk alleles are associated with ADHD. We chose the eight best SNPs of the recent genome-wide association study (GWAS) of BD patients of German ancestry and the nine SNPs from international GWAS meeting a 'genome-wide significance' level of ? = 5 × 10(-8). A GWAS was performed in 495 ADHD children and 1,300 population-based controls using HumanHap550v3 and Human660 W-Quadv1 BeadArrays. We found no significant association of childhood ADHD with single BD risk alleles surviving adjustment for multiple testing. Yet, risk alleles for BD and ADHD were directionally consistent at eight of nine loci with the strongest support for three SNPs in or near NCAN, BRE, and LMAN2L. The polygene analysis for the BP risk alleles at all 14 loci indicated a higher probability of being a BD risk allele carrier in the ADHD cases as compared to the controls. At a moderate power to detect association with ADHD, if true effects were close to estimates from GWAS for BD, our results suggest that the possible contribution of BD risk variants to childhood ADHD risk is considerably lower than for BD. Yet, our findings should encourage researchers to search for common genetic risk factors in BD and childhood ADHD in future studies. PMID:23712748

Schimmelmann, B G; Hinney, A; Scherag, A; Pütter, C; Pechlivanis, S; Cichon, S; Jöckel, K-H; Schreiber, S; Wichmann, H E; Albayrak, O; Dauvermann, M; Konrad, K; Wilhelm, C; Herpertz-Dahlmann, B; Lehmkuhl, G; Sinzig, J; Renner, T J; Romanos, M; Warnke, A; Lesch, K P; Reif, A; Hebebrand, J

2013-05-28

242

The European Solar Telescope  

NASA Astrophysics Data System (ADS)

In this presentation I will describe the current status of the European Solar Telescope (EST) project. The EST design has a 4-m aperture to achieve both a large photon collection and very high spatial resolution. It includes a multi-conjugate adaptive system integrated in the light path for diffraction-limited imaging. The optical train is optimized to minimize instrumental polarization and to keep it nearly constant as the telescope tracks the sky. A suite of visible and infrared instruments are planned with a light distribution system that accomodates full interoperability and simultaneous usage. The science drivers emphasize combined observations at multiple heights in the atmosphere to build a connected view of solar magnetism from the photosphere to the corona.

Socas-Navarro, H.

2012-12-01

243

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.

244

European project ISAWARE  

NASA Astrophysics Data System (ADS)

As air traffic is increasing, the probability of encountering 'surveillance' alerts during flight is also increasing. In order to ensure safety, new on board systems need to be developed to provide the crew with a better 'situation awareness' (SA) about its external environment and potential hazards. In addition, the means to manage the data generated by these new systems needs to be build up. Despite the tremendous amount of information, crew workload must not increase. This is where the ISAWARE project comes in with the Integrated Situation Awareness System (ISAS) concept. ISAWARE (Increasing Safety through collision Avoidance WARning intEgration) is a project partly funded by the European Community, executed by a well balanced composition of several European aerospace companies (airframers, a helicopter manufacturer, avionics suppliers, airlines), one research laboratory and one university. The overall objective of the ISAWARE project is to conduct research into the potential improvements to flight safety that can be achieved by providing the pilot with complete predictive situation awareness during all phases of the flight. The Integrated Situational Awareness System (ISAS) merges data from different safety systems concerning terrain, traffic, weather and other. The system ensures the alerts consistency, prioritises alerts and anticipates threats along a predicted trajectory earlier than current systems can provide. The second main axis of the research is the development of synthetic vision displays (PFD, ND and HUD) to enhance the Human-Machine Interface (HMI). The key focus of the project is the development of a ground-based demonstrator rig which is interfaced to a dynamic flight simulator. This rig is used for the evaluation of the ISAWARE concept by a representative range of active airline crews.

Kaiser, Jochen; Smietanski, Guillaume; Kubbat, Wolfgang

2001-08-01

245

European Schoolnet: Enabling School Networking  

ERIC Educational Resources Information Center

|School networking is increasingly important in a globalised world, where schools themselves can be actors on an international stage. This article builds on the activities and experience of the longest established European initiative in this area, European Schoolnet (EUN), a network of 31 Ministries of Education. First, we offer an introduction…

Scimeca, Santi; Dumitru, Petru; Durando, Marc; Gilleran, Anne; Joyce, Alexa; Vuorikari, Riina

2009-01-01

246

EUROPEAN INTEGRATION AND BALKAN COUNTRIES  

Microsoft Academic Search

Integration of the European economies has affected and will continue to affect almost every aspect of both domestic and international affairs of Balkan countries. Growth of intra-European trade, massive international financial flows, and the activities of multinational corporations are tying national economies more tightly to one another, thus making integration an important feature of the EU. Almost all economists and

Sasha Obradovic

2008-01-01

247

EUROPEAN INDUSTRIAL AND COMPETITION POLICY  

Microsoft Academic Search

This article discusses alternative perspectives on competition and industrial policies (IP) in theory and in practice and critically assesses recent European IP in this context. It develops a new framework for IP that emphasises the sustainability of value creation at the firm, meso and national levels, and explores its implications for IP in general and European IP in particular. It

Christos N. Pitelis

2007-01-01

248

Market forces in European soccer  

Microsoft Academic Search

Recent decades have witnessed major changes in the market for European soccer. The most profound were the Bosman ruling, which lifted restrictions in the European labor market for soccer talent, and the introduction of the Champions' League, a high-profile international competition that generates high revenues for participating clubs. This paper studies the effects of these changes on the closeness of

Marco Haan; Ruud H. Koning; Arjen van Witteloostuijn

2002-01-01

249

Haplotype and AGG interspersion analysis of FMR1 alleles in a Croatian population: no founder effect detected in patients with fragile X syndrome.  

PubMed

Several studies have suggested that fragile X syndrome (FRAXA), the most common inherited form of mental retardation, originated from a limited number of founder chromosomes. The aim of this study is to assess the genetic origin of fragile X syndrome in a Croatian population. We performed a haplotype analysis of the polymorphic loci DXS548 and FRAXAC1 in 18 unrelated fragile X and 56 control chromosomes. The AGG interspersion pattern of the FMR1 CGG repeat region was analyzed by sequencing. This is the first report on haplotype and AGG interspersion analysis of the fragile X syndrome gene in a Croatian population-the only eastern European population of Slavic origin analyzed so far. Our findings are intriguing, because they show a distinct distribution of the DXS548 and FRAXAC1 alleles in our fragile X population compared to other European fragile X populations. The DXS548/FRAXAC1 haplotype 194/154 (7-3), which is common among normal populations, was found to be the most frequent haplotype in our fragile X population as well. The AGG interspersion analysis indicated that AGG loss rather than haplotype may determine FMR1 allele instability. Our results suggest that no common ancestral X chromosome is associated with fragile X syndrome in the Croatian population studied. Further analysis of the origin of fragile X syndrome among other Slavic populations will be necessary to better define its eastern European distribution. PMID:19341325

Doki?, H; Barisi?, I; Culi?, V; Lozi?, B; He?imovi?, S

2008-10-01

250

The Number of Alleles at a Microsatellite Defines the Allele Frequency Spectrum and Facilitates Fast Accurate Estimation of ?  

PubMed Central

Theoretical work focused on microsatellite variation has produced a number of important results, including the expected distribution of repeat sizes and the expected squared difference in repeat size between two randomly selected samples. However, closed-form expressions for the sampling distribution and frequency spectrum of microsatellite variation have not been identified. Here, we use coalescent simulations of the stepwise mutation model to develop gamma and exponential approximations of the microsatellite allele frequency spectrum, a distribution central to the description of microsatellite variation across the genome. For both approximations, the parameter of biological relevance is the number of alleles at a locus, which we express as a function of ?, the population-scaled mutation rate, based on simulated data. Discovered relationships between ?, the number of alleles, and the frequency spectrum support the development of three new estimators of microsatellite ?. The three estimators exhibit roughly similar mean squared errors (MSEs) and all are biased. However, across a broad range of sample sizes and ? values, the MSEs of these estimators are frequently lower than all other estimators tested. The new estimators are also reasonably robust to mutation that includes step sizes greater than one. Finally, our approximation to the microsatellite allele frequency spectrum provides a null distribution of microsatellite variation. In this context, a preliminary analysis of the effects of demographic change on the frequency spectrum is performed. We suggest that simulations of the microsatellite frequency spectrum under evolutionary scenarios of interest may guide investigators to the use of relevant and sometimes novel summary statistics.

Haasl, Ryan J.; Payseur, Bret A.

2010-01-01

251

Sequencing of Lp-PLA2-encoding PLA2G7 gene in 2000 Europeans reveals several rare loss-of-function mutations  

PubMed Central

Elevated plasma levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity have been shown to be associated with increased risk of coronary heart disease and an inhibitor of this enzyme is under development for the treatment of that condition. A Val279Phe null allele in this gene, that may influence patient eligibility for treatment, is relatively common in East Asians but has not been observed in Europeans. We investigated the existence and functional effects of low frequency alleles in a Western European population by re-sequencing the exons of PLA2G7 in 2000 samples. In all, 19 non-synonymous single-nucleotide polymorphisms (nsSNPs) were found, 14 in fewer than four subjects (minor allele frequency <0.1%). Lp-PLA2 activity was significantly lower in rare nsSNP carriers compared with non-carriers (167.8±63.2 vs 204.6±41.8, P=0.01) and seven variants had enzyme activities consistent with a null allele. The cumulative frequency of these null alleles was 0.25%, so <1 in 10?000 Europeans would be expected to be homozygous, and thus not potentially benefit from treatment with an Lp-PLA2 inhibitor.

Song, K; Nelson, M R; Aponte, J; Manas, E S; Bacanu, S-A; Yuan, X; Kong, X; Cardon, L; Mooser, V E; Whittaker, J C; Waterworth, D M

2012-01-01

252

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

PubMed

Interpretation of DNA evidence depends upon the ability of the analyst to accurately compare the DNA profile obtained from an item of evidence and the DNA profile of a standard. This interpretation becomes progressively more difficult as the number of 'drop-out' and 'drop-in' events increase. Analytical thresholds (AT) are typically selected to ensure the false detection of noise is minimized. However, there exists a tradeoff between the erroneous labeling of noise as alleles and the false non-detection of alleles (i.e. drop-out). In this study, the effect ATs had on both types of error was characterized. Various ATs were tested, where three relied upon the analysis of baseline signals obtained from 31 negative samples. The fourth AT was determined by utilizing the relationship between RFU signal and DNA input. The other ATs were the commonly employed 50, 150 and 200 RFU thresholds. Receiver Operating Characteristic (ROC) plots showed that although high ATs completely negated the false labeling of noise, DNA analyzed with ATs derived using analysis of the baseline signal exhibited the lowest rates of drop-out and the lowest total error rates. In another experiment, the effect small changes in ATs had on drop-out was examined. This study showed that as the AT increased from ?10 to 60 RFU, the number of heterozygous loci exhibiting the loss of one allele increased. Between ATs of 60 and 150 RFU, the frequency of allelic drop-out remained constant at 0.27 (±0.02) and began to decrease when ATs of 150 RFU or greater were utilized. In contrast, the frequency of heterozygous loci exhibiting the loss of both alleles consistently increased with AT. In summary, for samples amplified with less than 0.5ng of DNA, ATs derived from baseline analysis of negatives were shown to decrease the frequency of drop-out by a factor of 100 without significantly increasing rates of erroneous noise detection. PMID:22796031

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

2012-07-12

253

European Science Notes. Volume 39, Number 6.  

National Technical Information Service (NTIS)

European Science Notes (ESN) is a monthly publication with brief articles on recent developments in European scientific research. The value of ESN articles to Americans is to call attention to current developments in European science and technology and to...

L. E. Shaffer

1985-01-01

254

The Fixation of Locally Beneficial Alleles in a Metapopulation  

PubMed Central

Extinction, recolonization, and local adaption are common in natural spatially structured populations. Understanding their effect upon genetic variation is important for systems such as genetically modified organism management or avoidance of drug resistance. Theoretical studies on the effect of extinction and recolonization upon genetic variance started appearing in the 1970s, but the role of local adaption still has no good theoretical basis. Here we develop a model of a haploid species in a metapopulation in which a locally adapted beneficial allele is introduced. We study the effect of different spatial patterns of local adaption, and different metapopulation dynamics, upon the fixation probability of the beneficial allele. Controlling for the average selection pressure, we find that a small area of positive selection can significantly increase the global probability of fixation. However, local adaption becomes less important as extinction rate increases. Deme extinction and recolonization have a spatial smoothing effect that effectively reduces spatial variation in fitness.

Vuilleumier, Severine; Yearsley, Jon M.; Perrin, Nicolas

2008-01-01

255

The fixation of locally beneficial alleles in a metapopulation.  

PubMed

Extinction, recolonization, and local adaptation are common in natural spatially structured populations. Understanding their effect upon genetic variation is important for systems such as genetically modified organism management or avoidance of drug resistance. Theoretical studies on the effect of extinction and recolonization upon genetic variance started appearing in the 1970s, but the role of local adaptation still has no good theoretical basis. Here we develop a model of a haploid species in a metapopulation in which a locally adapted beneficial allele is introduced. We study the effect of different spatial patterns of local adaptation, and different metapopulation dynamics, upon the fixation probability of the beneficial allele. Controlling for the average selection pressure, we find that a small area of positive selection can significantly increase the global probability of fixation. However, local adaptation becomes less important as extinction rate increases. Deme extinction and recolonization have a spatial smoothing effect that effectively reduces spatial variation in fitness. PMID:18202388

Vuilleumier, Séverine; Yearsley, Jon M; Perrin, Nicolas

2008-01-01

256

Allelic frequencies of 20 visible phenotype variants in the korean population.  

PubMed

The prediction of externally visible characteristics from DNA has been studied for forensic genetics over the last few years. Externally visible characteristics include hair, skin, and eye color, height, and facial morphology, which have high heritability. Recent studies using genome-wide association analysis have identified genes and variations that correlate with human visible phenotypes and developed phenotype prediction programs. However, most prediction models were constructed and validated based on genotype and phenotype information on Europeans. Therefore, we need to validate prediction models in diverse ethnic populations. In this study, we selected potentially useful variations for forensic science that are associated with hair and eye color, iris pattern, and facial morphology, based on previous studies, and analyzed their frequencies in 1,920 Koreans. Among 20 single nucleotide polymorphisms (SNPs), 10 SNPs were polymorphic, 6 SNPs were very rare (minor allele frequency < 0.005), and 4 SNPs were monomorphic in the Korean population. Even though the usability of these SNPs should be verified by an association study in Koreans, this study provides 10 potential SNP markers for forensic science for externally visible characteristics in the Korean population. PMID:23843775

Lim, Ji Eun; Oh, Bermseok

2013-06-30

257

Single nucleotide polymorphisms of the protoporphyrinogen oxidase gene: inter-population heterogeneity of allelic variation.  

PubMed

Five single nucleotide polymorphisms (SNPs) in the protoporphyrinogen oxidase gene (PPOX) were used for inter-population comparisons of six South African populations and two non-South African Caucasian populations. Novel polymorphisms identified in the promoter region and exon 11 of the PPOX gene, as well as three known variants in exon 1 and intron 2, were analysed using single-strand conformation polymorphism (SSCP) and restriction enzyme analyses. Significant population differences were found for four of the five polymorphisms analysed. A G-to-A transition was found at nucleotide position -1081 and is the first polymorphism to be identified in the 5' promoter region of the gene. A novel A-to-C substitution at nucleotide position 3880 in exon 11 was not detected in subjects of European descent. This study represents the first inter-population comparison of allelic variation at the PPOX locus. The significant differences observed between populations demonstrate the importance of population considerations when marker association studies are performed at this locus. PMID:11513556

Warnich, L; Waso, H F; Groenewald, I M; Bester, A E; de Villiers, J N; Kotze, M J; Lynch, A G; Louw, J H

2001-08-01

258

Allelic Frequencies of 20 Visible Phenotype Variants in the Korean Population  

PubMed Central

The prediction of externally visible characteristics from DNA has been studied for forensic genetics over the last few years. Externally visible characteristics include hair, skin, and eye color, height, and facial morphology, which have high heritability. Recent studies using genome-wide association analysis have identified genes and variations that correlate with human visible phenotypes and developed phenotype prediction programs. However, most prediction models were constructed and validated based on genotype and phenotype information on Europeans. Therefore, we need to validate prediction models in diverse ethnic populations. In this study, we selected potentially useful variations for forensic science that are associated with hair and eye color, iris pattern, and facial morphology, based on previous studies, and analyzed their frequencies in 1,920 Koreans. Among 20 single nucleotide polymorphisms (SNPs), 10 SNPs were polymorphic, 6 SNPs were very rare (minor allele frequency < 0.005), and 4 SNPs were monomorphic in the Korean population. Even though the usability of these SNPs should be verified by an association study in Koreans, this study provides 10 potential SNP markers for forensic science for externally visible characteristics in the Korean population.

Lim, Ji Eun

2013-01-01

259

European Southern Observatory  

NSDL National Science Digital Library

The European Southern Observatory (ESO) is an intergovernmental organization comprised of 14 member countries. Its headquarters are in Germany, but they have three observatories in Chile as well. Their website is loaded with information and visitors shouldn't miss going on the "Virtual Tours", on the far right side of the homepage. The tours are of the three observatories in Chile, and offer almost 360 degree views of beautiful, yet sparse landscapes. The tour of La Silla has two particularly beautiful views, "La Silla Moonlight" and "La Silla Sunset". Visitors interested in seeing a panning of an artist's 3D rendering of the Orion Nebula must go to the "Video" link on the left hand menu on the homepage. There are over 1400 videos to choose from, so for those not into the Orion Nebula, never fear, there are plenty of other video choices. Finally, visitors must go to the "Top 100 Images" link on the right side of the homepage to see amazing and gorgeous images taken from the ESO's various observatories.

2010-07-09

260

TRPV6 alleles do not influence prostate cancer progression  

Microsoft Academic Search

BACKGROUND: The transient receptor potential, subfamily V, member 6 (TRPV6) is a Ca2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed

Thorsten Kessler; Ulrich Wissenbach; Rainer Grobholz; Veit Flockerzi

2009-01-01

261

Fractionation of Non Allelic Histone Variants by Hydrophobic Interaction Chromatography  

Microsoft Academic Search

A method for the separation of non allelic hi stone variants is described.Sepharose-CL-4B was modified with dodecylamine by the carbonyldiimidazole-method. The matrix prepared contained 6 ?;mol\\/ml hydrophobic groups, C12-hydrocarbon chains. Proteins were loaded at high ionic strength and eluted from the column with an urea gradient. Histones H1, H2a and H2b from different mammalian tissues were loaded on the column

V. S. Ivanova

1984-01-01

262

The Friedreich ataxia GAA triplet repeat: premutation and normal alleles  

Microsoft Academic Search

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

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

1997-01-01

263

Genetic Tools for Allelic Replacement in Burkholderia Species  

Microsoft Academic Search

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

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

2008-01-01

264

Citrobacter spp. as a Source of qnrB Alleles ?  

PubMed Central

qnrB is the most common of the five qnr families and has the greatest number of allelic variants. Almost two-thirds of the qnrB alleles have been reported in Citrobacter spp., and several were shown to be located on the chromosome. In this study, PCR was used to investigate the prevalence of plasmid-mediated quinolone resistance genes in 71 clinical isolates belonging to the Citrobacter freundii complex. Thirty-seven percent contained qnrB alleles, including 7 (qnrB32 to qnrB38) that were novel and 1 pseudogene, while none contained qnrA, qnrC, qnrD, qnrS, or aac(6?)-Ib-cr. When the strains were arrayed by related 16S rRNA sequence and further separated into subspecies by biochemical criteria, clustering of qnrB-positive strains was evident. In only two strains with qnrB2 and qnrB4 was quinolone resistance transferable by conjugation, and only these strains contained the ISCR1 sequence that is often associated with qnrB on plasmids. Five of 26 qnrB-positive strains contained integrase genes, but these included the strains with qnrB2 and qnrB4 as well as two strains with other transmissible plasmids. In a fully sequenced genome of Citrobacter youngae, a member of the C. freundii complex, another novel qnrB allele, qnrB39, occurs in a sequence of genes that is 90% identical to sequence surrounding integron-associated qnrB4 incorporated into plasmids. The chromosome of Citrobacter is the likely source of plasmid-mediated qnrB.

Jacoby, George A.; Griffin, Caitlin M.; Hooper, David C.

2011-01-01

265

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

266

Allelic based gene-gene interactions in rheumatoid arthritis  

Microsoft Academic Search

The detection of gene-gene interaction is an important approach to understand the etiology of rheumatoid arthritis (RA). The goal of this study is to identify gene-gene interaction of SNPs at the allelic level contributing to RA using real data sets (Problem 1) of North American Rheumatoid Arthritis Consortium (NARAC) provided by Genetic Analysis Workshop 16 (GAW16). We applied our novel

Jeesun Jung; Joon Jin Song; Deukwoo Kwon

2009-01-01

267

The joint allele-frequency spectrum in closely related species.  

PubMed

We develop the theory for computing the joint frequency spectra of alleles in two closely related species. We allow for arbitrary population growth in both species after they had a common ancestor. We focus on the case in which a single chromosome is sequenced from one of the species. We use classical diffusion theory to show that, if the ancestral species was at equilibrium under mutation and drift and a chromosome from one of the descendant species carries the derived allele, the frequency spectrum in the other species is uniform, independently of the demographic history of both species. We also predict the expected densities of segregating and fixed sites when the chromosome from the other species carries the ancestral allele. We compare the predictions of our model with the site-frequency spectra of SNPs in the four HapMap populations of humans when the nucleotide present in the Neanderthal DNA sequence is ancestral or derived, using the chimp genome as the outgroup. PMID:17603120

Chen, Hua; Green, Richard E; Pääbo, Svante; Slatkin, Montgomery

2007-07-01

268

A survey of FRAXE allele sizes in three populations  

SciTech Connect

FRAXE is a fragile site located at Xq27-8, which contains polymorphic triplet GCC repeats associated with a CpG island. Similar to FRAXA, expansion of the GCC repeats results in an abnormal methylation of the CpG island and is associated with a mild mental retardation syndrome (FRAXE-MR). We surveyed the GCC repeat alleles of FRAXE from 3 populations. A total of 665 X chromosomes including 416 from a New York Euro-American sample (259 normal and 157 with FRAXA mutations), 157 from a Chinese sample (144 normal and 13 FRAXA), and 92 from a Finnish sample (56 normal and 36 FRAXA) were analyzed by polymerase chain reaction. Twenty-seven alleles, ranging from 4 to 39 GCC repeats, were observed. The modal repeat number was 16 in the New York and Finnish samples and accounted for 24% of all the chromosomes tested (162/665). The modal repeat number in the Chinese sample was 18. A founder effect for FRAXA was suggested among the Finnish FRAXA samples in that 75% had the FRAXE 16 repeat allele versus only 30% of controls. Sequencing of the FRAXE region showed no imperfections within the GCC repeat region, such as those commonly seen in FRAXA. The smaller size and limited range of repeats and the lack of imperfections suggests the molecular mechanisms underlying FRAXE triplet mutations may be different from those underlying FRAXA. 27 refs., 4 figs., 1 tab.

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

1996-08-09

269

Allelic Variants of Complement Genes Associated with Dense Deposit Disease  

PubMed Central

The alternative pathway of the complement cascade plays a role in the pathogenesis of dense deposit disease (DDD). Deficiency of complement factor H and mutations in CFH associate with the development of DDD, but it is unknown whether allelic variants in other complement genes also associate with this disease. We studied patients with DDD and identified previously unreported sequence alterations in several genes in addition to allelic variants and haplotypes common to patients with DDD. We found that the likelihood of developing DDD increases with the presence of two or more risk alleles in CFH and C3. To determine the functional consequence of this finding, we measured the activity of the alternative pathway in serum samples from phenotypically normal controls genotyped for variants in CFH and C3. Alternative pathway activity was higher in the presence of variants associated with DDD. Taken together, these data confirm that DDD is a complex genetic disease and may provide targets for the development of disease-specific therapies.

Abrera-Abeleda, Maria Asuncion; Nishimura, Carla; Frees, Kathy; Jones, Michael; Maga, Tara; Katz, Louis M.; Zhang, Yuzhou

2011-01-01

270

Functional characterization of 32 CYP2C9 allelic variants.  

PubMed

Genetic variations in cytochrome P450 2C9 (CYP2C9) contribute to interindividual variability in the metabolism of clinically used drugs such as warfarin and tolbutamide. We functionally characterized 32 types of allelic variant CYP2C9 proteins. Recombinant CYP2C9 proteins generated using a heterologous expression system are useful for comparing functional changes in CYP2C9 variant proteins expressed from low-frequency alleles. Wild-type CYP2C9 and its 31 variants were found to be transiently expressed in COS-7 cells, and the enzymatic activity of the CYP2C9 variants was characterized using S-warfarin as a representative substrate. Among the 32 types of CYP2C9 allelic variants tested, CYP2C9.18, CYP2C9.21, CYP2C9.24, CYP2C9.26, CYP2C9.33 and CYP2C9.35 exhibited no enzyme activity, and 12 types showed significantly decreased enzyme activity. In vitro analysis of CYP2C9 variant proteins should be useful for predicting CYP2C9 phenotypes and for application to personalized drug therapy.The Pharmacogenomics Journal advance online publication, 11 June 2013; doi:10.1038/tpj.2013.22. PMID:23752738

Niinuma, Y; Saito, T; Takahashi, M; Tsukada, C; Ito, Mi; Hirasawa, N; Hiratsuka, M

2013-06-11

271

Novel Reporter Alleles of GSK-3? and GSK-3?  

PubMed Central

Glycogen Synthase Kinase 3 (GSK-3) is a key player in development, physiology and disease. Because of this, GSK-3 inhibitors are increasingly being explored for a variety of applications. In addition most analyses focus on GSK-3? and overlook the closely related protein GSK-3?. Here, we describe novel GSK-3? and GSK-3? mouse alleles that allow us to visualise expression of their respective mRNAs by tracking ?-galactosidase activity. We used these new lacZ alleles to compare expression in the palate and cranial sutures and found that there was indeed differential expression. Furthermore, both are loss of function alleles and can be used to generate homozygous mutant mice; in addition, excision of the lacZ cassette from GSK-3? creates a Cre-dependent tissue-specific knockout. As expected, GSK3? mutants were viable, while GSK3? mutants died after birth with a complete cleft palate. We also assessed the GSK-3? mutants for cranial and sternal phenotypes and found that they were essentially normal. Finally, we observed gestational lethality in compound GSK-3??/?; GSK3?+/? mutants, suggesting that GSK-3 dosage is critical during embryonic development.

Barrell, William B.; Szabo-Rogers, Heather L.; Liu, Karen J.

2012-01-01

272

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

273

Distortion of allele frequency distributions provides a test for recent population bottlenecks  

Microsoft Academic Search

We use population genetics theory and computer simulations to demonstrate that population bottlenecks cause a characteristic mode-shift distortion in the distri- bution of allele frequencies at selectively neutral loci. Bottlenecks cause alleles at low frequency (,0.1) to become less abundant than alleles in one or more inter- mediate allele frequency class (e.g., 0.1-0.2). This distortion is transient and likely to

G. Luikart; F. W. Allendorf; J.-M. Cornuet; W. B. Sherwin

1998-01-01

274

High frequency of HLA-A?0103 allele in a Somali population  

Microsoft Academic Search

We report the existence of class I HLA allele A?0103 in an ethnic group (Somali) where this allele has not been reported. This allele was discovered in a study to examine the relationship between HLA alleles and humoral antibody response to measles vaccine among recent immigrants from Somalia to Olmsted County, Minnesota. We initially used polymerase chain reaction–sequence-specific primers (PCR-SSP)

Gregory A Poland; Youvraj Sohni; Michael Domanico; Cindy M Kroning; Steven R DeGoey; Mouhammed Jimale; Robert M Jacobson; S Breanndan Moore

2001-01-01

275

European pain management discussion forum.  

PubMed

Queries from European physicians about analgesic pharmacotherapy and responses from the author are presented. Topics addressed in this issue pertain to epidural injection for painful central lumbar stenosis and epicondolysis. PMID:23216190

Breivik, Harald

2012-12-01

276

Relative efficiency of European airports  

Microsoft Academic Search

Using data envelopment analysis, efficiency ratios for European airports are determined. It appears that most airports are operating under increasing returns to scale. This is also reflected in the most productive scale size determined for the airports.

Eric Pels; Peter Nijkamp; Piet Rietveld

2001-01-01

277

European Standards for Automatic Sprinklers.  

National Technical Information Service (NTIS)

European Automatic Sprinkler Standards were developed by the Comite Europeen des Assurances, and international association of insurance organizations of Western Europe, based on a detailed analysis of reliable fire statistics on sprinkler-protected proper...

P. Kirchhoff

1975-01-01

278

Allelic association of G72/G30 with schizophrenia and bipolar disorder: a comprehensive meta-analysis  

PubMed Central

The G72/G30 gene complex (G72 also known as D-amino acid oxidase activator, DAOA) and its chromosomal region 13q32–34 have been linked and associated with both schizophrenia (SCZ) and bipolar disorder (BP) in multiple studies, including our initial association report on BP. However, the inconsistency of associated variants across studies is obvious. Previous meta-analyses had small data sets. The present meta-analysis combined 18 association articles published before April of 2007. There were 19 independent studies of SCZ, with 4304 cases, 5423 controls, and 1384 families, and four independent studies of BP with 1145 cases, 1829 controls, and 174 families. Of 15 single nucleotide polymorphisms (SNPs) analyzed in the 95-kb G72/G30 gene region, M18/rs947267 and M22/rs778293 showed association with SCZ in Asians, and M24/rs1421292 with SCZ in Europeans. The associations of C allele at M18 and A allele at M22 with SCZ in Asians survived conservative Bonferroni correction for multiple testing for 15 markers and subgroup analysis (adjusted P = 0.0000253 for M18; adjusted P = 0.009 for M22). No single maker showed evidence of overall association with BP. These results suggest that G72/G30 may influence susceptibility to schizophrenia with weak effects.

Shi, Jiajun; Badner, Judith A.; Gershon, Elliot S.; Liu, Chunyu

2008-01-01

279

Deleterious alleles and differential viability in progeny of natural hemiclonal frogs.  

PubMed

Abstract.-Spontaneous deleterious mutations are expected to accumulate through Muller's ratchet in clonally reproducing organisms and may lead to their extinction. We study deleterious mutations and their effects in a system of European frogs. Rana esculenta (RL), natural hybrids R. ridibunda (RR) X R. lessonae (LL), reproduce hemiclonally; both sexes exclude the L genome in the germ line and produce unrecombined R gametes; hybridity is restored each generation by matings of RL with coexisting LL. Different allozyme-defined hybrid hemiclones (R genome haplotypes) are thought to have originated independently from primary hybridizations RR x LL. Natural matings between two hybrids usually lead to inviable RR tadpoles. This inviability is thought to result from unmasked deleterious alleles on the clonally transmitted R genomes. Most simply it reflects homozygosity for recessive deleterious alleles at particular loci; alternatively (consistent with absence of RR adults in multiclonal populations) it may reflect hemiclone-specific sets of incompletely recessive deleterious mutations that cumulatively cause inviability when two such genomes are combined. If inviability results from the former, progeny of two hybrids of different hemiclones, whether allopatric or coexisting, should be viable, because it is improbable that their R genomes share recessive deleterious alleles at the same set of loci; if inviability results from the latter, progeny of hybrids of different hemiclones should be inviable, especially when hybrid lineages are old. We tested these hypotheses in artificial crosses, using frogs from three regions: hemiclonal hybrids outside R. ridibunda's range from northern Switzerland (two abundant coexisting allozyme-defined hemiclones; estimated lineage age < or = 5,000 generations) and from Sicily, Italy (one hemiclone; estimated age > or = 25,000 generations) and R. ridibunda from Poland. We generated RR progeny, which we reared under benign conditions in the laboratory, by crossing (1) two hybrids from the same region (H x H local); (2) two hybrids from different regions (H X H foreign); (3) hybrids and R. ridibunda (H X R); and (4) two R. ridibunda (R X R). Survival to metamorphosis was similar and high for R x R, H X H foreign, and H X R, whereas all tadpoles of H X H local died before metamorphosis. This supports the hypothesis that homozygosity for recessive deleterious mutations at particular loci causes inviability. Crosses within and between the two coexisting hemiclones from Switzerland were, however, equally inviable. This result may reflect episodic sexual recombination in RR progeny from exceptional successful interclonal hybrid X hybrid matings, followed by matings of such RR with LL. This process would both slow down or halt Muller's ratchet and disrupt genetic independence of coexisting hemiclones, so that the same remaining deleterious R alleles could exist in different allozyme-defined hemiclones. Whereas all data are consistent with the prediction of Muller's ratchet operating on clonally transmitted R genomes of natural hybrid lineages, they are insufficient to demonstrate such operation, because deleterious recessives that mutated after clone formation and those that preexisted in the R. ridibunda source populations that formed the hemiclonal lineages are not distinguished. The possibility of episodic sexual recombination must be carefully taken into account when studying Muller's ratchet in natural populations of this Rana system. PMID:12093017

Guex, Gaston-Denis; Hotz, Hansjurg; Semlitsch, Raymond D

2002-05-01

280

North European Transect  

NASA Astrophysics Data System (ADS)

A nearly continuous, 3600 km long, NE-running North European Transect (NET) is combined from the existing deep seismic reflection data sets in the Baltic Sea (BABEL, 1600 km), Northern Finland (FIRE 4-4A, 580 km) and Barents Sea (1-AR, 1440 km;). The reflective image of the deep crust is highly dependent on the thickness of the sedimentary cover. The cover is few hundred meters in the Baltic sea, few tens of meters in the land areas and few kilometers in the Barents Sea area. In the Barents Sea area, the seismic image is dominated by the layered structure of the sedimentary basins and the middle and lower crust are poorly imaged. Therefore the Moho boundary in the Barents Sea has been determined from wide-angle reflections. Geologically the transect covers the transition from Phanerozoic Europe to Precambrian Europe and back to the Phanerozoic Barents Sea Shelf. It displays how Northern Europe grew around Baltica in several tectonic episodes involving the formation and destruction of Columbia/Hudsonland, Rodinia and Pangea supercontinents. The paleo plateboundaries are traversed by subvertical transparent zones suggesting transpressional and trantensional environments. The BABEL lines image how the core of Baltica was formed by sequential accretion of microcontinents and arc terranes at the old continental margin during the Svecofennian Orogeny ~1.9-1.8 Ga .When Baltica joined the Columbia supercontinent, new terranes were added to its southern edge in the Sveocbaltic Orogeny (~1.8 Ga). During the dispersal of the Columbia, the Baltic Sea failed rift was formed, rapakivi granitoids were intruded and sedimentary basins were developed. An extended plate margin structure has been imposed on the Rodinian (Sveconorwegian) and Pangean additions (Variscan-Caledonian). Major crustal thinning takes place along a series of subvertical faults across the Trans-European Suture Zone marking the transition from Phanerozoic to Proterozoic Europe. The FIRE lines in Northen Finland image a collage of older continental fragments and intervening basins that have been welded together in Svecofennian and Lapland-Kola orogenies. The Lapland-Kola orogen record the collision of Baltica and Laurentia during the compilation of the Columbia supercontinent. The collisional structures were overprinted by extension associated with the dispersal of Columbia. The Russian Arctic line 1-AR focuses on the Phanerozoic sedimentary cover of the Barents Sea Basin. The line images the transition from Paleoproterozoic Baltica to Neoproterozoic Barentsia. As part of the Rodinia supercontinent formation, Baltica collided with Barentsia resulting in Timanide orogeny. During the break-up of Rodinia an aborted rift was formed within the Barentsia. Later peripheral tectonic events modified the interior parts of Barentsia that acted first as a back arc basin and later as a foreland basin to the Uralian and Caledonian orogen during the formation of the Pangea supercontinent.

Korja, Annakaisa; Heikkinen, Pekka J.; Roslov, Yuri; Ivanova, Nina; Verba, Marc; Sakoulina, Tamara

2010-05-01

281

Yahoo! Groups: EuropeanArchaeology  

NSDL National Science Digital Library

This moderated mailing list is intended for a discussion of European prehistoric and historic archaeology, from the Early Paleolithic period through the 1800s. EuropeanArchaeology is a general purpose academic list that is designed to include book and article announcements, field school announcements, discuss new discoveries, theories and interpretations, and related topics. At the site, users can subscribe to the list and read the discussion logs.

282

The European Soil Information System  

Microsoft Academic Search

Summary In Europe, as in the rest of the world, a thorough knowledge of soil use and soil protection is of vital importance. The European Commission, in particular its Directorates General of Agriculture (DGVI), Environment (DGXI) and Research (DGXII), has supported several programmes with this objective in mind. The publication of the 1:1,000,000-scale Soil Map of the European Communities (EC)

Christine Le Bas; D. King; M. Jamagne; J. Daroussin

283

Autosomal microsatellite allele frequencies for 15 regionally defined Aboriginal Australian population datasets  

Microsoft Academic Search

DNA profiling results presented in court must be accompanied by a statistical estimate of its evidential weight. In calculating such statistics, allele frequencies from the tested loci are required. These allele frequencies should be collected at a level that appropriately represents the genetic diversity that exists in the population. This paper reports allele frequencies and the results of population genetic

Simon J. Walsh; John S. Buckleton

2007-01-01

284

Molecular polymorphism of O alleles in five populations of different ethnic origins  

Microsoft Academic Search

Sequences of exons 6 and 7 of the O allele of the ABO gene were studied in 317 individuals of the O phenotype from five different ethnic groups (Basques, Berbers, Akans from the Ivory Coast, and Amerindians: Cayapas from Ecuador and Aymaras from Bolivia). Twenty-one O alleles were characterized, among which 9 differed from all O alleles reported to date.

Francis Roubinet; Nathalie Kermarrec; Stéphanie Despiau; Pol-Andre Apoil; Jean Michel Dugoujon; Antoine Blancher

2001-01-01

285

TWO ALLELES OF MAIZE ALCOHOL DEHYDROGENASE 1 HAVE 3' STRUCTURAL AND POLY(A) ADDITION POLYMORPHISMS  

Microsoft Academic Search

Two standard electrophoretic alleles of the maize alcohol dehydrogenase I locus (Adhl-IS and Adhl-1F ) have been isolated and characterized. Restriction en- donuclease mapping shows that a region of less than 5 kb is conserved in both alleles and is flanked both 5' and 3' by regions highly polymorphic for restric- tion sites. Nucleotide sequence comparison of these two alleles

M. M. SACHS; E. S. DENNIS; W. L. GERLACH; W. J. PEACOCK

1986-01-01

286

Distinctions among Allelic Variants Associated with Chromosome 3 Inversions in DROSOPHILA PSEUDOOBSCURA and DROSOPHILA PERSIMILIS  

PubMed Central

Efforts were made to discriminate new genetic variants among electrophoretic alleles that are associated with chromosome 3 inversions of Drosophila pseudoobscura and D. persimilis. Apparent genetic similarities for electrophoretic alleles between these two species and among the common inversions they carry were reexamined by altering gel concentration and buffer pH. At the amylase locus, the 1.09 electrophoretic allele could be further separated into two allelic classes that differentiated the WT and KL arrangements. Similarly, the 0.84 electrophoretic allele was divided into two allelic classes, one characteristic of the Santa Cruz phylad arrangements, TL and SC, and the other found in strains of the Standard phylad arrangements and CH. Uncommon amylase alleles proved to be different alleles in the two species. No new allelic variants, however, could be found among strains with the amylase 1.00 allele, the commonest allele in the Standard phylad of both species. No major new allelic variation was detected for acid phosphatase-3 and larval protein-10 that revealed any further differentiation among species or inversions. Variation at all three loci in strains of the Bogota population remained genetically similar to variation in strains of mainland D. pseudoobscura.

Norman, R. A.; Prakash, Satya

1980-01-01

287

Expansion of an FMR1 grey-zone allele to a full mutation in two generations.  

PubMed

Fragile X Syndrome is caused by the expansion of an unstable CGG-repeat tract in the 5'-UTR of the FMR1 gene, which generally results in transcriptional silencing and consequent absence of the FMR1 protein. To date, the smallest premutation allele reported to expand to a full mutation allele in a single generation is 59 CGG repeats. Here, we report a single-generation expansion to a full mutation allele (male with approximately 538 CCG repeats) from a mother who is a carrier of a premutation allele of 56 CGG repeats. Furthermore, the maternal grandfather was a carrier of a gray (or intermediate)-zone allele (45 to 54 repeats) of 52 CGG repeats. Thus, in this family, a gray-zone allele expanded to the full mutation range in two generations. Interestingly, the two AGG interruptions present in the grandfather's allele were absent in the mother's premutation allele. These observations underscore the need to consider carriers of alleles of greater than 55 CGG repeats as being at risk for transmission of a full mutation allele in a single generation, and those with even smaller alleles in the gray zone as being at risk of having grandchildren with full mutation alleles. PMID:19525339

Fernandez-Carvajal, Isabel; Lopez Posadas, Blanca; Pan, Ruiqin; Raske, Christopher; Hagerman, Paul J; Tassone, Flora

2009-06-12

288

Computational Analysis of Whole-Genome Differential Allelic Expression Data in Human  

Microsoft Academic Search

Allelic imbalance (AI) is a phenomenon where the two alleles of a given gene are expressed at different levels in a given cell, either because of epigenetic inactivation of one of the two alleles, or because of genetic variation in regulatory regions. Recently, Bing et al. have described the use of genotyping arrays to assay AI at a high resolution

James R. Wagner; Bing Ge; Dmitry Pokholok; Kevin L. Gunderson; Tomi Pastinen; Mathieu Blanchette

2010-01-01

289

Whither Europeanization? Concept Stretching and Substantive Change  

Microsoft Academic Search

This paper discusses the concept of Europeanization in the light of recent research on the impact of the European Union politics and policy. Conceptual analysis is preliminary to empirical analysis. Accordingly, I examine the risk of 'concept stretching', discuss extension and intension of Europeanization, and propose a taxonomy to 'unpack' the concept and organize empirical research. The explanation of Europeanization

Claudio M. Radaelli

2002-01-01

290

Heterozygosity, shell length and metabolism in the european mussel, Dreissena polymorpha, from a recently established population in lake erie  

Microsoft Academic Search

Genetic variation at seven polymorphic enzyme loci in a recently established North American population of the European zebra mussel, Dreissena polymorpha, was high, with an average heterozygosity (H) of 0.307, and an average of 3.43 alleles per locus (range 2-6). 2. Mussel shell length was significantly correlated with multiple locus heterozygosity, although heterozygosity at these seven loci explained only 7%

D GARTON; W HAAG

1991-01-01

291

European football and the European union: Governance, participation and social cohesion — towards a policy research agenda  

Microsoft Academic Search

This article considers the changing relationship of European football to the European Union (EU). Given technological, commercial, financial and organizational changes in the political economy of elite European football, and given the application of European law to sports bodies epitomised by the Bosman ruling, this article begins to outline a policy research agenda. Debates within the European Commission have centred

Adam Brown

2000-01-01

292

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.

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.; Vila, Luis M.; Alarcon, 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

293

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(-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

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

2013-10-10

294

Genetic Susceptibility to Type 2 Diabetes and Breast Cancer Risk in Women of European and African Ancestry  

PubMed Central

Background Epidemiologic studies have reported a positive association between type 2 diabetes (T2D) and breast cancer risk, independent of body weight. Methods We investigated 40 genetic variants known to be associated with T2D in relation to breast cancer risk among 2651 breast cancer cases and 2520 controls of African or European ancestry that were pooled from seven studies. Results We found that two T2D risk alleles in Caucasian women (rs5945326-G, rs12518099-C) and one in women of African ancestry (rs7578597-T) were positively associated with breast cancer risk at a nominal significance level of 0.05, whereas two T2D risk alleles were inversely associated with breast cancer risk in Caucasian women (rs1111875-C, rs10923931-T). The composite T2D susceptibility score (the number of risk allele) was not significantly associated with breast cancer risk. Conclusion The association between established T2D genetic susceptibility variants and breast cancer risk in women of African or European ancestry is likely weak, if it does exist. Impact The pleiotropic effects of known T2D risk alleles cannot explain the association between T2D and breast cancer risk.

Hou, Ningqi; Zheng, Yonglan; Gamazon, Eric R.; Ogundiran, Temidayo O.; Adebamowo, Clement; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Simon, Michael S.; John, Esther M.; Hennis, Anselm; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina; Ambs, Stefan; Niu, Qun; Zhang, Jing; Pierce, Brandon; Cox, Nancy J.; Olopade, Olufunmilayo I.; Huo, Dezheng

2012-01-01

295

Bi-allelic gene targeting in mouse embryonic stem cells  

PubMed Central

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.

Tate, Peri H.; Skarnes, William C.

2013-01-01

296

Regional Italian allele frequencies at nine short tandem repeat loci.  

PubMed

An Italian population study was performed on the loci D3S1358, vWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317, D7S820 and a portion of the X-Y homologous gene Amelogenin for gender determination using the AmpFlSTR Profiler kit (PE Biosystems, Foster city, CA). This study was done on a population of 618 unrelated Italian individuals from 18 regions in Italy (except for Valle d'Aosta and Sardinia) to determine allele frequencies for each STR locus, and to evaluate STR technology for developing an Italian Offender DNA database. PMID:11056274

Biondo, R; Spinella, A; Montagna, P; Walsh, P S; Holt, C; Budowle, B

2001-01-01

297

Allele frequencies of eight STRs in Japanese and Chinese  

Microsoft Academic Search

Allele frequencies for the eight STR loci Hum-CSF1P0, F13A01, F13B, FES\\/FPS, LPL, TH01, TPOX and VWA were investigated in\\u000a Japanese and Chinese populations. No significant deviations from Hardy-Weinberg equilibrium could be found for all loci. In\\u000a the Japanese population VWA, CSF1PO, TH01, FES\\/FPS and TPOX were found to be useful for forensic applications and in the Chinese\\u000a population, VWA, CSF1PO,

M. Nata; T. Kimura; M. Hashiyada; P. He; W. Yan; X. Li; M. Funayama; K. Sagisaka

1999-01-01

298

C4 concentrations and C4 deficiency alleles in systemic lupus erythematosus.  

PubMed Central

In a study of 66 patients with systemic lupus erythematosus (SLE) and 80 controls it was found that the presence of two deficiency (null) alleles of C4 had a significant effect on mean C4 concentrations in serum. In six controls who each had two C4 null alleles the mean C4 concentration in serum was 56% lower than in 43 controls without C4 null alleles; the nadir of the C4 concentration in four patients with SLE with two null alleles was also lower by a mean of 55% than in 32 patients who did not have null alleles. Reduced production of C4 allotypes in subjects with two null alleles may be an important determinant of total C4 concentration in patients with SLE. For optimal interpretation of C4 concentrations in SLE, C4 allotyping appears to be indicated, particularly to identify patients who have two null alleles of C4.

Wilson, W A; Armatis, P E; Perez, M C

1989-01-01

299

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.

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

300

Effects of the APOE ?2 allele on mortality and cognitive function in the oldest old.  

PubMed

Some studies indicate that the APOE ?2 allele may have a protective effect on mortality and mental health among the elderly adults. We investigated the effect of the APOE ?2 allele on cognitive function and mortality in 1651 members of the virtually extinct Danish 1905 birth cohort. We found no protective effect of the APOE ?2 allele on mortality compared with the APOE ?3 allele. The point estimates indicated an increased protection against cognitive decline over time for persons with the APOE ?2 allele. Cognitive score did not significantly modify the mortality risk of the various APOE genotypes. We did not find a protective effect of the APOE ?2 allele on mortality among the oldest old, but in agreement with our previous findings, we found a 22% increased mortality risk for APOE ?4 carriers. The APOE ?2 allele may be protective on cognitive decline among the oldest old. PMID:23051975

Lindahl-Jacobsen, Rune; Tan, Qihua; Mengel-From, Jonas; Christensen, Kaare; Nebel, Almut; Christiansen, Lene

2012-10-09

301

European security framework for healthcare.  

PubMed

eHealth and telemedicine services are promising business areas in Europe. It is clear that eHealth products and services will be sold and ordered from a distance and over national borderlines in the future. However, there are many barriers to overcome. For both national and pan-European eHealth and telemedicine applications a common security framework is needed. These frameworks set security requirements needed for cross-border eHealth services. The next step is to build a security infrastructure which is independent of technical platforms. Most of the European eHealth platforms are regional or territorial. Some countries are looking for a Public Key Infrastructure, but no large scale solutions do exist in healthcare. There is no clear candidate solution for European-wide interoperable eHealth platform. Gross-platform integration seems to be the most practical integration method at a European level in the short run. The use of Internet as a European integration platform is a promising solution in the long run. PMID:15061534

Ruotsalainen, Pekka; Pohjonen, Hanna

2003-01-01

302

A CHRNA5 allele related to nicotine addiction and schizophrenia.  

PubMed

Schizophrenia and nicotine addiction are both highly heritable phenotypes. Because individuals with schizophrenia have a higher rate of smoking than those in the general population, one could hypothesize that genes associated with smoking might be overrepresented in schizophrenia and thus help explain their increased smoking incidence. Although a number of genes have been proposed to explain the increased smoking risk in schizophrenia, none of them have been consistently linked to smoking and schizophrenia, and thus difficult to explain the increased smoking in schizophrenia. A functional smoking-related nicotinic acetylcholine receptor ?5 subunit gene (CHRNA5) nonsynonymous single nucleotide polymorphism (SNP) rs16969968 (Asp398Asn) has recently been discovered and replicated. As such, we tested whether this variant contributes to smoking in schizophrenia in a sample of 313 schizophrenia patients and 525 controls. The Asp398Asn risk allele is significantly associated with smoking severity independently in schizophrenia patient smokers (P = 0.001) and control smokers (P = 0.029). Furthermore, the same risk allele is significantly associated with schizophrenia in both Caucasian (P = 0.022) and African-American (P = 0.006) nonsmoker schizophrenia patients compared with control nonsmokers. Intriguingly, this SNP was not significantly associated with smoking status (smokers vs. nonsmokers) in either schizophrenia patients or controls. Therefore, our study identifies a genetic variant that is simultaneously linked to smoking and schizophrenia in the same cohort, but whether this SNP contributes to the increased smoking prevalence in schizophrenia patients requires additional studies. PMID:21418140

Hong, L E; Yang, X; Wonodi, I; Hodgkinson, C A; Goldman, D; Stine, O C; Stein, E S; Thaker, G K

2011-04-06

303

A CHRNA5 Allele Related to Nicotine Addiction and Schizophrenia  

PubMed Central

Schizophrenia and nicotine addiction are both highly heritable phenotypes. Because individuals with schizophrenia have a higher rate of smoking than those in the general population, one could hypothesize that genes associated with smoking might be over-represented in schizophrenia and thus help explain their increased smoking incidence. Although a number of genes have been proposed to explain the increased smoking risk in schizophrenia, none of them have been consistently linked to smoking and schizophrenia and thus difficult to explain the increased smoking in schizophrenia. A functional smoking-related nicotinic acetylcholine receptor ?5 subunit gene (CHRNA5) nonsynonymous SNP rs16969968 (Asp398Asn) has recently been discovered and replicated. As such, we tested whether this variant contributes to smoking in schizophrenia in a sample of 313 schizophrenia patients and 525 controls. The Asp398Asn risk allele is significantly associated with smoking severity independently in schizophrenia patient smokers (p=0.001) and in control smokers (p=0.029). Furthermore, the same risk allele is significantly associated with schizophrenia in both Caucasian (p=0.022) and African American (p=0.006) nonsmoker schizophrenia patients compared to control nonsmokers. Intriguing, this SNP was not significantly associated with smoking status (smokers vs. nonsmokers) in either schizophrenia patients or controls. Therefore, our study identifies a genetic variant that is simultaneously linked to smoking and schizophrenia in the same cohort, but whether and how this SNP contributes to the increased smoking prevalence in schizophrenia patients requires additional studies.

Hong, L. Elliot; Yang, Xi; Wonodi, Ikwunga; Hodgkinson, Colin A.; Goldman, David; Stine, O. Colin; Stein, Elliot S.; Thaker, Gunvant K.

2011-01-01

304

Allele-specific quantification of Drosophila engrailed and invected transcripts.  

PubMed Central

Changes in levels of transcription can be difficult to gauge in animals with lethal mutations. For example, mutations in a regulatory region of an essential gene can have secondary consequences that complicate attempts to quantify the transcripts produced by the mutant gene. We describe a method that circumvents this problem by revealing the relative amount of transcript produced from each allele in a heterozygote. With this method, recessive lethal mutations can be analyzed in animals that are phenotypically wild type. We used this technique to analyze mutations in the regulatory region of the Drosophila engrailed gene and found that truncations reduce transcription to levels that depend both upon the tissue and upon the location of the chromosomal break. We also found that these mutations affect expression of the linked invected gene, suggesting that engrailed and invected share a complex set of regulatory elements that operate over at least 85 kb. We suggest that this technique will have general utility for the quantitation of allele-specific transcripts, even when amounts of tissue are limiting. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4

Goldsborough, A S; Kornberg, T B

1994-01-01

305

Measuring and Testing Genetic Differentiation with Ordered versus Unordered Alleles  

PubMed Central

Estimates and variances of diversity and differentiation measures in subdivided populations are proposed that can be applied to haplotypes (ordered alleles such as DNA sequences, which may contain a record of their own histories). Hence, two measures of differentiation can be compared for a single data set: one (G(ST)) that makes use only of the allelic frequencies and the other (N(ST)) for which similarities between the haplotypes are taken into account in addition. Tests are proposed to compare N(ST) and G(ST) with zero and with each other. The difference between N(ST) and G(ST) can be caused by several factors, including sampling artefacts, unequal effect of mutation rates and phylogeographic structure. The method presented is applied to a published data set where a nuclear DNA sequence had been determined from individuals of a grasshopper distributed in 24 regions of Europe. Additional insights into the genetic subdivision of these populations are obtained by progressively combining related haplotypes and reanalyzing the data each time.

Pons, O.; Petit, R. J.

1996-01-01

306

Allelic loss and linkage studies in prostate cancer  

SciTech Connect

Prostate cancer is the most common malignancy in U.S. males. Many examples of familial aggregation have been reported, and segregration analysis suggests that an autosomal dominant gene with a penetrance of 88% by age 85 accounts for 9% of all cases. Because many dominant cancer predisposition syndromes are related to germline mutations in tumor suppressor genes, we analyzed a series of sporadic and hereditary tumors for allelic loss. High grade sporadic, paraffin-embedded, primary prostate tumors were obtained from the archival collection in the Department of Pathology at Yale and hereditary tumors from three families were obtained by an advertisement in the New York Times and from referrals by urologists. PCR analysis showed loss in 4/7 informative sporadic prostate tumors with NEFL (8p21), in 8/22 informative tumors with D10S169 (10q26-qter), in 2/8 informative tumors with D10S108 (10q) and in 4/23 informative tumors with D10S89 (10p) in agreement with previous studies. PYGM on chromosome 11 and D9S127 on chromosome 9 showed no loss. Linkage analysis with NEFL in 3 prostate cancer families gave strongly negative results for close linkage (Z=-2.1 at {theta}=0.01) but LOD scores were very dependent on parameters, e.g. gene frequency, phenocopy rate, and penetrance. Linkage analysis with chromosome 10 markers and systematic analysis of the genome for other area of allelic loss are underway.

Johnson, D.R.; Bale, A.E.; Lytton, B. [Yale Univ. School of Medicine, New Haven, CT (United States)] [and others

1994-09-01

307

Arms control and European security  

SciTech Connect

In October 1987 on the eve of the Washington summit, the Committee on Atlantic Studies, a group of European and North American scholars established in 1964 to promote transatlantic dialogue, met in Toronto to discuss the implications of the new arms control for European security. This book is the fruit of that meeting. Incorporating subsequent developments, up to Grobachev's December 1988 speech to the U.N., it provides a timely assessment of arms control issues from a variety of European and North American perspectives. The contributors to this volume council caution, suggesting that while progress is possible, it will probably be slow. This volume stresses the interplay of strategic and regional arms control. It includes analyses of nuclear, conventional, and naval arms control questions and embodies a broader a broader conception of arms control. The book links arms control to such political measures as confidence-building, conflict avoidance and superpower agreement to the neutrality of particular states.

Auton, G.P.

1989-01-01

308

["Medical devices and European regulations"].  

PubMed

In order to put on the European Market, the medical devices shall be in conformity with two European Directives transcribed in national regulation: Directive 90/385/CEE--20 June 1990: concerning the implantable active medical devices, mandatory since the 1/01/95; Directive 93/42/CEE--13 June 1993: concerning the medical devices, applicable since the 1/01/95 and mandatory the 14/06/98. Both impose the conformity to essential requirements which can be proved by different procedures of evaluation verified by notify bodies. Then, the CE mark, technical passport, can be apposed. To demonstrate this conformity, the manufacturers can use harmonized european standards without obligation. The "Safety clause" allows to follow the "well-founded" of the CE marking and the national systems of vigilance to register and evaluate the incidents and to define corrective actions. PMID:9181704

Fleur, F

1997-01-01

309

European Register of Marine Species  

NSDL National Science Digital Library

This website presents the European Register of Marine Species, an EU-funded marine biodiversity research consortium involving research groups in nine European nations. An ultimate goal of the project was to "produce a register of marine species in Europe, linked with a bibliography of identification guides, register of taxonomic experts, locations of collections of reference specimens, and an Information Pack on European marine biodiversity (based on this project's results)." The site links to brief and full checklists for numerous taxa including information on genus, higher taxon, authority, specific epithet, distribution, and more. From the species pages, site users can link to information about the checklists, identification guides, and taxonomic hierarchy. The homepage provides links to information about project participants, project background, and a simple map illustrating the geographic scope of the project. This site is also reviewed in the April 2, 2004 _NSDL Life Sciences Report_.

310

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

2007-08-17

311

ALMA European Project Scientist Appointed  

NASA Astrophysics Data System (ADS)

The new ALMA European Project Scientist is Dr. Leonardo Testi. He took up the appointment in May 2007. Leonardo Testi received his Ph.D. from the University of Florence in 1997. Subsequently he was a postdoctoral fellow at the Owens Valley Radio Observatory of Caltech. In 1998 he joined staff of the Arcetri Astrophysical Observatory, and later on of INAF, for which he also served on the Science Council. Leonardo has been chair of the European ALMA Science Advisory committee and a member of the ALMA Science Advisory committee, so he well knows the details of the project as well as the science that can be carried out with ALMA.

Wilson, T.

2007-06-01

312

European Union a New Babylon?  

NASA Astrophysics Data System (ADS)

The growing European Union faces growing problems in personal communication. These problems cannot be overcome only by more language courses in school. As important is a better mutual knowledge of the culture of other countries, a knowledge that can be gained only by a personal, professional stay in foreign countries. On university level, such stays are best organized by networks connecting European universities. In the broad field of measurement, this IMEKO symposium might offer a unique forum to thoroughly discuss structure and realization of such a network with all interested colleagues.

Mesch, F.

2010-07-01

313

Western European Specialists Section (WESS)  

NSDL National Science Digital Library

This site, hosted by the University of Virginia Library, is devoted to research into Western European history, literature, culture, and politics. The site provides links to well-maintained, quality sites in the aforementioned fields, including regional and historical resources, Websites on contemporary Europe, e-texts and e-text collections, guides to Library Resources, and book review sites. In addition, WESS offers an online newsletter which features articles of particular relevance to Western European subject specialists. WESS is part of the Association of College and Research Libraries, a division of the American Library Association.

314

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

315

A new analysis tool for individual-level allele frequency for genomic studies  

PubMed Central

Background Allele frequency is one of the most important population indices and has been broadly applied to genetic/genomic studies. Estimation of allele frequency using genotypes is convenient but may lose data information and be sensitive to genotyping errors. Results This study utilizes a unified intensity-measuring approach to estimating individual-level allele frequencies for 1,104 and 1,270 samples genotyped with the single-nucleotide-polymorphism arrays of the Affymetrix Human Mapping 100K and 500K Sets, respectively. Allele frequencies of all samples are estimated and adjusted by coefficients of preferential amplification/hybridization (CPA), and large ethnicity-specific and cross-ethnicity databases of CPA and allele frequency are established. The results show that using the CPA significantly improves the accuracy of allele frequency estimates; moreover, this paramount factor is insensitive to the time of data acquisition, effect of laboratory site, type of gene chip, and phenotypic status. Based on accurate allele frequency estimates, analytic methods based on individual-level allele frequencies are developed and successfully applied to discover genomic patterns of allele frequencies, detect chromosomal abnormalities, classify sample groups, identify outlier samples, and estimate the purity of tumor samples. The methods are packaged into a new analysis tool, ALOHA (Allele-frequency/Loss-of-heterozygosity/Allele-imbalance). Conclusions This is the first time that these important genetic/genomic applications have been simultaneously conducted by the analyses of individual-level allele frequencies estimated by a unified intensity-measuring approach. We expect that additional practical applications for allele frequency analysis will be found. The developed databases and tools provide useful resources for human genome analysis via high-throughput single-nucleotide-polymorphism arrays. The ALOHA software was written in R and R GUI and can be downloaded at http://www.stat.sinica.edu.tw/hsinchou/genetics/aloha/ALOHA.htm.

2010-01-01

316

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.

Falcone, Guido J.; Biffi, Alessandro; Devan, William; Jagiella, Jeremiasz M.; Schmidt, Helena; Kissela, Brett; Hansen, Bjorn 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

317

European consortium studies intelligent forecasting  

Microsoft Academic Search

The European Union funds the thematic network for intelligent forecasting systems (IFS) by the Brite-EuRam program. This program is in the field of industrial and material technologies. The network brings together industry and universities all over Europe for cooperation in forecasting systems of refineries and power systems. This article describes the general tasks, objectives, and worksteps associated with the subproject

B. E. Bitzer

1997-01-01

318

Retinal projections in European Salamandridae  

Microsoft Academic Search

The retinal projections to the brain were studied in three species of European Salamandridae using anterograde transport of horseradish peroxidase and autoradiography. The results obtained were basically identical for all species and confirmed earlier findings on the fiber supply to the preoptic nucleus and the basal optic neuropil. In the anterior thalamus projections to three distinct terminal fields are clearly

Bernd Fritzsch

1980-01-01

319

European Market for Processed Mango.  

National Technical Information Service (NTIS)

The study analyzes the European market for processed mango products--juices, concentrates, pulps, chutney, dried mango, and others--to determine whether it would be in the interest of West African producers to invest in plants, equipment, and market devel...

T. J. Mooney

1993-01-01

320

European challenge: developing global organizations  

Microsoft Academic Search

In the twenty-first century more European organizations will have to go global in scope and operations. Increasing globalization is forcing such a transformation of corporations, associations, and agencies. If business expects to be competitive in the global marketplace, their use of information technology is not only a force in this trend, but a powerful tool to achieve this goal. This

Philip R. Harris

2002-01-01

321

BSE : the European regulatory context.  

PubMed

The Bovine Spongiform Encephalopathy crisis provoked a fundamental re-appraisal of the way in which the European Community approaches matters of food safety. Between 28 July 1989, when restrictions on the dispatch of certain live cattle from the UK starte PMID:12631966

Chalus, T; Peutz, I

2000-10-01

322

European Monetary Union in Crisis  

Microsoft Academic Search

The world economy has gone through two years of a mixed but relatively strong recovery. In the European Union, however, the rebound was much less pronounced than in the rest of the world. Strong exports to the fast-growing emerging economies lead to a powerful upswing in some countries of the euro area, notably in Germany, and suggested in spring 2010

Stefan Ederer

2011-01-01

323

European small geostationary communications satellites  

Microsoft Academic Search

Hispasat Advanced Generation 1 (HAG1) is the first satellite using the SGEO platform, which is under the development in the ESA Artes-11 program. Since the last presentation in the IAC 2007, a European industrial consortium led by OHB has completed the mission and spacecraft design. The platform Preliminary Design Review has been carried out in May 2008. The customer for

Wei Sun; Frank Ellmers; Andreas Winkler; Herbert Schuff; Manuel Julián Sansegundo Chamarro

2011-01-01

324

Magnetic Compass of European Robins  

Microsoft Academic Search

The magnetic compass of European robins does not use the polarity of the magnetic field for detecting the north direction. The birds derive their north direction from interpreting the inclination of the axial direction of the magnetic field lines in space, and they take the direction on the magnetic north-south axis for \\

Wolfgang Wiltschko; Roswitha Wiltschko

1972-01-01

325

Evolution of European bat lyssaviruses  

Microsoft Academic Search

Forty-seven European bat lyssaviruses (EBL) and two African insectivorous bat lyssaviruses (Duvenhage viruses) were selected for a comparison to be made of their evolutionary relationships. Studies were based on direct sequencing of the PCR-amplified products of the 400 nucleotides coding for the amino terminus of the nucleoprotein. Phylogenetic relationships were analysed after bootstrap resampling using the maximum parsi- mony and

B. Amengual; J. E. Whitby; A. King; J. Serra Cobo; H. Bourhy

1997-01-01

326

1998 European cataract outcome study  

Microsoft Academic Search

Purpose: To collect clinical data on cataract surgery to allow participating surgeons to compare their performance with that of their colleagues in an anonymous manner.Setting: Surgeons from 31 surgical units providing cataract surgery in 13 European countries.Methods: Every patient at each participating unit having surgery during 1 study month was evaluated. Data were reported to the coordinating center at the

Mats Lundström; Peter Barry; Eugenio Leite; Helen Seward; Ulf Stenevi

2001-01-01

327

Transatlantic Tensions and European Security  

Microsoft Academic Search

Any nuanced assessment of current transatlantic tensions requires an awareness of their historical context. An understanding of the legacy of the Cold War in particular helps to answer the following questions: (1) What are the sources of current US-European tensions? (2) Has the transatlantic connection sustained mortal damage, or can it endure? (3) What changes of attitude and of focus

Mary Elise Sarotte

2006-01-01

328

Britain and the European Constitution  

Microsoft Academic Search

ABSTRACTThe sequence of events which followed the signature of the Rome treaty in 2004 demonstrated the uncertainties of reconciling pan European policy objectives with national political opinion. Public opinion in the United Kingdom was cautiously handled by ministers, taking care to avoid the issue becoming a clash between the parties. With some exceptions, relative moderation became the hallmark of the

Lord Windlesham

2007-01-01

329

European norms in hand hygiene  

Microsoft Academic Search

In the area of hand hygiene, European Norms exist, or are under development, with regard to protective gloves and for assessing the antimicrobial efficacy of hand disinfectants. Important norms for gloves are EN 420 (General requirements), EN 374 (Protective gloves against chemicals and microorganisms) and EN 455 (Medical gloves for single use). A suspension test for the demonstration of bactericidal

M. L Rotter

2004-01-01

330

Adolescent Leisure across European Nations.  

ERIC Educational Resources Information Center

Examined variations in adolescent time use within Europe and their relation to culture, focusing on organization of free time, most frequent leisure activities, and resulting emotional states. Found that European adolescents spent free time in a range of activities, including electronic media, computer games, playing musical instruments, reading,…

Flammer, August; Schaffner, Brigitta

2003-01-01

331

European SEPG '97 Event Planner.  

National Technical Information Service (NTIS)

This Planner is designed to help you find your way around European SEPG'97 conference and tailor the event to your requirements. It contains: (1) a short abstract for each tutorial and conference presentation; (2) profile s of the speakers; and (3) a perm...

1997-01-01

332

The European Microwave Signature Laboratory  

Microsoft Academic Search

The following paper describes in short a new research facility which has been installed at the Joint Research Centre of the Commission of the European Communities in Ispra, Italy. This unique measurement laboratory for signature research has been inaugurated and presented to the public in April 1992. At this occasion the JRC also distributed an announcement of research and experiment

A. J. Sieber

1992-01-01

333

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

PubMed

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 calculated. The robustness of this combined European database was tested by estimating parameter d for every DNA profile, where d=log(10)(Pm(c)/Pm(E)) Pm(c) is the match probability of the profile calculated from its cognate database and Pm(E) is the match probability of the combined European database. Overall there was a small tendency for Pm(c)>Pm(E) primarily because of sampling bias. This bias was removed by the simple expediency of applying an adjustment factor to the calculation of Pm(E). These were selected from the Balding size bias correction, the Balding and Nichols Fst correction, a minimum allele proportion (between 0.01 and 0.02), an upper bound of a 95% confidence interval (CI) and a lower bound on the genotype match probability. It was demonstrated that a single European database is a feasible proposition. A combination of different adjustment methods can be used to ensure that the result is conservative relative to the cognate database, and their effect measured by parameter d. PMID:12590058

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

2003-01-28

334

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

PubMed

Previous studies characterizing the Theileria parva p67 gene in East Africa revealed two alleles. Cattle-derived isolates associated with East Coast fever (ECF) have a 129bp deletion in the central region of the p67 gene (allele 1), compared to buffalo-derived isolates with no deletion (allele 2). In South Africa, Corridor disease outbreaks occur if there is contact between infected buffalo and susceptible cattle in the presence of vector ticks. Although ECF was introduced into South Africa in the early 20th century, it has been eradicated and it is thought that there has been no cattle to cattle transmission of T. parva since. The variable region of the p67 gene was amplified and the gene sequences analyzed to characterize South African T. parva parasites that occur in buffalo, in cattle from farms where Corridor disease outbreaks were diagnosed and in experimentally infected cattle. Four p67 alleles were identified, including alleles 1 and 2 previously detected in East African cattle and buffalo, respectively, as well as two novel alleles, one with a different 174bp deletion (allele 3), the other with a similar sequence to allele 3 but with no deletion (allele 4). Sequence variants of allele 1 were obtained from field samples originating from both cattle and buffalo. Allele 1 was also obtained from a bovine that tested T. parva positive from a farm near Ladysmith in the KwaZulu-Natal Province. East Coast fever was not diagnosed on this farm, but the p67 sequence was identical to that of T. parva Muguga, an isolate that causes ECF in Kenya. Variants of allele 2 were obtained from all T. parva samples from both buffalo and cattle, except Lad 10 and Zam 5. Phylogenetic analysis revealed that alleles 3 and 4 are monophyletic and diverged early from the other alleles. These novel alleles were not identified from South African field samples collected from cattle; however allele 3, with a p67 sequence identical to those obtained in South African field samples from buffalo, was obtained from a Zambian field isolate of a naturally infected bovine diagnosed with ECF. The p67 genetic profiles appear to be more complex than previously thought and cannot be used to distinguish between cattle- and buffalo-derived T. parva isolates in South Africa. The significance of the different p67 alleles, particularly the novel variants, in the epidemiology of theileriosis in South Africa still needs to be determined. PMID:19836893

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

2009-09-20

335

New York State TrueAllele(®) Casework Validation Study.  

PubMed

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

2013-07-18

336

Non-Equilibrium Allele Frequency Spectra Via Spectral Methods  

PubMed Central

A major challenge in the analysis of population genomics data consists of isolating signatures of natural selection from background noise caused by random drift and gene flow. Analyses of massive amounts of data from many related populations require high-performance algorithms to determine the likelihood of different demographic scenarios that could have shaped the observed neutral single nucleotide polymorphism (SNP) allele frequency spectrum. In many areas of applied mathematics, Fourier Transforms and Spectral Methods are firmly established tools to analyze spectra of signals and model their dynamics as solutions of certain Partial Differential Equations (PDEs). When spectral methods are applicable, they have excellent error properties and are the fastest possible in high dimension; see [15]. In this paper we present an explicit numerical solution, using spectral methods, to the forward Kolmogorov equations for a Wright-Fisher process with migration of K populations, influx of mutations, and multiple population splitting events.

Hey, Jody; Chen, Kevin

2011-01-01

337

A measure of population subdivision based on microsatellite allele frequencies  

SciTech Connect

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

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

1995-01-01

338

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.

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.; Rodriguez-Santana, Jose R.; Rodriguez-Cintron, 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

339

Low frequency of the scrapie resistance-associated allele and presence of lysine-171 allele of the prion protein gene in Italian Biellese ovine breed.  

PubMed

Frequencies of polymorphisms at codons 136, 154 and 171 of the prion protein (PrP) gene were studied in 1207 pure-bred and cross-bred Italian Biellese rams, a small ovine breed of about 65 000 head in Italy. Aside from the five most common alleles (VRQ, ARQ, ARR, AHQ and ARH), the rare ARK allele was also found, with the highest frequency reported so far in an ovine breed (2.5 %). ARK/--- genotypes had a total frequency of 4.9 %. The resistance-associated ARR allele was seen at a low frequency (8.3 %). Only 1.4 % of animals examined had a resistant ARR/ARR PrP genotype. Semi-resistant (ARR/ARQ, ARR/ARH and ARR/AHQ) PrP genotypes had a total frequency of 12.6 % and PrP genotypes that are associated with high scrapie susceptibility (e.g. VRQ/VRQ and ARQ/ARQ) had a total frequency of 81.1 %. Statistical analysis comparing PrP allele frequencies between pure-bred and cross-bred animals showed that the ARR allele occurred at a significantly lower frequency in pure-bred rams. Furthermore, comparison of PrP allele frequencies between pure-bred rams over 18 months of age and those below 18 months of age showed a significant decrease in the ARR allele in breeding rams over 18 months of age. Based on these results, breeding for scrapie resistance in the Biellese breed will have to take into account the low frequency of the ARR allele, which also seems to be subject to negative selection by farmers. Further investigation is required to understand whether the ARK allele is also associated with resistance to transmissible spongiform encephalopathies. PMID:15448380

Acutis, P L; Sbaiz, L; Verburg, F; Riina, M V; Ru, G; Moda, G; Caramelli, M; Bossers, A

2004-10-01

340

DEMETER DNA glycosylase establishes MEDEA polycomb gene self-imprinting by allele-specific demethylation.  

PubMed

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

2006-02-10

341

Common HLA Alleles Associated with Health, but Not with Facial Attractiveness  

PubMed Central

Three adaptive hypotheses have been proposed to explain the link between the human leucocyte antigen (HLA) genes, health measures and facial attractiveness: inbreeding avoidance, heterozygote advantage and frequency-dependent selection. This paper reports findings that support a new hypothesis relating HLA to health. We suggest a new method to quantify the level of heterozygosity. HLA heterozygosity did not significantly predict health measures in women, but allele frequency did. Women with more common HLA alleles reported fewer cold and flu bouts per year, fewer illnesses in the previous year and rated themselves healthier than women with rare alleles. To our knowledge, this is the first study to show a positive correlation between HLA allele frequency and general health measures. We propose that certain common HLA alleles confer resistance to prevalent pathogens. Nevertheless, neither HLA heterozygosity nor allele frequency significantly predicted how healthy or attractive men rated the female volunteers. Three non-mutually exclusive explanations are put forward to explain this finding.

Coetzee, Vinet; Barrett, Louise; Greeff, Jaco M.; Henzi, S. Peter; Perrett, David I.; Wadee, Ahmed A.

2007-01-01

342

Two classes of deleterious recessive alleles in a natural population of zebrafish, Danio rerio.  

PubMed Central

Natural populations carry deleterious recessive alleles which cause inbreeding depression. We compared mortality and growth of inbred and outbred zebrafish, Danio rerio, between 6 and 48 days of age. Grandparents of the studied fish were caught in the wild. Inbred fish were generated by brother-sister mating. Mortality was 9% in outbred fish, and 42% in inbred fish, which implies at least 3.6 lethal equivalents of deleterious recessive alleles per zygote. There was no significant inbreeding depression in the growth, perhaps because the surviving inbred fish lived under less crowded conditions. In contrast to alleles that cause embryonic and early larval mortality in the same population, alleles responsible for late larval and early juvenile mortality did not result in any gross morphological abnormalities. Thus, deleterious recessive alleles that segregate in a wild zebrafish population belong to two sharply distinct classes: early-acting, morphologically overt, unconditional lethals; and later-acting, morphologically cryptic, and presumably milder alleles.

McCune, Amy R; Houle, David; McMillan, Kyle; Annable, Rebecca; Kondrashov, Alexey S

2004-01-01

343

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

2006-10-03

344

5HTTLPR Short Allele, Resilience and Successful Aging in Older Adults  

PubMed Central

Objective Resilience is proposed as a significant component of successful aging. Young adult carriers of the Serotonin Transporter Polymorphism (5HTTLPR) short(s) allele appear to have reduced resilience to stress. We examined if presence of the short allele was associated with poorer emotional resilience in older adults. Methods In a cross-sectional study of 99 healthy, community-dwelling, older adults we determined 5HTTLPR genotype status and administered the Connor-Davidson Resilience Scale and self-reported measures of successful aging, cognition and health. Results There was no significant association between the 5HTTLPR s allele and resilience. S allele carriers had worse cognition and self-report ratings of successful aging. Conclusions These findings suggest that the impact of the 5HTTLPR s allele on stress-related outcomes may attenuate with older age. However, s allele status appears to be a biomarker of poorer self-rated successful aging, and cognitive performance in older adults.

O'Hara, Ruth; Marcus, Peter; Thompson, Wesley K.; Flournoy, John; Vahia, Ipsit; Lin, Xiaoyan; Hallmayer, Joachim; Depp, Colin; Jeste, Dilip V.

2011-01-01

345

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.

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

346

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.

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

2008-01-01

347

Haplotype variation of glu-d1 locus and the origin of glu-d1d allele conferring superior end-use qualities in common wheat.  

PubMed

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

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

2013-09-30

348

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.

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

349

Allelic clustering and ancestry-dependent frequencies of rs6232, rs6234, and rs6235 PCSK1 SNPs in a Northern Ontario population sample.  

PubMed

The PCSK1 (proprotein convertase subtilisin/kexin type 1) locus encodes proprotein convertase 1/3, an endoprotease that converts prohormones and proneuropeptides to their active forms. Spontaneous loss-of-function mutations in the coding sequence of its gene have been linked to obesity in humans. Minor alleles of two common non-synonymous single-nucleotide polymorphisms (SNPs), rs6232 (T?>?C, N221D) and rs6235 (C?>?G, S690T), have been associated with increased risk of obesity in European populations. In this study, we compared the frequencies of the rs6232 and rs6234 (G?>?C, Q665E) SNPs in Aboriginal and Caucasian populations of Northern Ontario. The two SNPs were all relatively less frequent in Aboriginals: The minor allele frequency of the rs6232 SNP was 0.01 in Aboriginals and 0.08 in Caucasians (P?allele already carrying the latter. These data indicate that, in Northern Ontario Aboriginals, the triple-variant PCSK1 allele is relatively rare and might be of lesser significance for obesity risk in this population. PMID:22307923

Sirois, Francine; Kaefer, Nadine; Currie, Krista A; Chrétien, Michel; Nkongolo, Kabwe K; Mbikay, Majambu

2012-02-04

350

European Scientific Notes, Volume 23, Number 12.  

National Technical Information Service (NTIS)

The publication presents brief articles concerning recent developments in European scientific research. It is hoped that these articles (which do not constitute part of the scientific literature) may prove of value to both American and European scientists...

L. M. Slifkin V. S. Hewitson

1969-01-01

351

European Community Projects on Surface Electromyography.  

National Technical Information Service (NTIS)

Three European Projects dealing with Surface Electromyography (SEMG) are presented. Surface EMG for Non-invasive Assessment of Muscles (SENIAM, 1996- 2000) produced a set of European guidelines concerning EMG sensors, their positioning criteria, EMG proce...

R. Merletti H. Hermens R. Kadefors

2001-01-01

352

European Scientific Notes. Volume 37, Numbers 12.  

National Technical Information Service (NTIS)

European Scientific Notes (ESN) is a monthly publication with brief articles on recent developments in European scientific research. The publication is not intended to be part of the scientific literature. The value of ESN articles to Americans is to call...

L. E. Shaffer

1983-01-01

353

Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population  

Microsoft Academic Search

Mutations in the aldolase B gene (ALDOB) impairing enzyme activity toward fructose-1-phosphate cleavage cause hereditary fructose intolerance (HFI). Diagnosis of\\u000a the disease is possible by identifying known mutant ALDOB alleles in suspected patients; however, the frequencies of mutant alleles can differ by population. Here, 153 American HFI\\u000a patients with 268 independent alleles were analyzed to identify the prevalence of seven

Laura Yerkes; Elizabeth P. Ewen; Tiffany Zee; Dean R. Tolan

2010-01-01

354

Gorilla class I major histocompatibility complex alleles: comparison to human and chimpanzee class I  

PubMed Central

14 gorilla class I major histocompatibility complex (MHC) alleles have been isolated, sequenced, and compared to their counterparts in humans and chimpanzees. Gorilla homologues of HLA-A, -B, and -C were readily identified, and four Gogo-A, four Gogo-B, and five Gogo-C alleles were defined. In addition, an unusual Gogo class I gene with features in common with HLA-A and its related pseudogene, HLA-H, is described. None of the gorilla alleles is identical or even closely related to known class I alleles and each encodes a unique antigen recognition site. However, the majority of polymorphic substitutions and sequence motifs of gorilla class I alleles are shared with the human or chimpanzee systems. In particular, elements shared with HLA-A2 and HLA-B27 are found in Gogo-A and -B alleles. Diversity at the Gogo-B locus is less than at the Gogo-A locus, a trend the opposite of that seen for HLA-A and -B. The Gogo-C locus also appears to have limited polymorphism compared to Gogo-A. Two basic Gogo-C motifs were found and they segregate with distinctive sets of HLA-C alleles. HLA-A allels are divided into five families derived from two ancient lineages. All chimpanzee A alleles derived from one of these lineages and all gorilla alleles derive from the other. Unlike chimpanzee Patr-A alleles, the Gogo-A alleles do not clearly partition with one of the HLA-A families but have similarities with two. Overall, gorilla class I diversity appears from this sampling to show more distinctions from class I HLA than found for chimpanzee class I.

1991-01-01

355

Numbers of sporophytic self-incompatibility alleles in populations of wild radish  

Microsoft Academic Search

To estimate the numbers of sporophytic S-alleles in two adjacent populations of wild radish, we performed 701 reciprocal crosses among 50 individuals. Each cross was replicated five times in each direction. Sixteen plants were fully intercompatible, indicating the presence of at least 32 S-alleles in the two populations. A minimum of 22 S-alleles occur in a single population. The frequency

J. D. Karron; D. L. Marshall; D. M. Oliveras

1990-01-01

356

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

Microsoft Academic Search

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

Karin T. Berggren; Jennifer M. Seddon

2008-01-01

357

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

358

Phylogenetic history of hominoid DRB loci and alleles inferred from intron sequences.  

PubMed

The evolutionary relationships among the MHC class II DRB4, DRB5 and DRB6 loci as well as the allelic lineages and alleles of the DRB1 locus were studied based on intron 1 and intron 2 sequences from humans, chimpanzee (Pan troglodytes), bonobo (Pan paniscus) and gorilla (Gorilla gorilla). The phylogenetic trees for these sequences indicate that most of the DRB1 allelic lineages predate the separation of the hominoid species studied, consistent with previous analysis of the coding sequences of these lineages. However, the intron sequence variation among alleles within DRB1 allelic lineages is very limited, consistent with the notion that the majority of the contemporary alleles have been generated within the last 250,000 years. The clustering of the DRB1 allelic lineages *08 and *12 with *03 supports a common ancestry for the DR8 and DR52 haplotypes. Similarly, the clustering of DRB1 allelic lineages *15 and *01 with the DRB3 locus is consistent with a common ancestry for the DR1 and DR51 haplotypes. Two cases of recombination around the second exon were observed: 1) the HLA-DRB6 locus appears to have been generated through a recombination between a DRB5 allele and an ancestral DRB6 allele, and 2) the gorilla sequence Gogo-DRB1 *03 appears to have been generated through a recombination between the DRB3 locus and an allele from the DRB1 *03 allelic lineage. The nucleotide substitution rate of DRB introns was estimated to 0.85-1.63 x 10(-9) per site per year, based on comparisons between the most closely related sequences from different hominoid species. This estimate is similar to the substitution rate for other intronic regions of the primate genome. PMID:10319273

Bergström, T F; Erlandsson, R; Engkvist, H; Josefsson, A; Erlich, H A; Gyllensten, U

1999-02-01

359

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

360

Estimating Y-STR allelic drop-out rates and adjusting for interlocus balances.  

PubMed

Y chromosome short tandem repeats (Y-STRs) are valuable genetic markers in certain areas of forensic case-work. However, when the Y-STR DNA profile is weak, the observed Y-STR profile may not be complete--i.e. locus drop-out may have occurred. Another explanation could be that the stain DNA did not have a Y-STR allele that was detectable with the method used (the allele is a 'null allele'). If the Y-STR profile of a stain is strong, one would be reluctant to consider drop-out as a reasonable explanation of lack of a Y-STR allele and would maybe consider 'null allele' as an explanation. On the other hand, if the signal strengths are weak, one would most likely accept drop-out as a possible explanation. We created a logistic regression model to estimate the probability of allele drop-out with the Life Technologies/Applied Biosystems AmpFlSTR(®) Yfiler(®) kit such that the trade-off between drop-outs and null alleles could be quantified using a statistical model. The model to estimate the probability of drop-out uses information about locus imbalances, signal strength, the number of PCR cycles, and the fragment size of Yfiler. We made two temporarily separated experiments and found no evidence of temporal variation in the probability of drop-out. Using our model, we found that for 30 PCR cycles with a 150 bp allele, the probability of drop-out was 1:5000 corresponding to the average estimate of the probability of Y-STR null alleles at a signal strength of 1249 RFU. This means that the probability of a null allele is higher than that of an allele drop-out at e.g. 4000 RFU and the probability of drop-out is higher than that of a null allele at e.g. 75 RFU. PMID:23453365

Andersen, Mikkel Meyer; Mogensen, Helle Smidt; Eriksen, Poul Svante; Olofsson, Jill Katharina; Asplund, Maria; Morling, Niels

2013-02-27

361

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

362

Temporary Youth Migration and European Identity  

Microsoft Academic Search

\\u000a Every European Union citizen has the right to live and work in any EU member state they please. Although Europeans may have\\u000a been traditionally reluctant to undertake mobility in the past, an increasing number of young Europeans now exercise this\\u000a right to move via both individual actions and participation in EUmediated programmes. It may indeed be the case that European

Marion Hauvette

363

EAAE and Astronomy for European schools  

NASA Astrophysics Data System (ADS)

The aim of the European Association for Astronomy Education (EAAE) is to promote astronomy education in schools and to stimulate the interest of pupils and students for astronomy. European projects for students and teachers such as Catch a Star, Sea and Space Life in the Universe, Physics on Stage and EAAE-Summer Schools show the different EAAE activities. Science on Stage 2005 and the European Astronomy Day 2007, two joint European projects with EAAE involvement are presented.

Wagner, F.

2005-11-01

364

Maternal FMR1 premutation allele expansion and contraction in fraternal twins.  

PubMed

Fragile X syndrome results from an expansion of the CGG trinucleotide repeat in the 5' untranslated region of the Fragile X Mental Retardation 1 (FMR1) gene. Expansion of a maternal premutation allele is the mechanism by which a full mutation allele arises; contraction of a maternal premutation allele is rare. Here we report on both an expansion and contraction of a maternal FMR1 premutation allele in fraternal twins. The propositus was the product of a 29-week gestation twin pregnancy and was referred for FMR1 testing due to developmental delay. A FMR1 full mutation with complete methylation was observed on Southern blot analysis. Evaluation of the maternal FMR1 gene by PCR revealed a normal and premutation allele with CGG repeat numbers of 30 and 93, respectively. Subsequent FMR1 testing on the twin sister of the propositus detected CGG repeat numbers of 30 and 54. The FMR1 CGG repeat number of the reproductive partner was 30. The FMR1 CGG repeat 30 allele in the twin sister was determined to be of paternal origin and the FMR1 allele with a CGG repeat number of 54 was of maternal origin. This observation is particularly interesting not only because of the concomitant donation of a FMR1 expanded and contracted premutation allele in a twin pregnancy but also because of the significant degree of contraction (39 repeats) of the maternal premutation allele. © 2013 Wiley Periodicals, Inc. PMID:23949867

Alfaro, Maria P; Cohen, Melinda; Vnencak-Jones, Cindy L

2013-08-15

365

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

366

RAET1/ULBP alleles and haplotypes among Kolla South American Indians.  

PubMed

NK cell cytolysis of infected or transformed cells can be mediated by engagement of the activating immunoreceptor NKG2D with one of eight known ligands (MICA, MICB and RAET1E-N) and is essential for innate immunity. As well as diversity of NKG2D ligands having the same function, allelic polymorphism and ethnic diversity has been reported. We previously determined HLA class I allele and haplotype frequencies in Kolla South American Indians who inhabit the northwest provinces of Argentina, and were found to have a similar restricted allelic profile to other South American Indians and novel alleles not seen in other tribes. In our current study, we characterized retinoic acid early transcription-1 (RAET1) alleles by sequencing 58 unrelated Kolla people. Only three of six RAET1 ligands were polymorphic. RAET1E was most polymorphic with five alleles in the Kolla including an allele we previously described, RAET1E*009 (allele frequency (AF) 5.2%). Four alleles of RAET1L were also found and RAET1E*002 was most frequent (AF=78%). Potential functional diversity only affected RAET1E and RAET1L, which were in linkage disequilibrium indicating a selective advantage. The results suggest that limited RAET1 polymorphism in the Kolla was not detrimental to human survival but still necessary and may affect disease susceptibility or severity. PMID:23416094

Cox, Steven T; Arrieta-Bolaños, Esteban; Pesoa, Susanna; Vullo, Carlos; Madrigal, J Alejandro; Saudemont, Aurore

2013-02-13

367

Europeanizing Education: Governing a New Policy Space  

ERIC Educational Resources Information Center

|The study of common and diverse effects in the field of education across Europe is a growing field of inquiry and research. It is the result of many actions, networks and programmes over the last few decades and the development of common European education policies. "Europeanizing Education" describes the origins of European education policy, as…

Lawn, Martin; Grek, Sotiria

2012-01-01

368

The European Union: A Guide for Americans  

NSDL National Science Digital Library

The European Union (EU) presents the The European Union: A Guide for Americans as an introduction to the workings of the EU system as well as EU-US relations. Seven chapters span EU history, governance, and the euro, and a timeline of European Integration, maps, photos, and resource links enrich this useful text.

369

Natural gas demand surges among European customers  

Microsoft Academic Search

Europe's view of natural gas as a clean fuel is driving demand faster than European producers can supply the fuel. By 2010 European gas demand is expected to rise by 50%, so imports will need to rise in step. There are plenty of gas reserves within and in reach of the European market to meet increasing needs. But current low

1993-01-01

370

European Initiatives in Postgraduate Education in Gerontology  

ERIC Educational Resources Information Center

This paper describes three innovative European initiatives in postgraduate education in gerontology. The first is the European Masters Program in Gerontology (EuMaG), developed as an interdisciplinary joint program, supported and delivered by 22 European universities. Second, the Nordplus initiative to increase mobility of students and staff in…

van Rijsselt, Rene J. T.; Parkatti, Terttu; Troisi, Joseph

2007-01-01

371

A European Culture of Religious Tolerance  

Microsoft Academic Search

In the European integration process, the European Union continues to struggle for an identity that can generate widespread support amongst its peoples. In this context it has been suggested by some that the European Union should embrace the Christian values that underpin its national traditions and cultures. I shall argue that, instead of relying on a communitarian vision of a

Daniel Augenstein

2008-01-01

372

Unity and Plurality of the European Cycle  

Microsoft Academic Search

We apply uni- and multivariate unobserved components models to the study of European growth cycles. The multivariate dimension enables to search similar or, more strongly, common components among national GDP series (quarterly data from 1960 to 1999). Three successive ways to exhibit the European cycle satisfactorily converge: the direct decomposition of the aggregate European GDP; the aggregation of the member

Guilhem Bentoglio; Jacky Fayolle; Matthieu Lemoine

2002-01-01

373

A European perspective on Digital Earth  

Microsoft Academic Search

The purpose of this paper is to contribute to the definition of a European perspective on Digital Earth (DE), identify some actions that can contribute to raise the awareness of DE in the European context and thus strengthen the European contribution to the International Society for Digital Earth (ISDE). The paper identifies opportunities and synergies with the current policy priorities

Alessandro Annoni; Max Craglia; M. Ehlers; Y. Georgiadou; A. Giacomelli; M. Konecny; N. Ostlaender; G. Remetey-Fulopp; D. Rhind; P. Smits; S. Schade

2011-01-01

374

European cities and place-identity  

Microsoft Academic Search

Scholars concerned with different aspects of cities (formal, spatial, social, economic) converge in pointing place identity - the city's distinctive characteristics - as a powerful means to play right with intercity competition in the era of economic globalisation and European integration. To enhance place-identity in European cities, European Union and local governments have been supporting built heritage; financing research and

Aspa Gospodini

2002-01-01

375

Five political ideas of European contract law  

Microsoft Academic Search

This paper explores the possible implications of leading contemporary theories of political philosophy for some of the main questions that the political institutions of the European Union will have to decide on concerning the future of European contract law. Thus, it explores what a utilitarian, liberal-egalitarian, libertarian, communitarian, deliberative\\/citizenship idea of European contract law might look like. The primary aim

M. W. Hesselink

2011-01-01

376

Food and Health: A European Perspective  

Microsoft Academic Search

This paper addresses four issues which arise from increasing concerns about overweight and obesity in European countries. First, we explore the main stylized facts of the phenomenon. We show that although Europeans are not obese like Americans, there is robust evidence that adult and childhood obesity rates tend to increase substantially in many European countries. The second part of the

Luciano Venturini

2006-01-01

377

European Virtual Campus for Biomedical Engineering EVICAB  

Microsoft Academic Search

European Commission has funded building a curriculum on Biomedical Engineering to the Internet for European universities under the project EVICAB. EVICAB forms a curriculum which will be free access and available free of charge. Therefore, in addition to the European universities, it will be available worldwide. EVICAB will make high quality education available for everyone, not only for the university

J. A. Malmivuo; J. O. Nousiainen; K. V. Lindroos

2007-01-01

378

Development of Wind Energy in European Union  

Microsoft Academic Search

Nowadays, the European Union and the world as a whole find themselves in front of a crossroad concerning the future of the energy. Today's environmental policies are largely devoted to fostering the development and implementation in European Union of renewable energy technologies. This paper analyses the wind energy development in European Union in terms of legislative framework, wind potential and

D. ANDREEA ZAMFIR

2007-01-01

379

Engineering Europeanization: the role of the European institutions in shaping national media regulation  

Microsoft Academic Search

This article investigates the processes through which the European Union has become a major actor in national media regulation. The European Union is not viewed as a monolith but as a constellation of institutions that pursue Europeanization with different policy instruments and intersecting agendas. Therefore, the article illustrates how the European Commission (in turn, operating through different Directorates-General and the

Alison Harcourt

2002-01-01

380

Distribution of BoLA-DRB3 allelic frequencies and identification of a new allele in the iranian cattle breed sistani (Bos indicus).  

PubMed

The distribution of the frequencies of BoLA-DRB3 gene alleles in the Iranian cattle breed Sistani was studied by the PCR-RFLP ("hemi-nested") assay using restriction endonucleases RsaI, HaeIII and BstYI. In the examined cattle breed (65 animals) 32 alleles have been identified one of which being described for the first time (6.15% frequency). The nucleotide sequence of the polymorphic region of exon 2 of this allele has been determined and submitted in the GeneBank database under accession number DQ486519. The submitted sequence has maximum homology (92%) with the previously described sequence DRB3-mRNA from Bos indicus (AccN X79346) and differs from it by 24 nucleotide substitutions which result in 16 amino acid substitutions. The peptide (on the basis of the reconstructed amino acid sequence) has 89% identity to the sequence encoded by the BIDRBF 188 locus (Bos indicus). The results obtained permit the sequence described by us to be considered as a new allele of the BoLA-DRB3 gene (DRB3.2**X). The total frequency of the main six alleles (DRB3.2*X, *10, *11, *20, *34 and *X) occurring with a frequency of over 5% is about 60% in Iranian Sistani cattle. Fifteen alleles have <1% frequency. The highest frequency was observed for DRB3.2*8 allele (21.54%) like in other previously described breeds of Bos indicus (up to 23.07%). The Iranian breed Sistani has a high level of similarity by the spectrum of BoLA-DRB3 alleles and their frequencies to other Bos indicus breeds and significantly differs by these criteria from the Bos taurus breeds. The Iranian Sistani herd under study includes alleles associated with to resistance to leukemia (DRB3.2*ll and *23) and to different forms of mastitis (DRB3.2*2, *7, *11, *23 and *24) although their frequencies are low (from 0.77 to 5.37%). On the whole, a high level of diversity of BoLA-DRB3 gene alleles and the availability of alleles associated with resistance to different diseases makes this breed of interest for breeding practice. PMID:19334617

Mohammadi, A; Nassiry, M R; Mosafer, J; Mohammadabadi, M R; Sulimova, G E

2009-02-01

381

Integrating the European Securities Settlement  

NASA Astrophysics Data System (ADS)

The cross-border securities settlement in Europe is still said to be highly inefficient. One main reason can be seen in technical barriers between the different domestic settlement systems. Beside efforts to implement industry-specific communication standards an integration of the different settlement systems is necessary. The CSD-link model, the hub and spokes model, and the European CSD model aim to integrate European securities settlement. They have in common that they address the problem of interlinkage of national Central Securities Depositories and differ essentially in the way of achieving integration. These models are evaluated from a macro-economic perspective considering transaction costs, risks, and the integration of the cross-border securities settlement process.

Schaper, Torsten

382

European Space Agency: Mars Express  

NSDL National Science Digital Library

Europe reclaims a stake in Mars exploration! The European Space Agency has launched this informative site in conjunction with the Mars Express mission which lifted off on June 3, 2003. Before the live Webcast of the craft arrival in December, 2003, visitors to this well organized site can track the progress of the spacecraft. You can also learn a lot about early attempts to explore mars and investigate the possibility of life on Mars. The European Space Agency also has given the public detailed technical information on Mars Express and the Beagle 2 Lander that will actually land on the surface of the red planet. This site is an exciting way for educators, students and the general public to be actively involved with this historic event.

383

Ambiguous allele combinations in HLA Class I and Class II sequence-based typing: when precise nucleotide sequencing leads to imprecise allele identification  

Microsoft Academic Search

Sequence-based typing (SBT) is one of the most comprehensive methods utilized for HLA typing. However, one of the inherent problems with this typing method is the interpretation of ambiguous allele combinations which occur when two or more different allele combinations produce identical sequences. The purpose of this study is to investigate the probability of this occurrence. We performed HLA-A,-B SBT

Sharon D Adams; Kathleen C Barracchini; Deborah Chen; FuMeei Robbins; Lu Wang; Paula Larsen; Robert Luhm; David F Stroncek

2004-01-01

384

European consortium studies intelligent forecasting  

SciTech Connect

The European Union funds the thematic network for intelligent forecasting systems (IFS) by the BriteEuRam program. This program is in the field of industrial and material technologies. The network brings together industry and universities all over Europe for cooperation in forecasting systems of refineries and power systems. This article describes the general tasks, objectives, and worksteps associated with the subproject of forecasting in industrial and power systems.

Bitzer, B.E. [Univ. of Paderborn, Soest (Germany)

1997-04-01

385

European virtual classrooms: building effective \\  

Microsoft Academic Search

This paper presents Learning@Europe, an educational service, supported by VR, that has involved in year 2004–2005 more than\\u000a 1,000 students from 6 different European countries. L@E has fostered the creation\\/reinforcement of three different kinds of\\u000a communities: (1) the classroom community (reinforcing the bonds among students, and between students and their teachers),\\u000a (2) communities among different schools competing together through 3D

Nicoletta Di Blas; Caterina Poggi

2007-01-01

386

Environmental costs in European aviation  

Microsoft Academic Search

This paper presents estimates of environmental costs in a set of 36 European airline markets. Cost are calculated for noise, air pollution and accident risk using data on aircraft emissions, exposure-response parameters and economic valuation of environmental goods. The ‘medium value’ cost estimate is 0.0201ECU per passenger-km. This result suggests that environmental costs represent only a small fraction (2.5%) of

Youdi Schipper

2004-01-01

387

EST: The European Solar Telescope  

NASA Astrophysics Data System (ADS)

The European Solar Telescope (EST) is a project for a 4 meter-class ground-based telescope, to be located in the Canary Islands. The project is promoted by the European Association for Solar Telescopes (EAST), a consortium formed by research organizations from 15 European countries. EST will be optimized for studies of magnetic coupling between the deep photosphere and upper chromosphere. The project has been approved for funds by the European Union, within the FP-7 framework, to produce the design of all systems and subsystems of the telescope during the next three years. This includes the optical and optomechanical design of the telescope itself and of the instruments and their control. MCAO will be included in the optical path in a natural way to compensate for atmospheric disturbances in an optimum way. The design of EST will strongly emphasize the use of a large number of visible and near-infrared instruments simultaneously which will influence the telescope design from the very beginning. This communication will center mainly on the scientific objectives that EST will address. Generally speaking, they involve understanding how the magnetic field emerges through the solar surface, interacts with the plasma dynamics to transfer energy between different regions, and finally releases it in the form of heat or as violent events in the solar chromosphere and corona. Among the many topics of interest, one may cite, as described in the EST Science Requirements Document: small-scale flux emergence in quiet sun regions, large-scale magnetic structures, magnetic flux cancellation processes, polar magnetic fields, magnetic topology of the photosphere and chromosphere, conversion of mechanical to magnetic energy in the photosphere, wave propagation from photosphere to chromosphere, energy dissipation in the chromosphere at small and large scales, etc. The present status and future perspectives of the project will also be outlined.

Collados, M.

2008-09-01

388

Deutche Bahn European Train Timetables  

NSDL National Science Digital Library

Deutche Bahn AG offers this site, which is sure to be useful to European train travelers. The interactive train timetable allows the user to enter the city of departure and arrival, as well as the date and time, and returns the relevant train schedules. Users can also view station schedules, detailed route itineraries, and graphical route representations (Java). Pricing information is available for selected German routes only. The site is available in English and German.

389

European Counterpoint to Chapter 20  

Microsoft Academic Search

There exists little significant evidence on which to base the use of inferior vena cava (IVC) filters (1–3; see Table 1) and,\\u000a at present, there are no UK or European regulatory guidelines for their use. They are therefore used on a case-by-case basis\\u000a with moderate variation between centers. The Royal Liverpool University Hospital Interventional Radiology Department places\\u000a about 12 IVC

A. E. Healey; Derek A. Gould

390

European Association for International Education  

NSDL National Science Digital Library

More and more organizations are concerned with the future of higher education, and one dedicated to examining this quickly changing area is the European Association for International Education (EAIE). The primary aim of the EAIE is "the stimulation and facilitation of the internationalization of higher education in Europe and around the world." On their homepage, visitors can learn about their annual conference and also read about their latest policy statements and press releases.

391

Traceability from a European perspective  

Microsoft Academic Search

At pan-European level there is a need for traceability systems giving information on origin, processing, retailing and final destination of foodstuffs. Such systems shall enhance consumer confidence in food; enable the regulatory authorities to identify and to withdraw health hazardous and non-consumable foodstuffs from the market. Animal feeds are an element in this “food-to-farm” approach to public health. Such feedstuffs

F. Schwägele

2005-01-01

392

Warming permafrost in European mountains  

Microsoft Academic Search

Here we present the first systematic measurements of European mountain permafrost temperatures from a latitudinal transect of six boreholes extending from the Alps, through Scandinavia to Svalbard. Boreholes were drilled in bedrock to depths of at least 100 m between May 1998 and September 2000. Geothermal profiles provide evidence for regional-scale secular warming, since all are nonlinear, with near-surface warm-side

Charles Harris; Daniel Vonder Mühll; Ketil Isaksen; Wilfried Haeberli; Johan Ludvig Sollid; Lorenz King; Per Holmlund; Francesco Dramis; Mauro Guglielmin; David Palacios

2003-01-01

393

European foulbrood in honey bees.  

PubMed

European foulbrood (EFB) is a severe bacterial brood disease caused by the Gram-positive bacterium Melissocccus plutonius. The disease has a worldwide distribution and is an increasing problem in some areas. Although the causative agent of EFB was described almost a century ago, many basic aspects of its pathogenesis are still unknown. This review presents both historical results and recent molecular data to synthesize present knowledge of this enigmatic honey bee disease. PMID:20105559

Forsgren, Eva

2009-12-21

394

Origins, distribution and expression of the Duarte-2 (D2) allele of galactose-1-phosphate uridylyltransferase.  

PubMed

Duarte galactosemia is a mild to asymptomatic condition that results from partial impairment of galactose-1-phosphate uridylyltransferase (GALT). Patients with Duarte galactosemia demonstrate reduced GALT activity and carry one profoundly impaired GALT allele (G) along with a second, partially impaired GALT allele (Duarte-2, D2). Molecular studies reveal at least five sequence changes on D2 alleles: a p.N314D missense substitution, three intronic base changes and a 4 bp deletion in the 5' proximal sequence. The four non-coding sequence changes are unique to D2. The p.N314D substitution, however, is not; it is found together with a silent polymorphism, p.L218(TTA), on functionally normal Duarte-1 alleles (D1, also called Los Angeles or LA alleles). The HapMap database reveals that p.N314D is a common human variant, and cross-species comparisons implicate D314 as the ancestral allele. The p.N314D substitution is also functionally neutral in mammalian cell and yeast expression studies. In contrast, the 4 bp 5' deletion characteristic of D2 alleles appears to be functionally impaired in reporter gene transfection studies. Here we present allele-specific qRT-PCR evidence that D2 alleles express less mRNA in vivo than their wild-type counterparts; the difference is small but statistically significant. Furthermore, we characterize the prevalence of the 4 bp deletion in GG, NN and DG populations; the deletion appears exclusive to D2 alleles. Combined, these data strongly implicate the 4 bp 5' deletion as a causal mutation in Duarte galactosemia and suggest that direct tests for this deletion, as proposed here, could enhance or supplant current tests, which define D2 alleles on the basis of the presence and absence of linked coding sequence polymorphisms. PMID:19224951

Carney, Amanda E; Sanders, Rebecca D; Garza, Kerry R; McGaha, Lee Anne; Bean, Lora J H; Coffee, Bradford W; Thomas, James W; Cutler, David J; Kurtkaya, Natalie L; Fridovich-Keil, Judith L

2009-02-18

395

Origins, distribution and expression of the Duarte-2 (D2) allele of galactose-1-phosphate uridylyltransferase  

PubMed Central

Duarte galactosemia is a mild to asymptomatic condition that results from partial impairment of galactose-1-phosphate uridylyltransferase (GALT). Patients with Duarte galactosemia demonstrate reduced GALT activity and carry one profoundly impaired GALT allele (G) along with a second, partially impaired GALT allele (Duarte-2, D2). Molecular studies reveal at least five sequence changes on D2 alleles: a p.N314D missense substitution, three intronic base changes and a 4 bp deletion in the 5? proximal sequence. The four non-coding sequence changes are unique to D2. The p.N314D substitution, however, is not; it is found together with a silent polymorphism, p.L218(TTA), on functionally normal Duarte-1 alleles (D1, also called Los Angeles or LA alleles). The HapMap database reveals that p.N314D is a common human variant, and cross-species comparisons implicate D314 as the ancestral allele. The p.N314D substitution is also functionally neutral in mammalian cell and yeast expression studies. In contrast, the 4 bp 5? deletion characteristic of D2 alleles appears to be functionally impaired in reporter gene transfection studies. Here we present allele-specific qRT–PCR evidence that D2 alleles express less mRNA in vivo than their wild-type counterparts; the difference is small but statistically significant. Furthermore, we characterize the prevalence of the 4 bp deletion in GG, NN and DG populations; the deletion appears exclusive to D2 alleles. Combined, these data strongly implicate the 4 bp 5? deletion as a causal mutation in Duarte galactosemia and suggest that direct tests for this deletion, as proposed here, could enhance or supplant current tests, which define D2 alleles on the basis of the presence and absence of linked coding sequence polymorphisms.

Carney, Amanda E.; Sanders, Rebecca D.; Garza, Kerry R.; McGaha, Lee Anne; Bean, Lora J. H.; Coffee, Bradford W.; Thomas, James W.; Cutler, David J.; Kurtkaya, Natalie L.; Fridovich-Keil, Judith L.

2009-01-01

396

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

397

Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles.  

PubMed

The CGG repeat in the 5' untranslated region of the fragile X mental retardation 1 gene (FMR1) exhibits remarkable instability upon transmission from mothers with premutation alleles. A collaboration of 13 laboratories in eight countries was established to examine four issues concerning FMR1 CGG-repeat instability among females with premutation (approximately 55-200 repeats) and intermediate (approximately 46-60 repeats) alleles. Our central findings were as follows: (1) The smallest premutation alleles that expanded to a full mutation (>200 repeats) in one generation contained 59 repeats; sequence analysis of the 59-repeat alleles from these two females revealed no AGG interruptions within the FMR1 CGG repeat. (2) When we corrected for ascertainment and recalculated the risks of expansion to a full mutation, we found that the risks for premutation alleles with <100 repeats were lower than those previously published. (3) When we examined the possible influence of sex of offspring on transmission of a full mutation-by analysis of 567 prenatal fragile X studies of 448 mothers with premutation and full-mutation alleles-we found no significant differences in the proportion of full-mutation alleles in male or female fetuses. (4) When we examined 136 transmissions of intermediate alleles from 92 mothers with no family history of fragile X, we found that, in contrast to the instability observed in families with fragile X, most (99/136 [72.8%]) transmissions of intermediate alleles were stable. The unstable transmissions (37/136 [27.2%]) in these families included both expansions and contractions in repeat size. The instability increased with the larger intermediate alleles (19% for 49-54 repeats, 30.9% for 55-59, and 80% for 60-65 repeats). These studies should allow improved risk assessments for genetic counseling of women with premutation or intermediate-size alleles. PMID:12529854

Nolin, Sarah L; Brown, W Ted; Glicksman, Anne; Houck, George E; Gargano, Alice D; Sullivan, Amy; Biancalana, Valérie; Bröndum-Nielsen, Karen; Hjalgrim, Helle; Holinski-Feder, Elke; Kooy, Frank; Longshore, John; Macpherson, James; Mandel, Jean-Louis; Matthijs, Gert; Rousseau, Francois; Steinbach, Peter; Väisänen, Marja-Leena; von Koskull, Harriet; Sherman, Stephanie L

2003-01-14

398

BMP2/BMP4 colorectal cancer susceptibility loci in northern and southern European populations.  

PubMed

Genome-wide association studies have successfully identified 20 colorectal cancer susceptibility loci. Amongst these, four of the signals are defined by tagging single nucleotide polymorphisms (SNPs) on regions 14q22.2 (rs4444235 and rs1957636) and 20p12.3 (rs961253 and rs4813802). These markers are located close to two of the genes involved in bone morphogenetic protein (BMP) signaling (BMP4 and BMP2, respectively). By investigating these four SNPs in an initial cohort of Spanish origin, we found substantial evidence that minor allele frequencies (MAFs) may be different in northern and southern European populations. Therefore, we genotyped three additional southern European cohorts comprising a total of 2028 cases and 4273 controls. The meta-analysis results show that only one of the association signals (rs961253) is effectively replicated in the southern European populations, despite adequate power to detect all four. The other three SNPs (rs4444235, rs1957636 and rs4813802) presented discordant results in MAFs and linkage disequilibrium patterns between northern and southern European cohorts. We hypothesize that this lack of replication could be the result of differential tagging of the functional variant in both sets of populations. Were this true, it would have complex consequences in both our ability to understand the nature of the real causative variants, as well as for further study designs. PMID:23161572

Fernandez-Rozadilla, Ceres; Palles, Claire; Carvajal-Carmona, Luis; Peterlongo, Paolo; Nici, Carmela; Veneroni, Silvia; Pinheiro, Manuela; Teixeira, Manuel R; Moreno, Victor; Lamas, Maria-Jesus; Baiget, Montserrat; Lopez-Fernandez, L A; Gonzalez, Dolors; Brea-Fernandez, Alejandro; Clofent, Juan; Bujanda, Luis; Bessa, Xavier; Andreu, Montserrat; Xicola, Rosa; Llor, Xavier; Jover, Rodrigo; Castells, Antoni; Castellvi-Bel, Sergi; Carracedo, Angel; Tomlinson, Ian; Ruiz-Ponte, Clara

2012-11-16

399

European Ancestry Predominates in Neuromyelitis Optica and Multiple Sclerosis Patients from Brazil  

PubMed Central

Background Neuromyelitis optica (NMO) is considered relatively more common in non-Whites, whereas multiple sclerosis (MS) presents a high prevalence rate, particularly in Whites from Western countries populations. However, no study has used ancestry informative markers (AIMs) to estimate the genetic ancestry contribution to NMO patients. Methods Twelve AIMs were selected based on the large allele frequency differences among European, African, and Amerindian populations, in order to investigate the genetic contribution of each ancestral group in 236 patients with MS and NMO, diagnosed using the McDonald and Wingerchuck criteria, respectively. All 128 MS patients were recruited at the Faculty of Medicine of Ribeirão Preto (MS-RP), Southeastern Brazil, as well as 108 healthy bone marrow donors considered as healthy controls. A total of 108 NMO patients were recruited from five Neurology centers from different Brazilian regions, including Ribeirão Preto (NMO-RP). Principal Findings European ancestry contribution was higher in MS-RP than in NMO-RP (78.5% vs. 68.7%) patients. In contrast, African ancestry estimates were higher in NMO-RP than in MS-RP (20.5% vs. 12.5%) patients. Moreover, principal component analyses showed that groups of NMO patients from different Brazilian regions were clustered close to the European ancestral population. Conclusions Our findings demonstrate that European genetic contribution predominates in NMO and MS patients from Brazil.

Santos, Antonio Carlos; Lana-Peixoto, Marco Aurelio; Rocha, Cristiane Franklin; Brito, Maria Lucia; de Oliveira, Enedina Maria Lobato; Bichuetti, Denis Bernardi; Gabbai, Alberto Alan; Diniz, Denise Sisterolli; Kaimen-Maciel, Damacio Ramon; Comini-Frota, Elizabeth Regina; Vieira Wiezel, Claudia E.; Muniz, Yara Costa Netto; da Silva Costa, Roberta Martins; Mendes-Junior, Celso Teixeira; Donadi, Eduardo Antonio; Barreira, Amilton Antunes; Simoes, Aguinaldo Luiz

2013-01-01

400

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

PubMed

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

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

2006-09-01

401

HLA-DQ association and allele competition in Chinese narcolepsy.  

PubMed

In Japanese, Koreans and Caucasians, narcolepsy/hypocretin deficiency is tightly associated with the DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype. Studies in African-Americans suggest a primary effect of DQB1*06:02, but this observation has been difficult to confirm in other populations because of high linkage disequilibrium between DRB1*15:01/3 and DQB1*06:02 in most populations. In this study, we studied human leucocyte antigen (HLA) class II in 202 Chinese narcolepsy patients (11% from South China) and found all patients to be DQB1*06:02 positive. Comparing cases with 103 unselected controls, and 110 and 79 controls selected for the presence of DQB1*06:02 and DRB1*15:01, we found that the presence of DQB1*06:02 and not DRB1*15:01 was associated with narcolepsy. In particular, Southern Chinese haplotypes such as the DRB1*15:01-DQA1*01:02-DQB1*06:01 and DRB1*15:01-DQA1*01:02-DQB1*05 were not associated with narcolepsy. As reported in Japanese, Koreans, African-Americans and Caucasians, additional protective effects of DQA1*01 (non-DQA1*01:02) and susceptibility effects of DQB1*03:01 were observed. These results illustrate the extraordinary conservation of HLA class II effects in narcolepsy across populations and show that DRB1*15:01 has no effect on narcolepsy susceptibility in the absence of DQB1*06:02. The results are also in line with a previously proposed 'HLA-DQ allelic competition model' that involves competition between non-DQA1*01:02, non-DQB1*06:02 'competent' (able to dimerize together) DQ1 alleles and the major DQ?*01:02/ DQ?*06:02 narcolepsy heterodimer to reduce susceptibility. PMID:22862152

Han, F; Lin, L; Li, J; Dong, S X; An, P; Zhao, L; Liu, N Y; Li, Q Y; Yan, H; Gao, Z C; Faraco, J; Strohl, K P; Liu, X; Miyadera, H; Mignot, E

2012-08-04

402

National economic sovereignty and the Single European Currency  

Microsoft Academic Search

Considers how membership of a Single European Currency would affect Single European Currency members’ national economic sovereignty. First defines concisely national economic sovereignty. Explores economic life in the Single European Currency. A picture of a converged Single European Currency area economy emerges. Then considers what influence Single European Currency members would have on the Single European Currency area’s macroeconomic policy,

Nic Potts

1997-01-01

403

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

Microsoft Academic Search

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

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

1993-01-01

404

Method to identify specific alleles of a Phanerochaete chrysosporium gene encoding lignin peroxidase  

SciTech Connect

A method to identify and differentiate allelic variants of the gene encoding lignin peroxidase isozyme H8 is presented. The strategy involves amplifying a variable region of the gene's carboxy terminus by use of the polymerase chain reaction and then probing with allele-specific oligonucleotides.

Gaskell, J.; Wymelenberg, A.V.; Cullen, D. (Dept of Agriculture, Madison, WI (United States)); Stewart, P. (Univ. of Wisconsin, Madison (United States))

1992-04-01

405

Asymptotics of the allele frequency spectrum associated with the Bolthausen-Sznitman coalescent  

Microsoft Academic Search

We work in the context of the infinitely many alleles model. The allelic partition associated with a coalescent process started from n individuals is obtained by placing mutations along the skeleton of the coalescent tree; for each individual, we trace back to the most recent mutation affecting it and group together individuals whose most recent mutations are the same. The

Anne-Laure Basdevant; Christina Goldschmidt

2007-01-01

406

Isolation of the two allelic incompatibility genes s and S of the fungus Podospora anserina  

Microsoft Academic Search

The two allelic genes s and S are responsible for heterogenic incompatibility between wild type strains of the fungus Podospora anserina. The s gene has been cloned by SIB selection and expression in a strain containing a neutral allele of this locus. The S gene was isolated from a genomic library using the DNA of the s locus as a

Béatrice Turcq; Muriel Denayrolles; Joël Begueret

1990-01-01

407

Identification and characterization of novel organophosphate detoxifying esterase alleles in the Guangzhou area of China.  

PubMed

In the mosquito Culex pipiens, various alleles at the Ester locus provide insecticide resistance. These resistance alleles display a heterogeneous geographical distribution, particularly in China, where they are highly diverse. A new resistance allele, Ester9, coding for the overproduced esterases A9 and B9, is characterized and compared to the known resistant allele Ester8 isolated from the same southern China sample (from Guangzhou). Both alleles provide low but significant resistance to chlorpyrifos (relative synergism ratio [RSR] > 3) and temephos (RSR = 1.4), which is consistent with the low level of gene amplification they display (15 copies for Ester9 and 4 copies for Ester8). The full genomic sequence of the allele coding A8 and A9 is presented, which allowed us to set up a polymerase chain reaction assay to specifically identify these alleles. The peculiar situation in southern China, where numerous resistance alleles coexist, is discussed in comparison with the Mediterranean situation, the only one with a similar diversity of overproduced esterases. PMID:11804460

Weill, M; Marquine, M; Berthomieu, A; Dubois, M P; Bernard, C; Qiao, C L; Raymond, M

2001-12-01

408

High frequency of the Lebanese allele of the LDLr gene among Brazilian patients with familial hypercholesterolaemia  

Microsoft Academic Search

We analysed the LDL receptor (LDLr) gene in 18 Brazilian patients with familial hypercholesterolaemia (FH) from 10 unrelated families. The combination of a direct search for the Lebanese allele of the LDLr gene by a PCR method and Southern blotting using cDNA probes allowed the identification of the gene defect in six out of 10 families. The Lebanese allele was

M S Figueiredo; J E Dos Santos; F L Alberto; M A Zago

1992-01-01

409

Assessment of Plasma DNA Levels, Allelic Imbalance, and CA 125 as Diagnostic Tests for Cancer  

Microsoft Academic Search

Background: Allelic imbalance (AI), the loss or gain of chro- mosomal regions, is found in many cancers. AI can be de- tected in genomic tumor DNA released into the blood after necrosis or apoptosis. We evaluated plasma DNA concentra- tion, allelic status in plasma DNA, and serum CA 125 level as screening tests for ovarian and other cancers. Methods: Plasma

Hsueh-Wei Chang; Shing M. Lee; Steven N. Goodman; Gad Singer; Sarah K. R. Cho; Lori J. Sokoll; Fredrick J. Montz; Richard Roden; Zhen Zhang; Daniel W. Chan; Robert J. Kurman; Ie-Ming Shih

2002-01-01

410

Profiling of HLA-B Alleles for Association Studies with Ankylosing Spondylitis in the Chinese Population  

PubMed Central

Human leucocyte antigen (HLA) B*27 is a susceptibility allele to ankylosing spondylitis (AS). However, major AS-associated subtypes of HLA-B*27 and other HLA-B alleles vary in different ethnic populations. Herein, we examined HLA-B alleles in a total of 360 AS patients and 350 controls of Chinese Han ancestry. The HLA-B genotyping was performed with sequence-based typing (SBT) method. Six HLA-B*27 subtypes B*27:04, B*27:05, B*27:07, B*27:08, B*27:10 and B*27:15 were observed in the cohorts. HLA-B*27:04:01 and -B*27:05:02 appeared significantly increased in AS patients, which indicated as two major susceptibility alleles to AS. Homozygous B*27 was observed only in AS patients. There are 30 HLA-B alleles identified in the studies. HLA-B*15, especially B*15:01:01:01, appeared as the major allele type in the Chinese controls. Some common HLA-B alleles such as HLA-B*15, B*13, B*46 and B*51 were significantly reduced in Chinese AS patients. In conclusion, the studies profiled the HLA-B alleles, and identified major susceptibility subtypes of B27 to AS in Han Chinese population

Yi, Lin; Wang, Jiucun; Guo, Xinjian; Espitia, Maribel G.; Chen, Enuo; Assassi, Shervin; Jin, Li; Zou, Hejian; Reveille, John D.; Zhou, Xiaodong

2013-01-01

411

Models of frequency-dependent selection with mutation from parental alleles.  

PubMed

Frequency-dependent selection (FDS) remains a common heuristic explanation for the maintenance of genetic variation in natural populations. The pairwise-interaction model (PIM) is a well-studied general model of frequency-dependent selection, which assumes that a genotype's fitness is a function of within-population intergenotypic interactions. Previous theoretical work indicated that this type of model is able to sustain large numbers of alleles at a single locus when it incorporates recurrent mutation. These studies, however, have ignored the impact of the distribution of fitness effects of new mutations on the dynamics and end results of polymorphism construction. We suggest that a natural way to model mutation would be to assume mutant fitness is related to the fitness of the parental allele, i.e., the existing allele from which the mutant arose. Here we examine the numbers and distributions of fitnesses and alleles produced by construction under the PIM with mutation from parental alleles and the impacts on such measures due to different methods of generating mutant fitnesses. We find that, in comparison with previous results, generating mutants from existing alleles lowers the average number of alleles likely to be observed in a system subject to FDS, but produces polymorphisms that are highly stable and have realistic allele-frequency distributions. PMID:23852384

Trotter, Meredith V; Spencer, Hamish G

2013-07-12

412

Allelic Loss on Chromosome 8pl2-21 in Microdissected Prostatic Intraepithelial Neoplasia  

Microsoft Academic Search

The development and progression of human prostate cancer is associ ated with genetic abnormalities in tumor cells. Inactivation of tumor suppressor genes due to allelic loss is thought to be an important mech anism of gene alteration in prostatic neoplasms. In this study we examined allelic loss on chromosome Sp 12-21 in microdissected samples of normal prostatic epithelium, high grade

Michael R. Emmert-Buck; Cathy D. Vocke; Rudy O. Pozzatti; Paul H. Duray; Scott B. Jennings; Charles D. Florence; David G. Bostwick; Lance A. Liotta; W. Marston Linchan

1995-01-01

413

The Fixation Probability of a Beneficial Allele in a Population Dividing by Binary Fission  

Microsoft Academic Search

We derive formulae for the fixation probability, P, of a rare benefical allele segregating in a population of fixed size which reproduces by binary fission, in terms of the selection coefficient for the beneficial allele, s. We find that an earlier result P ? 4s does not depend on the assumption of binary fission, but depends on an assumption about

Toby Johnson; Philip J. Gerrish

2002-01-01

414

Mutation in the ap2-6 allele causes recognition of a cryptic splice site  

Microsoft Academic Search

Mutations in the homeotic gene APETALA2 of Arabidopsis thaliana cause severe developmental alterations, most prominently homeotic floral organ replacements from petals to carpels and petals to stamens in the outer two floral whorls. To date, ten different alleles have been identified conferring phe- notypes of various degrees. Of these ten alleles, only three have been characterized at the sequence level.

Michael P. Wakem; Susanne E. Kohalmi

2003-01-01

415

Geographical patterns of turnover and nestedness-resultant components of allelic diversity among populations.  

PubMed

The analysis of geographical patterns in population divergence has always been a powerful way to infer microevolutionary processes involved in population differentiation, and several approaches have been used to investigate such patterns. Most frequently, multivariate spatial patterns of population differentiation are analyzed by computing pairwise genetic distances or F(ST) (or related statistics, such as ?(ST) from AMOVA), which are then correlated with geographical distances or landscape features. However, when calculating distances, especially based on presence-absence of alleles in local populations, there would be a confounding effect of allelic richness differences in the population differentiation. Moreover, the relative magnitude of these components and their spatial patterns can help identifying microevolutionary processes driving population differentiation. Here we show how recent methodological advances in ecological community analyses that allows partitioning dissimilarity into turnover (turnover) and richness differences, or nestedness-resultant dissimilarity, can be applied to allelic variation data, using an endemic Cerrado tree (Dipteryx alata) as a case study. Individuals from 15 local populations were genotyped for eight microsatellite loci, and pairwise dissimilarities were computed based on presence-absence of alleles. The turnover of alleles among populations represented 69 % of variation in dissimilarity, but only the richness difference component shows a clear spatial structure, appearing as a westward decrease of allelic richness. We show that decoupling richness difference and turnover components of allelic variation reveals more clearly how similarity among populations reflects geographical patterns in allelic diversity that can be interpreted in respect to historical range expansion in the species. PMID:22886007

Diniz-Filho, Jose Alexandre Felizola; Collevatti, Rosane Garcia; Soares, Thannya Nascimento; Telles, Mariana Pires de Campos

2012-08-12

416

Influence of the apolipoprotein E ?4 allele on human embryonic development  

Microsoft Academic Search

Human apolipoprotein E (apoE) exists in three major isoforms encoded by distinct alleles (APOE ?2, ?3 and ?4) and has important functions in nerve development and repair. Inheritance of the ?4 allele is a major risk factor for the development of Alzheimer's disease. To investigate the role of APOE polymorphisms in embryonic development, we analyzed the APOE genotypes of 81

Henrik Zetterberg; Mona Palmér; Anne Ricksten; Judes Poirier; Lars Palmqvist; Lars Rymo; Alexander Zafiropoulos; Demetrios A Arvanitis; Demetrios A Spandidos; Kaj Blennow

2002-01-01

417

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

418

Chemokine Receptor 5 ?32 Allele in Patients with Severe Pandemic (H1N1) 2009  

PubMed Central

Because chemokine receptor 5 (CCR5) may have a role in pulmonary immune response, we explored whether patients with severe pandemic (H1N1) 2009 were more likely to carry the CCR5?32 allele than were members of the general population. We found a large proportion of heterozygosity for the CCR5?32 allele among white patients with severe disease.

Juno, Jennifer; Meyers, Adrienne; Ball, T. Blake; Kumar, Anand; Rubinstein, Ethan; Fowke, Keith R.

2010-01-01

419

Analysis of the methylation profiles in imprinted genes applicable to parental allele discrimination  

Microsoft Academic Search

This study investigated the distribution of methylated CpGs around several SNPs in five imprinted genes, which are useful to discriminate the differentially methylated parental allele (DMPA), by bisulfite-sequencing method. The genomic DNAs from peripheral blood, saliva and relatively fresh postmortem tissues except for testis showed a differentially methylated status in each parental allele, however, DNAs from the other sources (nail,

Nori Nakayashiki; Masataka Takamiya; Kirito Shimamoto; Yasuhiro Aoki

2009-01-01

420

PCR/RFLP-based allelic variants of streptokinase and their plasminogen activation potencies.  

PubMed

PCR-restriction fragment length polymorphism (PCR/RFLP)-based analysis of ?-domain variable region of streptokinase genes (sk) has previously identified 14 sk alleles (sk1-sk14) in group A (GAS), C (GCS) and G (GGS) streptococci isolates from a few geographically distinct regions. However, the relation of sk allelic variants to their plasminogen activation potencies remained as a matter of debate. Herein, employing the same PCR/RFLP assay, we analysed sk allelic variants of GAS and GCS/GGS isolates from Iranian patients. In total, 21 sk allelic variants including 14 new alleles (sk14-sk28) were identified. Results implied the horizontal gene transfer of sk fragments between GAS and GCS/GGS strains and did not prove the specificity of particular sk alleles to GCS/GGS or GAS groups. Measurement of streptokinase (SK) activity in streptococcal culture supernatants by colorimetric assay (S2251 substrate) ranged from 9 to 182 IU mL(-1). Although some strains with the highest SK activity were detected in definite variants, no significant correlation between sk alleles and plasminogen activation was detected (P value > 0.05). Analysis of DNA sequences and restriction site mapping of selective sk variants with similar SK activity pointed to the inadequacy of the currently available PCR/RFLP method for differentiation of critical/silent nucleotides to precisely categorize sk alleles for their functional properties. PMID:22812485

Keramati, Malihe; Roohvand, Farzin; Eslaminejad, Zahra; Mirzaie, Amir; Nikbin, Vajihe Sadat; Aslani, Mohammad Mehdi

2012-08-29

421

Expansion to full mutation of a FMR1 intermediate allele over two generations  

Microsoft Academic Search

Fragile X syndrome is due to an expanded CGG repeat in the 5? UTR of the FMR1 gene. According to repeat size, we distinguish four allele categories: normal (200 CGG). However, the boundaries among these categories are unclear, making it difficult to classify unstable alleles and to estimate the risk of expansion. We report a family with a proband, carrying

Alessandra Terracciano; Maria Grazia Pomponi; Grazia Maria Elisabetta Marino; Pietro Chiurazzi; Maria Michela Rinaldi; Marina Dobosz; Giovanni Neri; G Neri

2004-01-01

422

Allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with oligodendrogliomas  

Microsoft Academic Search

Introduction: Allelic loss of the short arm of chromosome 1 predicts radiographic response to chemotherapy and long overall survival times in patients with anaplastic oligodendrogliomas. Using a database of patients with oligodendrogliomas in whom chromosome 1p status was known, we explored whether allelic loss of 1p also predicted longer duration of tumor control when radiotherapy was part of the initial

G. S Bauman; Y Ino; K Ueki; M. C Zlatescu; B. J Fisher; D. R Macdonald; L Stitt; D. N Louis; J. G Cairncross

2000-01-01

423

Analysis of mechanisms regulating the expression of parental alleles at the GPD locus in mule erythrocytes  

Microsoft Academic Search

Erythrocyte glucose-6-phosphate dehydrogenase (G6PD) was examined by 13% starch gel electrophoresis in 74 mules (42 females and 32 males), 35 donkeys, and ten horses. The quantitative expression of the parental alleles at the Gpd locus varies greatly in female mules from the hemizygous expression of the maternal allele to that of the paternal. The data obtained indicate that the X

O. L. Serov; S. M. Zakijan; V. A. Kulichkov

1978-01-01