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Sample records for allele frequency variation

  1. FINDbase: a worldwide database for genetic variation allele frequencies updated

    PubMed Central

    Georgitsi, Marianthi; Viennas, Emmanouil; Antoniou, Dimitris I.; Gkantouna, Vassiliki; van Baal, Sjozef; Petricoin, Emanuel F.; Poulas, Konstantinos; Tzimas, Giannis; Patrinos, George P.

    2011-01-01

    Frequency of INherited Disorders database (FIND base; http://www.findbase.org) records frequencies of causative genetic variations worldwide. Database records include the population and ethnic group or geographical region, the disorder name and the related gene, accompanied by links to any related external resources and the genetic variation together with its frequency in that population. In addition to the regular data content updates, we report the following significant advances: (i) the systematic collection and thorough documentation of population/ethnic group-specific pharmacogenomic markers allele frequencies for 144 markers in 14 genes of pharmacogenomic interest from different classes of drug-metabolizing enzymes and transporters, representing 150 populations and ethnic groups worldwide; (ii) the development of new data querying and visualization tools in the expanded FINDbase data collection, built around Microsoft’s PivotViewer software (http://www.getpivot.com), based on Microsoft Silverlight technology (http://www.silverlight.net) that facilitates querying of large data sets and visualizing the results; and (iii) the establishment of the first database journal, by affiliating FINDbase with Human Genomics and Proteomics, a new open-access scientific journal, which would serve as a prime example of a non-profit model for sustainable database funding. PMID:21113021

  2. Natural Selection VS. Random Drift: Evidence from Temporal Variation in Allele Frequencies in Nature

    PubMed Central

    Mueller, Laurence D.; Barr, Lorraine G.; Ayala, Francisco J.

    1985-01-01

    We have obtained monthly samples of two species, Drosophila pseudoobscura and Drosophila persimilis, in a natural population from Napa County, California. In each species, about 300 genes have been assayed by electrophoresis for each of seven enzyme loci in each monthly sample from March 1972 to June 1975. Using statistical methods developed for the purpose, we have examined whether the allele frequencies at different loci vary in a correlated fashion. The methods used do not detect natural selection when it is deterministic (e.g., overdominance or directional selection), but only when alleles at different loci vary simultaneously in response to the same environmental variations. Moreover, only relatively large fitness differences (of the order of 15%) are detectable. We have found strong evidence of correlated allele frequency variation in 13–20% of the cases examined. We interpret this as evidence that natural selection plays a major role in the evolution of protein polymorphisms in nature. PMID:4054608

  3. Mutation Rate Variation is a Primary Determinant of the Distribution of Allele Frequencies in Humans

    PubMed Central

    Pritchard, Jonathan K.

    2016-01-01

    The site frequency spectrum (SFS) has long been used to study demographic history and natural selection. Here, we extend this summary by examining the SFS conditional on the alleles found at the same site in other species. We refer to this extension as the “phylogenetically-conditioned SFS” or cSFS. Using recent large-sample data from the Exome Aggregation Consortium (ExAC), combined with primate genome sequences, we find that human variants that occurred independently in closely related primate lineages are at higher frequencies in humans than variants with parallel substitutions in more distant primates. We show that this effect is largely due to sites with elevated mutation rates causing significant departures from the widely-used infinite sites mutation model. Our analysis also suggests substantial variation in mutation rates even among mutations involving the same nucleotide changes. In summary, we show that variable mutation rates are key determinants of the SFS in humans. PMID:27977673

  4. HLA class II variation in the Gila River Indian Community of Arizona: alleles, haplotypes, and a high frequency epitope at the HLA-DR locus.

    PubMed

    Williams, R C; McAuley, J E

    1992-01-01

    A genetic distribution for the HLA class II loci is described for 349 "full-blooded" Pima and Tohono O'odham Indians (Pimans) in the Gila River Indian Community. A high frequency epitope in the *DRw52 family was defined by reactions with 31 alloantisera, which we have designated *DR3X6. It segregates as a codominant allele at HLA-DR with alleles *DR2, *DR4, and *DRw8, and has the highest frequency yet reported for an HLA-DR specificity, 0.735. It forms a common haplotype with *DRw52 and *DQw3 that is a valuable marker for genetic admixture and anthropological studies. Phenotype and allele frequencies, and haplotype frequencies for two and three loci, are presented. Variation at these loci is highly restricted, the mean heterozygosity for HLA-DR and HLA-DQ being 0.361. The Pimans represent a contemporary model for the Paleo-Indians who first entered North America 20,000 to 40,000 years ago.

  5. Variation in meiotic recombination frequencies between allelic transgenes inserted at different sites in the Drosophila melanogaster genome.

    PubMed

    McMahan, Susan; Kohl, Kathryn P; Sekelsky, Jeff

    2013-08-07

    Meiotic crossovers are distributed nonrandomly across the genome. Classic studies in Drosophila suggest that the position of a gene along a chromosome arm can affect the outcome of the recombination process, with proximity to the centromere being associated with lower crossing over. To examine this phenomenon molecularly, we developed an assay that measures meiotic crossovers and noncrossover gene conversions between allelic transgenes inserted into different genomic positions. To facilitate collecting a large number of virgin females, we developed a useful genetic system that kills males and undesired classes of females. We found that the recombination frequency at a site in the middle of the X chromosome, where crossovers are normally frequent, was similar to the frequency at the centromere-proximal end of the euchromatin, where crossovers are normally infrequent. In contrast, we recovered no recombinants--crossovers or noncrossovers--at a site on chromosome 4 and at a site toward the distal end of the X chromosome. These results suggest that local sequence or chromatin features have a stronger impact on recombination rates in this transgene assay than position along the chromosome arm.

  6. Mutated tumor alleles are expressed according to their DNA frequency.

    PubMed

    Castle, John C; Loewer, Martin; Boegel, Sebastian; Tadmor, Arbel D; Boisguerin, Valesca; de Graaf, Jos; Paret, Claudia; Diken, Mustafa; Kreiter, Sebastian; Türeci, Özlem; Sahin, Ugur

    2014-04-22

    The transcription of tumor mutations from DNA into RNA has implications for biology, epigenetics and clinical practice. It is not clear if mutations are in general transcribed and, if so, at what proportion to the wild-type allele. Here, we examined the correlation between DNA mutation allele frequency and RNA mutation allele frequency. We sequenced the exome and transcriptome of tumor cell lines with large copy number variations, identified heterozygous single nucleotide mutations and absolute DNA copy number, and determined the corresponding DNA and RNA mutation allele fraction. We found that 99% of the DNA mutations in expressed genes are expressed as RNA. Moreover, we found a high correlation between the DNA and RNA mutation allele frequency. Exceptions are mutations that cause premature termination codons and therefore activate nonsense-mediated decay. Beyond this, we did not find evidence of any wide-scale mechanism, such as allele-specific epigenetic silencing, preferentially promoting mutated or wild-type alleles. In conclusion, our data strongly suggest that genes are equally transcribed from all alleles, mutated and wild-type, and thus transcribed in proportion to their DNA allele frequency.

  7. Deleterious alleles in the human genome are on average younger than neutral alleles of the same frequency.

    PubMed

    Kiezun, Adam; Pulit, Sara L; Francioli, Laurent C; van Dijk, Freerk; Swertz, Morris; Boomsma, Dorret I; van Duijn, Cornelia M; Slagboom, P Eline; van Ommen, G J B; Wijmenga, Cisca; de Bakker, Paul I W; Sunyaev, Shamil R

    2013-01-01

    Large-scale population sequencing studies provide a complete picture of human genetic variation within the studied populations. A key challenge is to identify, among the myriad alleles, those variants that have an effect on molecular function, phenotypes, and reproductive fitness. Most non-neutral variation consists of deleterious alleles segregating at low population frequency due to incessant mutation. To date, studies characterizing selection against deleterious alleles have been based on allele frequency (testing for a relative excess of rare alleles) or ratio of polymorphism to divergence (testing for a relative increase in the number of polymorphic alleles). Here, starting from Maruyama's theoretical prediction (Maruyama T (1974), Am J Hum Genet USA 6:669-673) that a (slightly) deleterious allele is, on average, younger than a neutral allele segregating at the same frequency, we devised an approach to characterize selection based on allelic age. Unlike existing methods, it compares sets of neutral and deleterious sequence variants at the same allele frequency. When applied to human sequence data from the Genome of the Netherlands Project, our approach distinguishes low-frequency coding non-synonymous variants from synonymous and non-coding variants at the same allele frequency and discriminates between sets of variants independently predicted to be benign or damaging for protein structure and function. The results confirm the abundance of slightly deleterious coding variation in humans.

  8. Allelic variation contributes to bacterial host specificity

    SciTech Connect

    Yue, Min; Han, Xiangan; Masi, Leon De; Zhu, Chunhong; Ma, Xun; Zhang, Junjie; Wu, Renwei; Schmieder, Robert; Kaushik, Radhey S.; Fraser, George P.; Zhao, Shaohua; McDermott, Patrick F.; Weill, François-Xavier; Mainil, Jacques G.; Arze, Cesar; Fricke, W. Florian; Edwards, Robert A.; Brisson, Dustin; Zhang, Nancy R.; Rankin, Shelley C.; Schifferli, Dieter M.

    2015-10-30

    Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population and functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. In conclusion, together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.

  9. Allelic variation contributes to bacterial host specificity

    DOE PAGES

    Yue, Min; Han, Xiangan; Masi, Leon De; ...

    2015-10-30

    Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population andmore » functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. In conclusion, together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.« less

  10. Allele surfing promotes microbial adaptation from standing variation.

    PubMed

    Gralka, Matti; Stiewe, Fabian; Farrell, Fred; Möbius, Wolfram; Waclaw, Bartlomiej; Hallatschek, Oskar

    2016-08-01

    The coupling of ecology and evolution during range expansions enables mutations to establish at expanding range margins and reach high frequencies. This phenomenon, called allele surfing, is thought to have caused revolutions in the gene pool of many species, most evidently in microbial communities. It has remained unclear, however, under which conditions allele surfing promotes or hinders adaptation. Here, using microbial experiments and simulations, we show that, starting with standing adaptive variation, range expansions generate a larger increase in mean fitness than spatially uniform population expansions. The adaptation gain results from 'soft' selective sweeps emerging from surfing beneficial mutations. The rate of these surfing events is shown to sensitively depend on the strength of genetic drift, which varies among strains and environmental conditions. More generally, allele surfing promotes the rate of adaptation per biomass produced, which could help developing biofilms and other resource-limited populations to cope with environmental challenges.

  11. Frequency of FCGR3B Alleles in Thai Blood Donors

    PubMed Central

    Kaset, Chollanot; Leetrakool, Nipapan; Intharanut, Kamphon

    2013-01-01

    Background Human neutrophil antigens (HNAs) are involved in autoimmune and alloimmune neutropenia and transfusion-related acute lung injury. The HNA-1 system is important in immunogenetics, and allele frequencies have been described in different populations. This study investigated the frequency of FCGR3B alleles encoding HNA-1a, HNA-1b, and HNA-1c among Thai blood donors and compared these frequencies with those previously reported for other populations. Methods Eight hundred DNA samples obtained from unrelated healthy blood donors at the National Blood Centre, Thai Red Cross Society, Bangkok, and the Blood Bank, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, were included. Samples were simultaneously typed for each FCGR3B allele using an in-house polymerase chain reaction with sequence-specific primer (PCR-SSP) technique. Results The frequencies of FCGR3B*1, FCGR3B*2, and FCGR3B*3 alleles in central Thai blood donors were 0.548, 0.452, and 0.004, respectively; only FCGR3B*1 and FCGR3B*2 alleles were found in northern Thai blood donors (0.68 and 0.32, respectively). Compared with other Asian populations, central Thais had higher frequencies of the FCGR3B*2 allele (P<0.001), while the frequencies of the FCGR3B*1 and FCGR3B*2 alleles in northern Thais were similar to those previously reported in Taiwanese and Japanese populations. In contrast, the frequencies of the FCGR3B*1 and FCGR3B*2 alleles in the northern Thai population were statistically different from those observed in central Thai, Korean, German, and Turkish populations. Conclusions FCGR3B allele frequencies were significantly different between central and northern Thai blood donors. Our in-house PCR-SSP method is a simple, cost-effective, and convenient method for FCGR3B allele detection. PMID:24205492

  12. Disparities in allele frequencies and population differentiation for 101 disease-associated single nucleotide polymorphisms between Puerto Ricans and non-Hispanic whites

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Variations in gene allele frequencies can contribute to differences in the prevalence of some common complex diseases among populations. Natural selection modulates the balance in allele frequencies across populations. Population differentiation (FST) can evidence environmental selection...

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

    PubMed

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

    2015-04-01

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

  14. The number of alleles at a microsatellite defines the allele frequency spectrum and facilitates fast accurate estimation of theta.

    PubMed

    Haasl, Ryan J; Payseur, Bret A

    2010-12-01

    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 θ, the population-scaled mutation rate, based on simulated data. Discovered relationships between θ, the number of alleles, and the frequency spectrum support the development of three new estimators of microsatellite θ. The three estimators exhibit roughly similar mean squared errors (MSEs) and all are biased. However, across a broad range of sample sizes and θ 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.

  15. Robust identification of local adaptation from allele frequencies.

    PubMed

    Günther, Torsten; Coop, Graham

    2013-09-01

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

  16. Disentangling the roles of history and local selection in shaping clinal variation of allele frequencies and gene expression in Norway spruce (Picea abies).

    PubMed

    Chen, Jun; Källman, Thomas; Ma, Xiaofei; Gyllenstrand, Niclas; Zaina, Giusi; Morgante, Michele; Bousquet, Jean; Eckert, Andrew; Wegrzyn, Jill; Neale, David; Lagercrantz, Ulf; Lascoux, Martin

    2012-07-01

    Understanding the genetic basis of local adaptation is challenging due to the subtle balance among conflicting evolutionary forces that are involved in its establishment and maintenance. One system with which to tease apart these difficulties is clines in adaptive characters. Here we analyzed genetic and phenotypic variation in bud set, a highly heritable and adaptive trait, among 18 populations of Norway spruce (Picea abies), arrayed along a latitudinal gradient ranging from 47°N to 68°N. We confirmed that variation in bud set is strongly clinal, using a subset of five populations. Genotypes for 137 single-nucleotide polymorphisms (SNPs) chosen from 18 candidate genes putatively affecting bud set and 308 control SNPs chosen from 264 random genes were analyzed for patterns of genetic structure and correlation to environment. Population genetic structure was low (F(ST) = 0.05), but latitudinal patterns were apparent among Scandinavian populations. Hence, part of the observed clinal variation should be attributable to population demography. Conditional on patterns of genetic structure, there was enrichment of SNPs within candidate genes for correlations with latitude. Twenty-nine SNPs were also outliers with respect to F(ST). The enrichment for clinal variation at SNPs within candidate genes (i.e., SNPs in PaGI, PaPhyP, PaPhyN, PaPRR7, and PaFTL2) indicated that local selection in the 18 populations, and/or selection in the ancestral populations from which they were recently derived, shaped the observed cline. Validation of these genes using expression studies also revealed that PaFTL2 expression is significantly associated with latitude, thereby confirming the central role played by this gene in the control of phenology in plants.

  17. Determination of allele frequency in pooled DNA: comparison of three PCR-based methods.

    PubMed

    Wilkening, Stefan; Hemminki, Kari; Thirumaran, Ranjit Kumar; Bermejo, Justo Lorenzo; Bonn, Stefan; Försti, Asta; Kumar, Rajiv

    2005-12-01

    Determination of allele frequency in pooled DNA samples is a powerful and efficient tool for large-scale association studies. In this study, we tested and compared three PCR-based methods for accuracy, reproducibility, cost, and convenience. The methods compared were: (i) real-time PCR with allele-specific primers, (ii) real-time PCR with allele-specific TaqMan probes, and (iii) quantitative sequencing. Allele frequencies of three single nucleotide polymorphisms in three different genes were estimated from pooled DNA. The pools were made of genomic DNA samples from 96 cases with basal cell carcinoma of the skin and 96 healthy controls with known genotypes. In this study, the allele frequency estimation made by real-time PCR with allele-specific primers had the smallest median deviation (MD) from the real allele frequency with 1.12% (absolute percentage points) and was also the cheapest method. However; this method required the most time for optimization and showed the highest variation between replicates (SD = 6.47%). Quantitative sequencing, the simplest method, was found to have intermediate accuracies (MD = 1.44%, SD = 4.2%). Real-time PCR with TaqMan probes, a convenient but very expensive method, had an MD of 1.47% and the lowest variation between replicates (SD = 3.18%).

  18. Allele Frequencies at Microsatellite Loci: The Stepwise Mutation Model Revisited

    PubMed Central

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

    1993-01-01

    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. PMID:8454213

  19. SSR allelic variation in almond (Prunus dulcis Mill.).

    PubMed

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

    2006-01-01

    Sixteen SSR markers including eight EST-SSR and eight genomic SSRs were used for genetic diversity analysis of 23 Chinese and 15 international almond cultivars. EST- and genomic SSR markers previously reported in species of Prunus, mainly peach, proved to be useful for almond genetic analysis. DNA sequences of 117 alleles of six of the 16 SSR loci were analysed to reveal sequence variation among the 38 almond accessions. For the four SSR loci with AG/CT repeats, no insertions or deletions were observed in the flanking regions of the 98 alleles sequenced. Allelic size variation of these loci resulted exclusively from differences in the structures of repeat motifs, which involved interruptions or occurrences of new motif repeats in addition to varying number of AG/CT repeats. Some alleles had a high number of uninterrupted repeat motifs, indicating that SSR mutational patterns differ among alleles at a given SSR locus within the almond species. Allelic homoplasy was observed in the SSR loci because of base substitutions, interruptions or compound repeat motifs. Substitutions in the repeat regions were found at two SSR loci, suggesting that point mutations operate on SSRs and hinder the further SSR expansion by introducing repeat interruptions to stabilize SSR loci. Furthermore, it was shown that some potential point mutations in the flanking regions are linked with new SSR repeat motif variation in almond and peach.

  20. Ethnic variation of the HLA-G*0105N allele in two Chinese populations.

    PubMed

    Lin, A; Li, M; Xu, D-P; Zhang, W-G; Yan, W-H

    2009-03-01

    Unlike high polymorphic classical human leukocyte antigen (HLA) class I molecules, the genetic polymorphism of HLA-G is very limited. However, the prevalence of HLA-G alleles among different ethnic populations varied dramatically. The HLA-G null allele (HLA-G*0105N) is defined by a cytosine deletion (Delta C) at position 1597 in exon 3, which disrupts the reading frame and alters the expression of HLA-G proteins. The HLA-G*0105N allelic frequency was investigated in previous studies and possible roles were addressed. In the current study, a total of 310 Chinese Han and 260 Chinese She ethnic minority population had been genotyped for the G*0105N polymorphism. Marked difference was observed that the G*0105N allelic frequency in Chinese Han was 1.61%, while no copy of the null allele was observed in the Chinese She minority population (P(c) = 0.0073). Data also revealed that no homozygote of HLA-G*0105N allele exists in this Chinese Han population. Furthermore, significant difference was found for the frequencies of HLA-G*0105N both in Chinese Han and in Chinese She populations when compared with other ethnic populations. Taken together, our results indicated that ethnic variation of the HLA-G*0105N polymorphism among different ethnic populations is possibly the result of evolution. However, the advantages of the selection of this allele are necessary to be further investigated.

  1. Biased gene conversion skews allele frequencies in human populations, increasing the disease burden of recessive alleles.

    PubMed

    Lachance, Joseph; Tishkoff, Sarah A

    2014-10-02

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

  2. Natural allelic variations in highly polyploidy Saccharum complex

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sugarcane (Saccharum spp.) as important sugar and biofuel crop are highly polypoid with complex genomes. A large amount of natural phenotypic variation exists in sugarcane germplasm. Understanding its allelic variance has been challenging but is a critical foundation for discovery of the genomic seq...

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

    PubMed

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

    2015-09-01

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

  4. Natural Allelic Variations in Highly Polyploidy Saccharum Complex

    PubMed Central

    Song, Jian; Yang, Xiping; Resende, Marcio F. R.; Neves, Leandro G.; Todd, James; Zhang, Jisen; Comstock, Jack C.; Wang, Jianping

    2016-01-01

    Sugarcane (Saccharum spp.) is an important sugar and biofuel crop with high polyploid and complex genomes. The Saccharum complex, comprised of Saccharum genus and a few related genera, are important genetic resources for sugarcane breeding. A large amount of natural variation exists within the Saccharum complex. Though understanding their allelic variation has been challenging, it is critical to dissect allelic structure and to identify the alleles controlling important traits in sugarcane. To characterize natural variations in Saccharum complex, a target enrichment sequencing approach was used to assay 12 representative germplasm accessions. In total, 55,946 highly efficient probes were designed based on the sorghum genome and sugarcane unigene set targeting a total of 6 Mb of the sugarcane genome. A pipeline specifically tailored for polyploid sequence variants and genotype calling was established. BWA-mem and sorghum genome approved to be an acceptable aligner and reference for sugarcane target enrichment sequence analysis, respectively. Genetic variations including 1,166,066 non-redundant SNPs, 150,421 InDels, 919 gene copy number variations, and 1,257 gene presence/absence variations were detected. SNPs from three different callers (Samtools, Freebayes, and GATK) were compared and the validation rates were nearly 90%. Based on the SNP loci of each accession and their ploidy levels, 999,258 single dosage SNPs were identified and most loci were estimated as largely homozygotes. An average of 34,397 haplotype blocks for each accession was inferred. The highest divergence time among the Saccharum spp. was estimated as 1.2 million years ago (MYA). Saccharum spp. diverged from Erianthus and Sorghum approximately 5 and 6 MYA, respectively. The target enrichment sequencing approach provided an effective way to discover and catalog natural allelic variation in highly polyploid or heterozygous genomes. PMID:27375658

  5. Natural Allelic Variations in Highly Polyploidy Saccharum Complex.

    PubMed

    Song, Jian; Yang, Xiping; Resende, Marcio F R; Neves, Leandro G; Todd, James; Zhang, Jisen; Comstock, Jack C; Wang, Jianping

    2016-01-01

    Sugarcane (Saccharum spp.) is an important sugar and biofuel crop with high polyploid and complex genomes. The Saccharum complex, comprised of Saccharum genus and a few related genera, are important genetic resources for sugarcane breeding. A large amount of natural variation exists within the Saccharum complex. Though understanding their allelic variation has been challenging, it is critical to dissect allelic structure and to identify the alleles controlling important traits in sugarcane. To characterize natural variations in Saccharum complex, a target enrichment sequencing approach was used to assay 12 representative germplasm accessions. In total, 55,946 highly efficient probes were designed based on the sorghum genome and sugarcane unigene set targeting a total of 6 Mb of the sugarcane genome. A pipeline specifically tailored for polyploid sequence variants and genotype calling was established. BWA-mem and sorghum genome approved to be an acceptable aligner and reference for sugarcane target enrichment sequence analysis, respectively. Genetic variations including 1,166,066 non-redundant SNPs, 150,421 InDels, 919 gene copy number variations, and 1,257 gene presence/absence variations were detected. SNPs from three different callers (Samtools, Freebayes, and GATK) were compared and the validation rates were nearly 90%. Based on the SNP loci of each accession and their ploidy levels, 999,258 single dosage SNPs were identified and most loci were estimated as largely homozygotes. An average of 34,397 haplotype blocks for each accession was inferred. The highest divergence time among the Saccharum spp. was estimated as 1.2 million years ago (MYA). Saccharum spp. diverged from Erianthus and Sorghum approximately 5 and 6 MYA, respectively. The target enrichment sequencing approach provided an effective way to discover and catalog natural allelic variation in highly polyploid or heterozygous genomes.

  6. Allelic variation at the VRN-1 promoter region in polyploid wheat.

    PubMed

    Yan, L; Helguera, M; Kato, K; Fukuyama, S; Sherman, J; Dubcovsky, J

    2004-11-01

    Vernalization, the requirement of a long exposure to low temperatures to induce flowering, is an essential adaptation of plants to cold winters. We have shown recently that the vernalization gene VRN-1 from diploid wheat Triticum monococcum is the meristem identity gene APETALA1, and that deletions in its promoter were associated with spring growth habit. In this study, we characterized the allelic variation at the VRN-1 promoter region in polyploid wheat. The Vrn-A1a allele has a duplication including the promoter region. Each copy has similar foldback elements inserted at the same location and is flanked by identical host direct duplications (HDD). This allele was found in more than half of the hexaploid varieties but not among the tetraploid lines analyzed here. The Vrn-A1b allele has two mutations in the HDD region and a 20-bp deletion in the 5' UTR compared with the winter allele. The Vrn-A1b allele was found in both tetraploid and hexaploid accessions but at a relatively low frequency. Among the tetraploid wheat accessions, we found two additional alleles with 32 bp and 54 bp deletions that included the HDD region. We found no size polymorphisms in the promoter region among the winter wheat varieties. The dominant Vrn-A1 allele from two spring varieties from Afghanistan and Egypt ( Vrn-A1c allele) and all the dominant Vrn-B1 and Vrn-D1 alleles included in this study showed no differences from their respective recessive alleles in promoter sequences. Based on these results, we concluded that the VRN-1 genes should have additional regulatory sites outside the promoter region studied here.

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

    PubMed

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

    2015-04-30

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

  8. Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection

    PubMed Central

    Chesler, Elissa J.; Gatti, Daniel M.; Morgan, Andrew P.; Strobel, Marge; Trepanier, Laura; Oberbeck, Denesa; McWeeney, Shannon; Hitzemann, Robert; Ferris, Martin; McMullan, Rachel; Clayshultle, Amelia; Bell, Timothy A.; Manuel de Villena, Fernando Pardo; Churchill, Gary A.

    2016-01-01

    Multi-parent populations (MPPs) capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles. We detected strong transmission ratio distortion in the Diversity Outbred (DO) mouse population on chromosome 2, caused by meiotic drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The distorted region harbors thousands of polymorphisms derived from the seven non-WSB founder strains and many of these would be lost if the sweep was allowed to continue. To ensure the utility of the DO population to study genetic variation on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed minimal disruption to allele frequencies across the rest of the autosomal genome. However, there was a shift in haplotype frequencies of the mitochondrial genome and an increase in the rate of an unusual sex chromosome aneuploidy. The DO population has been restored to genome-wide utility for genetic analysis, but our experience underscores that vigilant monitoring of similar genetic resource populations is needed to ensure their long-term utility. PMID:27694113

  9. Diversity Outbred Mice at 21: Maintaining Allelic Variation in the Face of Selection.

    PubMed

    Chesler, Elissa J; Gatti, Daniel M; Morgan, Andrew P; Strobel, Marge; Trepanier, Laura; Oberbeck, Denesa; McWeeney, Shannon; Hitzemann, Robert; Ferris, Martin; McMullan, Rachel; Clayshultle, Amelia; Bell, Timothy A; Manuel de Villena, Fernando Pardo; Churchill, Gary A

    2016-12-07

    Multi-parent populations (MPPs) capture and maintain the genetic diversity from multiple inbred founder strains to provide a resource for high-resolution genetic mapping through the accumulation of recombination events over many generations. Breeding designs that maintain a large effective population size with randomized assignment of breeders at each generation can minimize the impact of selection, inbreeding, and genetic drift on allele frequencies. Small deviations from expected allele frequencies will have little effect on the power and precision of genetic analysis, but a major distortion could result in reduced power and loss of important functional alleles. We detected strong transmission ratio distortion in the Diversity Outbred (DO) mouse population on chromosome 2, caused by meiotic drive favoring transmission of the WSB/EiJ allele at the R2d2 locus. The distorted region harbors thousands of polymorphisms derived from the seven non-WSB founder strains and many of these would be lost if the sweep was allowed to continue. To ensure the utility of the DO population to study genetic variation on chromosome 2, we performed an artificial selection against WSB/EiJ alleles at the R2d2 locus. Here, we report that we have purged the WSB/EiJ allele from the drive locus while preserving WSB/EiJ alleles in the flanking regions. We observed minimal disruption to allele frequencies across the rest of the autosomal genome. However, there was a shift in haplotype frequencies of the mitochondrial genome and an increase in the rate of an unusual sex chromosome aneuploidy. The DO population has been restored to genome-wide utility for genetic analysis, but our experience underscores that vigilant monitoring of similar genetic resource populations is needed to ensure their long-term utility.

  10. Fast spatial ancestry via flexible allele frequency surfaces

    PubMed Central

    Rañola, John Michael; Novembre, John; Lange, Kenneth

    2014-01-01

    Motivation: Unique modeling and computational challenges arise in locating the geographic origin of individuals based on their genetic backgrounds. Single-nucleotide polymorphisms (SNPs) vary widely in informativeness, allele frequencies change non-linearly with geography and reliable localization requires evidence to be integrated across a multitude of SNPs. These problems become even more acute for individuals of mixed ancestry. It is hardly surprising that matching genetic models to computational constraints has limited the development of methods for estimating geographic origins. We attack these related problems by borrowing ideas from image processing and optimization theory. Our proposed model divides the region of interest into pixels and operates SNP by SNP. We estimate allele frequencies across the landscape by maximizing a product of binomial likelihoods penalized by nearest neighbor interactions. Penalization smooths allele frequency estimates and promotes estimation at pixels with no data. Maximization is accomplished by a minorize–maximize (MM) algorithm. Once allele frequency surfaces are available, one can apply Bayes’ rule to compute the posterior probability that each pixel is the pixel of origin of a given person. Placement of admixed individuals on the landscape is more complicated and requires estimation of the fractional contribution of each pixel to a person’s genome. This estimation problem also succumbs to a penalized MM algorithm. Results: We applied the model to the Population Reference Sample (POPRES) data. The model gives better localization for both unmixed and admixed individuals than existing methods despite using just a small fraction of the available SNPs. Computing times are comparable with the best competing software. Availability and implementation: Software will be freely available as the OriGen package in R. Contact: ranolaj@uw.edu or klange@ucla.edu Supplementary information: Supplementary data are available at

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

    PubMed

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

    2014-04-01

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

  12. Genome Wide Allele Frequency Fingerprints (GWAFFs) of Populations via Genotyping by Sequencing

    PubMed Central

    Byrne, Stephen; Czaban, Adrian; Studer, Bruno; Panitz, Frank; Bendixen, Christian; Asp, Torben

    2013-01-01

    Genotyping-by-Sequencing (GBS) is an excellent tool for characterising genetic variation between plant genomes. To date, its use has been reported only for genotyping of single individuals. However, there are many applications where resolving allele frequencies within populations on a genome-wide scale would be very powerful, examples include the breeding of outbreeding species, varietal protection in outbreeding species, monitoring changes in population allele frequencies. This motivated us to test the potential to use GBS to evaluate allele frequencies within populations. Perennial ryegrass is an outbreeding species, and breeding programs are based upon selection on populations. We tested two restriction enzymes for their efficiency in complexity reduction of the perennial ryegrass genome. The resulting profiles have been termed Genome Wide Allele Frequency Fingerprints (GWAFFs), and we have shown how these fingerprints can be used to distinguish between plant populations. Even at current costs and throughput, using sequencing to directly evaluate populations on a genome-wide scale is viable. GWAFFs should find many applications, from varietal development in outbreeding species right through to playing a role in protecting plant breeders’ rights. PMID:23469194

  13. Monooxygenase Levels and Knockdown Resistance (kdr) Allele Frequencies in Anopheles gambiae and Anopheles arabiensis in Kenya

    PubMed Central

    Chen, Hong; Githeko, Andrew K; Githure, John I; Mutunga, James; Zhou, Guofa; Yan, Guiyun

    2013-01-01

    Pyrethroid-treated bed nets and indoor spray are important components of malaria control strategies in Kenya. Information on resistance to pyrethroid insecticides in Anopheles gambiae and An. arabiensis populations is essential to the selection of appropriate insecticides and the management of insecticide resistance. Monooxygenase activity and knockdown resistance (kdr) allele frequency are biochemical and molecular indicators of mosquito resistance to pyrethroids. This study determined baseline information on monooxygenase activity and kdr allele frequency in anopheline mosquitoes in the western region, the Great Rift Valley-central province region, and the coastal region of Kenya. A total of 1990 field-collected individuals, representing 12 An. gambiae and 22 An. arabiensis populations was analyzed. We found significant among-population variation in monooxygenase activity in An. gambiae and An. arabiensis and substantial variability among individuals within populations. Nine out of 12 An. gambiae populations exhibited significantly higher average monooxygenase activity than the susceptible Kisumu reference strain. The kdr alleles (L1014S) were detected in three An. gambiae populations, and one An. arabiensis population in western Kenya, but not in the Rift Valley-central region and the coastal Kenya region. All genotypes with the kdr alleles were heterozygous, and the conservative estimation of kdr allele frequency was below 1% in these four populations. Information on monooxygenase activity and kdr allele frequency reported in this study provided baseline data for monitoring insecticide resistance changes in Kenya during the era when large-scale insecticide-treated bednet and indoor residual spray campaigns were being implemented. PMID:18402140

  14. Analysis of allelic variation of the apolipoprotein B hypervariable locus in the Bashkir and Komi populations

    SciTech Connect

    Khusnutdinova, E.K.; Khidiatova, I.M.; Rafikov, H.S.

    1995-07-01

    Allelic variation of the hypervariable apolipoprotein B gene locus (APOB) in three groups of the Bashkir population and in the Komi population was analyzed. Among 219 individuals studied, 13 allelic variants were identified with a number of repeats ranging from 28 to 52. The frequency of alleles varied from 0.01 to 0.51 with the mean heterozygosity index being 0.66 in the Bashkir population and 0.74 in the Komi one. Considerable difference in the frequency distribution of the APOB loci genotypes between the Bashkir and Komi populations was observed, and the distribution patterns for Bashkirs from Abzelilovskii and Ilishevskii raions deviated from the Hardy-Weinberg equilibrium. The genetic distance between the Bashkir and Komi populations calculated on the basis of allele frequencies at the hypervariable APOB gene locus corresponded to the expected degree similarity of the population studied. Thus, this locus can be recommended as an informative marker for studying the gene pool and genetic processes in the populations because of the high level of its polymorphism and the heterozygosity in the populations. 19 refs., 1 fig., 4 tabs.

  15. Allele frequency of CODIS 13 in Indonesian population.

    PubMed

    Untoro, Evi; Atmadja, Djaja Surya; Pu, Chang-En; Wu, Fang-Chi

    2009-04-01

    Since the first application of DNA technology in 1985 in forensic cases, and the acceptance of this technology in 1988 at court, the DNA typing is widely used in personal identification, parentage cases and tracing the source of biological samples found in the crime scene. The FBI on 1990 had recommended the forensic labs to used 13 loci of Short Tandem Repeats (STR), known as CODIS 13, as the loci of choice for forensic use. The research on the population DNA database on these loci is extremely important for calculating the Paternity Index as well as Matching Probability for forensic application of DNA technology. As many as 402 unrelated persons, consisted of 322 from western part of Indonesia and 80 from eastern part of Indonesia, were chosen as the respondents of this research, after signing the informed consent. The peripheral blood sample was taken using sterile lancets and dropped onto FTA classic cards. The DNA was extracted by FTA purification solution (3x) and TE(-1) (2x), and amplified by PCR mix, either Cofiler or Profiler Plus (Perkin Elmers), followed by sequencing using ABI Prism type 3100 Avant Genetic Analyzer. The analysis showed that the alleles frequencies of Indonesian is specific, different with the other Asian populations with some specific alleles and microvariant were found.

  16. Non-Equilibrium Allele Frequency Spectra Via Spectral Methods

    PubMed Central

    Hey, Jody; Chen, Kevin

    2011-01-01

    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. PMID:21376069

  17. Recovering frequencies of known haplotype blocks from single-nucleotide polymorphism allele frequencies.

    PubMed Central

    Pe'er, Itsik; Beckmann, Jacques S

    2004-01-01

    Prospects for large-scale association studies rely on economical methods and powerful analysis. Representing available SNPs by small subsets and measuring allele frequencies on pooled DNA samples each improve genotyping cost effectiveness, while haplotype analysis may highlight associations in otherwise underpowered studies. This manuscript provides the mathematical framework to integrate these methodologies. PMID:15126415

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

    PubMed

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

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

  20. GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach.

    PubMed

    Kasthurinaidu, Senthilkumar Pitchalu; Ramasamy, Thirumurugan; Ayyavoo, Jayachitra; Dave, Dhvani Kirtikumar; Adroja, Divya Anantray

    2015-01-01

    Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME). Among the XMEs, glutathione-S-transferases (GST) gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs). Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs). The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions) and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

  1. Genotype and allele frequencies of isoniazid-metabolizing enzymes NAT2 and GSTM1 in Latvian tuberculosis patients.

    PubMed

    Igumnova, Viktorija; Capligina, Valentina; Krams, Alvils; Cirule, Andra; Elferts, Didzis; Pole, Ilva; Jansone, Inta; Bandere, Dace; Ranka, Renate

    2016-07-01

    Pharmacogenomic testing of tuberculosis drug-metabolizing enzyme genes was proposed as a strategy to identify patients at risk for suboptimal responses to medications. However, variations of the genotype frequencies among ethnic groups exist and new alleles are been identified. The aim of this study was to identify polymorphisms of genes encoding metabolic enzymes NAT2 and GSTM1 in tuberculosis patients in Latvia and to estimate the frequency of NAT2 slow acetylator and GSTM1 null genotypes. In total, 85 DNA samples were genotyped, all individuals were Caucasian. An ethnic heterogeneity reflecting the multiethnic population of the country was observed. 49 patients were Latvians, 30 were Russians and 6 of other ethnicity. In total, 7 NAT2 alleles were identified: *4, *5, *6, *7, *11, *12, * and *13. The most frequent was the slow acetylation allele NAT2*6 (frequency 0.388) followed by the slow acetylation allele NAT2*5 and the rapid acetylation allele NAT2*4 (frequencies 0.306 and 0.194, respectively). The predominance of slow (51.8%) and intermediate (43.5%) acetylators compared with rapid acetylators (4.7%) was observed. The GSTM1 null genotype was detected in 48.2% of tuberculosis patients. When subgroup analysis was performed according to ethnicity, the results showed that neither NAT2 allele frequencies nor GSTM1 null genotype frequency did not differ significantly in TB patients of Latvian or Russian ethnicity. Overall, genotyping results were similar with previous reports of a NAT2 gene variation and GSTM1 null genotype frequency in Caucasians. Our findings have a contribution for the pharmacogenetics-based tuberculosis therapy in Latvia in future.

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

    SciTech Connect

    Chang, F.M.; Kidd, J.R.; Livak, K.J.

    1994-09-01

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

  3. Dombrock genotyping in Brazilian blood donors reveals different regional frequencies of the HY allele

    PubMed Central

    Piassi, Fabiana Chagas Camargos; Santos, Silvana Maria Eloi; de Castilho, Lilian Maria; Baleotti Júnior, Wilson; Suzuki, Rodrigo Buzinaro; da Cunha, Débora Moura

    2013-01-01

    Background Dombrock blood group system genotyping has revealed various rearrangements of the Dombrock gene and identified new variant alleles in Brazil (i.e., DO*A-SH, DO*A-WL and DO*B-WL). Because of the high heterogeneity of the Brazilian population, interregional differences are expected during the investigation of Dombrock genotypes. Objective The present study aims to determine the frequencies of Dombrock genotypes in blood donors from Minas Gerais and compare the frequencies of the HY and JO alleles to those of another population in Brazil. Methods The frequencies of the DO alleles in Minas Gerais, a southeastern state of Brazil, were determined from the genotyping of 270 blood donors. Genotyping involved polymerase chain reaction and restriction fragment length polymorphism analysis to identify the 323G>T, 350C>T, 793A>G, and 898C>G mutations, which are related to the HY, JO, DO*A/DO*B, and DO*A-WL/DO*B-WL alleles, respectively. Moreover, the frequencies of rare HY and JO alleles were statistically compared using the chi-square test with data from another Brazilian region. Results The HY allele frequency in Minas Gerais (2.4%) was almost twice that of the JO allele (1.5%). The frequency of the HY allele was significantly higher (p-value = 0.001) than that in another Brazilian population and includes a rare homozygous donor with the Hy- phenotype. In addition, the DO*A-WL and DO*B-WL alleles, which were first identified in Brazil, were found in the state of Minas Gerais. Conclusions The data confirm that the frequencies of DO alleles differ between regions in Brazil. The population of Minas Gerais could be targeted in a screening strategy to identify the Hy- phenotype in order to develop a rare blood bank. PMID:24478605

  4. Frequency of HLA-A alleles in the Syrian population genotyped by sequence-based typing.

    PubMed

    Madania, A; Ghoury, I; Al-Ashkar, W; Nweder, S; Zarzour, H

    2014-10-01

    HLA-A molecules are highly polymorphic. Their accurate typing at a high-resolution level is crucial for successful organ, bone marrow and cord blood transplantation. Furthermore, several HLA alleles have been involved in susceptibility to autoimmune diseases, allergies, cancers and inflammations. In order to determine common HLA-A alleles in Syria and their frequencies, sequence-based typing (SBT) was used to genotype HLA-A alleles at high resolution (four digit level) among one hundred and thirty randomly selected Syrian individuals. Exons 2, 3 and 4 of the HLA-A gene were amplified by PCR and sequenced. The sbt-engine software was used for allele assignment. Ambiguities were solved using group-specific sequencing primers (GSSPs). We could identify 32 different HLA-A alleles which were divided into 3 groups: high frequency (approximately 10%, A*01:01; A*24:02; A*03:01; A*02:01), moderate frequency (approximately 3%, such as A*02:05, A*31:01 and A*33:01), and low frequency (approximately 1%, such as A*02:11, A*29:01, A*02:02 and A*36:01). Homozygosity rate was higher than expected (11.5% vs. 7.15%). For high frequency alleles, our results show similarity to neighbouring countries. However, 15 alleles (such as A*02:04, A*02:06, A*02:11 and A*02:17) found in our cohort in low frequencies were never reported in some or all neighbouring countries. This is the first report on HLA-A allele frequencies in Syria. In spite of the relatively low number of tested subjects, our results revealed a high degree of diversity, with 32 different alleles, reflecting the high ethnic heterogeneity of the Syrian population. The identification of alleles rarely or never reported in neighbouring countries indicates a higher genetic diversity in Syria.

  5. Natural allelic variation defines a role for ATMYC1: trichome cell fate determination.

    PubMed

    Symonds, V Vaughan; Hatlestad, Greg; Lloyd, Alan M

    2011-06-01

    The molecular nature of biological variation is not well understood. Indeed, many questions persist regarding the types of molecular changes and the classes of genes that underlie morphological variation within and among species. Here we have taken a candidate gene approach based on previous mapping results to identify the gene and ultimately a polymorphism that underlies a trichome density QTL in Arabidopsis thaliana. Our results show that natural allelic variation in the transcription factor ATMYC1 alters trichome density in A. thaliana; this is the first reported function for ATMYC1. Using site-directed mutagenesis and yeast two-hybrid experiments, we demonstrate that a single amino acid replacement in ATMYC1, discovered in four ecotypes, eliminates known protein-protein interactions in the trichome initiation pathway. Additionally, in a broad screen for molecular variation at ATMYC1, including 72 A. thaliana ecotypes, a high-frequency block of variation was detected that results in >10% amino acid replacement within one of the eight exons of the gene. This sequence variation harbors a strong signal of divergent selection but has no measurable effect on trichome density. Homologs of ATMYC1 are pleiotropic, however, so this block of variation may be the result of natural selection having acted on another trait, while maintaining the trichome density role of the gene. These results show that ATMYC1 is an important source of variation for epidermal traits in A. thaliana and indicate that the transcription factors that make up the TTG1 genetic pathway generally may be important sources of epidermal variation in plants.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  7. Frequency of the delta ccr5 deletion allele in the urban Brazilian population.

    PubMed

    Passos, G A; Picanço, V P

    1998-04-01

    Studies on screening genes conferring resistance to HIV-1 and AIDS onset have shown a direct relationship between a 32 base pair (bp) deletion in the CCR5 beta-chemokine receptor gene (delta ccr5 mutant allele) and long survival of HIV-1 infected individuals bearing this mutation. These findings led to an interest in studies of delta ccr5 allele distribution in human populations. In the present study, polymerase chain reactions (PCR) in genomic DNA samples, using specific CCR5 oligonucleotide primers surrounding the breakpoint deletion, detected a 193-bp product from the normal CCR5 allele and a 161-bp product from the 32-bp deletion allele. In an investigation of the urban Brazilian population we detected a 93% frequency of normal CCR5/CCR5 homozygous individuals and a 7% frequency of CCR5/delta ccr5 heterozygous individuals. The frequency of the delta ccr5 mutant allele in this population is 0.035; however, no homozygous delta ccr5 individual has been detected thus far. This is the first evidence for the contribution of the delta ccr5 allele to the genetic background of the urban Brazilian population, which is characterized by intense ethnic admixture. These findings open perspectives for further studies on the relationship between delta ccr5 allele frequency and AIDS onset in high-risk HIV-1 exposures individuals.

  8. Allelic variations of glut-1 deficiency syndrome: the chinese experience.

    PubMed

    Liu, Yanyan; Bao, Xinhua; Wang, Dong; Fu, Na; Zhang, Xiaoying; Cao, Guangna; Song, Fuying; Wang, Shuang; Zhang, Yuehua; Qin, Jiong; Yang, Hong; Engelstad, Kristin; De Vivo, Darryl C; Wu, Xiru

    2012-07-01

    Glucose transporter type 1 deficiency syndrome is characterized by infantile onset seizures, development delay, movement disorders, and acquired microcephaly. The phenotype includes allelic variants such as intermittent ataxia, choreoathetosis, dystonia, and alternating hemiplegia of childhood with or without epilepsy. Dystonias involve allelic variants of glucose transporter type 1 deficiency syndrome. Three Chinese patients presented with paroxysmal behavioral disturbance, weakness, ataxia (especially after fasting), and exercise intolerance. Electroencephalogram findings did not correlate with clinical manifestations. Cranial magnetic resonance imaging produced normal results or mild hypomyelination. Hypoglycorrhachia was evident in all cases. Cerebrospinal fluid glucose ranged from 1.63-2.45 mmol/L. Erythrocyte 3-O-methyl-d-glucose uptake was decreased to 58% in patient 1. Three SLC2A1 disease-causing mutations (761delA, P383H, and R400C) were observed. No patient tolerated ketogenic diets. Two patients responded to frequent meals with snacks. Cerebrospinal fluid evaluation constitutes the diagnostic testing permitting early treatment of glucose transporter type 1 deficiency syndrome. Early diagnosis and treatment improve prognoses.

  9. High-Throughput SNP Allele-Frequency Determination in Pooled DNA Samples by Kinetic PCR

    PubMed Central

    Germer, Søren; Holland, Michael J.; Higuchi, Russell

    2000-01-01

    We have developed an accurate, yet inexpensive and high-throughput, method for determining the allele frequency of biallelic polymorphisms in pools of DNA samples. The assay combines kinetic (real-time quantitative) PCR with allele-specific amplification and requires no post-PCR processing. The relative amounts of each allele in a sample are quantified. This is performed by dividing equal aliquots of the pooled DNA between two separate PCR reactions, each of which contains a primer pair specific to one or the other allelic SNP variant. For pools with equal amounts of the two alleles, the two amplifications should reach a detectable level of fluorescence at the same cycle number. For pools that contain unequal ratios of the two alleles, the difference in cycle number between the two amplification reactions can be used to calculate the relative allele amounts. We demonstrate the accuracy and reliability of the assay on samples with known predetermined SNP allele frequencies from 5% to 95%, including pools of both human and mouse DNAs using eight different SNPs altogether. The accuracy of measuring known allele frequencies is very high, with the strength of correlation between measured and known frequencies having an r2 = 0.997. The loss of sensitivity as a result of measurement error is typically minimal, compared with that due to sampling error alone, for population samples up to 1000. We believe that by providing a means for SNP genotyping up to thousands of samples simultaneously, inexpensively, and reproducibly, this method is a powerful strategy for detecting meaningful polymorphic differences in candidate gene association studies and genome-wide linkage disequilibrium scans. PMID:10673283

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

    PubMed

    Keinan, Alon; Mullikin, James C; Patterson, Nick; Reich, David

    2007-10-01

    Large data sets on human genetic variation have been collected recently, but their usefulness for learning about history and natural selection has been limited by biases in the ways polymorphisms were chosen. We report large subsets of SNPs from the International HapMap Project that allow us to overcome these biases and to provide accurate measurement of a quantity of crucial importance for understanding genetic variation: the allele frequency spectrum. Our analysis shows that East Asian and northern European ancestors shared the same population bottleneck expanding out of Africa but that both also experienced more recent genetic drift, which was greater in East Asians.

  11. Statistical Inference in the Wright-Fisher Model Using Allele Frequency Data.

    PubMed

    Tataru, Paula; Simonsen, Maria; Bataillon, Thomas; Hobolth, Asger

    2016-08-02

    The Wright-Fisher model provides an elegant mathematical framework for understanding allele frequency data. In particular, the model can be used to infer the demographic history of species and identify loci under selection. A crucial quantity for inference under the Wright-Fisher model is the distribution of allele frequencies (DAF). Despite the apparent simplicity of the model, the calculation of the DAF is challenging. We review and discuss strategies for approximating the DAF, and how these are used in methods that perform inference from allele frequency data. Various evolutionary forces can be incorporated in the Wright-Fisher model, and we consider these in turn. We begin our review with the basic bi-allelic Wright-Fisher model where random genetic drift is the only evolutionary force. We then consider mutation, migration, and selection. In particular, we compare diffusion-based and moment-based methods in terms of accuracy, computational efficiency, and analytical tractability. We conclude with a brief overview of the multi-allelic process with a general mutation model. [Allele frequency, diffusion, inference, moments, selection, Wright-Fisher.].

  12. Frequency of the arylsulphatase A pseudodeficiency allele in the Spanish population.

    PubMed

    Chabás, A; Castellvi, S; Bayés, M; Balcells, S; Grinberg, D; Vilageliu, L; Marfany, G; Lissens, W; Gonzàlez-Duarte, R

    1993-12-01

    Pseudodeficiency in arylsulphatase A (ASA) is a relatively frequent condition in healthy individuals. It produces a reduction in enzyme activity similar to that found in metachromatic leukodystrophy (MLD). Unambiguous discrimination between the two conditions cannot be achieved through conventional enzyme activity assays. A PCR method has been developed which detects the pseudodeficiency (pd) allele using a single pair of primers encompassing the mutation site and hair follicles as the source of DNA. The frequency of this allele in the Spanish population has been evaluated and correlations between different genotypes and ASA activity levels have been established. Ten out of 55 individuals were heterozygous for the ASA pd allele, while two were homozygous. The allele frequency was thus 12.7%.

  13. Effects of allele frequency estimation on genomic predictions and inbreeding coefficients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic calculations often require estimating allele frequencies, which differ across time due to selection and drift. Data were 50,000 simulated markers and 39,985 actual markers for 2391 genotyped Holstein bulls. Gene content of relatives and gene frequencies in the base (founder) population were ...

  14. HLA-DRB1 and -DRB3 allele frequencies and haplotypic associations in Koreans.

    PubMed

    Song, Eun Young; Park, Hyejin; Roh, Eun Youn; Park, Myoung Hee

    2004-03-01

    We have investigated the frequencies of human leukocyte antigen-DRB1 (HLA-DRB1) and -DRB3 alleles and DRB1-DRB3 haplotypic associations in 800 Koreans. DRB1 genotyping was done using polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) and PCR-single strand conformation polymorphism (SSCP) methods. DRB3 genotyping was done on 447 samples carrying DRB3-associated DRB1 alleles (DRB1*03, *11, *12, *13, and *14) using PCR-SSCP method. The allele frequencies of DRB3*0101, DRB3*0202, and DRB3*0301 were 0.073, 0.136, and 0.120, respectively, and we found one case of a probable new allele (DRB3*01new, 0.001). DRB1-DRB3 haplotypes with frequency (HF) > 0.005 exhibited strong associations between DRB3*0101 and DRB1*1201, *1301, and *1403; between DRB3*0301 and DRB1*1202 and *1302; between DRB3*0202 and DRB1*0301, *1101, *1401, *1405, and *1406 alleles. Most of the DRB1 alleles with frequency > 0.005 were exclusively associated with particular DRB3 alleles with relative linkage disequilibrium values of 1.0, except for DRB1*1201, *1202 and *1301; the rare presence (HF < 0.005) of DRB3*0202 associations were observed for these DRB1 alleles. We also investigated and presented rare DRB1-DRB3 associations in additional 6000 Koreans. Comparison with other ethnic groups revealed that DRB1*0301 and *1301 related DRB1-DRB3 haplotypes vary among different populations, in that Koreans and other Asian populations show less diversity compared with Caucasoids or African Americans.

  15. Extensive allelic variation in gene expression in populus F1 hybrids.

    PubMed

    Zhuang, Yan; Adams, Keith L

    2007-12-01

    Hybridization between plant species can induce speciation as well as phenotypic novelty and heterosis. Hybrids also can show genome rearrangements and gene expression changes compared with their parents. Here we determined the allelic variation in gene expression in Populus trichocarpa x Populus deltoides F(1) hybrids. Among 30 genes analyzed in four independently formed hybrids, 17 showed >1.5-fold expression biases for one of the two alleles, and there was monoallelic expression of one gene. Expression ratios of the alleles differed between leaves and stems for 10 genes. The results suggest differential regulation of the two parental alleles in the hybrids. To determine if the allelic expression biases were caused by hybridization we compared the ratios of species-specific transcripts between an F(1) hybrid and its parents. Thirteen of 19 genes showed allelic expression ratios in the hybrid that were significantly different from the ratios of the parental species. The P. deltoides allele of one gene was silenced in the hybrid. Modes of gene regulation were inferred from the hybrid-parent comparisons. Cis-regulation was inferred for 6 genes, trans-regulation for 1 gene, and combined cis- and trans-regulation for 9 genes. The results from this study indicate that hybridization between plant species can have extensive effects on allelic expression patterns, some of which might lead to phenotypic changes.

  16. Disparities in allele frequencies and population differentiation for 101 disease-associated single nucleotide polymorphisms between Puerto Ricans and non-Hispanic whites

    PubMed Central

    Mattei, Josiemer; Parnell, Laurence D; Lai, Chao-Qiang; Garcia-Bailo, Bibiana; Adiconis, Xian; Shen, Jian; Arnett, Donna; Demissie, Serkalem; Tucker, Katherine L; Ordovas, Jose M

    2009-01-01

    Background Variations in gene allele frequencies can contribute to differences in the prevalence of some common complex diseases among populations. Natural selection modulates the balance in allele frequencies across populations. Population differentiation (FST) can evidence environmental selection pressures. Such genetic information is limited in Puerto Ricans, the second largest Hispanic ethnic group in the US, and a group with high prevalence of chronic disease. We determined allele frequencies and population differentiation for 101 single nucleotide polymorphisms (SNPs) in 30 genes involved in major metabolic and disease-relevant pathways in Puerto Ricans (n = 969, ages 45–75 years) and compared them to similarly aged non-Hispanic whites (NHW) (n = 597). Results Minor allele frequency (MAF) distributions for 45.5% of the SNPs assessed in Puerto Ricans were significantly different from those of NHW. Puerto Ricans carried risk alleles in higher frequency and protective alleles in lower frequency than NHW. Patterns of population differentiation showed that Puerto Ricans had SNPs with exceptional FST values in intronic, non-synonymous and promoter regions. NHW had exceptional FST values in intronic and promoter region SNPs only. Conclusion These observations may serve to explain and broaden studies on the impact of gene polymorphisms on chronic diseases affecting Puerto Ricans. PMID:19682384

  17. Genotype and allele frequencies of drug-metabolizing enzymes and drug transporter genes affecting immunosuppressants in the Spanish white population.

    PubMed

    Bosó, Virginia; Herrero, María J; Buso, Enrique; Galán, Juan; Almenar, Luis; Sánchez-Lázaro, Ignacio; Sánchez-Plumed, Jaime; Bea, Sergio; Prieto, Martín; García, María; Pastor, Amparo; Sole, Amparo; Poveda, José Luis; Aliño, Salvador F

    2014-04-01

    Interpatient variability in drug response can be widely explained by genetically determined differences in metabolizing enzymes, drug transporters, and drug targets, leading to different pharmacokinetic and/or pharmacodynamic behaviors of drugs. Genetic variations affect or do not affect drug responses depending on their influence on protein activity and the relevance of such proteins in the pathway of the drug. Also, the frequency of such genetic variations differs among populations, so the clinical relevance of a specific variation is not the same in all of them. In this study, a panel of 33 single nucleotide polymorphisms in 14 different genes (ABCB1, ABCC2, ABCG2, CYP2B6, CYP2C19, CYP2C9, CYP3A4, CYP3A5, MTHFR, NOD2/CARD15, SLCO1A2, SLCO1B1, TPMT, and UGT1A9), encoding for the most relevant metabolizing enzymes and drug transporters relating to immunosuppressant agents, was analyzed to determine the genotype profile and allele frequencies in comparison with HapMap data. A total of 570 Spanish white recipients and donors of solid organ transplants were included. In 24 single nucleotide polymorphisms, statistically significant differences in allele frequency were observed. The largest differences (>100%) occurred in ABCB1 rs2229109, ABCG2 rs2231137, CYP3A5 rs776746, NOD2/CARD15 rs2066844, TPMT rs1800462, and UGT1A9 rs72551330. In conclusion, differences were recorded between the Spanish and other white populations in terms of allele frequency and genotypic distribution. Such differences may have implications in relation to dose requirements and drug-induced toxicity. These data are important for further research to help explain interindividual pharmacokinetic and pharmacodynamic variability in response to drug therapy.

  18. Using maximum likelihood to estimate population size from temporal changes in allele frequencies.

    PubMed Central

    Williamson, E G; Slatkin, M

    1999-01-01

    We develop a maximum-likelihood framework for using temporal changes in allele frequencies to estimate the number of breeding individuals in a population. We use simulations to compare the performance of this estimator to an F-statistic estimator of variance effective population size. The maximum-likelihood estimator had a lower variance and smaller bias. Taking advantage of the likelihood framework, we extend the model to include exponential growth and show that temporal allele frequency data from three or more sampling events can be used to test for population growth. PMID:10353915

  19. Haplotypic Background of a Private Allele at High Frequency in the Americas

    PubMed Central

    Schroeder, Kari B.; Jakobsson, Mattias; Crawford, Michael H.; Schurr, Theodore G.; Boca, Simina M.; Conrad, Donald F.; Tito, Raul Y.; Osipova, Ludmilla P.; Tarskaia, Larissa A.; Zhadanov, Sergey I.; Wall, Jeffrey D.; Pritchard, Jonathan K.; Malhi, Ripan S.; Smith, David G.; Rosenberg, Noah A.

    2009-01-01

    Recently, the observation of a high-frequency private allele, the 9-repeat allele at microsatellite D9S1120, in all sampled Native American and Western Beringian populations has been interpreted as evidence that all modern Native Americans descend primarily from a single founding population. However, this inference assumed that all copies of the 9-repeat allele were identical by descent and that the geographic distribution of this allele had not been influenced by natural selection. To investigate whether these assumptions are satisfied, we genotyped 34 single nucleotide polymorphisms across ∼500 kilobases (kb) around D9S1120 in 21 Native American and Western Beringian populations and 54 other worldwide populations. All chromosomes with the 9-repeat allele share the same haplotypic background in the vicinity of D9S1120, suggesting that all sampled copies of the 9-repeat allele are identical by descent. Ninety-one percent of these chromosomes share the same 76.26 kb haplotype, which we call the “American Modal Haplotype” (AMH). Three observations lead us to conclude that the high frequency and widespread distribution of the 9-repeat allele are unlikely to be the result of positive selection: 1) aside from its association with the 9-repeat allele, the AMH does not have a high frequency in the Americas, 2) the AMH is not unusually long for its frequency compared with other haplotypes in the Americas, and 3) in Latin American mestizo populations, the proportion of Native American ancestry at D9S1120 is not unusual compared with that observed at other genomewide microsatellites. Using a new method for estimating the time to the most recent common ancestor (MRCA) of all sampled copies of an allele on the basis of an estimate of the length of the genealogy descended from the MRCA, we calculate the mean time to the MRCA of the 9-repeat allele to be between 7,325 and 39,900 years, depending on the demographic model used. The results support the hypothesis that all

  20. Allele and genotype frequencies of CYP2B6 in a Turkish population.

    PubMed

    Yuce-Artun, Nazan; Kose, Gulcin; Suzen, H Sinan

    2014-06-01

    Increasing interest in cytochrome P450 2B6 (CYP2B6) genetic polymorphism was stimulated by revelations of a specific CYP2B6 genotype significantly affecting the metabolism of various drugs in common clinical use in terms of increasing drug efficacy and avoiding adverse drug reactions. The present study aimed to determine the frequencies of CYP2B6*4 CYP2B6*5, CYP2B6*6, CYP2B6*7 and CYP2B6*9 alleles in healthy Turkish individuals (n = 172). Frequencies of three single nucleotide polymorphisms were 516G>T (28%), 785A>G (33%), and 1459C>T (12%). The frequencies of CYP2B6*1, *4, *5, *6, *7, and *9 alleles were 54.3 (95% CI 49.04-59.56), 6.4% (95% CI 3.81-8.99), 11% (95% CI 7.69-14.31), 25.3% (95% CI 20.71-29.89), 0.87% (95% CI -0.11-1.85) and 2.0% (95% CI 0.52-3.48), respectively. Allele *6 was more frequent (25.3%) than the other variant alleles in Turkish subjects. The frequencies of CYP2B6*4, *5, *6, *7, and *9 alleles were similar to European populations but significantly different from that reported for Asian populations. This is the first study to document the frequencies of the CYP2B6*4, *5, *6, *7, *9 alleles in the healthy Turkish individuals and our results could provide clinically useful information on drug metabolism by CYP2B6 in Turkish population.

  1. Resistance allele frequency to bt cotton in field populations of helicoverpa armigera (Lepidoptera: Noctuidae) in China.

    PubMed

    Liu, Fengyi; Xu, Zhiping; Chang, Juhua; Chen, Jin; Meng, Fengxia; Zhu, Yu Cheng; Shen, Jinliang

    2008-06-01

    Resistance evolution in target insects to Bacillus thurningiensis (Bt) cotton, Gossypium hirsutum L., is a main threat to Bt cotton technology. An increasing trend of population density of Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) has been observed since 2001 in Qiuxian County (Hebei, China), where Bt cotton has been planted dominantly since 1998. This region was selected in 2006 and 2007 for estimating frequency of gene alleles conferring resistance to Bt cotton by screening the F1 progeny from single-pair cross between field-collected male and laboratory female of the Bt-resistant strain of H. armigera (F1 screen). F1 offspring from each single-pair line were screened for resistance alleles based on larval growth, development, and survival on Bt cotton leaves for 5 d. Two-year results indicated that approximately equal to 20% of field-collected males carried resistance alleles. The conservative estimate of the resistance allele frequency was 0.094 (95% CI, 0.044-0.145) for 2006 and 0.107 (95% CI, 0.055-0.159) for 2007. This is the first report of resistance allele frequency increase to such a high level in the field in China. Long-term adoption of Bt sprays, dominant planting of single-toxin-producing Bt cotton, and lack of conventional cotton refuge system might accelerate the resistance evolution in the region.

  2. Cytochrome P450 2D6 variants in a Caucasian population: Allele frequencies and phenotypic consequences

    SciTech Connect

    Sachse, C.; Brockmoeller, J.; Bauer, S.; Roots, I.

    1997-02-01

    Cytochrome P450 2D6 (CYP2D6) metabolizes many important drugs. CYP2D6 activity ranges from complete deficiency to ultrafast metabolism, depending on at least 16 different known alleles. Their frequencies were determined in 589 unrelated German volunteers and correlated with enzyme activity measured by phenotyping with dextromethorphan or debrisoquine. For genotyping, nested PCR-RFLP tests from a PCR amplificate of the entire CYP2D6 gene were developed. The frequency of the CYP2D6*1 allele coding for extensive metabolizer (EM) phenotype was .364. The alleles coding for slightly (CYP2D6*2) or moderately (*9 and *10) reduced activity (intermediate metabolizer phenotype [IM]) showed frequencies of .324, .018, and .015, respectively. By use of novel PCR tests for discrimination, CYP2D6 gene duplication alleles were found with frequencies of.005 (*1 x 2), .013 (* 2 x 2), and .001 (*4 x 2). Frequencies of alleles with complete deficiency (poor metabolizer phenotype [PM]) were .207 (*4), .020 (*3 and *5), .009 (*6), and .001 (*7, *15, and *16). The defective CYP2D6 alleles *8, *11, *12, *13, and *14 were not found. All 41 PMs (7.0%) in this sample were explained by five mutations detected by four PCR-RFLP tests, which may suffice, together with the gene duplication test, for clinical prediction of CYP2D6 capacity. Three novel variants of known CYP2D6 alleles were discovered: *1C (T{sub 1957}C), *2B (additional C{sub 2558}T), and *4E (additional C{sub 2938}T). Analysis of variance showed significant differences in enzymatic activity measured by the dextromethorphan metabolic ratio (MR) between carriers of EN/PM (mean MR = .006) and IM/PM (mean MR = .014) alleles and between carriers of one (mean MR = .009) and two (mean MR = .003) functional alleles. The results of this study provide a solid basis for prediction of CYP2D6 capacity, as required in drug research and routine drug treatment. 35 refs., 4 figs., 5 tabs.

  3. Estimation of the frequency of hexosaminidase a variant alleles in the American Jewish population.

    PubMed

    Greenberg, D A; Kaback, M M

    1982-05-01

    There appear to be several alleles of the hexosaminidase A (HEX A) gene that lead to different clinical syndromes. In addition to the infantile-onset Tay-Sachs disease (TSD), there is a juvenile-onset and an adult-onset form, which are also characterized by low HEX A levels. There are also apparently healthy adults with low HEX A activity. Based primarily on data from population screening for TSD carrier status, we estimate the allele frequency of the combined variant alleles for which data are available to be about 4.5 x 10(-4) and the frequency of adults showing zero HEX A levels (when tested using artificial substrate) to be about 1:67,000. The implications for population screening and prenatal diagnosis are discussed.

  4. Complex and multi-allelic copy number variation in human disease.

    PubMed

    Usher, Christina L; McCarroll, Steven A

    2015-09-01

    Hundreds of copy number variants are complex and multi-allelic, in that they have many structural alleles and have rearranged multiple times in the ancestors who contributed chromosomes to current humans. Not only are the relationships of these multi-allelic CNVs (mCNVs) to phenotypes generally unknown, but many mCNVs have not yet been described at the basic levels-alleles, allele frequencies, structural features-that support genetic investigation. To date, most reported disease associations to these variants have been ascertained through candidate gene studies. However, only a few associations have reached the level of acceptance defined by durable replications in many cohorts. This likely stems from longstanding challenges in making precise molecular measurements of the alleles individuals have at these loci. However, approaches for mCNV analysis are improving quickly, and some of the unique characteristics of mCNVs may assist future association studies. Their various structural alleles are likely to have different magnitudes of effect, creating a natural allelic series of growing phenotypic impact and giving investigators a set of natural predictions and testable hypotheses about the extent to which each allele of an mCNV predisposes to a phenotype. Also, mCNVs' low-to-modest correlation to individual single-nucleotide polymorphisms (SNPs) may make it easier to distinguish between mCNVs and nearby SNPs as the drivers of an association signal, and perhaps, make it possible to preliminarily screen candidate loci, or the entire genome, for the many mCNV-disease relationships that remain to be discovered.

  5. Complex and multi-allelic copy number variation in human disease

    PubMed Central

    McCarroll, Steven A.

    2015-01-01

    Hundreds of copy number variants are complex and multi-allelic, in that they have many structural alleles and have rearranged multiple times in the ancestors who contributed chromosomes to current humans. Not only are the relationships of these multi-allelic CNVs (mCNVs) to phenotypes generally unknown, but many mCNVs have not yet been described at the basic levels—alleles, allele frequencies, structural features—that support genetic investigation. To date, most reported disease associations to these variants have been ascertained through candidate gene studies. However, only a few associations have reached the level of acceptance defined by durable replications in many cohorts. This likely stems from longstanding challenges in making precise molecular measurements of the alleles individuals have at these loci. However, approaches for mCNV analysis are improving quickly, and some of the unique characteristics of mCNVs may assist future association studies. Their various structural alleles are likely to have different magnitudes of effect, creating a natural allelic series of growing phenotypic impact and giving investigators a set of natural predictions and testable hypotheses about the extent to which each allele of an mCNV predisposes to a phenotype. Also, mCNVs’ low-to-modest correlation to individual single-nucleotide polymorphisms (SNPs) may make it easier to distinguish between mCNVs and nearby SNPs as the drivers of an association signal, and perhaps, make it possible to preliminarily screen candidate loci, or the entire genome, for the many mCNV–disease relationships that remain to be discovered. PMID:26163405

  6. Predictable allele frequency changes due to habitat fragmentation in the Glanville fritillary butterfly.

    PubMed

    Fountain, Toby; Nieminen, Marko; Sirén, Jukka; Wong, Swee Chong; Hanski, Ilkka

    2016-03-08

    Describing the evolutionary dynamics of now extinct populations is challenging, as their genetic composition before extinction is generally unknown. The Glanville fritillary butterfly has a large extant metapopulation in the Åland Islands in Finland, but declined to extinction in the nearby fragmented southwestern (SW) Finnish archipelago in the 20th century. We genotyped museum samples for 222 SNPs across the genome, including SNPs from candidate genes and neutral regions. SW Finnish populations had significantly reduced genetic diversity before extinction, and their allele frequencies gradually diverged from those in contemporary Åland populations over 80 y. We identified 15 outlier loci among candidate SNPs, mostly related to flight, in which allele frequencies have changed more than the neutral expectation. At outlier loci, allele frequencies in SW Finland shifted in the same direction as newly established populations deviated from old local populations in contemporary Åland. Moreover, outlier allele frequencies in SW Finland resemble those in fragmented landscapes as opposed to continuous landscapes in the Baltic region. These results indicate selection for genotypes associated with good colonization capacity in the highly fragmented landscape before the extinction of the populations. Evolutionary response to habitat fragmentation may have enhanced the viability of the populations, but it did not save the species from regional extinction in the face of severe habitat loss and fragmentation. These results highlight a potentially common situation in changing environments: evolutionary changes are not strong enough to fully compensate for the direct adverse effects of environmental change and thereby rescue populations from extinction.

  7. Autosomal STR allele frequencies for the CODIS system from a large random population sample in Chile.

    PubMed

    Vergara, Ismael A; Villouta, Pamela; Herrera, Sandra; Melo, Francisco

    2012-05-01

    The thirteen autosomal STR loci of the CODIS system were typed from DNA of 732 unrelated male individuals sampled from different locations in Chile. This is the first report of allele frequencies for the thirteen STRs loci defined in the CODIS system from the Chilean population.

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

    PubMed

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

    2009-02-01

    The distribution of the frequencies of BoLA-DRB3 gene alleles in the Iranian cattle breed Sistani was studied by the PCR-RFLP ("hemi-nested") assay using restriction endonucleases RsaI, HaeIII and BstYI. In the examined cattle breed (65 animals) 32 alleles have been identified one of which being described for the first time (6.15% frequency). The nucleotide sequence of the polymorphic region of exon 2 of this allele has been determined and submitted in the GeneBank database under accession number DQ486519. The submitted sequence has maximum homology (92%) with the previously described sequence DRB3-mRNA from Bos indicus (AccN X79346) and differs from it by 24 nucleotide substitutions which result in 16 amino acid substitutions. The peptide (on the basis of the reconstructed amino acid sequence) has 89% identity to the sequence encoded by the BIDRBF 188 locus (Bos indicus). The results obtained permit the sequence described by us to be considered as a new allele of the BoLA-DRB3 gene (DRB3.2**X). The total frequency of the main six alleles (DRB3.2*X, *10, *11, *20, *34 and *X) occurring with a frequency of over 5% is about 60% in Iranian Sistani cattle. Fifteen alleles have <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.

  9. Determination of arylsulfatase A pseudodeficiency allele and haplotype frequency in the Tunisian population.

    PubMed

    Ben Halim, Nizar; Dorboz, Imen; Kefi, Rym; Kharrat, Najla; Eymard-Pierre, Eleonore; Nagara, Majdi; Romdhane, Lilia; Ben Alaya-Bouafif, Nissaf; Rebai, Ahmed; Miladi, Najoua; Boespflug-Tanguy, Odile; Abdelhak, Sonia

    2016-03-01

    Arylsulfatase A (ASA) is a lysosomal enzyme involved in the catabolism of cerebroside sulfate. ASA deficiency is associated with metachromatic leukodystrophy (MLD). Low ASA activities have also been reported in a more common condition with no apparent clinical consequences termed ASA pseudo-deficiency (ASA-PD) which is associated with two linked mutations in the ASA gene (c.1049A>G and c.*96A>G). This study aimed to investigate the frequency of the two ASA-PD variants and their linkage disequilibrium (LD) among Tunisians. ASA-PD variants were detected in 129 healthy Tunisians and their frequencies were compared to those described worldwide. The frequency of the PD allele was estimated at 17.4% for the overall sample, with c.1049A>G and c.*96A>G frequencies of 25.6 and 17.4%, respectively. This study also revealed a high LD between the two ASA-PD variants (r(2) = 0.61). Inter-population analysis revealed similarities in the ASA-PD genetic structure between Tunisians and populations from Middle East with c.*96A>G frequencies being the highest in the world. A significant North vs. South genetic differentiation in the ASA-PD frequency was also observed in Tunisian population who seems genetically intermediate between Africans, Middle-Easterners and Europeans. This is the first report on the allele frequency of the ASA-PD in North Africa, revealing a relatively high frequency of the PD allele among Tunisians. This study gives also evidence on the importance of discriminating ASA-PD allele from pathological mutations causing MLD and supporting enzymatic activity testing with both sulfatiduria determination and genetic testing in the differential diagnosis of MLD in the Tunisian population.

  10. Estimating the Effective Population Size from Temporal Allele Frequency Changes in Experimental Evolution

    PubMed Central

    Jónás, Ágnes; Taus, Thomas; Kosiol, Carolin; Schlötterer, Christian; Futschik, Andreas

    2016-01-01

    The effective population size (Ne) is a major factor determining allele frequency changes in natural and experimental populations. Temporal methods provide a powerful and simple approach to estimate short-term Ne. They use allele frequency shifts between temporal samples to calculate the standardized variance, which is directly related to Ne. Here we focus on experimental evolution studies that often rely on repeated sequencing of samples in pools (Pool-seq). Pool-seq is cost-effective and often outperforms individual-based sequencing in estimating allele frequencies, but it is associated with atypical sampling properties: Additional to sampling individuals, sequencing DNA in pools leads to a second round of sampling, which increases the variance of allele frequency estimates. We propose a new estimator of Ne, which relies on allele frequency changes in temporal data and corrects for the variance in both sampling steps. In simulations, we obtain accurate Ne estimates, as long as the drift variance is not too small compared to the sampling and sequencing variance. In addition to genome-wide Ne estimates, we extend our method using a recursive partitioning approach to estimate Ne locally along the chromosome. Since the type I error is controlled, our method permits the identification of genomic regions that differ significantly in their Ne estimates. We present an application to Pool-seq data from experimental evolution with Drosophila and provide recommendations for whole-genome data. The estimator is computationally efficient and available as an R package at https://github.com/ThomasTaus/Nest. PMID:27542959

  11. Allele frequency data of 15 autosomal STR loci in four major population groups of South Africa.

    PubMed

    Lucassen, Anton; Ehlers, Karen; Grobler, Paul J; Shezi, Adeline L

    2014-03-01

    Allele frequency distributions for 15 tetrameric short tandem repeat (STR) loci were determined using the AmpFlSTR® Identifiler Plus™ PCR amplification kit. There was little evidence of departures from Hardy-Weinberg equilibrium or association of alleles of different loci in the population samples. The probability of identity values for the different populations range from 1/3.3 × 10(17) (White) to 1/1.88 × 10(18) (Coloured). The combined probability of paternal exclusion for the different population groups ranges from 0.9995858 (Coloured) to 0.9997874 (Indian).

  12. MicroRNA Genetic Variation: From Population Analysis to Functional Implications of Three Allele Variants Associated with Cancer.

    PubMed

    Torruella-Loran, Ignasi; Laayouni, Hafid; Dobon, Begoña; Gallego, Alicia; Balcells, Ingrid; Garcia-Ramallo, Eva; Espinosa-Parrilla, Yolanda

    2016-10-01

    Nucleotide variants in microRNA regions have been associated with disease; nevertheless, few studies still have addressed the allele-dependent effect of these changes. We studied microRNA genetic variation in human populations and found that while low-frequency variants accumulate indistinctly in microRNA regions, the mature and seed regions tend to be depleted of high-frequency variants, probably as a result of purifying selection. Comparison of pairwise population fixation indexes among regions showed that the seed had higher population fixation indexes than the other regions, suggesting the existence of local adaptation in the seed region. We further performed functional studies of three microRNA variants associated with cancer (rs2910164:C > G in MIR146A, rs11614913:C > T in MIR196A2, and rs3746444:A > G in both MIR499A and MIR499B). We found differences in the expression between alleles and in the regulation of several genes involved in cancer, such as TP53, KIT, CDH1, CLH, and TERT, which may result in changes in regulatory networks related to tumorigenesis. Furthermore, luciferase-based assays showed that MIR499A could be regulating the cadherin CDH1 and the cell adhesion molecule CLH1 in an allele-dependent fashion. A better understanding of the effect of microRNA variants associated with disease could be key in our way to a more personalized medicine.

  13. Allele specific-PCR and melting curve analysis showed relatively high frequency of β-casein gene A1 allele in Iranian Holstein, Simmental and native cows.

    PubMed

    Gholami, M; Hafezian, S H; Rahimi, G; Farhadi, A; Rahimi, Z; Kahrizi, D; Kiani, S; Karim, H; Vaziri, S; Muhammadi, S; Veisi, F; Ghadiri, K; Shetabi, H; Zargooshi, J

    2016-10-31

    There are two allelic forms of A1 and A2 of β-casein gene in dairy cattle. Proteolytic digestion of bovine β-casein A1 type produces bioactive peptide of β-casomorphin-7 known as milk devil. β-casomorphin-7 causes many diseases, including type 1 diabetes, cardiovascular disease syndrome, sudden death and madness. The aim of the present study was to determine the different allelic forms of β-casein gene in Iranian Holstein, Simmental and native cattle in order to identify A1 and A2 variants. The blood samples were collected randomly and DNA was extracted using modified salting out method. An 854 bp fragment including part of exon 7 and part of intron 6 of β-casein gene was amplified by allele specific polymerase chain reaction (AS-PCR). Also, the accuracy of AS-PCR genotyping has been confirmed by melting temperature curve analysis using Real-time PCR machinery. The comparison of observed allele and genotype frequency among the studied breeds was performed using the Fisher exact and Chi-squared test, respectively by SAS program. Obtained results showed the A1 allele frequencies of 50, 51.57, 54.5, 49.4 and 46.6% in Holstein, Simmental, Sistani, Taleshi and Mazandarani cattle populations, respectively. The chi-square test was shown that no any populations were in Hardy-Weinberg equilibrium for studied marker locus. Comparison and analysis of the test results for allelic frequency showed no any significant differences between breeds (P>0.05). The frequency of observed genotypes only differs significantly between Holstein and Taleshi breeds but no any statistically significant differences were found for other breeds (P>0.05). A relatively high frequency of β-casein A1 allele was observed in Iranian native cattle. Therefore, determine the genotypes and preference alleles A2 in these native and commercial cattle is recommended.

  14. Crohn's Disease Risk Alleles on the NOD2 Locus Have Been Maintained by Natural Selection on Standing Variation

    PubMed Central

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

    2012-01-01

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

  15. Beyond orchids and dandelions: Testing the 5HTT “risky” allele for evidence of phenotypic capacitance and frequency dependent selection

    PubMed Central

    Conley, Dalton; Rauscher, Emily; Siegal, Mark L.

    2013-01-01

    The persistence of behaviorally deleterious genes in the human population poses an interesting question for population genetics: If certain alleles at these loci are deleterious, why have they survived in the population? We consider evidence for phenotypic capacitance and/or frequency dependent selection for an allele that has been putatively shown to have negative associations with human behaviors (the “short” 5-HTT promoter region allele) yet which has persisted in human and non-human primate populations. Using National Longitudinal Study of Adolescent Health data, we compare sibling and twin variation in depression by 5-HTT genotype (specified in several ways) and investigate sibship-level cross-person gene-gene interactions. In support of the “orchid / dandelion” hypothesis, we find evidence that the short allele increases variation in phenotypes in response to environmental (or genetic) differences (i.e. acts as a perturbation of a phenotypic capacitor). Further, we also find some evidence that the effects of allelic variation at this locus are moderated by the genetic environment of the sibship unit (i.e. may be susceptible to frequency dependent selection). We discuss implications of these findings for genetic models in general, specifically with respect to stable unit treatment value assumption violations (i.e. non-independence of units of analysis). PMID:23701535

  16. Correlated evolution of nucleotide substitution rates and allelic variation in Mhc-DRB lineages of primates

    PubMed Central

    Garamszegi, László Z; de Groot, Natasja G; Bontrop, Ronald E

    2009-01-01

    Background The major histocompatibility complex (MHC) is a key model of genetic polymorphism. Selection pressure by pathogens or other microevolutionary forces may result in a high rate of non-synonymous substitutions at the codons specifying the contact residues of the antigen binding sites (ABS), and the maintenance of extreme MHC allelic variation at the population/species level. Therefore, selection forces favouring MHC variability for any reason should cause a correlated evolution between substitution rates and allelic polymorphism. To investigate this prediction, we characterised nucleotide substitution rates and allelic polymorphism (i.e. the number of alleles detected in relation to the number of animals screened) of several Mhc class II DRB lineages in 46 primate species, and tested for a correlation between them. Results First, we demonstrate that species-specific and lineage-specific evolutionary constraints favour species- and lineage-dependent substitution rate at the codons specifying the ABS contact residues (i.e. certain species and lineages can be characterised by high substitution rate, while others have low rate). Second, we show that although the degree of the non-synonymous substitution rate at the ABS contact residues was systematically higher than the degree of the synonymous substitution rate, these estimates were strongly correlated when we controlled for species-specific and lineage-specific effects, and also for the fact that different studies relied on different sample size. Such relationships between substitution rates of different types could even be extended to the non-contact residues of the molecule. Third, we provide statistical evidence that increased substitution rate along a MHC gene may lead to allelic variation, as a high substitution rate can be observed in those lineages in which many alleles are maintained. Fourth, we show that the detected patterns were independent of phylogenetic constraints. When we used phylogenetic

  17. Allelic Variation in a Willow Warbler Genomic Region Is Associated with Climate Clines

    PubMed Central

    Larson, Keith W.; Liedvogel, Miriam; Addison, BriAnne; Kleven, Oddmund; Laskemoen, Terje; Lifjeld, Jan T.; Lundberg, Max; Åkesson, Susanne; Bensch, Staffan

    2014-01-01

    Local adaptation is an important process contributing to population differentiation which can occur in continuous or isolated populations connected by various amounts of gene flow. The willow warbler (Phylloscopus trochilus) is one of the most common songbirds in Fennoscandia. It has a continuous breeding distribution where it is found in all forested habitats from sea level to the tree line and therefore constitutes an ideal species for the study of locally adapted genes associated with environmental gradients. Previous studies in this species identified a genetic marker (AFLP-WW1) that showed a steep north-south cline in central Sweden with one allele associated with coastal lowland habitats and the other with mountainous habitats. It was further demonstrated that this marker is embedded in a highly differentiated chromosome region that spans several megabases. In the present study, we sampled 2,355 individuals at 128 sites across all of Fennoscandia to study the geographic and climatic variables associated with the allele frequency distributions of WW1. Our results demonstrate that 1) allele frequency patterns significantly differ between mountain and lowland populations, 2) these allele differences coincide with extreme temperature conditions and the short growing season in the mountains, and milder conditions in coastal areas, and 3) the northern-allele or “altitude variant” of WW1 occurs in willow warblers that occupy mountainous habitat regardless of subspecies. Finally these results suggest that climate may exert selection on the genomic region associated with these alleles and would allow us to develop testable predictions for the distribution of the genetic marker based on climate change scenarios. PMID:24788148

  18. Allele frequencies of microsatellite loci for genetic characterization of a Sicilian bovine population.

    PubMed

    Cosenza, M; Reale, S; Lupo, T; Vitale, F; Caracappa, S

    2015-01-30

    Short tandem repeats are used as an effective method to trace DNA markers in genotyping. Using a standardized kit, we tested 11 microsatellite markers recommended by the International Society for Animal Genetics (ISAG) in a sample of 495 Sicilian cattle. The aim of this study was to investigate the allele frequencies in the Sicilian cattle population to provide a reference database and at the same time to assess the use of the ISAG microsatellite panel for pedigree analysis. DNA samples were collected from blood and amplified in an 11-plex polymerase chain reaction (PCR); PCR products were injected in a 3130 Genetic Analyzer. All loci showed high mean polymorphism information content (0.768), and the observed mean heterozygosity was less than the expected value (0.732 vs 0.794, respectively). The exact test for Hardy-Weinberg proportions, allele number, and inbreeding coefficient were calculated. Our results indicated that equilibrium was not always maintained. The observed mean homozygote value exceeded the expected value (132.81 vs 102.14), but no evidence for allele dropout was found. These results could be explained by a non-random mating; further studies using a larger number of animals could confirm or invalidate this hypothesis. The probability of identity and exclusion of a locus were also estimated and proved to be useful in paternity testing. The ISAG microsatellite panel is useful to screen the Sicilian bovine kinship. Currently, an allele frequency database is being constructed.

  19. Allele frequency of antiretroviral host factor TRIMCyp in wild-caught cynomolgus macaques (Macaca fascicularis)

    PubMed Central

    Saito, Akatsuki; Kawamoto, Yoshi; Higashino, Atsunori; Yoshida, Tomoyuki; Ikoma, Tomoko; Suzaki, Yuriko; Ami, Yasushi; Shioda, Tatsuo; Nakayama, Emi E.; Akari, Hirofumi

    2012-01-01

    A recent study showed that the frequency of an antiretroviral factor TRIM5 gene-derived isoform, TRIMCyp, in cynomolgus macaques (Macaca fascicularis) varies widely according to the particular habitat examined. However, whether the findings actually reflect the prevalence of TRIMCyp in wild cynomolgus macaques is still uncertain because the previous data were obtained with captive monkeys in breeding and rearing facilities. Here, we characterized the TRIM5 gene in cynomolgus macaques captured in the wild, and found that the frequency of the TRIMCyp allele was comparable to those in captive monkeys. This suggests that the previous results with captive monkeys do indeed reflect the natural allele frequency and that breeding and rearing facilities may not affect the frequency of TRIM5 alleles. Interestingly, the prevalence of a minor haplotype of TRIMCyp in wild macaques from the Philippines was significantly lower than in captive ones, suggesting that it is advantageous for wild monkeys to possess the major haplotype of TRIMCyp. Overall, our results add to our understanding of the geographic and genetic prevalence of cynomolgus macaque TRIMCyp. PMID:22969754

  20. Allele frequency data for 15 autosomal STR loci in eight Indonesian subpopulations.

    PubMed

    Venables, Samantha J; Daniel, Runa; Sarre, Stephen D; Soedarsono, Nurtami; Sudoyo, Herawati; Suryadi, Helena; van Oorschot, Roland A H; Walsh, Simon J; Widodo, Putut T; McNevin, Dennis

    2016-01-01

    Evolutionary and cultural history can affect the genetic characteristics of a population and influences the frequency of different variants at a particular genetic marker (allele frequency). These characteristics directly influence the strength of forensic DNA evidence and make the availability of suitable allele frequency information for every discrete country or jurisdiction highly relevant. Population sub-structure within Indonesia has not been well characterised but should be expected given the complex geographical, linguistic and cultural architecture of the Indonesian population. Here we use forensic short tandem repeat (STR) markers to identify a number of distinct genetic subpopulations within Indonesia and calculate appropriate population sub-structure correction factors. This data represents the most comprehensive investigation of population sub-structure within Indonesia to date using these markers. The results demonstrate that significant sub-structure is present within the Indonesian population and must be accounted for using island specific allele frequencies and corresponding sub-structure correction factors in the calculation of forensic DNA match statistics.

  1. Cycle pattern of a R allelic variation. Progress report, 1 November 1978-31 January 1980

    SciTech Connect

    Kermicle, J.L.

    1980-01-01

    Two R alleles vary in cycle fashion. The original, intensely pigmenting forms change to weakly acting ones which revert in turn to the original. Neither direction of change is correlated with recombination of flanking markers. The reversion frequencies do not differ from the respective frequencies of change in the forward direction. The changes are restricted in the life cycle to about the time of meiosis. Modifying tthe incidence of crossing over in the R region altered the frequency of reversion proportionately. These features of instability could result from switching by intrachromosomal recombination between alternative arrangements of an R segment associated with an inverted duplication.

  2. Predictable allele frequency changes due to habitat fragmentation in the Glanville fritillary butterfly

    PubMed Central

    Fountain, Toby; Nieminen, Marko; Sirén, Jukka; Wong, Swee Chong; Lehtonen, Rainer; Hanski, Ilkka

    2016-01-01

    Describing the evolutionary dynamics of now extinct populations is challenging, as their genetic composition before extinction is generally unknown. The Glanville fritillary butterfly has a large extant metapopulation in the Åland Islands in Finland, but declined to extinction in the nearby fragmented southwestern (SW) Finnish archipelago in the 20th century. We genotyped museum samples for 222 SNPs across the genome, including SNPs from candidate genes and neutral regions. SW Finnish populations had significantly reduced genetic diversity before extinction, and their allele frequencies gradually diverged from those in contemporary Åland populations over 80 y. We identified 15 outlier loci among candidate SNPs, mostly related to flight, in which allele frequencies have changed more than the neutral expectation. At outlier loci, allele frequencies in SW Finland shifted in the same direction as newly established populations deviated from old local populations in contemporary Åland. Moreover, outlier allele frequencies in SW Finland resemble those in fragmented landscapes as opposed to continuous landscapes in the Baltic region. These results indicate selection for genotypes associated with good colonization capacity in the highly fragmented landscape before the extinction of the populations. Evolutionary response to habitat fragmentation may have enhanced the viability of the populations, but it did not save the species from regional extinction in the face of severe habitat loss and fragmentation. These results highlight a potentially common situation in changing environments: evolutionary changes are not strong enough to fully compensate for the direct adverse effects of environmental change and thereby rescue populations from extinction. PMID:26903642

  3. Allelic Variation on Murine Chromosome 11 Modifies Host Inflammatory Responses and Resistance to Bacillus anthracis

    DTIC Science & Technology

    2011-12-01

    Allelic Variation on Murine Chromosome 11 Modifies Host Inflammatory Responses and Resistance to Bacillus anthracis Jill K. Terra1, Bryan France1...of America Abstract Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by...Inflammatory Responses and Resistance to Bacillus anthracis. PLoS Pathog 7(12): e1002469. doi:10.1371/journal.ppat.1002469 Editor: Theresa M. Koehler, The

  4. The joint allele frequency spectrum of multiple populations: a coalescent theory approach.

    PubMed

    Chen, Hua

    2012-03-01

    The allele frequency spectrum is a series of statistics that describe genetic polymorphism, and is commonly used for inferring population genetic parameters and detecting natural selection. Population genetic theory on the allele frequency spectrum for a single population has been well studied using both coalescent theory and diffusion equations. Recently, the theory was extended to the joint allele frequency spectrum (JAFS) for three populations using diffusion equations and was shown to be very useful in inferring human demographic history. In this paper, I show that the JAFS can be analytically derived with coalescent theory for a basic model of two isolated populations and then extended to multiple populations and various complex scenarios, such as those involving population growth and bottleneck, migration, and positive selection. Simulation study is used to demonstrate the accuracy and applicability of the theoretical model. The coalescent theory-based approach for the JAFS can characterize the demographic history with comprehensive statistical models as the diffusion approach does, and in addition gains several novel advantages: the computational complexity of calculating the JAFS with coalescent theory is reduced, and thus it is feasible to analytically obtain the JAFS for multiple populations; the hitchhiking effect can be efficiently modeled in coalescent theory, enabling the development of methodologies for detecting selection via multi-population polymorphism data. As an alternative to the diffusion approximation approach, the coalescent theory for the JAFS also provides a foundation for population genetic inference with the advent of large-scale genomic polymorphism data.

  5. New CODIS core loci allele frequencies for 96,400 Brazilian individuals.

    PubMed

    Aguiar, Vitor R C; de Castro, Amanda M; Almeida, Vanessa C O; Malta, Frederico S V; Ferreira, Alessandro C S; Louro, Iúri D

    2014-11-01

    We have reported the allele frequencies of 15 STR loci, including the original 13 CODIS core loci, in over 100,000 Brazilian individuals. A new CODIS core loci has been proposed, but the recently established Brazilian Integrated Network of DNA Databases made a decision in 2010 to postpone the implementation of this new set of loci due to the lack of allele frequency data for the Brazilian population. We aimed to report allele frequencies of 20 loci, estimated from 96,400 Brazilian individuals undergoing paternity testing during 2011-2013. The percentage of missing data was less than 0.6% for all loci, except for CSF1PO (3.15%) and D7S820 (2.5%). The dropout rates estimated by the MicroDrop software were 0.013 for CSF1PO, 0.000037 for D7S820 and less than 0.000001 for other loci. Small missing data percentages and dropout rates reflect the high quality of the data.

  6. Microsatellite variation and rare alleles in a bottlenecked Hawaiian Islands endemic: implications for reintroductions

    USGS Publications Warehouse

    Reynolds, Michelle H.; Pearce, John M.; Lavretsky, Philip; Seixas, Pedro P.; Courtot, Karen

    2015-01-01

    Conservation of genetic biodiversity in endangered wildlife populations is an important challenge to address since the loss of alleles and genetic drift may influence future adaptability. Reintroduction aims to re-establish species to restored or protected ecosystems; however, moving a subset of individuals may result in loss of gene variants during the management-induced bottleneck (i.e. translocation). The endangered Laysan teal Anas laysanensis was once widespread across the Hawaiian archipelago, but became isolated on Laysan Island (415 ha) from the mid-1800s until 2004 when a translocation to Midway Atoll (596 ha) was undertaken to reduce extinction risks. We compared genetic diversity and quantified variation at microsatellite loci sampled from 230 individuals from the wild populations at Laysan (1999 to 2009) and Midway (2007 to 2010; n = 133 Laysan, n = 96 Midway birds). We identified polymorphic markers by screening nuclear microsatellites (N = 83). Low nuclear variation was detected, consistent with the species’ insular isolation and historical bottleneck. Six of 83 microsatellites were polymorphic. We found limited but similar estimates of allelic richness (2.58 alleles per locus) and heterozygosity within populations. However, 2 rare alleles found in the Laysan source population were not present in Midway’s reintroduced population, and a unique allele was discovered in an individual on Midway. Differentiation between island populations was low (FST = 0.6%), but statistically significant. Our results indicate that genetic drift had little effect on offspring generations 3 to 6 yr post-release and demonstrate the utility of using known founder events to help quantify genetic capture during translocations and to inform management decisions.

  7. On the maintenance of genetic variation: global analysis of Kimura's continuum-of-alleles model.

    PubMed

    Bürger, R

    1986-01-01

    Methods of functional analysis are applied to provide an exact mathematical analysis of Kimura's continuum-of-alleles model. By an approximate analysis, Kimura obtained the result that the equilibrium distribution of allelic effects determining a quantitative character is Gaussian if fitness decreases quadratically from the optimum and if production of new mutants follows a Gaussian density. Lande extended this model considerably and proposed that high levels of genetic variation can be maintained by mutation even when there is strong stabilizing selection. This hypothesis has been questioned recently by Turelli, who published analyses and computer simulations of some multiallele models, approximating the continuum-of-alleles model, and reviewed relevant data. He found that the Kimura and Lande predictions overestimate the amount of equilibrium variance considerably if selection is not extremely weak or mutation rate not extremely high. The present analysis provides the first proof that in Kimura's model an equilibrium in fact exists and, moreover, that it is globally stable. Finally, using methods from quantum mechanics, estimates of the exact equilibrium variance are derived which are in best accordance with Turelli's results. This shows that continuum-of-alleles models may be excellent approximations to multiallele models, if analysed appropriately.

  8. Allelic polymorphism of GIGANTEA is responsible for naturally occurring variation in circadian period in Brassica rapa.

    PubMed

    Xie, Qiguang; Lou, Ping; Hermand, Victor; Aman, Rashid; Park, Hee Jin; Yun, Dae-Jin; Kim, Woe Yeon; Salmela, Matti Juhani; Ewers, Brent E; Weinig, Cynthia; Khan, Sarah L; Schaible, D Loring P; McClung, C Robertson

    2015-03-24

    GIGANTEA (GI) was originally identified by a late-flowering mutant in Arabidopsis, but subsequently has been shown to act in circadian period determination, light inhibition of hypocotyl elongation, and responses to multiple abiotic stresses, including tolerance to high salt and cold (freezing) temperature. Genetic mapping and analysis of families of heterogeneous inbred lines showed that natural variation in GI is responsible for a major quantitative trait locus in circadian period in Brassica rapa. We confirmed this conclusion by transgenic rescue of an Arabidopsis gi-201 loss of function mutant. The two B. rapa GI alleles each fully rescued the delayed flowering of Arabidopsis gi-201 but showed differential rescue of perturbations in red light inhibition of hypocotyl elongation and altered cold and salt tolerance. The B. rapa R500 GI allele, which failed to rescue the hypocotyl and abiotic stress phenotypes, disrupted circadian period determination in Arabidopsis. Analysis of chimeric B. rapa GI alleles identified the causal nucleotide polymorphism, which results in an amino acid substitution (S264A) between the two GI proteins. This polymorphism underlies variation in circadian period, cold and salt tolerance, and red light inhibition of hypocotyl elongation. Loss-of-function mutations of B. rapa GI confer delayed flowering, perturbed circadian rhythms in leaf movement, and increased freezing and increased salt tolerance, consistent with effects of similar mutations in Arabidopsis. Collectively, these data suggest that allelic variation of GI-and possibly of clock genes in general-offers an attractive target for molecular breeding for enhanced stress tolerance and potentially for improved crop yield.

  9. Highly Connected Populations and Temporal Stability in Allelic Frequencies of a Harvested Crab from the Southern Pacific Coast.

    PubMed

    Rojas-Hernandez, Noemi; Veliz, David; Riveros, Marcela P; Fuentes, Juan P; Pardo, Luis M

    2016-01-01

    For marine invertebrates with a benthic adult form and a planktonic larva phase, the connectivity among populations is mainly based on larval dispersal. While an extended larval phase will promote gene flow, other factors such as an intensive fishery and geographical barriers could lead to changes in genetic variability. In this study, the population genetic structure of the commercial crab Metacarcinus edwardsii was analyzed along 700 km of the Chilean coast. The analysis, based on eight microsatellite loci genotyped from megalopae and adult crabs, considered temporal and spatial patterns of genetic variation. The results showed no evidence of spatial patterns in genetic structure, suggesting high connectivity among the sampling sites. The temporal analysis showed no evidence of changes in allele frequencies and no evidence of a recent bottleneck. The lack of spatial structure and allele variation over time could be explained by the interaction of factors such as i) low reproductive variance due to the capability of females to store sperm in the seminal receptacle, which can be used for successive broods, ii) high larval dispersal and iii) high individual reproductive output. Using our data as priors, a genetic modelling approach coincided, predicting this temporal and spatial stability. The same analysis showed that a reduction in population size leads to the loss of genetic variability in populations, as well as of the genetic cohesiveness between populations, pointing out the importance management for species under exploitation, such as M. edwardsii.

  10. Highly Connected Populations and Temporal Stability in Allelic Frequencies of a Harvested Crab from the Southern Pacific Coast

    PubMed Central

    Rojas-Hernandez, Noemi; Veliz, David; Riveros, Marcela P; Fuentes, Juan P.; Pardo, Luis M.

    2016-01-01

    For marine invertebrates with a benthic adult form and a planktonic larva phase, the connectivity among populations is mainly based on larval dispersal. While an extended larval phase will promote gene flow, other factors such as an intensive fishery and geographical barriers could lead to changes in genetic variability. In this study, the population genetic structure of the commercial crab Metacarcinus edwardsii was analyzed along 700 km of the Chilean coast. The analysis, based on eight microsatellite loci genotyped from megalopae and adult crabs, considered temporal and spatial patterns of genetic variation. The results showed no evidence of spatial patterns in genetic structure, suggesting high connectivity among the sampling sites. The temporal analysis showed no evidence of changes in allele frequencies and no evidence of a recent bottleneck. The lack of spatial structure and allele variation over time could be explained by the interaction of factors such as i) low reproductive variance due to the capability of females to store sperm in the seminal receptacle, which can be used for successive broods, ii) high larval dispersal and iii) high individual reproductive output. Using our data as priors, a genetic modelling approach coincided, predicting this temporal and spatial stability. The same analysis showed that a reduction in population size leads to the loss of genetic variability in populations, as well as of the genetic cohesiveness between populations, pointing out the importance management for species under exploitation, such as M. edwardsii. PMID:27814382

  11. Allele frequency distribution for 15 autosomal STR loci in Afridi Pathan population of Uttar Pradesh, India.

    PubMed

    Noor, Sabahat; Ali, Shahnaz; Eaaswarkhanth, Muthukrishnan; Haque, Ikramul

    2009-11-01

    Allele frequencies of the 15 autosomal short tandem repeat (STR) loci D8S1179, D21S11, D7S820, CSF1PO D19S433, vWA, TPOX, D18S51, D3S1358, THO1, D13S317, D16S539, D2S1338, D5S818 and FGA were determined in Afridi Pathan population of Uttar Pradesh, India. All the 15 STR loci studied were found to be highly polymorphic with respect to observed heterozygosity values. Adherence to the expectations of the Hardy-Weinberg equilibrium (HWE) was confirmed for all the loci with an exception of TPOX and FGA. The allele 12 in CSF1PO was found to be most frequent. The power of discrimination was found to be high ranging from a minimum of 0.858 for the locus CSFIPO to maximum of 0.962 for the locus FGA, thereby facilitating the validation and efficiency of these STR markers in human identification. Population differentiation test between the studied and neighboring populations revealed significant differences at several loci suggesting the endogamous nature of the studied population. To the best of our knowledge, Afridi Pathan population has not been explored genetically for generating forensic data on STR markers. Therefore, STR allele frequency data of this unique population is a valuable contribution to the existing DNA database on Indian populations.

  12. Comprehensive genetic testing with ethnic-specific filtering by allele frequency in a Japanese hearing-loss population

    PubMed Central

    Moteki, Hideaki; Azaiez, Hela; Booth, Kevin T; Shearer, A Eliot; Sloan, Christina M; Kolbe, Diana L; Nishio, Shin-ya; Hattori, Mitsuru; Usami, Shin-ichi; Smith, Richard J H

    2016-01-01

    Recent advances in targeted genomic enrichment with massively parallel sequencing (TGE+MPS) have made comprehensive genetic testing for non-syndromic hearing loss (NSHL) possible. After excluding NSHL subjects with causative mutations in GJB2 and the MT-RNR1 (1555A>G) variant by Sanger sequencing, we completed TGE+MPS on 194 probands with presumed NSHL identified across Japan. We used both publicly available minor allele frequency (MAF) datasets and ethnic-specific MAF filtering against an in-house database of 200 normal-hearing Japanese controls. Ethnic-specific MAF filtering allowed us to re-categorize as common 203 variants otherwise annotated as rare or novel in non-Japanese ethnicities. This step minimizes false-positive results and improves the annotation of identified variants. Causative variants were identified in 27% of probands with solve rates of 35%, 35% and 19% for dominant, recessive and sporadic NSHL, respectively. Mutations in MYO15A and CDH23 follow GJB2 as the frequent causes of recessive NSHL; copy number variations in STRC are a major cause of mild-to-moderate NSHL. Ethnic-specific filtering by allele frequency is essential to optimize the interpretation of genetic data. PMID:26346818

  13. The role of allelic variation in estrogen receptor genes and major depression in the Nurses Health Study

    PubMed Central

    Keyes, K.; Agnew-Blais, J.; Roberts, A.; Hamilton, A.; De Vivo, I.; Ranu, H.; Koenen, K.

    2015-01-01

    Purpose The role of exogenous and endogenous sex hormones in the etiology of depression remains elusive, in part because sex hormone variation is often correlated with behaviors, life stage changes, and other factors that may influence depression. Estrogen receptor alpha (ESR1) and beta (ESR2) are known to regulate gene expression and estrogen response in areas of the brain associated with major depression and are unlikely to be correlated with exogenous factors that may influence depression. Methods We examined whether functional polymorphisms in these genes are associated with lifetime major depression and chronic major depression among a sample of women from the Nurses’ Health Study II (N=2,576). DSM-IV depressive disorder symptoms were assessed by structured interview in 2007. Genotyping was performed on DNA extracted from blood using Taq-man. Results Women with the AA alleles of ESR2 RS4986938 had the higher prevalence of lifetime major depression than women with other allele frequencies (36.7% for those with AA versus 28.5% with GA and 29.1% with GG, p=0.02) and chronic major depression (14.7% for those with AA versus 9.3% with GA and 9.1 % with GG, p=0.01). History of post-menopausal hormone (PMH) use modified the association of ESR1 polymorphism RS2234693 with any lifetime depression; specifically, those with the TT allele had the highest risk of lifetime depression among PMH users, and the lowest risk of depression among non-PMH users (p-value for interaction=0.02). Further, carriers of the AA alleles in ESR1 polymorphism RS9340799 had increased prevalence of lifetime major depression only among lifetime PMH-users (p=0.007). Conclusions Our findings support the hypothesis that estrogen receptor polymorphisms influence risk for major depression; the role of estrogen receptors and other sex steroid-related genetic factors may provide unique insights into etiology. PMID:26169989

  14. Allelic imbalance identifies novel tissue specific cis-regulatory variation for human UGT2B15

    PubMed Central

    Sun, Chang; Southard, Catherine; Witonsky, David B.; Olopade, Olufunmilayo I.; Di Rienzo, Anna

    2010-01-01

    Allelic imbalance (AI) is a powerful tool to identify cis-regulatory variation for gene expression. UGT2B15 is an important enzyme involved in the metabolism of multiple endobiotics and xenobiotics. In this study, we measured the relative expression of two alleles at this gene by using SNP rs1902023:G>T. An excess of the G over the T allele was consistently observed in liver (P<0.001), but not in breast (P=0.06) samples, suggesting that SNPs in strong linkage disequilibrium with G253T regulate UGT2B15 expression in liver. Seven such SNPs were identified by resequencing the promoter and exon 1, which define two distinct haplotypes. Reporter gene assays confirmed that one haplotype displayed ~20% higher promoter activity compared to the other major haplotype in liver HepG2 (P<0.001), but not in breast MCF-7 (P=0.540) cells. Reporter gene assays with additional constructs pointed to rs34010522:G>T and rs35513228:C>T as the cis-regulatory variants; both SNPs were also evaluated in LNCaP and Caco-2 cells. By ChIP, we showed that the transcription factor Nrf2 binds to the region spanning rs34010522:G>T in all four cell lines. Our results provide a good example for how AI can be used to identify cis-regulatory variation and gain insights into the tissue specific regulation of gene expression. PMID:19847790

  15. Analysis of HLA DQ alpha allele and genotype frequencies in populations from Florida.

    PubMed

    Crouse, C A; Feuer, W J; Nippes, D C; Hutto, S C; Barnes, K S; Coffman, D; Livingston, S H; Ginsberg, L; Glidewell, D E

    1994-05-01

    HLA DQ alpha allele and genotype frequencies for Caucasian, African American, Haitian, and Hispanic populations in Florida have been estimated. The Florida laboratories involved in these studies collected donor samples from a variety of sites including clinical laboratories, victim and suspect standards, blood banks, county jail detainees, and laboratory personnel. We have determined that the Caucasian and African American DQ alpha genotype frequencies do not deviate significantly from Hardy-Weinberg expectations and as a result of this heterogeneity analyses, data from the four Florida Caucasian populations may be combined and data from the four Florida African American populations may be combined to form two large HLA DQ alpha genotype frequency databanks. Further, data from the Florida Haitian population may be combined with the Florida African American population. Comparison of the combined Florida Caucasian populations, combined Florida African American populations, the Palm Beach Sheriff's Office (PBSO) Hispanic, and PBSO Haitian population with other databases does not support combination because allele frequency distributions are heterogeneous.

  16. The non-equilibrium allele frequency spectrum in a Poisson random field framework.

    PubMed

    Kaj, Ingemar; Mugal, Carina F

    2016-10-01

    In population genetic studies, the allele frequency spectrum (AFS) efficiently summarizes genome-wide polymorphism data and shapes a variety of allele frequency-based summary statistics. While existing theory typically features equilibrium conditions, emerging methodology requires an analytical understanding of the build-up of the allele frequencies over time. In this work, we use the framework of Poisson random fields to derive new representations of the non-equilibrium AFS for the case of a Wright-Fisher population model with selection. In our approach, the AFS is a scaling-limit of the expectation of a Poisson stochastic integral and the representation of the non-equilibrium AFS arises in terms of a fixation time probability distribution. The known duality between the Wright-Fisher diffusion process and a birth and death process generalizing Kingman's coalescent yields an additional representation. The results carry over to the setting of a random sample drawn from the population and provide the non-equilibrium behavior of sample statistics. Our findings are consistent with and extend a previous approach where the non-equilibrium AFS solves a partial differential forward equation with a non-traditional boundary condition. Moreover, we provide a bridge to previous coalescent-based work, and hence tie several frameworks together. Since frequency-based summary statistics are widely used in population genetics, for example, to identify candidate loci of adaptive evolution, to infer the demographic history of a population, or to improve our understanding of the underlying mechanics of speciation events, the presented results are potentially useful for a broad range of topics.

  17. Upper bounds on FST in terms of the frequency of the most frequent allele and total homozygosity: the case of a specified number of alleles.

    PubMed

    Edge, Michael D; Rosenberg, Noah A

    2014-11-01

    FST is one of the most frequently-used indices of genetic differentiation among groups. Though FST takes values between 0 and 1, authors going back to Wright have noted that under many circumstances, FST is constrained to be less than 1. Recently, we showed that at a genetic locus with an unspecified number of alleles, FST for two subpopulations is strictly bounded from above by functions of both the frequency of the most frequent allele (M) and the homozygosity of the total population (HT). In the two-subpopulation case, FST can equal one only when the frequency of the most frequent allele and the total homozygosity are 1/2. Here, we extend this work by deriving strict bounds on FST for two subpopulations when the number of alleles at the locus is specified to be I. We show that restricting to I alleles produces the same upper bound on FST over much of the allowable domain for M and HT, and we derive more restrictive bounds in the windows M∈[1/I,1/(I-1)) and HT∈[1/I,I/(I(2)-1)). These results extend our understanding of the behavior of FST in relation to other population-genetic statistics.

  18. Allelic variation in Salmonella: an underappreciated driver of adaptation and virulence

    PubMed Central

    Yue, Min; Schifferli, Dieter M.

    2014-01-01

    Salmonella enterica causes substantial morbidity and mortality in humans and animals. Infection and intestinal colonization by S. enterica require virulence factors that mediate bacterial binding and invasion of enterocytes and innate immune cells. Some S. enterica colonization factors and their alleles are host restricted, suggesting a potential role in regulation of host specificity. Recent data also suggest that colonization factors promote horizontal gene transfer of antimicrobial resistance genes by increasing the local density of Salmonella in colonized intestines. Although a profusion of genes are involved in Salmonella pathogenesis, the relative importance of their allelic variation has only been studied intensely in the type 1 fimbrial adhesin FimH. Although other Salmonella virulence factors demonstrate allelic variation, their association with specific metadata (e.g., host species, disease or carrier state, time and geographic place of isolation, antibiotic resistance profile, etc.) remains to be interrogated. To date, genome-wide association studies (GWAS) in bacteriology have been limited by the paucity of relevant metadata. In addition, due to the many variables amid metadata categories, a very large number of strains must be assessed to attain statistically significant results. However, targeted approaches in which genes of interest (e.g., virulence factors) are specifically sequenced alleviates the time-consuming and costly statistical GWAS analysis and increases statistical power, as larger numbers of strains can be screened for non-synonymous single nucleotide polymorphisms (SNPs) that are associated with available metadata. Congruence of specific allelic variants with specific metadata from strains that have a relevant clinical and epidemiological history will help to prioritize functional wet-lab and animal studies aimed at determining cause-effect relationships. Such an approach should be applicable to other pathogens that are being collected

  19. POPTREE2: Software for constructing population trees from allele frequency data and computing other population statistics with Windows interface.

    PubMed

    Takezaki, Naoko; Nei, Masatoshi; Tamura, Koichiro

    2010-04-01

    Currently, there is a demand for software to analyze polymorphism data such as microsatellite DNA and single nucleotide polymorphism with easily accessible interface in many fields of research. In this article, we would like to make an announcement of POPTREE2, a computer program package, that can perform evolutionary analyses of allele frequency data. The original version (POPTREE) was a command-line program that runs on the Command Prompt of Windows and Unix. In POPTREE2 genetic distances (measures of the extent of genetic differentiation between populations) for constructing phylogenetic trees, average heterozygosities (H) (a measure of genetic variation within populations) and G(ST) (a measure of genetic differentiation of subdivided populations) are computed through a simple and intuitive Windows interface. It will facilitate statistical analyses of polymorphism data for researchers in many different fields. POPTREE2 is available at http://www.med.kagawa-u.ac.jp/ approximately genomelb/takezaki/poptree2/index.html.

  20. Detection, Validation, and Downstream Analysis of Allelic Variation in Gene Expression

    PubMed Central

    Ciobanu, Daniel C.; Lu, Lu; Mozhui, Khyobeni; Wang, Xusheng; Jagalur, Manjunatha; Morris, John A.; Taylor, William L.; Dietz, Klaus; Simon, Perikles; Williams, Robert W.

    2010-01-01

    Common sequence variants within a gene often generate important differences in expression of corresponding mRNAs. This high level of local (allelic) control—or cis modulation—rivals that produced by gene targeting, but expression is titrated finely over a range of levels. We are interested in exploiting this allelic variation to study gene function and downstream consequences of differences in expression dosage. We have used several bioinformatics and molecular approaches to estimate error rates in the discovery of cis modulation and to analyze some of the biological and technical confounds that contribute to the variation in gene expression profiling. Our analysis of SNPs and alternative transcripts, combined with eQTL maps and selective gene resequencing, revealed that between 17 and 25% of apparent cis modulation is caused by SNPs that overlap probes rather than by genuine quantitative differences in mRNA levels. This estimate climbs to 40–50% when qualitative differences between isoform variants are included. We have developed an analytical approach to filter differences in expression and improve the yield of genuine cis-modulated transcripts to ∼80%. This improvement is important because the resulting variation can be successfully used to study downstream consequences of altered expression on higher-order phenotypes. Using a systems genetics approach we show that two validated cis-modulated genes, Stk25 and Rasd2, are likely to control expression of downstream targets and affect disease susceptibility. PMID:19884314

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

    PubMed

    Sala, A; Penacino, G; Corach, D

    1998-10-01

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

  2. Using Next-Generation Sequencing for DNA Barcoding: Capturing Allelic Variation in ITS2

    PubMed Central

    Batovska, Jana; Cogan, Noel O. I.; Lynch, Stacey E.; Blacket, Mark J.

    2016-01-01

    Internal Transcribed Spacer 2 (ITS2) is a popular DNA barcoding marker; however, in some animal species it is hypervariable and therefore difficult to sequence with traditional methods. With next-generation sequencing (NGS) it is possible to sequence all gene variants despite the presence of single nucleotide polymorphisms (SNPs), insertions/deletions (indels), homopolymeric regions, and microsatellites. Our aim was to compare the performance of Sanger sequencing and NGS amplicon sequencing in characterizing ITS2 in 26 mosquito species represented by 88 samples. The suitability of ITS2 as a DNA barcoding marker for mosquitoes, and its allelic diversity in individuals and species, was also assessed. Compared to Sanger sequencing, NGS was able to characterize the ITS2 region to a greater extent, with resolution within and between individuals and species that was previously not possible. A total of 382 unique sequences (alleles) were generated from the 88 mosquito specimens, demonstrating the diversity present that has been overlooked by traditional sequencing methods. Multiple indels and microsatellites were present in the ITS2 alleles, which were often specific to species or genera, causing variation in sequence length. As a barcoding marker, ITS2 was able to separate all of the species, apart from members of the Culex pipiens complex, providing the same resolution as the commonly used Cytochrome Oxidase I (COI). The ability to cost-effectively sequence hypervariable markers makes NGS an invaluable tool with many applications in the DNA barcoding field, and provides insights into the limitations of previous studies and techniques. PMID:27799340

  3. Patterns of variation among distinct alleles of the Flag silk gene from Nephila clavipes.

    PubMed

    Higgins, Linden E; White, Sheryl; Nuñez-Farfán, Juan; Vargas, Jesus

    2007-02-20

    Spider silk proteins and their genes are very attractive to researchers in a wide range of disciplines because they permit linking many levels of organization. However, hypotheses of silk gene evolution have been built primarily upon single sequences of each gene each species, and little is known about allelic variation within a species. Silk genes are known for their repeat structure with high levels of homogenization of nucleotide and amino acid sequence among repeated units. One common explanation for this homogeneity is gene convergence. To test this model, we sequenced multiple alleles of one intron-exon segment from the Flag gene from four populations of the spider Nephila clavipes and compared the new sequences to a published sequence. Our analysis revealed very high levels of heterozygosity in this gene, with no pattern of population differentiation. There was no evidence of gene convergence within any of these alleles, with high levels of nucleotide and amino acid substitution among the repeating motifs. Our data suggest that minimally, there is relaxed selection on mutations in this gene and that there may actually be positive selection for heterozygosity.

  4. Lower Frequency of HLA-DRB1 Type 1 Diabetes Risk Alleles in Pediatric Patients with MODY

    PubMed Central

    López-Euba, Tamara; Velayos, Teresa; Martínez de LaPiscina, Idoia; Bilbao, José Ramón; Rica, Itxaso; Castaño, Luis

    2017-01-01

    Objective The aim of this study was to determine the frequency of susceptible HLA-DRB1 alleles for type 1 diabetes in a cohort of pediatric patients with a confirmed genetic diagnosis of MODY. Materials and Methods 160 families with a proband diagnosed with type 1 diabetes and 74 families with a molecular diagnosis of MODY (61 GCK-MODY and 13 HNF1A-MODY) were categorized at high definition for HLA-DRB1 locus. According to the presence or absence of the susceptible HLA-DRB1 alleles for type 1 diabetes, we considered three different HLA-DRB1 genotypes: 0 risk alleles (no DR3 no DR4); 1 risk allele (DR3 or DR4); 2 risk alleles (DR3 and/or DR4). Results Compared with type 1 diabetes, patients with MODY carried higher frequency of 0 risk alleles, OR 22.7 (95% CI: 10.7–48.6) and lower frequency of 1 or 2 risk alleles, OR 0.53 (95% CI: 0.29–0.96) and OR 0.06 (95% CI: 0.02–0.18), respectively. Conclusions The frequency of HLA-DRB1 risk alleles for type 1 diabetes is significantly lower in patients with MODY. In children and adolescents with diabetes, the presence of 2 risk alleles (DR3 and/or DR4) reduces the probability of MODY diagnosis, whereas the lack of risk alleles increases it. Therefore, we might consider that HLA-DRB1 provides additional information for the selection of patients with high probability of monogenic diabetes. PMID:28052112

  5. Initial frequency of alleles conferring resistance to Bacillus thuringiensis poplar in a field population of Chrysomela tremulae.

    PubMed Central

    Génissel, Anne; Augustin, Sylvie; Courtin, Claudine; Pilate, Gilles; Lorme, Philippe; Bourguet, Denis

    2003-01-01

    Globally, the estimated total area planted with transgenic plants producing Bacillus thuringiensis (Bt) toxins was 12 million hectares in 2001. The risk of target pests becoming resistant to these toxins has led to the implementation of resistance-management strategies. The efficiency and sustainability of these strategies, including the high-dose plus refuge strategy currently recommended for North American maize, depend on the initial frequency of resistance alleles. In this study, we estimated the initial frequencies of alleles conferring resistance to transgenic Bt poplars producing Cry3A in a natural population of the poplar pest Chrysomela tremulae (Coleoptera: Chrysomelidae). We used the F(2) screen method developed for detecting resistance alleles in natural pest populations. At least three parents of the 270 lines tested were heterozygous for a major Bt resistance allele. We estimated mean resistance-allele frequency for the period 1999-2001 at 0.0037 (95% confidence interval = 0.00045-0.0080) with a detection probability of 90%. These results demonstrate that (i) the F(2) screen method can be used to detect major alleles conferring resistance to Bt-producing plants in insects and (ii) the initial frequency of alleles conferring resistance to Bt toxin can be close to the highest theoretical values that are expected prior to the use of Bt plants if considering fitness costs and typical mutation rates. PMID:12737656

  6. Allelic variation of melanocortin-1 receptor locus in Saudi indigenous sheep exhibiting different color coats

    PubMed Central

    Mahmoud, Ahmed H.; Mashaly, Ashraf M.; Rady, Ahmed M.; Al-Anazi, Khalid M.; Saleh, Amgad A.

    2017-01-01

    Objective This study was designed to characterize the DNA polymorphisms of the melanocortin-1 receptor (MC1R) gene in indigenous Saudi Arabian sheep breeds exhibiting different color coats, along with individuals of the Sawaknee breed, an exotic sheep imported from Sudan. Methods The complete coding region of MC1R gene including parts of 3′ and 5′ untranslated regions was amplified and sequenced from three the indigenous Saudi sheep; Najdi (generally black, n = 41), Naeimi (generally white with brown faces, n = 36) and Herri (generally white, n = 18), in addition to 13 Sawaknee sheep. Results Five single nucleotide polymorphisms (SNPs) were detected in the MC1R gene: two led to nonsynonymous mutations (c.218 T>A, p.73 Met>Lys and c.361 G>A, p.121 Asp>Asn) and three led to synonymous mutations (c.429 C>T, p.143 Tyr>Tyr; c.600 T>G, p.200 Leu>Leu, and c.735 C>T, p.245 Ile>Ile). Based on these five SNPs, eight haplotypes representing MC1R Ed and E+ alleles were identified among the studied sheep breeds. The most common haplotype (H3) of the dominant Ed allele was associated with either black or brown coat color in Najdi and Sawaknee sheep, respectively. Two other haplotypes (H6 and H7) of Ed allele, with only the nonsynonymous mutation A218T, were detected for the first time in Saudi indigenous sheep. Conclusion In addition to investigating the MC1R allelic variation in Saudi indigenous sheep populations, the present study supports the assumption that the two independent nonsynonymous Met73Lys and Asp121Asn mutations in MC1R gene are associated with black or red coat colors in sheep breeds. PMID:27492350

  7. Genetic comparison of lake sturgeon populations: Differentiation based on allelic frequencies at seven microsatellite loci

    USGS Publications Warehouse

    McQuown, E.; Krueger, C.C.; Kincaid, H.L.; Gall, G.A.E.; May, B.

    2003-01-01

    The lake sturgeon (Acipenser fulvescens) has recently become a high priority for restoration management because of the near extinction of the species from many areas of North America. The identification of the level of population differentiation that naturally exists among lake sturgeon populations will be useful in the development of management plans to conserve and restore diversity, and in the choice of donor populations to use for re-introduction. Genetic variation among and within 210 lake sturgeon collected from seven locations (St. Lawrence River, Des Prairies River (tributary to the St. Lawrence River), Mattagami River (Hudson Bay drainage), Menominee River (Lake Michigan drainage), Wolf River (Lake Michigan drainage), Niagara River, and Lake Erie) was examined based on allelic variation at seven microsatellite loci (four disomic and three putative tetrasomic). High levels of variability were detected at these loci. Analyses revealed an average of 8.6 alleles per locus (range 5 to 12 alleles per locus) and heterozygosity values at the four disomic loci ranging from 0.46 to 0.66. Multivariate factor analysis of Nei's genetic distance values produced three distinct population groups that were organized by geography: 1) Mattagami (northern Quebec), 2) Menominee/ Wolf (Lake Michigan - Wisconsin), and 3) St. Lawrence/ Des Prairies/ Niagara/ Erie (lower Great Lakes). Differences based on G-tests summed over all loci occurred between all possible paired comparisons of the collections (P < 0.01). These analyses indicated that lake sturgeon populations are differentiated within the Great Lakes basin. Managers of this species will need to identify individual populations in their jurisdictions and provide separate consideration for their conservation and rehabilitation.

  8. Seasonal variations of volcanic eruption frequencies

    NASA Technical Reports Server (NTRS)

    Stothers, Richard B.

    1989-01-01

    Do volcanic eruptions have a tendency to occur more frequently in the months of May and June? Some past evidence suggests that they do. The present study, based on the new eruption catalog of Simkin et al.(1981), investigates the monthly statistics of the largest eruptions, grouped according to explosive magnitude, geographical latitude, and year. At the 2-delta level, no month-to-month variations in eruption frequency are found to be statistically significant. Examination of previously published month-to-month variations suggests that they, too, are not statistically significant. It is concluded that volcanism, at least averaged over large portions of the globe, is probably not periodic on a seasonal or annual time scale.

  9. Estimating Selection Coefficients in Spatially Structured Populations from Time Series Data of Allele Frequencies

    PubMed Central

    Mathieson, Iain; McVean, Gil

    2013-01-01

    Inferring the nature and magnitude of selection is an important problem in many biological contexts. Typically when estimating a selection coefficient for an allele, it is assumed that samples are drawn from a panmictic population and that selection acts uniformly across the population. However, these assumptions are rarely satisfied. Natural populations are almost always structured, and selective pressures are likely to act differentially. Inference about selection ought therefore to take account of structure. We do this by considering evolution in a simple lattice model of spatial population structure. We develop a hidden Markov model based maximum-likelihood approach for estimating the selection coefficient in a single population from time series data of allele frequencies. We then develop an approximate extension of this to the structured case to provide a joint estimate of migration rate and spatially varying selection coefficients. We illustrate our method using classical data sets of moth pigmentation morph frequencies, but it has wide applications in settings ranging from ecology to human evolution. PMID:23307902

  10. Allelic variation on murine chromosome 11 modifies host inflammatory responses and resistance to Bacillus anthracis.

    PubMed

    Terra, Jill K; France, Bryan; Cote, Christopher K; Jenkins, Amy; Bozue, Joel A; Welkos, Susan L; Bhargava, Ragini; Ho, Chi-Lee; Mehrabian, Margarete; Pan, Calvin; Lusis, Aldons J; Davis, Richard C; LeVine, Steven M; Bradley, Kenneth A

    2011-12-01

    Anthrax is a potentially fatal disease resulting from infection with Bacillus anthracis. The outcome of infection is influenced by pathogen-encoded virulence factors such as lethal toxin (LT), as well as by genetic variation within the host. To identify host genes controlling susceptibility to anthrax, a library of congenic mice consisting of strains with homozygous chromosomal segments from the LT-responsive CAST/Ei strain introgressed on a LT-resistant C57BL/6 (B6) background was screened for response to LT. Three congenic strains containing CAST/Ei regions of chromosome 11 were identified that displayed a rapid inflammatory response to LT similar to, but more severe than that driven by a LT-responsive allele of the inflammasome constituent NRLP1B. Importantly, increased response to LT in congenic mice correlated with greater resistance to infection by the Sterne strain of B. anthracis. The genomic region controlling the inflammatory response to LT was mapped to 66.36-74.67 Mb on chromosome 11, a region that encodes the LT-responsive CAST/Ei allele of Nlrp1b. However, known downstream effects of NLRP1B activation, including macrophage pyroptosis, cytokine release, and leukocyte infiltration could not fully explain the response to LT or the resistance to B. anthracis Sterne in congenic mice. Further, the exacerbated response in congenic mice is inherited in a recessive manner while the Nlrp1b-mediated response to LT is dominant. Finally, congenic mice displayed increased responsiveness in a model of sepsis compared with B6 mice. In total, these data suggest that allelic variation of one or more chromosome 11 genes in addition to Nlrp1b controls the severity of host response to multiple inflammatory stimuli and contributes to resistance to B. anthracis Sterne. Expression quantitative trait locus analysis revealed 25 genes within this region as high priority candidates for contributing to the host response to LT.

  11. Frequency detection of imidacloprid resistance allele in Aphis gossypii field populations by real-time PCR amplification of specific-allele (rtPASA).

    PubMed

    Zhang, Jing; Cui, Li; Xu, Xibao; Rui, Changhui

    2015-11-01

    The Aphis gossypii Glover (Hemiptera: Aphididae) is one of the most serious pests worldwide, and imidacloprid has been widely used to control this insect pest. Just like other classes of insecticides, the resistance to imidacloprid has been found in A. gossypii. An amino acid mutation (R81T) in the nicotinic acetylcholine receptor (nAChR) beta1 subunit was detected in the imidacloprid-resistant A. gossypii collected from Langfang (LF) and Dezhou (DZ) cities. To estimate the R81T mutation frequency of A. gossypii field populations, a simple, rapid and accurate rtPASA (real-time PCR amplification of specific allele) protocol was developed. The performance of the rtPASA protocol was evaluated by comparing with the data generated by a cPASA (competitive PCR amplification of specific allele) method from 50 individual genotypes. The R81T allele frequencies of the LF population (34.7%±1.3%) and DZ population (45.2%±5.2%) estimated by the rtPASA protocol matched the frequencies (LF 38.1%, DZ 48.2%) deduced by the cPASA method in specimens. The results indicated that the rtPASA format was applicable for the detection of mutation associated with imidacloprid resistance and will allow rapid and efficient monitoring of A. gossypii resistance in field populations in a high throughput format.

  12. Low-frequency and common genetic variation in ischemic stroke

    PubMed Central

    Malik, Rainer; Traylor, Matthew; Pulit, Sara L.; Bevan, Steve; Hopewell, Jemma C.; Holliday, Elizabeth G.; Zhao, Wei; Abrantes, Patricia; Amouyel, Philippe; Attia, John R.; Battey, Thomas W.K.; Berger, Klaus; Boncoraglio, Giorgio B.; Chauhan, Ganesh; Cheng, Yu-Ching; Chen, Wei-Min; Clarke, Robert; Cotlarciuc, Ioana; Debette, Stephanie; Falcone, Guido J.; Ferro, Jose M.; Gamble, Dale M.; Ilinca, Andreea; Kittner, Steven J.; Kourkoulis, Christina E.; Lemmens, Robin; Levi, Christopher R.; Lichtner, Peter; Lindgren, Arne; Liu, Jingmin; Meschia, James F.; Mitchell, Braxton D.; Oliveira, Sofia A.; Pera, Joana; Reiner, Alex P.; Rothwell, Peter M.; Sharma, Pankaj; Slowik, Agnieszka; Sudlow, Cathie L.M.; Tatlisumak, Turgut; Thijs, Vincent; Vicente, Astrid M.; Woo, Daniel; Seshadri, Sudha; Saleheen, Danish; Rosand, Jonathan; Markus, Hugh S.; Worrall, Bradford B.

    2016-01-01

    Objective: To investigate the influence of common and low-frequency genetic variants on the risk of ischemic stroke (all IS) and etiologic stroke subtypes. Methods: We meta-analyzed 12 individual genome-wide association studies comprising 10,307 cases and 19,326 controls imputed to the 1000 Genomes (1 KG) phase I reference panel. We selected variants showing the highest degree of association (p < 1E-5) in the discovery phase for replication in Caucasian (13,435 cases and 29,269 controls) and South Asian (2,385 cases and 5,193 controls) samples followed by a transethnic meta-analysis. We further investigated the p value distribution for different bins of allele frequencies for all IS and stroke subtypes. Results: We showed genome-wide significance for 4 loci: ABO for all IS, HDAC9 for large vessel disease (LVD), and both PITX2 and ZFHX3 for cardioembolic stroke (CE). We further refined the association peaks for ABO and PITX2. Analyzing different allele frequency bins, we showed significant enrichment in low-frequency variants (allele frequency <5%) for both LVD and small vessel disease, and an enrichment of higher frequency variants (allele frequency 10% and 30%) for CE (all p < 1E-5). Conclusions: Our findings suggest that the missing heritability in IS subtypes can in part be attributed to low-frequency and rare variants. Larger sample sizes are needed to identify the variants associated with all IS and stroke subtypes. PMID:26935894

  13. Geographical distribution of pyrethroid resistance allele frequency in head lice (Phthiraptera: Pediculidae) from Argentina.

    PubMed

    Toloza, Ariel Ceferino; Ascunce, Marina S; Reed, David; Picollo, María Inés

    2014-01-01

    The human head louse, Pediculus humanus capitis De Geer (Phthiraptera: Pediculidae), is an obligate ectoparasite that causes pediculosis capitis and has parasitized humans since the beginning of humankind. Head louse infestations are widespread throughout the world and have been increasing since the early 1990s partially because of ineffective pediculicides. In Argentina, the overuse of products containing pyrethroids has led to the development of resistant louse populations. Pyrethroid insecticides act on the nervous system affecting voltage-sensitive sodium channels. Three point mutations at the corresponding amino acid sequence positions M815I, T917I, and L920F in the voltage-gated sodium channel gene are responsible for contributing to knockdown resistance (kdr). The management of pyrethroid resistance requires either early detection or the characterization of the mechanisms involved in head louse populations. In the current study, we estimated the distribution of kdr alleles in 154 head lice from six geographical regions of Argentina. Pyrethroid resistance kdr alleles were found in high frequencies ranging from 67 to 100%. Of these, 131 (85.1%) were homozygous resistant, 13 (8.4%) were homozygous susceptible, and 10 (6.5%) were heterozygous. Exact tests for the Hardy-Weinberg equilibrium for each location showed that genotype frequencies differed significantly from expectation in four of the six sites studied. These results show that pyrethroid resistance is well established reaching an overall frequency of 88%, thus close to fixation. With 30 yr of pyrethroid-based pediculicides use in Argentina, kdr resistance has evolved rapidly among these head louse populations.

  14. Testing for Ancient Selection Using Cross-population Allele Frequency Differentiation

    PubMed Central

    Racimo, Fernando

    2016-01-01

    A powerful way to detect selection in a population is by modeling local allele frequency changes in a particular region of the genome under scenarios of selection and neutrality and finding which model is most compatible with the data. A previous method based on a cross-population composite likelihood ratio (XP-CLR) uses an outgroup population to detect departures from neutrality that could be compatible with hard or soft sweeps, at linked sites near a beneficial allele. However, this method is most sensitive to recent selection and may miss selective events that happened a long time ago. To overcome this, we developed an extension of XP-CLR that jointly models the behavior of a selected allele in a three-population tree. Our method - called “3-population composite likelihood ratio” (3P-CLR) - outperforms XP-CLR when testing for selection that occurred before two populations split from each other and can distinguish between those events and events that occurred specifically in each of the populations after the split. We applied our new test to population genomic data from the 1000 Genomes Project, to search for selective sweeps that occurred before the split of Yoruba and Eurasians, but after their split from Neanderthals, and that could have led to the spread of modern-human-specific phenotypes. We also searched for sweep events that occurred in East Asians, Europeans, and the ancestors of both populations, after their split from Yoruba. In both cases, we are able to confirm a number of regions identified by previous methods and find several new candidates for selection in recent and ancient times. For some of these, we also find suggestive functional mutations that may have driven the selective events. PMID:26596347

  15. Testing for Ancient Selection Using Cross-population Allele Frequency Differentiation.

    PubMed

    Racimo, Fernando

    2016-02-01

    A powerful way to detect selection in a population is by modeling local allele frequency changes in a particular region of the genome under scenarios of selection and neutrality and finding which model is most compatible with the data. A previous method based on a cross-population composite likelihood ratio (XP-CLR) uses an outgroup population to detect departures from neutrality that could be compatible with hard or soft sweeps, at linked sites near a beneficial allele. However, this method is most sensitive to recent selection and may miss selective events that happened a long time ago. To overcome this, we developed an extension of XP-CLR that jointly models the behavior of a selected allele in a three-population tree. Our method - called "3-population composite likelihood ratio" (3P-CLR) - outperforms XP-CLR when testing for selection that occurred before two populations split from each other and can distinguish between those events and events that occurred specifically in each of the populations after the split. We applied our new test to population genomic data from the 1000 Genomes Project, to search for selective sweeps that occurred before the split of Yoruba and Eurasians, but after their split from Neanderthals, and that could have led to the spread of modern-human-specific phenotypes. We also searched for sweep events that occurred in East Asians, Europeans, and the ancestors of both populations, after their split from Yoruba. In both cases, we are able to confirm a number of regions identified by previous methods and find several new candidates for selection in recent and ancient times. For some of these, we also find suggestive functional mutations that may have driven the selective events.

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

    PubMed

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

    2012-06-01

    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.

  17. Allelic diversity in an NLR gene BPH9 enables rice to combat planthopper variation

    PubMed Central

    Zhao, Yan; Huang, Jin; Wang, Zhizheng; Jing, Shengli; Wang, Yang; Ouyang, Yidan; Cai, Baodong; Xin, Xiu-Fang; Liu, Xin; Zhang, Chunxiao; Pan, Yufang; Ma, Rui; Li, Qiaofeng; Jiang, Weihua; Zeng, Ya; Shangguan, Xinxin; Wang, Huiying; Du, Bo; Zhu, Lili; Xu, Xun; Feng, Yu-Qi; He, Sheng Yang; Chen, Rongzhi; Zhang, Qifa; He, Guangcun

    2016-01-01

    Brown planthopper (BPH), Nilaparvata lugens Stål, is one of the most devastating insect pests of rice (Oryza sativa L.). Currently, 30 BPH-resistance genes have been genetically defined, most of which are clustered on specific chromosome regions. Here, we describe molecular cloning and characterization of a BPH-resistance gene, BPH9, mapped on the long arm of rice chromosome 12 (12L). BPH9 encodes a rare type of nucleotide-binding and leucine-rich repeat (NLR)-containing protein that localizes to the endomembrane system and causes a cell death phenotype. BPH9 activates salicylic acid- and jasmonic acid-signaling pathways in rice plants and confers both antixenosis and antibiosis to BPH. We further demonstrated that the eight BPH-resistance genes that are clustered on chromosome 12L, including the widely used BPH1, are allelic with each other. To honor the priority in the literature, we thus designated this locus as BPH1/9. These eight genes can be classified into four allelotypes, BPH1/9-1, -2, -7, and -9. These allelotypes confer varying levels of resistance to different biotypes of BPH. The coding region of BPH1/9 shows a high level of diversity in rice germplasm. Homologous fragments of the nucleotide-binding (NB) and leucine-rich repeat (LRR) domains exist, which might have served as a repository for generating allele diversity. Our findings reveal a rice plant strategy for modifying the genetic information to gain the upper hand in the struggle against insect herbivores. Further exploration of natural allelic variation and artificial shuffling within this gene may allow breeding to be tailored to control emerging biotypes of BPH. PMID:27791169

  18. Functional variation of MC1R alleles from red-haired individuals.

    PubMed

    Healy, E; Jordan, S A; Budd, P S; Suffolk, R; Rees, J L; Jackson, I J

    2001-10-01

    Red hair in humans is associated with variant alleles of the alphaMSH receptor gene, MC1R. Loss of MC1R function in other mammals results in red or yellow hair pigmentation. We show that a mouse bacterial artificial chromosome (BAC) which contains Mc1r will efficiently rescue loss of Mc1r in transgenic mice, and that overexpression of the receptor suppresses the effect of the endogenous antagonist, agouti protein. We engineered the BAC to replace the mouse coding region with the human MC1R sequence and used this in the transgenic assay. The human receptor also efficiently rescued Mc1r deficiency, and in addition, appeared to be completely resistant to the effects of agouti, suggesting agouti protein may not play a role in human pigmentary variation. Three human variant alleles account for 60% of all cases of red hair. We engineered each of these in turn into the BAC and find that they have reduced, but not completely absent, function in transgenic mice. Comparison of the phenotypes of alphaMSH-deficient mice and humans in conjunction with this data suggests that red hair may not be the null phenotype of MC1R.

  19. Initial frequency of alleles for resistance to Bacillus thuringiensis toxins in field populations of Heliothis virescens

    PubMed Central

    Gould, F.; Anderson, A.; Jones, A.; Sumerford, D.; Heckel, D. G.; Lopez, J.; Micinski, S.; Leonard, R.; Laster, M.

    1997-01-01

    The risk of rapid pest adaptation to an insecticide is highly dependent on the initial frequency of resistance alleles in field populations. Because we have lacked empirical estimates of these frequencies, population–genetic models of resistance evolution have relied on a wide range of theoretical estimates. The recent commercialization of genetically engineered cotton that constitutively produces an insecticidal protein derived from the biocontrol agent, Bacillus thuringiensis (Bt) has raised concern that we lack data needed to quantify the risk of insect pests such as Heliothis virescens rapidly adapting to this ecologically valuable class of toxins. By individually mating over 2,000 male H. virescens moths collected in four states to females of a Bt toxin-resistant laboratory strain, and screening F1 and F2 offspring for tolerance of the toxic protein, we were able to directly estimate the field frequency of alleles for resistance as 1.5 × 10−3. This high initial frequency underscores the need for caution in deploying transgenic cotton to control insect pests. Our single-pair mating technique greatly increases the efficiency of detecting recessive resistance alleles. Because alleles that decrease target site sensitivity to Bt toxins and other insecticides are often recessive, this technique could be useful in estimating resistance allele frequencies in other insects exposed to transgenic insecticidal crops or conventional insecticides. PMID:11038613

  20. Allele and genotype frequencies of polymorphisms in cytokine genes in ethnic Russian individuals from Moscow, Russia.

    PubMed

    Shadrina, Alexandra; Voronina, Elena; Zolotukhin, Igor; Filipenko, Maxim

    2017-02-01

    Two hundred and twenty eight ethnic Russian individuals from Moscow, Russia, were genotyped at 14 single nucleotide polymorphisms CCL2 A-2578G; VEGFA C-2578A, G-634C, and C+936T; TNF G+419A and G-308A; IL1A G-889A; IL1RN T+1018C; IL6G-174C and G-572C; IFNG T+874A; IL1B C-511T; IL10 A+1082G; TGFB1 C-509T. Genotypes were determined using real-time polymerase chain reaction with TaqMan probes and polymerase chain reaction followed by melting analysis of dual-labeled probe. Genotype distribution was in accordance with Hardy-Weinberg equilibrium for all studied polymorphisms. Genotype data are available in the Allele Frequencies Net Database under identifier AFND 3367 and the population name "Russia Moscow Cytokine".

  1. Utilizing Ethnic-Specific Differences in Minor Allele Frequency to Recategorize Reported Pathogenic Deafness Variants

    PubMed Central

    Shearer, A. Eliot; Eppsteiner, Robert W.; Booth, Kevin T.; Ephraim, Sean S.; Gurrola, José; Simpson, Allen; Black-Ziegelbein, E. Ann; Joshi, Swati; Ravi, Harini; Giuffre, Angelica C.; Happe, Scott; Hildebrand, Michael S.; Azaiez, Hela; Bayazit, Yildirim A.; Erdal, Mehmet Emin; Lopez-Escamez, Jose A.; Gazquez, Irene; Tamayo, Marta L.; Gelvez, Nancy Y.; Leal, Greizy Lopez; Jalas, Chaim; Ekstein, Josef; Yang, Tao; Usami, Shin-ichi; Kahrizi, Kimia; Bazazzadegan, Niloofar; Najmabadi, Hossein; Scheetz, Todd E.; Braun, Terry A.; Casavant, Thomas L.; LeProust, Emily M.; Smith, Richard J.H.

    2014-01-01

    Ethnic-specific differences in minor allele frequency impact variant categorization for genetic screening of nonsyndromic hearing loss (NSHL) and other genetic disorders. We sought to evaluate all previously reported pathogenic NSHL variants in the context of a large number of controls from ethnically distinct populations sequenced with orthogonal massively parallel sequencing methods. We used HGMD, ClinVar, and dbSNP to generate a comprehensive list of reported pathogenic NSHL variants and re-evaluated these variants in the context of 8,595 individuals from 12 populations and 6 ethnically distinct major human evolutionary phylogenetic groups from three sources (Exome Variant Server, 1000 Genomes project, and a control set of individuals created for this study, the OtoDB). Of the 2,197 reported pathogenic deafness variants, 325 (14.8%) were present in at least one of the 8,595 controls, indicating a minor allele frequency (MAF) >0.00006. MAFs ranged as high as 0.72, a level incompatible with pathogenicity for a fully penetrant disease like NSHL. Based on these data, we established MAF thresholds of 0.005 for autosomal-recessive variants (excluding specific variants in GJB2) and 0.0005 for autosomal-dominant variants. Using these thresholds, we recategorized 93 (4.2%) of reported pathogenic variants as benign. Our data show that evaluation of reported pathogenic deafness variants using variant MAFs from multiple distinct ethnicities and sequenced by orthogonal methods provides a powerful filter for determining pathogenicity. The proposed MAF thresholds will facilitate clinical interpretation of variants identified in genetic testing for NSHL. All data are publicly available to facilitate interpretation of genetic variants causing deafness. PMID:25262649

  2. Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume

    PubMed Central

    Lee, Han Kyu; Keum, Sehoon; Sheng, Huaxin; Warner, David S.; Lo, Donald C.

    2016-01-01

    Risk for ischemic stroke has a strong genetic basis, but heritable factors also contribute to the extent of damage after a stroke has occurred. We previously identified a locus on distal mouse chromosome 7 that contributes over 50% of the variation in postischemic cerebral infarct volume observed between inbred strains. Here, we used ancestral haplotype analysis to fine-map this locus to 12 candidate genes. The gene encoding the IL-21 receptor (Il21r) showed a marked difference in strain-specific transcription levels and coding variants in neonatal and adult cortical tissue. Collateral vessel connections were moderately reduced in Il21r-deficient mice, and cerebral infarct volume increased 2.3-fold, suggesting that Il21r modulates both collateral vessel anatomy and innate neuroprotection. In brain slice explants, oxygen deprivation (OD) activated apoptotic pathways and increased neuronal cell death in IL-21 receptor–deficient (IL-21R–deficient) mice compared with control animals. We determined that the neuroprotective effects of IL-21R arose from signaling through JAK/STAT pathways and upregulation of caspase 3. Thus, natural genetic variation in murine Il21r influences neuronal cell viability after ischemia by modulating receptor function and downstream signal transduction. The identification of neuroprotective genes based on naturally occurring allelic variations has the potential to inform the development of drug targets for ischemic stroke treatment. PMID:27400126

  3. Natural allelic variation of the IL-21 receptor modulates ischemic stroke infarct volume.

    PubMed

    Lee, Han Kyu; Keum, Sehoon; Sheng, Huaxin; Warner, David S; Lo, Donald C; Marchuk, Douglas A

    2016-08-01

    Risk for ischemic stroke has a strong genetic basis, but heritable factors also contribute to the extent of damage after a stroke has occurred. We previously identified a locus on distal mouse chromosome 7 that contributes over 50% of the variation in postischemic cerebral infarct volume observed between inbred strains. Here, we used ancestral haplotype analysis to fine-map this locus to 12 candidate genes. The gene encoding the IL-21 receptor (Il21r) showed a marked difference in strain-specific transcription levels and coding variants in neonatal and adult cortical tissue. Collateral vessel connections were moderately reduced in Il21r-deficient mice, and cerebral infarct volume increased 2.3-fold, suggesting that Il21r modulates both collateral vessel anatomy and innate neuroprotection. In brain slice explants, oxygen deprivation (OD) activated apoptotic pathways and increased neuronal cell death in IL-21 receptor-deficient (IL-21R-deficient) mice compared with control animals. We determined that the neuroprotective effects of IL-21R arose from signaling through JAK/STAT pathways and upregulation of caspase 3. Thus, natural genetic variation in murine Il21r influences neuronal cell viability after ischemia by modulating receptor function and downstream signal transduction. The identification of neuroprotective genes based on naturally occurring allelic variations has the potential to inform the development of drug targets for ischemic stroke treatment.

  4. The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

    PubMed

    Astle, William J; Elding, Heather; Jiang, Tao; Allen, Dave; Ruklisa, Dace; Mann, Alice L; Mead, Daniel; Bouman, Heleen; Riveros-Mckay, Fernando; Kostadima, Myrto A; Lambourne, John J; Sivapalaratnam, Suthesh; Downes, Kate; Kundu, Kousik; Bomba, Lorenzo; Berentsen, Kim; Bradley, John R; Daugherty, Louise C; Delaneau, Olivier; Freson, Kathleen; Garner, Stephen F; Grassi, Luigi; Guerrero, Jose; Haimel, Matthias; Janssen-Megens, Eva M; Kaan, Anita; Kamat, Mihir; Kim, Bowon; Mandoli, Amit; Marchini, Jonathan; Martens, Joost H A; Meacham, Stuart; Megy, Karyn; O'Connell, Jared; Petersen, Romina; Sharifi, Nilofar; Sheard, Simon M; Staley, James R; Tuna, Salih; van der Ent, Martijn; Walter, Klaudia; Wang, Shuang-Yin; Wheeler, Eleanor; Wilder, Steven P; Iotchkova, Valentina; Moore, Carmel; Sambrook, Jennifer; Stunnenberg, Hendrik G; Di Angelantonio, Emanuele; Kaptoge, Stephen; Kuijpers, Taco W; Carrillo-de-Santa-Pau, Enrique; Juan, David; Rico, Daniel; Valencia, Alfonso; Chen, Lu; Ge, Bing; Vasquez, Louella; Kwan, Tony; Garrido-Martín, Diego; Watt, Stephen; Yang, Ying; Guigo, Roderic; Beck, Stephan; Paul, Dirk S; Pastinen, Tomi; Bujold, David; Bourque, Guillaume; Frontini, Mattia; Danesh, John; Roberts, David J; Ouwehand, Willem H; Butterworth, Adam S; Soranzo, Nicole

    2016-11-17

    Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.

  5. Analysis and frequency of bovine lymphocyte antigen (BoLA-DRB3) alleles in Iranian Holstein cattle.

    PubMed

    Nassiry, M R; Shahroodi, F Eftekhar; Mosafer, J; Mohammadi, A; Manshad, E; Ghazanfari, S; Mohammad Abadi, M R; Sulimova, G E

    2005-06-01

    The bovine lymphocyte antigen (BoLA-DRB3) gene encodes cell surface glycoproteins that initiate immune response by presenting processed antigenic peptides to CD4 T helper cells. DRB3 is the most polymorphic bovine MHC class II gene which encodes the peptide-binding groove. DRB3 gene has been extensively evaluated as a candidate marker for association with various bovine diseases and immunological traits. This study describes genetic variability in the BoLA-DRB3 in Iranian Holstein cattle. This is the first study of the DNA polymorphism of the BoLA-DRB3 gene in Iranian Holstein cattle. Hemi-nested PCR-RFLP method is used for identification the frequency of BoLA-DRB3 alleles. The BoLA-DRB3 locus is highly polymorphic in the studied herd (26 alleles). Almost 67% of the alleles were accounted for four alleles (BoLA-DRB3.2*8, *24, *11 and *16) in Iranian Holstein cattle. The DRB3.2*8 allele frequency (26.6%) was higher than the others. The frequencies of the DRB3.2*54, *37, *36, *28, *25, *14, *13, *10, *1 alleles were lower than 1%. Significant distinctions have been found between Iranian Holstein cattle and other cattle breeds studied. In Iranian Holstein cattle the alleles (BoLA-DRB3.2*22, *2 and *16) associated with a lower risk of cystic ovarian disease in Holstein cattle are found. The alleles associated with the resistance to mastitis and to bovine leukemia virus infection BoLA-DRB3.2*11 and *23 are detected with the frequencies 10.4% and 4.4%, respectively. Thus in the Iranian Holstein cows studied are found alleles which are associated with resistance to various diseases. The method of DNA-typing of animals can be used in agricultural practice for BoLA-DRB3 allele genotyping of cattle in order to reduce spreading of alleles providing susceptibility to mastitis or leukemia in cattle herds.

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

    PubMed Central

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

    2011-01-01

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

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

    PubMed

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

    2011-01-01

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

  8. Controlling for P-value inflation in allele frequency change in experimental evolution and artificial selection experiments.

    PubMed

    Kemppainen, Petri; Rønning, Bernt; Kvalnes, Thomas; Hagen, Ingerid J; Ringsby, Thor Harald; Billing, Anna M; Pärn, Henrik; Lien, Sigbjørn; Husby, Arild; Saether, Bernt-Erik; Jensen, Henrik

    2016-11-04

    Experimental evolution studies can be used to explore genomic response to artificial and natural selection. In such studies, loci that display larger allele frequency change than expected by genetic drift alone are assumed to be directly or indirectly associated with traits under selection. However, such studies report surprisingly many loci under selection, suggesting that current tests for allele frequency change may be subject to P-value inflation and hence be anticonservative. One factor known from genomewide association (GWA) studies to cause P-value inflation is population stratification, such as relatedness among individuals. Here, we suggest that by treating presence of an individual in a population after selection as a binary response variable, existing GWA methods can be used to account for relatedness when estimating allele frequency change. We show that accounting for relatedness like this effectively reduces false-positives in tests for allele frequency change in simulated data with varying levels of population structure. However, once relatedness has been accounted for, the power to detect causal loci under selection is low. Finally, we demonstrate the presence of P-value inflation in allele frequency change in empirical data spanning multiple generations from an artificial selection experiment on tarsus length in two free-living populations of house sparrow and correct for this using genomic control. Our results indicate that since allele frequencies in large parts of the genome may change when selection acts on a heritable trait, such selection is likely to have considerable and immediate consequences for the eco-evolutionary dynamics of the affected populations.

  9. Patterns of human genetic variation inferred from comparative analysis of allelic mutations in blood group antigen genes.

    PubMed

    Patnaik, Santosh Kumar; Blumenfeld, Olga O

    2011-03-01

    Comparative analysis of allelic variation of a gene sheds light on the pattern and process of its diversification at the population level. Gene families for which a large number of allelic forms have been verified by sequencing provide a useful resource for such studies. In this regard, human blood group-encoding genes are unique in that differences of cell surface traits among individuals and populations can be readily detected by serological screening, and correlation between the variant cell surface phenotype and the genotype is, in most cases, unequivocal. Here, we perform a comprehensive analysis of allelic forms, compiled in the Blood Group Antigen Gene Mutation database, of ABO, RHD/CE, GYPA/B/E and FUT1/2 gene families that encode the ABO, RH, MNS, and H/h blood group system antigens, respectively. These genes are excellent illustrative examples showing distinct mutational patterns among the alleles, and leading to speculation on how their origin may have been driven by recurrent but different molecular mechanisms. We illustrate how alignment of alleles of a gene may provide an additional insight into the DNA variation process and its pathways, and how this approach may serve to catalog alleles of a gene, simplifying the task and content of mutation databases.

  10. Distribution of DI*A and DI*B Allele Frequencies and Comparisons among Central Thai and Other Populations

    PubMed Central

    Nathalang, Oytip; Panichrum, Puangpaka; Intharanut, Kamphon; Thattanon, Phatchira; Nathalang, Siriporn

    2016-01-01

    Alloantibodies to the Diego (DI) blood group system, anti-Dia and anti-Dib are clinically significant in causing hemolytic transfusion reactions (HTRs) and hemolytic disease of the fetus and newborn (HDFN), especially in Asian populations with Mongolian ancestry. This study aimed to report the frequency of the DI*A and DI*B alleles in a Central Thai population and to compare them with those of other populations previously published. Altogether, 1,011 blood samples from unrelated healthy blood donors at the National Blood Centre, Thai Red Cross Society, Bangkok were included. Only 391 samples were tested with anti-Dia by conventional tube technique. All samples were genotyped for DI*A and DI*B alleles using an in-house polymerase chain reaction with sequence-specific primer (PCR-SSP) technique. The DI phenotyping and genotyping results were in 100% concordance. The DI*A and DI*B allele frequencies among 1,011 Central Thais were 0.0183 (37/2,022) and 0.9817 (1,985/2,022), respectively. Allele frequencies were compared between Central Thai and other populations. Our data shows that DI*A and DI*B allele frequencies are similar to Southeast Asian, Brazilian, Southern Brazilian and American Native populations; whereas, these frequencies significantly differ from those reported in East Asian, Italian, Alaska Native/Aleut, Hawaiian/Pacific Islander and Filipino populations (P<0.05), corresponding to the results of a matrix of geometric genetic distances. This study confirms that the prevalence of DI*A and DI*B alleles among Central Thais is similar to Southeast Asians and different to others populations of the world. A PCR-based identification of DI genotyping should overcome some of the serological limitations in transfusion medicine and provides a complementary tool for further population-genetic studies. PMID:27764238

  11. 46 CFR 111.01-17 - Voltage and frequency variations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 4 2013-10-01 2013-10-01 false Voltage and frequency variations. 111.01-17 Section 111... ELECTRIC SYSTEMS-GENERAL REQUIREMENTS General § 111.01-17 Voltage and frequency variations. Unless otherwise stated, electrical equipment must function at variations of at least ±5 percent of rated...

  12. Variations of the Milankovitch frequencies in time

    NASA Technical Reports Server (NTRS)

    Loutre, Marie-France; Berger, A.

    1992-01-01

    The sensitivity of the amplitudes and frequencies in the development of the Earth's orbital and rotational elements involved in the astronomical theory of paleoclimates (eccentricity, obliquity, and climate precession), to the Earth-Moon distance and consequently to the length of the day and to the dynamical ellipticity of the Earth has been discussed for the last billions of years. The shortening of the Earth-Moon distance and of the length of the day, as well as the lengthening of the dynamical ellipticity of the Earth back in time induce a shortening of the fundamental astronomical periods for precession and obliquity. At the same time, the amplitudes of the different terms in the development of the obliquity are undergoing a relative enlargement of about 50 percent at 2 x 10(exp 9) yr BP but the independent term is increasing very weakly (less than 0.1 percent). In other words, the value of the obliquity, which lies within a range of 21.7 to 24.9 deg over the Quarternary was restricted to a range of 22.5 to 24.1 deg at 2 x 10(exp 9) yr BP. On the other hand, the amplitudes in the development of the climatic precession do not change. Moreover, these changes in the frequencies and amplitudes for both obliquity and climatic precession are larger for longer period terms. Finally, the periods in the eccentricity development are not influenced by the variation of the lunar distance. But the motion of the solar system, especially of the inner planets, was shown to be chaotic. It means that it is impossible to compute the exact motion of the planets over more than about 100 Myr, and the fundamental frequencies of the systems are not fixed quantities, but are slowly varying with time. As long as we consider the most important terms, the maximum deviation from the present-day value of the 19-kyr precessional period due to the chaotic motion of the solar system only does not reach more than a few tens of years around 80 Myr BP. Therefore the shortening of the obliquity

  13. Alarmingly High Segregation Frequencies of Quinolone Resistance Alleles within Human and Animal Microbiomes Are Not Explained by Direct Clinical Antibiotic Exposure

    PubMed Central

    Field, Wesley; Hershberg, Ruth

    2015-01-01

    Antibiotic resistance poses a major threat to human health. It is therefore important to characterize the frequency of resistance within natural bacterial environments. Many studies have focused on characterizing the frequencies with which horizontally acquired resistance genes segregate within natural bacterial populations. Yet, very little is currently understood regarding the frequency of segregation of resistance alleles occurring within the housekeeping targets of antibiotics. We surveyed a large number of metagenomic datasets extracted from a large variety of host-associated and non host-associated environments for such alleles conferring resistance to three groups of broad spectrum antibiotics: streptomycin, rifamycins, and quinolones. We find notable segregation frequencies of resistance alleles occurring within the target genes of each of the three antibiotics, with quinolone resistance alleles being the most frequent and rifamycin resistance alleles being the least frequent. Resistance allele frequencies varied greatly between different phyla and as a function of environment. The frequency of quinolone resistance alleles was especially high within host-associated environments, where it averaged an alarming ∼40%. Within host-associated environments, resistance to quinolones was most often conferred by a specific resistance allele. High frequencies of quinolone resistance alleles were also found within hosts that were not directly treated with antibiotics. Therefore, the high segregation frequency of quinolone resistance alleles occurring within the housekeeping targets of antibiotics in host-associated environments does not seem to be the sole result of clinical antibiotic usage. PMID:26019163

  14. Alarmingly High Segregation Frequencies of Quinolone Resistance Alleles within Human and Animal Microbiomes Are Not Explained by Direct Clinical Antibiotic Exposure.

    PubMed

    Field, Wesley; Hershberg, Ruth

    2015-05-26

    Antibiotic resistance poses a major threat to human health. It is therefore important to characterize the frequency of resistance within natural bacterial environments. Many studies have focused on characterizing the frequencies with which horizontally acquired resistance genes segregate within natural bacterial populations. Yet, very little is currently understood regarding the frequency of segregation of resistance alleles occurring within the housekeeping targets of antibiotics. We surveyed a large number of metagenomic datasets extracted from a large variety of host-associated and non host-associated environments for such alleles conferring resistance to three groups of broad spectrum antibiotics: streptomycin, rifamycins, and quinolones. We find notable segregation frequencies of resistance alleles occurring within the target genes of each of the three antibiotics, with quinolone resistance alleles being the most frequent and rifamycin resistance alleles being the least frequent. Resistance allele frequencies varied greatly between different phyla and as a function of environment. The frequency of quinolone resistance alleles was especially high within host-associated environments, where it averaged an alarming ∼ 40%. Within host-associated environments, resistance to quinolones was most often conferred by a specific resistance allele. High frequencies of quinolone resistance alleles were also found within hosts that were not directly treated with antibiotics. Therefore, the high segregation frequency of quinolone resistance alleles occurring within the housekeeping targets of antibiotics in host-associated environments does not seem to be the sole result of clinical antibiotic usage.

  15. No large-effect low-frequency coding variation found for myocardial infarction.

    PubMed

    Holmen, Oddgeir L; Zhang, He; Zhou, Wei; Schmidt, Ellen; Hovelson, Daniel H; Langhammer, Arnulf; Løchen, Maja-Lisa; Ganesh, Santhi K; Mathiesen, Ellisiv B; Vatten, Lars; Platou, Carl; Wilsgaard, Tom; Chen, Jin; Skorpen, Frank; Dalen, Håvard; Boehnke, Michael; Abecasis, Goncalo R; Njølstad, Inger; Hveem, Kristian; Willer, Cristen J

    2014-09-01

    Genome-wide association studies have identified variants, primarily common, that are associated with coronary artery disease or myocardial infarction (MI), but have not tested the majority of the low frequency and rare variation in the genome. We explored the hypothesis that previously untested low frequency (1-5% minor allele frequency) and rare (<1% minor allele frequency) coding variants are associated with MI. We genotyped 2906 MI cases and 6738 non-MI controls from Norway using the Illumina HumanExome Beadchip, allowing for direct genotyping of 85 972 polymorphic coding variants as well as 48 known GWAS SNPs. We followed-up 34 coding variants in an additional 2350 MI cases and 2318 controls from Norway. We evaluated exome array coverage in a subset of these samples using whole exome sequencing (N = 151). The exome array provided successful genotyping for an estimated 72.5% of Norwegian loss-of-function or missense variants with frequency >1% and 66.2% of variants <1% frequency observed more than once. Despite 80% power in the two-stage study (N = 14 312) to detect association with low-frequency variants with high effect sizes [odds ratio (OR) >1.86 and >1.36 for 1 and 5% frequency, respectively], we did not identify any novel genes or single variants that reached significance. This suggests that low-frequency coding variants with large effect sizes (OR >2) may not exist for MI. Larger sample sizes may identify coding variants with more moderate effects.

  16. Allele frequencies of D21S11, FGA, TH01, and VWA in populations of the Balkans.

    PubMed

    Huckenbeck, W; Scheil, H G; Schmidt, H D; Efremovska, L; Mikerezi, I

    2004-12-01

    This study is part of an extensive investigation of the genetic relationship between Balkan populations, especially the Aromuns. Allele frequencies of four STRs (D21S11, FGA, TH01, VWA) from Macedonians (Skopje), Gramostian Aromuns from the Stip region (Macedonia), Moskopolian Aromuns from Krusevo (Macedonia), and Musequiar Aromuns from Dukasi (Albania) are presented.

  17. A note on the change in gene frequency of a selected allele in partial full-sib mating populations

    SciTech Connect

    Caballero, A.

    1996-02-01

    The change in gene frequency of a selected allele in partial full-sib mating populations was analyzed. The implications of these papers is important in terms of the fixation probability of genes because, for the same equilibrium inbreeding coefficient, fixation rates of mutant genes would be larger for partial full-sib mating than for partial selfing. 4 refs.

  18. Natural variation in the Pto pathogen resistance gene within species of wild tomato (Lycopersicon). I. Functional analysis of Pto alleles.

    PubMed

    Rose, Laura E; Langley, Charles H; Bernal, Adriana J; Michelmore, Richard W

    2005-09-01

    Disease resistance to the bacterial pathogen Pseudomonas syringae pv. tomato (Pst) in the cultivated tomato, Lycopersicon esculentum, and the closely related L. pimpinellifolium is triggered by the physical interaction between plant disease resistance protein, Pto, and the pathogen avirulence protein, AvrPto. To investigate the extent to which variation in the Pto gene is responsible for naturally occurring variation in resistance to Pst, we determined the resistance phenotype of 51 accessions from seven species of Lycopersicon to isogenic strains of Pst differing in the presence of avrPto. One-third of the plants displayed resistance specifically when the pathogen expressed AvrPto, consistent with a gene-for-gene interaction. To test whether this resistance in these species was conferred specifically by the Pto gene, alleles of Pto were amplified and sequenced from 49 individuals and a subset (16) of these alleles was tested in planta using Agrobacterium-mediated transient assays. Eleven alleles conferred a hypersensitive resistance response (HR) in the presence of AvrPto, while 5 did not. Ten amino acid substitutions associated with the absence of AvrPto recognition and HR were identified, none of which had been identified in previous structure-function studies. Additionally, 3 alleles encoding putative pseudogenes of Pto were isolated from two species of Lycopersicon. Therefore, a large proportion, but not all, of the natural variation in the reaction to strains of Pst expressing AvrPto can be attributed to sequence variation in the Pto gene.

  19. Natural Variation in the Pto Pathogen Resistance Gene Within Species of Wild Tomato (Lycopersicon). I. Functional Analysis of Pto Alleles

    PubMed Central

    Rose, Laura E.; Langley, Charles H.; Bernal, Adriana J.; Michelmore, Richard W.

    2005-01-01

    Disease resistance to the bacterial pathogen Pseudomonas syringae pv. tomato (Pst) in the cultivated tomato, Lycopersicon esculentum, and the closely related L. pimpinellifolium is triggered by the physical interaction between plant disease resistance protein, Pto, and the pathogen avirulence protein, AvrPto. To investigate the extent to which variation in the Pto gene is responsible for naturally occurring variation in resistance to Pst, we determined the resistance phenotype of 51 accessions from seven species of Lycopersicon to isogenic strains of Pst differing in the presence of avrPto. One-third of the plants displayed resistance specifically when the pathogen expressed AvrPto, consistent with a gene-for-gene interaction. To test whether this resistance in these species was conferred specifically by the Pto gene, alleles of Pto were amplified and sequenced from 49 individuals and a subset (16) of these alleles was tested in planta using Agrobacterium-mediated transient assays. Eleven alleles conferred a hypersensitive resistance response (HR) in the presence of AvrPto, while 5 did not. Ten amino acid substitutions associated with the absence of AvrPto recognition and HR were identified, none of which had been identified in previous structure-function studies. Additionally, 3 alleles encoding putative pseudogenes of Pto were isolated from two species of Lycopersicon. Therefore, a large proportion, but not all, of the natural variation in the reaction to strains of Pst expressing AvrPto can be attributed to sequence variation in the Pto gene. PMID:15944360

  20. Natural variation in maize architecture is mediated by allelic differences at the PINOID co-ortholog barren inflorescence2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We characterized allelic variation at barren inflorescence2 (bif2), a maize co-ortholog of the Arabidopsis PINOID protein kinase (PID), and tested for trait associations with bif2 in both an association mapping population of 277 diverse maize inbreds and in the inter-mated B73-Mo17 (IBM) linkage pop...

  1. Frequencies of HKαα and anti-HKαα Alleles in Chinese Carriers of Silent Deletional α-Thalassemia.

    PubMed

    Wu, Man-Yu; Li, Jian; Li, Shu-Chen; Li, Yan; Li, Dong-Zhi

    2015-01-01

    The HKαα (HongKongαα) allele is an unusual rearrangement of the α-globin gene cluster containing both the -α(3.7) (rightward) and ααα(anti 4.2) crossover deletion/duplication. The anti-HKαα (anti-HongKongαα) allele is the reciprocal product containing both the -α(4.2) (leftward) and ααα(anti 3.7) unequal crossover deletion/duplication. In clinical practice of thalassemia screening, gap-polymerase chain reaction (gap-PCR) approaches are used to detect the common -α(3.7) and -α(4.2) deletions of α-thalassemia (α-thal). Because the HKαα and anti-HKαα alleles also contain the single α-globin gene deletion, individuals with these alleles would be misdiagnosed as -α(3.7) or -α(4.2) carriers. This would likely produce misleading or incorrect information in genetic counseling. In this study, we investigated the HKαα and anti-HKαα alleles in Chinese carriers of silent deletional α-thal, and reported their frequencies to be 2.27 and 0.35% in -α(3.7) and -α(4.2) carriers, respectively. Given the rarity of the HKαα and anti-HKαα alleles, a routine screening for these two rearrangements are unlikely to be necessary on most occasions.

  2. Genotypic and allelic frequencies of gene polymorphisms associated with meat tenderness in Nellore beef cattle.

    PubMed

    Carvalho, M E; Eler, J P; Bonin, M N; Rezende, F M; Biase, F H; Meirelles, F V; Regitano, L C A; Coutinho, L L; Balieiro, J C C; Ferraz, J B S

    2017-02-16

    The objectives of this study were to characterize the allelic and genotypic frequencies of polymorphisms in the µ-calpain and calpastatin genes, and to assess their association with meat tenderness and animal growth in Nellore cattle. We evaluated 605 Nellore animals at 24 months of age, on average, at slaughter. The polymorphisms were determined for the molecular markers CAPN316, CAPN530, CAPN4751, CAPN4753, and UOGACAST1. Analyses of meat tenderness at 7, 14, and 21 days of maturation were performed in samples of longissimus thoracis obtained between the 12th and 13th rib and sheared using a Warner Bratzler Shear Force. Significant effects were observed for meat tenderness at days 7, 14, and 21 of maturation for the marker CAPN4751, at day 21 for the marker CAPN4753, and at days 14 and 21 for the marker UOGCAST1. For genotypic combinations of markers, the results were significant for the combination CAPN4751/UOGCAST1 in the three maturation periods and CAPN4753/UOGCAST1 at days 14 and 21 of maturation.

  3. Allele frequencies of three factor VIII gene polymorphisms in Iranian populations and their application in hemophilia A carrier detection.

    PubMed

    Azimifar, S Babak; Seyedna, S Yoosef; Zeinali, Sirous

    2006-05-01

    Hemophilia A is an X-linked recessive bleeding disorder caused by a quantitative or qualitative deficiency of blood coagulation factor VIII (FVIII). ARMS (amplification refractory mutation system) primers were designed to determine allele frequencies of three FVIII gene linked markers, IVS7 nt 27 G/A SNP, BclI/intron 18, and HindIII/intron 19 among 85 normal Iranian women from unrelated families. Then same method was applied to perform carrier detection for hemophilia A families. The allele frequencies of IVS7 nt 27 "G"/"A" allele, BclI "T"/"A" allele, and HindIII "C"/"T" allele among normal women were 0.88/0.12, 0.52/0.48, and 0.48/0.52, respectively. The three polymorphisms were found to be in strong linkage disequilibrium, which decreased the overall heterozygosity to 51%. Twenty-one women from 15 unrelated hemophilia A families were referred to us for hemophilia A carrier detection. Taking advantage of these three biallelic polymorphisms in conjunction with multiallelic St14 VNTR (locus DXS52), IVS13 (CA)n STR, and IVS22 (CA)n STR, carrier status was determined in 16 women (16/21 or 76% of the at-risk women) from 11 families (11/15 or 73% of the families). The used ARMS methods are rapid and can easily be applied in conjunction with other FVIII gene linked polymorphisms for indirect mutation detection of hemophilia A where they are informative.

  4. Large allele frequency differences between human continental groups are more likely to have occurred by drift during range expansions than by selection.

    PubMed

    Hofer, T; Ray, N; Wegmann, D; Excoffier, L

    2009-01-01

    Several studies have found strikingly different allele frequencies between continents. This has been mainly interpreted as being due to local adaptation. However, demographic factors can generate similar patterns. Namely, allelic surfing during a population range expansion may increase the frequency of alleles in newly colonised areas. In this study, we examined 772 STRs, 210 diallelic indels, and 2834 SNPs typed in 53 human populations worldwide under the HGDP-CEPH Diversity Panel to determine to which extent allele frequency differs among four regions (Africa, Eurasia, East Asia, and America). We find that large allele frequency differences between continents are surprisingly common, and that Africa and America show the largest number of loci with extreme frequency differences. Moreover, more STR alleles have increased rather than decreased in frequency outside Africa, as expected under allelic surfing. Finally, there is no relationship between the extent of allele frequency differences and proximity to genes, as would be expected under selection. We therefore conclude that most of the observed large allele frequency differences between continents result from demography rather than from positive selection.

  5. High Susceptibility to Cry1Ac and Low Resistance Allele Frequency Reduce the Risk of Resistance of Helicoverpa armigera to Bt Soybean in Brazil

    PubMed Central

    Bacalhau, Fabiana B.; Amado, Douglas; Carvalho, Renato A.; Martinelli, Samuel; Head, Graham P.; Omoto, Celso

    2016-01-01

    The Old World bollworm, Helicoverpa armigera (Hübner), was recently introduced into Brazil, where it has caused extensive damage to cotton and soybean crops. MON 87701 × MON 89788 soybean, which expresses the Bt protein Cry1Ac, was recently deployed in Brazil, providing high levels of control against H. armigera. To assess the risk of resistance to the Cry1Ac protein expressed by MON 87701 × MON 89788 soybean in Brazil, we conducted studies to evaluate the baseline susceptibility of H. armigera to Cry1Ac, in planta efficacy including the assessment of the high-dose criterion, and the initial resistance allele frequency based on an F2 screen. The mean Cry1Ac lethal concentration (LC50) ranged from 0.11 to 1.82 μg·mL−1 of diet among all H. armigera field populations collected from crop seasons 2013/14 to 2014/15, which indicated about 16.5-fold variation. MON 87701 × MON 89788 soybean exhibited a high level of efficacy against H. armigera and most likely met the high dose criterion against this target species in leaf tissue dilution bioassays up to 50 times. A total of 212 F2 family lines of H. armigera were established from field collections sampled from seven locations across Brazil and were screened for the presence of MON 87701 × MON 89788 soybean resistance alleles. None of the 212 families survived on MON 87701 × MON 89788 soybean leaf tissue (estimated allele frequency = 0.0011). The responses of H. armigera to Cry1Ac protein, high susceptibility to MON 87701 × MON 89788 soybean, and low frequency of resistance alleles across the main soybean-producing regions support the assumptions of a high-dose/refuge strategy. However, maintenance of reasonable compliance with the refuge recommendation will be essential to delay the evolution of resistance in H. armigera to MON 87701 × MON 89788 soybean in Brazil. PMID:27532632

  6. High Susceptibility to Cry1Ac and Low Resistance Allele Frequency Reduce the Risk of Resistance of Helicoverpa armigers to Bt Soybean in Brazil.

    PubMed

    Dourado, Patrick M; Bacalhau, Fabiana B; Amado, Douglas; Carvalho, Renato A; Martinelli, Samuel; Head, Graham P; Omoto, Celso

    2016-01-01

    The Old World bollworm, Helicoverpa armigera (Hübner), was recently introduced into Brazil, where it has caused extensive damage to cotton and soybean crops. MON 87701 × MON 89788 soybean, which expresses the Bt protein Cry1Ac, was recently deployed in Brazil, providing high levels of control against H. armigera. To assess the risk of resistance to the Cry1Ac protein expressed by MON 87701 × MON 89788 soybean in Brazil, we conducted studies to evaluate the baseline susceptibility of H. armigera to Cry1Ac, in planta efficacy including the assessment of the high-dose criterion, and the initial resistance allele frequency based on an F2 screen. The mean Cry1Ac lethal concentration (LC50) ranged from 0.11 to 1.82 μg·mL-1 of diet among all H. armigera field populations collected from crop seasons 2013/14 to 2014/15, which indicated about 16.5-fold variation. MON 87701 × MON 89788 soybean exhibited a high level of efficacy against H. armigera and most likely met the high dose criterion against this target species in leaf tissue dilution bioassays up to 50 times. A total of 212 F2 family lines of H. armigera were established from field collections sampled from seven locations across Brazil and were screened for the presence of MON 87701 × MON 89788 soybean resistance alleles. None of the 212 families survived on MON 87701 × MON 89788 soybean leaf tissue (estimated allele frequency = 0.0011). The responses of H. armigera to Cry1Ac protein, high susceptibility to MON 87701 × MON 89788 soybean, and low frequency of resistance alleles across the main soybean-producing regions support the assumptions of a high-dose/refuge strategy. However, maintenance of reasonable compliance with the refuge recommendation will be essential to delay the evolution of resistance in H. armigera to MON 87701 × MON 89788 soybean in Brazil.

  7. Natural allelic variations of TCS1 play a crucial role in caffeine biosynthesis of tea plant and its related species.

    PubMed

    Jin, Ji-Qiang; Yao, Ming-Zhe; Ma, Chun-Lei; Ma, Jian-Qiang; Chen, Liang

    2016-03-01

    Tea caffeine synthase 1 (TCS1) is an enzyme that catalyzes the methylation of N-3 and N-1 and considered to be the most critical enzyme in the caffeine biosynthetic pathway of tea plant. This study shows that TCS1 has six types of allelic variations, namely, TCS1a, TCS1b, TCS1c, TCS1d, TCS1e, and TCS1f, with a 252 bp insertion/deletion mutation in the 5'-untranslated region. Among tea plant and its related species, TCS1a is the predominant allele, and TCS1b-f are the rare alleles that mainly appear in few wild germplasms. The full-length cDNA sequences of three new alleles, namely, TCS1d, TCS1e, and TCS1f, were isolated from specific germplasms, and all of recombinant proteins have higher caffeine synthase (CS, EC 2.1.1.160) activity than theobromine synthase (TS, EC 2.1.1.159). Amino acid residue 269 is responsible for the difference in TCS activity and substrate recognition, which was demonstrated by using site-directed mutagenesis experiments. Furthermore, natural variations in TCS1 change the transcription levels. There are two molecular mechanisms controlling the caffeine biosynthesis in low-caffeine-accumulating tea germplasms, i.e., TCS1 allele with low transcription level or its encoded protein with only TS activity. Allelic variations of TCS1 play a crucial role in caffeine biosynthesis. Taken together, our work provides valuable foundation for a comprehensive understanding of the mechanism of caffeine biosynthesis in section Thea plants and useful guidance for effective breeding.

  8. Retention of agronomically important variation in germplasm core collections: implications for allele mining

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The primary targets of allele mining efforts are loci of agronomic importance. Agronomic loci typically exhibit patterns of allelic diversity consistent with a history of natural or artificial selection. Natural or artificial selection causes the distribution of genetic diversity at such loci to d...

  9. BGMUT: NCBI dbRBC database of allelic variations of genes encoding antigens of blood group systems.

    PubMed

    Patnaik, Santosh Kumar; Helmberg, Wolfgang; Blumenfeld, Olga O

    2012-01-01

    Analogous to human leukocyte antigens, blood group antigens are surface markers on the erythrocyte cell membrane whose structures differ among individuals and which can be serologically identified. The Blood Group Antigen Gene Mutation Database (BGMUT) is an online repository of allelic variations in genes that determine the antigens of various human blood group systems. The database is manually curated with allelic information collated from scientific literature and from direct submissions from research laboratories. Currently, the database documents sequence variations of a total of 1251 alleles of all 40 gene loci that together are known to affect antigens of 30 human blood group systems. When available, information on the geographic or ethnic prevalence of an allele is also provided. The BGMUT website also has general information on the human blood group systems and the genes responsible for them. BGMUT is a part of the dbRBC resource of the National Center for Biotechnology Information, USA, and is available online at http://www.ncbi.nlm.nih.gov/projects/gv/rbc/xslcgi.fcgi?cmd=bgmut. The database should be of use to members of the transfusion medicine community, those interested in studies of genetic variation and related topics such as human migrations, and students as well as members of the general public.

  10. Frequency Specific Effects of ApoE ε4 Allele on Resting-State Networks in Nondemented Elders

    PubMed Central

    Liang, Ying; Li, Zhenzhen; Neuroimaging Initiative, Alzheimer's Disease

    2017-01-01

    We applied resting-state functional magnetic resonance imaging (fMRI) to examine the Apolipoprotein E (ApoE) ε4 allele effects on functional connectivity of the default mode network (DMN) and the salience network (SN). Considering the frequency specific effects of functional connectivity, we decomposed the brain network time courses into two bands: 0.01–0.027 Hz and 0.027–0.08 Hz. All scans were acquired by the Alzheimer's Disease Neuroscience Initiative (ADNI). Thirty-two nondemented subjects were divided into two groups based on the presence (n = 16) or absence (n = 16) of the ApoE ε4 allele. We explored the frequency specific effects of ApoE ε4 allele on the default mode network (DMN) and the salience network (SN) functional connectivity. Compared to ε4 noncarriers, the DMN functional connectivity of ε4 carriers was significantly decreased while the SN functional connectivity of ε4 carriers was significantly increased. Many functional connectivities showed significant differences at the lower frequency band of 0.01–0.027 Hz or the higher frequency band of 0.027–0.08 Hz instead of the typical range of 0.01–0.08 Hz. The results indicated a frequency dependent effect of resting-state signals when investigating RSNs functional connectivity.

  11. 46 CFR 111.01-17 - Voltage and frequency variations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 4 2012-10-01 2012-10-01 false Voltage and frequency variations. 111.01-17 Section 111.01-17 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS General § 111.01-17 Voltage and frequency variations....

  12. HLA-DRB and HLA-DQB Allele and Haplotype Frequencies in Iranian Patients with Recurrent Aphthous Stomatitis.

    PubMed

    Najafi, Shamsolmoulouk; Mohammadzadeh, Mahsa; Zare Bidoki, Alireza; Meighani, Ghasem; Aslani, Saeed; Mahmoudi, Mahdi; Rezaei, Nima

    Recurrent aphthous stomatitis (RAS) is known as the most common chronic disease of the oral cavity, which affects a range of 5-25% of the population. RAS appears to be associated with some human leukocyte antigen (HLA) class II alleles and haplotypes. This study attempts to survey the distribution of HLA-DRB and -DQB alleles among Iranian RAS patients and healthy controls. In order to evaluate the association of HLA-DR and DQ alleles and haplotypes, 54 patients with RAS and 100 unrelated healthy subjects as control group were investigated. Our data indicated that DRB1*13:17, DRB1*15:01, and DRB5*01 were significantly more frequent in RAS patients in comparison to controls. However, DRB3:01allele frequency was higher in the controls compared to the patients. The significantly frequent allele in the patients compared with the healthy subjects was HLA-DQB1*03:02. However, both HLA-DQB1*02:01 and HLA-DQB1*03:01 alleles were most frequent in the healthy individuals rather than the patients. The DRB*04/DQB1*03:01 and DRB*01:01/DQB1*02:01 haplotypes were significantly distributed in healthy subjects compared with patients. However, DRB*07:01/DQB1*03:02 haplotype was found to be significantly frequent in patients than controls. In respect of HLA genes, factors are involved in the incidence of RAS; various HLA-DRB and HLA-DQB1 alleles and the related haplotypes are suggested to be the three main RAS susceptibility factors in our population study.

  13. Prevalence of alpha-1 antitrypsin deficiency and allele frequency in patients with COPD in Brazil

    PubMed Central

    Russo, Rodrigo; Zillmer, Laura Russo; Nascimento, Oliver Augusto; Manzano, Beatriz; Ivanaga, Ivan Teruaki; Fritscher, Leandro; Lundgren, Fernando; Miravitlles, Marc; Gondim, Heicilainy Del Carlos; Santos, Gildo; Alves, Marcela Amorim; Oliveira, Maria Vera; de Souza, Altay Alves Lino; Sales, Maria Penha Uchoa; Jardim, José Roberto

    2016-01-01

    ABSTRACT Objective: To determine the prevalence of alpha 1-antitrypsin (AAT) deficiency (AATD), as well as allele frequency, in COPD patients in Brazil. Methods: This was a cross-sectional study involving 926 COPD patients 40 years of age or older, from five Brazilian states. All patients underwent determination of AAT levels in dried blood spot (DBS) samples by nephelometry. Those with DBS AAT levels ≤ 2.64 mg/dL underwent determination of serum AAT levels. Those with serum AAT levels of < 113 mg/dL underwent genotyping. In case of conflicting results, SERPINA1 gene sequencing was performed. Results: Of the 926 COPD patients studied, 85 had DBS AAT levels ≤ 2.64 mg/dL, and 24 (2.6% of the study sample) had serum AAT levels of < 113 mg/dL. Genotype distribution in this subset of 24 patients was as follows: PI*MS, in 3 (12.5%); PI*MZ, in 13 (54.2%); PI*SZ, in 1 (4.2%); PI*SS, in 1 (4.2%); and PI*ZZ, in 6 (25.0%). In the sample as a whole, the overall prevalence of AATD was 2.8% and the prevalence of the PI*ZZ genotype (severe AATD) was 0.8% Conclusions: The prevalence of AATD in COPD patients in Brazil is similar to that found in most countries and reinforces the recommendation that AAT levels be measured in all COPD patients. PMID:27812629

  14. No differences of butyrylcholinesterase protein activity and allele frequency in Lewy body diseases.

    PubMed

    Maetzler, Walter; Keller, Stefanie; Michelis, Joan; Koehler, Niklas; Stransky, Elke; Becker, Clemens; Schulte, Claudia; Melms, Arthur; Gasser, Thomas; Berg, Daniela

    2009-08-01

    Butyrylcholinesterase (BChE) genotypes and protein (BuChE) activity, especially in combination with Apolipoprotein E4 (ApoE4), have been investigated as risk factors for developing Alzheimer disease (AD) and may be associated with the rate of progression of cognitive decline. Despite similar pathologic (e.g. amyloid deposition) and neurochemical (e.g. cholinergic deficits) aspects between AD and Lewy body diseases (LBD), scarce data is obtainable about BChE genotypes and BuChE activity in LBD. We measured BuChE activity levels in serum and cerebrospinal fluid (CSF) of 114 LBD subjects (59 of them were demented) and 31 elderly controls. We found higher CSF BuChE activity in males compared to females, and a negative correlation of serum BuChE activity with age and cognitive function. Demented LBD patients, non-demented LBD patients and controls did not differ significantly with regard to serum and CSF BuChE activity. Furthermore, BChE K variant and ApoE4 allele frequencies were determined. The BChE K variant was significantly associated with lower serum activity; the same trend was observable in CSF. The subgroups did not differ significantly with regard to BChE K/ApoE4 occurrence. These data confirm and extend previous results on the relationship between BChE gene and BuChE activity, and argue rather against a major impact of BuChE on LBD-associated pathologies.

  15. Conformational variation between allelic variants of cell-surface ovine prion protein.

    PubMed

    Thackray, Alana M; Yang, Sujeong; Wong, Edmond; Fitzmaurice, Tim J; Morgan-Warren, Robert J; Bujdoso, Raymond

    2004-07-01

    The distribution of prion infectivity and PrPSc between peripheral lymphoid tissues suggests their possible haematogenic spread during the progression of natural scrapie in susceptible sheep. Since ovine PBMCs (peripheral blood mononuclear cells) express PrPC, they have the potential to carry or harbour disease-associated forms of PrP. To detect the possible presence of disease-associated PrP on the surface of blood cells, an understanding is required of the conformations that normal ovine cell-surface PrPC may adopt. In the present study, we have used monoclonal antibodies that recognize epitopes in either the N- or C-terminal portions of PrP to probe the conformations of PrPC on ovine PBMCs by flow cytometry. Although PBMCs from scrapie-susceptible and -resistant genotypes of sheep expressed similar levels of cell-surface PrPC, as judged by their reactivity with N-terminal-specific anti-PrP monoclonal antibodies, there was considerable genotypic heterogeneity in the region between helix-1 and residue 171. Cells from PrP-VRQ (V136R154Q171) sheep showed uniform reactivity with monoclonal antibodies that bound to epitopes around helix-1, whereas cells from PrP-ARQ (A136R154Q171) and PrP-ARR (A136R154R171) sheep showed variable binding. The region between b-strand-2 and residue 171, which includes a YYR motif, was buried or obscured in cell-surface PrPC on PBMCs from scrapie-susceptible and -resistant sheep. However, an epitope of PrPC that is influenced by residue 171 was more exposed on PBMCs from PrP-VRQ sheep than on PBMCs from the PrP-ARQ genotype. Our results highlight conformational variation between scrapie-susceptible and -resistant forms of cell-surface PrPC and also between allelic variants of susceptible genotypes.

  16. Allelic variation in TLR4 is linked to resistance to Salmonella Enteritidis infection in chickens.

    PubMed

    Li, Peng; Wang, Huihua; Zhao, Xingwang; Gou, Zhongyong; Liu, Ranran; Song, Yongmei; Li, Qinghe; Zheng, Maiqing; Cui, Huanxian; Everaert, Nadia; Zhao, Guiping; Wen, Jie

    2017-03-01

    Salmonella Enteritidis (SE) is a foodborne pathogen that negatively affects both animal and human health. Polymorphisms of the TLR4 gene may affect recognition by Toll-like receptor 4 (TLR4) of bacterial lipopolysaccharide (LPS), leading to differences in host resistance to pathogenic infections. The present study has investigated polymorphic loci of chicken TLR4 (ChTLR4) in ten chicken breeds, electrostatic potentials of mutant structures of TLR4, and a linkage analysis between allelic variation and survival ratio to infection with SE in specific-pathogen-free (SPF) White Leghorns. A total of 19 Single Nucleotide Polymorphisms (SNPs), of which 10 were novel, were found in chicken breeds. Seven newly identified amino acid variants (C68G, G674A, G782A, A896T, T959G, T986A, and A1104C) and previously reported important mutations (G247A, G1028A, C1147T, and A1832G) were demonstrated in the extracellular domain of the ChTLR4 gene. Significant changes in surface electrostatic potential of the ectodomain of TLR4, built by homology modeling, were observed at the Glu83Lys (G247A), Arg298Ser (A896T), Ser368Arg (A1104C), and Gln611Arg (A1832G) substitutions. Linkage analysis showed that one polymorphic locus G247A of TLR4 gene, common in all breeds examined, was significantly associated with increased resistance to SE in SPF White Leghorns chicks (log-rank P-value = 0.04). The genotypes from A1832G SNPs did not show statistically significant survival differences. This study has provided the first direct evidence that G247A substitution in ChTLR4 is associated with increased resistance to Salmonella Enteritidis.

  17. Parental allelic variation at COL6A1 and congenital heart defects in trisomy 21

    SciTech Connect

    Kessling, A.M.; Howard, C.M.; Farrer, M.J.

    1994-09-01

    Overt congenital heart defects (CHD) affect over 40% of newborns with Down syndrome. On the hypothesis that genetic variation on chromosome 21 determines this clinical variability, we studied a CHD candidate locus (COL6A1) on 21q22.3. We studied three RFLP loci in COL6A1 in 37 families of known British/Irish population of ancestral origin, and in population-matched controls. Each family had a child with trisomy 21 with or without accompanying congenital heart defect (CHD). Parental and meiotic origin of nondisjunction were determined using peri-centromeric markers. For the analysis, we considered groups of families with trisomic children with and without CHD, and subsets of nondisjoining and disjoining parents. Parental genotypes at nine control RFLP loci on chromosome 21 showed no association with CHD in the trisomic child. By contrast, parental genotypes at all three individual RFLP loci within COL6A1 showed statistically significant association with the trisomic child`s CHD status. Pairwise consideration of these loci in groups of families of trisomic children with and without CHD showed subsets of nondisjoining and disjoining parents to have different linkage disequilibrium patterns at these loci than population-matched controls. This suggests that the COL6A1 alleles of the parents are not representative of the population as a whole. Consideration of all three loci together as haplotypes supports this conclusion. Four results suggest that a functional mutation within, or in linkage disequilibrium with COL6A1 influences CHD outcome in trisomy 21.

  18. Allelic genome structural variations in maize detected by array comparative genome hybridization.

    PubMed

    Beló, André; Beatty, Mary K; Hondred, David; Fengler, Kevin A; Li, Bailin; Rafalski, Antoni

    2010-01-01

    DNA polymorphisms such as insertion/deletions and duplications affecting genome segments larger than 1 kb are known as copy-number variations (CNVs) or structural variations (SVs). They have been recently studied in animals and humans by using array-comparative genome hybridization (aCGH), and have been associated with several human diseases. Their presence and phenotypic effects in plants have not been investigated on a genomic scale, although individual structural variations affecting traits have been described. We used aCGH to investigate the presence of CNVs in maize by comparing the genome of 13 maize inbred lines to B73. Analysis of hybridization signal ratios of 60,472 60-mer oligonucleotide probes between inbreds in relation to their location in the reference genome (B73) allowed us to identify clusters of probes that deviated from the ratio expected for equal copy-numbers. We found CNVs distributed along the maize genome in all chromosome arms. They occur with appreciable frequency in different germplasm subgroups, suggesting ancient origin. Validation of several CNV regions showed both insertion/deletions and copy-number differences. The nature of CNVs detected suggests CNVs might have a considerable impact on plant phenotypes, including disease response and heterosis.

  19. Prion protein genotype survey confirms low frequency of scrapie-resistant K222 allele in British goat herds

    PubMed Central

    Goldmann, W.; Stewart, P.; Konold, T.; Street, S.; Langeveld, J.; Windl, O.; Ortiz-Pelaez, A.

    2016-01-01

    Scrapie in goats is a transmissible, fatal prion disease, which is endemic in the British goat population. The recent success in defining caprine PRNP gene variants that provide resistance to experimental and natural classical scrapie has prompted the authors to conduct a survey of PRNP genotypes in 10 goat breeds and 52 herds to find goats with the resistant K222 allele. They report here the frequencies in 1236 tested animals of the resistance-associated K222 and several other alleles by breed and herd. Eight animals were found to be heterozygous QK222 goats (0.64 per cent genotype frequency, 95 per cent CI 0.28 to 1.27 per cent) but no homozygous KK222 goats were detected. The K222 allele was found in Saanen, Toggenburg and Anglo-Nubian goats. The fact that only a few goats with the K222 allele have been identified does not preclude the possibility to design and implement successful breeding programmes at national level. PMID:26755614

  20. Prion protein genotype survey confirms low frequency of scrapie-resistant K222 allele in British goat herds.

    PubMed

    Goldmann, W; Marier, E; Stewart, P; Konold, T; Street, S; Langeveld, J; Windl, O; Ortiz-Pelaez, A

    2016-02-13

    Scrapie in goats is a transmissible, fatal prion disease, which is endemic in the British goat population. The recent success in defining caprine PRNP gene variants that provide resistance to experimental and natural classical scrapie has prompted the authors to conduct a survey of PRNP genotypes in 10 goat breeds and 52 herds to find goats with the resistant K222 allele. They report here the frequencies in 1236 tested animals of the resistance-associated K222 and several other alleles by breed and herd. Eight animals were found to be heterozygous QK222 goats (0.64 per cent genotype frequency, 95 per cent CI 0.28 to 1.27 per cent) but no homozygous KK222 goats were detected. The K222 allele was found in Saanen, Toggenburg and Anglo-Nubian goats. The fact that only a few goats with the K222 allele have been identified does not preclude the possibility to design and implement successful breeding programmes at national level.

  1. Comprehensive analysis of imprinted genes in maize reveals allelic variation for imprinting and limited conservation with other species.

    PubMed

    Waters, Amanda J; Bilinski, Paul; Eichten, Steven R; Vaughn, Matthew W; Ross-Ibarra, Jeffrey; Gehring, Mary; Springer, Nathan M

    2013-11-26

    In plants, a subset of genes exhibit imprinting in endosperm tissue such that expression is primarily from the maternal or paternal allele. Imprinting may arise as a consequence of mechanisms for silencing of transposons during reproduction, and in some cases imprinted expression of particular genes may provide a selective advantage such that it is conserved across species. Separate mechanisms for the origin of imprinted expression patterns and maintenance of these patterns may result in substantial variation in the targets of imprinting in different species. Here we present deep sequencing of RNAs isolated from reciprocal crosses of four diverse maize genotypes, providing a comprehensive analysis that allows evaluation of imprinting at more than 95% of endosperm-expressed genes. We find that over 500 genes exhibit statistically significant parent-of-origin effects in maize endosperm tissue, but focused our analyses on a subset of these genes that had >90% expression from the maternal allele (69 genes) or from the paternal allele (108 genes) in at least one reciprocal cross. Over 10% of imprinted genes show evidence of allelic variation for imprinting. A comparison of imprinting in maize and rice reveals that 13% of genes with syntenic orthologs in both species exhibit conserved imprinting. Genes that exhibit conserved imprinting between maize and rice have elevated nonsynonymous to synonymous substitution ratios compared with other imprinted genes, suggesting a history of more rapid evolution. Together, these data suggest that imprinting only has functional relevance at a subset of loci that currently exhibit imprinting in maize.

  2. Functional relationships of phytoene synthase 1 alleles on chromosome 7A controlling flour colour variation in selected Australian wheat genotypes.

    PubMed

    Crawford, A C; Stefanova, K; Lambe, W; McLean, R; Wilson, R; Barclay, I; Francki, M G

    2011-06-01

    Flour colour measured as a Commission Internationale de l'Eclairage (CIE) b* value is an important wheat quality attribute for a range of end-products, with genes and enzymes of the xanthophyll biosynthesis pathway providing potential sources of trait variation. In particular, the phytoene synthase 1 (Psy1) gene has been associated with quantitative trait loci (QTL) for flour b* colour variation. Several Psy1 alleles on chromosome 7A (Psy-A1) have been described, along with proposed mechanisms for influencing flour b* colour. This study sought to identify evolutionary relationships among known Psy-A1 alleles, to establish which Psy-A1 alleles are present in selected Australian wheat genotypes and establish their role in controlling variation for flour b* colour via QTL analysis. Phylogenetic analyses showed seven of eight known Psy-A1 alleles clustered with sequences from T. urartu, indicating the majority of alleles in Australian germplasm share a common evolutionary lineage. In this regard, Psy-A1a, Psy-A1c, Psy-A1e and Psy-A1p were common in Australian genotypes with flour b* colour ranging from white to yellow. In contrast Psy-A1s was found to be related to A. speltoides, indicating a possible A-B genome translocation during wheat polyploidisation. A new allele Psy-A1t (similar to Psy-A1s) was discovered in genotypes with yellow flour, with QTL analyses indicating Psy-A1t strongly influences flour b* colour in Australian germplasm. QTL LOD value maxima did not coincide with Psy-A1 gene locus in two of three populations and, therefore, Psy-A1a and Psy-A1p may not be involved in flour colour. Instead two other QTL were identified, one proximal and one distal to Psy-A1 in Australian wheat lines. Comparison of Psy-A1t and Psy-A1p predicted protein sequences suggests differences in putative sites for post-translational modification may influence enzyme activity and subsequent xanthophyll accumulation in the wheat endosperm. Psy-A1a and Psy-A1p were not involved in

  3. Allelic Variation in Developmental Genes and Effects on Winter Wheat Heading Date in the U.S. Great Plains.

    PubMed

    Grogan, Sarah M; Brown-Guedira, Gina; Haley, Scott D; McMaster, Gregory S; Reid, Scott D; Smith, Jared; Byrne, Patrick F

    2016-01-01

    Heading date in wheat (Triticum aestivum L.) and other small grain cereals is affected by the vernalization and photoperiod pathways. The reduced-height loci also have an effect on growth and development. Heading date, which occurs just prior to anthesis, was evaluated in a population of 299 hard winter wheat entries representative of the U.S. Great Plains region, grown in nine environments during 2011-2012 and 2012-2013. The germplasm was evaluated for candidate genes at vernalization (Vrn-A1, Vrn-B1, and Vrn-D1), photoperiod (Ppd-A1, Ppd-B1 and Ppd-D1), and reduced-height (Rht-B1 and Rht-D1) loci using polymerase chain reaction (PCR) and Kompetitive Allele Specific PCR (KASP) assays. Our objectives were to determine allelic variants known to affect flowering time, assess the effect of allelic variants on heading date, and investigate changes in the geographic and temporal distribution of alleles and haplotypes. Our analyses enhanced understanding of the roles developmental genes have on the timing of heading date in wheat under varying environmental conditions, which could be used by breeding programs to improve breeding strategies under current and future climate scenarios. The significant main effects and two-way interactions between the candidate genes explained an average of 44% of variability in heading date at each environment. Among the loci we evaluated, most of the variation in heading date was explained by Ppd-D1, Ppd-B1, and their interaction. The prevalence of the photoperiod sensitive alleles Ppd-A1b, Ppd-B1b, and Ppd-D1b has gradually decreased in U.S. Great Plains germplasm over the past century. There is also geographic variation for photoperiod sensitive and reduced-height alleles, with germplasm from breeding programs in the northern Great Plains having greater incidences of the photoperiod sensitive alleles and lower incidence of the semi-dwarf alleles than germplasm from breeding programs in the central or southern plains.

  4. Allelic Variation in Developmental Genes and Effects on Winter Wheat Heading Date in the U.S. Great Plains

    PubMed Central

    Brown-Guedira, Gina; Haley, Scott D.; McMaster, Gregory S.; Reid, Scott D.; Smith, Jared; Byrne, Patrick F.

    2016-01-01

    Heading date in wheat (Triticum aestivum L.) and other small grain cereals is affected by the vernalization and photoperiod pathways. The reduced-height loci also have an effect on growth and development. Heading date, which occurs just prior to anthesis, was evaluated in a population of 299 hard winter wheat entries representative of the U.S. Great Plains region, grown in nine environments during 2011–2012 and 2012–2013. The germplasm was evaluated for candidate genes at vernalization (Vrn-A1, Vrn-B1, and Vrn-D1), photoperiod (Ppd-A1, Ppd-B1 and Ppd-D1), and reduced-height (Rht-B1 and Rht-D1) loci using polymerase chain reaction (PCR) and Kompetitive Allele Specific PCR (KASP) assays. Our objectives were to determine allelic variants known to affect flowering time, assess the effect of allelic variants on heading date, and investigate changes in the geographic and temporal distribution of alleles and haplotypes. Our analyses enhanced understanding of the roles developmental genes have on the timing of heading date in wheat under varying environmental conditions, which could be used by breeding programs to improve breeding strategies under current and future climate scenarios. The significant main effects and two-way interactions between the candidate genes explained an average of 44% of variability in heading date at each environment. Among the loci we evaluated, most of the variation in heading date was explained by Ppd-D1, Ppd-B1, and their interaction. The prevalence of the photoperiod sensitive alleles Ppd-A1b, Ppd-B1b, and Ppd-D1b has gradually decreased in U.S. Great Plains germplasm over the past century. There is also geographic variation for photoperiod sensitive and reduced-height alleles, with germplasm from breeding programs in the northern Great Plains having greater incidences of the photoperiod sensitive alleles and lower incidence of the semi-dwarf alleles than germplasm from breeding programs in the central or southern plains. PMID:27058239

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

    PubMed Central

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

    2011-01-01

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

  6. Polymorphism and predictability at the alpha-glycerophosphate dehydrogenase locus in Colias butterflies: gradients in allele frequency within single populations.

    PubMed

    Johnson, G B

    1976-06-01

    Heterozygosity at the alpha-glycerophosphate dehydrogenase locus of five species of Colias butterflies is widespread in montane populations; alpine and lowland populations are not heterozygous. Within a single demographically characterized population of C. meadii where the population extends from alpine down into montane habitats, a marked cline in allele frequency is seen. Such within-population clines suggest the involvement of strong selection across the marked ecological interface. Thermal factors are the most likely causative agents, but associative overdominance is not excluded.

  7. Insecticide Resistance Allele Frequencies in Anopheles gambiae before and after Anti-Vector Interventions in Continental Equatorial Guinea

    PubMed Central

    Reddy, Michael R.; Godoy, Adrian; Dion, Kirstin; Matias, Abrahan; Callender, Kevin; Kiszewski, Anthony E.; Kleinschmidt, Immo; Ridl, Frances C.; Powell, Jeffrey R.; Caccone, Adalgisa; Slotman, Michel A.

    2013-01-01

    Anti-malaria interventions that rely on insecticides can be compromised by insecticide-resistance alleles among malaria vectors. We examined frequency changes of resistance alleles at two loci, knockdown resistance (kdr) and acetylcholinesterase-1 (ace-1), which confer resistance to pyrethroids and DDT, and carbamates, respectively. A total of 7,059 Anopheles gambiae sensu stricto mosquitoes were analyzed from multiple sites across continental Equatorial Guinea. A subset of sites included samples collected pre-intervention (2007) and post-intervention (2009–2011). Both L1014S and L1014F resistance alleles were observed in almost all pre-intervention collections. In particular, L1014F was already at substantial frequencies in M form populations (17.6–74.6%), and at high frequencies (> 50%) in all but two S form populations. Comparison before and throughout anti-vector interventions showed drastic increases in L1014F, presumably caused by intensified selection pressure imposed by pyrethroids used in vector control efforts. In light of these findings, inclusion of other insecticide classes in any anti-vector intervention can be considered prudent. PMID:23438768

  8. Allelic and genotype frequencies of catechol-O-methyltransferase (Val158Met) and CYP2D6*10 (Pro34Ser) single nucleotide polymorphisms in the Philippines

    PubMed Central

    Baclig, Michael O; Predicala, Rey Z; Mapua, Cynthia A; Lozano-Kühne, Jingky P; Daroy, Maria Luisa G; Natividad, Filipinas F; Javier, Francis O

    2012-01-01

    A hospital-based cross-sectional study was conducted to determine the allelic and genotype frequencies in the genes encoding for catechol-O-methyltransferase and CYP2D6*10 among healthy volunteers and patients clinically diagnosed with cancer pain. PCR-RFLP was used to identify COMT and CYP2D6*10 genotypes. Allelic frequencies among healthy volunteer Filipinos were 0.83 and 0.17 for the COMT Val and COMT Met alleles, respectively. Calculated frequencies in Hardy-Weinberg equilibrium (HWE) were 73% for COMT Val/Val, 26% for COMT Val/Met, and 1% for COMT Met/Met genotype. For CYP2D6*10, allelic frequencies in HWE among volunteers were 0.46 for the C allele and 0.54 for the T allele. Twenty percent were identified as homozygous for the wild-type C/C genotype, 56% were identified as heterozygous for the C/T genotype, and 24% were identified as homozygous for the T/T variant genotype. No significant differences in COMT and CYP2D6*10 allele frequencies between cancer patients and healthy volunteers were noted. Our data demonstrated that the allele frequencies of COMT and CYP2D6*10 in the Filipino healthy volunteers were similar with other Asians but markedly different from Caucasian populations. PMID:22724048

  9. Allelic and genotype frequencies of catechol-O-methyltransferase (Val158Met) and CYP2D6*10 (Pro34Ser) single nucleotide polymorphisms in the Philippines.

    PubMed

    Baclig, Michael O; Predicala, Rey Z; Mapua, Cynthia A; Lozano-Kühne, Jingky P; Daroy, Maria Luisa G; Natividad, Filipinas F; Javier, Francis O

    2012-01-01

    A hospital-based cross-sectional study was conducted to determine the allelic and genotype frequencies in the genes encoding for catechol-O-methyltransferase and CYP2D6*10 among healthy volunteers and patients clinically diagnosed with cancer pain. PCR-RFLP was used to identify COMT and CYP2D6*10 genotypes. Allelic frequencies among healthy volunteer Filipinos were 0.83 and 0.17 for the COMT Val and COMT Met alleles, respectively. Calculated frequencies in Hardy-Weinberg equilibrium (HWE) were 73% for COMT Val/Val, 26% for COMT Val/Met, and 1% for COMT Met/Met genotype. For CYP2D6*10, allelic frequencies in HWE among volunteers were 0.46 for the C allele and 0.54 for the T allele. Twenty percent were identified as homozygous for the wild-type C/C genotype, 56% were identified as heterozygous for the C/T genotype, and 24% were identified as homozygous for the T/T variant genotype. No significant differences in COMT and CYP2D6*10 allele frequencies between cancer patients and healthy volunteers were noted. Our data demonstrated that the allele frequencies of COMT and CYP2D6*10 in the Filipino healthy volunteers were similar with other Asians but markedly different from Caucasian populations.

  10. Stochastic modelling of shifts in allele frequencies reveals a strongly polygynous mating system in the re-introduced Asiatic wild ass.

    PubMed

    Renan, Sharon; Greenbaum, Gili; Shahar, Naama; Templeton, Alan R; Bouskila, Amos; Bar-David, Shirli

    2015-04-01

    Small populations are prone to loss of genetic variation and hence to a reduction in their evolutionary potential. Therefore, studying the mating system of small populations and its potential effects on genetic drift and genetic diversity is of high importance for their viability assessments. The traditional method for studying genetic mating systems is paternity analysis. Yet, as small populations are often rare and elusive, the genetic data required for paternity analysis are frequently unavailable. The endangered Asiatic wild ass (Equus hemionus), like all equids, displays a behaviourally polygynous mating system; however, the level of polygyny has never been measured genetically in wild equids. Combining noninvasive genetic data with stochastic modelling of shifts in allele frequencies, we developed an alternative approach to paternity analysis for studying the genetic mating system of the re-introduced Asiatic wild ass in the Negev Desert, Israel. We compared the shifts in allele frequencies (as a measure of genetic drift) that have occurred in the wild ass population since re-introduction onset to simulated scenarios under different proportions of mating males. We revealed a strongly polygynous mating system in which less than 25% of all males participate in the mating process each generation. This strongly polygynous mating system and its potential effect on the re-introduced population's genetic diversity could have significant consequences for the long-term persistence of the population in the Negev. The stochastic modelling approach and the use of allele-frequency shifts can be further applied to systems that are affected by genetic drift and for which genetic data are limited.

  11. Frequency of the CCR5-delta32 allele in Brazilian populations: A systematic literature review and meta-analysis.

    PubMed

    Silva-Carvalho, Wlisses Henrique Veloso; de Moura, Ronald Rodrigues; Coelho, Antonio Victor Campos; Crovella, Sergio; Guimarães, Rafael Lima

    2016-09-01

    The CCR5 is a chemokine receptor widely expressed by several immune cells that are engaged in inflammatory responses. Some populations have individuals exhibiting a 32bp deletion in the CCR5 gene (CCR5-delta32) that produces a truncated non-functional protein not expressed on the cell surface. This polymorphism, known to be associated with susceptibility to infectious and inflammatory diseases, such as osteomyelitis, pre-eclampsia, systemic lupus erythematous, juvenile idiopathic arthritis, rheumatoid arthritis and HIV/AIDS, is more commonly found in European populations with average frequency of 10%. However, it is also possible to observe a significant frequency in other world populations, such as the Brazilian one. We performed a systematic review and meta-analysis of CCR5-delta32 genetic association studies in Brazilian populations throughout the country to estimate the frequency of this polymorphism. We also compared CCR5-delta32 frequencies across Brazilian regions. The systematic literature reviewed studies involving delta32 allele in Brazilian populations published from 1995 to 2015. Among the reviewed literature, 25 studies including 30 Brazilian populations distributed between the North, Northeast, South and Southeast regions were included in our meta-analysis. We observed an overall allelic frequency of 4% (95%-CI, 0.03-0.05), that was considered moderate and, notably, higher than some European populations, such as Cyprus (2.8%), Italy (3%) and Greece (2.4%). Regarding the regional frequency comparisons between North-Northeast (N-NE) and South-Southeast (S-SE) regions, we observed an allelic frequency of 3% (95%-CI, 0.02-0.04) and 4% (95%-CI, 0.03-0.05), respectively. The populations from S-SE regions had a slightly higher CCR5-delta32 frequency than N-NE regions (OR=1.41, p=0.002). Although there are several studies about the CCR5-delta32 polymorphism and its effect on the immune response of some infectious diseases, this report is the first meta

  12. Increase of TCR V beta accessibility within E beta regulatory region influences its recombination frequency but not allelic exclusion.

    PubMed

    Senoo, Makoto; Wang, Lili; Suzuki, Daisuke; Takeda, Naoki; Shinkai, Yoichi; Habu, Sonoko

    2003-07-15

    Seventy percent of the murine TCRbeta locus (475 kb) was deleted to generate a large deleted TCRbeta (beta(LD)) allele to investigate a possible linkage between germline transcription, recombination frequency, and allelic exclusion of the TCR Vbeta genes. In these beta(LD/LD) mice, the TCRbeta gene locus contained only four Vbeta genes at the 5' side of the locus, and consequently, the Vbeta10 gene was located in the original Dbeta1-Jbeta1cluster within the Ebeta regulatory region. We showed that the frequency of recombination and expression of the Vbeta genes are strongly biased to Vbeta10 in these mutant mice even though the proximity of the other three 5'Vbeta genes was also greatly shortened toward the Dbeta-Jbeta cluster and the Ebeta enhancer. Accordingly, the germline transcription of the Vbeta10 gene in beta(LD/LD) mice was exceptionally enhanced in immature double negative thymocytes compared with that in wild-type mice. During double negative-to-double positive transition of thymocytes, the level of Vbeta10 germline transcription was prominently increased in beta(LD/LD) recombination activating gene 2-deficient mice receiving anti-CD3epsilon Ab in vivo. Interestingly, however, despite the increased accessibility of the Vbeta10 gene in terms of transcription, allelic exclusion of this Vbeta gene was strictly maintained in beta(LD/LD) mice. These results provide strong evidence that increase of Vbeta accessibility influences frequency but not allelic exclusion of the TCR Vbeta rearrangement if the Vbeta gene is located in the Ebeta regulatory region.

  13. Prevalence of CYP2C19 alleles, pharmacokinetic and pharmacodynamic variation of clopidogrel and prasugrel in Bangladeshi population.

    PubMed

    Bin Sayeed, Muhammad Shahdaat; Hasan Apu, Mohd Nazmul; Munir, Maliha Tabassum; Ahmed, Maizbha Uddin; Islam, Mohammad Safiqul; Haq, M Maksumul; Ahsan, Chowdhury H; Rashid, M A; Shin, Jae Gook; Hasnat, Abul

    2015-05-01

    The extent to which cytochrome P450 (CYP) 2C19 genotype influences the effectiveness of clopidogrel remains uncertain due to considerable heterogeneity between studies. We used the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method for genotyping loss of function (LOF) allele, CYP2C19*2 and gain of function (GOF) allele, CYP2C19*17 in 163 patients undergoing PCI and 165 healthy volunteers from an ethnically distinctive Bangladeshi population. Thirty-eight patients took prasugrel and 125 patients took clopidogrel among whom 30 patients had their clopidogrel active metabolites (CAM) determined by LC-MS/MS 1-1.5 h after clopidogrel intake. All patients who underwent PCI had their P2Y12 per cent inhibition (PRI) measured by VerifyNow System. The impact of different genotypes on CAM and PRI were also determined. We did not find significant variation of CYP2C19*2 (P > 0.05) and CYP2C9*17 (P > 0.05) alleles among healthy volunteers and patients. CAM concentration as well as PRI by clopidogrel varied significantly (P < 0.05) based on genotypic variation of CYP2C19*2 and CYP2C19*17 individually. Such influence was not observed in case of prasugrel. Genotypic variation did not impact PRI but as a whole PRI by prasugrel was better than that of clopidogrel (P < 0.05). Due to presence of both of alleles the effect on PRI by clopidogrel could not be predicted, effectively indicating possible involvement of other factors. Genotype guided clopidogrel dose adjustment would be beneficial and therefore we propose mandatory genotyping before clopidogrel dosing. Prasugrel proved to be less affected by genotypic variability, but due to lack of sufficient long-term toxicity data, caution would be adopted before substituting clopidogrel.

  14. Frequency of alleles conferring resistance to the Bt toxins Cry1Ac and Cry2Ab in Australian populations of Helicoverpa armigera (Lepidoptera: Noctuidae).

    PubMed

    Mahon, R J; Olsen, K M; Downes, S; Addison, S

    2007-12-01

    Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) is an important lepidopteran pest of cotton (Gossypium spp.) in Australia and the Old World. From 2002, F2 screens were used to examine the frequency of resistance alleles in Australian populations of H. armigera to Bacillus thuringiensis (Bt) CrylAc and Cry2Ab, the two insecticidal proteins present in the transgenic cotton Bollgard II. At that time, Ingard (expressing Cry1Ac) cotton had been grown in Australia for seven seasons, and Bollgard II was about to be commercially released. The principal objective of our study was to determine whether sustained exposure caused an elevated frequency of alleles conferring resistance to Cry1Ac in a species with a track record of evolving resistance to conventional insecticides. No major alleles conferring resistance to Cry1Ac were found. The frequency of resistance alleles for Cry1Ac was <0.0003, with a 95% credibility interval between 0 and 0.0009. In contrast, alleles conferring resistance to Cry2Ab were found at a frequency of 0.0033 (0.0017, 0.0055). The first isolation of this allele was found before the widespread deployment of Bollgard II. For both toxins the experiment-wise detection probability was 94.4%. Our results suggest that alleles conferring resistance to Cry1Ac are rare and that a relatively high baseline frequency of alleles conferring resistance to Cry2Ab existed before the introduction of Bt cotton containing this toxin.

  15. Interdecadal variation of TC frequency in Japan

    NASA Astrophysics Data System (ADS)

    Choi, Ki-Seon; Cha, Yu-Mi; Kang, Sung-Dae; Kim, Hae-Dong

    2015-07-01

    This study analyzed the climate regime shift using statistical change-point analysis on the time-series tropical cyclone (TC) frequency that affected Japan in July to September. The result showed that there was a significant change in 1995, and since then, it showed a trend of rapidly decreasing frequency. To determine the reason for this, differences between 1995 to 2012 (9512) period and 1978 to 1994 (7894) period were analyzed. First, regarding TC genesis, TCs during the 9512 period showed a characteristic of genesis from the southeast quadrant of the tropical and subtropical western North Pacific and TCs during the 7894 period showed their genesis from the northwest quadrant. Regarding a TC track, TCs in the 7894 period had a strong trend of moving from the far east sea of the Philippines via the East China Sea to the mid-latitude region in East Asia while TCs in the 9512 period showed a trend of moving from the Philippines toward the southern part of China westward. Thus, TC intensity in the 7894 period, which can absorb sufficient energy from the sea as they moved a long distance over the sea, was stronger than that of 9512. Large-scale environments were analyzed to determine the cause of such difference in TC activity occurred between two periods. During the 9512 period, anomalous cold and dry anticyclones were developed strongly in the East Asia continent. As a result, Korea and Japan were affected by the anomalous northerlies thereby preventing TCs in this period from moving toward the mid-latitude region in East Asia. Instead, anomalous easterlies (anomalous trade wind) were developed in the tropical western Pacific so that a high passage frequency from the Philippines to the south China region along the anomalous steering flows was revealed. The characteristics of the anomalous cold and dry anticyclone developed in the East Asia continent were also confirmed by the analysis of air temperature, relative humidity, and sensible heat net flux showing that

  16. Plasminogen Activator Inhibitor-1 (PAI-1) gene 4G/5G alleles frequency distribution in the Lebanese population.

    PubMed

    Shammaa, Dina M R; Sabbagh, Amira S; Taher, Ali T; Zaatari, Ghazi S; Mahfouz, Rami A R

    2008-09-01

    Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of fibrinolysis. Increased plasma PAI-1 levels play an essential role in the pathogenesis of cardiovascular risk and other diseases associated with thrombosis. The 4G/5G polymorphism of the PAI-1 promoter region has been extensively studied in different populations. We studied 160 healthy unrelated Lebanese individuals using a reverse hybridization PCR assay to detect the 5G/5G, 4G/5G and, 4G/4G genotypes of the PAI-1 gene and the frequencies of the 4G and 5G alleles. We found that 4G/5G genotype was the most prevalent (45.6%) followed by 5G/5G (36.9%) and 4G/4G (17.5%). The frequencies of the 4G and 5G alleles were calculated to be 0.403 and 0.597, respectively. Compared to other ethnic communities, the Lebanese population was found to harbour a relatively high prevalence of the rare 4G allele. This, in turn, may predispose this population to develop cardiovascular diseases and other thrombotic clinical conditions. This study aids to enhance our understanding of the genetic features of the Lebanese population.

  17. Mytilus galloprovincialis-type foot-protein-1 alleles occur at low frequency among mussels in the Dutch Wadden Sea

    NASA Astrophysics Data System (ADS)

    Luttikhuizen, Pieternella C.; Koolhaas, Anita; Bol, Anneke; Piersma, Theunis

    2002-11-01

    The presence of M. galloprovincialis-type genes among the population of mussels in the Dutch Wadden Sea, historically described as M. edulis, was assessed. We applied the molecular technique in which a fragment of the gene coding for an adhesive protein of the byssus of mussels is amplified by PCR and assayed for length using electrophoresis. Among 321 individual mussels collected in August-October 2001 at 14 sites (5 intertidal, 9 subtidal) widely dispersed over the Dutch Wadden Sea, 6 specimens (collected at 5 sites) were found that showed a heterozygote genotype with both the M. edulis- and the M. galloprovincialis-type alleles being amplified; all others were identified as homozygotes for the M. edulis-type allele. Differentiation in frequencies of heterozygotes among sites was not detected. The fact that the M. galloprovincialis-type allele was present at low frequency (0.0093) may be attributed to one of three possible, and not mutually exclusive, causes: incomplete diagnosticity of this marker, an historically stable introgression zone in the Wadden Sea, or a recent invasion.

  18. Allele frequencies of combined DNA index system (CODIS) and non-CODIS short tandem repeat loci in Goiás, Central Brazil.

    PubMed

    Rodovalho, R G; Santos, G S; Cavalcanti, L M; Moura, B F S M; Rodrigues, E L; Lima, P R; Gigonzac, M A D; Vieira, T C

    2015-07-03

    In studies of human identification, obtaining a high standard of outcomes and satisfactory conclusions are directly related to the use of highly polymorphic molecular markers. In addition to the combined DNA index system (CODIS) group, it is also important to implement non-CODIS markers into the analysis, as they increase the power of discrimination. During the identification process, it is essential to consider the genetic variation among distinct groups of populations, as the allele frequencies are directly associated with the power of discrimination. However, the population of Goiás, a State located in Central Brazil, is characterized by a highly mixed population due to its diverse ethnic origins. In this study, a survey of the allelic frequencies in the Goiás population was carried out using a molecular assembly composed of 21 autosomal loci both from and external to the CODIS group. The new data, for some of the markers used, were statistically similar to those from previous studies. This consistency means that the use of these markers might serve as a parameter for future population comparisons. The results from these analyses further our knowledge of the study of human identification.

  19. 46 CFR 111.01-17 - Voltage and frequency variations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ....01-17 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS General § 111.01-17 Voltage and frequency variations. Unless otherwise stated, electrical equipment must function at variations of at least ±5 percent of rated...

  20. 46 CFR 111.01-17 - Voltage and frequency variations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....01-17 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS General § 111.01-17 Voltage and frequency variations. Unless otherwise stated, electrical equipment must function at variations of at least ±5 percent of rated...

  1. 46 CFR 111.01-17 - Voltage and frequency variations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ....01-17 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) ELECTRICAL ENGINEERING ELECTRIC SYSTEMS-GENERAL REQUIREMENTS General § 111.01-17 Voltage and frequency variations. Unless otherwise stated, electrical equipment must function at variations of at least ±5 percent of rated...

  2. Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects.

    PubMed

    Gelernter, J; Kranzler, H; Cubells, J F

    1997-12-01

    The SLC6A4 locus encodes the serotonin transporter, which in turn mediates the synaptic inactivation of the neurotransmitter serotonin. Two PCR-formatted polymorphisms at this locus have been described, the first of which is a variable number tandem repeat located in exon 2, and the second a repeat sequence polymorphism located in the promoter region. The latter polymorphism alters transcriptional activity of SLC6A4, and has been reported to be associated with anxiety and depression-related traits. We studied allele frequencies, and computed haplotype frequencies and linkage disequilibrium measures, for these two polymorphisms in European-American, African-American, and Japanese populations, and in a set of alcohol-dependent European-American subjects. Allele frequencies for both systems showed variation, with significant differences overall for each system, and significant differences between each pair of populations for both systems. Linkage disequilibrium also varied among the populations. There were no significant differences in allele or haplotype frequencies between the European-American population samples and alcohol-dependent subjects. The population differences demonstrate a potential for population stratification in association studies of either of these SLC6A4 polymorphisms. If genetic variation at this locus really is associated with behavioral variation, these results could reflect either different behavioral adaptations in different populations, or random genetic drift of a behaviorally important but selectively neutral polymorphism.

  3. Unequal allelic frequencies at the self-incompatibility locus within local populations of Prunus avium L.: an effect of population structure?

    PubMed

    Stoeckel, S; Castric, V; Mariette, S; Vekemans, X

    2008-05-01

    In this paper, we investigated the genetic structure and distribution of allelic frequencies at the gametophytic self-incompatibility locus in three populations of Prunus avium L. In line with theoretical predictions under balancing selection, genetic structure at the self-incompatibility locus was almost three times lower than at seven unlinked microsatellites. Furthermore, we found that S-allele frequencies in wild cherry populations departed significantly from the expected isoplethic distribution towards which balancing selection is expected to drive allelic frequencies (i.e. identical frequency equal to the inverse of the number of alleles in the population). To assess whether this departure could be caused either by drift alone or by population structure, we used numerical simulations to compare our observations with allelic frequency distributions expected : (1) within a single deme from a subdivided population with various levels of differentiation; and (2) within a finite panmictic population with identical allelic diversity. We also investigated the effects of sample size and degree of population structure on tests of departure from isoplethic equilibrium. Overall, our results showed that the observed allele frequency distributions were consistent with a model of subdivided population with demes linked by moderate migration rate.

  4. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations.

    PubMed

    González-Galarza, Faviel F; Takeshita, Louise Y C; Santos, Eduardo J M; Kempson, Felicity; Maia, Maria Helena Thomaz; da Silva, Andrea Luciana Soares; Teles e Silva, André Luiz; Ghattaoraya, Gurpreet S; Alfirevic, Ana; Jones, Andrew R; Middleton, Derek

    2015-01-01

    It has been 12 years since the Allele Frequency Net Database (AFND; http://www.allelefrequencies.net) was first launched, providing the scientific community with an online repository for the storage of immune gene frequencies in different populations across the world. There have been a significant number of improvements from the first version, making AFND a primary resource for many clinical and scientific areas including histocompatibility, immunogenetics, pharmacogenetics and anthropology studies, among many others. The most widely used part of AFND stores population frequency data (alleles, genes or haplotypes) related to human leukocyte antigens (HLA), killer-cell immunoglobulin-like receptors (KIR), major histocompatibility complex class I chain-related genes (MIC) and a number of cytokine gene polymorphisms. AFND now contains >1400 populations from more than 10 million healthy individuals. Here, we report how the main features of AFND have been updated to include a new section on 'HLA epitope' frequencies in populations, a new section capturing the results of studies identifying HLA associations with adverse drug reactions (ADRs) and one for the examination of infectious and autoimmune diseases associated with KIR polymorphisms-thus extending AFND to serve a new user base in these growing areas of research. New criteria on data quality have also been included.

  5. The GM2 gangliosidoses databases: allelic variation at the HEXA, HEXB, and GM2A gene loci.

    PubMed

    Cordeiro, P; Hechtman, P; Kaplan, F

    2000-01-01

    The GM2 gangliosidoses are a group of recessive disorders characterized by accumulation of GM2 ganglioside in neuronal cells. The genes responsible for these disorders are HEXA (Tay-Sachs disease and variants), HEXB (Sandhoff disease and variants), and GM2A (AB variant of GM2 gangliosidosis). We report the establishment of three relational locus-specific databases recording allelic variation at the HEXA, HEXB, and GM2A genes and accessed at the GM2 gangliosidoses home page (http://data.mch.mcgill.ca/gm2-gangliosidoses). Submission forms are available for the addition of new mutations to the databases. The databases are available online for users to search and retrieve information about specific alleles by a number of fields describing mutations, phenotypes, or author(s).

  6. Description and Power Analysis of Two Tests for Detecting Recent Population Bottlenecks from Allele Frequency Data

    PubMed Central

    Cornuet, J. M.; Luikart, G.

    1996-01-01

    When a population experiences a reduction of its effective size, it generally develops a heterozygosity excess at selectively neutral loci, i.e., the heterozygosity computed from a sample of genes is larger than the heterozygosity expected from the number of alleles found in the sample if the population were at mutation drift equilibrium. The heterozygosity excess persists only a certain number of generations until a new equilibrium is established. Two statistical tests for detecting a heterozygosity excess are described. They require measurements of the number of alleles and heterozygosity at each of several loci from a population sample. The first test determines if the proportion of loci with heterozygosity excess is significantly larger than expected at equilibrium. The second test establishes if the average of standardized differences between observed and expected heterozygosities is significantly different from zero. Type I and II errors have been evaluated by computer simulations, varying sample size, number of loci, bottleneck size, time elapsed since the beginning of the bottleneck and level of variability of loci. These analyses show that the most useful markers for bottleneck detection are those evolving under the infinite allele model (IAM) and they provide guidelines for selecting sample sizes of individuals and loci. The usefulness of these tests for conservation biology is discussed. PMID:8978083

  7. Allelic variation at the vernalization and photoperiod sensitivity loci in Chinese winter wheat cultivars (Triticum aestivum L.).

    PubMed

    Zhang, Xiangfen; Gao, Manxia; Wang, Shasha; Chen, Feng; Cui, Dangqun

    2015-01-01

    A total of 205 wheat cultivars from the Yellow and Huai valley of China were used to identify allelic variations of vernalization and photoperiod response genes, as well as the copy number variations (CNVs) of Ppd-B1 and Vrn-A1 genes. A novel Vrn-D1 allele with 174-bp insertion in the promoter region of the recessive allele vrn-D1 was discovered in three Chinese wheat cultivars and designated as Vrn-D1c. Quantitative real-time polymerase chain reaction showed that cultivars with the Vrn-D1c allele exhibited significantly higher expression of the Vrn-D1 gene than that in cultivars with the recessive allele vrn-D1, indicating that the 174-bp insertion of Vrn-D1c contributed to the increase in Vrn-D1 gene expression and caused early heading and flowering. The five new cis-elements (Box II-like, 3-AF1 binding site, TC-rich repeats, Box-W1 and CAT-box) in the 174-bp insertion possibly promoted the basal activity level of Vrn-D1 gene. Two new polymorphism combinations of photoperiod genes were identified and designated as Ppd-D1_Hapl-IX and Ppd-D1_Hapl-X. Association of the CNV of Ppd-B1 gene with the heading and flowering days showed that the cultivars with Ppd-B1_Hapl-VI demonstrated the earliest heading and flowering times, and those with Ppd-B1_Hapl-IV presented the latest heading and flowering times in three cropping seasons. Distribution of the vernalization and photoperiod response genes indicated that all recessive alleles at the four vernalization response loci, Ppd-B1_Hapl-I at Ppd-B1 locus, and Ppd-D1_Hapl-I at the Ppd-D1 locus were predominant in Chinese winter wheat cultivars. This study can provide useful information for wheat breeding programs to screen wheat cultivars with relatively superior adaptability and maturity.

  8. Allelic variation at the vernalization and photoperiod sensitivity loci in Chinese winter wheat cultivars (Triticum aestivum L.)

    PubMed Central

    Zhang, Xiangfen; Gao, Manxia; Wang, Shasha; Chen, Feng; Cui, Dangqun

    2015-01-01

    A total of 205 wheat cultivars from the Yellow and Huai valley of China were used to identify allelic variations of vernalization and photoperiod response genes, as well as the copy number variations (CNVs) of Ppd-B1 and Vrn-A1 genes. A novel Vrn-D1 allele with 174-bp insertion in the promoter region of the recessive allele vrn-D1 was discovered in three Chinese wheat cultivars and designated as Vrn-D1c. Quantitative real-time polymerase chain reaction showed that cultivars with the Vrn-D1c allele exhibited significantly higher expression of the Vrn-D1 gene than that in cultivars with the recessive allele vrn-D1, indicating that the 174-bp insertion of Vrn-D1c contributed to the increase in Vrn-D1 gene expression and caused early heading and flowering. The five new cis-elements (Box II-like, 3-AF1 binding site, TC-rich repeats, Box-W1 and CAT-box) in the 174-bp insertion possibly promoted the basal activity level of Vrn-D1 gene. Two new polymorphism combinations of photoperiod genes were identified and designated as Ppd-D1_Hapl-IX and Ppd-D1_Hapl-X. Association of the CNV of Ppd-B1 gene with the heading and flowering days showed that the cultivars with Ppd-B1_Hapl-VI demonstrated the earliest heading and flowering times, and those with Ppd-B1_Hapl-IV presented the latest heading and flowering times in three cropping seasons. Distribution of the vernalization and photoperiod response genes indicated that all recessive alleles at the four vernalization response loci, Ppd-B1_Hapl-I at Ppd-B1 locus, and Ppd-D1_Hapl-I at the Ppd-D1 locus were predominant in Chinese winter wheat cultivars. This study can provide useful information for wheat breeding programs to screen wheat cultivars with relatively superior adaptability and maturity. PMID:26191066

  9. Physics of systematic frequency variations in hydrogen masers

    NASA Technical Reports Server (NTRS)

    Mattison, Edward M.

    1990-01-01

    The frequency stability of hydrogen masers for intervals longer that 10(exp 4) seconds is limited at present by systematic processes. Researchers discuss the physics of frequency-determining mechanisms internal to the maser that are susceptible to systematic variations, and the connections between these internal mechanisms and external environmental factors. Based upon estimates of the magnitudes of systematic effects, they find that the primary internal mechanisms currently limiting long-term maser frequency stability are cavity pulling, at the level parts in 10(exp 15) per day, and wall shift variations, at the level of parts in 10(exp 16) to parts in 10(exp 15) per day. They discuss strategies for reducing systematic frequency variations.

  10. Physics of systematic frequency variations in hydrogen masers

    NASA Technical Reports Server (NTRS)

    Mattison, Edward M.

    1992-01-01

    The frequency stability of hydrogen masers for intervals longer than 10 exp 4 s is currently limited by systematic processes. The physics of frequency-determining mechanisms internal to the maser that are susceptible to systematic variations, and the connections between these internal mechanisms and external environmental factors are discussed. From estimates of the magnitudes of systematic effects, it is found that the primary internal mechanisms limiting long-term maser frequency stability are cavity pulling, at the level of parts in 1015 per day, and wall shift variations, at the level of parts in 10 exp 16 to parts in 10 exp 15 per day. Strategies for reducing systematic frequency variations are discussed.

  11. Maximum-likelihood and markov chain monte carlo approaches to estimate inbreeding and effective size from allele frequency changes.

    PubMed Central

    Laval, Guillaume; SanCristobal, Magali; Chevalet, Claude

    2003-01-01

    Maximum-likelihood and Bayesian (MCMC algorithm) estimates of the increase of the Wright-Malécot inbreeding coefficient, F(t), between two temporally spaced samples, were developed from the Dirichlet approximation of allelic frequency distribution (model MD) and from the admixture of the Dirichlet approximation and the probabilities of fixation and loss of alleles (model MDL). Their accuracy was tested using computer simulations in which F(t) = 10% or less. The maximum-likelihood method based on the model MDL was found to be the best estimate of F(t) provided that initial frequencies are known exactly. When founder frequencies are estimated from a limited set of founder animals, only the estimates based on the model MD can be used for the moment. In this case no method was found to be the best in all situations investigated. The likelihood and Bayesian approaches give better results than the classical F-statistics when markers exhibiting a low polymorphism (such as the SNP markers) are used. Concerning the estimations of the effective population size all the new estimates presented here were found to be better than the F-statistics classically used. PMID:12871924

  12. Incorporating allelic variation for reconstructing the evolutionary history of organisms from multiple genes: An example from Rosa in North America.

    PubMed

    Joly, Simon; Bruneau, Anne

    2006-08-01

    Allelic variation within individuals holds information regarding the relationships of organisms, which is expected to be particularly important for reconstructing the evolutionary history of closely related taxa. However, little effort has been committed to incorporate such information for reconstructing the phylogeny of organisms. Haplotype trees represent a solution when one nonrecombinant marker is considered, but there is no satisfying method when multiple genes are to be combined. In this paper, we propose an algorithm that converts a distance matrix of alleles to a distance matrix among organisms. This algorithm allows the incorporation of allelic variation for reconstructing the phylogeny of organisms from one or more genes. The method is applied to reconstruct the phylogeny of the seven native diploid species of Rosa sect. Cinnamomeae in North America. The glyceralgehyde 3-phosphate dehydrogenase (GAPDH), the triose phosphate isomerase (TPI), and the malate synthase (MS) genes were sequenced for 40 individuals from these species. The three genes had little genetic variation, and most species showed incomplete lineage sorting, suggesting these species have a recent origin. Despite these difficulties, the networks (NeighborNet) of organisms reconstructed from the matrix obtained with the algorithm recovered groups that more closely match taxonomic boundaries than did the haplotype trees. The combined network of individuals shows that species west of the Rocky Mountains, Rosa gymnocarpa and R. pisocarpa, form exclusive groups and that together they are distinct from eastern species. In the east, three groups were found to be exclusive: R. nitida-R. palustris, R. foliolosa, and R. blanda-R. woodsii. These groups are congruent with the morphology and the ecology of species. The method is also useful for representing hybrid individuals when the relationships are reconstructed using a phylogenetic network.

  13. Beta-thalassemia mutations in Rome. A high frequency of the IVSII-745 allele in subjects of latium origin.

    PubMed

    Massa, A; Cianciulli, P; Cianetti, L; Iazzone, R; Cenci, A; Sorrentino, F; Franco, G; Pecci, G; Papa, G; Peschle, C

    1994-01-01

    We studied the molecular bases of beta-thalassemia in Rome, a city centrally located in Latium, which is a region with a low incidence of beta-carriers. People also come to Rome from other regions for specific or prenatal diagnostic assessment. Only 11 patients (20%) out of 62 characterized beta-thalassemia subjects were of Latium family origin. They presented five mutations with an uncommonly high frequency of the IVSII-745 allele, that was found in homozygosis in 4 unrelated patients from a southeastern area in the province of Frosinone. These data may indicate a founder effect.

  14. vidence of low genetic variation and rare alleles in a bottlenecked endangered island endemic, the Lasan Teal (Anas laysanensis)

    USGS Publications Warehouse

    Reynolds, Michelle H.; Pearce, John M.; Lavretsky, Philip; Peters Jeffrey L,; Courtot, Karen; Seixas, Pedro P.

    2015-01-01

    Genetic diversity is assumed to reflect the evolutionary potential and adaptability of populations, and thus quantifying the genetic diversity of endangered species is useful for recovery programs. In particular, if conservation strategies include reintroductions, periodic genetic assessments are useful to evaluate whether management efforts have resulted in the maximization or loss of genetic variation within populations over generations. In this study, we collected blood, feather, and tissue samples during 1999–2009 and quantified genetic diversity for a critically endangered waterfowl species endemic to the Hawaiian archipelago, the Laysan teal or duck (Anas laysanensis; n = 239 individual birds sampled). The last extant population of this species at Laysan Island was sourced in 2004–2005 for a ‘wild to wild’ translocation of 42 individuals for an experimental reintroduction to Midway Atoll. To inform future management strategies, we compared genetic diversity sampled from the source population (n = 133 Laysan birds) including 23 of Midway’s founders and offspring of the translocated population 2–5 years post release (n = 96 Midway birds). We attempted to identify polymorphic markers by screening nuclear microsatellite (N = 83) and intronic loci (N = 19), as well as the mitochondrial control region (mtDNA) for a subset of samples. Among 83 microsatellite loci screened, six were variable. We found low nuclear variation consistent with the species’ historical population bottlenecks and sequence variation was observed at a single intron locus. We detected no variation within the mtDNA. We found limited but similar estimates of allelic richness (2.58 alleles per locus) and heterozygosity within islands. Two rare alleles found in the Laysan Island source population were not present in the Midway translocated group, and a rare allele was discovered in an individual on Midway in 2008. We found similar genetic diversity and low, but statistically

  15. Inheritance of Cry1F resistance, cross-resistance and frequency of resistant alleles in Spodoptera frugiperda (Lepidoptera: Noctuidae).

    PubMed

    Vélez, A M; Spencer, T A; Alves, A P; Moellenbeck, D; Meagher, R L; Chirakkal, H; Siegfried, B D

    2013-12-01

    Transgenic maize, Zea maize L., expressing the Cry1F protein from Bacillus thuringiensis has been registered for Spodoptera frugiperda (J. E. Smith) control since 2003. Unexpected damage to Cry1F maize was reported in 2006 in Puerto Rico and Cry1F resistance in S. frugiperda was documented. The inheritance of Cry1F resistance was characterized in a S. frugiperda resistant strain originating from Puerto Rico, which displayed >289-fold resistance to purified Cry1F. Concentration-response bioassays of reciprocal crosses of resistant and susceptible parental populations indicated that resistance is recessive and autosomal. Bioassays of the backcross of the F1 generation crossed with the resistant parental strain suggest that a single locus is responsible for resistance. In addition, cross-resistance to Cry1Aa, Cry1Ab, Cry1Ac, Cry1Ba, Cry2Aa and Vip3Aa was assessed in the Cry1F-resistant strain. There was no significant cross-resistance to Cry1Aa, Cry1Ba and Cry2Aa, although only limited effects were observed in the susceptible strain. Vip3Aa was highly effective against susceptible and resistant insects indicating no cross-resistance with Cry1F. In contrast, low levels of cross-resistance were observed for both Cry1Ab and Cry1Ac. Because the resistance is recessive and conferred by a single locus, an F1 screening assay was used to measure the frequency of Cry1F-resistant alleles from populations of Florida and Texas in 2010 and 2011. A total frequency of resistant alleles of 0.13 and 0.02 was found for Florida and Texas populations, respectively, indicating resistant alleles could be found in US populations, although there have been no reports of reduced efficacy of Cry1F-expressing plants.

  16. Lack of adaptation from standing genetic variation despite the presence of putatively adaptive alleles in introduced sweet vernal grass (Anthoxanthum odoratum).

    PubMed

    Gould, B; Geber, M

    2016-01-01

    Population genetic theory predicts that the availability of appropriate standing genetic variation should facilitate rapid evolution when species are introduced to new environments. However, few tests of rapid evolution have been paired with empirical surveys for the presence of previously identified adaptive genetic variants in natural populations. In this study, we examined local adaptation to soil Al toxicity in the introduced range of sweet vernal grass (Anthoxanthum odoratum), and we genotyped populations for the presence of Al tolerance alleles previously identified at the long-term ecological Park Grass Experiment (PGE, Harpenden, UK) in the species native range. We found that markers associated with Al tolerance at the PGE were present at appreciable frequency in introduced populations. Despite this, there was no strong evidence of local adaptation to soil Al toxicity among populations. Populations demonstrated significantly different intrinsic root growth rates in the absence of Al. This suggests that selection on correlated root growth traits may constrain the ability of populations to evolve significantly different root growth responses to Al. Our results demonstrate that genotype-phenotype associations may differ substantially between the native and introduced parts of a species range and that adaptive alleles from a native species range may not necessarily promote phenotypic differentiation in the introduced range.

  17. Allelic sequence variation of the HLA-DQ loci: relationship to serology and to insulin-dependent diabetes susceptibility.

    PubMed Central

    Horn, G T; Bugawan, T L; Long, C M; Erlich, H A

    1988-01-01

    Analysis of sequence variation in the polymorphic second exon of the major histocompatibility complex genes HLA-DQ alpha and -DQ beta has revealed 8 allelic variants at the alpha locus and 13 variants at the beta locus. Correlation of sequence variation with serologic typing suggests that the DQw2, DQw3, and DQ(blank) types are determined by the DQ beta subunit, while the DQw1 specificity is determined by DQ alpha. The nature of the amino acid at position 57 in the DQ beta subunit is correlated with susceptibility to insulin-dependent diabetes mellitus. This region of the DQ beta chain contains shared peptides with Epstein-Barr virus and rubella virus. PMID:2842756

  18. Positive Selection of Deleterious Alleles through Interaction with a Sex-Ratio Suppressor Gene in African Buffalo: A Plausible New Mechanism for a High Frequency Anomaly

    PubMed Central

    van Hooft, Pim; Greyling, Ben J.; Getz, Wayne M.; van Helden, Paul D.; Zwaan, Bas J.; Bastos, Armanda D. S.

    2014-01-01

    Although generally rare, deleterious alleles can become common through genetic drift, hitchhiking or reductions in selective constraints. Here we present a possible new mechanism that explains the attainment of high frequencies of deleterious alleles in the African buffalo (Syncerus caffer) population of Kruger National Park, through positive selection of these alleles that is ultimately driven by a sex-ratio suppressor. We have previously shown that one in four Kruger buffalo has a Y-chromosome profile that, despite being associated with low body condition, appears to impart a relative reproductive advantage, and which is stably maintained through a sex-ratio suppressor. Apparently, this sex-ratio suppressor prevents fertility reduction that generally accompanies sex-ratio distortion. We hypothesize that this body-condition-associated reproductive advantage increases the fitness of alleles that negatively affect male body condition, causing genome-wide positive selection of these alleles. To investigate this we genotyped 459 buffalo using 17 autosomal microsatellites. By correlating heterozygosity with body condition (heterozygosity-fitness correlations), we found that most microsatellites were associated with one of two gene types: one with elevated frequencies of deleterious alleles that have a negative effect on body condition, irrespective of sex; the other with elevated frequencies of sexually antagonistic alleles that are negative for male body condition but positive for female body condition. Positive selection and a direct association with a Y-chromosomal sex-ratio suppressor are indicated, respectively, by allele clines and by relatively high numbers of homozygous deleterious alleles among sex-ratio suppressor carriers. This study, which employs novel statistical techniques to analyse heterozygosity-fitness correlations, is the first to demonstrate the abundance of sexually-antagonistic genes in a natural mammal population. It also has important

  19. Positive selection of deleterious alleles through interaction with a sex-ratio suppressor gene in African Buffalo: a plausible new mechanism for a high frequency anomaly.

    PubMed

    van Hooft, Pim; Greyling, Ben J; Getz, Wayne M; van Helden, Paul D; Zwaan, Bas J; Bastos, Armanda D S

    2014-01-01

    Although generally rare, deleterious alleles can become common through genetic drift, hitchhiking or reductions in selective constraints. Here we present a possible new mechanism that explains the attainment of high frequencies of deleterious alleles in the African buffalo (Syncerus caffer) population of Kruger National Park, through positive selection of these alleles that is ultimately driven by a sex-ratio suppressor. We have previously shown that one in four Kruger buffalo has a Y-chromosome profile that, despite being associated with low body condition, appears to impart a relative reproductive advantage, and which is stably maintained through a sex-ratio suppressor. Apparently, this sex-ratio suppressor prevents fertility reduction that generally accompanies sex-ratio distortion. We hypothesize that this body-condition-associated reproductive advantage increases the fitness of alleles that negatively affect male body condition, causing genome-wide positive selection of these alleles. To investigate this we genotyped 459 buffalo using 17 autosomal microsatellites. By correlating heterozygosity with body condition (heterozygosity-fitness correlations), we found that most microsatellites were associated with one of two gene types: one with elevated frequencies of deleterious alleles that have a negative effect on body condition, irrespective of sex; the other with elevated frequencies of sexually antagonistic alleles that are negative for male body condition but positive for female body condition. Positive selection and a direct association with a Y-chromosomal sex-ratio suppressor are indicated, respectively, by allele clines and by relatively high numbers of homozygous deleterious alleles among sex-ratio suppressor carriers. This study, which employs novel statistical techniques to analyse heterozygosity-fitness correlations, is the first to demonstrate the abundance of sexually-antagonistic genes in a natural mammal population. It also has important

  20. HLA-DRB1 and HLA-DQB1 allele associations in an Albanian patient population with rheumatoid arthritis: correlations with the specific autoantibody markers and inter-population DRB1 allele frequency variability.

    PubMed

    Prifti-Kurti, Margarita; Nunes, José Manuel; Shyti, Erkena; Ylli, Zamira; Sanchez-Mazas, Alicia; Sulcebe, Genc

    2014-08-01

    The prevalence of rheumatoid arthritis and its specific autoantibodies varies in different populations. This variability depends on the genetic polymorphism of the immune response genes among which the HLA system plays a major role. In this context, we studied the HLA-DRB1 and HLA-DQB1 first-level allele frequencies in 100 Albanian patients with rheumatoid arthritis (RA), and taking into account their rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA) serologic subgroups, we compared them with the respective frequencies in a population of 191 Albanian individuals without known pathology. No differences were found between the controls and the RA patient group as a whole, but three statistically significant differences were found: an increase in DRB1*04 among ACPA+, RF+ and ACPA+/RF+ patients, a significant decrease in DRB1*11 among ACPA+/RF+ and also a decrease in DRB1*13 among RF+ patient subgroups. Comparing allele frequencies of putatively associated RA alleles in different European populations revealed a significant negative correlation between the RA predisposing DRB1*04 and protective DRB1*11 allele frequencies. A statistically significant correlation was also found between RA prevalence rates and DRB1*04 as well as DRB1*11 frequencies. The relatively low frequencies of DRB1*04 and high DRB1*11 in the Albanian population might explain the rather low positivity rate of ACPA and RF antibodies among the Albanian RA patients. These specific association patterns suggest that this first study of RA in an Albanian population should be followed up to include second level or higher definition of HLA alleles and to compare RA patterns among European populations.

  1. Allelic variation in PtoPsbW associated with photosynthesis, growth, and wood properties in Populus tomentosa.

    PubMed

    Wang, Longxin; Wang, Bowen; Du, Qingzhang; Chen, Jinhui; Tian, Jiaxing; Yang, Xiaohui; Zhang, Deqiang

    2017-02-01

    Photosynthesis is one of the most important reactions on earth. PsbW, a nuclear-encoded subunit of photosystem II (PSII), stabilizes PSII structure and plays an important role in photosynthesis. Here, we used candidate gene-based linkage disequilibrium (LD) mapping to detect significant associations between allelic variations of PtoPsbW and traits related to photosynthesis, growth, and wood properties in Populus tomentosa. PtoPsbW showed the highest expression in leaves and it increased during the development of these leaves, suggesting that PtoPsbW may play an important role in plant growth and development. Analysis of nucleotide diversity and LD revealed that PtoPsbW has low single-nucleotide polymorphism (SNP) diversity (π tot = 0.0048 and θ w = 0.0050) and relatively low average value of LD (0.1500), indicating that PtoPsbW is conserved due to its indispensable function. Using single-SNP associations in an association population of 435 individuals, we identified five significant associations at the threshold of P ≤ 0.05, explaining 3.28-15.98 % of the phenotypic variation. Haplotype-based association analyses indicated that 13 haplotypes (P ≤ 0.05) from six blocks were associated with photosynthesis, growth, and wood properties. Our work shows that identifying allelic variation and LD can help to decipher the genetic basis of photosynthesis and could potentially be applied for molecular marker-assisted selection in Populus.

  2. Copy number variation and genetic diversity of MHC Class IIb alleles in an alien population of Xenopus laevis.

    PubMed

    Mable, Barbara K; Kilbride, Elizabeth; Viney, Mark E; Tinsley, Richard C

    2015-10-01

    Xenopus laevis (the African clawed frog), which originated through hybridisation and whole genome duplication, has been used as a model for genetics and development for many years, but surprisingly little is known about immune gene variation in natural populations. The purpose of this study was to use an isolated population of X. laevis that was introduced to Wales, UK in the past 50 years to investigate how variation at the MHC compares to that at other loci, following a severe population bottleneck. Among 18 individuals, we found nine alleles based on exon 2 sequences of the Class IIb region (which includes the peptide binding region). Individuals carried from one to three of the loci identified from previous laboratory studies. Genetic variation was an order of magnitude higher at the MHC compared with three single-copy nuclear genes, but all loci showed high levels of heterozygosity and nucleotide diversity and there was not an excess of homozygosity or decrease in diversity over time that would suggest extensive inbreeding in the introduced population. Tajima's D was positive for all loci, which is consistent with a bottleneck. Moreover, comparison with published sequences identified the source of the introduced population as the Western Cape region of South Africa, where most commercial suppliers have obtained their stocks. These factors suggest that despite founding by potentially already inbred individuals, the alien population in Wales has maintained substantial genetic variation at both adaptively important and neutral genes.

  3. Allelic variation, aneuploidy, and nongenetic mechanisms suppress a monogenic trait in yeast.

    PubMed

    Sirr, Amy; Cromie, Gareth A; Jeffery, Eric W; Gilbert, Teresa L; Ludlow, Catherine L; Scott, Adrian C; Dudley, Aimée M

    2015-01-01

    Clinically relevant features of monogenic diseases, including severity of symptoms and age of onset, can vary widely in response to environmental differences as well as to the presence of genetic modifiers affecting the trait's penetrance and expressivity. While a better understanding of modifier loci could lead to treatments for Mendelian diseases, the rarity of individuals harboring both a disease-causing allele and a modifying genotype hinders their study in human populations. We examined the genetic architecture of monogenic trait modifiers using a well-characterized yeast model of the human Mendelian disease classic galactosemia. Yeast strains with loss-of-function mutations in the yeast ortholog (GAL7) of the human disease gene (GALT) fail to grow in the presence of even small amounts of galactose due to accumulation of the same toxic intermediates that poison human cells. To isolate and individually genotype large numbers of the very rare (∼0.1%) galactose-tolerant recombinant progeny from a cross between two gal7Δ parents, we developed a new method, called "FACS-QTL." FACS-QTL improves upon the currently used approaches of bulk segregant analysis and extreme QTL mapping by requiring less genome engineering and strain manipulation as well as maintaining individual genotype information. Our results identified multiple distinct solutions by which the monogenic trait could be suppressed, including genetic and nongenetic mechanisms as well as frequent aneuploidy. Taken together, our results imply that the modifiers of monogenic traits are likely to be genetically complex and heterogeneous.

  4. Genetic Diversity and Allelic Frequency of Glutamate-Rich Protein (GLURP) in Plasmodium falciparum Isolates from Sub-Saharan Africa

    PubMed Central

    Duru, Kimberley C; Thomas, Bolaji N

    2014-01-01

    Glutamate-rich protein is a Plasmodium falciparum (Pf) antigen found in all stages of the parasite and has been reported to induce clinical immunity. The R0 and R2 regions have been found to exhibit a high degree of conservation, therefore serving as a good vaccine design material. We assayed the genetic diversity of Pf glurp genes in the R0 and R2 regions, as well as evaluated the role of seasonality on allelic frequency. A total of 402 genomic DNA samples, extracted from filter paper blood samples, were screened by nested polymerase chain reaction (PCR) analysis of Pf glurp R0 and R2 regions, in addition to fragment analysis of the polymorphic regions to identify allelic diversity of the parasite population. We found an extensive heterogeneity in the R2 region in general, and this heterogeneity is seasonally dependent, indicative of region plasticity. The R0 region displayed genetic conservation, as expected. We conclude that positive genotyping results with glurp R0 region should be seen as indicative of an active Pf infection, requiring adequate treatment. In addition, we advocate extending the possibility that an R0 region genotypic positivity could serve as diagnostic tool, thereby reducing cases of untreated or poorly treated infection, contributory to recrudescence or treatment failure. PMID:25452699

  5. Peculiar variations of white dwarf pulsation frequencies and maestro

    NASA Astrophysics Data System (ADS)

    Dalessio, James Ruland

    In Part I we report on variations of the normal mode frequencies of the pulsating DB white dwarfs EC 20058-5234 and KIC 8626021 and the pulsating DA white dwarf GD 66. The observations of EC 20058-5234 and KIC 8626021 were motivated by the possibility of measuring the plasmon neutrino production rate of a white dwarf, while the observations of GD 66 were part of a white dwarf pulsation timing based planet search. We announce the discovery of periodic and quasi-periodic variations of multiple normal mode frequencies that cannot be due to the presence of planetary companions. We note the possible signature of a planetary companion to EC 20058-5234 and show that GD 66 cannot have a planet in a several AU orbit down to half a Jupiter mass. We also announce the discovery of secular variations of the normal mode frequencies of all three stars that are inconsistent with cooling alone. Importantly, the rates of period change of several modes of KIC 8626021 are consistent with evolutionary cooling, but are not yet statistically significant. These modes offer the best possibility of measuring the neutrino production rate in a white dwarf. We also observe periodic and secular variations in the frequency of a combination mode that exactly matches the variations predicted by the parent modes, strong observational evidence that combination modes are created by the convection zone and are not normal modes. Periodic variations in the amplitudes of many of these modes is also noted. We hypothesize that these frequency variations are caused by complex variations of the magnetic field strength and geometry, analogous to behavior observed in the Sun. In Part II we describe the MAESTRO software framework and the MAESTRO REDUCE algorithm. MAESTRO is a collection of astronomy specific MatLab software developed by the Whole Earth Telescope. REDUCE is an an algorithm that can extract the brightness of stars on a set of CCD images with minimal configuration and human interaction. The key to

  6. Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma.

    PubMed

    Jannot, Anne-Sophie; Meziani, Roubila; Bertrand, Guylene; Gérard, Benedicte; Descamps, Vincent; Archimbaud, Alain; Picard, Catherine; Ollivaud, Laurence; Basset-Seguin, Nicole; Kerob, Delphine; Lanternier, Guy; Lebbe, Celeste; Saiag, P; Crickx, Beatrice; Clerget-Darpoux, Françoise; Grandchamp, Bernard; Soufir, Nadem; Melan-Cohort

    2005-08-01

    The occuloalbinism 2 (OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer. We wondered whether allele variations at this locus could influence susceptibility to malignant melanoma (MM). In all, 10 intragenic single-nucleotide polymorphisms (SNPs) were genotyped in 113 patients with melanomas and in 105 Caucasian control subjects with no personal or family history of skin cancer. By comparing allelic distribution between cases and controls, we show that MM and OCA2 are associated (p value=0.030 after correction for multiple testing). Then, a recently developed strategy, the 'combination test' enabled us to show that a combination formed by two SNPs was most strongly associated to MM, suggesting a possible interaction between intragenic SNPs. In addition, the role of OCA2 on MM risk was also detected using a logistic model taking into account the presence of variants of the melanocortin 1 receptor gene (MC1R, a key pigmentation gene) and all pigmentation characteristics as melanoma risk factors. Our data demonstrate that a second pigmentation gene, in addition to MC1R, is involved in genetic susceptibility to melanoma.

  7. An analysis of HLA-A, -B, and -DRB1 allele and haplotype frequencies of 21,918 residents living in Liaoning, China.

    PubMed

    Li, Xiao-Feng; Zhang, Xu; Chen, Yang; Zhang, Kun-Lian; Liu, Xiang-Jun; Li, Jian-Ping

    2014-01-01

    HLA-A, -B and -DRB1 allele frequencies and their haplotype frequencies in 21,918 Chinese residents living in Liaoning Province, who were registered as volunteer donors of China Marrow Donor Registry, were investigated. They are composed of 93.37% Han Chinese, 5.1% Manchus, 0.57% Mongols, 0.46% Hui persons, 0.29% Koreans and 0.14% Xibe ethnic group. In total eighteen different HLA-A alleles, forty-eight different HLA-B alleles and fourteen different HLA-DRB1 alleles have been identified. Their frequencies are in agreement with the Hardy-Weinberg equilibrium. For Han Chinese in Liaoning, 1,534 different HLA-A-B-DRB1 haplotypes were identified, with a frequency of higher than 0.01%. A*30-B*13-DRB1*07, A*02-B*46-DRB1*09 and A*02-B*13-DRB1*12 are the most frequent haplotypes among Liaoning Han. While Liaoning Han, Liaoning Manchu, Liaoning Mongol, Liaoning Hui and Liaoning Korean share the northern Han characteristic haplotypes, all minority ethnic groups with the exception of Liaoning Manchu have developed their own unique HLA profiles. This dataset characterizes the HLA allele and haplotype frequencies in the Liaoning area and suggests that it is different from those in other parts of China and ethnic groups, which implicates transplant donor searching strategies and studies on population genetics.

  8. Allele frequencies data and statistic parameters for 13 STR loci in a population of the Brazilian Amazon Region.

    PubMed

    Rodrigues, Elzemar Martins Ribeiro; Palha, Teresinha de Jesus Brabo Ferreira; dos Santos, Sidney Emanuel Batista

    2007-05-24

    Allele frequencies for 13 short tandem repeat (D3S1358, vWA, D21S11, D18S51, D5S818, D13S317, D7S820, TH01, TPOX, D16S539, CSF1PO, D8S1179 and FGA) loci were determined in a sample of 325 unrelated individuals from the population of the Amazon of Belém, Brazil. These loci are the most commonly used in forensic and paternity testing. The forensic parameters investigated presented high values. The power of discrimination and the probability of exclusion for these 13 STRs are 99.999999999992% and 99.9998%, respectively. In conclusion, these 13 markers are suitable for forensic analysis and paternity tests of the Amazonian population.

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

    PubMed

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

    2013-02-01

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

  10. Allelic Variation, Aneuploidy, and Nongenetic Mechanisms Suppress a Monogenic Trait in Yeast

    PubMed Central

    Sirr, Amy; Cromie, Gareth A.; Jeffery, Eric W.; Gilbert, Teresa L.; Ludlow, Catherine L.; Scott, Adrian C.; Dudley, Aimée M.

    2015-01-01

    Clinically relevant features of monogenic diseases, including severity of symptoms and age of onset, can vary widely in response to environmental differences as well as to the presence of genetic modifiers affecting the trait’s penetrance and expressivity. While a better understanding of modifier loci could lead to treatments for Mendelian diseases, the rarity of individuals harboring both a disease-causing allele and a modifying genotype hinders their study in human populations. We examined the genetic architecture of monogenic trait modifiers using a well-characterized yeast model of the human Mendelian disease classic galactosemia. Yeast strains with loss-of-function mutations in the yeast ortholog (GAL7) of the human disease gene (GALT) fail to grow in the presence of even small amounts of galactose due to accumulation of the same toxic intermediates that poison human cells. To isolate and individually genotype large numbers of the very rare (∼0.1%) galactose-tolerant recombinant progeny from a cross between two gal7Δ parents, we developed a new method, called “FACS-QTL.” FACS-QTL improves upon the currently used approaches of bulk segregant analysis and extreme QTL mapping by requiring less genome engineering and strain manipulation as well as maintaining individual genotype information. Our results identified multiple distinct solutions by which the monogenic trait could be suppressed, including genetic and nongenetic mechanisms as well as frequent aneuploidy. Taken together, our results imply that the modifiers of monogenic traits are likely to be genetically complex and heterogeneous. PMID:25398792

  11. Gravitational dynamos and the low-frequency geomagnetic secular variation

    PubMed Central

    Olson, P.

    2007-01-01

    Self-sustaining numerical dynamos are used to infer the sources of low-frequency secular variation of the geomagnetic field. Gravitational dynamo models powered by compositional convection in an electrically conducting, rotating fluid shell exhibit several regimes of magnetic field behavior with an increasing Rayleigh number of the convection, including nearly steady dipoles, chaotic nonreversing dipoles, and chaotic reversing dipoles. The time average dipole strength and dipolarity of the magnetic field decrease, whereas the dipole variability, average dipole tilt angle, and frequency of polarity reversals increase with Rayleigh number. Chaotic gravitational dynamos have large-amplitude dipole secular variation with maximum power at frequencies corresponding to a few cycles per million years on Earth. Their external magnetic field structure, dipole statistics, low-frequency power spectra, and polarity reversal frequency are comparable to the geomagnetic field. The magnetic variability is driven by the Lorentz force and is characterized by an inverse correlation between dynamo magnetic and kinetic energy fluctuations. A constant energy dissipation theory accounts for this inverse energy correlation, which is shown to produce conditions favorable for dipole drift, polarity reversals, and excursions. PMID:18048345

  12. Gravitational dynamos and the low-frequency geomagnetic secular variation.

    PubMed

    Olson, P

    2007-12-18

    Self-sustaining numerical dynamos are used to infer the sources of low-frequency secular variation of the geomagnetic field. Gravitational dynamo models powered by compositional convection in an electrically conducting, rotating fluid shell exhibit several regimes of magnetic field behavior with an increasing Rayleigh number of the convection, including nearly steady dipoles, chaotic nonreversing dipoles, and chaotic reversing dipoles. The time average dipole strength and dipolarity of the magnetic field decrease, whereas the dipole variability, average dipole tilt angle, and frequency of polarity reversals increase with Rayleigh number. Chaotic gravitational dynamos have large-amplitude dipole secular variation with maximum power at frequencies corresponding to a few cycles per million years on Earth. Their external magnetic field structure, dipole statistics, low-frequency power spectra, and polarity reversal frequency are comparable to the geomagnetic field. The magnetic variability is driven by the Lorentz force and is characterized by an inverse correlation between dynamo magnetic and kinetic energy fluctuations. A constant energy dissipation theory accounts for this inverse energy correlation, which is shown to produce conditions favorable for dipole drift, polarity reversals, and excursions.

  13. Pool-hmm: a Python program for estimating the allele frequency spectrum and detecting selective sweeps from next generation sequencing of pooled samples

    PubMed Central

    Boitard, Simon; Kofler, Robert; Françoise, Pierre; Robelin, David; Schlötterer, Christian; Futschik, Andreas

    2013-01-01

    Due to its cost effectiveness, next generation sequencing of pools of individuals (Pool-Seq) is becoming a popular strategy for genome-wide estimation of allele frequencies in population samples. As the allele frequency spectrum provides information about past episodes of selection, Pool-seq is also a promising design for genomic scans for selection. However, no software tool has yet been developed for selection scans based on Pool-Seq data. We introduce Pool-hmm, a Python program for the estimation of allele frequencies and the detection of selective sweeps in a Pool-Seq sample. Pool-hmm includes several options that allow a flexible analysis of Pool-Seq data, and can be run in parallel on several processors. Source code and documentation for Pool-hmm is freely available at https://qgsp.jouy.inra.fr/. PMID:23311589

  14. Association between allelic variation due to short tandem repeats in tRNA gene of Entamoeba histolytica and clinical phenotypes of amoebiasis.

    PubMed

    Jaiswal, Virendra; Ghoshal, Ujjala; Mittal, Balraj; Dhole, Tapan N; Ghoshal, Uday C

    2014-05-01

    Genotypes of Entamoeba histolytica (E. histolytica) may contribute clinical phenotypes of amoebiasis such as amoebic liver abscess (ALA), dysentery and asymptomatic cyst passers state. Hence, we evaluated allelic variation due to short tandem repeats (STRs) in tRNA gene of E. histolytica and clinical phenotypes of amoebiasis. Asymptomatic cyst passers (n=24), patients with dysentery (n=56) and ALA (n=107) were included. Extracted DNA from stool (dysentery, asymptomatic cyst passers) and liver aspirate was amplified using 6 E. histolytica specific tRNA-linked STRs (D-A, A-L, N-K2, R-R, S-Q, and S(TGA)-D) primers. PCR products were subjected to sequencing. Association between allelic variation and clinical phenotypes was analyzed. A total of 9 allelic variations were found in D-A, 8 in A-L, 4 in N-K2, 5 in R-R, 10 in S(TAG)-D and 7 in S-Q loci. A significant association was found between allelic variants and clinical phenotypes of amoebiasis. This study reveals that allelic variation due to short tandem repeats (STRs) in tRNA gene of E. histolytica is associated different clinical outcome of amoebiasis.

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

    PubMed Central

    Faure, Eric

    2008-01-01

    Background In Europe, the north-south downhill cline frequency of the chemokine receptor CCR5 allele with a 32-bp deletion (CCR5-Δ32) raises interesting questions for evolutionary biologists. We had suggested first that, in the past, the European colonizers, principally Romans, might have been instrumental of a progressively decrease of the frequencies southwards. Indeed, statistical analyses suggested strong negative correlations between the allele frequency and historical parameters including the colonization dates by Mediterranean civilisations. The gene flows from colonizers to native populations were extremely low but colonizers are responsible of the spread of several diseases suggesting that the dissemination of parasites in naive populations could have induced a breakdown rupture of the fragile pathocenosis changing the balance among diseases. The new equilibrium state has been reached through a negative selection of the null allele. Results Most of the human diseases are zoonoses and cat might have been instrumental in the decrease of the allele frequency, because its diffusion through Europe was a gradual process, due principally to Romans; and that several cat zoonoses could be transmitted to man. The possible implication of a feline lentivirus (FIV) which does not use CCR5 as co-receptor is discussed. This virus can infect primate cells in vitro and induces clinical signs in macaque. Moreover, most of the historical regions with null or low frequency of CCR5-Δ32 allele coincide with historical range of the wild felid species which harbor species-specific FIVs. Conclusion We proposed the hypothesis that the actual European CCR5 allelic frequencies are the result of a negative selection due to a disease spreading. A cat zoonosis, could be the most plausible hypothesis. Future studies could provide if CCR5 can play an antimicrobial role in FIV pathogenesis. Moreover, studies of ancient DNA could provide more evidences regarding the implications of

  16. dbQSNP: a database of SNPs in human promoter regions with allele frequency information determined by single-strand conformation polymorphism-based methods.

    PubMed

    Tahira, Tomoko; Baba, Shingo; Higasa, Koichiro; Kukita, Yoji; Suzuki, Yutaka; Sugano, Sumio; Hayashi, Kenshi

    2005-08-01

    We present a database, dbQSNP (http://qsnp.gen.kyushu-u.ac.jp/), that provides sequence and allele frequency information for single-nucleotide polymorphisms (SNPs) located in the promoter regions of human genes, which were defined by the 5' ends of full-length cDNA clones. We searched for the SNPs in these regions by sequencing or single-strand conformation polymorphism (SSCP) analysis. The allele frequencies of the identified SNPs in two ethnic groups were quantified by SSCP analyses of pooled DNA samples. The accuracy of our estimation is supported by strong correlations between the frequencies in our data and those in other databases for the same ethnic groups. The frequencies vary considerably between the two ethnic groups studied, suggesting the need for population-based collections and allele frequency determination of SNPs, in, e.g., association studies of diseases. We show profiles of SNP densities that are characteristic of transcription start site regions. A fraction of the SNPs revealed a significantly different allele frequency between the groups, suggesting differential selection of the genes involved.

  17. Comparative Systems Biology Reveals Allelic Variation Modulating Tocochromanol Profiles in Barley (Hordeum vulgare L.)

    PubMed Central

    Oliver, Rebekah E.; Islamovic, Emir; Obert, Donald E.; Wise, Mitchell L.; Herrin, Lauri L.; Hang, An; Harrison, Stephen A.; Ibrahim, Amir; Marshall, Juliet M.; Miclaus, Kelci J.; Lazo, Gerard R.; Hu, Gongshe; Jackson, Eric W.

    2014-01-01

    Tocochromanols are recognized for nutritional content, plant stress response, and seed longevity. Here we present a systems biological approach to characterize and develop predictive assays for genes affecting tocochromanol variation in barley. Major QTL, detected in three regions of a SNP linkage map, affected multiple tocochromanol forms. Candidate genes were identified through barley/rice orthology and sequenced in genotypes with disparate tocochromanol profiles. Gene-specific markers, designed based on observed polymorphism, mapped to the originating QTL, increasing R2 values at the respective loci. Polymorphism within promoter regions corresponded to motifs known to influence gene expression. Quantitative PCR analysis revealed a trend of increased expression in tissues grown at cold temperatures. These results demonstrate utility of a novel method for rapid gene identification and characterization, and provide a resource for efficient development of barley lines with improved tocochromanol profiles. PMID:24820172

  18. Allele and genotype frequencies of CYP2B6 and CYP2C19 polymorphisms in Egyptian agricultural workers.

    PubMed

    Ellison, Corie A; Abou El-Ella, Soheir S; Tawfik, Maha; Lein, Pamela J; Olson, James R

    2012-01-01

    Genetic variability in cytochrome P-450 (CYP) has the potential to modify pharmacological and toxicological responses to many chemicals. Both CYP2B6 and CYP2C19 are pharmacologically and toxicologically relevant due to their ability to metabolize multiple drugs and environmental contaminants, including the organophosphorus (OP) pesticide chlorpyrifos. The aim of this study was to determine the prevalence of CYP2B6 and CYP2C19 variants in an indigenous Egyptian population (n = 120) that was shown to be occupationally exposed to chlorpyrifos. Further, the genotyping data was compared for Egyptians with previously studied populations to determine between population differences. Allelic frequencies were CYP2B6 1459C > T (3.8%), CYP2B6 785A > G (30.4%), CYP2B6 516G > T (28.8%), CYP2C19 681G > A (3.8%), and CYP2C19 431G > A (0%). The most prevalent CYP2B6 genotype combinations were CYP2B6 *1/*1 (44%), *1/*6 (38%), *6/*6 (8%), and *1/*5 (6%). The frequency of the CYP2C19 genotype combinations were CYP2C19 *1/*1 (93%), *1/*2 (6%), and *2/*2 (1%). The frequency of the CYP2B6 516G > T and CYP2B6 785A > G polymorphisms in this Egyptian cohort is similar to that found North American and European populations but significantly different from that reported for West African populations, while that of CYP2B6 1459C > T is similar to that found in Africans and African Americans. The observed frequency of CYP2C19 681G > A in Egyptians is similar to that of African pygmies but significantly different from other world populations, while CYP2C19 431 G > A was significantly different from that of African pygmies but similar to other world populations.

  19. Colloquium paper: human adaptations to diet, subsistence, and ecoregion are due to subtle shifts in allele frequency.

    PubMed

    Hancock, Angela M; Witonsky, David B; Ehler, Edvard; Alkorta-Aranburu, Gorka; Beall, Cynthia; Gebremedhin, Amha; Sukernik, Rem; Utermann, Gerd; Pritchard, Jonathan; Coop, Graham; Di Rienzo, Anna

    2010-05-11

    Human populations use a variety of subsistence strategies to exploit an exceptionally broad range of ecoregions and dietary components. These aspects of human environments have changed dramatically during human evolution, giving rise to new selective pressures. To understand the genetic basis of human adaptations, we combine population genetics data with ecological information to detect variants that increased in frequency in response to new selective pressures. Our approach detects SNPs that show concordant differences in allele frequencies across populations with respect to specific aspects of the environment. Genic and especially nonsynonymous SNPs are overrepresented among those most strongly correlated with environmental variables. This provides genome-wide evidence for selection due to changes in ecoregion, diet, and subsistence. We find particularly strong signals associated with polar ecoregions, with foraging, and with a diet rich in roots and tubers. Interestingly, several of the strongest signals overlap with those implicated in energy metabolism phenotypes from genome-wide association studies, including SNPs influencing glucose levels and susceptibility to type 2 diabetes. Furthermore, several pathways, including those of starch and sucrose metabolism, are enriched for strong signals of adaptations to a diet rich in roots and tubers, whereas signals associated with polar ecoregions are overrepresented in genes associated with energy metabolism pathways.

  20. [Differences in allele frequency at the BAIB locus, determining the level of expression of beta-aminoisobutyric acid, in healthy donors and coronary artery atherosclerosis patients from Buryat and Lithuanian populations].

    PubMed

    Spitsyn, V A; Afanas'eva, I S

    2001-12-01

    Phenotype and allele frequencies of the genetically dimorphic system determining urinary excretion of beta-aminoisobutyric acid (BAIB) were studied in population samples of Buryats from the Aginskii Buryat Autonomous District and Lithuanians from Vilnius and in patients with coronary atherosclerosis (CA) from both populations. Frequency of allele BAIB*b, which determines high BAIB excretion, proved to be more than twice higher in Buryats compared with the population sample of Lithuanians (0.620 versus 0.289, respectively). The proportion of individuals with high BAIB excretion in CA patients of either ethnic sample was twice higher than in the corresponding control sample. Frequency of allele BAIB*b in CA patients and healthy individuals was 0.348 and 0.242, respectively, in the Lithuanian population and 0.775 and 0.557, respectively, in the Buryat population. Thus, assessment of urinary excretion of BAIB proved to be prognostically valuable. The method used to detect a variation in BAIB excretion is relatively inexpensive, simple, and suitable for mass screening of patients and healthy individuals (population control). After additional testing with representative samples, the method can be used as an accessory diagnostic test in patients with cardiovascular disorders.

  1. Natural variation in rosette size under salt stress conditions corresponds to developmental differences between Arabidopsis accessions and allelic variation in the LRR-KISS gene

    PubMed Central

    Julkowska, Magdalena M.; Klei, Karlijn; Fokkens, Like; Haring, Michel A.; Schranz, M. Eric; Testerink, Christa

    2016-01-01

    Natural variation among Arabidopsis accessions is an important genetic resource to identify mechanisms underlying plant development and stress tolerance. To evaluate the natural variation in salinity stress tolerance, two large-scale experiments were performed on two populations consisting of 160 Arabidopsis accessions each. Multiple traits, including projected rosette area, and fresh and dry weight were collected as an estimate for salinity tolerance. Our results reveal a correlation between rosette size under salt stress conditions and developmental differences between the accessions grown in control conditions, suggesting that in general larger plants were more salt tolerant. This correlation was less pronounced when plants were grown under severe salt stress conditions. Subsequent genome wide association study (GWAS) revealed associations with novel candidate genes for salinity tolerance such as LRR-KISS (At4g08850), flowering locus KH-domain containing protein and a DUF1639-containing protein. Accessions with high LRR-KISS expression developed larger rosettes under salt stress conditions. Further characterization of allelic variation in candidate genes identified in this study will provide more insight into mechanisms of salt stress tolerance due to enhanced shoot growth. PMID:26873976

  2. Polymorphism of the bovine POU1F1 gene: allele frequencies and effects on milk production in three Iranian native breeds and Holstein cattle of Iran.

    PubMed

    Zakizadeh, S; Reissmann, M; Rahimi, G; Javaremi, A Nejati; Reinecke, P; Mirae-Ashtiani, S R; Shahrbabak, M Moradi

    2007-08-01

    The aim of this study was to estimate the allele frequencies in polymorphic site of exon six of POU1F1 gene in three Iranian native and Holstein cattle. Genomic DNA was extracted from 3 Iranian native cattle breeds, including 97 Mazandarani, 87 Sarabi, 112 Golpaygani and also 110 Holstein cattle. A 451 bp fragment of intron 5 and exon 6 were amplified and digested with HinfI restriction enzyme. Frequencies of allele A were 0.37, 0.27, 0.34 and 0.21 for Mazandarani, Sarabi, Golpaygani and Holstein cattle, respectively. Significant differences in genotype frequencies were found between Mazandarani or Golpaygani and Holstein cattle. No significant differences in genotype frequencies were found between Sarabi and Holstein cattle. Transition A to G in nucleotide 1256 is responsible for HinfI(-) allele. No significant association was observed between POU1F1 polymorphism and milk production. Differences in allelic frequency between native Bos indicus breeds (Mazandarani, Golpaygani) and Holstein at the present study might be due to differences in origin breeds, low number of samples and/or as the effect of natural selection in native breeds.

  3. Allelic frequency distributions of 21 non-combined DNA index system STR loci in a Russian ethnic minority group from Inner Mongolia, China*

    PubMed Central

    Wang, Hong-dan; Shen, Chun-mei; Liu, Wen-juan; Zhang, Yu-dang; Yang, Guang; Yan, Jiang-wei; Qin, Hai-xia; Zhu, Bo-feng

    2013-01-01

    We studied the allelic frequency distributions and statistical forensic parameters of 21 new short tandem repeat (STR) loci and the amelogenin locus, which are not included in the combined DNA index system (CODIS), in a Russian ethnic minority group from the Inner Mongolia Autonomous Region, China. A total of 114 bloodstain samples from unrelated individuals were extracted and co-amplified with four fluorescence-labeled primers in a multiplex polymerase chain reaction (PCR) system. Using capillary electrophoresis, the PCR products of the 21 STR loci were separated and genotyped. A total of 161 alleles were observed in the Russian ethnic minority group, and corresponding allelic frequencies ranged from 0.0044 to 0.5965. The 21 non-CODIS STR loci of the Russian ethnic minority group were characterized by high genetic diversity and therefore may be useful for elucidating the population’s genetic background, for individual identification, and for paternity testing in forensic practice. PMID:23733431

  4. Frequencies of 32 base pair deletion of the (Delta 32) allele of the CCR5 HIV-1 co-receptor gene in Caucasians: a comparative analysis.

    PubMed

    Lucotte, Gérard

    2002-05-01

    The CCR5 gene encodes for the co-receptor for the major macrophage-tropics strains of human immunodeficiency virus (HIV-1), and a mutant allele of this gene (Delta 32) provide to homozygotes a strong resistance against infection by HIV. The frequency of the Delta 32 allele was investigated in 40 populations of 8842 non-infected subjects coming from Europe, the Middle-East and North Africa. A clear north-south decreasing gradient was evident for Delta 32 frequencies, with a significant correlation coefficient (r=0.83). The main frequency value of Delta 32 for Sweden, Norway, Denmark, Finland and Iceland (0.134) is significantly (chi(2)=63.818, P<0.001) highest than the Delta 32 mean value, indicating that probably the Vikings might have been instrumental in disseminating the Delta 32 allele during the eighth to the tenth centuries during historical times. Possibly variola virus has discriminated the Delta 32 carriers in Europe since the eighth century AD, explaining the high frequency of the Delta 32 allele in Europe today.

  5. OutLyzer: software for extracting low-allele-frequency tumor mutations from sequencing background noise in clinical practice

    PubMed Central

    Muller, Etienne; Goardon, Nicolas; Brault, Baptiste; Rousselin, Antoine; Paimparay, Germain; Legros, Angelina; Fouillet, Robin; Bruet, Olivia; Tranchant, Aurore; Domin, Florian; San, Chankannira; Quesnelle, Céline; Frebourg, Thierry; Ricou, Agathe; Krieger, Sophie; Vaur, Dominique; Castera, Laurent

    2016-01-01

    Highlighting tumoral mutations is a key step in oncology for personalizing care. Considering the genetic heterogeneity in a tumor, software used for detecting mutations should clearly distinguish real tumor events of interest that could be predictive markers for personalized medicine from false positives. OutLyzer is a new variant-caller designed for the specific and sensitive detection of mutations for research and diagnostic purposes. It is based on statistic and local evaluation of sequencing background noise to highlight potential true positive variants. 130 previously genotyped patients were sequenced after enrichment by capturing the exons of 22 genes. Sequencing data were analyzed by HaplotypeCaller, LofreqStar, Varscan2 and OutLyzer. OutLyzer had the best sensitivity and specificity with a fixed limit of detection for all tools of 1% for SNVs and 2% for Indels. OutLyzer is a useful tool for detecting mutations of interest in tumors including low allele-frequency mutations, and could be adopted in standard practice for delivering targeted therapies in cancer treatment. PMID:27825131

  6. Phenol sulphotransferase SULT1A1 polymorphism: molecular diagnosis and allele frequencies in Caucasian and African populations.

    PubMed Central

    Coughtrie, M W; Gilissen, R A; Shek, B; Strange, R C; Fryer, A A; Jones, P W; Bamber, D E

    1999-01-01

    Sulphation, catalysed by members of the sulphotransferase (SULT) enzyme family, is an important component of the body's chemical defence mechanism, but also acts to bioactivate mutagens such as hydroxylated aryl and heterocyclic amines. A major human sulphotransferase, SULT1A1 (P-PST), metabolizes and/or bioactivates many drugs, iodothyronines and hydroxylated aromatic amines. The enzyme activity varies widely within the population and is under genetic control. We have developed an assay detecting a G-->A transition in SULT1A1 that causes an Arg213-->His substitution associated with low SULT activity and altered enzyme properties, and have used it to assess the SULT1A1 genotype in Caucasian (n=293) and African (Nigerian, n=52) populations. We show that the mutant SULT1A1*2 allele is present at frequencies of 0.321 and 0.269 in the Caucasian and African populations respectively. We also demonstrate a significant age-related difference in SULT1A1 genotype within our Caucasian population, with increasing incidence of SULT1A1*1 homozygosity and decreasing incidence of SULT1A1*2 homozygosity with increasing age, indicating a potential association of SULT1A1*1 allozyme(s) with protection against cell and/or tissue damage during aging. PMID:9854023

  7. Allele frequencies for 40 autosomal SNP loci typed for US population samples using electrospray ionization mass spectrometry

    PubMed Central

    Kiesler, Kevin M.; Vallone, Peter M.

    2013-01-01

    Aim To type a set of 194 US African American, Caucasian, and Hispanic samples (self-declared ancestry) for 40 autosomal single nucleotide polymorphism (SNP) markers intended for human identification purposes. Methods Genotyping was performed on an automated commercial electrospray ionization time-of-flight mass spectrometer, the PLEX-ID. The 40 SNP markers were amplified in eight unique 5plex PCRs, desalted, and resolved based on amplicon mass. For each of the three US sample groups statistical analyses were performed on the resulting genotypes. Results The assay was found to be robust and capable of genotyping the 40 SNP markers consuming approximately 4 nanograms of template per sample. The combined random match probabilities for the 40 SNP assay ranged from 10−16 to 10−21. Conclusion The multiplex PLEX-ID SNP-40 assay is the first fully automated genotyping method capable of typing a panel of 40 forensically relevant autosomal SNP markers on a mass spectrometry platform. The data produced provided the first allele frequencies estimates for these 40 SNPs in a National Institute of Standards and Technology US population sample set. No population bias was detected although one locus deviated from its expected level of heterozygosity. PMID:23771752

  8. Allelic Variation in TAS2R Bitter Receptor Genes Associates with Variation in Sensations from and Ingestive Behaviors toward Common Bitter Beverages in Adults

    PubMed Central

    Hayes, John E.; Wallace, Margaret R.; Knopik, Valerie S.; Herbstman, Deborah M.; Bartoshuk, Linda M.

    2011-01-01

    The 25 human bitter receptors and their respective genes (TAS2Rs) contain unusually high levels of allelic variation, which may influence response to bitter compounds in the food supply. Phenotypes based on the perceived bitterness of single bitter compounds were first linked to food preference over 50 years ago. The most studied phenotype is propylthiouracil bitterness, which is mediated primarily by the TAS2R38 gene and possibly others. In a laboratory-based study, we tested for associations between TAS2R variants and sensations, liking, or intake of bitter beverages among healthy adults who were primarily of European ancestry. A haploblock across TAS2R3, TAS2R4, and TAS2R5 explained some variability in the bitterness of espresso coffee. For grapefruit juice, variation at a TAS2R19 single nucleotide polymorphism (SNP) was associated with increased bitterness and decreased liking. An association between a TAS2R16 SNP and alcohol intake was identified, and the putative TAS2R38–alcohol relationship was confirmed, although these polymorphisms did not explain sensory or hedonic responses to sampled scotch whisky. In summary, TAS2R polymorphisms appear to influence the sensations, liking, or intake of common and nutritionally significant beverages. Studying perceptual and behavioral differences in vivo using real foods and beverages may potentially identify polymorphisms related to dietary behavior even in the absence of known ligands. PMID:21163912

  9. Genetic Adaptation to Climate in White Spruce Involves Small to Moderate Allele Frequency Shifts in Functionally Diverse Genes.

    PubMed

    Hornoy, Benjamin; Pavy, Nathalie; Gérardi, Sébastien; Beaulieu, Jean; Bousquet, Jean

    2015-11-11

    Understanding the genetic basis of adaptation to climate is of paramount importance for preserving and managing genetic diversity in plants in a context of climate change. Yet, this objective has been addressed mainly in short-lived model species. Thus, expanding knowledge to nonmodel species with contrasting life histories, such as forest trees, appears necessary. To uncover the genetic basis of adaptation to climate in the widely distributed boreal conifer white spruce (Picea glauca), an environmental association study was conducted using 11,085 single nucleotide polymorphisms representing 7,819 genes, that is, approximately a quarter of the transcriptome.Linear and quadratic regressions controlling for isolation-by-distance, and the Random Forest algorithm, identified several dozen genes putatively under selection, among which 43 showed strongest signals along temperature and precipitation gradients. Most of them were related to temperature. Small to moderate shifts in allele frequencies were observed. Genes involved encompassed a wide variety of functions and processes, some of them being likely important for plant survival under biotic and abiotic environmental stresses according to expression data. Literature mining and sequence comparison also highlighted conserved sequences and functions with angiosperm homologs.Our results are consistent with theoretical predictions that local adaptation involves genes with small frequency shifts when selection is recent and gene flow among populations is high. Accordingly, genetic adaptation to climate in P. glauca appears to be complex, involving many independent and interacting gene functions, biochemical pathways, and processes. From an applied perspective, these results shall lead to specific functional/association studies in conifers and to the development of markers useful for the conservation of genetic resources.

  10. Genetic Adaptation to Climate in White Spruce Involves Small to Moderate Allele Frequency Shifts in Functionally Diverse Genes

    PubMed Central

    Hornoy, Benjamin; Pavy, Nathalie; Gérardi, Sébastien; Beaulieu, Jean; Bousquet, Jean

    2015-01-01

    Understanding the genetic basis of adaptation to climate is of paramount importance for preserving and managing genetic diversity in plants in a context of climate change. Yet, this objective has been addressed mainly in short-lived model species. Thus, expanding knowledge to nonmodel species with contrasting life histories, such as forest trees, appears necessary. To uncover the genetic basis of adaptation to climate in the widely distributed boreal conifer white spruce (Picea glauca), an environmental association study was conducted using 11,085 single nucleotide polymorphisms representing 7,819 genes, that is, approximately a quarter of the transcriptome. Linear and quadratic regressions controlling for isolation-by-distance, and the Random Forest algorithm, identified several dozen genes putatively under selection, among which 43 showed strongest signals along temperature and precipitation gradients. Most of them were related to temperature. Small to moderate shifts in allele frequencies were observed. Genes involved encompassed a wide variety of functions and processes, some of them being likely important for plant survival under biotic and abiotic environmental stresses according to expression data. Literature mining and sequence comparison also highlighted conserved sequences and functions with angiosperm homologs. Our results are consistent with theoretical predictions that local adaptation involves genes with small frequency shifts when selection is recent and gene flow among populations is high. Accordingly, genetic adaptation to climate in P. glauca appears to be complex, involving many independent and interacting gene functions, biochemical pathways, and processes. From an applied perspective, these results shall lead to specific functional/association studies in conifers and to the development of markers useful for the conservation of genetic resources. PMID:26560341

  11. Allelic variation in the canine Cox-2 promoter causes hypermethylation of the canine Cox-2 promoter in clinical cases of renal dysplasia

    PubMed Central

    2014-01-01

    Background Novel allelic variants in the promoter of the canine cyclooxygenase-2 (Cox-2) gene are associated with renal dysplasia (RD). These variants consist of either deletions of putative SP1 transcription factor-binding sites or insertions of tandem repeats of SP1-binding sites located in the CpG island just upstream of the ATG translation initiation site. The canine Cox-2 gene was studied because Cox-2-deficient mice have renal abnormalities and a pathology that is strikingly similar to RD in dogs. Findings The allelic variants were associated with hypermethylation of the Cox-2 promoter only in clinical cases of RD. The wild-type allele was never methylated, even in clinical cases that were heterozygous for a mutant allele. In cases that were biopsy-negative, the promoter remained unmethylated, regardless of the genotype. Methylated DNA was found in DNA from various adult tissues of dogs with clinical RD. Conclusions The mechanism of action of the allelic variation in the canine Cox-2 promoter most likely involves variation in the extent of epigenetic downregulation of this gene. This epigenetic downregulation must have occurred early in development because methylated Cox-2 promoter DNA sequences are found in various adult tissues. PMID:24708682

  12. Comprehensively Evaluating cis-Regulatory Variation in the Human Prostate Transcriptome by Using Gene-Level Allele-Specific Expression

    PubMed Central

    Larson, Nicholas B.; McDonnell, Shannon; French, Amy J.; Fogarty, Zach; Cheville, John; Middha, Sumit; Riska, Shaun; Baheti, Saurabh; Nair, Asha A.; Wang, Liang; Schaid, Daniel J.; Thibodeau, Stephen N.

    2015-01-01

    The identification of cis-acting regulatory variation in primary tissues has the potential to elucidate the genetic basis of complex traits and further our understanding of transcriptomic diversity across cell types. Expression quantitative trait locus (eQTL) association analysis using RNA sequencing (RNA-seq) data can improve upon the detection of cis-acting regulatory variation by leveraging allele-specific expression (ASE) patterns in association analysis. Here, we present a comprehensive evaluation of cis-acting eQTLs by analyzing RNA-seq gene-expression data and genome-wide high-density genotypes from 471 samples of normal primary prostate tissue. Using statistical models that integrate ASE information, we identified extensive cis-eQTLs across the prostate transcriptome and found that approximately 70% of expressed genes corresponded to a significant eQTL at a gene-level false-discovery rate of 0.05. Overall, cis-eQTLs were heavily concentrated near the transcription start and stop sites of affected genes, and effects were negatively correlated with distance. We identified multiple instances of cis-acting co-regulation by using phased genotype data and discovered 233 SNPs as the most strongly associated eQTLs for more than one gene. We also noted significant enrichment (25/50, p = 2E−5) of previously reported prostate cancer risk SNPs in prostate eQTLs. Our results illustrate the benefit of assessing ASE data in cis-eQTL analyses by showing better reproducibility of prior eQTL findings than of eQTL mapping based on total expression alone. Altogether, our analysis provides extensive functional context of thousands of SNPs in prostate tissue, and these results will be of critical value in guiding studies examining disease of the human prostate. PMID:25983244

  13. Comprehensively evaluating cis-regulatory variation in the human prostate transcriptome by using gene-level allele-specific expression.

    PubMed

    Larson, Nicholas B; McDonnell, Shannon; French, Amy J; Fogarty, Zach; Cheville, John; Middha, Sumit; Riska, Shaun; Baheti, Saurabh; Nair, Asha A; Wang, Liang; Schaid, Daniel J; Thibodeau, Stephen N

    2015-06-04

    The identification of cis-acting regulatory variation in primary tissues has the potential to elucidate the genetic basis of complex traits and further our understanding of transcriptomic diversity across cell types. Expression quantitative trait locus (eQTL) association analysis using RNA sequencing (RNA-seq) data can improve upon the detection of cis-acting regulatory variation by leveraging allele-specific expression (ASE) patterns in association analysis. Here, we present a comprehensive evaluation of cis-acting eQTLs by analyzing RNA-seq gene-expression data and genome-wide high-density genotypes from 471 samples of normal primary prostate tissue. Using statistical models that integrate ASE information, we identified extensive cis-eQTLs across the prostate transcriptome and found that approximately 70% of expressed genes corresponded to a significant eQTL at a gene-level false-discovery rate of 0.05. Overall, cis-eQTLs were heavily concentrated near the transcription start and stop sites of affected genes, and effects were negatively correlated with distance. We identified multiple instances of cis-acting co-regulation by using phased genotype data and discovered 233 SNPs as the most strongly associated eQTLs for more than one gene. We also noted significant enrichment (25/50, p = 2E-5) of previously reported prostate cancer risk SNPs in prostate eQTLs. Our results illustrate the benefit of assessing ASE data in cis-eQTL analyses by showing better reproducibility of prior eQTL findings than of eQTL mapping based on total expression alone. Altogether, our analysis provides extensive functional context of thousands of SNPs in prostate tissue, and these results will be of critical value in guiding studies examining disease of the human prostate.

  14. The Frequency of HLA-A, HLA-B, and HLA-DRB1 Alleles in Patients with Acute Lymphoblastic Leukemia in the Turkish Population: A Case-Control Study

    PubMed Central

    Patıroğlu, Türkan; Akar, H. Haluk

    2016-01-01

    We studied the frequencies of human leukocyte antigen alleles (A, B, and DRB1) in 90 patients with acute lymphoblastic leukemia (ALL) and then compared them with 126 controls in this study. Although the frequencies of the A*03 allele, the DRB1*03 allele, the DRB1*04 allele, the A*02/B*35/DRB1*13 haplotype, and homozygosity of A*02 were higher in patients (p=0.006, p=0.003, p=0.002, p=0.01, and p=0.02, respectively), the frequencies of the A*23, B*13, B*40, and DRB1*13 alleles were lower (p=0.002, p=0.07, p=0.002, and p=0.003, respectively) in patients than controls. The frequencies of the DRB1*04 and DRB1*07 alleles were higher in patients in the high-risk group and standard-risk group, respectively (p=0.009 and p=0.007, respectively). This study indicated that the frequency of the A*03 allele, the DRB1*03 allele, the DRB1*04 allele, the A*02/B*35/DRB1*13 haplotype, and A*02 homozygosity may play a predisposing role in patients with ALL in the Turkish population. The frequency of the DRB1*04 and DRB1*07 alleles may also be associated with high risk and standard risk in patients with ALL, respectively. PMID:27095065

  15. The Frequency of HLA-A, HLA-B, and HLA-DRB1 Alleles in Patients with Acute Lymphoblastic Leukemia in the Turkish Population: A Case-Control Study.

    PubMed

    Patıroğlu, Türkan; Akar, H Haluk

    2016-12-01

    We studied the frequencies of human leukocyte antigen alleles (A, B, and DRB1) in 90 patients with acute lymphoblastic leukemia (ALL) and then compared them with 126 controls in this study. Although the frequencies of the A*03 allele, the DRB1*03 allele, the DRB1*04 allele, the A*02/B*35/DRB1*13 haplotype, and homozygosity of A*02 were higher in patients (p=0.006, p=0.003, p=0.002, p=0.01, and p=0.02, respectively), the frequencies of the A*23, B*13, B*40, and DRB1*13 alleles were lower (p=0.002, p=0.07, p=0.002, and p=0.003, respectively) in patients than controls. The frequencies of the DRB1*04 and DRB1*07 alleles were higher in patients in the high-risk group and standard-risk group, respectively (p=0.009 and p=0.007, respectively). This study indicated that the frequency of the A*03 allele, the DRB1*03 allele, the DRB1*04 allele, the A*02/B*35/DRB1*13 haplotype, and A*02 homozygosity may play a predisposing role in patients with ALL in the Turkish population. The frequency of the DRB1*04 and DRB1*07 alleles may also be associated with high risk and standard risk in patients with ALL, respectively.

  16. Geographically Distinct and Domain-Specific Sequence Variations in the Alleles of Rice Blast Resistance Gene Pib

    PubMed Central

    Vasudevan, Kumar; Vera Cruz, Casiana M.; Gruissem, Wilhelm; Bhullar, Navreet K.

    2016-01-01

    Rice blast is caused by Magnaporthe oryzae, which is the most destructive fungal pathogen affecting rice growing regions worldwide. The rice blast resistance gene Pib confers broad-spectrum resistance against Southeast Asian M. oryzae races. We investigated the allelic diversity of Pib in rice germplasm originating from 12 major rice growing countries. Twenty-five new Pib alleles were identified that have unique single nucleotide polymorphisms (SNPs), insertions and/or deletions, in addition to the polymorphic nucleotides that are shared between the different alleles. These partially or completely shared polymorphic nucleotides indicate frequent sequence exchange events between the Pib alleles. In some of the new Pib alleles, nucleotide diversity is high in the LRR domain, whereas, in others it is distributed among the NB-ARC and LRR domains. Most of the polymorphic amino acids in LRR and NB-ARC2 domains are predicted as solvent-exposed. Several of the alleles and the unique SNPs are country specific, suggesting a diversifying selection of alleles in various geographical locations in response to the locally prevalent M. oryzae population. Together, the new Pib alleles are an important genetic resource for rice blast resistance breeding programs and provide new information on rice-M. oryzae interactions at the molecular level. PMID:27446145

  17. Geographically Distinct and Domain-Specific Sequence Variations in the Alleles of Rice Blast Resistance Gene Pib.

    PubMed

    Vasudevan, Kumar; Vera Cruz, Casiana M; Gruissem, Wilhelm; Bhullar, Navreet K

    2016-01-01

    Rice blast is caused by Magnaporthe oryzae, which is the most destructive fungal pathogen affecting rice growing regions worldwide. The rice blast resistance gene Pib confers broad-spectrum resistance against Southeast Asian M. oryzae races. We investigated the allelic diversity of Pib in rice germplasm originating from 12 major rice growing countries. Twenty-five new Pib alleles were identified that have unique single nucleotide polymorphisms (SNPs), insertions and/or deletions, in addition to the polymorphic nucleotides that are shared between the different alleles. These partially or completely shared polymorphic nucleotides indicate frequent sequence exchange events between the Pib alleles. In some of the new Pib alleles, nucleotide diversity is high in the LRR domain, whereas, in others it is distributed among the NB-ARC and LRR domains. Most of the polymorphic amino acids in LRR and NB-ARC2 domains are predicted as solvent-exposed. Several of the alleles and the unique SNPs are country specific, suggesting a diversifying selection of alleles in various geographical locations in response to the locally prevalent M. oryzae population. Together, the new Pib alleles are an important genetic resource for rice blast resistance breeding programs and provide new information on rice-M. oryzae interactions at the molecular level.

  18. Real-time PCR genotyping assay for canine progressive rod-cone degeneration and mutant allele frequency in Toy Poodles, Chihuahuas and Miniature Dachshunds in Japan

    PubMed Central

    KOHYAMA, Moeko; TADA, Naomi; MITSUI, Hiroko; TOMIOKA, Hitomi; TSUTSUI, Toshihiko; YABUKI, Akira; RAHMAN, Mohammad Mahbubur; KUSHIDA, Kazuya; MIZUKAMI, Keijiro; YAMATO, Osamu

    2015-01-01

    Canine progressive rod-cone degeneration (PRCD) is a middle- to late-onset, autosomal recessive, inherited retinal disorder caused by a substitution (c.5G>A) in the canine PRCD gene that has been identified in 29 or more purebred dogs. In the present study, a TaqMan probe-based real-time PCR assay was developed and evaluated for rapid genotyping and large-scale screening of the mutation. Furthermore, a genotyping survey was carried out in a population of the three most popular breeds in Japan (Toy Poodles, Chihuahuas and Miniature Dachshunds) to determine the current mutant allele frequency. The assay separated all the genotypes of canine PRCD rapidly, indicating its suitability for large-scale surveys. The results of the survey showed that the mutant allele frequency in Toy Poodles was high enough (approximately 0.09) to allow the establishment of measures for the prevention and control of this disorder in breeding kennels. The mutant allele was detected in Chihuahuas for the first time, but the frequency was lower (approximately 0.02) than that in Toy Poodles. The mutant allele was not detected in Miniature Dachshunds. This assay will allow the selective breeding of dogs from the two most popular breeds (Toy Poodle and Chihuahua) in Japan and effective prevention or control of the disorder. PMID:26549343

  19. Novel KIR3DL1 Alleles and Their Expression Levels on NK Cells: Convergent Evolution of KIR3DL1 Phenotype Variation?1,2

    PubMed Central

    Thomas, Rasmi; Yamada, Eriko; Alter, Galit; Martin, Maureen P.; Bashirova, Arman A.; Norman, Paul J.; Altfeld, Marcus; Parham, Peter; Anderson, Stephen K.; McVicar, Daniel W.; Carrington, Mary

    2009-01-01

    KIR3DL1 shows extensive polymorphism, and its variation has functional significance in terms of cell-surface expression levels and inhibitory capacity. We characterized nine KIR3DL1 alleles (*022, *028, *029, *033, *035, *051, *052, *053, and *054), four of which were identified for the first time in this study, and compared them to known alleles in phylogenetic analysis. Blood was available from eight individuals with these alleles, and cell-surface expression on NK cells could be determined for six of them using the KIR3DL1-specific Ab DX9. Four of the alleles were expressed at clearly detectable levels, and two others showed exceptionally low levels of expression. Site-directed mutagenesis demonstrated that single amino acid changes can result in either diminished or enhanced DX9 staining compared with the respective related KIR3DL1 allotypes. These results raise the possibility that KIR3DL1 evolution maintains variation in KIR3DL1 cell-surface expression levels, potentially due to the effect of such variation on functional capacity. PMID:18453594

  20. Determination of cis/trans phase of variations in the MC1R gene with allele-specific PCR and single base extension.

    PubMed

    Mengel-From, Jonas; Børsting, Claus; Sanchez, Juan J; Eiberg, Hans; Morling, Niels

    2008-12-01

    The MC1R gene encodes a protein with key regulatory functions in the melanin synthesis. A multiplex PCR and a multiplex single base extension protocol were established for genotyping six exonic MC1R variations highly penetrant for red hair (R), four exonic MC1R variations weakly penetrant for red hair (r), two frameshift variations highly penetrant for red hair (R) and three variations in the promoter region. We genotyped 600 individuals from Denmark using either CE or MALDI-TOF MS as the detection platform. A total of 62 individuals were genotyped R/R and among the 62 individuals, 57 had red hair and five had blond hair colour. Two different R alleles may be located in cis (RR/-) position or trans (R/R) position, and the phenotype associated with RR/- and R/R may be different. Two allele-specific PCRs were established with primers targeting the -G445A variation in the MC1R promoter and the allele-specific PCR products were used in the multiplex single base extension assay. In all 62 individuals, the MC1R variants were situated in trans position. Another 18 individuals with red hair colour were either genotyped R/- or R/r, suggesting that other genes influence hair colour.

  1. Allelic frequencies of 3' Ig heavy chain locus enhancer HS1,2-A associated with Ig levels in patients with schizophrenia and healthy control subjects

    PubMed Central

    Frezza, Domenico; Giambra, Vincenzo; Mattioli, Claudia; Piccoli, Katia; Massoud, Renato; Siracusano, Alberto; Giannantonio, Massimo Di; Birshtein, Barbara K.; Rubino, I. Alex

    2009-01-01

    Infectious and autoimmune pathogenic hypotheses of schizophrenia have been proposed, prompting searches for antibodies against viruses or brain structures, and for altered levels of immunoglobulins. Previous experiments have shown that allele frequencies of the Ig heavy chain 3' enhancer HS1,2*A are associated with several autoimmune diseases, suggesting a possible correlation between HS1,2 alleles and Ig production. To test this, we analyzed levels of serum Igs and HS1,2*A genotypes in two independent cohorts, one of 88 schizophrenic inpatients (24 women) and a second of 133 healthy subjects (59 women). Both groups were similar in the frequency of individuals with altered serum concentration of Ig classes and IgG subclasses (schizophrenia panel-80%; controls-68%). With the possible exception of a stabilizing effect of olanzapine, no psychopharmacological drug consumed during the month prior to serum sampling in the schizophrenia group significantly affected Ig levels. In both patient and control cohorts, an increased frequency of the HS1,2 *2A allele corresponded to increased Ig plasma levels, while an increased frequency of the HS1,2*1A allele corresponded to decreased Ig plasma levels. EMSA analysis with nuclear extracts from human B cells showed that the transcription factor SP1 bound to the polymorphic region of both HS1,2*1A and HS1,2*2A while NF-κB bound only to the HS1,2*2A. We predict that differences in transcription factor binding sites in the two allelic variants of the 3' IgH enhancer HS1,2 may provide a mechanism by which differences in Ig expression are affected. PMID:19309558

  2. Frequencies of 23 Functionally Significant Variant Alleles Related with Metabolism of Antineoplastic Drugs in the Chilean Population: Comparison with Caucasian and Asian Populations

    PubMed Central

    Roco, Ángela; Quiñones, Luis; Agúndez, José A. G.; García-Martín, Elena; Squicciarini, Valentina; Miranda, Carla; Garay, Joselyn; Farfán, Nancy; Saavedra, Iván; Cáceres, Dante; Ibarra, Carol; Varela, Nelson

    2012-01-01

    Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000 inhabitants and it is the second cause of death, after cardiovascular diseases. Most of the antineoplastic drugs are metabolized to be detoxified, and some of them to be activated. Genetic polymorphisms of drug-metabolizing enzymes can induce deep changes in enzyme activity, leading to individual variability in drug efficacy and/or toxicity. The present research describes the presence of genetic polymorphisms in the Chilean population, which might be useful in public health programs for personalized treatment of cancer, and compares these frequencies with those reported for Asian and Caucasian populations, as a contribution to the evaluation of ethnic differences in the response to chemotherapy. We analyzed 23 polymorphisms in a group of 253 unrelated Chilean volunteers from the general population. The results showed that CYP2A6*2, CYP2A6*3, CYP2D6*3, CYP2C19*3, and CYP3A4*17 variant alleles are virtually absent in Chileans. CYP1A1*2A allele frequency (0.37) is similar to that of Caucasians and higher than that reported for Japanese people. Allele frequencies for CYP3A5*3(0.76) and CYP2C9*3(0.04) are similar to those observed in Japanese people. CYP1A1*2C(0.32), CYP1A2*1F(0.77), CYP3A4*1B(0.06), CYP2D6*2(0.41), and MTHFR T(0.52) allele frequencies are higher than the observed either in Caucasian or in Japanese populations. Conversely, CYP2C19*2 allelic frequency (0.12), and genotype frequencies for GSTT1 null (0.11) and GSTM1 null (0.36) are lower than those observed in both populations. Finally, allele frequencies for CYP2A6*4(0.04), CYP2C8*3(0.06), CYP2C9*2(0.06), CYP2D6*4(0.12), CYP2E1*5B(0.14), CYP2E1*6(0.19), and UGT2B7*2(0.40) are intermediate in relation to those described in Caucasian and in Japanese populations, as expected according to the ethnic origin of the Chilean population. In conclusion, our findings support the idea that ethnic variability must be

  3. Inferring microevolutionary patterns from allele-size frequency distributions of minisatellite loci: a worldwide study of the APOB 3' hypervariable region polymorphism.

    PubMed

    Destro-Bisol, G; Capelli, C; Belledi, M

    2000-10-01

    The availability of numerous population and molecular data makes the apolipoprotein B 3' hypervariable region (APOB 3' HVR) polymorphism ideal for a pilot study of the relationships between the allele-size frequency distributions (referred to as allele-size distributions) of minisatellite loci and the microevolutionary processes underlying their present-day polymorphism in human populations. In this paper, we present a worldwide APOB 3' HVR study, based on published and unpublished data, which refers to 36 populations. We systematically compare APOB 3' HVR within-group diversity (in terms of heterozygosity, number of alleles, and allele-size variance) in numerous human populations, including African, European, Asian, Amerindian, Australomelanesian, and Polynesian groups. Overall, our analyses indicate a greater APOB 3' HVR diversity in Africans than non-Africans. Then, we compare APOB 3' HVR allele-size distributions. The APOB 3' HVR allele-size distribution is found to be quasi-unimodal in Africans and bimodal or nonunimodal in non-African populations. The analysis of the distribution of pairwise comparisons suggests that Africans expanded earlier and/or that their ancestral population was larger than other continental groups. As a final step, we examine APOB 3' HVR interpopulational relationships by using three genetic distances. The F(ST) genetic distance, which assumes genetic drift as being the agent that differentiates populations, provides results that are more congruent with established anthropological knowledge than mutation-based distances (D(SW) and R(ST)). We hypothesize that the ancestral population was characterized by a high heterozygosity, an extended range of allele size, and a quasi-unimodal allele-size distribution centered on allele *37, features persisting in examined African populations. Sampling processes during "out-of-Africa" migrations would be responsible for the decrease in APOB 3' HVR gene diversity and the nonunimodal allele

  4. Frequency of streptococcal upper respiratory tract infections and HLA-Cw*06 allele in 70 patients with guttate psoriasis from northern Poland

    PubMed Central

    Szczerkowska-Dobosz, Aneta; Rębała, Krzysztof; Wysocka, Joanna; Roszkiewicz, Jadwiga; Szczerkowska, Zofia; Placek, Waldemar

    2015-01-01

    Introduction The association of guttate psoriasis with a streptococcal throat infection and HLA-Cw*06 allele is well established in different populations. Nevertheless, only few studies on this form of disease have been performed in the Polish population. Aim To analyze the frequencies of streptococcal-induced guttate psoriasis and HLA-Cw*06 allele in 70 patients with guttate psoriasis originating from northern Poland. Material and methods Seventy patients with guttate psoriasis and 24 healthy volunteers were enrolled into the study. Both groups were sex- and age-matched. The evidence of streptococcal infection was based on the positive throat swabs and/or elevated ASO titers. The modified method, including PCR-SSP and PCR-RFLP, was applied to HLA-Cw*06 genotyping. Results HLA-Cw*06 allele was confirmed in 49 (70%) out of 70 patients, which is significantly higher than in the control population (30%) (p = 0.001). Evidence for streptococcal infection was found in 34 (48.5%) subjects with psoriasis. Twenty-seven of them (79%) carried HLA-Cw*06 allele. In 36 individuals in whom no evidence of streptococcal infection was found, 14 (39%) did not carry HLA-Cw*06 allele. Conclusions Our data confirm that HLA-Cw*06 is a major, but not imperative, genetic determinant for guttate psoriasis. PMID:26755910

  5. High Frequency of Copy Number Variations and Sequence Variants at CYP21A2 Locus: Implication for the Genetic Diagnosis of 21-Hydroxylase Deficiency

    PubMed Central

    Parajes, Silvia; Quinteiro, Celsa; Domínguez, Fernando; Loidi, Lourdes

    2008-01-01

    Background The systematic study of the human genome indicates that the inter-individual variability is greater than expected and it is not only related to sequence polymorphisms but also to gene copy number variants (CNVs). Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (21OHD) is the most common autosomal recessive disorder with a carrier frequency of 1∶25 to 1∶10. The gene that encodes 21-hydroxylase enzyme, CYP21A2, is considered to be one of the most polymorphic human genes. Copy number variations, such as deletions, which are severe mutations common in 21OHD patients, or gene duplications, which have been reported as rare events, have also been described. The correct characterization of 21OHD alleles is important for disease carrier detection and genetic counselling Methodology and Findings CYP21A2 genotyping by sequencing has been performed in a random sample of the Spanish population, where 144 individuals recruited from university students and employees of the hospital were studied. The frequency of CYP21A2 mutated alleles in our sample was 15.3% (77.3% were mild mutations, 9% were severe mutations and 13.6% were novel variants). Gene dosage assessment was also performed when CYP21A2 gene duplication was suspected. This analysis showed that 7% of individuals bore a chromosome with a duplicated CYP21A2 gene, where one of the copies was mutated. Conclusions As far as we know, the present study has shown the highest frequency of 21OHD carriers reported by a genotyping analysis. In addition, a high frequency of alleles with CYP21A2 duplications, which could be misinterpreted as 21OHD alleles, was found. Moreover, a high frequency of novel genetic variations with an unknown effect on 21-hydroxylase activity was also found. The high frequency of gene duplications, as well as novel variations, should be considered since they have an important involvement in carrier testing and genetic counseling. PMID:18478071

  6. Identification of internal variation in the pseudoautosomal VNTR DXYS17, with nonrandom distribution of the alleles on the X and the Y chromosomes

    SciTech Connect

    Decorte, R.; Wu, R.; Marynen, P.; Cassiman, J.J.

    1994-03-01

    The PCR technique was used to analyze the DXYS17 locus in the pseudoautosomal region of the X and the Y chromosomes. Analysis on an automated DNA sequencer allowed for sensitive and highly accurate typing of 16 different alleles with a size between 480 and 1,100 bp. Two DXYS17 alleles migrated with the same size on agarose or denaturing polyacrylamide gels but with different mobilities on nondenaturing polyacrylamide gels. Sequence analysis showed that, while an identical number of repeats were present in both alleles, differences in the composition of the units were observed. The origin of these differences was found in the 28- and 33-bp units, which only had a specific repeat pattern at the 5' and 3' ends of the region. The genotype distribution for DXYS17 in a Caucasian population did not deviate from the values expected under Hardy-Weinberg equilibrium. However, the frequency of one allele and one genotype was significantly different between males and females. Segregation analysis showed that this difference was the result of a nonrandom distribution of certain alleles on the sex chromosomes in males. 31 refs., 4 figs., 2 tabs.

  7. Allelic and genotypic frequencies in polymorphic Booroola fecundity gene and their association with multiple birth and postnatal growth in Chhotanagpuri sheep

    PubMed Central

    Oraon, Thanesh; Singh, D. K.; Ghosh, Mayukh; Kullu, S. S.; Kumar, Rajesh; Singh, L. B.

    2016-01-01

    Aim: Chhotanagpuri breed of sheep reared for mutton in Jharkhand, India, having problem of low litter size and body weight. The response of genetic improvement for traits with low heritability through traditional selection method is time-consuming. Therefore, marker-assisted selection based on a polymorphism study of suitable candidate gene can response quickly. Thus, this study was aimed at identification of different allelic and genotypic frequencies of Booroola fecundity (FecB) gene and its association with multiple birth and postnatal growth in Chhotanagpuri sheep. Materials and Methods: DNA isolation and gene-specific amplification of FecB gene was performed from blood samples of from 92 Chhotanagpuri lambs maintained under similar feeding and management conditions. Custom nucleotide sequencing and single-strand conformational polymorphism analysis were performed to identify different genotypes with respect to the target gene. Statistical analysis was performed for determination of allelic and genotypic frequencies of FecB gene polymorphisms and its association with multiple birth and postnatal growth of lambs from birth to 52 weeks age. Results: “AA,” “AB,” and “BB” genotypes were found at locus-1 as it is polymorphic for FecB gene while locus-2 was found to be monomorphic for FecB gene. Higher frequency of “A” allele at locus-1 was found in single born lambs, whereas “B” allele was predominant among multiple born lambs. The lambs having “BB” genotype weighed significantly (p≤0.01) heavier than those of “AB” and “AA” genotype at 52 weeks of age. Conclusion: “BB” genotype has emerged as favored genotype for multiple births and better growth indicator. Therefore, homozygous lambs for “B” allele should be selected and utilized in breeding program for better growth rate. PMID:27956784

  8. THE REAL McCOIL: A method for the concurrent estimation of the complexity of infection and SNP allele frequency for malaria parasites

    PubMed Central

    Chang, Hsiao-Han; Worby, Colin J.; Yeka, Adoke; Nankabirwa, Joaniter; Kamya, Moses R.; Staedke, Sarah G.; Hubbart, Christina; Amato, Roberto; Kwiatkowski, Dominic P.

    2017-01-01

    As many malaria-endemic countries move towards elimination of Plasmodium falciparum, the most virulent human malaria parasite, effective tools for monitoring malaria epidemiology are urgent priorities. P. falciparum population genetic approaches offer promising tools for understanding transmission and spread of the disease, but a high prevalence of multi-clone or polygenomic infections can render estimation of even the most basic parameters, such as allele frequencies, challenging. A previous method, COIL, was developed to estimate complexity of infection (COI) from single nucleotide polymorphism (SNP) data, but relies on monogenomic infections to estimate allele frequencies or requires external allele frequency data which may not available. Estimates limited to monogenomic infections may not be representative, however, and when the average COI is high, they can be difficult or impossible to obtain. Therefore, we developed THE REAL McCOIL, Turning HEterozygous SNP data into Robust Estimates of ALelle frequency, via Markov chain Monte Carlo, and Complexity Of Infection using Likelihood, to incorporate polygenomic samples and simultaneously estimate allele frequency and COI. This approach was tested via simulations then applied to SNP data from cross-sectional surveys performed in three Ugandan sites with varying malaria transmission. We show that THE REAL McCOIL consistently outperforms COIL on simulated data, particularly when most infections are polygenomic. Using field data we show that, unlike with COIL, we can distinguish epidemiologically relevant differences in COI between and within these sites. Surprisingly, for example, we estimated high average COI in a peri-urban subregion with lower transmission intensity, suggesting that many of these cases were imported from surrounding regions with higher transmission intensity. THE REAL McCOIL therefore provides a robust tool for understanding the molecular epidemiology of malaria across transmission settings. PMID

  9. Human leukocyte antigen class II (DRB1 and DQB1) alleles and haplotypes frequencies in patients with pemphigus vulgaris among the Serbian population.

    PubMed

    Zivanovic, D; Bojic, S; Medenica, L; Andric, Z; Popadic, D

    2016-05-01

    The etiology of pemphigus vulgaris (PV) is multifactorial and includes genetic, environmental, hormonal, and immunological factors. Inheritance of certain Human class II leukocyte antigen (HLA) alleles is by far the best-established predisposing factor for the development of PV. Class II HLA alleles vary among racial/ethnic backgrounds. We have determined an association between HLA class II alleles and PV among the Serbian population. A total of 72 patients with confirmed diagnosis of PV were genotyped for HLA class II alleles. HLA frequencies were compared with unrelated healthy bone marrow donors. The statistical significance of differences between patients and controls was evaluated using Fisher's exact test. The DRB1*04 and DRB1*14 allelic groups were associated with PV (P adj = 4.45 × 10(-13) and 4.06 × 10(-19) respectively), while HLA-DRB1*11 was negatively associated with PV (P adj = 0.0067) suggesting a protective role. DRB1*04:02, DRB1*14:04, DQB1*03:02 and DQB1*05:03 alleles were shown to be strongly associated with PV (P adj = 1.63 × 10(-12), 5.20 × 10(-7), 1.28 × 10(-6), and 4.44 × 10(-5), respectively). The frequency of HLA DRB1*04-DQB1*03 and HLA DRB1*14-DQB1*05 haplotypes in PV patients was significantly higher than in controls (31.3% vs 8.8%, P adj =7.66 × 10(-8) and 30.6% vs 6.3%, P adj = 3.22 × 10(-10), respectively). At high-resolution level, statistical significance was observed in HLA-DRB1*04:02-DQB1*03:02 and HLA-DRB1*14:04-DQB1*05:03 haplotypes (P adj = 5.55 × 10(-12), and P adj = 3.91 × 10(-6), respectively). Our findings suggest that HLA-DRB1*04:02, DRB1*14:04, HLA-DQB1* 03:02 and DQB1*05:03 alleles and HLA-DRB1*04:02-DQB1*03:02 and HLA-DRB1*14:04-DQB1*05:03 haplotypes are genetic markers for susceptibility for PV, while DRB1*11 allelic group appears protective in Serbian population.

  10. A non-synonymous SNP with the allele frequency correlated with the altitude may contribute to the hypoxia adaptation of Tibetan chicken

    PubMed Central

    Wang, Yan; Yin, Huadong; Zhou, Lanyun; Zhong, Chengling

    2017-01-01

    The hypoxia adaptation to high altitudes is of considerable interest in the biological sciences. As a breed with adaptability to highland environments, the Tibetan chicken (Gallus gallus domestics), provides a biological model to search for genetic differences between high and lowland chickens. To address mechanisms of hypoxia adaptability at high altitudes for the Tibetan chicken, we focused on the Endothelial PAS domain protein 1 (EPAS1), a key regulatory factor in hypoxia responses. Detected were polymorphisms of EPAS1 exons in 157 Tibetan chickens from 8 populations and 139 lowland chickens from 7 breeds. We then designed 15 pairs of primers to amplify exon sequences by Sanger sequencing methods. Six single nucleotide polymorphisms (SNPs) were detected, including 2 missense mutations (SNP3 rs316126786 and SNP5 rs740389732) and 4 synonymous mutations (SNP1 rs315040213, SNP4 rs739281102, SNP6 rs739010166, and SNP2 rs14330062). There were negative correlations between altitude and mutant allele frequencies for both SNP6 (rs739010166, r = 0.758, p<0.001) and SNP3 (rs316126786, r = 0.844, P<0.001). We also aligned the EPAS1 protein with ortholog proteins from diverse vertebrates and focused that SNP3 (Y333C) was a conserved site among species. Also, SNP3 (Y333C) occurred in a well-defined protein domain Per-AhR-Arnt-Sim (PAS domain). These results imply that SNP3 (Y333C) is the most likely casual mutation for the high-altitude adaption in Tibetan chicken. These variations of EPAS1 provide new insights into the gene’s function. PMID:28222154

  11. Genotype prevalence and allele frequencies of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T mutation in two caste groups of India.

    PubMed

    Rai, V; Yadav, U; Kumar, P

    2012-06-15

    The aim of the present study was to investigate the distribution of 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphism in two caste group populations of eastern Uttar Pradesh. This mutation has been suggested to be positively associated with the risk of several congenital and multifactorial disorders. Frequency of mutant T allele differs in various ethnic and geographical populations of the world. MTHFR C677T mutation analysis was carried out by PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism) method and the samples studied were randomly selected from the healthy individuals belonging to two caste populations. In Brahmin samples, genotype frequencies of CC, CT and TT were 0.727, 0.25 and 0.023 respectively whereas in Rajput samples, CC genotype was observed in 88 samples, CT genotype in 25 and TT genotype was found in 2 samples. Frequency of mutant T allele was found to be 0.147 in Brahmin and 0.126 in Rajput populations. The percentage of CT genotype and C allele were high in both the populations.

  12. Recommendations of the DNA Commission of the International Society for Forensic Genetics (ISFG) on quality control of autosomal Short Tandem Repeat allele frequency databasing (STRidER).

    PubMed

    Bodner, Martin; Bastisch, Ingo; Butler, John M; Fimmers, Rolf; Gill, Peter; Gusmão, Leonor; Morling, Niels; Phillips, Christopher; Prinz, Mechthild; Schneider, Peter M; Parson, Walther

    2016-09-01

    The statistical evaluation of autosomal Short Tandem Repeat (STR) genotypes is based on allele frequencies. These are empirically determined from sets of randomly selected human samples, compiled into STR databases that have been established in the course of population genetic studies. There is currently no agreed procedure of performing quality control of STR allele frequency databases, and the reliability and accuracy of the data are largely based on the responsibility of the individual contributing research groups. It has been demonstrated with databases of haploid markers (EMPOP for mitochondrial mtDNA, and YHRD for Y-chromosomal loci) that centralized quality control and data curation is essential to minimize error. The concepts employed for quality control involve software-aided likelihood-of-genotype, phylogenetic, and population genetic checks that allow the researchers to compare novel data to established datasets and, thus, maintain the high quality required in forensic genetics. Here, we present STRidER (http://strider.online), a publicly available, centrally curated online allele frequency database and quality control platform for autosomal STRs. STRidER expands on the previously established ENFSI DNA WG STRbASE and applies standard concepts established for haploid and autosomal markers as well as novel tools to reduce error and increase the quality of autosomal STR data. The platform constitutes a significant improvement and innovation for the scientific community, offering autosomal STR data quality control and reliable STR genotype estimates.

  13. Frequency distribution of Q188R, N314D, Duarte 1, and Duarte 2 GALT variant alleles in an Indian galactosemia population.

    PubMed

    Singh, Ramandeep; Thapa, Babu R; Kaur, Gurjit; Prasad, Rajendra

    2012-12-01

    Classical galactosemia is a genetic disorder caused by mutations in the galactose-1-phosphate uridyltransferase (GALT) gene. The Q188R and N314D mutations are the most frequently cited GALT gene mutations. N314D is further associated with two variants, Duarte 1 and Duarte 2. Nevertheless, no reports are available on the clinical and molecular spectrum of galactosemia from the Indian population. The present study was designed to establish the frequency of these two most common mutations and their variants in Indian galactosemia patients so as to determine a single most common mutation/polymorphism for establishing the DNA-based diagnosis of galactosemia. Three alleles were found to be present at a frequency of 0.036 (Q188R), 0.40 (N314D), and 0.39 (D2); no D1 alleles were found. A significantly higher frequency of the Duarte 2 allele in our population suggests the presence of a milder form of galactosemia, which can be well managed by early diagnosis and dietary management.

  14. Estimation of the 6-digit level allele and haplotype frequencies of HLA-A, -B, and -C in Koreans using ambiguity-solving DNA typing.

    PubMed

    Jun, J-H; Hwang, K; Kim, S-K; Oh, H-B; Cho, M-C; Lee, K-J

    2014-09-01

    Because Korean society is fast becoming multi-ethnic, the determination of ambiguous human leukocyte antigen (HLA) types using HLA allele frequencies is becoming less applicable. In this study, we focused on the development of new technical methods to directly resolve the ambiguities arising from HLA genotyping. One hundred and fifty unrelated healthy Korean adults were included in this study. All alleles from each HLA locus were first divided into 2-4 groups, with each group amplified in a single PCR tube (multi-group-specific amplification, MGSA). To resolve phase ambiguities, some allele groups were also amplified separately in small group-specific amplification (SGSA) tubes. In order to then resolve incomplete sequence ambiguities, primers for MGSA and SGSA were initially designed to cover additional exons. If needed, a heterozygous ambiguity resolving primer (HARP) or sequence specific primer (SSP) was also used. When MGSA and SGSA methods were applied, the rate of phase ambiguity was greatly reduced to an average of 6% (1.3% in HLA-A, 15.7% in -B, and 2.0% in -C). Additional HARP and SSP methods could resolve all the phase ambiguities. Using our proposed method, we also detected three alleles that have not been previously reported in Korea, C*04:82, C*07:18, and C*08:22, and report 6-digit level HLA allele and haplotype frequencies among Koreans. In conclusion, the use of MGSA/SGSA for the initial amplification step is a cost-effective method facilitating timely and accurate reporting, given the continuing increase in the ethnic diversity of the Korean population. The MGSA described here can be applicable to various populations and thus could be shared by the majority of HLA typing laboratories. However, efforts to solve HLA ambiguity should continue, because SGSA, HARPs and SSPs would be specific to a particular population.

  15. Allelic variation of Ets1 does not contribute to NK and NKT cell deficiencies in type 1 diabetes susceptible NOD mice.

    PubMed

    Jordan, Margaret A; Poulton, Lynn D; Fletcher, Julie M; Baxter, Alan G

    2009-01-01

    The NOD mouse is a well characterized model of type 1 diabetes that shares several of the characteristics of Ets1-deficient targeted mutant mice, viz: defects in TCR allelic exclusion, susceptibility to a lupus like disease characterized by IgM and IgG autoantibodies and immune complex-mediated glomerulonephritis, and deficiencies of NK and NKT cells. Here, we sought evidence for allelic variation of Ets1 in mice contributing to the NK and NKT cell phenotypes of the NOD strain. ETS1 expression in NK and NKT cells was reduced in NOD mice, compared to C57BL/6 mice. Although NKT cells numbers were significantly correlated with ETS1 expression in both strains, NKT cell numbers were not linked to the Ets1 gene in a first backcross from NOD to C57BL/6 mice. These results indicate that allelic variation of Ets1 did not contribute to variation in NKT cell numbers in these mice. It remains possible that a third factor not linked to the Ets1 locus controls both ETS1 expression and subsequently NK and NKT cell phenotypes.

  16. Somatic homologous recombination in planta: the recombination frequency is dependent on the allelic state of recombining sequences and may be influenced by genomic position effects.

    PubMed

    Swoboda, P; Hohn, B; Gal, S

    1993-02-01

    We have previously described a non-selective method for scoring somatic recombination in the genome of whole plants. The recombination substrate consists of a defective partial dimer of Cauliflower Mosaic Virus (CaMV) sequences, which can code for production of viable virus only upon homologous recombination; this leads to disease symptoms on leaves. Brassica napus plants (rapeseed) harbouring the recombination substrate as a transgene were used to examine the time in plant development at which recombination takes place. The analysis of three transgene loci revealed recombination frequencies specific for each locus. Recombination frequencies were increased if more than one transgene locus was present per genome, either in allelic (homozygosity of the transgene locus) or in non-allelic positions. In both cases, the overall recombination frequency was found to be elevated to approximately the sum of the frequencies for the individual transgene loci or slightly higher, suggesting that the respective transgene loci behave largely independently of each other. For all plants tested (single locus, two or multiple loci) maximal recombination frequencies were of the order of 10(-6) events per cell division.

  17. MICA genetic polymorphism and HLA-A,C,B,MICA and DRB1 haplotypic variation in a southern Chinese Han population: identification of two new MICA alleles, MICA*060 and MICA*062.

    PubMed

    Tian, Wei; Cai, JinHong; Liu, XueXiang

    2011-06-01

    In this study, 201 healthy, unrelated Han subjects in Hunan province, southern China, were investigated by sequence-based typing (SBT) for the allelic variation of the human major histocompatibility complex (MHC) class I chain-related gene A (MICA). Nineteen MICA alleles were observed, among which MICA*008:01 predominated with gene frequency of 30.35%. There was significant linkage disequilibrium (LD) of MICA*012:01 with HLA-B*54 and HLA-B*55, which was not observed in a northern Chinese Han population. Haplotype HLA-A*11-C*07-B60-MICA*008:01 (9.16%) was highly specific to this southern Chinese Han population. The most common five-locus haplotype in this population was HLA-A*02-C*01-B*46-MICA*010-DRB1*09 (8.73%). A new MICA allele, MICA*060, was identified on an HLA-A*02-C*01-B*55:02-DRB1*14 haplotype through extended family analysis. MICA*060 has probably arisen from MICA*012:01. Another new MICA allele, MICA*062, was identified by screening 1432 subjects using polymerase chain reaction-sequence-specific priming technology. MICA*062 has probably derived from MICA*010. Of particular interest is that MICA*062 was carried on an HLA-C*08-B*48:01-DRB1*14 haplotypic segment, as HLA-B*48 has been consistently shown to be primarily linked to MICA gene deletion in east Asian populations. Our results provide new insight into MICA genetic polymorphism in human populations. The findings reported here are of importance for future studies on the potential role of MICA in allogeneic organ transplantation and disease association in populations of Chinese ancestry.

  18. Neonatal screening for hereditary fructose intolerance: frequency of the most common mutant aldolase B allele (A149P) in the British population.

    PubMed

    James, C L; Rellos, P; Ali, M; Heeley, A F; Cox, T M

    1996-10-01

    Hereditary fructose intolerance (HFI) causes severe and sometimes fatal metabolic disturbances in infants and children but responds to dietary treatment. To determine the practicability of screening newborn infants for HFI, we have investigated the frequency of the most common and widespread mutant allele of aldolase B, A149P, in the neonatal population. The polymerase chain reaction was used to amplify aldolase B exon 5 genomic sequences in DNA present in dried blood specimens preserved on Guthrie cards. The A149P mutation was identified by discriminatory hybridisation to allele specific oligonucleotides and confirmed independently by digestion with the restriction endonuclease BsaHI. Twenty-seven A149P heterozygotes were identified by the molecular analysis of aldolase B genes in blood samples obtained from a random cohort of 2050 subjects born in 1994 and 1995, 1.32 +/- 0.49% (95% confidence level). Although no A149P homozygotes were identified, the data allow the frequency of 1 in 23,000 homozygotes for this allele to be predicted. Our findings have implications for establishing an interventional mass screening programme to identify newborn infants with HFI in the UK.

  19. Frequency variations of discrete cranial traits in major human populations. III. Hyperostotic variations

    PubMed Central

    HANIHARA, TSUNEHIKO; ISHIDA, HAJIME

    2001-01-01

    Seven discrete cranial traits usually categorised as hyperostotic characters, the medial palatine canal, hypoglossal canal bridging, precondylar tubercle, condylus tertius, jugular foramen bridging, auditory exostosis, and mylohyoid bridging were investigated in 81 major human population samples from around the world. Significant asymmetric occurrences of the bilateral traits were detected in the medial palatine canal and jugular foramen bridging in several samples. Significant intertrait associations were found between some pairs of the traits, but not consistently across the large geographical samples. The auditory exostosis showed a predominant occurrence in males. With the exception of the auditory exostosis and mylohyoid bridging in a few samples, significant sex differences were slight. The frequency distributions of the traits (except for the auditory exostosis) showed some interregional clinality and intraregional discontinuity, suggesting that genetic drift could have contributed to the observed pattern of variation. PMID:11554504

  20. Association between a high-expressing interferon-gamma allele and a lower frequency of kidney angiomyolipomas in TSC2 patients.

    PubMed

    Dabora, Sandra L; Roberts, Penelope; Nieto, Andres; Perez, Ron; Jozwiak, Sergiusz; Franz, David; Bissler, John; Thiele, Elizabeth A; Sims, Katherine; Kwiatkowski, David J

    2002-10-01

    Tuberous sclerosis complex (TSC) is a familial hamartoma syndrome in which renal involvement is common and, at times, life threatening. We have investigated the potential effect of a non-TSC gene on renal disease in a cohort of 172 TSC patients with TSC2 mutations. Patients were genotyped for an interferon-gamma (IFN-gamma) microsatellite polymorphism, within intron 1, for which one common allele (allele 2, with 12 CA repeats) has been shown to have a higher expression of IFN-gamma. A chi(2) analysis was used to examine the association between IFN-gamma allele 2 and the development of kidney angiomyolipomas (KAMLs) in this TSC2 cohort. Because of the age-dependent development of KAMLs in TSC, we initially focused on the 127 patients who were >5 years old. Additional subgroup analyses were done to investigate the influence of age and gender. The transmission/disequilibrium test (TDT) was also performed in a subset of this cohort (46 probands) for whom parent and/or sibling samples were available for analysis. Both chi(2) analysis and TDT suggested an association between IFN-gamma allele 2 and the absence of KAMLs in patients who have known TSC2 mutations. Among the 127 patients who were >5 years old, KAMLs were present in 95 (75%) and were absent in 32 (25%). In the group with KAML present, the frequency of IFN-gamma allele 2 was 56%; in the group with KAML absent, the frequency of IFN-gamma allele 2 was significantly higher, at 78% (P=.02, by chi(2) analysis). The family-based TDT analysis gave similar results, with a TDT statistic (TDT chi2=5.45) corresponding to a P value of.02. Subgroup analyses show that both age and gender may influence the impact of this association. Although these results should be replicated in other populations with TSC, the present study suggests that modifier genes play a role in the variable expression of TSC and also suggests a potential therapy for KAMLs in patients with TSC.

  1. Read distance performance and variation of 5 low-frequency radio frequency identification panel transceiver manufacturers.

    PubMed

    Ryan, S E; Blasi, D A; Anglin, C O; Bryant, A M; Rickard, B A; Anderson, M P; Fike, K E

    2010-07-01

    Use of electronic animal identification technologies by livestock managers is increasing, but performance of these technologies can be variable when used in livestock production environments. This study was conducted to determine whether 1) read distance of low-frequency radio frequency identification (RFID) transceivers is affected by type of transponder being interrogated; 2) read distance variation of low-frequency RFID transceivers is affected by transceiver manufacturer; and 3) read distance of various transponder-transceiver manufacturer combinations meet the 2004 United States Animal Identification Plan (USAIP) bovine standards subcommittee minimum read distance recommendation of 60 cm. Twenty-four transceivers (n = 5 transceivers per manufacturer for Allflex, Boontech, Farnam, and Osborne; n = 4 transceivers for Destron Fearing) were tested with 60 transponders [n = 10 transponders per type for Allflex full duplex B (FDX-B), Allflex half duplex (HDX), Destron Fearing FDX-B, Farnam FDX-B, and Y-Tex FDX-B; n = 6 for Temple FDX-B (EM Microelectronic chip); and n = 4 for Temple FDX-B (HiTag chip)] presented in the parallel orientation. All transceivers and transponders met International Organization for Standardization 11784 and 11785 standards. Transponders represented both one-half duplex and full duplex low-frequency air interface technologies. Use of a mechanical trolley device enabled the transponders to be presented to the center of each transceiver at a constant rate, thereby reducing human error. Transponder and transceiver manufacturer interacted (P < 0.0001) to affect read distance, indicating that transceiver performance was greatly dependent upon the transponder type being interrogated. Twenty-eight of 30 combinations of transceivers and transponders evaluated met the minimum recommended USAIP read distance. The mean read distance across all 30 combinations was 45.1 to 129.4 cm. Transceiver manufacturer and transponder type interacted to affect read

  2. Allelic Variation in a Simple Sequence Repeat Element of Neisserial pglB2 and Its Consequences for Protein Expression and Protein Glycosylation

    PubMed Central

    Viburiene, Raimonda; Vik, Åshild; Koomey, Michael

    2013-01-01

    Neisseria species express an O-linked glycosylation system in which functionally distinct proteins are elaborated with variable glycans. A major source of glycan diversity in N. meningitidis results from two distinct pglB alleles responsible for the synthesis of either N,N′-diacetylbacillosamine or glyceramido-acetamido trideoxyhexose that occupy the reducing end of the oligosaccharides. Alternative modifications at C-4 of the precursor UDP-4-amino are attributable to distinct C-terminal domains that dictate either acetyltransferase or glyceramidotransferase activity, encoded by pglB and pglB2, respectively. Naturally occurring alleles of pglB2 have homopolymeric tracts of either 7 or 8 adenosines (As) bridging the C-terminal open reading frame (ORF) and the ORF encompassing the conserved N-terminal domain associated with phosphoglycosyltransferase activity. In the work presented here, we explored the consequences of such pglB2 allele variation and found that, although both alleles are functional vis-à-vis glycosylation, the 7A form results in the expression of a single, multidomain protein, while the 8A variant elicits two single-domain proteins. We also found that the glyceramidotransferase activity-encoding domain is essential to protein glycosylation, showing the critical role of the C-4 modification of the precursor UDP-4-amino in the pathway. These findings were further extended and confirmed by examining the phenotypic consequences of extended poly(A) tract length variation. Although ORFs related to those of pglB2 are broadly distributed in eubacteria, they are primarily found as two distinct, juxtaposed ORFs. Thus, the neisserial pglB2 system provides novel insights into the potential influence of hypermutability on modular evolution of proteins by providing a unique snapshot of the progression of ongoing gene fusion. PMID:23729645

  3. Polymorphisms and allele frequencies of glutathione S-transferases A1 and P1 genes in the Polish population.

    PubMed

    Skrzypczak-Zielinska, M; Zakerska-Banaszak, O; Tamowicz, B; Sobieraj, I; Drweska-Matelska, N; Szalata, M; Slomski, R; Mikstacki, A

    2015-03-31

    Glutathione S-transferases (GST) A1 and P1 are crucial enzymes involved in the biotransformation of drugs, carcinogens, and toxins, and their activity may influence drug response, susceptibility to diseases, and carcinogenesis. The genes encoding these enzymes, GSTA1 and GSTP1, have been examined in many studies because of their genetic variability, which may affect enzymatic activity. The goal of this study was to determine the distribution of the alleles GSTA1*A/*B and GSTP1*A, *B, and *C in the Polish population. A total of 160 subjects from the Polish population were genotyped for 2 polymorphisms (I105V and A114V) in the GSTP1 gene using pyrosequencing. The promoter region of the GSTA1 gene was screened using sequencing. The detected variants were subjected to haplotype analysis. We found that the distribution of the alleles GSTA1*A/*B and GSTP1*A, *B, and *C in the Polish population correspond to the results of studies in Caucasians. Furthermore, we identified additional single nucleotide polymorphisms, excluding 3 well-known changes (G-52A, C-69T, T-567G), which are linked to alleles GSTA1*A/*B, that affect enzyme activity. A total of 4 haplotypes were identified in 160 Polish individuals.

  4. Frequency of Cry1F Non-Recessive Resistance Alleles in North Carolina Field Populations of Spodoptera frugiperda (Lepidoptera: Noctuidae)

    PubMed Central

    Li, Guoping; Reisig, Dominic; Miao, Jin; Gould, Fred; Huang, Fangneng; Feng, Hongqiang

    2016-01-01

    Fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), is a target species of transgenic corn (Zea mays L.) that expresses single and pyramided Bacillus thuringiensis (Bt) toxin. In 2014, S. frugiperda were collected from a light trap in North Carolina, and a total of 212 F1/F2 isofemale lines of S. frugiperda were screened for resistance to Bt and non-Bt corn. All of the 212 isolines were susceptible to corn tissue expressing Cry1A.105 + Cry2Ab, Cry1F + Cry1A.105 + Cry2Ab, and Cry1F + Cry1Ab + Vip3Aa20. Growth rate bioassays were performed to isolate non-recessive Bt resistance alleles. Seven individuals out of the 212 isofemale lines carried major non-recessive alleles conferring resistance to Cry1F. A pooled colony was created from the seven individuals. This colony was 151.21 times more resistant to Cry1F than a known-susceptible population and was also resistant to Cry1A.105, but was not resistant to Cry2Ab and Vip3Aa20. The results demonstrate that field populations of S. frugiperda collected from North Carolina are generally susceptible to Cry1F, but that some individuals carry resistant alleles. The data generated in this study can be used as baseline data for resistance monitoring. PMID:27119741

  5. Short communication: The combined use of linkage disequilibrium-based haploblocks and allele frequency-based haplotype selection methods enhances genomic evaluation accuracy in dairy cattle.

    PubMed

    Jónás, Dávid; Ducrocq, Vincent; Croiseau, Pascal

    2017-04-01

    The construction and use of haploblocks [adjacent single nucleotide polymorphisms (SNP) in strong linkage disequilibrium] for genomic evaluation is advantageous, because the number of effects to be estimated can be reduced without discarding relevant genomic information. Furthermore, haplotypes (the combination of 2 or more SNP) can increase the probability of capturing the quantitative trait loci effect compared with individual SNP markers. With regards to haplotypes, the allele frequency parameter is also of interest, because as a selection criterion, it allows the number of rare alleles to be reduced, and the effects of those alleles are usually difficult to estimate. We have proposed a simple pipeline that simultaneously incorporates linkage disequilibrium and allele frequency information in genomic evaluation, and here we present the first results obtained with this procedure. We used a population of 2,235 progeny-tested bulls from the Montbéliarde breed for the tests. Phenotype data were available in the form of daughter yield deviations on 5 production traits, and genotype data were available from the 50K SNP chip. We conducted a classical validation study by splitting the population into training (80% oldest animals) and validation (20% youngest animals) sets to emulate a real-life scenario in which the selection candidates had no available phenotype data. We measured all reported parameters for the validation set. Our results proved that the proposed method was indeed advantageous, and that the accuracy of genomic evaluation could be improved. Compared with results from a genomic BLUP analysis, correlations between daughter yield deviations (a proxy for true) and genomic estimated breeding values increased by an average of 2.7 percentage points for the 5 traits. Inflation of the genomic evaluation of the selection candidates was also significantly reduced. The proposed method outperformed the other SNP and haplotype-based tests we had evaluated in a

  6. Allelic variation in two distinct Pseudomonas syringae flagellin epitopes modulates the strength of plant immune responses but not bacterial motility

    PubMed Central

    Clarke, Christopher R.; Chinchilla, Delphine; Hind, Sarah R.; Taguchi, Fumiko; Miki, Ryuji; Ichinose, Yuki; Martin, Gregory B.; Leman, Scotland; Felix, Georg; Vinatzer, Boris A.

    2013-01-01

    Summary The bacterial flagellin (FliC) epitopes flg22 and flgII-28 are microbe-associated molecular patterns (MAMPs). While flg22 is recognized by many plant species via the pattern recognition receptor FLS2, neither the flgII-28 receptor nor the extent of flgII-28 recognition by different plant families is known.Here we tested the significance of flgII-28 as a MAMP and the importance of allelic diversity in flg22 and flgII-28 in plant–pathogen interactions using purified peptides and a Pseudomonas syringae ΔfliC mutant complemented with different fliC alleles.Plant genotype and allelic diversity in flg22 and flgII-28 were found to significantly affect the plant immune response but not bacterial motility. Recognition of flgII-28 is restricted to a number of Solanaceous species. While the flgII-28 peptide does not trigger any immune response in Arabidopsis, mutations in both flg22 and flgII-28 have FLS2-dependent effects on virulence. However, expression of a tomato allele of FLS2 does not confer to Nicotiana benthamiana the ability to detect flgII-28 and tomato plants silenced for FLS2 are not altered in flgII-28 recognition.Therefore, MAMP diversification is an effective pathogen virulence strategy and flgII-28 appears to be perceived by a yet unidentified receptor in the Solanaceae although it has an FLS2-dependent virulence effect in Arabidopsis. PMID:23865782

  7. μ-Calpain, calpastatin, and growth hormone receptor genetic effects on preweaning performance, carcass quality traits, and residual variance of tenderness in Angus cattle selected to increase minor haplotype and allele frequencies.

    PubMed

    Tait, R G; Shackelford, S D; Wheeler, T L; King, D A; Casas, E; Thallman, R M; Smith, T P L; Bennett, G L

    2014-02-01

    Genetic marker effects and interactions are estimated with poor precision when minor marker allele frequencies are low. An Angus population was subjected to marker assisted selection for multiple years to increase divergent haplotype and minor marker allele frequencies to 1) estimate effect size and mode of inheritance for previously reported SNP on targeted beef carcass quality traits; 2) estimate effects of previously reported SNP on nontarget performance traits; and 3) evaluate tenderness SNP specific residual variance models compared to a single residual variance model for tenderness. Divergent haplotypes within µ-calpain (CAPN1), and SNP within calpastatin (CAST) and growth hormone receptor (GHR) were successfully selected to increase their frequencies. Traits evaluated were birth BW, weaning BW, final BW, fat thickness, LM area, USDA marbling score, yield grade, slice shear force (SSF), and visible and near infrared predicted slice shear force. Both CAPN1 and CAST exhibited additive (P < 0.001) modes of inheritance for SSF and neither exhibited dominance (P ≥ 0.19). Furthermore, the interaction between CAPN1 and CAST for SSF was not significant (P = 0.55). Estimated additive effects of CAPN1 (1.049 kg) and CAST (1.257 kg) on SSF were large in this study. Animals homozygous for tender alleles at both CAPN1 and CAST would have 4.61 kg lower SSF (38.6% of the mean) than animals homozygous tough for both markers. There was also an effect of CAST on yield grade (P < 0.02). The tender CAST allele was associated with more red meat yield and less trimmable fat. There were no significant effects (P ≥ 0.23) for GHR on any of the traits evaluated in this study. Furthermore, CAST specific residual variance models were found to fit significantly better (P < 0.001) than single residual variance models for SSF, with the tougher genotypes having larger residual variance. Thus, the risk of a tough steak from the undesired CAST genotype is increased through both an

  8. SNP development from RNA-seq data in a nonmodel fish: how many individuals are needed for accurate allele frequency prediction?

    PubMed

    Schunter, C; Garza, J C; Macpherson, E; Pascual, M

    2014-01-01

    Single nucleotide polymorphisms (SNPs) are rapidly becoming the marker of choice in population genetics due to a variety of advantages relative to other markers, including higher genomic density, data quality, reproducibility and genotyping efficiency, as well as ease of portability between laboratories. Advances in sequencing technology and methodologies to reduce genomic representation have made the isolation of SNPs feasible for nonmodel organisms. RNA-seq is one such technique for the discovery of SNPs and development of markers for large-scale genotyping. Here, we report the development of 192 validated SNP markers for parentage analysis in Tripterygion delaisi (the black-faced blenny), a small rocky-shore fish from the Mediterranean Sea. RNA-seq data for 15 individual samples were used for SNP discovery by applying a series of selection criteria. Genotypes were then collected from 1599 individuals from the same population with the resulting loci. Differences in heterozygosity and allele frequencies were found between the two data sets. Heterozygosity was lower, on average, in the population sample, and the mean difference between the frequencies of particular alleles in the two data sets was 0.135 ± 0.100. We used bootstrap resampling of the sequence data to predict appropriate sample sizes for SNP discovery. As cDNA library production is time-consuming and expensive, we suggest that using seven individuals for RNA sequencing reduces the probability of discarding highly informative SNP loci, due to lack of observed polymorphism, whereas use of more than 12 samples does not considerably improve prediction of true allele frequencies.

  9. Real-Time PCR Genotyping Assay for GM2 Gangliosidosis Variant 0 in Toy Poodles and the Mutant Allele Frequency in Japan

    PubMed Central

    RAHMAN, Mohammad Mahbubur; YABUKI, Akira; KOHYAMA, Moeko; MITANI, Sawane; MIZUKAMI, Keijiro; UDDIN, Mohammad Mejbah; CHANG, Hye-Sook; KUSHIDA, Kazuya; KISHIMOTO, Miori; YAMABE, Remi; YAMATO, Osamu

    2013-01-01

    ABSTRACT GM2 gangliosidosis variant 0 (Sandhoff disease, SD) is a fatal, progressive neurodegenerative lysosomal storage disease caused by mutations of the HEXB gene. In canine SD, a pathogenic mutation (c.283delG) of the canine HEXB gene has been identified in toy poodles. In the present study, a TaqMan probe-based real-time PCR genotyping assay was developed and evaluated for rapid and large-scale genotyping and screening for this mutation. Furthermore, a genotyping survey was carried out in a population of toy poodles in Japan to determine the current mutant allele frequency. The real-time PCR assay clearly showed all genotypes of canine SD. The assay was suitable for large-scale survey as well as diagnosis, because of its high throughput and rapidity. The genotyping survey demonstrated a carrier frequency of 0.2%, suggesting that the current mutant allele frequency is low in Japan. However, there may be population stratification in different places, because of the founder effect by some carriers. Therefore, this new assay will be useful for the prevention and control of SD in toy poodles. PMID:24161966

  10. HLA-Cw Allele Frequency in Definite Meniere’s Disease Compared to Probable Meniere’s Disease and Healthy Controls in an Iranian Sample

    PubMed Central

    Dabiri, Sasan; Ghadimi, Fatemeh; Firouzifar, Mohammadreza; Yazdani, Nasrin; Mohammad-Amoli, Mahsa; Vakili, Varasteh; Mahvi, Zahra

    2016-01-01

    Introduction Several lines of evidence support the contribution of autoimmune mechanisms in the pathogenesis of Meniere’s disease. The aim of this study was determining the association between HLA-Cw Alleles in patients with definite Meniere’s disease and patients with probable Meniere’s disease and a control group. Materials and Methods: HLA-Cw genotyping was performed in 23 patients with definite Meniere’s disease, 24 with probable Meniere’s disease, and 91 healthy normal subjects, using sequence specific primers polymerase chain reaction technique. The statistical analysis was performed using stata 8 software. Results: There was a significant association between HLA-Cw*04 and HLA-Cw*16 in both definite and probable Meniere’s disease compared to normal healthy controls. We observed a significant difference in HLA-Cw*12 frequencies between patients with definite Meniere’s disease compared to patients with probable Meniere’s disease (P=0.04). The frequency of HLA-Cw*18 is significantly higher in healthy controls (P=0.002). Conclusion: Our findings support the rule of HLA-Cw Alleles in both definite and probable Meniere’s disease. In addition, differences in HLA-Cw*12 frequency in definite and probable Meniere’s disease in our study’s population might indicate distinct immune and inflammatory mechanisms involved in each condition. PMID:27602337

  11. Allelic variations of α-gliadin genes from species of Aegilops section Sitopsis and insights into evolution of α-gliadin multigene family among Triticum and Aegilops.

    PubMed

    Huang, Zhuo; Long, Hai; Wei, Yu-Ming; Yan, Ze-Hong; Zheng, You-Liang

    2016-04-01

    The α-gliadins account for 15-30 % of the total storage protein in wheat endosperm and play important roles in the dough extensibility and nutritional quality. On the other side, they act as a main source of toxic peptides triggering celiac disease. In this study, 37 α-gliadins were isolated from three species of Aegilops section Sitopsis. Sequence similarity and phylogenetic analyses revealed novel allelic variation at Gli-2 loci of species of Sitopsis and regular organization of motifs in their repetitive domain. Based on the comprehensive analyses of a large number of known sequences of bread wheat and its diploid genome progenitors, the distributions of four T cell epitopes and length variations of two polyglutamine domains are analyzed. Additionally, according to the organization of repeat motifs, we classified the α-gliadins of Triticum and Aegilops into eight types. Their most recent common ancestor and putative divergence patterns were further considered. This study provides new insights into the allelic variations of α-gliadins in Aegilops section Sitopsis, as well as evolution of α-gliadin multigene family among Triticum and Aegilops species.

  12. Contemporary evolution of sea urchin gamete-recognition proteins: experimental evidence of density-dependent gamete performance predicts shifts in allele frequencies over time.

    PubMed

    Levitan, Don R

    2012-06-01

    Species whose reproductive strategies evolved at one density regime might be poorly adapted to other regimes. Field and laboratory experiments on the sea urchin Strongylocentrotus franciscanus examined the influences of the two most common sperm-bindin alleles, which differ at two amino acid sites, on fertilization success. In the field experiment, the arginine/glycine (RG) genotype performed best at low densities and the glycine/arginine (GR) genotype at high densities. In the laboratory experiment, the RG genotype had a higher affinity with available eggs, whereas the GR genotype was less likely to induce polyspermy. These sea urchins can reach 200 years of age. The RG allele dominates in larger/old sea urchins, whereas smaller/younger sea urchins have near-equal RG and GR allele frequencies. A latitudinal cline in RG and GR genotypes is consistent with longer survival of sea urchins in the north and with predominance of RG genotypes in older individuals. The largest/oldest sea urchins were likely conceived at low densities, before sea-urchin predators, such as sea otters, were overharvested and sea-urchin densities exploded off the west coast of North America. Contemporary evolution of gamete-recognition proteins might allow species to adapt to shifts in abundances and reduces the risk of reproductive failure in altered populations.

  13. Identification of the e allele at the Extension locus (MC1R) in Brazilian Creole sheep and its role in wool color variation.

    PubMed

    Hepp, D; Gonçalves, G L; Moreira, G R P; Freitas, T R O; Martins, C T D C; Weimer, T A; Passos, D T

    2012-08-29

    The melanocortin 1 receptor (MC1R) gene has been described as responsible for the black color in some breeds of sheep, but little is known about its function in many colored breeds, particularly those with a wide range of pigmentation phenotypes. The Brazilian Creole is a local breed of sheep from southern Brazil that has a wide variety of wool colors. We examined the MC1R gene (Extension locus) to search for the e allele and determine its role in controlling wool color variation in this breed. One hundred and twenty-five animals, covering the most common Creole sheep phenotypes (black, brown, dark gray, light gray, and white), were sequenced to detect the mutations p.M73K and p.D121N. Besides these two mutations, three other synonymous sites (429, 600, and 725) were found. The dominant allele (E(D): p.73K, and p.121N) was found only in colored animals, whereas the recessive allele (E⁺: p.73M, and p.121D) was homozygous only in white individuals. We concluded that MC1R is involved in the control of wool color in Brazilian Creole sheep, particularly the dark phenotypes, although a second gene may be involved in the expression of the white phenotype in this breed.

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

    PubMed Central

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

    1995-01-01

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

  15. Microsatellite variation in honey bee (Apis mellifera L.) populations: hierarchical genetic structure and test of the infinite allele and stepwise mutation models.

    PubMed

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

    1995-06-01

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

  16. Variation in the Input: A Case Study of Manner Class Frequencies

    ERIC Educational Resources Information Center

    Daland, Robert

    2013-01-01

    What are the sources of variation in the input, and how much do they matter for language acquisition? This study examines frequency variation in manner-of-articulation classes in child and adult input. The null hypothesis is that segmental frequency distributions of language varieties are unigram (modelable by stationary, ergodic processes), and…

  17. The frequency of different CGG-repeat alleles in the FMR-1 gene in the general population and special populations

    SciTech Connect

    Holden, J.J.A. |; Chalifoux, M.; Wing, M.

    1994-09-01

    The fragile X (FRAXA) syndrome is the most common inherited form of developmental disability and was the first genetic disorder in which the mechanism of mutation is triplet repeat expansion. The normal fragile X mental retardation-1 gene has 6-52 copies of the CGG-repeat; affected males have extensive amplification, coupled with methylation and gene inactivation; and carriers have between about 55 and 200 copies. There is some overlap in the 45-55 repeat range, with some alleles showing stable and othres unstable transmission. There have been several estimates of the incidence of the FRAXA syndrome, based on testing of special populations using chromosome analysis and the range is 1/750-1/2000. Because of the high burden associated with this syndrome, and in the face of discussions about population screening, it is important to know the actual incidence of mutations in this gene, as well as the distribution of unstable repeats above 45 copes. We have initiated a general population screening to examine 50,000 newborn samples using PCR, and have developed a rapid, inexpensive and reliable method for amplifying the CGG-repeat from Guthrie spots. In the first 1600 samples examined, we found 15 alleles with greater than 45 CGG-repeats, with the highest being 61 repeats.

  18. Frequency variations of solar radio zebras and their power-law spectra

    NASA Astrophysics Data System (ADS)

    Karlický, M.

    2014-01-01

    Context. During solar flares several types of radio bursts are observed. The fine striped structures of the type IV solar radio bursts are called zebras. Analyzing them provides important information about the plasma parameters of their radio sources. We present a new analysis of zebras. Aims: Power spectra of the frequency variations of zebras are computed to estimate the spectra of the plasma density variations in radio zebra sources. Methods: Frequency variations of zebra lines and the high-frequency boundary of the whole radio burst were determined with and without the frequency fitting. The computed time dependencies of these variations were analyzed with the Fourier method. Results: First, we computed the variation spectrum of the high-frequency boundary of the whole radio burst, which is composed of several zebra patterns. This power spectrum has a power-law form with a power-law index -1.65. Then, we selected three well-defined zebra-lines in three different zebra patterns and computed the spectra of their frequency variations. The power-law indices in these cases are found to be in the interval between -1.61 and -1.75. Finally, assuming that the zebra-line frequency is generated on the upper-hybrid frequency and that the plasma frequency ωpe is much higher than the electron-cyclotron frequency ωce, the Fourier power spectra are interpreted to be those of the electron plasma density in zebra radio sources.

  19. Frequency spectra of short-period variations of cosmic ray

    NASA Technical Reports Server (NTRS)

    Antonova, V. P.; Zusmanovich, A. G.

    1985-01-01

    Frequency spectra for different periods of solar activity were calculated by 5-minutes data of a neutron super-monitor, (altitude 3340 m, cutoff rigidity is 6, 7 GV, counting rate is about 4.5.10 per hour). It was shown that shifting of the spectrum power from low-frequency range to high-frequency range takes place from minimum to maximum of the solar activity. It was reliably distinguished the peak with 160-minutes period coincided with the period of the Sun's atmosphere oscillation and some types of geomagnetic pulsation by the method of accumulation of the frequency spectra. It was conducted the comparison of cosmic ray spectra with spectra of geomagnetic field for the same point of the registration and at the same period.

  20. Mutant allele frequencies among domestic cats in some eastern areas of Canada: regional homogeneity of factors in Canadian Atlantic Provinces and the French colony of Saint Pierre.

    PubMed

    Todd, N B; Todd, L M

    1976-01-01

    Surveys to determine mutant allele frequencies in domestic cats of the Canadian Atlantic Provinces (Halifax, Nova Scotia; Fredericton, New Brunswick; Charlottetown, Prince Edward Island; St. John's Newfoundland) and the French colony of Saint Pierre, Saint Pierre et Miquelon, reveal a general regional homogeneity for most factors. Despite diverse historical patterns of settlement, a strong common component of origin is indicated. This is tentatively identified as late 18th and early 19th century British. One mutant, polydactyly, which is of New England origin appears to have been distributed largely by loyalist refugees from New England at the time of the American Rebellion. No elements of a specific Acadian (French) character have yet been identified. Siamese cats have been "introduced" to the region in recent years and are now so abundant that they will undoubtedly cause a significant change in some mutant allele frequencies over the next few decades. Interregional exchanges of cats no doubt are contributing to homogenizing the populations of the area, but the practice of sterilization of pets offsets this to some degree.

  1. Temporal changes in allele frequencies in a small marble trout Salmo marmoratus population threatened by extreme flood events.

    PubMed

    Pujolar, J M; Vincenzi, S; Zane, L; Crivelli, A J

    2016-03-01

    The effect of extreme floods on the genetic composition of marble trout Salmo marmoratus living in Lipovscek, a tributary of the Soca River in Slovenia, which has been affected by multiple destructive flood events for centuries was investigated. By monitoring genetic variability during the period 2004-2011, apparent signatures of genetic erosion including a decline in observed and expected heterozygosities and allelic richness were observed. Contemporary effective population size was estimated between 11 and 55 individuals, which is congruent with census data. The data suggest asymmetric gene flow between the two sections of the river. The existence of substantial downstream migration (15-19%) was confirmed by paternity analysis. A small (1-3%) upstream migration was also suggested, which was confirmed by tagging data. Overall, low genetic diversity has not prevented the survival of the Lipovscek population, which might be a common feature of salmonid freshwater populations.

  2. The Adaptive Change of HLA-DRB1 Allele Frequencies Caused by Natural Selection in a Mongolian Population That Migrated to the South of China.

    PubMed

    Sun, Hao; Yang, Zhaoqing; Lin, Keqin; Liu, Shuyuan; Huang, Kai; Wang, Xiuyun; Chu, Jiayou; Huang, Xiaoqin

    2015-01-01

    Pathogen-driven balancing selection determines the richness of human leukocyte antigen (HLA) alleles. Changes in the pathogen spectrum may cause corresponding changes in HLA loci. Approximately 700 years ago, a Mongolian population moved from the north of China to the Yunnan region in the south of China. The pathogen spectrum in the south of China differs from that in the north. In this study, changes in the HLA genes in the Yunnan Mongolian population, as well as the underlying mechanism, were investigated. A sequence-based typing method (SBT) was used to genotype HLA-DRB1 in 470 individuals from two Mongolian populations and another five ethnic groups. Meanwhile, 10 autosomal short tandem repeats (STRs) were genotyped to assess the influence of genetic background on HLA-DRB1 frequencies. The frequencies of certain alleles changed significantly in the Mongolian population that migrated to Yunnan. For example, DRB1*12:02:01 increased from 6.1% to 35.4%. STR analysis excluded the possibility of a recent bottleneck and indicated that 50% of the genetic consistency between northern and southern Mongolians; Tajima's D value for HLA-DRB1 exon2 and dN/dS analysis showed that the HLA-DRB1 genes in both Mongolian populations were under balancing selection. However, the sites under natural selection changed. We proposed that the dramatically change of HLA frequencies in southern Mongolian was caused by a combination of inter-population gene flow and natural selection. Certain diseases specific to the south of China, such as malaria, may be the driving force behind the enhanced DRB1*12:02:01 frequency.

  3. The Adaptive Change of HLA-DRB1 Allele Frequencies Caused by Natural Selection in a Mongolian Population That Migrated to the South of China

    PubMed Central

    Sun, Hao; Yang, Zhaoqing; Lin, Keqin; Liu, Shuyuan; Huang, Kai; Wang, Xiuyun; Chu, Jiayou; Huang, Xiaoqin

    2015-01-01

    Pathogen-driven balancing selection determines the richness of human leukocyte antigen (HLA) alleles. Changes in the pathogen spectrum may cause corresponding changes in HLA loci. Approximately 700 years ago, a Mongolian population moved from the north of China to the Yunnan region in the south of China. The pathogen spectrum in the south of China differs from that in the north. In this study, changes in the HLA genes in the Yunnan Mongolian population, as well as the underlying mechanism, were investigated. A sequence-based typing method (SBT) was used to genotype HLA-DRB1 in 470 individuals from two Mongolian populations and another five ethnic groups. Meanwhile, 10 autosomal short tandem repeats (STRs) were genotyped to assess the influence of genetic background on HLA-DRB1 frequencies. The frequencies of certain alleles changed significantly in the Mongolian population that migrated to Yunnan. For example, DRB1*12:02:01 increased from 6.1% to 35.4%. STR analysis excluded the possibility of a recent bottleneck and indicated that 50% of the genetic consistency between northern and southern Mongolians; Tajima's D value for HLA-DRB1 exon2 and dN/dS analysis showed that the HLA-DRB1 genes in both Mongolian populations were under balancing selection. However, the sites under natural selection changed. We proposed that the dramatically change of HLA frequencies in southern Mongolian was caused by a combination of inter-population gene flow and natural selection. Certain diseases specific to the south of China, such as malaria, may be the driving force behind the enhanced DRB1*12:02:01 frequency. PMID:26230582

  4. Likelihood-based estimation of the effective population size using temporal changes in allele frequencies: a genealogical approach.

    PubMed Central

    Berthier, Pierre; Beaumont, Mark A; Cornuet, Jean-Marie; Luikart, Gordon

    2002-01-01

    A new genetic estimator of the effective population size (N(e)) is introduced. This likelihood-based (LB) estimator uses two temporally spaced genetic samples of individuals from a population. We compared its performance to that of the classical F-statistic-based N(e) estimator (N(eFk)) by using data from simulated populations with known N(e) and real populations. The new likelihood-based estimator (N(eLB)) showed narrower credible intervals and greater accuracy than (N(eFk)) when genetic drift was strong, but performed only slightly better when genetic drift was relatively weak. When drift was strong (e.g., N(e) = 20 for five generations), as few as approximately 10 loci (heterozygosity of 0.6; samples of 30 individuals) are sufficient to consistently achieve credible intervals with an upper limit <50 using the LB method. In contrast, approximately 20 loci are required for the same precision when using the classical F-statistic approach. The N(eLB) estimator is much improved over the classical method when there are many rare alleles. It will be especially useful in conservation biology because it less often overestimates N(e) than does N(eLB) and thus is less likely to erroneously suggest that a population is large and has a low extinction risk. PMID:11861575

  5. Novel rapid genotyping assays for neuronal ceroid lipofuscinosis in Border Collie dogs and high frequency of the mutant allele in Japan.

    PubMed

    Mizukami, Keijiro; Chang, Hye-Sook; Yabuki, Akira; Kawamichi, Takuji; Kawahara, Natsuko; Hayashi, Daisuke; Hossain, Mohammad A; Rahman, Mohammad M; Uddin, Mohammad M; Yamato, Osamu

    2011-11-01

    Neuronal ceroid lipofuscinosis (NCL) constitutes a group of recessively inherited lysosomal storage diseases that primarily affect neuronal cells. Such diseases share certain clinical and pathologic features in human beings and animals. Neuronal ceroid lipofuscinosis in Border Collie dogs was first detected in Australia in the 1980s, and the pathogenic mutation was shown to be a nonsense mutation (c.619C>T) in exon 4 in canine CLN5 gene. In the present study, novel rapid genotyping assays including polymerase chain reaction (PCR)-restriction fragment length polymorphism, PCR primer-induced restriction analysis, mutagenically separated PCR, and real-time PCR with TaqMan minor groove binder probes, were developed. The utility of microchip electrophoresis was also evaluated. Furthermore, a genotyping survey was carried out in a population of Border Collies in Japan using these assays to determine the current allele frequency in Japan, providing information to control and prevent this disease in the next stage. All assays developed in the current study are available to discriminate these genotypes, and microchip electrophoresis showed a timesaving advantage over agarose gel electrophoresis. Of all assays, real-time PCR was the most suitable for large-scale examination because of its high throughput. The genotyping survey demonstrated that the carrier frequency was 8.1%. This finding suggested that the mutant allele frequency of NCL in Border Collies is high enough in Japan that measures to control and prevent the disease would be warranted. The genotyping assays developed in the present study could contribute to the prevention of NCL in Border Collies.

  6. Effect of allelic variations at the Glu-D1, Glu-A3, Glu-B3 and Pinb-D1 loci on flour characteristics and bread loaf volume

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Doubled haploid wheat lines developed from a cross between Keumkang, a hard white winter wheat, and Olgeuru, soft red winter wheat were used to determine the effects of allelic variation in Glu-D1, Glu-A3, Glu-B3 and Pinb-D1 loci on physiochemical properties of flour and bread loaf volume. Variation...

  7. Genetic recombination variation in wild Robertsonian mice: on the role of chromosomal fusions and Prdm9 allelic background

    PubMed Central

    Capilla, Laia; Medarde, Nuria; Alemany-Schmidt, Alexandra; Oliver-Bonet, Maria; Ventura, Jacint; Ruiz-Herrera, Aurora

    2014-01-01

    Despite the existence of formal models to explain how chromosomal rearrangements can be fixed in a population in the presence of gene flow, few empirical data are available regarding the mechanisms by which genome shuffling contributes to speciation, especially in mammals. In order to shed light on this intriguing evolutionary process, here we present a detailed empirical study that shows how Robertsonian (Rb) fusions alter the chromosomal distribution of recombination events during the formation of the germline in a Rb system of the western house mouse (Mus musculus domesticus). Our results indicate that both the total number of meiotic crossovers and the chromosomal distribution of recombination events are reduced in mice with Rb fusions and that this can be related to alterations in epigenetic signatures for heterochromatinization. Furthermore, we detected novel house mouse Prdm9 allelic variants in the Rb system. Remarkably, mean recombination rates were positively correlated with a decrease in the number of ZnF domains in the Prdm9 gene. The suggestion that recombination can be modulated by both chromosomal reorganizations and genetic determinants that control the formation of double-stranded breaks during meiosis opens new avenues for understanding the role of recombination in chromosomal speciation. PMID:24850922

  8. Genetic recombination variation in wild Robertsonian mice: on the role of chromosomal fusions and Prdm9 allelic background.

    PubMed

    Capilla, Laia; Medarde, Nuria; Alemany-Schmidt, Alexandra; Oliver-Bonet, Maria; Ventura, Jacint; Ruiz-Herrera, Aurora

    2014-07-07

    Despite the existence of formal models to explain how chromosomal rearrangements can be fixed in a population in the presence of gene flow, few empirical data are available regarding the mechanisms by which genome shuffling contributes to speciation, especially in mammals. In order to shed light on this intriguing evolutionary process, here we present a detailed empirical study that shows how Robertsonian (Rb) fusions alter the chromosomal distribution of recombination events during the formation of the germline in a Rb system of the western house mouse (Mus musculus domesticus). Our results indicate that both the total number of meiotic crossovers and the chromosomal distribution of recombination events are reduced in mice with Rb fusions and that this can be related to alterations in epigenetic signatures for heterochromatinization. Furthermore, we detected novel house mouse Prdm9 allelic variants in the Rb system. Remarkably, mean recombination rates were positively correlated with a decrease in the number of ZnF domains in the Prdm9 gene. The suggestion that recombination can be modulated by both chromosomal reorganizations and genetic determinants that control the formation of double-stranded breaks during meiosis opens new avenues for understanding the role of recombination in chromosomal speciation.

  9. Polymorphism of ethanol-metabolism genes and alcoholism: correlation of allelic variations with the pharmacokinetic and pharmacodynamic consequences.

    PubMed

    Chen, Yi-Chyan; Peng, Giia-Sheun; Wang, Ming-Fang; Tsao, Tien-Ping; Yin, Shih-Jiun

    2009-03-16

    Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes responsible for metabolism of ethanol. Both ADH and ALDH exhibit genetic polymorphisms among racial populations. Functional variant alleles ADH1B*2 and ALDH2*2 have been consistently replicated to show protection against developing alcohol dependence. Multiple logistic regression analyses suggest that ADH1B*2 and ALDH2*2 may independently influence the risk for alcoholism. It has been well documented that homozygosity of ALDH2*2 almost fully protects against developing alcoholism and that the heterozygosity only affords a partial protection to varying degrees. Correlations of blood ethanol and acetaldehyde concentrations, cardiovascular hemodynamic responses, and subjective perceptions have been investigated in men with different combinatorial ADH1B and ALDH2 genotypes following challenge with ethanol for a period of 130 min. The pharmacokinetic and pharmacodynamic consequences indicate that acetaldehyde, rather than ethanol, is primarily responsible for the observed alcohol sensitivity reactions, suggesting that the full protection by ALDH2*2/*2 can be ascribed to the intense unpleasant physiological and psychological reactions caused by persistently elevated blood acetaldehyde after ingesting a small amount of alcohol and that the partial protection by ALDH2*1/*2 can be attributed to a faster elimination of acetaldehyde and the lower accumulation in circulation. ADH1B polymorphism does not significantly contribute to buildup of the blood acetaldehyde. Physiological tolerance or innate insensitivity to acetaldehyde may be crucial for development of alcohol dependence in alcoholics carrying ALDH2*2.

  10. Determining Optimum C-Field Settings that Minimize Output Frequency Variations in Cesium Atomic Frequency Standards

    DTIC Science & Technology

    1989-11-01

    current setting is probably on the order of parts in lo4 in our laboratory environment over the three months during which data were taken; this...hardware and long-term frequency-stability measurements. This work was supported, in part , by the U.S. Air Force Space Systems Division under Contract...Long-Term Stability in Cesium Beam Frequency Standards," IEEE Trans. Ultrasonics , Ferroelectronics, and Frequency Control UFFC-34 [6], 598-601 (Novem

  11. Frequency of the CCR5 delta 32 mutant allele in HIV-1-positive patients, female sex workers, and a normal population in Taiwan.

    PubMed

    Li, C; Yan, Y P; Shieh, B; Lee, C M; Lin, R Y; Chen, Y M

    1997-12-01

    A specific 32-nucleotide deletion mutant of the CCR5 gene (Accr5), the coreceptor gene for human immunodeficiency virus type 1 (HIV-1), can effectively suppress the transmission and pathogenesis of the virus. Individuals homozygous for the delta ccr5 allele resist primary macrophage-tropic HIV-1 infection, despite multiple high-risk sexual exposures. This gene deletion is relatively common among Caucasians but uncommon among Africans, Asians, and South Americans. We used polymerase chain reaction (PCR) technology to determine the frequency of the delta ccr5 allele in a Taiwanese population with diverse health status and social backgrounds. Subjects included 24 HIV-1-infected persons in the northern and southern parts of Taiwan; 131 HIV-1 high-risk, licensed female sex workers in the northern part of the island (21% of whom were aborigines); and 187 unrelated, healthy, HIV-1-negative individuals in southern Taiwan. PCR with primers encompassing the entire CCR5 gene was used to explore possible deletions at regions other than the 32-nucleotide area in the female sex workers. No ccr5 deletions were detected, indicating that they are rare or absent in the Taiwanese population. This finding implies that delta ccr5 is not likely to be part of the defense against the spread of HIV-1-infection in Taiwanese.

  12. Natural variation in male-induced ‘cost-of-mating’ and allele-specific association with male reproductive genes in Drosophila melanogaster

    PubMed Central

    Fiumera, Anthony C; Dumont, Bethany L; Clark, Andrew G

    2006-01-01

    One of the most sharply defined sexual conflicts arises when the act of mating is accompanied by an inflated risk of death. Several reports have documented an increased death rate of female Drosophila as a result of recurrent mating. Transgenic and mutation experiments have further identified components of seminal fluid that are at least in part responsible for this toxicity. Variation among males in their tendency for matings to be toxic to their partners has also been documented, but here for the first time we identify polymorphism within particular genes conferring differential post-mating female mortality. Such polymorphism is important, as it raises the challenge of whether sexual conflict models can provide means for maintenance of polymorphism. Using a set of second chromosome extraction lines, we scored differences in post-mating female fecundity and longevity subsequent to mating, and identified significant among-line differences. Seventy polymorphisms in ten male reproductive genes were scored and permutation tests were used to identify significant associations between genotype and phenotype. One polymorphism upstream of PEBII and an amino acid substitution in CG17331 were both associated with male-induced female mortality. The same allele of CG17331 that is toxic to females also induces greater refractoriness to remating in the females, providing an example of an allele-specific sexual conflict. Postcopulatory sexual selection could lead to sexual conflict by favouring males that prevent their mates from mating, even when there is a viability cost to those females. PMID:16612893

  13. Stable Allele Frequency Distribution of the Plasmodium falciparum clag Genes Encoding Components of the High Molecular Weight Rhoptry Protein Complex

    PubMed Central

    Alexandre, Jean Semé Fils; Xangsayarath, Phonepadith; Kaewthamasorn, Morakot; Yahata, Kazuhide; Sattabongkot, Jetsumon; Udomsangpetch, Rachanee; Kaneko, Osamu

    2012-01-01

    Plasmodium falciparum Clag protein is a candidate component of the plasmodial surface anion channel located on the parasite-infected erythrocyte. This protein is encoded by 5 separated clag genes and forms a RhopH complex with the other components. Previously, a signature of positive diversifying selection was detected on the hypervariable region of clag2 and clag8 by population-based analyses using P. falciparum originating from Thailand in 1988–1989. In this study, we obtained the sequence of this region of 3 clag genes (clag2, clag8, and clag9) in 2005 and evaluated the changes over time in the frequency distribution of the polymorphism of these gene products by comparison with the sequences obtained in 1988–1989. We found no difference in the frequency distribution of 18 putatively neutral loci between the 2 groups, evidence that the background of the parasite population structure has remained stable over 14 years. Although the frequency distribution of most of the polymorphic sites in the hypervariable region of Clag2, Clag8, and Clag9 was stable over 14 years, we found that a proportion of the major Clag2 group and one amino acid position of Clag8 changed significantly. This may be a response to a certain type of pressure. PMID:23264726

  14. Stable Allele Frequency Distribution of the Plasmodium falciparum clag Genes Encoding Components of the High Molecular Weight Rhoptry Protein Complex.

    PubMed

    Alexandre, Jean Semé Fils; Xangsayarath, Phonepadith; Kaewthamasorn, Morakot; Yahata, Kazuhide; Sattabongkot, Jetsumon; Udomsangpetch, Rachanee; Kaneko, Osamu

    2012-09-01

    Plasmodium falciparum Clag protein is a candidate component of the plasmodial surface anion channel located on the parasite-infected erythrocyte. This protein is encoded by 5 separated clag genes and forms a RhopH complex with the other components. Previously, a signature of positive diversifying selection was detected on the hypervariable region of clag2 and clag8 by population-based analyses using P. falciparum originating from Thailand in 1988-1989. In this study, we obtained the sequence of this region of 3 clag genes (clag2, clag8, and clag9) in 2005 and evaluated the changes over time in the frequency distribution of the polymorphism of these gene products by comparison with the sequences obtained in 1988-1989. We found no difference in the frequency distribution of 18 putatively neutral loci between the 2 groups, evidence that the background of the parasite population structure has remained stable over 14 years. Although the frequency distribution of most of the polymorphic sites in the hypervariable region of Clag2, Clag8, and Clag9 was stable over 14 years, we found that a proportion of the major Clag2 group and one amino acid position of Clag8 changed significantly. This may be a response to a certain type of pressure.

  15. Allele frequencies for 15 autosomal STR loci and haplotype data for 17 Y-STR loci in a population from Belize.

    PubMed

    Flores, Shahida; Sun, Jie; King, Jonathan; Eisenberg, Arthur; Budowle, Bruce

    2015-11-01

    Allele frequencies for 15 autosomal STR loci (N = 290) and haplotype data for 17 Y-STR loci (N = 157) were determined for an admixed population from Belize. There were no detectable departures from Hardy-Weinberg equilibrium expectations at any autosomal STR loci except for the D8S1179 locus (p = 0.002). The combined power of discrimination (PD) and combined power of exclusion (PE) were greater than 0.99999999 and 0.99999951, respectively. In addition, a total of 144 distinct Y-STR haplotypes were observed with 133 Y-STR haplotypes observed only once. The most common Y-STR haplotype was observed three times for two separate haplotypes. The various analyses of these forensically relevant STR loci showed that these markers are informative in the Belize population for forensic and parentage testing applications.

  16. DNA-PCR system FGA (FIBRA)--genotype and allele frequencies in a sample of western Germany (Düsseldorf region).

    PubMed

    Huckenbeck, W; Scheil, H G; Kuntze, K

    1999-12-01

    Frequency data for the STR system FGA (HumFibra) were obtained from a Caucasoid German population sample (Düsseldorf area) of 424 unrelated individuals. PCR products were detected by horizontal polyacrylamid gel electrophoresis and a total of 16 alleles was identified by side-by-side comparison with a commercially available sequenced ladder. The observed genotype distribution showed no significant deviation from the Hardy-Weinberg equilibrium. The high information content (pooled German data: rate of heterozygosity = 0.8626; probability of match = 0.0344; mean exclusion chance = 0.7240) render this system a useful tool not only in forensic casework (criminal and paternity cases) but in population genetics too.

  17. Life satisfaction in the new country: a multilevel longitudinal analysis of effects of culture and 5-HTT allele frequency distribution in country of origin.

    PubMed

    Kashima, Emiko S; Kent, Stephen; Kashima, Yoshihisa

    2015-01-01

    Life satisfaction of migrants to Australia from 17 countries, assessed at 4-5 months, 16-17 months and 3½ years after arrival, was analyzed with a longitudinal, multilevel analysis. The results indicated that migrants were more satisfied, if the national average life satisfaction was higher in their country of origin, after adjustment for individual-level income, age, and sex and a linear temporal trend. Simultaneously, the migrants were also happier if people in their country of origin had a higher frequency of 5-HTT long allele, a genotype known to be associated with resilience under life stresses. These two relationships were independent, suggesting that both culture and gene matter in international transitions.

  18. Life satisfaction in the new country: a multilevel longitudinal analysis of effects of culture and 5-HTT allele frequency distribution in country of origin

    PubMed Central

    Kent, Stephen; Kashima, Yoshihisa

    2015-01-01

    Life satisfaction of migrants to Australia from 17 countries, assessed at 4–5 months, 16–17 months and 3½ years after arrival, was analyzed with a longitudinal, multilevel analysis. The results indicated that migrants were more satisfied, if the national average life satisfaction was higher in their country of origin, after adjustment for individual-level income, age, and sex and a linear temporal trend. Simultaneously, the migrants were also happier if people in their country of origin had a higher frequency of 5-HTT long allele, a genotype known to be associated with resilience under life stresses. These two relationships were independent, suggesting that both culture and gene matter in international transitions. PMID:24532702

  19. Silent (painless) thyroiditis. Evidence of a geographic variation in frequency

    SciTech Connect

    Vitug, A.C.; Goldman, J.M.

    1985-03-01

    Recent reports suggest that 14% to 23% of thyrotoxic patients have silent (painless) thyroiditis, a newly described syndrome characterized by transient thyrotoxicosis with a low radioactive iodine uptake. A three-year review at a Brooklyn (NY) hospital showed only one definite and three possible cases of silent thyroiditis among 86 thyrotoxic patients. At most, 4% to 5% of thyrotoxic patients had silent thyroiditis. The authors suggest a geographic variation in this syndrome. Most cases and the largest series are from Japan and the Great Lakes area of North America. The latter may be related to increased iodine intake over many years in a previously endemic area of hypoiodidism and goiter, although other local factors may also be involved.

  20. Allelic variations at the haploid TBX1 locus do not influence the cardiac phenotype in cases of 22q11 microdeletion.

    PubMed

    Voelckel, Marie-Antoinette; Girardot, Lydie; Giusiano, Bernard; Levy, Nicolas; Philip, Nicole

    2004-01-01

    Microdeletion at the 22q11 locus is characterised by a high clinical variability. Congenital heart defects (CHD) are the most life-threatening manifestations of the syndrome and affect approximately 50% of patients carrying the deleted chromosome 22. The causes of this phenotype variability remain unknown although several hypotheses have been raised. It has been suggested that allelic variations at the haploid locus could modify the phenotypic expression. Regarding this hypothesis, TBX1 was thought to be a major candidate to the cardiac phenotype or its severity in patients carrying the 22q11 microdeletion. A mutational screening was performed in this gene, in a series of 39 deleted patients, with and without CHD. The results indicate that mutations in TBX1 are not likely to be involved in the cardiac phenotype observed in del22q11 patients.

  1. Allele-Specific Polymerase Chain Reaction-Based Genotyping of a Normal Variation in Human Color Vision

    NASA Astrophysics Data System (ADS)

    Wilson, Beth; Lubin, Ira M.; Grant, Kathryn B.

    2003-11-01

    This laboratory exercise offers undergraduate biochemistry students the opportunity to gain experience in a variety of techniques employed in modern molecular biology and biochemistry laboratories. Students utilize microcentrifugation and silica-gel column chromatography to extract DNA from their own buccal (cheek) epithelial cells. The polymerase chain reaction and agarose gel electrophoresis are then employed to identify a single nucleotide polymorphism that is responsible for a commonly encountered variation in human red color vision.

  2. Whole Genome Re-Sequencing and Characterization of Powdery Mildew Disease-Associated Allelic Variation in Melon

    PubMed Central

    Natarajan, Sathishkumar; Kim, Hoy-Taek; Thamilarasan, Senthil Kumar; Veerappan, Karpagam; Park, Jong-In; Nou, Ill-Sup

    2016-01-01

    Powdery mildew is one of the most common fungal diseases in the world. This disease frequently affects melon (Cucumis melo L.) and other Cucurbitaceous family crops in both open field and greenhouse cultivation. One of the goals of genomics is to identify the polymorphic loci responsible for variation in phenotypic traits. In this study, powdery mildew disease assessment scores were calculated for four melon accessions, ‘SCNU1154’, ‘Edisto47’, ‘MR-1’, and ‘PMR5’. To investigate the genetic variation of these accessions, whole genome re-sequencing using the Illumina HiSeq 2000 platform was performed. A total of 754,759,704 quality-filtered reads were generated, with an average of 82.64% coverage relative to the reference genome. Comparisons of the sequences for the melon accessions revealed around 7.4 million single nucleotide polymorphisms (SNPs), 1.9 million InDels, and 182,398 putative structural variations (SVs). Functional enrichment analysis of detected variations classified them into biological process, cellular component and molecular function categories. Further, a disease-associated QTL map was constructed for 390 SNPs and 45 InDels identified as related to defense-response genes. Among them 112 SNPs and 12 InDels were observed in powdery mildew responsive chromosomes. Accordingly, this whole genome re-sequencing study identified SNPs and InDels associated with defense genes that will serve as candidate polymorphisms in the search for sources of resistance against powdery mildew disease and could accelerate marker-assisted breeding in melon. PMID:27311063

  3. Whole Genome Re-Sequencing and Characterization of Powdery Mildew Disease-Associated Allelic Variation in Melon.

    PubMed

    Natarajan, Sathishkumar; Kim, Hoy-Taek; Thamilarasan, Senthil Kumar; Veerappan, Karpagam; Park, Jong-In; Nou, Ill-Sup

    2016-01-01

    Powdery mildew is one of the most common fungal diseases in the world. This disease frequently affects melon (Cucumis melo L.) and other Cucurbitaceous family crops in both open field and greenhouse cultivation. One of the goals of genomics is to identify the polymorphic loci responsible for variation in phenotypic traits. In this study, powdery mildew disease assessment scores were calculated for four melon accessions, 'SCNU1154', 'Edisto47', 'MR-1', and 'PMR5'. To investigate the genetic variation of these accessions, whole genome re-sequencing using the Illumina HiSeq 2000 platform was performed. A total of 754,759,704 quality-filtered reads were generated, with an average of 82.64% coverage relative to the reference genome. Comparisons of the sequences for the melon accessions revealed around 7.4 million single nucleotide polymorphisms (SNPs), 1.9 million InDels, and 182,398 putative structural variations (SVs). Functional enrichment analysis of detected variations classified them into biological process, cellular component and molecular function categories. Further, a disease-associated QTL map was constructed for 390 SNPs and 45 InDels identified as related to defense-response genes. Among them 112 SNPs and 12 InDels were observed in powdery mildew responsive chromosomes. Accordingly, this whole genome re-sequencing study identified SNPs and InDels associated with defense genes that will serve as candidate polymorphisms in the search for sources of resistance against powdery mildew disease and could accelerate marker-assisted breeding in melon.

  4. Tectorial Membrane Morphological Variation: Effects upon Stimulus Frequency Otoacoustic Emissions

    PubMed Central

    Bergevin, Christopher; Velenovsky, David S.; Bonine, Kevin E.

    2010-01-01

    The tectorial membrane (TM) is widely believed to play an important role in determining the ear's ability to detect and resolve incoming acoustic information. While it is still unclear precisely what that role is, the TM has been hypothesized to help overcome viscous forces and thereby sharpen mechanical tuning of the sensory cells. Lizards present a unique opportunity to further study the role of the TM given the diverse inner-ear morphological differences across species. Furthermore, stimulus-frequency otoacoustic emissions (SFOAEs), sounds emitted by the ear in response to a tone, noninvasively probe the frequency selectivity of the ear. We report estimates of auditory tuning derived from SFOAEs for 12 different species of lizards with widely varying TM morphology. Despite gross anatomical differences across the species examined herein, low-level SFOAEs were readily measurable in all ears tested, even in non-TM species whose basilar papilla contained as few as 50–60 hair cells. Our measurements generally support theoretical predictions: longer delays/sharper tuning features are found in species with a TM relative to those without. However, SFOAEs from at least one non-TM species (Anolis) with long delays suggest there are likely additional micromechanical factors at play that can directly affect tuning. Additionally, in the one species examined with a continuous TM (Aspidoscelis) where cell-to-cell coupling is presumably relatively stronger, delays were intermediate. This observation appears consistent with recent reports that suggest the TM may play a more complex macromechanical role in the mammalian cochlea via longitudinal energy distribution (and thereby affect tuning). Although significant differences exist between reptilian and mammalian auditory biophysics, understanding lizard OAE generation mechanisms yields significant insight into fundamental principles at work in all vertebrate ears. PMID:20712989

  5. High-Resolution Analyses of Human Leukocyte Antigens Allele and Haplotype Frequencies Based on 169,995 Volunteers from the China Bone Marrow Donor Registry Program

    PubMed Central

    Zhou, Xiao-Yang; Zhu, Fa-Ming; Li, Jian-Ping; Mao, Wei; Zhang, De-Mei; Liu, Meng-Li; Hei, Ai-Lian; Dai, Da-Peng; Jiang, Ping; Shan, Xiao-Yan; Zhang, Bo-Wei; Zhu, Chuan-Fu; Shen, Jie; Deng, Zhi-Hui; Wang, Zheng-Lei; Yu, Wei-Jian; Chen, Qiang; Qiao, Yan-Hui; Zhu, Xiang-Ming; Lv, Rong; Li, Guo-Ying; Li, Guo-Liang; Li, Heng-Cong; Zhang, Xu; Pei, Bin; Jiao, Li-Xin; Shen, Gang; Liu, Ying; Feng, Zhi-Hui; Su, Yu-Ping; Xu, Zhao-Xia; Di, Wen-Ying; Jiang, Yao-Qin; Fu, Hong-Lei; Liu, Xiang-Jun; Liu, Xiang; Zhou, Mei-Zhen; Du, Dan; Liu, Qi; Han, Ying; Zhang, Zhi-Xin; Cai, Jian-Ping

    2015-01-01

    Allogeneic hematopoietic stem cell transplantation is a widely used and effective therapy for hematopoietic malignant diseases and numerous other disorders. High-resolution human leukocyte antigen (HLA) haplotype frequency distributions not only facilitate individual donor searches but also determine the probability with which a particular patient can find HLA-matched donors in a registry. The frequencies of the HLA-A, -B, -C, -DRB1, and -DQB1 alleles and haplotypes were estimated among 169,995 Chinese volunteers using the sequencing-based typing (SBT) method. Totals of 191 HLA-A, 244 HLA-B, 146 HLA-C, 143 HLA-DRB1 and 47 HLA-DQB1 alleles were observed, which accounted for 6.98%, 7.06%, 6.46%, 9.11% and 7.91%, respectively, of the alleles in each locus in the world (IMGT 3.16 Release, Apr. 2014). Among the 100 most common haplotypes from the 169,995 individuals, nine distinct haplotypes displayed significant regionally specific distributions. Among these, three were predominant in the South China region (i.e., the 20th, 31st, and 81sthaplotypes), another three were predominant in the Southwest China region (i.e., the 68th, 79th, and 95th haplotypes), one was predominant in the South and Southwest China regions (the 18th haplotype), one was relatively common in the Northeast and North China regions (the 94th haplotype), and one was common in the Northeast, North and Northwest China (the 40th haplotype). In conclusion, this is the first to analyze high-resolution HLA diversities across the entire country of China, based on a detailed and complete data set that covered 31 provinces, autonomous regions, and municipalities. Specifically, we also evaluated the HLA matching probabilities within and between geographic regions and analyzed the regional differences in the HLA diversities in China. We believe that the data presented in this study might be useful for unrelated HLA-matched donor searches, donor registry planning, population genetic studies, and anthropogenesis

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  8. Allele-dependent recombination frequency: homology requirement in meiotic recombination at the hot spot in the mouse major histocompatibility complex.

    PubMed

    Yoshino, M; Sagai, T; Lindahl, K F; Toyoda, Y; Moriwaki, K; Shiroishi, T

    1995-05-20

    Meiotic recombination break joints in the mouse major histocompatibility complex (MHC) are clustered within short segments known as hot spots. We systematically investigated the requirement for sequence homology between two chromosomes for recombination activity at the hot spot next to the Lmp2 gene. The results indicated that a high rate of recombination required a high degree of similarity of overall genome structure at the hot spot. In particular, the same copy number of repetitive sequences within the hot spot was essential for a high frequency of recombination, suggesting that recombination in mouse meiosis is more sensitive to heterozygous deletion or insertion of DNA than to mismatches of single-base substitutions.

  9. Solar-cycle variations of large frequency separations of acoustic modes: implications for asteroseismology

    NASA Astrophysics Data System (ADS)

    Broomhall, A.-M.; Chaplin, W. J.; Elsworth, Y.; New, R.

    2011-06-01

    We have studied solar-cycle changes in the large frequency separations that can be observed in Birmingham Solar Oscillations Network (BiSON) data. The large frequency separation is often one of the first outputs from asteroseismic studies because it can help constrain stellar properties like mass and radius. We have used three methods for estimating the large separations: use of individual p-mode frequencies, computation of the autocorrelation of frequency-power spectra, and computation of the power spectrum of the power spectrum. The values of the large separations obtained by the different methods are offset from each other and have differing sensitivities to the realization noise. A simple model was used to predict solar-cycle variations in the large separations, indicating that the variations are due to the well-known solar-cycle changes to mode frequency. However, this model is only valid over a restricted frequency range. We discuss the implications of these results for asteroseismology.

  10. 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

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

    2010-01-01

    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. PMID:20974205

  11. Experimental Studies of Variations in the Maximum Usable Frequency on Oblique Sounding Paths

    NASA Astrophysics Data System (ADS)

    Cherkashin, Yu. N.; Egorov, I. B.; Uryadov, V. P.; Ponyatov, A. A.

    2003-12-01

    We present the results of experimental studies of variations in the maximum usable frequency (MUF) on the latitudinal (England-Moscow and Khabarovsk-Nizhny Novgorod) and meridional (Cyprus-Moscow) paths. It is found that the quasi-period of MUF variations ranges from 20 min to several hours in spring 2002. The absolute value of the MUF varied in the range from 0.2 to 2 MHz. We show that variations in distance-frequency characteristics of HF signals propagated over the long-distance latitudinal path are strongly affected by quasi-periodic disturbances being the ionospheric response to acoustic-gravity waves excited by the terminator.

  12. A fast-settling frequency-presetting PLL frequency synthesizer with process variation compensation and spur reduction

    NASA Astrophysics Data System (ADS)

    Xiaozhou, Yan; Xiaofei, Kuang; Nanjian, Wu

    2009-04-01

    This paper proposes a fast-settling frequency-presetting PLL frequency synthesizer. A mixed-signal VCO and a digital processor are developed to accurately preset the frequency of VCO and greatly reduce the settling time. An auxiliary tuning loop is introduced in order to reduce reference spur caused by leakage current. The digital processor can automatically compensate presetting frequency variation with process and temperature, and control the operation of the auxiliary tuning loop. A 1.2 GHz integer-N synthesizer with 1 MHz reference input was implemented in a 0.18 μm process. The measured results demonstrate that the typical settling time of the synthesizer is less than 3 μs, and the phase noise is -108 dBc/Hz@ 1MHz. The reference spur is -52 dBc.

  13. Identification of a member of the catalase multigene family on wheat chromosome 7A associated with flour b* colour and biological significance of allelic variation.

    PubMed

    Li, Dora A; Walker, Esther; Francki, Michael G

    2015-12-01

    Carotenoids (especially lutein) are known to be the pigment source for flour b* colour in bread wheat. Flour b* colour variation is controlled by a quantitative trait locus (QTL) on wheat chromosome 7AL and one gene from the carotenoid pathway, phytoene synthase, was functionally associated with the QTL on 7AL in some, but not all, wheat genotypes. A SNP marker within a sequence similar to catalase (Cat3-A1snp) derived from full-length (FL) cDNA (AK332460), however, was consistently associated with the QTL on 7AL and implicated in regulating hydrogen peroxide (H2O2) to control carotenoid accumulation affecting flour b* colour. The number of catalase genes on chromosome 7AL was investigated in this study to identify which gene may be implicated in flour b* variation and two were identified through interrogation of the draft wheat genome survey sequence consisting of five exons and a further two members having eight exons identified through comparative analysis with the single catalase gene on rice chromosome 6, PCR amplification and sequencing. It was evident that the catalase genes on chromosome 7A had duplicated and diverged during evolution relative to its counterpart on rice chromosome 6. The detection of transcripts in seeds, the co-location with Cat3-A1snp marker and maximised alignment of FL-cDNA (AK332460) with cognate genomic sequence indicated that TaCat3-A1 was the member of the catalase gene family associated with flour b* colour variation. Re-sequencing identified three alleles from three wheat varieties, TaCat3-A1a, TaCat3-A1b and TaCat3-A1c, and their predicted protein identified differences in peroxisomal targeting signal tri-peptide domain in the carboxyl terminal end providing new insights into their potential role in regulating cellular H2O2 that contribute to flour b* colour variation.

  14. Optimization of short tandem repeats (STR) typing method and allele frequency of 8 STR markers in referring to forensic medicine of Semnan Province.

    PubMed

    Eskandarion, M; Najafi, M; Akbari Eidgahi, M; Alipour Tabrizi, A; Golmohamadi, T

    2015-01-01

    Background and Objective: Short Tandem Repeats (STR) show considerable differences among individuals in the population from which they used for identification. There are various methods for analysis of these STR loci, and capillary electrophoresis method already used as an international standard. Due to the high costs of this process, this study aimed to set up a Multiplex PCR method in some standard STR loci so that we can use its PCR product in STR analysis with different methods of HPLC, GC-Mass, and Capillary Electrophoresis. Materials and Methods: 8 typical STR loci in the identification selected according to their size in the two groups of four (CSF1PO, VWA, D18S51, PentaD and TPOX, Amelogenin, FGA, SE33) from NIST (National Institute of Standards and Technology). The above SSR primers prepared from Genbank and Monoplex PCR was designed based on their size. Then, with the changes in temperature conditions, magnesium ion, primers concentration, and setting-up, Hot Start Multiplex PCR of four markers was carried out. PCR product investigated on the agarose gel electrophoresis (3%) and the results of genotyping analyzed by Genetic Analyzer. Results: The Results showed that all STR loci under study are detectable as Monoplex PCR at a temperature of 62°-66° and 1.5 mM magnesium ion. Moreover, Multiplex PCR results showed that when the concentration of primer and temperature measured by the fixed concentration of magnesium, CSF1PO, and D18S51 loci bands are weaker than desired. Using a standard buffer and set Magnesium conditions against changes in the primer concentration and temperature, when Taq polymerase enzyme is added to test tubes at a temperature of 94°, Multiplex PCR bands are visible desirably. Capillary electrophoresis genotyping results obtained in all eight loci and the Locus FGA had the most allelic diversity and the loci TPOX and CSF1PO had the lowest allelic diversity. TPOX and CSF1PO loci had the lowest allelic frequencies, and FGA locus had

  15. Optimization of short tandem repeats (STR) typing method and allele frequency of 8 STR markers in referring to forensic medicine of Semnan Province

    PubMed Central

    Eskandarion, M; Najafi, M; Akbari Eidgahi, M; Alipour Tabrizi, A; Golmohamadi, T

    2015-01-01

    Background and Objective: Short Tandem Repeats (STR) show considerable differences among individuals in the population from which they used for identification. There are various methods for analysis of these STR loci, and capillary electrophoresis method already used as an international standard. Due to the high costs of this process, this study aimed to set up a Multiplex PCR method in some standard STR loci so that we can use its PCR product in STR analysis with different methods of HPLC, GC-Mass, and Capillary Electrophoresis. Materials and Methods: 8 typical STR loci in the identification selected according to their size in the two groups of four (CSF1PO, VWA, D18S51, PentaD and TPOX, Amelogenin, FGA, SE33) from NIST (National Institute of Standards and Technology). The above SSR primers prepared from Genbank and Monoplex PCR was designed based on their size. Then, with the changes in temperature conditions, magnesium ion, primers concentration, and setting-up, Hot Start Multiplex PCR of four markers was carried out. PCR product investigated on the agarose gel electrophoresis (3%) and the results of genotyping analyzed by Genetic Analyzer. Results: The Results showed that all STR loci under study are detectable as Monoplex PCR at a temperature of 62°-66° and 1.5 mM magnesium ion. Moreover, Multiplex PCR results showed that when the concentration of primer and temperature measured by the fixed concentration of magnesium, CSF1PO, and D18S51 loci bands are weaker than desired. Using a standard buffer and set Magnesium conditions against changes in the primer concentration and temperature, when Taq polymerase enzyme is added to test tubes at a temperature of 94°, Multiplex PCR bands are visible desirably. Capillary electrophoresis genotyping results obtained in all eight loci and the Locus FGA had the most allelic diversity and the loci TPOX and CSF1PO had the lowest allelic diversity. TPOX and CSF1PO loci had the lowest allelic frequencies, and FGA locus had

  16. Frequencies of cystic fibrosis mutations in the Maine population: high proportion of unknown alleles in individuals of French-Canadian ancestry.

    PubMed

    Bayleran, J K; Yan, H; Hopper, C A; Simpson, E M

    1996-08-01

    Cystic fibrosis (CF) is one of the most common severe autosomal recessive disorders in Caucasian populations. A mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene causes this disorder. Reported here is the first analysis of CF mutations in the Maine population. We have screened 263 CF chromosomes for 16 previously reported mutations. Analysis of DNA from 124 apparently unrelated CF patients and 15 obligate carrier parents (whose partner and affected child were unavailable for study) resulted in the identification of 91% of the CF alleles and complete genotyping of 85% of the patients. The frequencies (%) of these mutations in the Maine population are delta F508 (75% of the chromosomes), G85E (0.76), R117H (0.76), I148T (1.1), 621 + 1G --> T (1.1), 711 + 1G --> T (3.0), A455E (1.1), 1717-1G --> A (1.1), G542X (1.9), G551D (1.9), R560T (0.76), Y1092X (0.38), W1282X (0.38), and N1303K (1.5). The exon 10 mutation, delta I507, and the exon 11 mutation, R553X, were not observed. Surprisingly, whereas only 5% of the alleles remain unidentified in the non-French population, the unidentified proportion in the French population is 19%. CF testing for the Maine population will be further improved as the as yet unidentified CF mutations in this population are characterized.

  17. Allelic frequencies of PRKAG3 in several pig breeds and its technological consequences on a Duroc × Landrace-Large White cross.

    PubMed

    Galve, A; Burgos, C; Varona, L; Carrodeguas, J A; Cánovas, Á; López-Buesa, P

    2013-10-01

    The allelic frequencies of PRKAG3 gene (the RN gene) have been investigated in several pig breeds. R200Q mutation appear only in Hampshire pigs, whereas V199I mutation is most abundant in Iberian, Porco Celta or Bizaro, and less in breeds selected for muscularity as Duroc, Landrace and Pietrain. A thorough study of phenotypic effects of V1991 has been performed in a Duroc × Landrace-Large White cross. 199I homozygous pigs show increased pH24 values in ham homogenates and loin (0.14 and 0.16 pH units, respectively) compared to 199V homozygous ones. Meat of 199I homozygous pigs exudates 42.6% less fluid and is darker (2.46 'L'-value units). 199I homozygous pigs are fatter (4.2 mm more backfat thickness) and contain less muscle mass in ham (1.0 percentage points) and shoulder (2.7 percentage points), than 199V homozygous ones. 199I homozygous pigs contain 7.3% less protein in the belly and 8.5% more fat in shoulder muscle mass than 199V homozygous pigs. 199I homozygous pigs have also superior functional properties: better gelling (22.8% larger G' value) and emulsion capacities (14 percentage points less of total exuded fluid), and higher curing yield in the belly (6 percentage points more). These data support the adipogenic character of the V199I mutation. The advantages and disadvantages of selecting any of the two PRKAG3 alleles for position 199 are discussed.

  18. Dual Cry2Ab and Vip3A resistant strains of Helicoverpa armigera and Helicoverpa punctigera (Lepidoptera: Noctuidae); testing linkage between loci and monitoring of allele frequencies.

    PubMed

    Walsh, T K; Downes, S J; Gascoyne, J; James, W; Parker, T; Armstrong, J; Mahon, R J

    2014-08-01

    Considerable attention has been given to delaying the evolution of insect resistance to toxins produced by transgenic crops. The major pests of cotton in Australia are the Lepidoptera Helicoverpa armigera (Hubner, 1805) and Helicoverpa punctigera (Wallengren), and the toxins deployed in current and imminent transgenic cotton varieties are Cry1Ac, Cry2Ab and Vip3A from Bacillus thuringiensis. In this study, lines that carry alleles conferring resistance to Cry2Ab and Vip3A were isolated using F2 tests. Extensive work on the Cry2Ab resistant lines, and preliminary work on the Vip3A resistant lines, suggested a single common resistance to each toxin in both species thereby justifying the use of more efficient F1 tests as the primary means for monitoring changes over time. A potential further efficiency could be gained by developing a single resistant line that carries both types of Bt resistance. Herein we report on work with both H. armigera and H. punctigera that tests whether dual Cry2Ab-Vip3A resistant lines can be developed and, if so, whether they can be used to effectively monitor resistance frequencies. Furthermore, the creation of dual resistant lines allowed linkage between the Cry2Ab and Vip3A resistances to be investigated for H. punctigera. We show that dual resistant lines can be used to increase the efficiency of the F1 screen for recessive alleles, and that in H. punctigera there is no linkage between Cry2Ab and Vip3A resistance.

  19. Expanded national database collection and data coverage in the FINDbase worldwide database for clinically relevant genomic variation allele frequencies

    PubMed Central

    Viennas, Emmanouil; Komianou, Angeliki; Mizzi, Clint; Stojiljkovic, Maja; Mitropoulou, Christina; Muilu, Juha; Vihinen, Mauno; Grypioti, Panagiota; Papadaki, Styliani; Pavlidis, Cristiana; Zukic, Branka; Katsila, Theodora; van der Spek, Peter J.; Pavlovic, Sonja; Tzimas, Giannis; Patrinos, George P.

    2017-01-01

    FINDbase (http://www.findbase.org) is a comprehensive data repository that records the prevalence of clinically relevant genomic variants in various populations worldwide, such as pathogenic variants leading mostly to monogenic disorders and pharmacogenomics biomarkers. The database also records the incidence of rare genetic diseases in various populations, all in well-distinct data modules. Here, we report extensive data content updates in all data modules, with direct implications to clinical pharmacogenomics. Also, we report significant new developments in FINDbase, namely (i) the release of a new version of the ETHNOS software that catalyzes development curation of national/ethnic genetic databases, (ii) the migration of all FINDbase data content into 90 distinct national/ethnic mutation databases, all built around Microsoft's PivotViewer (http://www.getpivot.com) software (iii) new data visualization tools and (iv) the interrelation of FINDbase with DruGeVar database with direct implications in clinical pharmacogenomics. The abovementioned updates further enhance the impact of FINDbase, as a key resource for Genomic Medicine applications. PMID:27924022

  20. Expanded national database collection and data coverage in the FINDbase worldwide database for clinically relevant genomic variation allele frequencies.

    PubMed

    Viennas, Emmanouil; Komianou, Angeliki; Mizzi, Clint; Stojiljkovic, Maja; Mitropoulou, Christina; Muilu, Juha; Vihinen, Mauno; Grypioti, Panagiota; Papadaki, Styliani; Pavlidis, Cristiana; Zukic, Branka; Katsila, Theodora; van der Spek, Peter J; Pavlovic, Sonja; Tzimas, Giannis; Patrinos, George P

    2017-01-04

    FINDbase (http://www.findbase.org) is a comprehensive data repository that records the prevalence of clinically relevant genomic variants in various populations worldwide, such as pathogenic variants leading mostly to monogenic disorders and pharmacogenomics biomarkers. The database also records the incidence of rare genetic diseases in various populations, all in well-distinct data modules. Here, we report extensive data content updates in all data modules, with direct implications to clinical pharmacogenomics. Also, we report significant new developments in FINDbase, namely (i) the release of a new version of the ETHNOS software that catalyzes development curation of national/ethnic genetic databases, (ii) the migration of all FINDbase data content into 90 distinct national/ethnic mutation databases, all built around Microsoft's PivotViewer (http://www.getpivot.com) software (iii) new data visualization tools and (iv) the interrelation of FINDbase with DruGeVar database with direct implications in clinical pharmacogenomics. The abovementioned updates further enhance the impact of FINDbase, as a key resource for Genomic Medicine applications.

  1. Collective frequency variation in network synchronization and reverse PageRank

    NASA Astrophysics Data System (ADS)

    Skardal, Per Sebastian; Taylor, Dane; Sun, Jie; Arenas, Alex

    2016-04-01

    A wide range of natural and engineered phenomena rely on large networks of interacting units to reach a dynamical consensus state where the system collectively operates. Here we study the dynamics of self-organizing systems and show that for generic directed networks the collective frequency of the ensemble is not the same as the mean of the individuals' natural frequencies. Specifically, we show that the collective frequency equals a weighted average of the natural frequencies, where the weights are given by an outflow centrality measure that is equivalent to a reverse PageRank centrality. Our findings uncover an intricate dependence of the collective frequency on both the structural directedness and dynamical heterogeneity of the network, and also reveal an unexplored connection between synchronization and PageRank, which opens the possibility of applying PageRank optimization to synchronization. Finally, we demonstrate the presence of collective frequency variation in real-world networks by considering the UK and Scandinavian power grids.

  2. Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6-Tas1r3 congenic mice.

    PubMed

    Inoue, Masashi; Glendinning, John I; Theodorides, Maria L; Harkness, Sarah; Li, Xia; Bosak, Natalia; Beauchamp, Gary K; Bachmanov, Alexander A

    2007-12-19

    The Tas1r3 gene encodes the T1R3 receptor protein, which is involved in sweet taste transduction. To characterize ligand specificity of the T1R3 receptor and the genetic architecture of sweet taste responsiveness, we analyzed taste responses of 129.B6-Tas1r3 congenic mice to a variety of chemically diverse sweeteners and glucose polymers with three different measures: consumption in 48-h two-bottle preference tests, initial licking responses, and responses of the chorda tympani nerve. The results were generally consistent across the three measures. Allelic variation of the Tas1r3 gene influenced taste responsiveness to nonnutritive sweeteners (saccharin, acesulfame-K, sucralose, SC-45647), sugars (sucrose, maltose, glucose, fructose), sugar alcohols (erythritol, sorbitol), and some amino acids (D-tryptophan, D-phenylalanine, L-proline). Tas1r3 genotype did not affect taste responses to several sweet-tasting amino acids (L-glutamine, L-threonine, L-alanine, glycine), glucose polymers (Polycose, maltooligosaccharide), and nonsweet NaCl, HCl, quinine, monosodium glutamate, and inosine 5'-monophosphate. Thus Tas1r3 polymorphisms affect taste responses to many nutritive and nonnutritive sweeteners (all of which must interact with a taste receptor involving T1R3), but not to all carbohydrates and amino acids. In addition, we found that the genetic architecture of sweet taste responsiveness changes depending on the measure of taste response and the intensity of the sweet taste stimulus. Variation in the T1R3 receptor influenced peripheral taste responsiveness over a wide range of sweetener concentrations, but behavioral responses to higher concentrations of some sweeteners increasingly depended on mechanisms that could override input from the peripheral taste system.

  3. Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6-Tas1r3 congenic mice

    PubMed Central

    Inoue, Masashi; Glendinning, John I.; Theodorides, Maria L.; Harkness, Sarah; Li, Xia; Bosak, Natalia; Beauchamp, Gary K.; Bachmanov, Alexander A.

    2008-01-01

    The Tas1r3 gene encodes the T1R3 receptor protein, which is involved in sweet taste transduction. To characterize ligand specificity of the T1R3 receptor and the genetic architecture of sweet taste responsiveness, we analyzed taste responses of 129.B6-Tas1r3 congenic mice to a variety of chemically diverse sweeteners and glucose polymers with three different measures: consumption in 48-h two-bottle preference tests, initial licking responses, and responses of the chorda tympani nerve. The results were generally consistent across the three measures. Allelic variation of the Tas1r3 gene influenced taste responsiveness to nonnutritive sweeteners (saccharin, acesulfame-K, sucralose, SC-45647), sugars (sucrose, maltose, glucose, fructose), sugar alcohols (erythritol, sorbitol), and some amino acids (d-tryptophan, d-phenylalanine, l-proline). Tas1r3 genotype did not affect taste responses to several sweet-tasting amino acids (l-glutamine, l-threonine, l-alanine, glycine), glucose polymers (Polycose, maltooligosaccharide), and nonsweet NaCl, HCl, quinine, monosodium glutamate, and inosine 5′-monophosphate. Thus Tas1r3 polymorphisms affect taste responses to many nutritive and nonnutritive sweeteners (all of which must interact with a taste receptor involving T1R3), but not to all carbohydrates and amino acids. In addition, we found that the genetic architecture of sweet taste responsiveness changes depending on the measure of taste response and the intensity of the sweet taste stimulus. Variation in the T1R3 receptor influenced peripheral taste responsiveness over a wide range of sweetener concentrations, but behavioral responses to higher concentrations of some sweeteners increasingly depended on mechanisms that could override input from the peripheral taste system. PMID:17911381

  4. Analysis of the CCR5 gene coding region diversity in five South American populations reveals two new non-synonymous alleles in Amerindians and high CCR5*D32 frequency in Euro-Brazilians

    PubMed Central

    2009-01-01

    The CC chemokine receptor 5 (CCR5) molecule is an important co-receptor for HIV. The effect of the CCR5*D32 allele in susceptibility to HIV infection and AIDS disease is well known. Other alleles than CCR5*D32 have not been analysed before, neither in Amerindians nor in the majority of the populations all over the world. We investigated the distribution of the CCR5 coding region alleles in South Brazil and noticed a high CCR5*D32 frequency in the Euro-Brazilian population of the Paraná State (9.3%), which is the highest thus far reported for Latin America. The D32 frequency is even higher among the Euro-Brazilian Mennonites (14.2%). This allele is uncommon in Afro-Brazilians (2.0%), rare in the Guarani Amerindians (0.4%) and absent in the Kaingang Amerindians and the Oriental-Brazilians. R223Q is common in the Oriental-Brazilians (7.7%) and R60S in the Afro-Brazilians (5.0%). A29S and L55Q present an impaired response to β-chemokines and occurred in Afro- and Euro-Brazilians with cumulative frequencies of 4.4% and 2.7%, respectively. Two new non-synonymous alleles were found in Amerindians: C323F (g.3729G > T) in Guarani (1.4%) and Y68C (g.2964A > G) in Kaingang (10.3%). The functional characteristics of these alleles should be defined and considered in epidemiological investigations about HIV-1 infection and AIDS incidence in Amerindian populations. PMID:21637640

  5. Frequency of alleles conferring resistance to the Bacillus thuringiensis toxins Cry1Ac and Cry2Ab in Australian populations of Helicoverpa punctigera (Lepidoptera: Noctuidae) from 2002 to 2006.

    PubMed

    Downes, S; Parker, T L; Mahon, R J

    2009-04-01

    Helicoverpa punctigera and Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) are important pests of field and horticultural crops in Australia. The former is endemic to the continent, whereas the latter is also distributed in Africa and Asia. Although H. armigera rapidly developed resistance to virtually every group of insecticide used against it, there is only one report of resistance to an insecticide in H. punctigera. In 1996 the Australian cotton industry adopted Ingard, which expresses the Bacillus thuringiensis (Bt) toxin gene cry1Ac. In 2004/2005, Bollgard II (which expresses Cry1Ac and Cry2Ab) replaced Ingard and has subsequently been grown on 80% of the area planted to cotton, Gossypium hirsutum L. From 2002/2003 to 2006/2007, F2 screens were used to detect resistance to Cry1Ac or Cry2Ab. We detected no alleles conferring resistance to Cry1Ac; the frequency was < 0.0005 (n = 2,180 alleles), with a 95% credibility interval between 0 and 0.0014. However, during the same period, we detected alleles that confer resistance to Cry2Ab at a frequency of 0.0018 (n = 2,192 alleles), with a 95% credibility interval between 0.0005 and 0.0040. For both toxins, the experiment-wise detection probability was 94%, i.e., if there actually was a resistance allele in any tested lines, we would have detected it 94% of the time. The first isolation of Cry2Ab resistance in H. punctigera was before the widespread deployment of Bollgard II. This finding supports our published notion for H. armigera that alleles conferring resistance to Cry2Ab may be present at detectable frequencies in populations before selection by transgenic crops.

  6. Negative frequency-dependent preferences and variation in male facial hair.

    PubMed

    Janif, Zinnia J; Brooks, Robert C; Dixson, Barnaby J

    2014-01-01

    Negative frequency-dependent sexual selection maintains striking polymorphisms in secondary sexual traits in several animal species. Here, we test whether frequency of beardedness modulates perceived attractiveness of men's facial hair, a secondary sexual trait subject to considerable cultural variation. We first showed participants a suite of faces, within which we manipulated the frequency of beard thicknesses and then measured preferences for four standard levels of beardedness. Women and men judged heavy stubble and full beards more attractive when presented in treatments where beards were rare than when they were common, with intermediate preferences when intermediate frequencies of beardedness were presented. Likewise, clean-shaven faces were least attractive when clean-shaven faces were most common and more attractive when rare. This pattern in preferences is consistent with negative frequency-dependent selection.

  7. [The normotensive carriers of the MTHFR 677T allele, displaying the increased risk of development of the abdominal aortic aneurysm (AAA), occur at the highest frequency among the smoking patients].

    PubMed

    Strauss, Ewa; Waliszewski, Krzysztof; Pawlak, Andrzej L

    2004-01-01

    Abdominal aortic aneurysm (AAA) presents itself as a progressive dilation of the abdominal aorta, leading--if untreated--to rupture. It is a common disease of the elderly, with a complex etiology. Smoking, hypertension and several genetic factors are recognized as relevant for the pathogenesis of AAA. We studied association between the polymorphism of the MTHFR (methylenetetrahydrofolate reductase) gene within the fourth exon (677C>T) and the occurrence of hypertension and smoking status in the group of 74 male patients with AAA. In the patients group, the smoking hypertensive persons represented the largest subgroup (43%). We determined the the MTHFR 677C>T polymorphism in AAA patients and compared it to that in 71 healthy normotensive males. The frequencies of the 677T allele and MTHFR 677C>T genotypes were similar in both groups, but the subgroup of normotensive AAA patients (n=29) displayed significantly increased frequencies of 677T allele (0.4) and of 677CT and TT genotypes (69%), as compared to those in the control group (0.28 and 46%, respectively). This corresponds to the 3.3-fold greater risk of AAA in normotensive subjects with the 677T allele of MTHFR, as compared to the homo-zygotes 677CC (p<0.03; 95% CI=1.2-9.2). The highest frequencies of MTHFR 677T allele (0.43) and 677CT and TT genotypes (73%) were found in the subgroup of normotensive smoking patients (n=22).

  8. Amplitude Variation of Bottom Simulating Reflection with Respect to Frequency - Transitional Base or Attenuation?

    USGS Publications Warehouse

    Lee, Myung W.

    2007-01-01

    The amplitude of a bottom simulating reflection (BSR), which occurs near the phase boundary between gas hydrate-bearing sediments and underlying gas-filled sediments, strongly depends on the frequency content of a seismic signal, as well as the impedance contrast across the phase boundary. A strong-amplitude BSR, detectable in a conventional seismic profile, is a good indicator of the presence of free gas beneath the phase boundary. However, the BSR as observed in low-frequency multichannel seismic data is generally difficult to identify in high-frequency, single-channel seismic data. To investigate the frequency dependence of BSR amplitudes, single-channel seismic data acquired with an air gun source at Blake Ridge, which is located off the shore of South Carolina, were analyzed in the frequency range of 10-240 Hz. The frequency-dependent impedance contrast caused by the velocity dispersion in partially gas saturated sediments is important to accurately analyze BSR amplitude. Analysis indicates that seismic attenuation of gas hydrate-bearing sediments, velocity dispersion, and a transitional base all contribute to the frequency-dependent BSR amplitude variation in the frequency range of 10-500 Hz. When velocity dispersion is incorporated into the BSR amplitude analysis, the frequency-dependent BSR amplitude at Blake Ridge can be explained with gas hydrate-bearing sediments having a quality factor of about 250 and a transitional base with a thickness of about 1 meter.

  9. Analysis of all-frequency variational behavior of the Kirchhoff approximation for a classic surface-scattering model

    NASA Technical Reports Server (NTRS)

    Bird, J. F.

    1985-01-01

    In testing a stochastic variational principle at high frequencies by using a Kirchhoffean trial function in an idealized model for surface scattering - a randomly embossed plane - we have found not only the predicted high-frequency improvement but also an unexpected low-frequency improvement in the calculated scattering amplitudes. To investigate systematically the all-frequency variational behavior, we consider here the deterministic one-boss case - Rayleigh's classic model whose exact solution is available for comparison - over all wavelengths, polarizations, and configurations of incidence and scattering. We examine analytically in particular the long-wave limit of the variational-Kirchhoff amplitudes; the results demonstrate improvements in both wavelength and angle depedence for horizontal (TM) polarization and some variational improvements for vertical (TE) polarization. This low-frequency behavior in tandem with the foreseen high-frequency improvement leads to good variational-Kirchhoff results through the intermediate resonance-frequency regime for this model.

  10. Systems for controlling the intensity variations in a laser beam and for frequency conversion thereof

    DOEpatents

    Skupsky, Stanley; Craxton, R. Stephen; Soures, John

    1990-01-01

    In order to control the intensity of a laser beam so that its intensity varies uniformly and provides uniform illumination of a target, such as a laser fusion target, a broad bandwidth laser pulse is spectrally dispersed spatially so that the frequency components thereof are spread apart. A disperser (grating) provides an output beam which varies spatially in wavelength in at least one direction transverse to the direction of propagation of the beam. Temporal spread (time delay) across the beam is corrected by using a phase delay device (a time delay compensation echelon). The dispersed beam may be amplified with laser amplifiers and frequency converted (doubled, tripled or quadrupled in frequency) with nonlinear optical elements (birefringent crystals). The spectral variation across the beam is compensated by varying the angle of incidence on one of the crystals with respect to the crystal optical axis utilizing a lens which diverges the beam. Another lens after the frequency converter may be used to recollimate the beam. The frequency converted beam is recombined so that portions of different frequency interfere and, unlike interference between waves of the same wavelength, there results an intensity pattern with rapid temoral oscillations which average out rapidly in time thereby producing uniform illumination on target. A distributed phase plate (also known as a random phase mask), through which the spectrally dispersed beam is passed and then focused on a target, is used to provide the interference pattern which becomes nearly modulation free and uniform in intensity in the direction of the spectral variation.

  11. Systems for controlling the intensity variations in a laser beam and for frequency conversion thereof

    DOEpatents

    Skupsky, S.; Craxton, R.S.; Soures, J.

    1990-10-02

    In order to control the intensity of a laser beam so that its intensity varies uniformly and provides uniform illumination of a target, such as a laser fusion target, a broad bandwidth laser pulse is spectrally dispersed spatially so that the frequency components thereof are spread apart. A disperser (grating) provides an output beam which varies spatially in wavelength in at least one direction transverse to the direction of propagation of the beam. Temporal spread (time delay) across the beam is corrected by using a phase delay device (a time delay compensation echelon). The dispersed beam may be amplified with laser amplifiers and frequency converted (doubled, tripled or quadrupled in frequency) with nonlinear optical elements (birefringent crystals). The spectral variation across the beam is compensated by varying the angle of incidence on one of the crystals with respect to the crystal optical axis utilizing a lens which diverges the beam. Another lens after the frequency converter may be used to recollimate the beam. The frequency converted beam is recombined so that portions of different frequency interfere and, unlike interference between waves of the same wavelength, there results an intensity pattern with rapid temporal oscillations which average out rapidly in time thereby producing uniform illumination on target. A distributed phase plate (also known as a random phase mask), through which the spectrally dispersed beam is passed and then focused on a target, is used to provide the interference pattern which becomes nearly modulation free and uniform in intensity in the direction of the spectral variation. 16 figs.

  12. Rare HLA Drive Additional HIV Evolution Compared to More Frequent Alleles

    PubMed Central

    Lockhart, David W.; Listgarten, Jennifer; Maley, Stephen N.; Kadie, Carl; Learn, Gerald H.; Nickle, David C.; Heckerman, David E.; Deng, Wenjie; Brander, Christian; Ndung'u, Thumbi; Coovadia, Hoosen; Goulder, Philip J.R.; Korber, Bette T.; Walker, Bruce D.; Mullins, James I.

    2009-01-01

    Abstract HIV-1 can evolve HLA-specific escape variants in response to HLA-mediated cellular immunity. HLA alleles that are common in the host population may increase the frequency of such escape variants at the population level. When loss of viral fitness is caused by immune escape variation, these variants may revert upon infection of a new host who does not have the corresponding HLA allele. Furthermore, additional escape variants may appear in response to the nonconcordant HLA alleles. Because individuals with rare HLA alleles are less likely to be infected by a partner with concordant HLA alleles, viral populations infecting hosts with rare HLA alleles may undergo a greater amount of evolution than those infecting hosts with common alleles due to the loss of preexisting escape variants followed by new immune escape. This hypothesis was evaluated using maximum likelihood phylogenetic trees of each gene from 272 full-length HIV-1 sequences. Recent viral evolution, as measured by the external branch length, was found to be inversely associated with HLA frequency in nef (p < 0.02), env (p < 0.03), and pol (p ≤ 0.05), suggesting that rare HLA alleles provide a disproportionate force driving viral evolution compared to common alleles, likely due to the loss of preexisting escape variants during early stages postinfection. PMID:19327049

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

    PubMed

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

    2015-02-01

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

  14. Mutations of the GLA gene in Korean patients with Fabry disease and frequency of the E66Q allele as a functional variant in Korean newborns.

    PubMed

    Lee, Beom Hee; Heo, Sun Hee; Kim, Gu-Hwan; Park, Jung-Young; Kim, Woo-Shik; Kang, Duk-Hee; Choe, Kyung Hoon; Kim, Won-Ho; Yang, Song Hyun; Yoo, Han-Wook

    2010-08-01

    Fabry disease is caused by an alpha-galactosidase A (GLA) deficiency. In this study, we identified 28 unrelated Korean families with Fabry disease with 25 distinct mutations in the GLA gene including six novel mutations (p.W47X, p.C90X, p.D61EfsX32, IVS4(-11)T>A, p.D322E and p.W349). Notably, five subjects from four unrelated families carried the p.E66Q variant, previously known as a pathogenic mutation in atypical Fabry disease. Among these patients, only one had proteinuria and two had hypertrophic cardiomyopathy without any other systemic manifestation of Fabry disease. Substantial residual GLA activity was shown both in the leukocytes of p.E66Q patients (19.0-30.3% of normal activity) and in transiently overexpressed COS-7 cells (43.8 + or - 3.03% of normal activity). Although GLA harboring p.E66Q is unstable at neutral pH, the enzyme is efficiently expressed in the lysosomes of COS-7 cells. The location of p.E66 is distant from both the active site and the dimer interface, and has a more accessible surface area than have other mutations of atypical Fabry disease. In addition, the allele frequency of p.E66Q determined in 833 unrelated Korean individuals was remarkably high at 1.046% (95% confidence interval, 0.458-1.634%). These results indicate that p.E66Q is a functional polymorphism rather than a pathogenic mutation.

  15. Parametrizing the time variation of the `surface term' of stellar p-mode frequencies: application to helioseismic data

    NASA Astrophysics Data System (ADS)

    Howe, R.; Basu, S.; Davies, G. R.; Ball, W. H.; Chaplin, W. J.; Elsworth, Y.; Komm, R.

    2017-02-01

    The solar-cycle variation of acoustic mode frequencies has a frequency dependence related to the inverse mode inertia. The discrepancy between model predictions and measured oscillation frequencies for solar and solar-type stellar acoustic modes includes a significant frequency-dependent term known as the surface term, which is also related to the inverse mode inertia. We parametrize both the surface term and the frequency variations for low-degree solar data from Birmingham Solar-Oscillations Network (BiSON) and medium-degree data from the Global Oscillations Network Group (GONG) using the mode inertia together with cubic and inverse frequency terms. We find that for the central frequency of rotationally split multiplets, the cubic term dominates both the average surface term and the temporal variation, but for the medium-degree case, the inverse term improves the fit to the temporal variation. We also examine the variation of the even-order splitting coefficients for the medium-degree data and find that, as for the central frequency, the latitude-dependent frequency variation, which reflects the changing latitudinal distribution of magnetic activity over the solar cycle, can be described by the combination of a cubic and an inverse function of frequency scaled by inverse mode inertia. The results suggest that this simple parametrization could be used to assess the activity-related frequency variation in solar-like asteroseismic targets.

  16. Frequency variations of the earth's obliquity and the 100-kyr ice-age cycles

    NASA Technical Reports Server (NTRS)

    Liu, Han-Shou

    1992-01-01

    Changes in the earth's climate are induced by variations in the earth's orbital parameters which modulate the seasonal distribution of solar radiation. Periodicities in the geological climate record with cycles of 100, 41, and 23 kyr have been linked with changes in obliquity, eccentricity, and precession of the equinoxes. The effect of variations of eccentricity during a 100 kyr period is weak relative to the signals from obliquity and precession variations and it may therefore be expected that the 100 kyr signal in the climate record would be of low intensity. However, this signal dominates the climate record and internal nonlinear processes within the climate system have previously been proposed to account for this fact. The author shows that variations in the frequency of the obliquity cycle can give rise to strong 100-kyr forcing of climate.

  17. Frequency-independent approach to calculate physical optics radiations with the quadratic concave phase variations

    NASA Astrophysics Data System (ADS)

    Wu, Yu Mao; Teng, Si Jia

    2016-11-01

    In this work, we develop the numerical steepest descent path (NSDP) method to calculate the physical optics (PO) radiations with the quadratic concave phase variations. With the surface integral equation method, the physical optics (PO) scattered fields are formulated and further reduced to the surface integrals. The high frequency physical critical points contributions, including the stationary phase points, the boundary resonance points and the vertex points are comprehensively studied via the proposed NSDP method. The key contributions of this work are twofold. One is that together with the PO integrals taking the quadratic parabolic and hyperbolic phase terms, this work makes the NSDP theory be complete for treating the PO integrals with quadratic phase variations. Another is that, in order to illustrate the transition effect of the high frequency physical critical points, in this work, we consider and further extend the NSDP method to calculate the PO integrals with the coalescence of the high frequency critical points. Numerical results for the highly oscillatory PO integral with the coalescence of the critical points are given to verify the efficiency of the proposed NSDP method. The NSDP method could achieve the frequency independent computational workload and error controllable accuracy in all the numerical experiments, especially for the case of the coalescence of the high frequency critical points.

  18. Top down and bottom up selection drives variations in frequency and form of a visual signal

    PubMed Central

    Yeh, Chien-Wei; Blamires, Sean J.; Liao, Chen-Pan; Tso, I.-Min

    2015-01-01

    The frequency and form of visual signals can be shaped by selection from predators, prey or both. When a signal simultaneously attracts predators and prey, selection may favour a strategy that minimizes risks while attracting prey. Accordingly, varying the frequency and form of the silken decorations added to their web may be a way that Argiope spiders minimize predation while attracting prey. Nonetheless, the role of extraneous factors renders the influences of top down and bottom up selection on decoration frequency and form variation difficult to discern. Here we used dummy spiders and decorations to simulate four possible strategies that the spider Argiope aemula may choose and measured the prey and predator attraction consequences for each in the field. The strategy of decorating at a high frequency with a variable form attracted the most prey, while that of decorating at a high frequency with a fixed form attracted the most predators. These results suggest that mitigating the cost of attracting predators while maintaining prey attraction drives the use of variation in decoration form by many Argiope spp. when decorating frequently. Our study highlights the importance of considering top-down and bottom up selection pressure when devising evolutionary ecology experiments. PMID:25828030

  19. Theoretical analysis of the EAST 4-strap ion cyclotron range of frequency antenna with variational theory

    NASA Astrophysics Data System (ADS)

    Zhang, Jia-Hui; Zhang, Xin-Jun; Zhao, Yan-Ping; Qin, Cheng-Ming; Chen, Zhao; Yang, Lei; Wang, Jian-Hua

    2016-08-01

    A variational principle code which can calculate self-consistently currents on the conductors is used to assess the coupling characteristic of the EAST 4-strap ion cyclotron range of frequency (ICRF) antenna. Taking into account two layers of antenna conductors without lateral frame but with slab geometry, the antenna impedances as a function of frequency and the structure of RF field excited inside the plasma in various phasing cases are discussed in this paper. Project supported by the National Magnetic Confinement Fusion Science Program, China (Grant No. 2015GB101001) and the National Natural Science Foundation of China (Grant Nos. 11375236 and 11375235).

  20. High Frequency Variations of Earth Rotation Parameters from GPS and GLONASS Observations

    PubMed Central

    Wei, Erhu; Jin, Shuanggen; Wan, Lihua; Liu, Wenjie; Yang, Yali; Hu, Zhenghong

    2015-01-01

    The Earth's rotation undergoes changes with the influence of geophysical factors, such as Earth's surface fluid mass redistribution of the atmosphere, ocean and hydrology. However, variations of Earth Rotation Parameters (ERP) are still not well understood, particularly the short-period variations (e.g., diurnal and semi-diurnal variations) and their causes. In this paper, the hourly time series of Earth Rotation Parameters are estimated using Global Positioning System (GPS), Global Navigation Satellite System (GLONASS), and combining GPS and GLONASS data collected from nearly 80 sites from 1 November 2012 to 10 April 2014. These new observations with combining different satellite systems can help to decorrelate orbit biases and ERP, which improve estimation of ERP. The high frequency variations of ERP are analyzed using a de-trending method. The maximum of total diurnal and semidiurnal variations are within one milli-arcseconds (mas) in Polar Motion (PM) and 0.5 milli-seconds (ms) in UT1-UTC. The semidiurnal and diurnal variations are mainly related to the ocean tides. Furthermore, the impacts of satellite orbit and time interval used to determinate ERP on the amplitudes of tidal terms are analyzed. We obtain some small terms that are not described in the ocean tide model of the IERS Conventions 2010, which may be caused by the strategies and models we used or the signal noises as well as artifacts. In addition, there are also small differences on the amplitudes between our results and IERS convention. This might be a result of other geophysical excitations, such as the high-frequency variations in atmospheric angular momentum (AAM) and hydrological angular momentum (HAM), which needs more detailed analysis with more geophysical data in the future. PMID:25635416

  1. High frequency variations of Earth Rotation Parameters from GPS and GLONASS observations.

    PubMed

    Wei, Erhu; Jin, Shuanggen; Wan, Lihua; Liu, Wenjie; Yang, Yali; Hu, Zhenghong

    2015-01-28

    The Earth's rotation undergoes changes with the influence of geophysical factors, such as Earth's surface fluid mass redistribution of the atmosphere, ocean and hydrology. However, variations of Earth Rotation Parameters (ERP) are still not well understood, particularly the short-period variations (e.g., diurnal and semi-diurnal variations) and their causes. In this paper, the hourly time series of Earth Rotation Parameters are estimated using Global Positioning System (GPS), Global Navigation Satellite System (GLONASS), and combining GPS and GLONASS data collected from nearly 80 sites from 1 November 2012 to 10 April 2014. These new observations with combining different satellite systems can help to decorrelate orbit biases and ERP, which improve estimation of ERP. The high frequency variations of ERP are analyzed using a de-trending method. The maximum of total diurnal and semidiurnal variations are within one milli-arcseconds (mas) in Polar Motion (PM) and 0.5 milli-seconds (ms) in UT1-UTC. The semidiurnal and diurnal variations are mainly related to the ocean tides. Furthermore, the impacts of satellite orbit and time interval used to determinate ERP on the amplitudes of tidal terms are analyzed. We obtain some small terms that are not described in the ocean tide model of the IERS Conventions 2010, which may be caused by the strategies and models we used or the signal noises as well as artifacts. In addition, there are also small differences on the amplitudes between our results and IERS convention. This might be a result of other geophysical excitations, such as the high-frequency variations in atmospheric angular momentum (AAM) and hydrological angular momentum (HAM), which needs more detailed analysis with more geophysical data in the future.

  2. Variational approach to low-frequency kinetic-MHD in the current coupling scheme

    NASA Astrophysics Data System (ADS)

    Burby, Joshua W.; Tronci, Cesare

    2017-04-01

    Hybrid kinetic-MHD models describe the interaction of an MHD bulk fluid with an ensemble of hot particles, which obeys a kinetic equation. In this work we apply Hamilton’s variational principle to formulate new current-coupling kinetic-MHD models in the low-frequency approximation (i.e. large Larmor frequency limit). More particularly, we formulate current-coupling schemes, in which energetic particle dynamics are expressed in either guiding center or gyrocenter coordinates. When guiding center theory is used to model the hot particles, we show how energy conservation requires corrections to the standard magnetization term. On the other hand, charge and momentum conservation in gyrokinetic-MHD lead to extra terms in the usual definition of the hot current density as well as modifications to conventional gyrocenter dynamics. All these new features arise naturally from the underlying variational structure of the proposed models.

  3. Variational approach to low-frequency kinetic-MHD in the current-coupling scheme

    NASA Astrophysics Data System (ADS)

    Tronci, Cesare; Burby, Joshua

    2016-10-01

    Hybrid kinetic-MHD models describe the interaction of an MHD bulk fluid with an ensemble of hot particles, which is described by a kinetic equation. When the Vlasov description is adopted for the energetic particles, different Vlasov-MHD models have been shown to lack an exact energy balance, unless non-inertial force terms are inserted in the kinetic equation. These force terms arise from fundamental approaches based on Hamiltonian and variational methods. In this work we apply Hamilton's variational principle to formulate new current-coupling kinetic-MHD models in the low-frequency approximation (i.e. large Larmor frequency limit). More particularly, we formulate current-coupling hybrid schemes, in which energetic particle dynamics are expressed in either guiding-center or gyrocenter coordinates. Financial support by the Leverhulme Trust Research Project Grant No. 2014-112 is greatly acknowledged.

  4. The role of low-frequency variation in the manifestation of warming trend and ENSO amplitude

    NASA Astrophysics Data System (ADS)

    Yeo, Sae-Rim; Yeh, Sang-Wook; Kim, Kwang-Yul; Kim, WonMoo

    2016-10-01

    Despite the increase in greenhouse gas concentration, the sea surface temperature (SST) over the tropical eastern Pacific during the period of 1999-2014 exhibits less warming trend compared to the earlier decades. It has been noted that this warming hiatus is accompanied by a negative phase of the Pacific Decadal Oscillation (PDO), which represents low-frequency variability over the Pacific. On the other hand, the 2015/2016 El Niño is among the strongest comparable to the 1997/1998 event, which coincides with the recently altered PDO phase from negative to positive. These observational evidences have generated substantial interest in the role of low-frequency variations in modulating El Niño-Southern Oscillation amplitude as well as manifestation of warming signal in the tropical Pacific. Therefore, it is necessary to appropriately separate low-frequency variability and global warming signal from SST records. Here, we present three primary modes of global SST that include secular warming trend, low-frequency variability, and biennial oscillation. Based on the independent behavior of these three modes, global warming is clearly continuing but its manifestation is enhanced (depressed) when the low-frequency variation is in the positive (negative) phase. Further, possibility of strong El Niño increases under the positive phase of the low-frequency mode, which amplifies warming over the tropical eastern Pacific. Indeed, the strong 2015/2016 El Niño is largely attributed to the positive phase of the low-frequency mode. In order to examine the climate models' ability to simulate the three SST modes as obtained in the observational record, the Coupled Model Intercomparison Project phase 5 (CMIP5) datasets are also analyzed. The spatial and temporal characteristics of the three modes have been replicated closely by the selected CMIP5 models forced by the historical condition, which provides an analogy of the interplay of three modes in the observed tropical Pacific SST.

  5. The new chirp-Wigner higher order spectra for transient signals with any known nonlinear frequency variation

    NASA Astrophysics Data System (ADS)

    Gelman, L.; Petrunin, I.; Komoda, J.

    2010-02-01

    The new chirp-Wigner higher order spectra (CWHOS) are proposed for transient signals with any known nonlinear polynomial variation of instantaneous frequency. The proposed technique is effective for nonlinearity detection for transient signals with nonlinear polynomial time variation of the instantaneous frequency.

  6. PULSAR TIMING ERRORS FROM ASYNCHRONOUS MULTI-FREQUENCY SAMPLING OF DISPERSION MEASURE VARIATIONS

    SciTech Connect

    Lam, M. T.; Cordes, J. M.; Chatterjee, S.; Dolch, T.

    2015-03-10

    Free electrons in the interstellar medium cause frequency-dependent delays in pulse arrival times due to both scattering and dispersion. Multi-frequency measurements are used to estimate and remove dispersion delays. In this paper, we focus on the effect of any non-simultaneity of multi-frequency observations on dispersive delay estimation and removal. Interstellar density variations combined with changes in the line of sight from pulsar and observer motions cause dispersion measure (DM) variations with an approximately power-law power spectrum, augmented in some cases by linear trends. We simulate time series, estimate the magnitude and statistical properties of timing errors that result from non-simultaneous observations, and derive prescriptions for data acquisition that are needed in order to achieve a specified timing precision. For nearby, highly stable pulsars, measurements need to be simultaneous to within about one day in order for the timing error from asynchronous DM correction to be less than about 10 ns. We discuss how timing precision improves when increasing the number of dual-frequency observations used in DM estimation for a given epoch. For a Kolmogorov wavenumber spectrum, we find about a factor of two improvement in precision timing when increasing from two to three observations but diminishing returns thereafter.

  7. Allele frequencies and genetic diversity in two groups of wild tufted capuchin monkeys (Cebus apella nigritus) living in an urban forest fragment.

    PubMed

    Amaral, Jeanne Margareth Jimenes; Simões, Aguinaldo Luiz; De Jong, David

    2005-12-30

    There have been numerous studies genetically characterizing Old World Primates using microsatellites. However, few studies have been made of New World species and none on free-ranging Cebus apella, even though it is probably the most widely distributed species of monkey in the New World. The paucity of studies is due, in part, to the lack of polymorphisms described for this species. We studied two groups of wild tufted capuchins, Cebus apella nigritus, which inhabit Mata Santa Teresa, the Ecological Reserve of Ribeirão Preto, a 158-ha forest fragment in a semi-urban zone of Ribeirão Preto, SP, Brazil. Group 1 had about 60 animals, 35 of which were sampled, and group 2 had about 40 animals, 20 of which were sampled. These group sizes are much larger than the published reports of 6-30 for this species, despite, or perhaps due to the isolation and the size of the forest fragment. Allele PEPC59*1 was the most frequent of all alleles at all loci in both groups (55.7 and 55%), allele PEPC8*1 was the most common allele in group 2 (46.9%) and PEPC8*4 in group 1 (41.1%), allele PEPC3*2 was the most common in group 1 (35.7%) and allele PEPC3*4 in group 2 (31.6%). The genetic diversity, considering each locus in each group, varied from 61.9% at locus PEPC59 to 78.6% at locus PEPC3, both in group 1. The mean genetic diversity (H(S)), considering both groups for all of the loci, was 71.1%. The inter-group diversity (F(ST)) was 1.9%, indicating that these groups belong to the same population. These groups apparently have a high genetic diversity, despite their isolation in a limited forest fragment, although more data are needed to adequately characterize this population.

  8. Cyclic variations of high-frequency ultrasonic backscattering from blood under pulsatile flow.

    PubMed

    Huang, Chih-Chung

    2009-08-01

    It was shown previously that ultrasonic scattering from whole blood varies during the flow cycle under pulsatile flow both in vitro and in vivo. It has been postulated that the cyclic variations of the backscattering signal are associated with red blood cell (RBC) aggregation in flowing whole blood. To obtain a better understanding of the relationship between blood backscattering and RBC aggregation behavior for pulsatile flowing blood, the present study used high-frequency ultrasound to characterize blood properties. The backscattering signals from both whole blood and an RBC suspension at different peak flow velocities (from 10 to 30 cm/s) and hematocrits (20% and 40%) under pulsatile flow (stroke rate of 20 beats/min) were measured with 3 single-element transducers at frequencies of 10, 35, and 50 MHz in a mock flow loop. To avoid the frequency response problem of a Doppler flowmeter, the integrated backscatter (IB) and flow velocity as functions of time were calculated directly using RF signals from flowing blood. The experimental results showed that cyclic variations of the IB curve were clearly observed at a low flow velocity and a hematocrit of 40% when using 50 MHz ultrasound, and that these variations became weaker as the peak flow velocity increased. However, these cyclic variations were detected only at 10 cm/s when using 10 MHz ultrasound. These results demonstrate that a high flow velocity can stop the formation of rouleaux and that a high hematocrit can promote RBC aggregation to produce cyclic variations of the backscattering signal under pulsatile flow. In addition, slight cyclic variations of the IB curve for an RBC suspension were observed at 35 and 50 MHz. Furthermore, the peak of the IB curve from whole blood led the peak of the velocity waveform when using high-frequency ultrasound, which could be explained by the assumption that a rapid flow can promote RBC aggregation under pulsatile flow. Together, the experimental results showed that the

  9. Allelic variants of the amylose extender mutation of maize demonstrate phenotypic variation in starch structure resulting from modified protein–protein interactions

    PubMed Central

    Liu, Fushan; Ahmed, Zaheer; Lee, Elizabeth A.; Donner, Elizabeth; Liu, Qiang; Ahmed, Regina; Morell, Matthew K.; Emes, Michael J.; Tetlow, Ian J.

    2012-01-01

    amylose extender (ae−) starches characteristically have modified starch granule morphology resulting from amylopectin with reduced branch frequency and longer glucan chains in clusters, caused by the loss of activity of the major starch branching enzyme (SBE), which in maize endosperm is SBEIIb. A recent study with ae− maize lacking the SBEIIb protein (termed ae1.1 herein) showed that novel protein–protein interactions between enzymes of starch biosynthesis in the amyloplast could explain the starch phenotype of the ae1.1 mutant. The present study examined an allelic variant of the ae− mutation, ae1.2, which expresses a catalytically inactive form of SBEIIb. The catalytically inactive SBEIIb in ae1.2 lacks a 28 amino acid peptide (Val272–Pro299) and is unable to bind to amylopectin. Analysis of starch from ae1.2 revealed altered granule morphology and physicochemical characteristics distinct from those of the ae1.1 mutant as well as the wild-type, including altered apparent amylose content and gelatinization properties. Starch from ae1.2 had fewer intermediate length glucan chains (degree of polymerization 16–20) than ae1.1. Biochemical analysis of ae1.2 showed that there were differences in the organization and assembly of protein complexes of starch biosynthetic enzymes in comparison with ae1.1 (and wild-type) amyloplasts, which were also reflected in the composition of starch granule-bound proteins. The formation of stromal protein complexes in the wild-type and ae1.2 was strongly enhanced by ATP, and broken by phosphatase treatment, indicating a role for protein phosphorylation in their assembly. Labelling experiments with [γ-32P]ATP showed that the inactive form of SBEIIb in ae1.2 was phosphorylated, both in the monomeric form and in association with starch synthase isoforms. Although the inactive SBEIIb was unable to bind starch directly, it was strongly associated with the starch granule, reinforcing the conclusion that its presence in the

  10. BaalChIP: Bayesian analysis of allele-specific transcription factor binding in cancer genomes.

    PubMed

    de Santiago, Ines; Liu, Wei; Yuan, Ke; O'Reilly, Martin; Chilamakuri, Chandra Sekhar Reddy; Ponder, Bruce A J; Meyer, Kerstin B; Markowetz, Florian

    2017-02-24

    Allele-specific measurements of transcription factor binding from ChIP-seq data are key to dissecting the allelic effects of non-coding variants and their contribution to phenotypic diversity. However, most methods of detecting an allelic imbalance assume diploid genomes. This assumption severely limits their applicability to cancer samples with frequent DNA copy-number changes. Here we present a Bayesian statistical approach called BaalChIP to correct for the effect of background allele frequency on the observed ChIP-seq read counts. BaalChIP allows the joint analysis of multiple ChIP-seq samples across a single variant and outperforms competing approaches in simulations. Using 548 ENCODE ChIP-seq and six targeted FAIRE-seq samples, we show that BaalChIP effectively corrects allele-specific analysis for copy-number variation and increases the power to detect putative cis-acting regulatory variants in cancer genomes.

  11. The Variability of Sesquiterpenes Emitted from Two Zea mays Cultivars Is Controlled by Allelic Variation of Two Terpene Synthase Genes Encoding Stereoselective Multiple Product Enzymes

    PubMed Central

    Köllner, Tobias G.; Schnee, Christiane; Gershenzon, Jonathan; Degenhardt, Jörg

    2004-01-01

    The mature leaves and husks of Zea mays release a complex blend of terpene volatiles after anthesis consisting predominantly of bisabolane-, sesquithujane-, and bergamotane-type sesquiterpenes. The varieties B73 and Delprim release the same volatile constituents but in significantly different proportions. To study the molecular genetic and biochemical mechanisms controlling terpene diversity and distribution in these varieties, we isolated the closely related terpene synthase genes terpene synthase4 (tps4) and tps5 from both varieties. The encoded enzymes, TPS4 and TPS5, each formed the same complex mixture of sesquiterpenes from the precursor farnesyl diphosphate but with different proportions of products. These mixtures correspond to the sesquiterpene blends observed in the varieties B73 and Delprim, respectively. The differences in the stereoselectivity of TPS4 and TPS5 are determined by four amino acid substitutions with the most important being a Gly instead of an Ala residue at position 409 at the catalytic site of the enzyme. Although both varieties contain tps4 and tps5 alleles, their differences in terpene composition result from the fact that B73 has only a single functional allele of tps4 and no functional alleles of tps5, whereas Delprim has only a functional allele of tps5 and no functional alleles of tps4. Lack of functionality was shown to be attributable to frame-shift mutations or amino acid substitutions that greatly reduce the activity of their encoded proteins. Therefore, the diversity of sesquiterpenes in these two maize cultivars is strongly influenced by single nucleotide changes in the alleles of two terpene synthase genes. PMID:15075399

  12. Allele Frequencies of the Epidermal Growth Factor Receptors Polymorphism R521K in Colorectal Cancer Patients and Healthy Subjects Indicate a Risk-Reducing Effect of K521 in Syrian Population

    PubMed Central

    Mustafa, Ola Haj; Hamzeh, Abdul Rezzak; Ghabreau, Lina; Akil, Nizar; Almoustafa, Ala-Eddin; Alachkar, Amal

    2013-01-01

    Background: Colorectal cancer contributes heavily to cancer morbidity and mortality worldwide. Numerous therapies are currently in use, including monoclonal antibodies against cellular components involved in tumorigenesis such as epidermal growth factor receptors (EGFRs). Studies showed the polymorphism [R521K] GàA in the EGFR gene to be involved in both colorectal cancer susceptibility and clinical response to therapeutics (e.g., Cetuximab). Aim: We aimed at uncovering allele frequencies of this polymorphism among Syrian colorectal cancer patients and healthy individuals. Materials and Methods: Forty-seven patients with colorectal cancer were included in a case-control study along with 48 healthy subjects, all native Syrians. Individuals were genotyped using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) and results were statistically analyzed to elucidate significant differences between the two groups. Results: Allele frequencies were 40.4% (G/G), 57.4% (G/A) and 2.1% (A/A) in colorectal cancer patients and 41.6% (G/G), 43.7% (G/A) and 14.5% (A/A) in healthy subjects. The A/A genotype was significantly lower in colorectal cancer patients than in the control group. Conclusions: Homozygosity for the A allele is linked to reducing the risk of developing colorectal cancer in Syrian patients. The lower prevalence of (A/A) locally may predict sub-optimal rates of clinical response to Cetuximab compared with populations with higher frequencies of the A allele. Larger scale investigations are needed for a stronger conclusion. PMID:23626956

  13. Linkage disequilibrium levels in Bos indicus and Bos taurus cattle using medium and high density SNP chip data and different minor allele frequency distributions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Linkage disequilibrium (LD), the observed correlation between alleles at different loci in the genome, is a determinant parameter in many applications of molecular genetics. With the wider use of genomic technologies in animal breeding and animal genetics, it is worthwhile revising and improving the...

  14. Variation in relapse frequency and the transmission potential of Plasmodium vivax malaria

    PubMed Central

    White, Michael T.; Shirreff, George; Karl, Stephan; Ghani, Azra C.; Mueller, Ivo

    2016-01-01

    There is substantial variation in the relapse frequency of Plasmodium vivax malaria, with fast-relapsing strains in tropical areas, and slow-relapsing strains in temperate areas with seasonal transmission. We hypothesize that much of the phenotypic diversity in P. vivax relapses arises from selection of relapse frequency to optimize transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of P. vivax transmission and calculate the basic reproduction number R0 to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year-round transmission, transmission potential is optimized at intermediate relapse frequencies of two to three months: slower-relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster-relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be six to nine months, coinciding with the duration between seasonal transmission peaks. We predict that there is a threshold degree of seasonality, below which fast-relapsing tropical strains are selected for, and above which slow-relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes. PMID:27030414

  15. Variation in relapse frequency and the transmission potential of Plasmodium vivax malaria.

    PubMed

    White, Michael T; Shirreff, George; Karl, Stephan; Ghani, Azra C; Mueller, Ivo

    2016-03-30

    There is substantial variation in the relapse frequency of Plasmodium vivax malaria, with fast-relapsing strains in tropical areas, and slow-relapsing strains in temperate areas with seasonal transmission. We hypothesize that much of the phenotypic diversity in P. vivax relapses arises from selection of relapse frequency to optimize transmission potential in a given environment, in a process similar to the virulence trade-off hypothesis. We develop mathematical models of P. vivax transmission and calculate the basic reproduction number R0 to investigate how transmission potential varies with relapse frequency and seasonality. In tropical zones with year-round transmission, transmission potential is optimized at intermediate relapse frequencies of two to three months: slower-relapsing strains increase the opportunity for onward transmission to mosquitoes, but also increase the risk of being outcompeted by faster-relapsing strains. Seasonality is an important driver of relapse frequency for temperate strains, with the time to first relapse predicted to be six to nine months, coinciding with the duration between seasonal transmission peaks. We predict that there is a threshold degree of seasonality, below which fast-relapsing tropical strains are selected for, and above which slow-relapsing temperate strains dominate, providing an explanation for the observed global distribution of relapse phenotypes.

  16. A thorough analysis of the short- and mid-term activity-related variations in the solar acoustic frequencies

    NASA Astrophysics Data System (ADS)

    Santos, A. R. G.; Cunha, M. S.; Avelino, P. P.; Chaplin, W. J.; Campante, T. L.

    2017-02-01

    The frequencies of the solar acoustic oscillations vary over the activity cycle. The variations in other activity proxies are found to be well correlated with the variations in the acoustic frequencies. However, each proxy has a slightly different time behaviour. Our goal is to characterize the differences between the time behaviour of the frequency shifts and of two other activity proxies, namely the area covered by sunspots and the 10.7-cm flux. We define a new observable that is particularly sensitive to the short-term frequency variations. We then compare the observable when computed from model frequency shifts and from observed frequency shifts obtained with the Global Oscillation Network Group (GONG) for cycle 23. Our analysis shows that on the shortest time-scales, the variations in the frequency shifts seen in the GONG observations are strongly correlated with the variations in the area covered by sunspots. However, a significant loss of correlation is still found. We verify that the times when the frequency shifts and the sunspot area do not vary in a similar way tend to coincide with the times of the maxima of the quasi-biennial variations seen in the solar seismic data. A similar analysis of the relation between the 10.7-cm flux and the frequency shifts reveals that the short-time variations in the frequency shifts follow even more closely those of the 10.7-cm flux than those of the sunspot area. However, a loss of correlation between frequency shifts and 10.7-cm flux variations is still found around the same times.

  17. Measuring frequency changes due to microwave power variations as a function of C-field setting in a rubidium frequency standard

    NASA Technical Reports Server (NTRS)

    Sarosy, E. B.; Johnson, Walter A.; Karuza, Sarunas K.; Voit, Frank J.

    1992-01-01

    It has been shown in previous studies that in some cesium frequency standards there exist certain C-field settings that minimize frequency changes that are due to variations in the microwave power. In order to determine whether similar results could be obtained with rubidium (Rb) frequency standards (clocks), we performed a similar study, using a completely automated measurement system, on a commercial Rb standard. From our measurements we found that changing the microwave power to the filter cell resulted in significant changes in frequency, and that the magnitude of these frequency changes at low C-field levels went to zero and decreased as the C-field was increased.

  18. Regional and yearly variations of hail frequency and intensity in France

    NASA Astrophysics Data System (ADS)

    Berthet, C.; Dessens, J.; Sanchez, J. L.

    2011-06-01

    In addition to the ground seeding hail prevention project, the Association Nationale d'Etude et de Lutte contre les Fléaux Atmosphériques (ANELFA) operates hailpad networks in four of the most hailed regions of France: Atlantic, Pyrenean, Central and Mediterranean. During the past 22 years of continuous measurements, more than five thousand point hailfalls have been recorded at 922 stations (mean annual value) installed in a 66,500 km² area. At the scale of a region and of a hail season, hail is found to be the product of two nearly independent parameters, the frequency and the mean intensity of hailfalls. The frequency is highest in the Pyrenean region, while the intensity is highest both in the Pyrenean and Central regions. This can be explained, for the frequency, by the proximity of Spain, and, for the intensity, by the mean hailstone size distributions which are different in the continental and maritime regions. The time variations and trends of hail during the 1989-2009 period are computed from the data at 457 stations which never changed during this period. The annual frequency is subject to cyclic variations, while the yearly mean intensity is affected by irregular severe hail events. The frequency did not change significantly during the period, while the intensity increased by 70%. The mean monthly distribution of hail is bimodal, with two maximums in May and July, suggesting that two types of meteorological conditions are at the origin of hailstorms. April and May are solely responsible for the mean hail increase observed during the period. A computation of the year-to-year correlation between hail intensity and mean minimum surface temperature for each month suggests that the large hail increase in April and May is at least partially due to the observed concomitant increase in temperature, and then may be a consequence of global warning.

  19. Atrial signal variations and pacemaker malsensing during exercise: a study in the time and frequency domain.

    PubMed

    Fröhlig, G; Schwerdt, H; Schieffer, H; Bette, L

    1988-04-01

    To give some explanation for atrial malsensing in dual chamber pacing that occurs only during exercise, atrial electrograms from 33 patients were telemetrically recorded and analyzed in both the time and frequency domains. During exercise, an overall decrease from 6.4 +/- 1.9 to 5.6 +/- 1.9 mV (-11%) in the atrial signal amplitude was noted. Despite considerable variability among patients, marked changes occurred in 15 patients whose signals diminished by 11 to 49%. Slew rates showed a similar decrease from 1.35 +/- 0.45 to 1.18 +/- 0.45 V/s (-10.8%), with individual changes of as much as -51%. Signal attenuation in the time domain correlated well with frequency data, exhibiting a highly significant reduction of signal energy between 25 and 105 Hz. However, spectral distribution changed from rest to exercise, with a relative increase of signal energy in the range between 5 and 25 Hz and a decrease at higher frequencies. Individual changes differed widely when low (15 to 65 Hz) and high (65 to 115 Hz) frequencies were compared, but in a group of 11 patients signal attenuation in the high frequency band was more pronounced (-45%) than in the low frequency band (-23%). The clinical impact of the change in frequency distribution during ergometry was visualized by computer simulation of two different (low and high bandpass) filters. Although in individual patients, both characteristics may be favorable with respect to atrial sensing, it was observed in 11 patients that high pass filtering attenuates signal amplitudes by 10 to 24% in excess of the variation without filtering.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Does infectious disease cause global variation in the frequency of intrastate armed conflict and civil war?

    PubMed

    Letendre, Kenneth; Fincher, Corey L; Thornhill, Randy

    2010-08-01

    Geographic and cross-national variation in the frequency of intrastate armed conflict and civil war is a subject of great interest. Previous theory on this variation has focused on the influence on human behaviour of climate, resource competition, national wealth, and cultural characteristics. We present the parasite-stress model of intrastate conflict, which unites previous work on the correlates of intrastate conflict by linking frequency of the outbreak of such conflict, including civil war, to the intensity of infectious disease across countries of the world. High intensity of infectious disease leads to the emergence of xenophobic and ethnocentric cultural norms. These cultures suffer greater poverty and deprivation due to the morbidity and mortality caused by disease, and as a result of decreased investment in public health and welfare. Resource competition among xenophobic and ethnocentric groups within a nation leads to increased frequency of civil war. We present support for the parasite-stress model with regression analyses. We find support for a direct effect of infectious disease on intrastate armed conflict, and support for an indirect effect of infectious disease on the incidence of civil war via its negative effect on national wealth. We consider the entanglements of feedback of conflict into further reduced wealth and increased incidence of disease, and discuss implications for international warfare and global patterns of wealth and imperialism.

  1. Haplotype variation of Glu-D1 locus and the origin of Glu-D1d allele conferring superior end-use qualities in common wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In common wheat (Triticum aestivum, AABBDD), the Glu-D1 locus possesses multiple alleles, with Glu-D1a (coding for 1Dx2 and 1Dy12 subunits) and Glu-D1d (encoding 1Dx5 and 1Dy10 subunits) being intensively used in the genetic improvement of end-use qualities. Here, we studied the molecular variatio...

  2. Allelic variation of LMW-GS composition in Chinese wheat landraces of the Yangtze-River region detected by MALDI-TOF-MS

    PubMed Central

    Peng, Yanchun; Yu, Zitong; Islam, Shahidul; Zhang, Yujuan; Wang, Xiaolong; Lei, Zhensheng; Yu, Kan; Sun, Dongfa; Ma, Wujun

    2016-01-01

    Low molecular weight glutenin subunits are important components of wheat storage proteins, which play an important role in determining end-use quality of common wheat. A newly established matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) procedure was used to analyze 478 landraces of bread wheat collected from the Yangtze-River region in China. Results indicated that 17 alleles at three loci: Glu-A3, Glu-B3 and Glu-D3 were identified, resulting in 87 different allele combinations. Of the 17 alleles detected at all the Glu-3 loci, five belonged to Glu-A3, seven to Glu-B3 and five to Glu-D3 locus. MALDI-TOF-MS indicated Glu-A3a/c was present in 72.8%, Glu-A3b in 8.4%, Glu-A3d in 8.4%, Glu-A3f in 5.2% and Glu-A3e in 3.6% lines. Seven types of alleles were identified at the Glu-B3 locus: Glu-B3d/i (25.5%), Glu-B3b (21.3%), Glu-B3c (16.9%), Glu-B3h (13.8%), Glu-B3f (8.4%), Glu-B3a (8.2%), and Glu-B3g (5.2%). Five types of Glu-D3 alleles were detected: Glu-D3a (58.4%), Glu-D3c (22.6%), Glu-D3d (15.5%), Glu-D3b (3.3%) and Glu-D3f (0.2%). Four new alleles that showed abnormal MALDI-TOF spectrum patterns were identified at the Glu-A3 and Glu-B3 loci. A detailed study is needed to further characterize these alleles and their potential usage for wheat improvement. PMID:27795690

  3. Effect of Allelic Variation at the Glu-3/Gli-1 Loci on Breadmaking Quality Parameters in Hexaploid Wheat (Triticum aestivum L.)

    PubMed Central

    Bonafede, Marcos D.; Tranquilli, Gabriela; Pflüger, Laura A.; Peña, Roberto J.; Dubcovsky, Jorge

    2016-01-01

    Low molecular weight glutenin subunits (LMW-GS) encoded by the Glu-3 loci are known to contribute to wheat breadmaking quality. However, the specific effect of individual Glu-3 alleles is not well understood due to their complex protein banding patterns in SDS-PAGE and tight linkage with gliadins at the Gli-1 locus. Using DNA markers and a backcross program we developed a set of nine near isogenic lines (NILs) including different Glu-A3/GliA-1 or Glu-B3/Gli-B1 alleles in the genetic background of the Argentine variety ProINTA Imperial. The nine NILs and the control were evaluated in three different field trials in Argentina. Significant genotype-by-environment interactions were detected for most quality parameters indicating that the effects of the Glu-3/Gli-1 alleles are modulated by environmental differences. None of the NILs showed differences in total flour protein content, but relative changes in the abundance of particular classes of proteins cannot be ruled out. On average, the Glu-A3f, Glu-B3b, Glu-B3g and Glu-B3iMan alleles were associated with the highest values in gluten strength-related parameters, while Glu-A3e, Glu-B3a and Glu-B3iChu were consistently associated with weak gluten and low quality values. The value of different Glu3/Gli-1 allele combinations to improve breadmaking quality is discussed. PMID:27818572

  4. Effect of Allelic Variation at the Glu-3/Gli-1 Loci on Breadmaking Quality Parameters in Hexaploid Wheat (Triticum aestivum L.).

    PubMed

    Bonafede, Marcos D; Tranquilli, Gabriela; Pflüger, Laura A; Peña, Roberto J; Dubcovsky, Jorge

    2015-03-01

    Low molecular weight glutenin subunits (LMW-GS) encoded by the Glu-3 loci are known to contribute to wheat breadmaking quality. However, the specific effect of individual Glu-3 alleles is not well understood due to their complex protein banding patterns in SDS-PAGE and tight linkage with gliadins at the Gli-1 locus. Using DNA markers and a backcross program we developed a set of nine near isogenic lines (NILs) including different Glu-A3/GliA-1 or Glu-B3/Gli-B1 alleles in the genetic background of the Argentine variety ProINTA Imperial. The nine NILs and the control were evaluated in three different field trials in Argentina. Significant genotype-by-environment interactions were detected for most quality parameters indicating that the effects of the Glu-3/Gli-1 alleles are modulated by environmental differences. None of the NILs showed differences in total flour protein content, but relative changes in the abundance of particular classes of proteins cannot be ruled out. On average, the Glu-A3f, Glu-B3b, Glu-B3g and Glu-B3iMan alleles were associated with the highest values in gluten strength-related parameters, while Glu-A3e, Glu-B3a and Glu-B3iChu were consistently associated with weak gluten and low quality values. The value of different Glu3/Gli-1 allele combinations to improve breadmaking quality is discussed.

  5. Ecological drivers of variation in tool-use frequency across sea otter populations

    USGS Publications Warehouse

    Fujii, Jessica A; Ralls, Katherine; Tinker, M. Tim

    2015-01-01

    Sea otters are well-known tool users, employing objects such as rocks or shells to break open hard-shelled invertebrate prey. However, little is known about how the frequency of tool use varies among sea otter populations and the factors that drive these differences. We examined 17 years of observational data on prey capture and tool use from 8 sea otter populations ranging from southern California to the Aleutian Islands in Alaska. There were significant differences in the diets of these populations as well as variation in the frequency of tool use. Sea otters at Amchitka Island, Alaska, used tools on less than 1% of dives that resulted in the capture of prey compared with approximately 16% in Monterey, California. The percentage of individuals in the population that used tools ranged from 10% to 93%. In all populations, marine snails and thick-shelled bivalves were most likely to be associated with tool use, whereas soft-bodied prey items such as worms and sea stars were the least likely. The probability that a tool would be used on a given prey type varied across populations. The morphology of the prey item being handled and the prevalence of various types of prey in local diets were major ecological drivers of tool use: together they accounted for about 64% of the variation in tool-use frequency among populations. The remaining variation may be related to changes in the relative costs and benefits to an individual otter of learning to use tools effectively under differing ecological circumstances.

  6. The variations of ionosphere critical frequency of E layer over Chumphon during solar cycle 24

    NASA Astrophysics Data System (ADS)

    Kenpankho, Prasert; Tsugawa, Takuya; Supnithi, Pornchai; Wongcharoen, Poramintra

    The values of the critical frequency of the ionospheric E layer, foE, obtained at Chumphon ionospheric observatory station (geographic 99.37 E, 10.72 N, 3 dip), Thailand, during the year 2007-2012, have been used to investigate the variations of foE over the geomagnetic equatorial region during the solar cycle 24. The investigation, including variations with local time, day, seasons and solar cycle, is in agreement with the observations. A comparison between the observation data and International Reference Ionosphere (IRI) 2012 model has also been made. The IRI 2012 model underestimates foE especially during the period of 7-11 am and after 6 pm for each day and all seasons. Combining with previous investigations, we suggest that underestimation of ionospheric foE by IRI 2012 model is very helpful for the correction of IRI model in an equatorial Asia region.

  7. Active noise control using noise source having adaptive resonant frequency tuning through stiffness variation

    NASA Technical Reports Server (NTRS)

    Pla, Frederic G. (Inventor); Rajiyah, Harindra (Inventor); Renshaw, Anthony A. (Inventor); Hedeen, Robert A. (Inventor)

    1995-01-01

    A noise source for an aircraft engine active noise cancellation system in which the resonant frequency of a noise radiating element is tuned to permit noise cancellation over a wide range of frequencies. The resonant frequency of the noise radiating element is tuned by a plurality of force transmitting mechanisms which contact the noise radiating element. Each one of the force transmitting mechanisms includes an expandable element and a spring in contact with the noise radiating element so that excitation of the element varies the spring force applied to the noise radiating element. The elements are actuated by a controller which receives input of a signal proportional to displacement of the noise radiating element and a signal corresponding to the blade passage frequency of the engine's fan. In response, the controller determines a control signal which is sent to the elements and causes the spring force applied to the noise radiating element to be varied. The force transmitting mechanisms can be arranged to either produce bending or linear stiffness variations in the noise radiating element.

  8. Frequency of the HLA-B*1502 allele contributing to carbamazepine-induced hypersensitivity reactions in a cohort of Malaysian epilepsy patients.

    PubMed

    Then, Sue-Mian; Rani, Zam Zureena Mohd; Raymond, Azman Ali; Ratnaningrum, Safrina; Jamal, Rahman

    2011-09-01

    We describe the association of the HLA-B*1502 allele in 27 epilepsy patients (19 Malays, 8 Chinese) treated with carbamazepine (CBZ) at the UKM Medical Center (UKMMC), 6 with CBZ-Steven Johnson Syndrome (CBZ-SJS), 11 with CBZ-induced rash, 2 with suspected phenytoin-induced rash and 8 negative controls. Our study showed that 10 (6 Malay, 4 Chinese) patients were positive for HLA-B*1502. Out of the 10 patients, six were confirmed to have CBZ-SJS (p = 0.0006), while four patients developed a skin rash. However there were 6 Malay patients and 1 Chinese patient that developed a skin rash after CBZ administration who were not positive for the allele, indicating that there might be more that one allele associated with CBZ-induced hypersensitivity. Another 2 patients were suspected of having phenytoin-induced rash, instead of CBZ, and these patients did not have HLA-B*1502. In conclusion, this study confirmed the association of HLA-B*1502 with CBZ-SJS among Malaysian epilepsy patients, however there might be other genes that could be responsible for the CBZ-induced rash.

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

    PubMed Central

    Blouin, Michael S.

    2008-01-01

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

  10. Allelic asymmetry of the Lethal hybrid rescue (Lhr) gene expression in the hybrid between Drosophila melanogaster and D. simulans: confirmation by using genetic variations of D. melanogaster.

    PubMed

    Shirata, Mika; Araye, Quenta; Maehara, Kazunori; Enya, Sora; Takano-Shimizu, Toshiyuki; Sawamura, Kyoichi

    2014-02-01

    In the cross between Drosophila melanogaster females and D. simulans males, hybrid males die at the late larval stage, and the sibling females also die at later stages at high temperatures. Removing the D. simulans allele of the Lethal hybrid rescue gene (Lhr (sim) ) improves the hybrid incompatibility phenotypes. However, the loss-of-function mutation of Lhr (sim) (Lhr (sim0) ) does not rescue the hybrid males in crosses with several D. melanogaster strains. We first describe the genetic factor possessed by the D. melanogaster strains. It has been suggested that removing the D. melanogaster allele of Lhr (Lhr (mel) ), that is Lhr (mel0) , does not have the hybrid male rescue effect, contrasting to Lhr (sim0) . Because the expression level of the Lhr gene is known to be Lhr (sim) > Lhr (mel) in the hybrid, Lhr (mel0) may not lead to enough of a reduction in total Lhr expression. Then, there is a possibility that the D. melanogaster factor changes the expression level to Lhr (sim) < Lhr (mel) . But in fact, the expression level was Lhr (sim) > Lhr (mel) in the hybrid irrespectively of the presence of the factor. At last, we showed that Lhr (mel0) slightly improves the viability of hybrid females, which was not realized previously. All of the present results are consistent with the allelic asymmetry model of the Lhr gene expression in the hybrid.

  11. Wolbachia in European Populations of the Invasive Pest Drosophila suzukii: Regional Variation in Infection Frequencies

    PubMed Central

    Gibert, Patricia; Martinez, Julien; Fraimout, Antoine; Jiggins, Francis; Andrieux, Thibault; Siozios, Stefanos; Anfora, Gianfranco; Miller, Wolfgang; Rota-Stabelli, Omar; Mouton, Laurence

    2016-01-01

    The invasive pest Drosophila suzukii is characterized by a specific fresh-fruit targeting behavior and has quickly become a menace for the fruit economy of newly infested North American and European regions. D. suzukii carries a strain of the endosymbiotic bacterium Wolbachia, named wSuz, which has a low infection frequency and no reproductive manipulation capabilities in American populations of D. suzukii. To further understand the nature of wSuz biology and assess its utility as a tool for controlling this pest’s populations, we investigated the prevalence of Wolbachia in 23 European D. suzukii populations, and compared our results with those available in American populations. Our data showed a highly variable infection frequency with a mean prevalence of 46%, which is significantly higher than the 17% found in American populations. Based on Multilocus Sequence Typing analysis, a single wSuz strain was diagnosed in all European populations of D. suzukii. In agreement with American data, we found no evidence of cytoplasmic incompatibility induced by wSuz. These findings raise two questions: a) why Wolbachia is maintained in field populations of D. suzukii and b) what are the selective forces responsible for the variation in prevalence within populations, particularly between European and American continents? Our results provide new insights into the D. suzukii-Wolbachia association and highlight regional variations that await further investigation and that should be taken into account for using Wolbachia-based pest management programs. PMID:26809119

  12. Wolbachia in European Populations of the Invasive Pest Drosophila suzukii: Regional Variation in Infection Frequencies.

    PubMed

    Cattel, Julien; Kaur, Rupinder; Gibert, Patricia; Martinez, Julien; Fraimout, Antoine; Jiggins, Francis; Andrieux, Thibault; Siozios, Stefanos; Anfora, Gianfranco; Miller, Wolfgang; Rota-Stabelli, Omar; Mouton, Laurence

    2016-01-01

    The invasive pest Drosophila suzukii is characterized by a specific fresh-fruit targeting behavior and has quickly become a menace for the fruit economy of newly infested North American and European regions. D. suzukii carries a strain of the endosymbiotic bacterium Wolbachia, named wSuz, which has a low infection frequency and no reproductive manipulation capabilities in American populations of D. suzukii. To further understand the nature of wSuz biology and assess its utility as a tool for controlling this pest's populations, we investigated the prevalence of Wolbachia in 23 European D. suzukii populations, and compared our results with those available in American populations. Our data showed a highly variable infection frequency with a mean prevalence of 46%, which is significantly higher than the 17% found in American populations. Based on Multilocus Sequence Typing analysis, a single wSuz strain was diagnosed in all European populations of D. suzukii. In agreement with American data, we found no evidence of cytoplasmic incompatibility induced by wSuz. These findings raise two questions: a) why Wolbachia is maintained in field populations of D. suzukii and b) what are the selective forces responsible for the variation in prevalence within populations, particularly between European and American continents? Our results provide new insights into the D. suzukii-Wolbachia association and highlight regional variations that await further investigation and that should be taken into account for using Wolbachia-based pest management programs.

  13. Increasing long term response by selecting for favorable minor alleles

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. Quantitative Sequencing for the Determination of Kdr-type Resistance Allele (V419L, L925I, I936F) Frequencies in Common Bed Bug (Hemiptera: Cimicidae) Populations Collected from Israel.

    PubMed

    Palenchar, Daniel J; Gellatly, Kyle J; Yoon, Kyong Sup; Mumcuoglu, Kosta Y; Shalom, Uri; Clark, J Marshall

    2015-09-01

    Human bed bug infestations have dramatically increased worldwide since the mid-1990s. A similar phenomenon was also observed in Israel since 2005, when infestations were reported from all over the country. Two single nucleotide polymorphisms (V419L and L925I) in the bed bug voltage-sensitive sodium channel confer kdr-type resistance to pyrethroids. Using quantitative sequencing (QS), the resistance allele frequencies of Israeli bed bug populations from across the country were determined. Genomic DNA was extracted from samples of 12 populations of bed bugs collected from Israel and DNA fragments containing the V419L or L925I and I936F mutations sites were PCR amplified. The PCR products were analyzed by QS and the nucleotide signal ratios calculated and used to predict the resistance allele frequencies of the unknown populations. Results of the genetic analysis show that resistant nucleotide signals are highly correlated to resistance allele frequencies for both mutations. Ten of the 12 tested populations had 100% of the L925I mutation and 0% of the V419L mutation. One population was heterogeneous for the L925I mutation and had 0% of the V419L mutation and another population was heterogeneous for the V419L mutation and had 100% of the L925I mutation. I936F occurred only at low levels. These results indicate that bed bugs in Israel are genetically resistant to pyrethroids. Thus, pyrethroids should only be used for bed bug management with caution using effective application and careful monitoring procedures. Additionally, new and novel-acting insecticides and nonchemical means of controlling bed bugs should be explored.

  15. Forensic animal DNA typing: Allele nomenclature and standardization of 14 feline STR markers.

    PubMed

    Schury, N; Schleenbecker, U; Hellmann, A P

    2014-09-01

    Since the domestic cat (Felis catus) has become one of the most popular pets and owners usually develop a close relationship to their cats, it is necessary to take traces of cats into account for forensic casework. For this purpose feline short tandem (STR) repeat markers have been investigated in several earlier studies, but no detailed description of sequence data, allelic variations or a repeat-based nomenclature is available. The aim of the study was to provide a suggestion for the allele nomenclature of 14 cat STR markers according to the recommendations of the International Society for Forensic Genetics (ISFG) for human DNA typing and to present a standardized system for a secure DNA typing of samples. Samples of 122 unrelated cats from a local animal shelter and private owners in Germany were used to generate a population database with allele frequencies and to analyze the tandemly repeated sequence variations within the alleles of each STR marker. These markers could be grouped into two STR classes: simple repeat STRs and complex STRs (some with the supplement highly complex), consisting of di- and tetranucleotide repeat motifs. After analyzing the repeat structure and elaborating a repeat based nomenclature, allelic ladders of common and rarely occurring alleles for each marker were designed to enable accurate typing of alleles that differ in fragment length and to facilitate data exchange.

  16. Regional frequency analysis to asses wind resource spatial and temporal variations in Washington State

    NASA Astrophysics Data System (ADS)

    Mortuza, M.; Demissie, D.

    2013-12-01

    According to the U.S. Department of Energy's annual wind technologies market report, the wind power capacity in the country grew from 2.5 gigawatts in early 2000 to 60 gigawatts in 2012, making it one of the largest new sources of electric capacity additions in the U.S. in recent years. With over 2.8 gigawatts of current capacity (eighth largest in the nation), Washington State plays a significant role in this rapidly increasing energy resource. To further expand and/or optimize these capacities, assessment of wind resource and its spatial and temporal variations are important. However, since at-site frequency analysis using meteorological data is not adequate for extending wind frequency to locations with no data, longer return period, and heterogeneous topography and surface, a regional frequency analysis based on L-moment method is adopted in this study to estimate regional wind speed patterns and return periods in Washington State using hourly mean wind speed data from 1979 - 2010. The analysis applies the k-means, hierarchical and self-organizing map clustering techniques to explore potential clusters or regions; statistical tests are then applied to identify homogeneous regions and appropriate probability distribution models. The result from the analysis is expected to provide essential knowledge about the areas with potential capacity of constructing wind power plants, which can also be readily extended to assist decisions on their daily operations.

  17. The influence of human leukocyte antigen class I alleles and their population frequencies on human immunodeficiency virus type 1 control among African Americans.

    PubMed

    Lazaryan, Aleksandr; Song, Wei; Lobashevsky, Elena; Tang, Jianming; Shrestha, Sadeep; Zhang, Kui; McNicholl, Janet M; Gardner, Lytt I; Wilson, Craig M; Klein, Robert S; Rompalo, Anne; Mayer, Kenneth; Sobel, Jack; Kaslow, Richard A

    2011-04-01

    Populations of African ancestry continue to account for a disproportionate burden of the human immunodeficiency virus type 1 (HIV-1) epidemic in the United States. We investigated the effects of human leukocyte antigen (HLA) class I markers in association with virologic and immunologic control of HIV-1 infection among 338 HIV-1 subtype B-infected African Americans in 2 cohorts: Reaching for Excellence in Adolescent Care and Health (REACH) and HIV Epidemiology Research Study (HERS). One-year treatment-free interval measurements of HIV-1 RNA viral loads and CD4(+) T cells were examined both separately and combined to represent 3 categories of HIV-1 disease control (76 controllers, 169 intermediates, and 93 noncontrollers). Certain previously or newly implicated HLA class I alleles (A*32, A*36, A*74, B*14, B*1510, B*3501, B*45, B*53, B*57, Cw*04, Cw*08, Cw*12, and Cw*18) were associated with 1 or more of the endpoints in univariate analyses. After multivariable adjustments for other genetic and nongenetic risk factors of HIV-1 progression, the subset of alleles more strongly or consistently associated with HIV-1 disease control included A*32, A*74, B*14, B*45, B*53, B*57, and Cw*08. Carriage of infrequent HLA-B but not HLA-A alleles was associated with more favorable disease outcomes. Certain HLA class I associations with control of HIV-1 infection cross the boundaries of race and viral subtype, whereas others appear confined within one or the other of those boundaries.

  18. Robustness of Frequency Division Technique for Online Myoelectric Pattern Recognition against Contraction-Level Variation

    PubMed Central

    Tolooshams, Bahareh; Jiang, Ning

    2017-01-01

    Contraction-level invariant surface electromyography pattern recognition introduces the decrease of training time and decreases the limitation of clinical prostheses. This study intended to examine whether a signal pre-processing method named frequency division technique (FDT) for online myoelectric pattern recognition classification is robust against contraction-level variation, and whether this pre-processing method has an advantage over traditional time-domain pattern recognition techniques even in the absence of muscle contraction-level variation. Eight healthy and naïve subjects performed wrist contractions during two degrees of freedom goal-oriented tasks, divided in three groups of type I, type II, and type III. The performance of these tasks, when the two different methods were used, was quantified by completion rate, completion time, throughput, efficiency, and overshoot. The traditional and the FDT method were compared in four runs, using combinations of normal or high muscle contraction level, and the traditional method or FDT. The results indicated that FDT had an advantage over traditional methods in the tested real-time myoelectric control tasks. FDT had a much better median completion rate of tasks (95%) compared to the traditional method (77.5%) among non-perfect runs, and the variability in FDT was strikingly smaller than the traditional method (p < 0.001). Moreover, the FDT method outperformed the traditional method in case of contraction-level variation between the training and online control phases (p = 0. 005 for throughput in type I tasks with normal contraction level, p = 0.006 for throughput in type II tasks, and p = 0.001 for efficiency with normal contraction level of all task types). This study shows that FDT provides advantages in online myoelectric control as it introduces robustness over contraction-level variations. PMID:28220147

  19. Starch phosphorylation in potato tubers is influenced by allelic variation in the genes encoding glucan water dikinase, starch branching enzymes I and II, and starch synthase III.

    PubMed

    Carpenter, Margaret A; Joyce, Nigel I; Genet, Russell A; Cooper, Rebecca D; Murray, Sarah R; Noble, Alasdair D; Butler, Ruth C; Timmerman-Vaughan, Gail M

    2015-01-01

    Starch phosphorylation is an important aspect of plant metabolism due to its role in starch degradation. Moreover, the degree of phosphorylation of starch determines its physicochemical properties and is therefore relevant for industrial uses of starch. Currently, starch is chemically phosphorylated to increase viscosity and paste stability. Potato cultivars with elevated starch phosphorylation would make this process unnecessary, thereby bestowing economic and environmental benefits. Starch phosphorylation is a complex trait which has been previously shown by antisense gene repression to be influenced by a number of genes including those involved in starch synthesis and degradation. We have used an association mapping approach to discover genetic markers associated with the degree of starch phosphorylation. A diverse collection of 193 potato lines was grown in replicated field trials, and the levels of starch phosphorylation at the C6 and C3 positions of the glucosyl residues were determined by mass spectrometry of hydrolyzed starch from tubers. In addition, the potato lines were genotyped by amplicon sequencing and microsatellite analysis, focusing on candidate genes known to be involved in starch synthesis. As potato is an autotetraploid, genotyping included determination of allele dosage. Significant associations (p < 0.001) were found with SNPs in the glucan water dikinase (GWD), starch branching enzyme I (SBEI) and the starch synthase III (SSIII) genes, and with a SSR allele in the SBEII gene. SNPs in the GWD gene were associated with C6 phosphorylation, whereas polymorphisms in the SBEI and SBEII genes were associated with both C6 and C3 phosphorylation and the SNP in the SSIII gene was associated with C3 phosphorylation. These allelic variants have potential as genetic markers for starch phosphorylation in potato.

  20. Temporal and spatial variations in road traffic noise for different frequency components in metropolitan Taichung, Taiwan.

    PubMed

    Wang, Ven-Shing; Lo, Ei-Wen; Liang, Chih-Hsiang; Chao, Keh-Ping; Bao, Bo-Ying; Chang, Ta-Yuan

    2016-12-01

    Road traffic noise exposure has been associated with auditory and non-auditory health effects, but few studies report noise characteristics. This study determines 24-h noise levels and analyzes their frequency components to investigate associations between seasons, meteorology, land-use types, and traffic. We set up 50 monitoring stations covering ten different land-use types and conducted measurements at three times of the year to obtain 24-h-average A-weighted equivalent noise levels (LAeq,24h) and frequency analyses from 2013 to 2014 in Taichung, Taiwan. Information on land-use types, road parameters, traffic flow rates, and meteorological variables was also collected for analysis with the annual averages of road traffic noise and its frequency components. The annual average LAeq,24h in Taichung was 66.4 ± 4.7 A-weighed decibels (dBA). Significant differences in LAeq,24h and frequency components were observed between land-use types (all p-values < 0.001), but not between seasons, with the highest two noise levels of 71.2 ± 1.0 dBA and 70.0 ± 2.6 dBA measured in stream-channel and commercial areas, with the highest component being 61.4 ± 5.3 dBA at 1000 Hz. Road width, traffic flow rates, and land-use types were significantly associated with annual average LAeq,24h (all p-values < 0.050). Noise levels at 125 Hz had the highest correlation with total traffic (Spearman's coefficient = 0.795) and the highest prediction in the multiple linear regression (R(2) = 0.803; adjusted R(2) = 0.765). These findings reveal the spatial variation in road traffic noise exposure in Taichung. The highest correlation and predictive capacity was observed between this variation and noise levels at 125 Hz. We recommend that governmental agencies should take actions to reduce noise levels from traffic vehicles.

  1. Allelic diversity of metallothionein in Orchesella cincta (L.): traces of natural selection by environmental pollution.

    PubMed

    Timmermans, M J T N; Ellers, J; Van Straalen, N M

    2007-05-01

    The advances made in statistical methods to detect selection from DNA sequence variation has resulted in an enormous increase in the number of studies reporting positive selection. However, a disadvantage of such statistical tests is that often no insight into the actual source of selection is obtained. Finer understanding of evolution can be obtained when those statistical tests are combined with field observations on allele frequencies. We assessed whether the metallothionein (mt) gene of Orchesella cincta (Collembola), which codes for a metal-binding protein, is subject to selection, by investigating alleles and allele frequencies among European metal-stressed and reference populations. Eight highly divergent alleles were resolved in Northwest Europe. At the nucleotide level, a total of 51 polymorphic sites (five of them implying amino-acid changes) were observed. Although statistical tests applied to the sequences alone showed no indication of selection, a G-test rejected the null hypothesis that alleles are homogeneously distributed over metal-stressed and reference populations. Analysis of molecular variance assigned a small, but significant amount of the total variance to differences between metal-stressed and non-stressed populations. In addition, it was shown that metal-stressed populations tend to be more genetically diversified at this locus than non-stressed ones. These results suggest that the mt gene and its surrounding DNA region are affected by environmental metal contamination. This study illustrates that, in addition to statistical tests, field observations on allele frequencies are needed to gain understanding of selection and adaptive evolution.

  2. Regional Variations in Low Frequency Transport Variability of the Southern Ocean

    NASA Astrophysics Data System (ADS)

    Makowski, Jessica; Chambers, Don

    2016-04-01

    Using ocean bottom pressure data from the Gravity Recovery and Climate Experiment (GRACE) and the ECCO2 state estimate, we estimate the variability of the low frequency zonal transport in the Southern Ocean. The interannual variations and trend estimates from calculated transport variability differ as the east-west averaging area and north-south boundaries change. We look at various study areas throughout the Southern Ocean, including west of the Drake Passage, in order to determine the regional variability and coherency within the Southern Ocean. We have observed a high coherency between the Southern Annular Mode (SAM) and interannual variability in the transport south of Australia, and further investigate how other regions respond to the SAM and zonally averaged Southern Hemisphere winds.

  3. High-frequency Earth rotation variations deduced from altimetry-based ocean tides

    NASA Astrophysics Data System (ADS)

    Madzak, Matthias; Schindelegger, Michael; Böhm, Johannes; Bosch, Wolfgang; Hagedoorn, Jan

    2016-11-01

    A model of diurnal and semi-diurnal variations in Earth rotation parameters (ERP) is constructed based on altimetry-measured tidal heights from a multi-mission empirical ocean tide solution. Barotropic currents contributing to relative angular momentum changes are estimated for nine major tides in a global inversion algorithm that solves the two-dimensional momentum equations on a regular 0.5° grid with a heavily weighted continuity constraint. The influence of 19 minor tides is accounted for by linear admittance interpolation of ocean tidal angular momentum, although the assumption of smooth admittance variations with frequency appears to be a doubtful concept for semi-diurnal mass terms in particular. A validation of the newly derived model based on post-fit corrections to polar motion and universal time (Δ UT1) from the analysis of Very Long Baseline Interferometry (VLBI) observations shows a variance reduction for semi-diurnal Δ UT1 residuals that is significant at the 0.05 level with respect to the conventional ERP model. Improvements are also evident for the explicitly modeled K_1, Q_1, and K_2 tides in individual ERP components, but large residuals of more than 15 μ as remain at the principal lunar frequencies of O_1 and M_2. We attribute these shortcomings to uncertainties in the inverted relative angular momentum changes and, to a minor extent, to violation of mass conservation in the empirical ocean tide solution. Further dedicated hydrodynamic modeling efforts of these anomalous constituents are required to meet the accuracy standards of modern space geodesy.

  4. Frequency variation and sensor contribution assessment: Application to an offshore platform in the South China Sea

    NASA Astrophysics Data System (ADS)

    Liu, Fushun; Li, Huajun; Wang, Weiying; Li, Wei; Wang, Bin

    2015-02-01

    In this paper, a time-frequency and multiple-sensor assessment method is presented and then applied to an offshore platform in the South China Sea with the goal of providing a more suitable time duration of measured signals and evaluating each sensor's contribution to mode shapes of interest. By processing all measured signals simultaneously, a series of linear parameters are used to fit the measured signals. A moving window in overlapping steps along the time record of a non-stationary signal is used for time-frequency analysis while a series of amplitude matrices are obtained for all sliced segments. These segments are then used to evaluate each sensor's contribution to some mode(s) of interest. Compared with the short-time Fourier transform (STFT) or S-transform method, the frequencies used in this time-frequency analysis are shared by the sensors involved so that the variations in the results due to the characteristics of different sensors are avoided. In addition, the approach requires only a short-duration segment to obtain high-frequency resolution, which will improve the computing efficiency of modal analysis using measured seat est data. The proposed method could also be used to estimate damping ratios and each sensor's contribution to modes of interest based on the analysis of the series of amplitude matrices; this could be used to guide the installation of sensors in field tests of offshore structures. To demonstrate the proposed method with a time-frequency analysis, a numerical example of a synthesized signal with five segments, each with its owns different frequency componentsincluding a relatively weaker component, is constructed; numerical results from the analysis of this example signal indicate that the approach could yield a sharper image with a good computing efficiency. The second example simulates three signals that represent multiple measurements; this example is used to study each sensor

  5. Data on IL-6 c.-174 G>C genotype and allele frequencies in patients with coronary heart disease in dependence of cardiovascular outcome.

    PubMed

    Reichert, Stefan; Schlitt, Axel; Benten, Ann-Christin; Hofmann, Britt; Schaller, Hans-Günter; Schulz, Susanne

    2016-09-01

    In this data article we present data on the distribution of alleles and genotypes of the interleukin (IL)-6 c.-174 G>C polymorphism (rs 1800795) in patients with coronary heart disease (CHD) in dependence of the incidence of new cardiovascular events (combined endpoint: myocardial infarction, stroke/TIA, cardiac death, death according to stroke) within three years follow-up. Moreover, we investigated putative associations between individual expression of IL-6 genotypes and IL-6 serum level. This investigation is a subanalysis of the article entitled "The Interleukin 6 c.-174 CC genotype is a predictor for new cardiovascular events in patients with coronary heart disease within three years follow-up" (ClinicalTrials.gov identifier: NCT01045070) (Reichert et al., 2016) [1].

  6. Demeter/ICE Experiment: Study of low frequency transmitter intensity variations

    NASA Astrophysics Data System (ADS)

    Boudjada, M. Y.; Moldovan, I.; Schwingenschuh, K.; Al-Haddad, E.; Biagi, P. F.; Parrot, M.

    2012-04-01

    We report on low frequency (LF) transmitter signal recorded by the 'Instrument Capteur Electrique' (ICE) experiment onboard the DEMETER micro-satellite. We mainly consider the signal emitted by the Brasov broadcasting station (25.60E, 45.75N) at frequency of about 153 kHz. We analyze the reception conditions of this transmitter several weeks before the occurrence of the Vrancea earthquakes, on October, 27th, 2004. Ground-based observations revealed the presence of sudden decrease of the Y-component of the magnetic field at Muntele Rosu Observatory (Romania), at about 68 km from the epicenter, as reported by Moldovan et al. (Rom. Journ. Phys., Vol. 54, Nos. 1-2, p. 249-261, Bucharest, 2009). In this contribution we attempt to check if the LF Brasov signal was also subject to similar disturbances as observed by the ground-station. We focus on the variation of the LF transmitter intensity levels, several weeks before and after the Vrancea earthquake occurrence. We discuss the physical parameters which may disturb the signal reception in particular the geomagnetic activity and the signal to noise ratios.

  7. Periodic Variations in the O - C Diagrams of Five Pulsation Frequencies of the DB White Dwarf EC 20058-5234

    NASA Astrophysics Data System (ADS)

    Dalessio, J.; Sullivan, D. J.; Provencal, J. L.; Shipman, H. L.; Sullivan, T.; Kilkenny, D.; Fraga, L.; Sefako, R.

    2013-03-01

    Variations in the pulsation arrival time of five independent pulsation frequencies of the DB white dwarf EC 20058-5234 individually imitate the effects of reflex motion induced by a planet or companion but are inconsistent when considered in unison. The pulsation frequencies vary periodically in a 12.9 year cycle and undergo secular changes that are inconsistent with simple neutrino plus photon-cooling models. The magnitude of the periodic and secular variations increases with the period of the pulsations, possibly hinting that the corresponding physical mechanism is located near the surface of the star. The phase of the periodic variations appears coupled to the sign of the secular variations. The standards for pulsation-timing-based detection of planetary companions around pulsating white dwarfs, and possibly other variables such as subdwarf B stars, should be re-evaluated. The physical mechanism responsible for this surprising result may involve a redistribution of angular momentum or a magnetic cycle. Additionally, variations in a supposed combination frequency are shown to match the sum of the variations of the parent frequencies to remarkable precision, an expected but unprecedented confirmation of theoretical predictions. Based on observations obtained at the Southern Astrophysical Research (SOAR) telescope, which is a joint project of the Ministério da Ciência, Tecnologia, e Inovação (MCTI) da República Federativa do Brasil, the US National Optical Astronomy Observatory (NOAO), the University of North Carolina at Chapel Hill (UNC), and Michigan State University (MSU).

  8. PERIODIC VARIATIONS IN THE O - C DIAGRAMS OF FIVE PULSATION FREQUENCIES OF THE DB WHITE DWARF EC 20058-5234

    SciTech Connect

    Dalessio, J.; Provencal, J. L.; Shipman, H. L.; Sullivan, D. J.; Sullivan, T.; Kilkenny, D.; Fraga, L.; Sefako, R.

    2013-03-01

    Variations in the pulsation arrival time of five independent pulsation frequencies of the DB white dwarf EC 20058-5234 individually imitate the effects of reflex motion induced by a planet or companion but are inconsistent when considered in unison. The pulsation frequencies vary periodically in a 12.9 year cycle and undergo secular changes that are inconsistent with simple neutrino plus photon-cooling models. The magnitude of the periodic and secular variations increases with the period of the pulsations, possibly hinting that the corresponding physical mechanism is located near the surface of the star. The phase of the periodic variations appears coupled to the sign of the secular variations. The standards for pulsation-timing-based detection of planetary companions around pulsating white dwarfs, and possibly other variables such as subdwarf B stars, should be re-evaluated. The physical mechanism responsible for this surprising result may involve a redistribution of angular momentum or a magnetic cycle. Additionally, variations in a supposed combination frequency are shown to match the sum of the variations of the parent frequencies to remarkable precision, an expected but unprecedented confirmation of theoretical predictions.

  9. The tRNA-Tyr gene family of Saccharomyces cerevisiae: agents of phenotypic variation and position effects on mutation frequency.

    PubMed Central

    Ito-Harashima, Sayoko; Hartzog, Phillip E; Sinha, Himanshu; McCusker, John H

    2002-01-01

    Extensive phenotypic diversity or variation exists in clonal populations of microorganisms and is thought to play a role in adaptation to novel environments. This phenotypic variation or instability, which occurs by multiple mechanisms, may be a form of cellular differentiation and a stochastic means for modulating gene expression. This work dissects a case of phenotypic variation in a clinically derived Saccharomyces cerevisiae strain involving a cox15 ochre mutation, which acts as a reporter. The ochre mutation reverts to sense at a low frequency while tRNA-Tyr ochre suppressors (SUP-o) arise at a very high frequency to produce this phenotypic variation. The SUP-o mutations are highly pleiotropic. In addition, although all SUP-o mutations within the eight-member tRNA-Tyr gene family suppress the ochre mutation reporter, there are considerable phenotypic differences among the different SUP-o mutants. Finally, and of particular interest, there is a strong position effect on mutation frequency within the eight-member tRNA-Tyr gene family, with one locus, SUP6, mutating at a much higher than average frequency and two other loci, SUP2 and SUP8, mutating at much lower than average frequencies. Mechanisms for the position effect on mutation frequency are evaluated. PMID:12196388

  10. Variation in the gene frequencies of three generations of humans from Monterrey, Nuevo León, Mexico.

    PubMed

    Cerda-Flores, R M; Garza-Chapa, R

    1989-04-01

    Allele frequencies for the ABO, Rh, MNSs, Duffy, Kidd, Lutheran, P and Lewis blood group systems in 207 persons whose 4 grandparents were born in the Monterrey Metropolitan area (MMA), grouped into 3 generations, were ascertained along with other related population from the MMA, Mestizos from Saltillo, Coahuila and Tlaxcala, and from the populations thought to have contributed to their genetic constitution (native Mexican Indians and Spanish). Genetic admixture and distance estimates were calculated. Gene frequencies of the three generations from MMA are intermediate to those of the ancestral populations, indicating that they are Mestizo but with a genetic structure different from Mestizos of Saltillo and Tlaxcala. Both genetic admixture and distance estimates indicate that the oldest generation exhibits the greatest Spanish influence which decreases in the youngest generation and in the other MMA populations as a result of the immigration from the central states of Mexico.

  11. High frequency of SLC22A12 variants causing renal hypouricemia 1 in the Czech and Slovak Roma population; simple and rapid detection method by allele-specific polymerase chain reaction.

    PubMed

    Gabrikova, Dana; Bernasovska, Jarmila; Sokolova, Jitka; Stiburkova, Blanka

    2015-10-01

    Renal hypouricemia is a rare heterogeneous inherited disorder characterized by impaired tubular uric acid transport with severe complications, such as acute kidney injury. Type 1 and 2 are caused by loss-of-function mutations in the SLC22A12 and SLC2A9 gene, respectively. A cohort of 881 randomly chosen ethnic Roma from two regions in Eastern Slovakia and two regions in the Czech Republic participated. Genomic DNA was isolated from buccal swabs and/or from blood samples. The c.1245_1253del and c.1400C>T genotypes were determined using polymerase chain reaction with allele-specific primers in a multiplex arrangement and/or direct sequencing of exon 7 and 9. Allele frequencies and genotypes were tested for Hardy-Weinberg equilibrium using the Chi-square test. 25 subjects were heterozygous and three were homozygous for the c.1245_1253del, while 92 subjects were heterozygous and two were homozygous for the c.1400C>T. Moreover, two participants were compound heterozygotes. Frequencies of the c.1245_1253del and c.1400C>T variants were 1.87 and 5.56 %, respectively. Our finding confirms an uneven geographical and ethnic distribution of SLC22A12 mutant variants. We found that the c.1245_1253del and c.1400C>T variants were present in the Czech and Slovak Roma population at unexpectedly high frequencies. Renal hypouricemia should be kept in mind during differential diagnostic on Roma patients with low serum uric acid concentrations.

  12. Distribution of the mutated delta 32 allele of the CCR5 gene in a Sicilian population.

    PubMed

    Sidoti, A; D'Angelo, R; Rinaldi, C; De Luca, G; Pino, F; Salpietro, C; Giunta, D E; Saltalamacchia, F; Amato, A

    2005-06-01

    The CCR5 gene encodes a cell-surface chemokine receptor molecule that serves as a co-receptor for macrophage-tropic strains of human immunodeficiency virus type 1 (HIV-1). A mutation in this gene may alter the expression or the function of the protein product, thereby altering chemokine binding and/or signalling or HIV-1 infection of cells that normally express CCR5 protein. Individuals homozygous for a 32-bp deletion allele of CCR5 (CCR5 delta32), heritable as a Mendelian trait, are relatively resistant to HIV-1 infection. The CCR5 delta32 mutation is present in the Caucasian population at different frequencies. The aim of this study was to investigate the frequency of truncated alleles of the CCR5 delta32 gene in a Sicilian population, as the interpopulation variation in CCR5 delta32 frequency may be a significant factor in the prediction of AIDS endemicity in future studies. We examined 901 healthy individuals from several Sicilian provinces. We found a mean (+/- standard deviation) delta32 allele frequency (fr) of 0.04 +/- 0.012. The highest value was observed in the province of Messina, with a mean delta32 allele frequency of 0.06 +/- 0.024, where we collected samples from a cohort of 114 HIV-1-infected individuals. The observed frequency amongst these patients was quite low (fr = 0.03 +/- 0.031) compared to the healthy population, although the difference was not statistically significant.

  13. Allelic Variation in CXCL16 Determines CD3+ T Lymphocyte Susceptibility to Equine Arteritis Virus Infection and Establishment of Long-Term Carrier State in the Stallion

    PubMed Central

    Cook, R. Frank; Eberth, John; Chelvarajan, R. Lakshman; Artiushin, Sergey; Timoney, Peter J.

    2016-01-01

    Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10–70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s) of CD3+ T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3+ T lymphocyte susceptible phenotype are at less risk of becoming long-term virus carriers. A genome wide association study (GWAS) using the Illumina Equine SNP50 chip revealed that the ability of EAV to infect CD3+ T lymphocytes and establish long-term carrier status in stallions correlated with a region within equine chromosome 11. Here we identified the gene and mutations responsible for these phenotypes. Specifically, the work implicated three allelic variants of the equine orthologue of CXCL16 (EqCXCL16) that differ by four non-synonymous nucleotide substitutions (XM_00154756; c.715 A → T, c.801 G → C, c.804 T → A/G, c.810 G → A) within exon 1. This resulted in four amino acid changes with EqCXCL16S (XP_001504806.1) having Phe, His, Ile and Lys as compared to EqCXL16R having Tyr, Asp, Phe, and Glu at 40, 49, 50, and 52, respectively. Two alleles (EqCXCL16Sa, EqCXCL16Sb) encoded identical protein products that correlated strongly with long-term EAV persistence in stallions (P<0.000001) and are required for in vitro CD3+ T lymphocyte susceptibility to EAV infection. The third (EqCXCL16R) was associated with in vitro CD3+ T lymphocyte resistance to EAV infection and a significantly lower probability for establishment of the long-term carrier state (viral persistence) in the male reproductive tract. EqCXCL16Sa and Eq

  14. Perceptual Qualities of Ethanol Depend on Concentration, and Variation in These Percepts Associates with Drinking Frequency

    PubMed Central

    Nolden, Alissa A.

    2016-01-01

    Introduction Ethanol, the pharmaceutically active ingredient in all alcoholic beverages, elicits multiple percepts including sweet, bitter, drying, and burning. However, quality-specific perceptual dose-response functions have not been previously reported. Also, individual differences in ethanol perception may associate with differences in alcoholic beverage use. Here, we describe the chemosensory profile of ethanol across concentrations in a convenience sample of mixed-age adults; secondarily, we explore whether individual differences in various qualities from ethanol associate with alcohol use behaviors. Methods Participants (n=100, 33 men) aged 21 to 55 (mean 33 years) tasted ethanol in water (4, 8, 16, 32, and 48 % v/v) and rated sweetness, bitterness, drying, and burning/tingling on four general Labeled Magnitude Scales. Demographic question and alcohol use measures (years drinking and reported frequency of drinking occasions) were also collected. Results Intensity of most qualities increased as a function of ethanol concentration, although the dominant sensation differed with concentration. The dominant sensation for 8 and 16 % ethanol was bitterness (7.4±1.0; 13.5±1.4), whereas for 32 and 48 % ethanol, burning/tingling was the dominant sensation (29.7±2.1; 44.7±2.4). Variation in quality-specific intensities of sampled ethanol explained variability in the reported intake frequency for beer, wine, straight spirits, and number of drinking occasions. The number of years reported drinking (grand mean 10.5±0.8) was not significantly associated with perceptual ratings for sampled ethanol. Conclusions In a convenience sample of mixed-aged adults, the sensations from suprathreshold ethanol varied by concentration: bitterness dominated at lower concentrations, while burn dominated at higher concentrations. Exploratory analyses also suggest that differences in chemosensory responses across participants may associate with measures of alcohol use. PMID:27594968

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

    PubMed

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

    2014-01-01

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

  16. Frequency of and variation in low-value care in primary care: a retrospective cohort study

    PubMed Central

    Pendrith, Ciara; Bhatia, Meghan; Ivers, Noah M.; Mecredy, Graham; Tu, Karen; Hawker, Gillian A.; Jaglal, Susan B.; Wilson, Lynn; Wintemute, Kimberly; Glazier, Richard H.; Levinson, Wendy; Bhatia, R. Sacha

    2017-01-01

    Background: Low-value care, defined as care with a lack of benefit, can lead to higher health care costs, inconvenience to patients and, in some cases, harm to patients. The objectives of this study are to conduct exploratory analyses to understand how frequently selected low-value tests are ordered, to assess the degree of variation in ordering that exists across regions and practices, and to identify services that may warrant further investigation and targeted interventions. Methods: We conducted a population-based retrospective cohort study using administrative health care databases from Ontario to identify rates of use of the following low-value services between fiscal years 2008/09 and 2012/13: computed tomography (CT) or magnetic resonance imaging (MRI) after a diagnosis of low back pain, Papanicolaou testing in women less than 21 years of age or older than 69 years of age and repeated dual-energy X-ray absorptiometry (DEXA) scanning within 2 years of an index scan. Regional and practice-level rates were calculated. Bivariate analyses were conducted to explore associations between patient factors and repeat DEXA scans. Results: Repeated DEXA scans were the most common service (21.0%), whereas cervical cancer screening among women less than 21 years of age or older than 69 years of age (8.0%) and CT or MRI imaging for low back pain (4.5%) were less common. There was substantial variation across practices with rates of repeated DEXA scans, ranging from 4.0% to 54.9%, and cervical cancer screening, ranging from 0.9% to 35.2%. Patients with a high-risk index DEXA were more likely to receive a repeat scan (28.1%) than those with a baseline (8.9%) or low-risk (8.1%) scan. Interpretation: There is significant, practice-level variation in the frequency of low-value testing for DEXA scans, back imaging and cervical cancer screening. There is a particular need for interventions that aim to reduce unnecessary DEXA scans.

  17. A novel allelic variant of the human TSG-6 gene encoding an amino acid difference in the CUB module. Chromosomal localization, frequency analysis, modeling, and expression.

    PubMed

    Nentwich, Hilke A; Mustafa, Zehra; Rugg, Marilyn S; Marsden, Brian D; Cordell, Martin R; Mahoney, David J; Jenkins, Suzanne C; Dowling, Barbara; Fries, Erik; Milner, Caroline M; Loughlin, John; Day, Anthony J

    2002-05-03

    Tumor necrosis factor-stimulated gene-6 (TSG-6) encodes a 35-kDa protein, which is comprised of contiguous Link and CUB modules. TSG-6 protein has been detected in the articular joints of osteoarthritis (OA) patients, with little or no constitutive expression in normal adult tissues. It interacts with components of cartilage matrix (e.g. hyaluronan and aggrecan) and thus may be involved in extracellular remodeling during joint disease. In addition, TSG-6 has been found to have anti-inflammatory properties in models of acute and chronic inflammation. Here we have mapped the human TSG-6 gene to 2q23.3, a region of chromosome 2 linked with OA. A single nucleotide polymorphism was identified that involves a non-synonymous G --> A transition at nucleotide 431 of the TSG-6 coding sequence, resulting in an Arg to Gln alteration in the CUB module (at residue 144 in the preprotein). Molecular modeling of the CUB domain indicated that this amino acid change might lead to functional differences. Typing of 400 OA cases and 400 controls revealed that the A(431) variant identified here is the major TSG-6 allele in Caucasians (with over 75% being A(431) homozygotes) but that this polymorphism is not a marker for OA susceptibility in the patients we have studied. Expression of the Arg(144) and Gln(144) allotypes in Drosophila Schneider 2 cells, and functional characterization, showed that there were no significant differences in the ability of these full-length proteins to bind hyaluronan or form a stable complex with inter-alpha-inhibitor.

  18. Quantitative resistance affects the speed of frequency increase but not the diversity of the virulence alleles overcoming a major resistance gene to Leptosphaeria maculans in oilseed rape.

    PubMed

    Delourme, R; Bousset, L; Ermel, M; Duffé, P; Besnard, A L; Marquer, B; Fudal, I; Linglin, J; Chadœuf, J; Brun, H

    2014-10-01

    Quantitative resistance mediated by multiple genetic factors has been shown to increase the potential for durability of major resistance genes. This was demonstrated in the Leptosphaeria maculans/Brassica napus pathosystem in a 5year recurrent selection field experiment on lines harboring the qualitative resistance gene Rlm6 combined or not with quantitative resistance. The quantitative resistance limited the size of the virulent isolate population. In this study we continued this recurrent selection experiment in the same way to examine whether the pathogen population could adapt and render the major gene ineffective in the longer term. The cultivars Eurol, with a susceptible background, and Darmor, with quantitative resistance, were used. We confirmed that the combination of qualitative and quantitative resistance is an effective approach for controlling the pathogen epidemics over time. This combination did not prevent isolates virulent against the major gene from amplifying in the long term but the quantitative resistance significantly delayed for 5years the loss of effectiveness of the qualitative resistance and disease severity was maintained at a low level on the genotype with both types of resistance after the fungus population had adapted to the major gene. We also showed that diversity of AvrLm6 virulence alleles was comparable in isolates recovered after the recurrent selection on lines carrying either the major gene alone or in combination with quantitative resistance: a single repeat-induced point mutation and deletion events were observed in both situations. Breeding varieties which combine qualitative and quantitative resistance can effectively contribute to disease control by increasing the potential for durability of major resistance genes.

  19. Seasonal Variation and Frequency Distribution of Ectoparasites in Crossbreed Cattle in Southeastern Brazil

    PubMed Central

    Ferraz da Costa, Maria do Socorro; Guimarães, Marcos Pezzi; Lima, Walter dos Santos; Ferraz da Costa, Ana Julia; Facury Filho, Elias Jorge; Araujo, Ricardo Nascimento

    2014-01-01

    The aims of this study were to evaluate the seasonal variation and frequency distribution of Rhipicephalus (Boophilus) microplus, Haematobia irritans, and Dermatobia hominis on crossbred heifers under field conditions in the northeast of Minas Gerais state, southeastern Brazil. From November 2007 to September 2009 (23 months), 40 heifers aged 16.6 ± 2.4 months were divided into groups A (1/4 Holstein × 3/4 Gir) and B (1/2 Holstein × 1/2 Gir) and had the monthly infestation estimated along with the climatic conditions. The mean maximum and minimum temperatures were 28.5 and 19°C, respectively. The ectoparasites were present on animals in all months of the year. The levels of ticks on the animals were low (3.0 ± 0.2 ticks/animal), with the highest density in midwinter. The temperature was the climatic factor that most influenced the tick levels. The population of H. irritans (13.9 ± 0.3 flies/animal) and D. hominis (1.5 ± 0.2 larvae/animal) on heifers was more influenced by rainfall and exhibited two population peaks during the year. 1/2 Holstein heifers harbored significantly more H. irritans and D. hominis than 1/4 Holstein heifers. The results are discussed considering the most appropriate periods to apply ectoparasiticides and the genetic make-up of the animals. PMID:26464941

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

    SciTech Connect

    Slatkin, M.; Rannala, B.

    1997-02-01

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

  1. MspI allelic pattern of bovine growth hormone gene in Indian zebu cattle (Bos indicus) breeds.

    PubMed

    Sodhi, M; Mukesh, M; Prakash, B; Mishra, B P; Sobti, R C; Singh, Karn P; Singh, Satbir; Ahlawat, S P S

    2007-02-01

    The MspI allelic variation in intron III of the bovine growth hormone (bGH) gene was explored using PCR-RFLP in 750 animals belonging to 17 well-recognized breeds of Indian zebu cattle (Bos indicus) reared in different geographic locations of the country. Restriction digestion analysis of a 329-bp PCR fragment of the bGH intron III region with MspI restriction enzyme revealed two alleles (MspI- and MspI+) and two genotypes (-/- and +/-) across the 17 cattle breeds studied. The allelic frequency varied from 0.67 to 0.94 for MspI (-) and from 0.06 to 0.33 for MspI (+) across the 17 breeds, with a combined average frequency of 0.87 and 0.13, respectively. No animal with +/+ genotype was detected across the samples analyzed. The chi-square test showed that the difference in MspI allelic frequency was not significant (p > 0.05), regardless of the geographic origin, coat color, or utility of the cattle breed. The high MspI (-) allele frequencies obtained for Indian zebu cattle in this study are in sharp contrast to those reported for taurine breeds from northern Europe, Mediterranean countries, and America. Findings of this study further substantiate the hypothesis that the MspI (-) allele has an Indian origin.

  2. HS1,2 Ig enhancer alleles association to AIDS progression in a pediatric cohort infected with a monophyletic HIV-strain.

    PubMed

    Montesano, Carla; Giambra, Vincenzo; Frezza, Domenico; Palma, Paolo; Serone, Eliseo; Gattinara, Guido Castelli; Mattei, Maurizio; Mancino, Giorgio; Colizzi, Vittorio; Amicosante, Massimo

    2014-01-01

    Alteration in the humoral immune response has been observed during HIV infection. The polymorphisms of enhancer HS1,2, member of the 3(') regulatory region of the Ig heavy chain cluster, may play a role in the variation of the humoral response leading to pathological conditions. To assess the role of the HS1,2 polymorphic variants in the progression of AIDS, the HS1,2-A allelic frequencies were investigated in a cohort of HIV infected pediatric subjects from a nosocomial outbreak with a monophyletic strain of HIV. From a total group of 418 HIV infected children in the outbreak cohort, 42 nonprogressors and 31 progressors without bias due to antiretroviral therapy were evaluated. HS1,2 allele (∗)1 has been associated with nonprogressors (allelic frequency: 51.19% versus 33.87% in progressors, OR 0.5, and P = 0.0437), while allele (∗)2 has been associated with progression (allelic frequency: 48.39% versus 30.95% in nonprogressors, OR 2.1, and P = 0.0393). Further, only subjects carrying allele (∗)2 in absence of allele (∗)1, either in homozygous condition for allele (∗)2 [nonprogressors 2/42 (4.76%), Progressors 7/31 (22.58%), OR 5.8, and P = 0.0315] or in combination with other allelic variants [nonprogressors 7/42 (16.67%), Progressors 13/31 (41.93%), OR 3.61, and P = 0.0321], have been associated with HIV progression to AIDS. In conclusion, while the HS1,2 allele (∗)1 has a protective effect on HIV progression when present, allele (∗)2 is associated with progression toward AIDS when allele (∗)1 is absent.

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

    PubMed Central

    Stanciu, Florin; Vladu, Simona; Cuţăr, Veronica; Cocioabă, Daniela; Iancu, Florentina; Cotolea, Adnana; Stoian, Ionel Marius

    2013-01-01

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

  4. High-frequency variations in Earth rotation from Global Positioning System data

    NASA Astrophysics Data System (ADS)

    Rothacher, M.; Beutler, G.; Weber, R.; Hefty, J.

    2001-01-01

    Using the data of the global, dense Global Positioning System (GPS) network established by the International GPS Service a continuous, uninterrupted series of subdaily Earth rotation parameters (ERPs) with a time resolution of 2 hours has been generated at the Center for Orbit Determination in Europe. The series starts in January 1995 and has a length of more than 3 years. Starting from the 2-hour ERP values of this, to our knowledge, unique time series, the high-frequency variations in Universal Time (UT1) and polar motion (PM) due to ocean tides are studied and a set of sine and cosine coefficients is estimated for all the major tidal terms at nearly diurnal and semidiurnal frequencies. The GPS series is not very homogeneous (various processing changes during the 3 years) and still short compared to the length of very long baseline interferometry (VLBI) and satellite laser ranging (SLR) data sets. However, the results derived from this series are already of the same quality as the results from VLBI and SLR. A comparison of the tidal coefficients stemming from all three space-geodetic techniques shows an agreement on the 1 μs level for UT1 and 10 microarc seconds (μas) for PM, respectively. The RMS difference between the ocean tide amplitudes estimated from GPS data and from TOPEX/Poseidon altimeter data amounts to 0.7-0.9 μs in UT1 and 9-13 μas in PM. The residual spectrum that remains after the removal of all tidal terms has a noise level of ˜5-10 μas in PM and 0.5-1 μs in UT1 and contains nontidal signals (up to 55 μas in PM and 3 μs in UT1) that might be due to the impact of the satellite orbit modeling (12-hour revolution period of the satellites) or, alternatively, due to atmospheric or oceanic normal modes.

  5. Allelic variation of polyphenol oxidase (PPO) genes located on chromosomes 2A and 2D and development of functional markers for the PPO genes in common wheat.

    PubMed

    He, X Y; He, Z H; Zhang, L P; Sun, D J; Morris, C F; Fuerst, E P; Xia, X C

    2007-06-01

    Polyphenol oxidase (PPO) activity is highly related to the undesirable browning of wheat-based end products, especially Asian noodles. Characterization of PPO genes and the development of their functional markers are of great importance for marker-assisted selection in wheat breeding. In the present study, complete genomic DNA sequences of two PPO genes, one each located on chromosomes 2A and 2D and their allelic variants were characterized by means of in silico cloning and experimental validation. Sequences were aligned at both DNA and protein levels. Two haplotypes on chromosome 2D showed 95.2% sequence identity at the DNA level, indicating much more sequence diversity than those on chromosome 2A with 99.6% sequence identity. Both of the PPO genes on chromosomes 2A and 2D contain an open reading frame (ORF) of 1,731 bp, encoding a PPO precursor peptide of 577 amino acids with a predicted molecular mass of approximately 64 kD. Two complementary dominant STS markers, PPO16 and PPO29, were developed based on the PPO gene haplotypes located on chromosome 2D; they amplify a 713-bp fragment in cultivars with low PPO activity and a 490-bp fragment in those with high PPO activity, respectively. The two markers were mapped on chromosome 2DL using a doubled haploid population derived from the cross Zhongyou 9507/CA9632, and a set of nullisomic-tetrasomic lines and ditelosomic line 2DS of Chinese Spring. QTL analysis indicated that the PPO gene co-segregated with the two STS markers and was closely linked to SSR marker Xwmc41 on chromosome 2DL, explaining from 9.6 to 24.4% of the phenotypic variance for PPO activity across three environments. In order to simultaneously detect PPO loci on chromosomes 2A and 2D, a multiplexed marker combination PPO33/PPO16 was developed and yielded distinguishable DNA patterns in a number of cultivars. The STS marker PPO33 for the PPO gene on chromosome 2A was developed from the same gene sequences as PPO18 that we reported previously, and

  6. Impact of atmospheric changes on the low-frequency variations of convective afternoon rainfall activity over Taiwan

    NASA Astrophysics Data System (ADS)

    Huang, Wan-Ru; Hsu, Huang-Hsiung; Wang, Shih-Yu; Chen, Jian-Pu

    2015-09-01

    This study examines the characteristics of low-frequency variations (defined as decadal-scale changes) in summer (June-August) convective afternoon rainfall (CAR) activity over Taiwan during 1961-2012. Using 3-hourly rain gauge data, it was found that (1) the CAR frequency exhibits a secular trend and the 10-20 decadal oscillation, (2) the trend in CAR frequency is positive in northern Taiwan but negative in central and southern Taiwan, and (3) the CAR rate increased over most of the lower plains but decreased over the mountain range of Taiwan. Diagnoses using the Japanese ReAnalysis (JRA-55) data and surface observations indicate that the low-frequency variations in CAR frequency are closely associated with the variations in monsoon southwesterly winds over the South China Sea and island-wide sea breeze convergence. The regional low-level circulation changes are linked to sea surface temperature anomalies over the Niño-4 region and its 10-20 year (quasi-decadal) oscillation. Regarding the processes that change the CAR rate in the trending patterns, it was found that increases in the moisture flux convergence and the moist (conditional) instability over the lower plains together explain the stronger CAR events in the long run.

  7. A mechanism for decadal variations in the frequency of extreme El Niño events

    NASA Astrophysics Data System (ADS)

    Wang, G.; Cai, W.

    2015-12-01

    The El Niño Southern Oscillation (ENSO), the largest source of Earth's climate variability on interannual time scales, has massive impacts on extreme weathers, agriculture and ecosystems, particularly during extreme El Niño events, such as the 1982/83 and 1997/98 episodes. However, the associated mechanism is not fully understood, hindering their forecasts, as attested by the false alarm of an extreme El Niño in 2014 predicted by many models. Recent studies have identified additional precursors beyond westerly wind anomalies and oceanic heat content along the equatorial Pacific, including the southwest Pacific southerly jets, which tend to occur strongly and concurrently with equatorial westerly anomalies during extreme El Niño, but NOT during weak El Niño events. Here we show that the concurrences of southwest Pacific southerlies, anomalous equatorial westerlies, and their relationship, are modulated by the Pacific Decadal Oscillation (PDO)/Interdecadal Pacific Oscillation (IPO), even on daily timescales. During a positive phase of the PDO/IPO, occurrences of westerly wind events (WWEs), in the region between the Maritime continent and the eastern Pacific Ocean, are reinforced by the southwest Pacific southerly surges (SPSSs) in austral winter. By contrast, during a negative phase of the PDO/IPO, such SPSSs are not reinforcing WWEs; instead stronger SPSSs are associated with weaker WWEs. This interdecadal contrast in the relationship between SPSSs and WWEs contributes to the decadal variations in the frequency of extreme El Niño events. The associated mechanism will be discussed.

  8. Galactosemia in the Turkish population with a high frequency of Q188R mutation and distribution of Duarte-1 and Duarte-2 variations.

    PubMed

    Özgül, Rıza Köksal; Güzel-Ozantürk, Ayşegül; Dündar, Halil; Yücel-Yılmaz, Didem; Coşkun, Turgay; Sivri, Serap; Aydoǧdu, Sultan; Tokatlı, Ayşegül; Dursun, Ali

    2013-10-01

    Classical galactosemia is an inherited recessive disorder of galactose metabolism caused by deficiency of the enzyme galactose-1-phosphate uridyl transferase (GALT), which is caused by mutations in the GALT gene. In this study, 56 Turkish patients diagnosed with galactosemia were screened for GALT gene mutations using Affymetrix resequencing microarrays. Eleven types of mutations were detected in these patients, including two novel mutations (R258G and G310fsX49) and nine recurrent mutations. We detected six patients who were homozygous for the E340* mutation and for N314D, L218L silent substitutions (Duarte-1 variant) in this study. The haplotype E340*, N314D and L218L has been reported only in Turkish patients, which suggests that the E340* mutation is specific for our population and might be spread by a Turk ancestor. In patients, the Duarte-1 allele was found with a frequency of 10.71%, whereas the Duarte-2 allele was not detected. Duarte-1 and Duarte-2 alleles were found to be present at a frequency of 2.3% and 1.4%, respectively, in the screening of 105 healthy individuals. Considering all detected mutations, it is a very important finding that exons 6 and 10 of the GALT gene account for 79% of all mutant alleles in the Turkish population. The most common mutation is Q188R, with a frequency of 55.35%.

  9. Characterization of the treefrog null allele, 1991

    SciTech Connect

    Guttman, S.I.

    1992-04-01

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

  10. Characterization of the treefrog null allele

    SciTech Connect

    Guttman, S.I. . Dept. of Zoology)

    1990-12-01

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

  11. HLA-A, HLA-B, HLA-DRB1 allele and haplotype frequencies in 6384 umbilical cord blood units and transplantation matching and engraftment statistics in the Zhejiang cord blood bank of China.

    PubMed

    Wang, F; He, J; Chen, S; Qin, F; Dai, B; Zhang, W; Zhu, F M; Lv, H J

    2014-02-01

    Umbilical cord blood (UCB) is a widely accepted source of progenitor cells, and now, many cord blood banks were established. Here, we analysed the HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies, HLA matching possibilities for searching potential donors and outcome of UCB transplantations in Zhejiang cord blood bank of China. A total of 6384 UCB units were characterized for 17 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles at the first field resolution level. Additionally, B*14, B*15 and B*40 were typed to the second field level. A total of 1372 distinct A-B-DRB1 haplotypes were identified. The frequencies of 7 haplotypes were more than 1%, and 439 haplotypes were <0.01%. A*02-B*46-DRB1*09, A*33-B*58-DRB1*03 and A*30-B*13-DRB1*07 were the most common haplotypes, with frequencies of 4.4%, 3.3%, and 2.9%, respectively. Linkage disequilibrium(LD) analysis showed that there were 83 A-B, 106 B-DRB1, 54 A-DRB1 haplotypes with positive LD, in which 51 A-B, 60 B-DRB1, 32 A-DRB1 haplotypes exhibited a significant LD (P < 0.05). In 682 search requests, 12.9%, 40.0% and 42.7% of patients were found to have 6 of 6, 5 of 6 and 4 of 6 HLA-A, HLA-B and HLA-DRB1 matching donors, respectively. A total of 30 UCB units were transplanted to 24 patients (3 patients not evaluated due to early death); 14 of 21 patients (66.7%) engrafted. This study reveals the HLA distribution and its transplantation application in the cord blood bank of Zhejiang province. These data can help to select potential UCB donors for transplantation and used to assess the scale of new cord blood banking endeavours.

  12. SU-E-T-408: Evaluation of the Type and Frequency of Variations Discovered During Routine Secondary Patient Chart Review

    SciTech Connect

    Hardin, M; Harrison, A; Lockamy, V; Li, J; Peng, C; Potrebko, P; Yu, Y; Doyle, L; Cao, J

    2015-06-15

    Purpose: Desire to improve efficiency and throughput inspired a review of our physics chart check procedures. Departmental policy mandates plan checks pre-treatment, after first treatment and weekly every 3–5 days. This study examined the effectiveness of the “after first” check with respect to improving patient safety and clinical efficiency. Type and frequency of variations discovered during this redundant secondary review was examined over seven months. Methods: A community spreadsheet was created to record variations in care discovered during chart review following the first fraction of treatment and before the second fraction (each plan reviewed prior to treatment). Entries were recorded from August 2014 through February 2015, amounting to 43 recorded variations out of 906 reviewed charts. The variations were divided into categories and frequencies were assessed month-to-month. Results: Analysis of recorded variations indicates an overall variation rate of 4.7%. The initial rate was 13.5%; months 2–7 average 3.7%. The majority of variations related to discrepancies in documentation at 46.5%, followed by prescription, plan deficiency, and dose tracking related variations at 25.5%, 12.8%, and 12.8%, respectively. Minor variations (negligible consequence on patient treatment) outweighed major variations 3 to 1. Conclusion: This work indicates that this redundant secondary check is effective. The first month spike in rates could be due to the Hawthorne/observer effect, but the consistent 4% variation rate suggests the need for periodical re-training on variations noted as frequent to improve awareness and quality of the initial chart review process, which may lead to improved treatment quality, patient safety and increased clinical efficiency. Utilizing these results, a continuous quality improvement process following Deming’s Plan-Do-Study-Act (PDSA) methodology was generated. The first iteration of this PDSA was adding a specific dose tracking

  13. Temporal and spatial trends in allozyme frequencies in house fly populations, Musca domestica L.

    PubMed

    Black, W C; Krafsur, E S

    1986-02-01

    Allelic and genotypic frequencies were sampled from a single age class of the common house fly, Musca domestica L., at five farms on six dates from July 6 to October 12, 1982. Allozymes at six loci were resolved with vertical polyacrylamide gel electrophoresis. No consistent departures from random mating were detected. No consistent linkage disequilibrium was observed. Allele frequencies at the farms changed in independent and unpredictable ways. Gene frequencies at the five farms were initially divergent, converged in midsummer, and then progressively diverged. The divergence occured in mid-August when fly populations were large. Variation in gene frequencies at adjacent farms accounted for a large proportion of the variance in allele frequencies among all farms. These observations are consistent with the hypothesis that allele frequencies in young adult flies reflected the habitat in which they matured as larvae.

  14. Variation in the resting frequency of Rhinolophus pusillus in Mainland China: effect of climate and implications for conservation.

    PubMed

    Jiang, Tinglei; Metzner, Walter; You, Yuyan; Liu, Sen; Lu, Guanjun; Li, Shi; Wang, Lei; Feng, Jiang

    2010-10-01

    This study describes variation patterns in the constant frequency of echolocation calls emitted at rest and when not flying ("resting frequency" RF) of the least horseshoe bat, Rhinolophus pusillus, on a broad geographical scale and in response to local climatic variables. Significant differences in RF were observed among populations throughout the species range in Mainland China, and this variation was positively and significantly related to climate conditions, especially environmental humidity, but the variability was only weakly associated with geographical distance. Sex dimorphism in the RF of R. pusillus may imply that female and male might keep their frequencies within a narrow range for sex recognition. Moreover, bats adjusted resting frequency to humidity, which may imply partitioning diet by prey size or the influence of rainfall noise. The results indicate that bats adjust echolocation call frequency to adapt to environmental conditions. Therefore, environmental selection shape the diversity of echolocation call structure of R. pusillus in geographically separated populations, and conservation efforts should focus on changes in local climate and effects of environmental noise.

  15. Allele frequencies in the VRN-A1, VRN-B1 and VRN-D1 vernalization response and PPD-B1 and PPD-D1 photoperiod sensitivity genes, and their effects on heading in a diverse set of wheat cultivars (Triticum aestivum L.).

    PubMed

    Kiss, Tibor; Balla, Krisztina; Veisz, Ottó; Láng, László; Bedő, Zoltán; Griffiths, Simon; Isaac, Peter; Karsai, Ildikó

    2014-01-01

    Heading of cereals is determined by complex genetic and environmental factors in which genes responsible for vernalization and photoperiod sensitivity play a decisive role. Our aim was to use diagnostic molecular markers to determine the main allele types in VRN-A1, VRN-B1, VRN-D1, PPD-B1 and PPD-D1 in a worldwide wheat collection of 683 genotypes and to investigate the effect of these alleles on heading in the field. The dominant VRN-A1, VRN-B1 and VRN-D1 alleles were present at a low frequency. The PPD-D1a photoperiod-insensitive allele was carried by 57 % of the cultivars and was most frequent in Asian and European cultivars. The PPD-B1 photoperiod-insensitive allele was carried by 22 % of the genotypes from Asia, America and Europe. Nine versions of the PPD-B1-insensitive allele were identified based on gene copy number and intercopy structure. The allele compositions in PPD-D1, PPD-B1 and VRN-D1 significantly influenced heading and together explained 37.5 % of the phenotypic variance. The role of gene model increased to 39.1 % when PPD-B1 intercopy structure was taken into account instead of overall PPD-B1 type (sensitive vs. insensitive). As a single component, PPD-D1 had the most important role (28.0 % of the phenotypic variance), followed by PPD-B1 (12.3 % for PPD-B1_overall, and 15.1 % for PPD-B1_intercopy) and VRN-D1 (2.2 %). Significant gene interactions were identified between the marker alleles within PPD-B1 and between VRN-D1 and the two PPD1 genes. The earliest heading genotypes were those with the photoperiod-insensitive allele in PPD-D1 and PPD-B1, and with the spring allele for VRN-D1 and the winter alleles for VRN-A1 and VRN-B1. This combination could only be detected in genotypes from Southern Europe and Asia. Late-heading genotypes had the sensitivity alleles for both PPD1 genes, regardless of the allelic composition of the VRN1 genes. There was a 10-day difference in heading between the earliest and latest groups under field conditions.

  16. Variation in high-frequency wave radiation from small repeating earthquakes as revealed by cross-spectral analysis

    NASA Astrophysics Data System (ADS)

    Hatakeyama, Norishige; Uchida, Naoki; Matsuzawa, Toru; Okada, Tomomi; Nakajima, Junichi; Matsushima, Takeshi; Kono, Toshio; Hirahara, Satoshi; Nakayama, Takashi

    2016-11-01

    We examined the variation in the high-frequency wave radiation for three repeating earthquake sequences (M = 3.1-4.1) in the northeastern Japan subduction zone by waveform analyses. Earthquakes in each repeating sequence are located at almost the same place and show low-angle thrust type focal mechanisms, indicating that they represent repeated ruptures of a seismic patch on the plate boundary. We calculated cross-spectra of the waveforms and obtained the phases and coherences for pairs of events in the respective repeating sequences in order to investigate the waveform differences. We used waveform data sampled at 1 kHz that were obtained from temporary seismic observations we conducted immediately after the 2011 Tohoku earthquake near the source area. For two repeating sequences, we found that the interevent delay times for the two waveforms in a frequency band higher than the corner frequencies are different from those in a lower frequency band for particular event pairs. The phases and coherences show that there are coherent high-frequency waves for almost all the repeaters regardless of the high-frequency delays. These results indicate that high-frequency waves are always radiated from the same vicinity (subpatch) for these events but the time intervals between the ruptures of the subpatch and the centroid times can vary. We classified events in the sequence into two subgroups according to the high-frequency band interevent delays relative to the low-frequency band. For one sequence, we found that all the events that occurred just after (within 11 days) larger nearby earthquakes belong to one subgroup while other events belong to the other subgroup. This suggests that the high-frequency wave differences were caused by stress perturbations due to the nearby earthquakes. In summary, our observations suggest that high-frequency waves from the repeating sequence are radiated not from everywhere but from a long-duration subpatch within the seismic slip area. The

  17. High frequency and allele-specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus.

    PubMed

    Bogdanova, N V; Antonenkova, N N; Rogov, Y I; Karstens, J H; Hillemanns, P; Dörk, T

    2010-10-01

    Breast cancer and ovarian cancer are common malignancies in Belarus accounting for about 3500 and 800 new cases per year, respectively. For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. We assessed the frequency and distribution of three BRCA1 founder mutations 5382insC, 4153delA and Cys61Gly in two hospital-based series of 1945 unselected breast cancer patients and of 201 unselected ovarian cancer patients from Belarus as well as in 1019 healthy control females from the same population. Any of these mutations were identified in 4.4% of the breast cancer patients, 26.4% of the ovarian cancer patients and 0.5% of the controls. In the breast cancer patients, BRCA1 mutations were strongly associated with earlier age at diagnosis, with oestrogen receptor (ER) negative tumours and with a first-degree family history of breast cancer, although only 35% of the identified BRCA1 mutation carriers had such a family history. There were no marked differences in the regional distribution of BRCA1 mutations, so that the significant differences in age at diagnosis and family history of breast cancer patients from areas afflicted by the Chernobyl accident could not be explained by BRCA1. We next observed a higher impact and a shifted mutational spectrum of BRCA1 in the series of Byelorussian ovarian cancer patients where the three founder mutations accounted for 26.4% (53/201). While the Cys61Gly mutation appeared underrepresented in ovarian cancer as compared with breast cancer cases from the same population (p = 0.01), the 4153delA mutation made a higher contribution to ovarian cancer than to breast cancer (p < 0.01). BRCA1 mutations were significantly enriched among ovarian cancer cases with a first-degree family history of breast or ovarian cancer, whereas the median age at ovarian cancer diagnosis was not different between mutation carriers and non-carriers. Taken together, these results

  18. Allele-specific disparity in breast cancer

    PubMed Central

    2011-01-01

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

  19. Microsatellite frequencies vary with body mass and body temperature in mammals, suggesting correlated variation in mutation rate

    PubMed Central

    Filipe, Laura N.S.

    2014-01-01

    Substitution rate is often found to correlate with life history traits such as body mass, a predictor of population size and longevity, and body temperature. The underlying mechanism is unclear but most models invoke either natural selection or factors such as generation length that change the number of mutation opportunities per unit time. Here we use published genome sequences from 69 mammals to ask whether life history traits impact another form of genetic mutation, the high rates of predominantly neutral slippage in microsatellites. We find that the length-frequency distributions of three common dinucleotide motifs differ greatly between even closely related species. These frequency differences correlate with body mass and body temperature and can be used to predict the phenotype of an unknown species. Importantly, different length microsatellites show complicated patterns of excess and deficit that cannot be explained by a simple model where species with short generation lengths have experienced more mutations. Instead, the patterns probably require changes in mutation rate that impact alleles of different length to different extents. Body temperature plausibly influences mutation rate by modulating the propensity for slippage. Existing hypotheses struggle to account for a link between body mass and mutation rate. However, body mass correlates inversely with population size, which in turn predicts heterozygosity. We suggest that heterozygote instability, HI, the idea that heterozygous sites show increased mutability, could provide a plausible link between body mass and mutation rate. PMID:25392761

  20. Variation.

    ERIC Educational Resources Information Center

    Hamilton City Board of Education (Ontario).

    Suggestions for studying the topic of variation of individuals and objects (balls) to help develop elementary school students' measurement, comparison, classification, evaluation, and data collection and recording skills are made. General suggestions of variables that can be investigated are made for the study of human variation. Twelve specific…

  1. Annual ionospheric variations of the critical frequency foF2 at the equatorial stations during the solar minima

    NASA Astrophysics Data System (ADS)

    Biktash, Lilia

    2016-07-01

    We have analyzed annual ionospheric variations of the critical frequency foF2 at the equatorial stations during the solar minima. There are essential distinctions between the global TEC (total electron content) and foF2 annual variations during the last two solar minima. Many authors concluded that the annual means of foF2 and the global TEC were reduced, while others investigations no found essential variations as compared with the previous solar minimum. Most if not all of authors suppose that the possible source of this phenomenon is the low level of the EUV (extreme ultraviolet) during the solar minima. The aim of our paper is to amplify these conclusions or to propose new factor which can change ionosphere parameters during the solar minima. We calculated annual variations of foF2 at the equatorial stations and compared these data with Dst annual variations. We found that in addition to low level of the EUV during the solar minima, geomagnetic storms effects have to be included as the influencing factor on annual ionospheric variations.

  2. High frequency genetic variation of purine biosynthesis genes is a mechanism of success in Campylobacter jejuni

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phenotypic variation is prevalent among progeny of the zoonotic pathogen Campylobacter jejuni, the leading agent of enterocolitis in the developed world. Heterogeneity bestows increased survival to bacterial populations because variable phenotypes ensure some cells will be protected against future s...

  3. Low frequency electric field variations during HF transmissions on a mother-daughter rocket

    NASA Technical Reports Server (NTRS)

    Rosenberg, T. J.; Maynard, M. C.; Holtet, J. A.; Karlsen, N. O.; Egeland, A.; Moe, T. E.; Troim, J.

    1977-01-01

    HF wave propagation experiments were conducted on Mother-Daughter rockets in the polar ionosphere. Swept frequency transmissions from the Mother, nominally covering the range from 0.5 to 5 MHz in both CW and pulse modes, are received by the Daughter. In the most recent rocket of the series, the Mother also contained an AC electric field spectrometer covering the frequency range from 10 Hz to 100 kHz in four decade bands. The low frequency response of the ionosphere with respect to waves emitted from the onboard HF transmitter is examined.

  4. The impact of variation in low-frequency interaural cross correlation on auditory spatial imagery in stereophonic loudspeaker reproduction

    NASA Astrophysics Data System (ADS)

    Martens, William

    2005-04-01

    Several attributes of auditory spatial imagery associated with stereophonic sound reproduction are strongly modulated by variation in interaural cross correlation (IACC) within low frequency bands. Nonetheless, a standard practice in bass management for two-channel and multichannel loudspeaker reproduction is to mix low-frequency musical content to a single channel for reproduction via a single driver (e.g., a subwoofer). This paper reviews the results of psychoacoustic studies which support the conclusion that reproduction via multiple drivers of decorrelated low-frequency signals significantly affects such important spatial attributes as auditory source width (ASW), auditory source distance (ASD), and listener envelopment (LEV). A variety of methods have been employed in these tests, including forced choice discrimination and identification, and direct ratings of both global dissimilarity and distinct attributes. Contrary to assumptions that underlie industrial standards established in 1994 by ITU-R. Recommendation BS.775-1, these findings imply that substantial stereophonic spatial information exists within audio signals at frequencies below the 80 to 120 Hz range of prescribed subwoofer cutoff frequencies, and that loudspeaker reproduction of decorrelated signals at frequencies as low as 50 Hz can have an impact upon auditory spatial imagery. [Work supported by VRQ.

  5. Variation in the resting frequency of Rhinolophus pusillus in Mainland China: Effect of climate and implications for conservation

    PubMed Central

    Jiang, Tinglei; Metzner, Walter; You, Yuyan; Liu, Sen; Lu, Guanjun; Li, Shi; Wang, Lei; Feng, Jiang

    2010-01-01

    This study describes variation patterns in the constant frequency of echolocation calls emitted at rest and when not flying (“resting frequency” RF) of the least horseshoe bat, Rhinolophus pusillus, on a broad geographical scale and in response to local climatic variables. Significant differences in RF were observed among populations throughout the species range in Mainland China, and this variation was positively and significantly related to climate conditions, especially environmental humidity, but the variability was only weakly associated with geographical distance. Sex dimorphism in the RF of R. pusillus may imply that female and male might keep their frequencies within a narrow range for sex recognition. Moreover, bats adjusted resting frequency to humidity, which may imply partitioning diet by prey size or the influence of rainfall noise. The results indicate that bats adjust echolocation call frequency to adapt to environmental conditions. Therefore, environmental selection shape the diversity of echolocation call structure of R. pusillus in geographically separated populations, and conservation efforts should focus on changes in local climate and effects of environmental noise. PMID:20968390

  6. Variation in the Frequency and Extent of Hybridization between Leucosceptrum japonicum and L. stellipilum (Lamiaceae) in the Central Japanese Mainland

    PubMed Central

    Li, Yue; Maki, Masayuki

    2015-01-01

    Variations in the frequency and extent of hybridization among mixed populations located in the same contact zone provide natural laboratories for the study of extrinsic reproductive isolation maintaining species integrity. In this study, we examined the pattern of hybridization between L. japonicum and L. stellipilum among mixed populations in different localities of a contact zone. The genetic structures from three sympatric populations and six mixed populations in the hybrid zone, and five reference populations far from the contact zone, were characterized using 10 neutral nuclear microsatellite markers. Evidence from genetic distance-based clustering analysis, the frequency distribution of admixture proportion values, and the hybrid category assignment approaches indicated that the frequency and extent of hybridization varied considerably among populations in the contact zone between L. japonicum and L. stellipilum. One likely explanation is that variation in exogenous (ecological) selection among populations might contribute to differences in frequency and extent of hybridization. The present study will facilitate future research exploring the evolution of reproductive isolation between L. japonicum and L. stellipilum. PMID:25738505

  7. Time-Frequency Analysis of Beach Bacteria Variations and its Implication for Recreational Water Quality Modeling

    EPA Science Inventory

    This paper explores the potential of time-frequency wavelet analysis in resolving beach bacteria concentration and possible explanatory variables across multiple time scales with temporal information still preserved. The wavelet scalograms of E. coli concentrations and the explan...

  8. Studies of the variations of the first Schumann resonance frequency during the solar flare on 7 March 2012

    NASA Astrophysics Data System (ADS)

    Zhou, Hongjuan; Qiao, Xiaolin

    2015-05-01

    The ELF measurements at the YS station in China during the X5.4 solar flare on 7 March 2012 are examined. The first modal Schumann resonance (SR) frequencies of the horizontal magnetic field components were found to increase by 0.1-0.2 Hz during the X-ray burst. During the enhancement of the proton flux, the first modal frequency of the east-west magnetic field component decreases by approximately 0.6 Hz at most, while the variation in the north-south magnetic field component is less well defined. The mechanisms of the variations are simulated with a finite difference time domain technique by modeling the perturbed conductivity profile in the day-night asymmetric Earth-ionosphere cavity and modeling the global lightning source with the raw flash data measured by satellites. The simulated varying trends of the SR frequencies observed near the ground with the altitudes of the conductivity perturbations are nearly the same as those previously reported and are interpreted by the two characteristic height model first proposed by Greifinger and Greifinger. It is concluded that the SR frequencies increase for enhanced conductivity above the altitude of 60-70 km because of the lowered magnetic height and decrease for enhanced conductivity below this altitude due to the lowered electric height. This finding can explain the opposite behaviors of the SR frequencies during X-ray bursts and strong solar proton events (SPEs). The simulation model in this work proved to be effective, with the simulated shifts in the values of SR frequencies during X-ray bursts and SPEs being close to the practical measurements.

  9. Frequency-Dependent Amplitude Versus Offset Variations in Porous Rocks with Aligned Fractures

    NASA Astrophysics Data System (ADS)

    Yang, Xiaohui; Cao, Siyuan; Guo, Quanshi; Kang, Yonggan; Yu, Pengfei; Hu, Wei

    2017-03-01

    The theory of frequency-dependent amplitude versus offset (AVO) was developed for patchy-saturated model. In this work, we consider this theory in the case of an anisotropic medium based on a fractured-sandstone model. Thus, building on viscoelastic theory, we introduce a method for the computation of frequency-dependent AVO that is suitable for use in the case of an anisotropic medium. We use both analytical methods and numerical simulations to study P-P and P-S reflection coefficients, and results suggest that dispersion and anisotropy should not be neglected in AVO analysis. Indeed, for class I AVO reservoirs, the reflection magnitude of P-wave increases with frequency, while the responses of class II AVO reservoirs suggest that phase reversal occurs as frequency increases positively. In the case of class III AVO reservoirs, reflection magnitude decreases as frequency increases positively, while in the offset domain, the presence of anisotropy can distort or even reverse AVO responses. Thus, when compared to reflection coefficients for P-wave, reflection magnitude features of S-wave are more complex. The frequency-dependent AVO responses reported in this study provide insights for the interpretation of seismic anomalies in vertical transverse isotropy (VTI) dispersive reservoirs.

  10. Frequency-Dependent Amplitude Versus Offset Variations in Porous Rocks with Aligned Fractures

    NASA Astrophysics Data System (ADS)

    Yang, Xiaohui; Cao, Siyuan; Guo, Quanshi; Kang, Yonggan; Yu, Pengfei; Hu, Wei

    2016-11-01

    The theory of frequency-dependent amplitude versus offset (AVO) was developed for patchy-saturated model. In this work, we consider this theory in the case of an anisotropic medium based on a fractured-sandstone model. Thus, building on viscoelastic theory, we introduce a method for the computation of frequency-dependent AVO that is suitable for use in the case of an anisotropic medium. We use both analytical methods and numerical simulations to study P-P and P-S reflection coefficients, and results suggest that dispersion and anisotropy should not be neglected in AVO analysis. Indeed, for class I AVO reservoirs, the reflection magnitude of P-wave increases with frequency, while the responses of class II AVO reservoirs suggest that phase reversal occurs as frequency increases positively. In the case of class III AVO reservoirs, reflection magnitude decreases as frequency increases positively, while in the offset domain, the presence of anisotropy can distort or even reverse AVO responses. Thus, when compared to reflection coefficients for P-wave, reflection magnitude features of S-wave are more complex. The frequency-dependent AVO responses reported in this study provide insights for the interpretation of seismic anomalies in vertical transverse isotropy (VTI) dispersive reservoirs.

  11. HLA class II alleles and risk for peripheral neuropathy in type 2 diabetes patients

    PubMed Central

    Marzban, Ahmad; Kiani, Javad; Hajilooi, Mehrdad; Rezaei, Hamzeh; Kahramfar, Zohreh; Solgi, Ghasem

    2016-01-01

    The potential impact of human leukocyte antigen (HLA) genotype variations on development of diabetic peripheral neuropathy (DPN) is not well determined. This study aimed to identify the association of HLA class II alleles with DPN in type 2 diabetes (T2D) patients. Totally 106 T2D patients, 49 with DPN and 57 without DPN, and 100 ethnic-matched healthy controls were analyzed. Both groups of the patients were matched based on sex, age, body mass index (BMI) and duration of T2D. Polyneuropathy was diagnosed using electrodiagnostic methods. HLA-DRB1 and DQB1 genotyping was performed in all subjects by the polymerase chain reaction with sequence-specific primers (PCR-SSP) method. T2D patients with DPN showed higher frequencies of HLA-DRB1*10 and DRB1*12 alleles compared to control group (P = 0.04). HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype were associated with a decreased risk for developing DPN in T2D patients (P = 0.02 and P = 0.05 respectively). Also, patients with severe neuropathy showed higher frequencies of DRB1*07 (P = 0.003) and DQB1*02 (P = 0.02) alleles than those with mild-to-moderate form of neuropathy. The distribution of DRB1 and DQB1 alleles and haplotypes were not statistically different between all patients and healthy controls. Our findings implicate a possible protective role of HLA-DQB1*02 allele and HLA-DRB1*07-DQB1*02 haplotype against development of peripheral neuropathy in T2D patients. Therefore, variations in HLA genotypes might be used as genetic markers for prediction and potentially management of neuropathy in T2D patients. PMID:28123430

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

    PubMed

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

    2015-05-01

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

  13. Genetic Heterogeneity within Electrophoretic "Alleles" of Xanthine Dehydrogenase in DROSOPHILA PSEUDOOBSCURA

    PubMed Central

    Singh, R. S.; Lewontin, R. C.; Felton, A. A.

    1976-01-01

    An experimental plan for an exhaustive determination of genic variation at structural gene loci is presented. In the initial steps of this program, 146 isochromosomal lines from 12 geographic populations of D. pseudoobscura were examined for allelic variation of xanthine dehydrogenase by the serial use of 4 different electrophoretic conditions and a heat stability test. The 5 criteria revealed a total of 37 allelic classes out of the 146 genomes examined where only 6 had been previously revealed by the usual method of gel electrophoresis. This immense increase in genic variation also showed previously unsuspected population differences between the main part of the species distribution and the isolated population of Bogotá, Colombia, in conformity with the known partial reproductive isolation of the Bogotá population. The average heterozygosity at the Xdh locus is at least 72% in natural populations. This result, together with the very large number of alleles segregating and the pattern of allelic frequencies, has implications for theories of genetic polymorphism which are discussed. PMID:1001881

  14. Geographic Variation in Festuca rubra L. Ploidy Levels and Systemic Fungal Endophyte Frequencies.

    PubMed

    Dirihan, Serdar; Helander, Marjo; Väre, Henry; Gundel, Pedro E; Garibaldi, Lucas A; Irisarri, J Gonzalo N; Saloniemi, Irma; Saikkonen, Kari

    2016-01-01

    Polyploidy and symbiotic Epichloë fungal endophytes are common and heritable characteristics that can facilitate environmental range expansion in grasses. Here we examined geographic patterns of polyploidy and the frequency of fungal endophyte colonized plants in 29 Festuca rubra L. populations from eight geographic sites across latitudes from Spain to northernmost Finland and Greenland. Ploidy seemed to be positively and negatively correlated with latitude and productivity, respectively. However, the correlations were nonlinear; 84% of the plants were hexaploids (2n = 6x = 42), and the positive correlation between ploidy level and latitude is the result of only four populations skewing the data. In the southernmost end of the gradient 86% of the plants were tetraploids (2n = 4x = 28), whereas in the northernmost end of the gradient one population had only octoploid plants (2n = 8x = 56). Endophytes were detected in 22 out of the 29 populations. Endophyte frequencies varied among geographic sites, and populations and habitats within geographic sites irrespective of ploidy, latitude or productivity. The highest overall endophyte frequencies were found in the southernmost end of the gradient, Spain, where 69% of plants harbored endophytes. In northern Finland, endophytes were detected in 30% of grasses but endophyte frequencies varied among populations from 0% to 75%, being higher in meadows compared to riverbanks. The endophytes were detected in 36%, 30% and 27% of the plants in Faroe Islands, Iceland and Switzerland, respectively. Practically all examined plants collected from southern Finland and Greenland were endophyte-free, whereas in other geographic sites endophyte frequencies were highly variable among populations. Common to all populations with high endophyte frequencies is heavy vertebrate grazing. We propose that the detected endophyte frequencies and ploidy levels mirror past distribution history of F. rubra after the last glaciation period, and local

  15. Geographic Variation in Festuca rubra L. Ploidy Levels and Systemic Fungal Endophyte Frequencies

    PubMed Central

    Dirihan, Serdar; Helander, Marjo; Väre, Henry; Gundel, Pedro E.; Garibaldi, Lucas A.; Irisarri, J. Gonzalo N.; Saloniemi, Irma; Saikkonen, Kari

    2016-01-01

    Polyploidy and symbiotic Epichloë fungal endophytes are common and heritable characteristics that can facilitate environmental range expansion in grasses. Here we examined geographic patterns of polyploidy and the frequency of fungal endophyte colonized plants in 29 Festuca rubra L. populations from eight geographic sites across latitudes from Spain to northernmost Finland and Greenland. Ploidy seemed to be positively and negatively correlated with latitude and productivity, respectively. However, the correlations were nonlinear; 84% of the plants were hexaploids (2n = 6x = 42), and the positive correlation between ploidy level and latitude is the result of only four populations skewing the data. In the southernmost end of the gradient 86% of the plants were tetraploids (2n = 4x = 28), whereas in the northernmost end of the gradient one population had only octoploid plants (2n = 8x = 56). Endophytes were detected in 22 out of the 29 populations. Endophyte frequencies varied among geographic sites, and populations and habitats within geographic sites irrespective of ploidy, latitude or productivity. The highest overall endophyte frequencies were found in the southernmost end of the gradient, Spain, where 69% of plants harbored endophytes. In northern Finland, endophytes were detected in 30% of grasses but endophyte frequencies varied among populations from 0% to 75%, being higher in meadows compared to riverbanks. The endophytes were detected in 36%, 30% and 27% of the plants in Faroe Islands, Iceland and Switzerland, respectively. Practically all examined plants collected from southern Finland and Greenland were endophyte-free, whereas in other geographic sites endophyte frequencies were highly variable among populations. Common to all populations with high endophyte frequencies is heavy vertebrate grazing. We propose that the detected endophyte frequencies and ploidy levels mirror past distribution history of F. rubra after the last glaciation period, and local

  16. Space Shuttle Redesigned Solid Rocket Motor nozzle natural frequency variations with burn time

    NASA Technical Reports Server (NTRS)

    Lui, C. Y.; Mason, D. R.

    1991-01-01

    The effects of erosion and thermal degradation on the Space Shuttle Redesigned Solid Rocket Motor (RSRM) nozzle's structural dynamic characteristics were analytically evaluated. Also considered was stiffening of the structure due to internal pressurization. A detailed NASTRAN finite element model of the nozzle was developed and used to evaluate the influence of these effects at several discrete times during motor burn. Methods were developed for treating erosion and thermal degradation, and a procedure was developed to account for internal pressure stiffening using differential stiffness matrix techniques. Results were verified using static firing test accelerometer data. Fast Fourier Transform and Maximum Entropy Method techniques were applied to the data to generate waterfall plots which track modal frequencies with burn time. Results indicate that the lower frequency nozzle 'vectoring' modes are only slightly affected by erosion, thermal effects and internal pressurization. The higher frequency shell modes of the nozzle are, however, significantly reduced.

  17. Searches for high frequency variations in the 8-B neutrino flux at the Sudbury neutrino observatory

    SciTech Connect

    Rielage, Keith; Seibert, Stanley R; Hime, Andrew; Elliott, Steven R; Stonehill, L C; Wouters, J M; Aharmim, B; Ahmed, S N; Anthony, A E; Barros, N; Beier, E W; Bellerive, A; Belttran, B; Bergevin, M; Biller, S D; Boudjemline, K; Burritt, T H; Cai, B; Chan, Y D; Chauhan, D; Chen, M; Cleveland, B T; Cox - Mobrand, G A; Dai, X; Deng, H; Detwiler, J; Dimarco, M; Doe, P J; Drouin, P - L; Duba, C A; Duncan, F A; Dunford, M; Earle, E D; Evans, H C; Ewan, G T; Farine, J; Fergani, H; Fleurot, F; Ford, R J; Formaggilo, J A; Gagnon, N; Goon, J Tm; Guillian, E; Habib, S; Hahn, R L; Hallin, A L; Hallman, E D; Harvey, P J; Hazama, R; Heintzelman, W J; Heise, J; Helmer, R L; Howard, C; Howe, M A; Huang, M; Jamieson, B; Jelley, N A; Keeter, K J; Klein, J R; Kos, M; Kraus, C; Krauss, C B; Kutter, T; Kyba, C C M; Law, J; Lawson, I T; Lesko, K T; Leslie, J R; Loach, J C; Maclellan, R; Majerus, S; Mak, H B; Maneira, J; Martin, R; Mccauley, N; Mc Donald, A B; Mcgee, S; Miffin, C; Miller, M L; Monreal, B; Monroe, J; Morissette, B; Nickel, B G; Noble, A J; O' Keeffe, H M; Oblath, N S; Orebi Gann, G D; Oser, S M; Ott, R A; Peeters, S J M; Poon, A W P; Prior, G; Reitzner, S D; Robertson, B C; Robertson, R G H; Rollin, E; Schwendener, M H; Secrest, J A; Seibert, S R; Simard, O; Sinclair, D; Sinclair, L; Skensved, P; Sonley, T J; Tesic, G; Tolich, N; Tsui, T; Tunnell, C D; Van Berg, R; Van Devender, B A; Virtue, C J; Wall, B L; Waller, D; Wan Chan Tseung, H; West, N; Wilkerson, J F; Wilson, J R; Wright, A; Yeh, M; Zhang, F; Zuber, K

    2009-01-01

    We have peformed three searches for high-frequency signals in the solar neutrino flux measured by the Sudbury Neutrino Observatory (SNO), motivated by the possibility that solar g-mode oscillations could affect the production or propagation of solar {sup 8}B neutrinos. The first search looked for any significant peak in the frequency range l/day to 144/day, with a sensitivity to sinusoidal signals with amplitudes of 12% or greater. The second search focused on regions in which g-mode signals have been claimed by experiments aboard the SoHO satellite, and was sensitive to signals with amplitudes of 10% or greater. The third search looked for extra power acros