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Sample records for allele frequency variation

  1. 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

  2. Population-ethnic group specific genome variation allele frequency data: a querying and visualization journey.

    PubMed

    Viennas, Emmanouil; Gkantouna, Vassiliki; Ioannou, Marina; Georgitsi, Marianthi; Rigou, Maria; Poulas, Konstantinos; Patrinos, George P; Tzimas, Giannis

    2012-08-01

    National/ethnic mutation databases aim to document the genetic heterogeneity in various populations and ethnic groups worldwide. We have previously reported the development and upgrade of FINDbase (www.findbase.org), a database recording causative mutations and pharmacogenomic marker allele frequencies in various populations around the globe. Although this database has recently been upgraded, we continuously try to enhance its functionality by providing more advanced visualization tools that would further assist effective data querying and comparisons. We are currently experimenting in various visualization techniques on the existing FINDbase causative mutation data collection aiming to provide a dynamic research tool for the worldwide scientific community. We have developed an interactive web-based application for population-based mutation data retrieval. It supports sophisticated data exploration allowing users to apply advanced filtering criteria upon a set of multiple views of the underlying data collection and enables browsing the relationships between individual datasets in a novel and meaningful way. PMID:22659238

  3. The allele frequency spectrum in genome-wide human variation data reveals signals of differential demographic history in three large world populations.

    PubMed Central

    Marth, Gabor T; Czabarka, Eva; Murvai, Janos; Sherry, Stephen T

    2004-01-01

    We have studied a genome-wide set of single-nucleotide polymorphism (SNP) allele frequency measures for African-American, East Asian, and European-American samples. For this analysis we derived a simple, closed mathematical formulation for the spectrum of expected allele frequencies when the sampled populations have experienced nonstationary demographic histories. The direct calculation generates the spectrum orders of magnitude faster than coalescent simulations do and allows us to generate spectra for a large number of alternative histories on a multidimensional parameter grid. Model-fitting experiments using this grid reveal significant population-specific differences among the demographic histories that best describe the observed allele frequency spectra. European and Asian spectra show a bottleneck-shaped history: a reduction of effective population size in the past followed by a recent phase of size recovery. In contrast, the African-American spectrum shows a history of moderate but uninterrupted population expansion. These differences are expected to have profound consequences for the design of medical association studies. The analytical methods developed for this study, i.e., a closed mathematical formulation for the allele frequency spectrum, correcting the ascertainment bias introduced by shallow SNP sampling, and dealing with variable sample sizes provide a general framework for the analysis of public variation data. PMID:15020430

  4. Global patterns of variation in allele and haplotype frequencies and linkage disequilibrium across the CYP2E1 gene

    PubMed Central

    Lee, Mi-Young; Mukherjee, Namita; Pakstis, Andrew J.; Khaliq, Shagufta; Mohyuddin, Aisha; Mehdi, S. Qasim; Speed, William C.; Kidd, Judith R.; Kidd, Kenneth K.

    2009-01-01

    Cytochrome P450 2E1, gene symbol CYP2E1, is one of a family of enzymes with a central role in activating and detoxifying xenobiotics and endogenous compounds. Genetic variation at this gene has been reported in different human populations, and some association studies have reported increased risk for cancers and other diseases. To the best of our knowledge, multi-SNP haplotypes and linkage disequilibrium (LD) have not been systematically studied for CYP2E1 in multiple populations. Haplotypes can greatly increase the power both to identify patterns of genetic variation relevant for gene expression as well as to detect disease-related susceptibility mutations. We present frequency and LD data and analyses for 11 polymorphisms and their haplotypes that we have studied on over 2,600 individuals from 50 human population samples representing the major geographical regions of the world. The diverse patterns of haplotype variation found in the different populations we have studied show that ethnicity may be an important variable helping to explain inconsistencies that have been reported by association studies. More studies clearly are needed of the variants we have studied, especially those in the 5′ region, such as the VNTR, as well as studies of additional polymorphisms known for this gene to establish evidence relating any systematic differences in gene expression that exist to the haplotypes at this gene. PMID:18663376

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

    PubMed Central

    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

    2014-01-01

    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. PMID:24752137

  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

    2014-01-01

    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. PMID:24752137

  7. Bayesian Inference of Natural Selection from Allele Frequency Time Series.

    PubMed

    Schraiber, Joshua G; Evans, Steven N; Slatkin, Montgomery

    2016-05-01

    The advent of accessible ancient DNA technology now allows the direct ascertainment of allele frequencies in ancestral populations, thereby enabling the use of allele frequency time series to detect and estimate natural selection. Such direct observations of allele frequency dynamics are expected to be more powerful than inferences made using patterns of linked neutral variation obtained from modern individuals. We developed a Bayesian method to make use of allele frequency time series data and infer the parameters of general diploid selection, along with allele age, in nonequilibrium populations. We introduce a novel path augmentation approach, in which we use Markov chain Monte Carlo to integrate over the space of allele frequency trajectories consistent with the observed data. Using simulations, we show that this approach has good power to estimate selection coefficients and allele age. Moreover, when applying our approach to data on horse coat color, we find that ignoring a relevant demographic history can significantly bias the results of inference. Our approach is made available in a C++ software package. PMID:27010022

  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 PAGESBeta

    Yue, Min; Han, Xiangan; Masi, Leon De; Zhu, Chunhong; Ma, Xun; Zhang, Junjie; Wu, Renwei; Schmieder, Robert; Kaushik, Radhey S.; Fraser, George P.; et al

    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. Allelic variation contributes to bacterial host specificity

    PubMed Central

    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.

    2015-01-01

    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. Together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts. PMID:26515720

  11. Allelic variation contributes to bacterial host specificity.

    PubMed

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

    2015-01-01

    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. Together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts. PMID:26515720

  12. 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. PMID:27307400

  13. 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...

  14. The frequency of HLA alleles in the Romanian population.

    PubMed

    Constantinescu, Ileana; Boșcaiu, Voicu; Cianga, Petru; Dinu, Andrei-Antoniu; Gai, Elena; Melinte, Mihaela; Moise, Ana

    2016-03-01

    Knowledge of human leukocyte antigen (HLA) allele frequencies is essential for bone marrow and kidney donor searches. The Romanian Caucasian population is heterogeneous and information on HLA polymorphism has not been well studied. We characterized the HLA genetic profile and allele frequencies of regional populations in Romania. HLA-A, B and DRB1 alleles were examined in 8252 individuals, belonging to the four main regions of Romania. The most common alleles found in the Romanian population are the following: HLA-A*01, A*02, A*03, A*11, A*24; HLA-B*18, B*35, B*44, B*51 and HLA-DRB1*01, DRB1*03, DRB1*07, DRB1*11, DRB1*13, DRB1*15, DRB1*16. More than half of the alleles are non-homogeneously spread in Romania. These results provide a starting point for future analyses of genetic heterogeneity in Romania. PMID:26711124

  15. Allele frequencies at microsatellite loci: The stepwise mutation model revisited

    SciTech Connect

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

    1993-03-01

    The authors 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. They 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. It is also shown 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. 39 refs., 6 figs., 4 tabs.

  16. 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...

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

    PubMed

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

    2002-06-01

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

  18. Systematic Detection of Epistatic Interactions Based on Allele Pair Frequencies

    PubMed Central

    Ackermann, Marit; Beyer, Andreas

    2012-01-01

    Epistatic genetic interactions are key for understanding the genetic contribution to complex traits. Epistasis is always defined with respect to some trait such as growth rate or fitness. Whereas most existing epistasis screens explicitly test for a trait, it is also possible to implicitly test for fitness traits by searching for the over- or under-representation of allele pairs in a given population. Such analysis of imbalanced allele pair frequencies of distant loci has not been exploited yet on a genome-wide scale, mostly due to statistical difficulties such as the multiple testing problem. We propose a new approach called Imbalanced Allele Pair frequencies (ImAP) for inferring epistatic interactions that is exclusively based on DNA sequence information. Our approach is based on genome-wide SNP data sampled from a population with known family structure. We make use of genotype information of parent-child trios and inspect 3×3 contingency tables for detecting pairs of alleles from different genomic positions that are over- or under-represented in the population. We also developed a simulation setup which mimics the pedigree structure by simultaneously assuming independence of the markers. When applied to mouse SNP data, our method detected 168 imbalanced allele pairs, which is substantially more than in simulations assuming no interactions. We could validate a significant number of the interactions with external data, and we found that interacting loci are enriched for genes involved in developmental processes. PMID:22346757

  19. 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. PMID:26197946

  20. 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

  1. 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. PMID:27375658

  2. Natural Allelic Variations in Highly Polyploidy Saccharum Complex

    DOE PAGESBeta

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

    2016-06-08

    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 basedmore » 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. BWAmem 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.« less

  3. Allelic disequilibrium and allele frequency distribution as a function of social and demographic history.

    PubMed Central

    Thompson, E A; Neel, J V

    1997-01-01

    Allelic disequilibrium between closely linked genes is a common observation in human populations and often gives rise to speculation concerning the role of selective forces. In a previous treatment, we have developed a population model of the expected distribution of rare variants (including private polymorphisms) in Amerindians and have argued that, because of the great expansion of Amerindian numbers with the advent of agriculture, most of these rare variants are of relatively recent origin. Many other populations have similar histories of striking recent expansions. In this treatment, we demonstrate that, in consequence of this fact, a high degree of linkage disequilibrium between two nonhomologous alleles <0.5 cM apart is the "normal" expectation, even in the absence of selection. This expectation is enhanced by the previous subdivision of human populations into relatively isolated tribes characterized by a high level of endogamy and inbreeding. We also demonstrate that the alleles associated with a recessive disease phenotype are expected to exist in a population in very variable frequencies: there is no need to postulate positive selection with respect to the more common disease-associated alleles for such entities as phenylketonuria or cystic fibrosis. PMID:8981963

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

    PubMed

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

    2015-01-01

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

  5. High throughput automated allele frequency estimation by pyrosequencing.

    PubMed

    Doostzadeh, Julie; Shokralla, Shadi; Absalan, Farnaz; Jalili, Roxana; Mohandessi, Sharareh; Langston, James W; Davis, Ronald W; Ronaghi, Mostafa; Gharizadeh, Baback

    2008-01-01

    Pyrosequencing is a DNA sequencing method based on the principle of sequencing-by-synthesis and pyrophosphate detection through a series of enzymatic reactions. This bioluminometric, real-time DNA sequencing technique offers unique applications that are cost-effective and user-friendly. In this study, we have combined a number of methods to develop an accurate, robust and cost efficient method to determine allele frequencies in large populations for association studies. The assay offers the advantage of minimal systemic sampling errors, uses a general biotin amplification approach, and replaces dTTP for dATP-apha-thio to avoid non-uniform higher peaks in order to increase accuracy. We demonstrate that this newly developed assay is a robust, cost-effective, accurate and reproducible approach for large-scale genotyping of DNA pools. We also discuss potential improvements of the software for more accurate allele frequency analysis. PMID:18628978

  6. High Throughput Automated Allele Frequency Estimation by Pyrosequencing

    PubMed Central

    Absalan, Farnaz; Jalili, Roxana; Mohandessi, Sharareh; Langston, James W.; Davis, Ronald W.; Ronaghi, Mostafa; Gharizadeh, Baback

    2008-01-01

    Pyrosequencing is a DNA sequencing method based on the principle of sequencing-by-synthesis and pyrophosphate detection through a series of enzymatic reactions. This bioluminometric, real-time DNA sequencing technique offers unique applications that are cost-effective and user-friendly. In this study, we have combined a number of methods to develop an accurate, robust and cost efficient method to determine allele frequencies in large populations for association studies. The assay offers the advantage of minimal systemic sampling errors, uses a general biotin amplification approach, and replaces dTTP for dATP-apha-thio to avoid non-uniform higher peaks in order to increase accuracy. We demonstrate that this newly developed assay is a robust, cost-effective, accurate and reproducible approach for large-scale genotyping of DNA pools. We also discuss potential improvements of the software for more accurate allele frequency analysis. PMID:18628978

  7. 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

  8. Cost-effective genome-wide estimation of allele frequencies from pooled DNA in Atlantic salmon (Salmo salar L.)

    PubMed Central

    2013-01-01

    Background New sequencing technologies have tremendously increased the number of known molecular markers (single nucleotide polymorphisms; SNPs) in a variety of species. Concurrently, improvements to genotyping technology have now made it possible to efficiently genotype large numbers of genome-wide distributed SNPs enabling genome wide association studies (GWAS). However, genotyping significant numbers of individuals with large number of SNPs remains prohibitively expensive for many research groups. A possible solution to this problem is to determine allele frequencies from pooled DNA samples, such ‘allelotyping’ has been presented as a cost-effective alternative to individual genotyping and has become popular in human GWAS. In this article we have tested the effectiveness of DNA pooling to obtain accurate allele frequency estimates for Atlantic salmon (Salmo salar L.) populations using an Illumina SNP-chip. Results In total, 56 Atlantic salmon DNA pools from 14 populations were analyzed on an Atlantic salmon SNP-chip containing probes for 5568 SNP markers, 3928 of which were bi-allelic. We developed an efficient quality control filter which enables exclusion of loci showing high error rate and minor allele frequency (MAF) close to zero. After applying multiple quality control filters we obtained allele frequency estimates for 3631 bi-allelic loci. We observed high concordance (r > 0.99) between allele frequency estimates derived from individual genotyping and DNA pools. Our results also indicate that even relatively small DNA pools (35 individuals) can provide accurate allele frequency estimates for a given sample. Conclusions Despite of higher level of variation associated with array replicates compared to pool construction, we suggest that both sources of variation should be taken into account. This study demonstrates that DNA pooling allows fast and high-throughput determination of allele frequencies in Atlantic salmon enabling cost

  9. MHC allele frequency distributions under parasite-driven selection: A simulation model

    PubMed Central

    2010-01-01

    Background The extreme polymorphism that is observed in major histocompatibility complex (MHC) genes, which code for proteins involved in recognition of non-self oligopeptides, is thought to result from a pressure exerted by parasites because parasite antigens are more likely to be recognized by MHC heterozygotes (heterozygote advantage) and/or by rare MHC alleles (negative frequency-dependent selection). The Ewens-Watterson test (EW) is often used to detect selection acting on MHC genes over the recent history of a population. EW is based on the expectation that allele frequencies under balancing selection should be more even than under neutrality. We used computer simulations to investigate whether this expectation holds for selection exerted by parasites on host MHC genes under conditions of heterozygote advantage and negative frequency-dependent selection acting either simultaneously or separately. Results In agreement with simple models of symmetrical overdominance, we found that heterozygote advantage acting alone in populations does, indeed, result in more even allele frequency distributions than expected under neutrality, and this is easily detectable by EW. However, under negative frequency-dependent selection, or under the joint action of negative frequency-dependent selection and heterozygote advantage, distributions of allele frequencies were less predictable: the majority of distributions were indistinguishable from neutral expectations, while the remaining runs resulted in either more even or more skewed distributions than under neutrality. Conclusions Our results indicate that, as long as negative frequency-dependent selection is an important force maintaining MHC variation, the EW test has limited utility in detecting selection acting on these genes. PMID:20979635

  10. Frequency of Bt resistance alleles in H. armigera during 2006-2008 in Northern China.

    PubMed

    Gao, Yulin; Wu, Kongming; Gould, Fred

    2009-08-01

    Helicoverpa armigera is an important lepidopteran pest of cotton in China. From 2002, the frequency of Bt resistance alleles and quantitative shifts in larval Cry1Ac tolerance of field H. armigera population were monitored using bioassays of F(1) and F(2) offspring of isofemale lines from Xiajin County of Shandong Province (an intensive Bt cotton planting area) and Anci County of Hebei Province (a multiple-crop system including corn, soybean, peanut, and Bt cotton) in northern China. During 2006-2008, a total of 2,306 isofemale lines from the Xiajin population and a total of 1,270 isofemale lines from the Anci population were successfully screened on Cry1Ac diets. For each year, it was estimated that the major resistance gene frequency in Xiajin population in 2006, 2007, and 2008 was 0, 0.00022, and 0.00033, respectively. No major alleles conferring resistance to Cry1Ac were found in the Anci population; the frequency of resistance alleles for Cry1Ac was 0. Based on the relative average development rates (RADRs) of H. armigera larvae in F(1) tests, no substantial increase in Cry1Ac tolerance was found in either location over the 3-yr period. There were also significantly positive correlations between RADR of lines in the F(1) generation and the RADR of their F(2) offspring, indicating genetic variation in response to toxin. The low frequency of resistance alleles found in this study and in our previous results from 2002 to 2005 suggest the frequency of resistance alleles has remained low and that natural refugia resistance management strategy maybe effective for delaying resistance evolution in H. armigera to Bt cotton in northern China. PMID:19689916

  11. 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. PMID:19261522

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

    ERIC Educational Resources Information Center

    Nussbaum, Francis, Jr.

    1988-01-01

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

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

    PubMed

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

    2012-01-01

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

  14. GST M1-T1 null Allele Frequency Patterns in Geographically Assorted Human Populations: A Phylogenetic Approach

    PubMed Central

    Ramasamy, Thirumurugan; Ayyavoo, Jayachitra

    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. PMID:25867025

  15. 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. PMID:25867025

  16. Microsatellite allele frequencies in humans and chimpanzees, with implications for constraints on allele size.

    PubMed

    Garza, J C; Slatkin, M; Freimer, N B

    1995-07-01

    The distributions of allele sizes at eight simple-sequence repeat (SSR) or microsatellite loci in chimpanzees are found and compared with the distributions previously obtained from several human populations. At several loci, the differences in average allele size between chimpanzees and humans are sufficiently small that there might be a constraint on the evolution of average allele size. Furthermore, a model that allows for a bias in the mutation process shows that for some loci a weak bias can account for the observations. Several alleles at one of the loci (Mfd 59) were sequenced. Differences between alleles of different lengths were found to be more complex than previously assumed. An 8-base-pair deletion was present in the nonvariable region of the chimpanzee locus. This locus contains a previously unrecognized repeated region, which is imperfect in humans and perfect in chimpanzees. The apparently greater opportunity for mutation conferred by the two perfect repeat regions in chimpanzees is reflected in the higher variance in repeat number at Mfd 59 in chimpanzees than in humans. These data indicate that interspecific differences in allele length are not always attributable to simple changes in the number of repeats. PMID:7659015

  17. 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. PMID:27236516

  18. Population based allele frequencies of disease associated polymorphisms in the Personalized Medicine Research Project

    PubMed Central

    2010-01-01

    Background There is a lack of knowledge regarding the frequency of disease associated polymorphisms in populations and population attributable risk for many populations remains unknown. Factors that could affect the association of the allele with disease, either positively or negatively, such as race, ethnicity, and gender, may not be possible to determine without population based allele frequencies. Here we used a panel of 51 polymorphisms previously associated with at least one disease and determined the allele frequencies within the entire Personalized Medicine Research Project population based cohort. We compared these allele frequencies to those in dbSNP and other data sources stratified by race. Differences in allele frequencies between self reported race, region of origin, and sex were determined. Results There were 19544 individuals who self reported a single racial category, 19027 or (97.4%) self reported white Caucasian, and 11205 (57.3%) individuals were female. Of the 11,208 (57%) individuals with an identifiable region of origin 8337 or (74.4%) were German. 41 polymorphisms were significantly different between self reported race at the 0.05 level. Stratification of our Caucasian population by self reported region of origin revealed 19 polymorphisms that were significantly different (p = 0.05) between individuals of different origins. Further stratification of the population by gender revealed few significant differences in allele frequencies between the genders. Conclusions This represents one of the largest population based allele frequency studies to date. Stratification by self reported race and region of origin revealed wide differences in allele frequencies not only by race but also by region of origin within a single racial group. We report allele frequencies for our Asian/Hmong and American Indian populations; these two minority groups are not typically selected for population allele frequency detection. Population wide allele frequencies are

  19. HLA-G allele and haplotype frequencies in a healthy population of Iran.

    PubMed

    Kuroshli, Zahra; Gourabi, Hamid; Bazrgar, Masoud; Sanati, Mohammad Hossein; Bahraminejad, Elmira; Anisi, Khadije

    2014-06-01

    The human leukocyte antigen (HLA)-G molecule is expressed in cytotrophoblast cells, adult thymic epithelial cells, erythroblasts, pancreatic islets and mesenchymal stem cells. Although, HLA-G expression in allotransplanted patients is correlated with a better allograft acceptance, it is associated with an advanced grade of the tumor in cancer. In addition to the role on the immune system, HLA-G is also involved in successful pregnancy through the embryo implantation, fetal survival and the initial steps of hematopoiesis and angiogenesis. The aim of this study was determination of HLA-G allele frequencies in a healthy population of Iran. In this research, we selected 100 samples from healthy Iranian individuals and henceforth, we used polymerase chain reaction (PCR) followed by sequencing technique for exon 2, 3, 4 and intron 2 of the gene for evaluating the HLA-G alleles frequencies. Investigation of intronic (intron 2) variation is the novelty of our study. The obtained results indicated thirteen alleles of HLA-G in Iranian individuals including G*01:01:01:01, G*01:06, G*01:01:01:06, G*01:01:02, G*01:01:03, G*01:01:05, G*01:01:06, G*01:01:07, G*01:01:08, G*01:03, G*01:04:01, G*01:04:03, and G*01:04:04. According to this study, the most prevalent alleles in the Iranian population were G*01:01:01:01 (52.5%), G*01:01:02 (16%) and G*01:04:03 (14.5%) and also the lowest alleles regarding the frequency were G*01:01:01:06 (0.5%) and G*01:03 (0.5%). The results of G*01:01:01:01 and G*01:04:01 frequencies showed some similarities with the polish population. Our results were similar to the north Indian population for the frequencies of G*01:06 and G*01:01:02. PMID:24659125

  20. 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).

  1. Functional Allelic Variation at Key Photoperiod Response QTL in Maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. On the Bayesness, minimaxity and admissibility of point estimators of allelic frequencies.

    PubMed

    Martínez, Carlos Alberto; Khare, Kshitij; Elzo, Mauricio A

    2015-10-21

    In this paper, decision theory was used to derive Bayes and minimax decision rules to estimate allelic frequencies and to explore their admissibility. Decision rules with uniformly smallest risk usually do not exist and one approach to solve this problem is to use the Bayes principle and the minimax principle to find decision rules satisfying some general optimality criterion based on their risk functions. Two cases were considered, the simpler case of biallelic loci and the more complex case of multiallelic loci. For each locus, the sampling model was a multinomial distribution and the prior was a Beta (biallelic case) or a Dirichlet (multiallelic case) distribution. Three loss functions were considered: squared error loss (SEL), Kulback-Leibler loss (KLL) and quadratic error loss (QEL). Bayes estimators were derived under these three loss functions and were subsequently used to find minimax estimators using results from decision theory. The Bayes estimators obtained from SEL and KLL turned out to be the same. Under certain conditions, the Bayes estimator derived from QEL led to an admissible minimax estimator (which was also equal to the maximum likelihood estimator). The SEL also allowed finding admissible minimax estimators. Some estimators had uniformly smaller variance than the MLE and under suitable conditions the remaining estimators also satisfied this property. In addition to their statistical properties, the estimators derived here allow variation in allelic frequencies, which is closer to the reality of finite populations exposed to evolutionary forces. PMID:26271891

  3. Minor Allele Frequency Changes the Nature of Genotype by Environment Interactions.

    PubMed

    Verhulst, Brad; Neale, Michael C

    2016-09-01

    In the classical twin study, phenotypic variation is often partitioned into additive genetic (A), common (C) and specific environment (E) components. From genetical theory, the outcome of genotype by environment interaction is expected to inflate A when the interacting factor is shared (i.e., C) between the members of a twin pair. We show that estimates of both A and C can be inflated. When the shared interacting factor changes the size of the difference between homozygotes' means, the expected sibling or DZ twin correlation is .5 if and only if the minor allele frequency (MAF) is .5; otherwise the expected DZ correlation is greater than this value, consistent (and confounded) with some additional effect of C. This result is considered in the light of the distribution of minor allele frequencies for polygenic traits. Also discussed is whether such interactions take place at the locus level or affect an aggregated biological structure or system. Interactions with structures or endophenotypes that result from the aggregated effects of many loci will generally emerge as part of the A estimate. PMID:27105628

  4. 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...

  5. Linkage disequilibrium in the insulin gene region: Size variation at the 5{prime} flanking polymorphism and bimodality among {open_quotes}Class I{close_quotes} alleles

    SciTech Connect

    McGinnis, R.E.; Spielman, R.S.

    1994-09-01

    The 5{prime} flanking polymorphism (5{prime}FP), a hypervariable region at the 5{prime} end of the insulin gene, has {open_quotes}class 1{close_quotes} alleles (650-900 bp long) that are in positive linkage disequilibrium with insulin-dependent diabetes mellitus (IDDM). The authors report that precise sizing of the 5{prime}FP yields a bimodal frequency distribution of class 1 allele lengths. Class 1 alleles belonging to the lower component (650-750 bp) of the bimodal distribution were somewhat more highly associated with IDDM than were alleles from the upper component (760-900 bp), but the difference was not statistically significant. They also examined 5{prime}FP length variation in relation to allelic variation at nearby polymorphisms. At biallelic RFLPs on both sides of the 5{prime}FP, they found that one allele exhibits near-total association with the upper component of the 5FP class 1 distribution. Such associations represent a little-known but potentially wide-spread form of linkage disequilibrium. In this type of disequilibrium, a flanking allele has near-complete association with a single mode of VNTR alleles whose lengths represent consecutive numbers of tandem repeats (CNTR). Such extreme disequilibrium between a CNTR mode and flanking alleles may originate and persist because length mutations at some VNTR loci usually add or delete only one or two repeat units. 22 refs., 5 figs., 6 tabs.

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

    PubMed

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

    2012-05-01

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

  7. HLA-B27 allele frequency in Sri Lankan patients with spondyloarthritides.

    PubMed

    Kidnapillai, S; Sirisena, N D; Dissanayake, V H

    2016-06-01

    This preliminary study aims to describe the HLA-B27 allele frequency in Sri Lankan patients with spondyloarthritides (SA). An anonymised database of 373 Sri Lankan patients with SA referred for HLA-B27 testing was retrospectively analysed. Eighty five (22.8%) patients were positive for the HLA-B27 allele. A male preponderance was observed among the positives. The HLA-B27 allele frequency in this sample of patients with SA was relatively low compared to published studies in other populations. Further research is needed to identify the predominant subtypes of the allele to determine which subtypes are the most prevalent in a larger sample of Sri Lankan patients with SA, and to define their association with the specific types of SA. PMID:27423748

  8. 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 ...

  9. PoMo: An Allele Frequency-Based Approach for Species Tree Estimation

    PubMed Central

    De Maio, Nicola; Schrempf, Dominik; Kosiol, Carolin

    2015-01-01

    Incomplete lineage sorting can cause incongruencies of the overall species-level phylogenetic tree with the phylogenetic trees for individual genes or genomic segments. If these incongruencies are not accounted for, it is possible to incur several biases in species tree estimation. Here, we present a simple maximum likelihood approach that accounts for ancestral variation and incomplete lineage sorting. We use a POlymorphisms-aware phylogenetic MOdel (PoMo) that we have recently shown to efficiently estimate mutation rates and fixation biases from within and between-species variation data. We extend this model to perform efficient estimation of species trees. We test the performance of PoMo in several different scenarios of incomplete lineage sorting using simulations and compare it with existing methods both in accuracy and computational speed. In contrast to other approaches, our model does not use coalescent theory but is allele frequency based. We show that PoMo is well suited for genome-wide species tree estimation and that on such data it is more accurate than previous approaches. PMID:26209413

  10. Accounting for genotype uncertainty in the estimation of allele frequencies in autopolyploids.

    PubMed

    Blischak, Paul D; Kubatko, Laura S; Wolfe, Andrea D

    2016-05-01

    Despite the increasing opportunity to collect large-scale data sets for population genomic analyses, the use of high-throughput sequencing to study populations of polyploids has seen little application. This is due in large part to problems associated with determining allele copy number in the genotypes of polyploid individuals (allelic dosage uncertainty-ADU), which complicates the calculation of important quantities such as allele frequencies. Here, we describe a statistical model to estimate biallelic SNP frequencies in a population of autopolyploids using high-throughput sequencing data in the form of read counts. We bridge the gap from data collection (using restriction enzyme based techniques [e.g. GBS, RADseq]) to allele frequency estimation in a unified inferential framework using a hierarchical Bayesian model to sum over genotype uncertainty. Simulated data sets were generated under various conditions for tetraploid, hexaploid and octoploid populations to evaluate the model's performance and to help guide the collection of empirical data. We also provide an implementation of our model in the R package polyfreqs and demonstrate its use with two example analyses that investigate (i) levels of expected and observed heterozygosity and (ii) model adequacy. Our simulations show that the number of individuals sampled from a population has a greater impact on estimation error than sequencing coverage. The example analyses also show that our model and software can be used to make inferences beyond the estimation of allele frequencies for autopolyploids by providing assessments of model adequacy and estimates of heterozygosity. PMID:26607217

  11. HLA Allele Frequencies in 5802 Koreans: Varied Allele Types Associated with SJS/TEN According to Culprit Drugs

    PubMed Central

    Park, Hye Jung; Kim, Young Joo; Kim, Dong Hyun; Kim, Junho; Park, Kyung Hee; Park, Jung-Won

    2016-01-01

    Purpose Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are very serious forms of drug-induced cutaneous adverse reaction. SJS/TEN induced by certain drug is well known to be associated with some human leukocyte antigen (HLA) gene type. We aimed to explore HLA allele frequencies and their association with SJS/TEN according to culprit drugs in Korea. Materials and Methods We enrolled 5802 subjects who had results of HLA typing test from August 2005 to July 2014. Total 28 SJS/TEN patients were categorized based on culprit drugs (allopurinol, lamotrigine, carbamazepine) and identified the presence of HLA-B*58:01, HLA-B*44:03, HLA-B*15:02, and HLA-A*31:01. Results HLA-A*24:02 (20.5%), HLA-B*44:03 (10.0%), and HLA-Cw*01:02 (17.1%) were the most frequent type in HLA-A, -B, and -C genes, respectively. Allele frequencies of HLA-B*58:01, HLA-B*44:03, HLA-A*31:01, and HLA-B*15:02 were 7.0%, 10.0%, 5.0%, and 0.3%, respectively. In 958 allopurinol users, 9 subjects (0.9%) were diagnosed with SJS/TEN. Among them, 8 subjects possessed HLA-B*58:01 allele. SJS/TEN induced by allopurinol was more frequently developed in subjects with HLA-B*58:01 than in subjects without it [odds ratio: 57.4; confidence interval (CI) 7.12-463.50; p<0.001]. Allopurinol treatment, based on screening by HLA-B*58:01 genotyping, could be more cost-effective than that not based on screening. HLA-B*44:03 may be associated with lamotrigine-induced SJS/TEN (odds ratio: 12.75; CI 1.03-157.14; p=0.053). Among carbamazepine users, only two patients experienced SJS/TEN and possessed neither HLA-B*15:02 nor HLA-A*31:03. Conclusion HLA gene frequencies varied in Korea. Screening of HLA-B*58:01 before the use of allopurinol might be needed to anticipate probability of SJS/TEN. PMID:26632391

  12. Dynamic variation in allele-specific gene expression of Paraoxonase-1 in murine and human tissues

    PubMed Central

    Parker-Katiraee, Layla; Bousiaki, Eleni; Monk, David; Moore, Gudrun E.; Nakabayashi, Kazuhiko; Scherer, Stephen W.

    2008-01-01

    Differential allelic expression has been shown to be common in mice, humans and maize, and variability in the expression of polymorphic alleles has been associated with human disease. Here, we describe the differential expression pattern of Paraoxonase-1, a gene involved in lipid metabolism and implicated in the formation of atherosclerotic lesions. We measured the expression of the murine Paraoxonase-1 gene (Pon1) in livers at different stages of embryonic development using F1 hybrid crosses and quantified the transcriptional level of both parental alleles. Using human foetal tissues, we analysed the expression of the human orthologue (PON1) and found monoallelic or preferential allelic expression in 6/7 and 4/4 samples from liver and pancreas, respectively. We observed that Pon1 does not show a parent-of-origin preference in its allelic expression, but has dramatic variations in allele-specific expression occurring throughout development. This study has important repercussions in the analysis of haplotypes at disease loci, since it implies that the expression of polymorphic alleles can be unequal and dynamic. PMID:18678600

  13. 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. PMID:24232128

  14. A novel fluorescent quadruplex STR typing system and the allele frequency distributions in a Thai population.

    PubMed

    Yoshimoto, Takashi; Yamamoto, Toshimichi; Mizutani, Masaki; Uchihi, Rieko; Ohtaki, Hiroyuki; Katsumata, Yoshinao; Waiyawuth, Worawee; Songsivilai, Sirirurg

    2003-01-01

    We have previously reported a new triplex amplification and typing system by silver staining for three short tandem repeat (STR) loci, 9q2h2 (D2S3020), D15S233, and D14S299 without "microvariant" alleles such as .1, .2, and, .3 alleles in the Japanese population. In the present study, we established a new quadruplex system with an additional locus D7S809 using primer sets labeled with fluorescent multi-color dyes. Using this system, we genotyped 183 Thai people, found only one "microvariant" allele (allele 20.2) at D7S809, and calculated allele frequencies and some statistical properties at these four STR loci. From these allele frequencies at four STR loci, we performed three statistical analyses including a homozygosity test, a likelihood ratio test, and an exact test for Hardy-Weinberg equilibrium (HWE). Deviations from HWE (p < 0.05) were observed only in the two tests at the locus D7S809. In the present study, we compared the allele frequencies at these four loci in the Thai population to those in the Japanese population described previously. Consequently, all observed heterozygosities and power of discrimination (PD) at those loci in the Thai population were higher than 0.8 and 0.9, respectively, and all statistical values for discriminating power in the Thai population were slightly higher than those in the Japanese population. The combined paternity exclusion rate (combined PE) in the Thai population (0.978) was almost the same as that in the Japanese population (0.971). Therefore, this novel PCR amplification and typing system for four STR loci would be a convenient and informative DNA profiling system in the forensic field. PMID:12570210

  15. 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

  16. Determination of permethrin resistance allele frequency of human head louse populations by quantitative sequencing.

    PubMed

    Kwon, Deok Ho; Yoon, Kyong Sup; Strycharz, Joseph P; Clark, J Marshall; Lee, Si Hyeock

    2008-09-01

    A quantitative sequencing (QS) protocol that detects the frequencies of sodium channel mutations (M815I, T917I, and L920F) responsible for knockdown resistance in permethrin-resistant head lice (Pediculus humanus capitis De Geer) was tested as a population genotyping method for use as a preliminary resistance monitoring tool. Genomic DNA fragments of the sodium channel a-subunit gene that encompass the three mutation sites were polymerase chain reaction (PCR)-1 amplified from individual head lice with either resistant or susceptible genotypes, and combined in various ratios to generate standard DNA template mixtures for QS. After sequencing, the signal ratios between resistant and susceptible nucleotides were calculated and plotted against the corresponding resistance allele frequencies. Quadratic regression coefficients of the plots were close to 1, demonstrating that the signal ratios are highly correlated with the resistance allele frequencies. Resistance allele frequencies predicted by QS, using either "pooled DNA" (DNA extracted from individual louse specimens and pooled) or "pooled specimen DNA" (DNA simultaneously extracted from multiple louse specimens), agreed well with those determined by individual sequencing, confirming the reliability and accuracy of QS as a population genotyping method and validating our approach of using the pooled specimen DNA as the DNA template for QS. Our protocol for QS was determined to be highly reliable for the prediction of resistance allele frequencies higher than approximately 7.4% at the 95% confidence level. According to the resistance allele frequencies determined by QS, pyrethroid resistance varies substantially among different geographical regions, emphasizing the importance of early resistance detection and proper management strategies. PMID:18826035

  17. Frequency of CCR5Δ32 allele in healthy Bosniak population

    PubMed Central

    Adler, Grażyna; Valjevac, Amina; Skonieczna-Żydecka, Karolina; Mackic-Djurovic, Mirela; Parczewski, Miłosz; Urbańska, Anna; Salkic, Nermin N

    2014-01-01

    Recent evidence has demonstrated the role of CCR5Δ32 in a variety of human diseases: from infectious and inflammatory diseases to cancer. Several studies have confirmed that genetic variants in chemokine receptor CCR5 gene are correlated with susceptibility and resistance to HIV infection. A 32-nucleotide deletion within the CCR5 reading frame is associated with decreased susceptibility to HIV acquisition and a slower progression to AIDS. Mean frequency of CCR5Δ32 allele in Europe is approximately 10%. The highest allele frequency is observed among Nordic populations (about 12%) and the lowest in the regions of Southeast Mediterranean (about 5%). Although the frequency of CCR5Δ32 was determined in numerous European populations, there is a lack of studies on this variant in the Bosnia and Herzegovina population. Therefore, the aim of our study was to assess the frequency of CCR5Δ32 allele in the cohort of Bosniaks and compare the results with European reports. CCR5Δ32 was detected by sequence-specific PCR in a sample of 100 healthy Bosniaks (DNA collected 2011-2013). Mean age of the cohort being 58.8 (±10.7) years, with 82% of women. We identified 17 heterozygotes and one mutant homozygote in study group, with mean ∆32 allele frequency of 9.5%. CCR5∆32 allele frequency among Bosniaks is comparable to that found in Caucasian populations and follows the pattern of the north-southern gradient observed for Europe. Further studies on larger cohorts with adequate female-to-male ratio are necessary. PMID:25172974

  18. Genotype and allelic frequencies of a newly identified mutation causing blindness in jordanian awassi sheep flocks.

    PubMed

    Jawasreh, K I Z; Ababneh, H; Awawdeh, F T; Al-Massad, M A; Al-Majali, A M

    2012-01-01

    A total of 423 blood samples were collected (during 2009 and 2010) from all the ram holdings at three major Jordanian governmental Awassi breeding stations (Al-Khanasry, Al-Mushairfa and Al-Fjaje) and two private flocks. All blood samples were screened for the presence of mutations at the CNGA3 gene (responsible for day blindness in Awassi sheep) using RFLP-PCR. The day blindness mutation was detected in all studied flocks. The overall allele and genotype frequencies of all studied flocks of the day blindness mutation were 0.088 and 17.49%, respectively. The genotype and allele frequencies were higher in station flocks than the farmer flocks (0.121, 24.15 and 0.012, 2.32, respectively). Al-Mushairfa and Al-Khanasry stations have the highest genotype and allele frequencies for the day blindness mutation that were 27.77, 30.00% and 0.14, 0.171, respectively. The investigated farmer flocks have low percentages (0.03, 5.88% at Al-Shoubak and 0.005 and 1.05%, at Al-Karak, respectively for genotype and allele frequencies) compared with the breeding stations. Ram culling strategy was applied throughout the genotyping period in order to gradually eradicate this newly identified day blindness mutation from Jordanian Breeding station, since they annually distribute a high percentage of improved rams to farmer's flocks. PMID:25049475

  19. Genotype and Allelic Frequencies of a Newly Identified Mutation Causing Blindness in Jordanian Awassi Sheep Flocks

    PubMed Central

    Jawasreh, K. I. Z.; Ababneh, H.; Awawdeh, F. T.; Al-Massad, M. A.; Al-Majali, A. M.

    2012-01-01

    A total of 423 blood samples were collected (during 2009 and 2010) from all the ram holdings at three major Jordanian governmental Awassi breeding stations (Al-Khanasry, Al-Mushairfa and Al-Fjaje) and two private flocks. All blood samples were screened for the presence of mutations at the CNGA3 gene (responsible for day blindness in Awassi sheep) using RFLP-PCR. The day blindness mutation was detected in all studied flocks. The overall allele and genotype frequencies of all studied flocks of the day blindness mutation were 0.088 and 17.49%, respectively. The genotype and allele frequencies were higher in station flocks than the farmer flocks (0.121, 24.15 and 0.012, 2.32, respectively). Al-Mushairfa and Al-Khanasry stations have the highest genotype and allele frequencies for the day blindness mutation that were 27.77, 30.00% and 0.14, 0.171, respectively. The investigated farmer flocks have low percentages (0.03, 5.88% at Al-Shoubak and 0.005 and 1.05%, at Al-Karak, respectively for genotype and allele frequencies) compared with the breeding stations. Ram culling strategy was applied throughout the genotyping period in order to gradually eradicate this newly identified day blindness mutation from Jordanian Breeding station, since they annually distribute a high percentage of improved rams to farmer’s flocks. PMID:25049475

  20. Variation in lipoprotein(a) concentration associated with different apolipoprotein(a) alleles.

    PubMed Central

    Perombelon, Y F; Soutar, A K; Knight, B L

    1994-01-01

    Plasma lipoprotein(a) (Lp(a)) concentrations vary considerably between individuals. To examine the variation for products of the same and different apolipoprotein(a) (apo(a)) alleles, conditions were established whereby phenotyping immunoblots could be used to estimate the concentration of Lp(a) associated with the constituent apo(a) isoforms. In these studies 28 distinct isoforms were identified, each differing by a single kringle IV unit. Tracking the isoforms through 10 families showed that there could be up to 200-fold difference in the Lp(a) concentration associated with the same-sized isoform produced from different alleles. In contrast there was typically < 2.5-fold variation in the Lp(a) concentration associated with the same allele. However, there were four occasions where the concentration associated with a particular allele was reduced below the typical range from one generation to the next. A nonlinear, inverse trend with isoform size was apparently superimposed upon the other factors that determine Lp(a) concentration. Inheritance of familial hypercholesterolemia or familial-defective apoB100 had little consistent effect upon Lp(a) concentration. In both the families and in other unrelated individuals the distribution of isoforms and their associated concentrations provided evidence for the presence of at least two and possibly more subpopulations of apo(a) alleles with different sizes and expression. Images PMID:8163653

  1. Validation of SNP Allele Frequencies Determined by Pooled Next-Generation Sequencing in Natural Populations of a Non-Model Plant Species

    PubMed Central

    Rellstab, Christian; Zoller, Stefan; Tedder, Andrew; Gugerli, Felix; Fischer, Martin C.

    2013-01-01

    Sequencing of pooled samples (Pool-Seq) using next-generation sequencing technologies has become increasingly popular, because it represents a rapid and cost-effective method to determine allele frequencies for single nucleotide polymorphisms (SNPs) in population pools. Validation of allele frequencies determined by Pool-Seq has been attempted using an individual genotyping approach, but these studies tend to use samples from existing model organism databases or DNA stores, and do not validate a realistic setup for sampling natural populations. Here we used pyrosequencing to validate allele frequencies determined by Pool-Seq in three natural populations of Arabidopsis halleri (Brassicaceae). The allele frequency estimates of the pooled population samples (consisting of 20 individual plant DNA samples) were determined after mapping Illumina reads to (i) the publicly available, high-quality reference genome of a closely related species (Arabidopsis thaliana) and (ii) our own de novo draft genome assembly of A. halleri. We then pyrosequenced nine selected SNPs using the same individuals from each population, resulting in a total of 540 samples. Our results show a highly significant and accurate relationship between pooled and individually determined allele frequencies, irrespective of the reference genome used. Allele frequencies differed on average by less than 4%. There was no tendency that either the Pool-Seq or the individual-based approach resulted in higher or lower estimates of allele frequencies. Moreover, the rather high coverage in the mapping to the two reference genomes, ranging from 55 to 284x, had no significant effect on the accuracy of the Pool-Seq. A resampling analysis showed that only very low coverage values (below 10-20x) would substantially reduce the precision of the method. We therefore conclude that a pooled re-sequencing approach is well suited for analyses of genetic variation in natural populations. PMID:24244686

  2. Natural allelic variations of xenobiotic-metabolizing enzymes affect sexual dimorphism in Oryzias latipes

    PubMed Central

    Katsumura, Takafumi; Oda, Shoji; Nakagome, Shigeki; Hanihara, Tsunehiko; Kataoka, Hiroshi; Mitani, Hiroshi; Kawamura, Shoji; Oota, Hiroki

    2014-01-01

    Sexual dimorphisms, which are phenotypic differences between males and females, are driven by sexual selection. Interestingly, sexually selected traits show geographical variations within species despite strong directional selective pressures. This paradox has eluded many evolutionary biologists for some time, and several models have been proposed (e.g. ‘indicator model’ and ‘trade-off model’). However, disentangling which of these theories explains empirical patterns remains difficult, because genetic polymorphisms that cause variation in sexual differences are still unknown. In this study, we show that polymorphisms in cytochrome P450 (CYP) 1B1, which encodes a xenobiotic-metabolizing enzyme, are associated with geographical differences in sexual dimorphism in the anal fin morphology of medaka fish (Oryzias latipes). Biochemical assays and genetic cross experiments show that high- and low-activity CYP1B1 alleles enhanced and declined sex differences in anal fin shapes, respectively. Behavioural and phylogenetic analyses suggest maintenance of the high-activity allele by sexual selection, whereas the low-activity allele possibly has experienced positive selection due to by-product effects of CYP1B1 in inferred ancestral populations. The present data can elucidate evolutionary mechanisms behind genetic variations in sexual dimorphism and indicate trade-off interactions between two distinct mechanisms acting on the two alleles with pleiotropic effects of xenobiotic-metabolizing enzymes. PMID:25377463

  3. HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies of 10 918 Koreans from bone marrow donor registry in Korea.

    PubMed

    Park, H; Lee, Y-J; Song, E Y; Park, M H

    2016-10-01

    The human leucocyte antigen (HLA) system is the most polymorphic genetic system in humans, and HLA matching is crucial in organ transplantation, especially in hematopoietic stem cell transplantation. We investigated HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies at allelic level in 10 918 Koreans from bone marrow donor registry in Korea. Intermediate resolution HLA typing was performed using Luminex technology (Wakunaga, Japan), and additional allelic level typing was performed using PCR-single-strand conformation polymorphism method and/or sequence-based typing (Abbott Molecular, USA). Allele and haplotype frequencies were calculated by direct counting and maximum likelihood methods, respectively. A total of 39 HLA-A, 66 HLA-B and 47 HLA-DRB1 alleles were identified. High-frequency alleles found at a frequency of ≥5% were 6 HLA-A (A*02:01, *02:06, *11:01, *24:02, *31:01 and *33:03), 6 HLA-B (B*15:01, *35:01, *44:03, *51:01, 54:01 and *58:01) and 8 HLA-DRB1 (DRB1*01:01, *04:05, *04:06, *07:01, *08:03, *09:01, *13:02 and *15:01) alleles. At each locus, A*02, B*15 and DRB1*14 generic groups were most diverse at allelic level, consisting of 9, 12 and 11 different alleles, respectively. A total of 366, 197 and 21 different HLA-A-B-DRB1 haplotypes were estimated with frequencies of ≥0.05%, ≥0.1% and ≥0.5%, respectively. The five most common haplotypes with frequencies of ≥2.0% were A*33:03-B*44:03-DRB1*13:02 (4.97%), A*33:03-B*58:01-DRB1*13:02, A*33:03-B*44:03-DRB1*07:01, A*24:02-B*07:02-DRB1*01:01 and A*24:02-B*52:01-DRB1*15:02. Among 34 serologic HLA-A-B-DR haplotypes with frequencies of ≥0.5%, 17 haplotypes revealed allele-level diversity and majority of the allelic variation was arising from A2, A26, B61, B62, DR4 and DR14 specificities. Haplotype diversity obtained in this study is the most comprehensive data thus far reported in Koreans, and the information will be useful for unrelated stem cell transplantation as well as for disease

  4. DNA-PKcs mutations in dogs and horses: allele frequency and association with neoplasia.

    PubMed

    Ding, Qi; Bramble, Lori; Yuzbasiyan-Gurkan, Vilma; Bell, Thomas; Meek, Katheryn

    2002-01-23

    Previously, spontaneous genetic immunodeficiencies in mice, Arabian foals, and recently in Jack Russell terriers have been ascribed to defects in DNA-PKcs (catalytic subunit of the DNA dependent protein kinase) expression. In severe combined immunodeficiency (SCID) foals, a 5 bp deletion at codon 9480 results in a frameshift and a 967 amino acid deletion from the C terminus (including the entire PI3 kinase domain) and an unstable mutant protein. In SCID mice, a single base pair mutation results in a premature stop codon and deletion of 83 amino acids; as in SCID foals, the mutant protein is unstable. Here, we define the mutation within the canine DNA-PKcs gene that results in SCID. In this case, a point mutation results in a stop codon at nucleotide 10,828 and premature termination at a position 517 amino acids before the normal C terminus resulting in a functionally null allele. Thus, this is the third documentation of a spontaneous germline mutation in the C terminus of DNA-PKcs. Emerging data implicate DNA repair factors as potential tumor suppressors. Here, we have ascertained the carrier frequency of the defective DNA-PKcs genes in Arabian horses and in Jack Russell terriers. Our data indicate (in good agreement with a previous report) that the carrier frequency of the equine SCID allele is approximately 8%; in contrast, the carrier frequency of the canine SCID allele is less than 1.1%. We also assessed the frequency of the equine SCID allele in a series of 295 tumors from Arabian horses. We find a statistically significant correlation between the development of a virally induced tumor (sarcoid) and heterozygosity for the equine SCID allele. These data provide further support for an emerging consensus: that DNA-PK may normally act as a tumor suppressor through its caretaker role in maintaining chromosomal stability. PMID:11867233

  5. 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

  6. Polymorphism discovery and allele frequency estimation using high-throughput DNA sequencing of target-enriched pooled DNA samples

    PubMed Central

    2012-01-01

    Background The central role of the somatotrophic axis in animal post-natal growth, development and fertility is well established. Therefore, the identification of genetic variants affecting quantitative traits within this axis is an attractive goal. However, large sample numbers are a pre-requisite for the identification of genetic variants underlying complex traits and although technologies are improving rapidly, high-throughput sequencing of large numbers of complete individual genomes remains prohibitively expensive. Therefore using a pooled DNA approach coupled with target enrichment and high-throughput sequencing, the aim of this study was to identify polymorphisms and estimate allele frequency differences across 83 candidate genes of the somatotrophic axis, in 150 Holstein-Friesian dairy bulls divided into two groups divergent for genetic merit for fertility. Results In total, 4,135 SNPs and 893 indels were identified during the resequencing of the 83 candidate genes. Nineteen percent (n = 952) of variants were located within 5' and 3' UTRs. Seventy-two percent (n = 3,612) were intronic and 9% (n = 464) were exonic, including 65 indels and 236 SNPs resulting in non-synonymous substitutions (NSS). Significant (P < 0.01) mean allele frequency differentials between the low and high fertility groups were observed for 720 SNPs (58 NSS). Allele frequencies for 43 of the SNPs were also determined by genotyping the 150 individual animals (Sequenom® MassARRAY). No significant differences (P > 0.1) were observed between the two methods for any of the 43 SNPs across both pools (i.e., 86 tests in total). Conclusions The results of the current study support previous findings of the use of DNA sample pooling and high-throughput sequencing as a viable strategy for polymorphism discovery and allele frequency estimation. Using this approach we have characterised the genetic variation within genes of the somatotrophic axis and related pathways, central to mammalian post

  7. 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

  8. 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

  9. 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

  10. 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. PMID:26517173

  11. Allele Frequencies Net Database: Improvements for storage of individual genotypes and analysis of existing data.

    PubMed

    Dos Santos, Eduardo Jose Melos; McCabe, Antony; Gonzalez-Galarza, Faviel F; Jones, Andrew R; Middleton, Derek

    2016-03-01

    The Allele Frequencies Net Database (AFND) is a freely accessible database which stores population frequencies for alleles or genes of the immune system in worldwide populations. Herein we introduce two new tools. We have defined new classifications of data (gold, silver and bronze) to assist users in identifying the most suitable populations for their tasks. The gold standard datasets are defined by allele frequencies summing to 1, sample sizes >50 and high resolution genotyping, while silver standard datasets do not meet gold standard genotyping resolution and/or sample size criteria. The bronze standard datasets are those that could not be classified under the silver or gold standards. The gold standard includes >500 datasets covering over 3 million individuals from >100 countries at one or more of the following loci: HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1 and -DRB1 - with all loci except DPA1 present in more than 220 datasets. Three out of 12 geographic regions have low representation (the majority of their countries having less than five datasets) and the Central Asia region has no representation. There are 18 countries that are not represented by any gold standard datasets but are represented by at least one dataset that is either silver or bronze standard. We also briefly summarize the data held by AFND for KIR genes, alleles and their ligands. Our second new component is a data submission tool to assist users in the collection of the genotypes of the individuals (raw data), facilitating submission of short population reports to Human Immunology, as well as simplifying the submission of population demographics and frequency data. PMID:26585775

  12. 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

    2016-03-01

    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

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

    PubMed Central

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

  14. 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.

  15. Allelic variation in CRHR1 predisposes to panic disorder: evidence for biased fear processing.

    PubMed

    Weber, H; Richter, J; Straube, B; Lueken, U; Domschke, K; Schartner, C; Klauke, B; Baumann, C; Pané-Farré, C; Jacob, C P; Scholz, C-J; Zwanzger, P; Lang, T; Fehm, L; Jansen, A; Konrad, C; Fydrich, T; Wittmann, A; Pfleiderer, B; Ströhle, A; Gerlach, A L; Alpers, G W; Arolt, V; Pauli, P; Wittchen, H-U; Kent, L; Hamm, A; Kircher, T; Deckert, J; Reif, A

    2016-06-01

    Corticotropin-releasing hormone (CRH) is a major regulator of the hypothalamic-pituitary-adrenal axis. Binding to its receptor CRHR1 triggers the downstream release of the stress response-regulating hormone cortisol. Biochemical, behavioral and genetic studies revealed CRHR1 as a possible candidate gene for mood and anxiety disorders. Here we aimed to evaluate CRHR1 as a risk factor for panic disorder (PD). Allelic variation of CRHR1 was captured by 9 single-nucleotide polymorphisms (SNPs), which were genotyped in 531 matched case/control pairs. Four SNPs were found to be associated with PD, in at least one sub-sample. The minor allele of rs17689918 was found to significantly increase risk for PD in females after Bonferroni correction and furthermore decreased CRHR1 mRNA expression in human forebrains and amygdalae. When investigating neural correlates underlying this association in patients with PD using functional magnetic resonance imaging, risk allele carriers of rs17689918 showed aberrant differential conditioning predominantly in the bilateral prefrontal cortex and safety signal processing in the amygdalae, arguing for predominant generalization of fear and hence anxious apprehension. Additionally, the risk allele of rs17689918 led to less flight behavior during fear-provoking situations but rather increased anxious apprehension and went along with increased anxiety sensitivity. Thus reduced gene expression driven by CRHR1 risk allele leads to a phenotype characterized by fear sensitization and hence sustained fear. These results strengthen the role of CRHR1 in PD and clarify the mechanisms by which genetic variation in CRHR1 is linked to this disorder. PMID:26324098

  16. Detection of Allelic Frequency Differences between the Sexes in Humans: A Signature of Sexually Antagonistic Selection.

    PubMed

    Lucotte, Elise A; Laurent, Romain; Heyer, Evelyne; Ségurel, Laure; Toupance, Bruno

    2016-01-01

    Sexually antagonistic (SA) selection, a form of selection that can occur when both sexes have different fitness optima for a trait, is a major force shaping the evolution of organisms. A seminal model developed by Rice (Rice WR. 1984. Sex chromosomes and the evolution of sexual dimorphism. Evolution 38:735-742.) predicts that the X chromosome should be a hotspot for the accumulation of loci under SA selection as compared with the autosomes. Here, we propose a methodological framework designed to detect a specific signature of SA selection on viability, differences in allelic frequencies between the sexes. Applying this method on genome-wide single nucleotide polymorphism (SNP) data in human populations where no sex-specific population stratification could be detected, we show that there are overall significantly more SNPs exhibiting differences in allelic frequencies between the sexes on the X chromosome as compared with autosomes, supporting the predictions of Rice's model. This pattern is consistent across populations and is robust to correction for potential biases such as differences in linkage disequilibrium, sample size, and genotyping errors between chromosomes. Although SA selection is not the only factor resulting in allelic frequency differences between the sexes, we further show that at least part of the identified X-linked loci is caused by such a sex-specific processes. PMID:27189992

  17. Detection of Allelic Frequency Differences between the Sexes in Humans: A Signature of Sexually Antagonistic Selection

    PubMed Central

    Lucotte, Elise A.; Laurent, Romain; Heyer, Evelyne; Ségurel, Laure; Toupance, Bruno

    2016-01-01

    Sexually antagonistic (SA) selection, a form of selection that can occur when both sexes have different fitness optima for a trait, is a major force shaping the evolution of organisms. A seminal model developed by Rice (Rice WR. 1984. Sex chromosomes and the evolution of sexual dimorphism. Evolution 38:735–742.) predicts that the X chromosome should be a hotspot for the accumulation of loci under SA selection as compared with the autosomes. Here, we propose a methodological framework designed to detect a specific signature of SA selection on viability, differences in allelic frequencies between the sexes. Applying this method on genome-wide single nucleotide polymorphism (SNP) data in human populations where no sex-specific population stratification could be detected, we show that there are overall significantly more SNPs exhibiting differences in allelic frequencies between the sexes on the X chromosome as compared with autosomes, supporting the predictions of Rice’s model. This pattern is consistent across populations and is robust to correction for potential biases such as differences in linkage disequilibrium, sample size, and genotyping errors between chromosomes. Although SA selection is not the only factor resulting in allelic frequency differences between the sexes, we further show that at least part of the identified X-linked loci is caused by such a sex-specific processes. PMID:27189992

  18. Association of ABO Blood Group Phenotype and Allele Frequency with Chikungunya Fever

    PubMed Central

    Rujirojindakul, Pairaya; Chongsuvivatwong, Virasakdi; Limprasert, Pornprot

    2015-01-01

    Background. The objective of this study was to investigate the association of the ABO blood group phenotype and allele frequency with CHIK fever. Methods. A rural community survey in Southern Thailand was conducted in August and September 2010. A total of 506 villagers were enrolled. Cases were defined as individuals having anti-CHIK IgG by hemagglutination ≥1 : 10. Results. There were 314 cases (62.1%) with CHIK seropositivity. Females were less likely to have positive anti-CHIK IgG with odds ratio (OR) (95% CI) of 0.63 (0.43, 0.93). All samples tested were Rh positive. Distribution of CHIK seropositivity versus seronegativity (P value) in A, B, AB, and O blood groups was 80 versus 46 (0.003), 80 versus 48 (0.005), 24 versus 20 (0.55), and 130 versus 78 (<0.001), respectively. However, chi-square test between ABO and CHIK infection showed no statistical significance (P = 0.76). Comparison of the ABO blood group allele frequency between CHIK seropositivity and seronegativity was not statistically significant. Conclusion. This finding demonstrated no association of the ABO blood group phenotypes and allele frequencies with CHIK infection. PMID:25977691

  19. Estimation of population allele frequencies from next-generation sequencing data: pool-versus individual-based genotyping.

    PubMed

    Gautier, Mathieu; Foucaud, Julien; Gharbi, Karim; Cézard, Timothée; Galan, Maxime; Loiseau, Anne; Thomson, Marian; Pudlo, Pierre; Kerdelhué, Carole; Estoup, Arnaud

    2013-07-01

    Molecular markers produced by next-generation sequencing (NGS) technologies are revolutionizing genetic research. However, the costs of analysing large numbers of individual genomes remain prohibitive for most population genetics studies. Here, we present results based on mathematical derivations showing that, under many realistic experimental designs, NGS of DNA pools from diploid individuals allows to estimate the allele frequencies at single nucleotide polymorphisms (SNPs) with at least the same accuracy as individual-based analyses, for considerably lower library construction and sequencing efforts. These findings remain true when taking into account the possibility of substantially unequal contributions of each individual to the final pool of sequence reads. We propose the intuitive notion of effective pool size to account for unequal pooling and derive a Bayesian hierarchical model to estimate this parameter directly from the data. We provide a user-friendly application assessing the accuracy of allele frequency estimation from both pool- and individual-based NGS population data under various sampling, sequencing depth and experimental error designs. We illustrate our findings with theoretical examples and real data sets corresponding to SNP loci obtained using restriction site-associated DNA (RAD) sequencing in pool- and individual-based experiments carried out on the same population of the pine processionary moth (Thaumetopoea pityocampa). NGS of DNA pools might not be optimal for all types of studies but provides a cost-effective approach for estimating allele frequencies for very large numbers of SNPs. It thus allows comparison of genome-wide patterns of genetic variation for large numbers of individuals in multiple populations. PMID:23730833

  20. The Serotonin Transporter Polymorphism (5-HTTLPR): Allelic Variation and Links with Depressive Symptoms

    PubMed Central

    Goldman, Noreen; Glei, Dana A.; Lin, Yu-Hsuan; Weinstein, Maxine

    2009-01-01

    Background We compare the genotype distribution for the serotonin transporter polymorphism (5-HTTLPR) in a sample of older Taiwanese adults with samples of various racial and ethnic groups collected in other studies. We also explore interactions among sex, stressors, and 5-HTTLPR genotype on depressive symptoms in our sample. Methods Using a nationally-representative sample of 984 Taiwanese aged 53 and older, we model depressive symptoms as a function of 5-HTTLPR genotype and two classes of stressors: lifetime trauma and recent major life events. We test two- and three-way interactions among stressors, 5 HTTLPR, and sex. Results This sample exhibits higher frequency of S/S and lower frequency of L/L genotype than Western samples, but the distribution is comparable to those in East Asian populations. Nearly 9% carry an allele (XL) that has rarely been reported in the literature. Although the gene-environment (GxE) interaction with recent major life events is not significant, our results suggest that trauma has a worse effect on depressive symptoms for those with S/S or S/L genotype than for those who do not carry the S allele (p<0.05). We find no evidence that this GxE interaction varies by sex. Conclusions Previous studies of this GxE interaction have been inconclusive, perhaps because interactions between genotype and stressful events are more prominent under extreme stressors. Our findings underscore the need to move beyond a bi-allelic parameterization of the 5-HTTLPR polymorphism and raise questions about why East Asian populations exhibit low rates of depression despite a high frequency of the S allele. PMID:20196101

  1. Combining allele frequency uncertainty and population substructure corrections in forensic DNA calculations.

    PubMed

    Cowell, Robert

    2016-07-01

    In forensic DNA calculations of relatedness of individuals and in DNA mixture analyses, at least two sources of uncertainty are present concerning the allele frequencies used for evaluating genotype probabilities when evaluating likelihoods. They are: (i) imprecision in the estimates of the allele frequencies in the population by using an inevitably finite database of DNA profiles to estimate them; and (ii) the existence of population substructure. Green and Mortera [6] showed that these effects may be taken into account individually using a common Dirichlet model within a Bayesian network formulation, but that when taken in combination this is not the case; however they suggested an approximation that could be used. Here we develop a slightly different approximation that is shown to be exact in the case of a single individual. We demonstrate the numerical closeness of the approximation using a published database of allele counts, and illustrate the effect of incorporating the approximation into calculations of a recently published statistical model of DNA mixtures. PMID:27231804

  2. ACTN3 Allele Frequency in Humans Covaries with Global Latitudinal Gradient

    PubMed Central

    Lek, Monkol; North, Kathryn N.; Organ, Chris L.

    2013-01-01

    A premature stop codon in ACTN3 resulting in α-actinin-3 deficiency (the ACTN3 577XX genotype) is common in humans and reduces strength, muscle mass, and fast-twitch fiber diameter, but increases the metabolic efficiency of skeletal muscle. Linkage disequilibrium data suggest that the ACTN3 R577X allele has undergone positive selection during human evolution. The allele has been hypothesized to be adaptive in environments with scarce resources where efficient muscle metabolism would be selected. Here we test this hypothesis by using recently developed comparative methods that account for evolutionary relatedness and gene flow among populations. We find evidence that the ACTN3 577XX genotype evolved in association with the global latitudinal gradient. Our results suggest that environmental variables related to latitudinal variation, such as species richness and mean annual temperature, may have influenced the adaptive evolution of ACTN3 577XX during recent human history. PMID:23359641

  3. Microarray-based estimation of SNP allele-frequency in pooled DNA using the Langmuir kinetic model

    PubMed Central

    Yin, Bin-Cheng; Li, Honghua; Ye, Bang-Ce

    2008-01-01

    Background High throughput genotyping of single nucleotide polymorphisms (SNPs) for genome-wide association requires technologies for generating millions of genotypes with relative ease but also at a reasonable cost and with high accuracy. In this work, we have developed a theoretical approach to estimate allele frequency in pooled DNA samples, based on the physical principles of DNA immobilization and hybridization on solid surface using the Langmuir kinetic model and quantitative analysis of the allelic signals. Results This method can successfully distinguish allele frequencies differing by 0.01 in the actual pool of clinical samples, and detect alleles with a frequency as low as 2%. The accuracy of measuring known allele frequencies is very high, with the strength of correlation between measured and actual frequencies having an r2 = 0.9992. These results demonstrated that this method could allow the accurate estimation of absolute allele frequencies in pooled samples of DNA in a feasible and inexpensive way. Conclusion We conclude that this novel strategy for quantitative analysis of the ratio of SNP allelic sequences in DNA pools is an inexpensive and feasible alternative for detecting polymorphic differences in candidate gene association studies and genome-wide linkage disequilibrium scans. PMID:19087310

  4. 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

  5. Allelic variation at a single gene increases food value in a drought-tolerant staple cereal.

    PubMed

    Gilding, Edward K; Frère, Celine H; Cruickshank, Alan; Rada, Anna K; Prentis, Peter J; Mudge, Agnieszka M; Mace, Emma S; Jordan, David R; Godwin, Ian D

    2013-01-01

    The production of adequate agricultural outputs to support the growing human population places great demands on agriculture, especially in light of ever-greater restrictions on input resources. Sorghum is a drought-adapted cereal capable of reliable production where other cereals fail, and thus represents a good candidate to address food security as agricultural inputs of water and arable land grow scarce. A long-standing issue with sorghum grain is that it has an inherently lower digestibility. Here we show that a low-frequency allele type in the starch metabolic gene, pullulanase, is associated with increased digestibility, regardless of genotypic background. We also provide evidence that the beneficial allele type is not associated with deleterious pleiotropic effects in the modern field environment. We argue that increasing the digestibility of an adapted crop is a viable way forward towards addressing food security while maximizing water and land-use efficiency. PMID:23403584

  6. A Chromosomal Rearrangement Hotspot Can Be Identified from Population Genetic Variation and Is Coincident with a Hotspot for Allelic Recombination

    PubMed Central

    Lindsay, Sarah J.; Khajavi, Mehrdad; Lupski, James R.; Hurles, Matthew E.

    2006-01-01

    Insights into the origins of structural variation and the mutational mechanisms underlying genomic disorders would be greatly improved by a genomewide map of hotspots of nonallelic homologous recombination (NAHR). Moreover, our understanding of sequence variation within the duplicated sequences that are substrates for NAHR lags far behind that of sequence variation within the single-copy portion of the genome. Perhaps the best-characterized NAHR hotspot lies within the 24-kb-long Charcot-Marie-Tooth disease type 1A (CMT1A)–repeats (REPs) that sponsor deletions and duplications that cause peripheral neuropathies. We investigated structural and sequence diversity within the CMT1A-REPs, both within and between species. We discovered a high frequency of retroelement insertions, accelerated sequence evolution after duplication, extensive paralogous gene conversion, and a greater than twofold enrichment of SNPs in humans relative to the genome average. We identified an allelic recombination hotspot underlying the known NAHR hotspot, which suggests that the two processes are intimately related. Finally, we used our data to develop a novel method for inferring the location of an NAHR hotspot from sequence variation within segmental duplications and applied it to identify a putative NAHR hotspot within the LCR22 repeats that sponsor velocardiofacial syndrome deletions. We propose that a large-scale project to map sequence variation within segmental duplications would reveal a wealth of novel chromosomal-rearrangement hotspots. PMID:17033965

  7. Hardy-Weinberg equilibrium revisited for inferences on genotypes featuring allele and copy-number variations.

    PubMed

    Recke, Andreas; Recke, Klaus-Günther; Ibrahim, Saleh; Möller, Steffen; Vonthein, Reinhard

    2015-01-01

    Copy number variations represent a substantial source of genetic variation and are associated with a plethora of physiological and pathophysiological conditions. Joint copy number and allelic variations (CNAVs) are difficult to analyze and require new strategies to unravel the properties of genotype distributions. We developed a Bayesian hidden Markov model (HMM) approach that allows dissecting intrinsic properties and metastructures of the distribution of CNAVs within populations, in particular haplotype phases of genes with varying copy numbers. As a key feature, this approach incorporates an extension of the Hardy-Weinberg equilibrium, allowing both a comprehensive and parsimonious model design. We demonstrate the quality of performance and applicability of the HMM approach with a real data set describing the Fcγ receptor (FcγR) gene region. Our concept, using a dynamic process to analyze a static distribution, establishes the basis for a novel understanding of complex genomic data sets. PMID:25765626

  8. Hardy-Weinberg equilibrium revisited for inferences on genotypes featuring allele and copy-number variations

    PubMed Central

    Recke, Andreas; Recke, Klaus-Günther; Ibrahim, Saleh; Möller, Steffen; Vonthein, Reinhard

    2015-01-01

    Copy number variations represent a substantial source of genetic variation and are associated with a plethora of physiological and pathophysiological conditions. Joint copy number and allelic variations (CNAVs) are difficult to analyze and require new strategies to unravel the properties of genotype distributions. We developed a Bayesian hidden Markov model (HMM) approach that allows dissecting intrinsic properties and metastructures of the distribution of CNAVs within populations, in particular haplotype phases of genes with varying copy numbers. As a key feature, this approach incorporates an extension of the Hardy-Weinberg equilibrium, allowing both a comprehensive and parsimonious model design. We demonstrate the quality of performance and applicability of the HMM approach with a real data set describing the Fcγ receptor (FcγR) gene region. Our concept, using a dynamic process to analyze a static distribution, establishes the basis for a novel understanding of complex genomic data sets. PMID:25765626

  9. Variant mapping of the Apo(B) AT rich minisatellite. Dependence on nucleotide sequence of the copy number variations. Instability of the non-canonical alleles.

    PubMed Central

    Desmarais, E; Vigneron, S; Buresi, C; Cambien, F; Cambou, J P; Roizes, G

    1993-01-01

    Because of its variations in length, the AT rich Hyper-Variable Region (HVR) of the 3' end of the Apolipoprotein B gene is used as a polymorphic maker in genetic studies. It contains a SspI site in its repeated motif and we used this feature to precisely analyse the internal structure of the different alleles found at this locus in a Caucasian population. We performed total digestion on 194 alleles as well as Minisatellite Variant Repeat mapping (MVR mapping: partial digestion) on 54. The results show that the level of length variability (in copy number) of the 5' end of this locus is at least two times higher than that of the 3' end. This could be correlated with the difference in nucleotide sequence between the two parts of the HVR and suggests the dependence on the primary structure of the mechanism that produces length variability. A molecular model is proposed to explain this result. Moreover, the sharp analysis of the minisatellite structure by the distribution of SspI sites reveals differences between long and short alleles, indicating that in most cases, no recombination occurs between alleles of different sizes. Finally the rare alleles exhibit a non-canonical structure. These important points could explain the bimodal distribution of the frequencies of the alleles in the population. Images PMID:8502559

  10. Frequency and characterization of known and novel RHD variant alleles in 37 782 Dutch D-negative pregnant women.

    PubMed

    Stegmann, Tamara C; Veldhuisen, Barbera; Bijman, Renate; Thurik, Florentine F; Bossers, Bernadette; Cheroutre, Goedele; Jonkers, Remco; Ligthart, Peter; de Haas, Masja; Haer-Wigman, Lonneke; van der Schoot, C Ellen

    2016-05-01

    To guide anti-D prophylaxis, Dutch D- pregnant women are offered a quantitative fetal-RHD-genotyping assay to determine the RHD status of their fetus. This allowed us to determine the frequency of different maternal RHD variants in 37 782 serologically D- pregnant women. A variant allele is present in at least 0·96% of Dutch D- pregnant women The D- serology could be confirmed after further serological testing in only 54% of these women, which emphasizes the potential relevance of genotyping of blood donors. 43 different RHD variant alleles were detected, including 15 novel alleles (11 null-, 2 partial D- and 2 DEL-alleles). Of those novel null alleles, one allele contained a single missense mutation (RHD*443C>G) and one allele had a single amino acid deletion (RHD*424_426del). The D- phenotype was confirmed by transduction of human D- erythroblasts, consolidating that, for the first time, a single amino acid change or deletion causes the D- phenotype. Transduction also confirmed the phenotypes for the two new variant DEL-alleles (RHD*721A>C and RHD*884T>C) and the novel partial RHD*492C>A allele. Notably, in three additional cases the DEL phenotype was observed but sequencing of the coding sequence, flanking introns and promoter region revealed an apparently wild-type RHD allele without mutations. PMID:27018217

  11. Relationship between allozymes, heterozygosity and morphological characters in red deer (Cervus elaphus), and the influence of selective hunting on allele frequency distribution.

    PubMed

    Hartl, G B; Lang, G; Klein, F; Willing, R

    1991-06-01

    Morphological characters in red deer (Cervus elaphus), which serve as criteria for selective hunting, were examined in relation to electrophoretic variation in three populations from the Vosges in eastern France. From the polymorphic loci examined, certain alleles at Idh-2, Me-1 and Acp-1 showed significant associations with a special development of body and antler characters selected for by hunters. Idh-2(125) was associated with larger hind foot length in females and a higher number of antler points in males. Me-1(90) and Acp-1(100) were associated with small spikes. The populations studied differed from one another in the duration and intensity of selective hunting and the increase or decrease in the respective allele frequencies could be explained by selection for large body size, a high number of antler points and against small spikes in yearlings, rather than by genetic drift. Among other morphological characters examined, the length of the main beam was significantly associated with the allele Acp-2(100). In contrast, no associations could be detected between overall heterozygosity and the development or the degree of asymmetry (in paired structures) of any of the morphological traits in question. Although no obvious differences in the overall values of polymorphism or heterozygosity were found between the populations, selective hunting leads towards a change in allele frequencies and eventually to the loss of one or the other rare allele. PMID:1880046

  12. Natural variation involving deletion alleles of FRIGIDA modulate temperature-sensitive flowering responses in Arabidopsis thaliana.

    PubMed

    Sanchez-Bermejo, Eduardo; Balasubramanian, Sureshkumar

    2016-06-01

    Ambient temperature is one of the major environmental factors that modulate plant growth and development. There is extensive natural genetic variation in thermal responses of plants exemplified by the variation exhibited by the accessions of Arabidopsis thaliana. In this work we have studied the enhanced temperature response in hypocotyl elongation and flowering shown by the Tsu-0 accession in long days. Genetic mapping in the Col-0 × Tsu-0 recombinant inbred line (RIL) population identified several QTLs for thermal response including three major effect loci encompassing candidate genes FRIGIDA (FRI), FLOWERING LOCUS C (FLC) and FLOWERING LOCUS T (FT). We confirm and validate these QTLs. We show that the Tsu-0 FRI allele, which is the same as FRI-Ler is associated with late flowering but only at lower temperatures in long days. Using transgenic lines and accessions, we show that the FRI-Ler allele confers temperature-sensitive late flowering confirming a role for FRI in photoperiod-dependent thermal response. Through quantitative complementation with heterogeneous inbred families, we further show that cis-regulatory variation at FT contributes to the observed hypersensitivity of Tsu-0 to ambient temperature. Overall our results suggest that multiple loci that interact epistatically govern photoperiod-dependent thermal responses of A. thaliana. PMID:26662639

  13. Semantic Web-based integration of cancer pathways and allele frequency data.

    PubMed

    Holford, Matthew E; Rajeevan, Haseena; Zhao, Hongyu; Kidd, Kenneth K; Cheung, Kei-Hoi

    2009-01-01

    We demonstrate the use of Semantic Web technology to integrate the ALFRED allele frequency database and the Starpath pathway resource. The linking of population-specific genotype data with cancer-related pathway data is potentially useful given the growing interest in personalized medicine and the exploitation of pathway knowledge for cancer drug discovery. We model our data using the Web Ontology Language (OWL), drawing upon ideas from existing standard formats BioPAX for pathway data and PML for allele frequency data. We store our data within an Oracle database, using Oracle Semantic Technologies. We then query the data using Oracle's rule-based inference engine and SPARQL-like RDF query language. The ability to perform queries across the domains of population genetics and pathways offers the potential to answer a number of cancer-related research questions. Among the possibilities is the ability to identify genetic variants which are associated with cancer pathways and whose frequency varies significantly between ethnic groups. This sort of information could be useful for designing clinical studies and for providing background data in personalized medicine. It could also assist with the interpretation of genetic analysis results such as those from genome-wide association studies. PMID:19458791

  14. Semantic Web-Based Integration of Cancer Pathways and Allele Frequency Data

    PubMed Central

    Holford, Matthew E.; Rajeevan, Haseena; Zhao, Hongyu; Kidd, Kenneth K.; Cheung, Kei-Hoi

    2009-01-01

    We demonstrate the use of Semantic Web technology to integrate the ALFRED allele frequency database and the Starpath pathway resource. The linking of population-specific genotype data with cancer-related pathway data is potentially useful given the growing interest in personalized medicine and the exploitation of pathway knowledge for cancer drug discovery. We model our data using the Web Ontology Language (OWL), drawing upon ideas from existing standard formats BioPAX for pathway data and PML for allele frequency data. We store our data within an Oracle database, using Oracle Semantic Technologies. We then query the data using Oracle’s rule-based inference engine and SPARQL-like RDF query language. The ability to perform queries across the domains of population genetics and pathways offers the potential to answer a number of cancer-related research questions. Among the possibilities is the ability to identify genetic variants which are associated with cancer pathways and whose frequency varies significantly between ethnic groups. This sort of information could be useful for designing clinical studies and for providing background data in personalized medicine. It could also assist with the interpretation of genetic analysis results such as those from genome-wide association studies. PMID:19458791

  15. The Equilibrium Allele Frequency Distribution for a Population with Reproductive Skew

    PubMed Central

    Der, Ricky; Plotkin, Joshua B.

    2014-01-01

    We study the population genetics of two neutral alleles under reversible mutation in a model that features a skewed offspring distribution, called the Λ-Fleming–Viot process. We describe the shape of the equilibrium allele frequency distribution as a function of the model parameters. We show that the mutation rates can be uniquely identified from this equilibrium distribution, but the form of the offspring distribution cannot itself always be so identified. We introduce an estimator for the mutation rate that is consistent, independent of the form of reproductive skew. We also introduce a two-allele infinite-sites version of the Λ-Fleming–Viot process, and we use it to study how reproductive skew influences standing genetic diversity in a population. We derive asymptotic formulas for the expected number of segregating sites as a function of sample size and offspring distribution. We find that the Wright–Fisher model minimizes the equilibrium genetic diversity, for a given mutation rate and variance effective population size, compared to all other Λ-processes. PMID:24473932

  16. Allele frequency distribution of 13 X-chromosomal STR loci in Pakistani population.

    PubMed

    Tariq, Muhammad Akram; Ullah, Obaid; Riazuddin, S Amer; Riazuddin, Sheikh

    2008-11-01

    Short tandem repeat (STR) markers are extensively being used for human identification as well as paternity and forensic case work. X-chromosome STR (X-STR) markers are a powerful complementary system especially in deficiency paternity testing. Many X-linked microsatellites have been evaluated but further studies are required to determine population specific statistics. Here, we report allele frequencies of 13 X-linked microsatellites (DXS8378, DXS9902, DXS6810, DXS7132, DXS981, DXS6793, DXS6801, DXS6789, GATA172D05, HPRTB, GATA31E08, DXS8377, and DXS7423) in the Pakistani population. Blood samples were collected from individuals representing all major ethnic groups of the Pakistan population. A total of 5-18 alleles were observed for each locus and altogether 109 alleles for all 13 X-STR loci. Heterozygosity in females ranged from 0.524 to 0.884. No significant deviation was observed from Hardy-Weinberg equilibrium for all 13 microsatellites. In addition, there was no evidence of linkage disequilibrium in any pairs of these markers. These results strongly suggest that the X-linked microsatellites described here can potentially serve as an extension to autosomal systems currently used in parentage analysis and forensic case work. PMID:18629532

  17. 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

  18. Genotyping of infectious laryngotracheitis virus using allelic variations from multiple genomic regions.

    PubMed

    Choi, Eun-Jung; La, Tae-Min; Choi, In-Soo; Song, Chang-Seon; Park, Seung-Yong; Lee, Joong-Bok; Lee, Sang-Won

    2016-08-01

    Live attenuated vaccines are extensively used worldwide to control the outbreak of infectious laryngotracheitis. Virulent field strains showing close genetic relationship with the infectious laryngotracheitis virus (ILTV) vaccines of chicken embryo origin have been detected in the poultry industry. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, a reliable molecular epidemiological method, of multiple genomic regions was performed. The PCR-RFLP is a time-consuming method that requires considerable amount of intact viral genomic DNA to amplify genomic regions greater than 4 kb. In this study, six variable genomic regions were selected and amplified for sequencing. The multi-allelic PCR-sequence genotyping showed better discrimination power than that of previous PCR-sequencing schemes using single or two target regions. The allelic variation patterns yielded 16 strains of ILTV classified into 14 different genotypes. Three Korean field strains, 550/05/Ko, 0010/05/Ko and 40032/08/Ko, were found to have the same genotype as the commercial vaccine strain, Laryngo Vac (Zoetis, Florham Park, NJ, USA). Three other Korean field strains, 40798/10/Ko, 12/07/Ko, and 30678/14/Ko, showed recombined allelic patterns. The multi-allelic PCR-sequencing method was proved to be an efficient and practical procedure to classify the different strains of ILTV. The method could serve as an alternate diagnostic and differentiating tool for the classification of ILTV, and contribute to understanding of the epidemiology of the disease at a global level. PMID:26956802

  19. 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.

  20. Effects of allelic variations in starch synthesis-related genes on grain quality traits of Korean nonglutinous rice varieties under different temperature conditions

    PubMed Central

    Mo, Young-Jun; Jeung, Ji-Ung; Shin, Woon-Chul; Kim, Ki-Young; Ye, Changrong; Redoña, Edilberto D.; Kim, Bo-Kyeong

    2014-01-01

    Influences of allelic variations in starch synthesis-related genes (SSRGs) on rice grain quality were examined. A total of 187 nonglutinous Korean rice varieties, consisting of 170 Japonica and 17 Tongil-type varieties, were grown in the field and in two greenhouse conditions. The percentages of head rice and chalky grains, amylose content, alkali digestion value, and rapid visco-analysis characteristics were evaluated in the three different environments. Among the 10 previously reported SSRG markers used in this study, seven were polymorphic, and four of those showed subspecies-specific allele distributions. Six out of the seven polymorphic SSRG markers were significantly associated with at least one grain quality trait (R2 > 0.1) across the three different environments. However, the association level and significance were markedly lower when the analysis was repeated using only the 170 Japonica varieties. Similarly, the significant associations between SSRG allelic variations and changes in grain quality traits under increased temperature were largely attributable to the biased allele frequency between the two subpopulations. Our results suggest that within Korean Japonica varieties, these 10 major SSRG loci have been highly fixed during breeding history and variations in grain quality traits might be influenced by other genetic factors. PMID:24987303

  1. A Generalized Approach for Estimating Effective Population Size from Temporal Changes in Allele Frequency

    PubMed Central

    Waples, R. S.

    1989-01-01

    The temporal method for estimating effective population size (N(e)) from the standardized variance in allele frequency change (F) is presented in a generalized form. Whereas previous treatments of this method have adopted rather limiting assumptions, the present analysis shows that the temporal method is generally applicable to a wide variety of organisms. Use of a revised model of gene sampling permits a more generalized interpretation of N(e) than that used by some other authors studying this method. It is shown that two sampling plans (individuals for genetic analysis taken before or after reproduction) whose differences have been stressed by previous authors can be treated in a uniform way. Computer simulations using a wide variety of initial conditions show that different formulas for computing F have much less effect on N(e) than do sample size (S), number of generations between samples (t), or the number of loci studied (L). Simulation results also indicate that (1) bias of F is small unless alleles with very low frequency are used; (2) precision is typically increased by about the same amount with a doubling of S, t, or L; (3) confidence intervals for N(e) computed using a χ(2) approximation are accurate and unbiased under most conditions; (4) the temporal method is best suited for use with organisms having high juvenile mortality and, perhaps, a limited effective population size. PMID:2731727

  2. Allele and genotype frequencies of metabolic genes in Native Americans from Argentina and Paraguay.

    PubMed

    Bailliet, G; Santos, M R; Alfaro, E L; Dipierri, J E; Demarchi, D A; Carnese, F R; Bianchi, N O

    2007-03-01

    Interethnic differences in the allele frequencies of CYP2D6, NAT2, GSTM1 and GSTT1 deletions have been documented for Caucasians, Asians, and Africans population. On the other hand, data on Amerindians are scanty and limited to a few populations from southern areas of South America. In this report we analyze the frequencies of 11 allele variants of CYP2D6 and 4 allele variants of NAT2 genes, and the frequency of GSTM1 and GSTT1 homozygous deleted genotypes in a sample of 90 donors representing 8 Native American populations from Argentina and Paraguay, identified as Amerindians on the basis of their geographic location, genealogical data, mitochondrial- and Y-chromosome DNA markers. For CYP2D6, 88.6% of the total allele frequency corresponded to *1, *2, *4 and *10 variants. Average frequencies for NAT2 *4, *5, *6 and *7 alleles were 51.2%, 25%, 6.1%, and 20.1%, respectively. GSTM1 deletion ranged from 20% to 66%, while GSTT1 deletion was present in four populations in less than 50%. We assume that CYP2D6 *2, *4, *10, *14; NAT2 *5, *7 alleles and GSTM1 and GSTT1 *0/*0 genotypes are founder variants brought to America by the first Asian settlers. PMID:17194620

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

    PubMed Central

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

    2014-01-01

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

  4. Temporal variation of allozyme frequencies in Aedes albifasciatus (Diptera: Culicidae) from Argentina.

    PubMed

    de Sousa, G B; Jiménez, A; Blanco, A; Gardenal, C N

    1997-12-01

    Aedes albifasciatus is a floodwater mosquito widely distributed in Argentina. It is important from economic and medical points of view. A 4-year survey of seasonal variation in allele frequencies in a population of this species was undertaken to determine possible changes in the genetic structure and their correlation with environmental conditions. Significant temporal variation was detected at most of the loci, but it did not follow a cyclic or seasonal pattern. Multivariate analysis of principal components showed a remarkable homogeneity of samples collected from December 1993 to April 1995 and a clear differentiation of the November 1991, March 1992, and November 1993 samples. This variation could be correlated with the magnitude of rainfall occurring in the area. Passive transport of larvae by water streams and river freshets produced by floods would have mixed larvae from breeding sites with different allele frequencies, causing the genetic differentiation observed. PMID:9559091

  5. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector.

    PubMed

    Ibrahim, Sulaiman S; Riveron, Jacob M; Bibby, Jaclyn; Irving, Helen; Yunta, Cristina; Paine, Mark J I; Wondji, Charles S

    2015-10-01

    Scale up of Long Lasting Insecticide Nets (LLINs) has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethroid resistance in the major African malaria vector Anopheles funestus and detected key mutations controlling this resistance. An Africa-wide polymorphism analysis of the duplicated genes CYP6P9a and CYP6P9b revealed that both genes are directionally selected with alleles segregating according to resistance phenotypes. Modelling and docking simulations predicted that resistant alleles were better metabolizers of pyrethroids than susceptible alleles. Metabolism assays performed with recombinant enzymes of various alleles confirmed that alleles from resistant mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression in Drosophila showed that flies expressing resistant alleles of both genes were significantly more resistant to pyrethroids compared with those expressing the susceptible alleles, indicating that allelic variation is the key resistance mechanism. Furthermore, site-directed mutagenesis and functional analyses demonstrated that three amino acid changes (Val109Ile, Asp335Glu and Asn384Ser) from the resistant allele of CYP6P9b were key pyrethroid resistance mutations inducing high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of DNA-based diagnostic tools to detect and track resistance associated with bednets scale up, which will improve the design of evidence-based resistance management strategies. PMID:26517127

  6. Allelic Variation of Cytochrome P450s Drives Resistance to Bednet Insecticides in a Major Malaria Vector

    PubMed Central

    Ibrahim, Sulaiman S.; Riveron, Jacob M.; Bibby, Jaclyn; Irving, Helen; Yunta, Cristina; Paine, Mark J. I.; Wondji, Charles S.

    2015-01-01

    Scale up of Long Lasting Insecticide Nets (LLINs) has massively contributed to reduce malaria mortality across Africa. However, resistance to pyrethroid insecticides in malaria vectors threatens its continued effectiveness. Deciphering the detailed molecular basis of such resistance and designing diagnostic tools is critical to implement suitable resistance management strategies. Here, we demonstrated that allelic variation in two cytochrome P450 genes is the most important driver of pyrethroid resistance in the major African malaria vector Anopheles funestus and detected key mutations controlling this resistance. An Africa-wide polymorphism analysis of the duplicated genes CYP6P9a and CYP6P9b revealed that both genes are directionally selected with alleles segregating according to resistance phenotypes. Modelling and docking simulations predicted that resistant alleles were better metabolizers of pyrethroids than susceptible alleles. Metabolism assays performed with recombinant enzymes of various alleles confirmed that alleles from resistant mosquitoes had significantly higher activities toward pyrethroids. Additionally, transgenic expression in Drosophila showed that flies expressing resistant alleles of both genes were significantly more resistant to pyrethroids compared with those expressing the susceptible alleles, indicating that allelic variation is the key resistance mechanism. Furthermore, site-directed mutagenesis and functional analyses demonstrated that three amino acid changes (Val109Ile, Asp335Glu and Asn384Ser) from the resistant allele of CYP6P9b were key pyrethroid resistance mutations inducing high metabolic efficiency. The detection of these first DNA markers of metabolic resistance to pyrethroids allows the design of DNA-based diagnostic tools to detect and track resistance associated with bednets scale up, which will improve the design of evidence-based resistance management strategies. PMID:26517127

  7. 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. PMID:24605463

  8. 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. PMID:26596347

  9. Allelic Variation of the Capsule Promoter Diversifies Encapsulation and Virulence In Streptococcus pneumoniae

    PubMed Central

    Wen, Zhensong; Liu, Yanni; Qu, Fen; Zhang, Jing-Ren

    2016-01-01

    The polysaccharide capsule is the major virulence factor of Streptococcus pneumoniae (pneumococcus), a major human pathogen. The sequences in the promoter and coding regions of the capsule gene locus undergo extensive variations through the natural transformation-mediated horizontal gene transfer. The sequence variations in the coding region have led to at least 97 capsular serotypes. However, it remains unclear whether the sequence polymorphisms in the promoter region have any biological significance. In this study, we determined the sequences of the cps promoter region from 225 invasive pneumococcal isolates, and identified modular composition and remarkable inter-strain sequence variations in this region. The strain-to strain variations in the cps promoter are characterized by diversity in sequence and size, mosaic combinations of nucleotide polymorphisms and sequence modules, selective preservation of the sequence combinations, and promiscuous assortments of the sequences between the promoter and coding regions. Isogenic pneumococci carrying allelic variants of the cps promoter displayed significant differences in the transcription of the capsule genes, capsule production, adhesion to host epithelial cells, anti-phagocytosis and virulence in mouse bacteremia model. This study has thus indicated that the sequence polymorphisms in the cps promoter represent a novel mechanism for fine-tuning the level of encapsulation and virulence among S. pneumoniae strains. PMID:27465908

  10. Frequency of Bt resistance alleles in Helicoverpa armigera in the Xinjiang cotton-planting region of China.

    PubMed

    Li, Guoping; Feng, Hongqiang; Gao, Yulin; Wyckhuys, Kris A G; Wu, Kongming

    2010-10-01

    Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) is a key insect pest of cotton in Xinjiang cotton-planting region of northwest China. In this region, cotton is grown on average ≈ 1.65 million ha (1.53 ≈ 1.80 million ha) annually in largely monoculture agricultural landscapes, similarly to cropping systems in the United States or Australia. Under such cropping regimes, naturally occurring refuges (with non-Bt crops) may be insufficient to prevent H. armigera resistance development to Bt toxins. Therefore, we assessed frequency of alleles conferring resistance to Cry1Ac toxin of F(1) and F(2) offspring of H. armigera isofemale lines from two distinct localities in the region during 2005-2009. More specifically, a total of 224 isofemale lines was collected from Korla County (≈ 70% Bt cotton adoption) and 402 lines from Shache County (≈ 5% Bt cotton planting). Subsequent offspring was screened on Cry1Ac artificial diet. From 2005 to 2009, resistance gene frequency in Korla fluctuated between 0.0000 and 0.0040, while being 0.0000-0.0008 in individuals collected from Shache, and there were no significant increases in both counties from 2005 to 2009. Relative average development rates (RADRs) of larvae in F(1) tests showed significant increases from Korla, but not in Shache. RADR of F(1) larvae is significantly correlated with RADR of F(2) offspring, indicating genetic variation in response to toxin in field H. armigera population. Although the occurrence of Cry1Ac resistance alleles was low in Xinjiang cotton-planting region of China, particular attention should be given to H. armigera resistance development in Korla County. PMID:22546469

  11. Frequency of null allele of Human Leukocyte Antigen-G (HLA-G) locus in subjects to recurrent miscarriage

    PubMed Central

    Alizadeh, Nazila; Mosaferi, Elnaz; Farzadi, Laya; Majidi, Jafar; Monfaredan, Amir; Yousefi, Bahman; Baradaran, Behzad

    2016-01-01

    Background: Human leukocyte antigen-G (HLA-G) is a non-classical class I molecule highly expressed by extravillous cytotrophoblast cells. Due to a single base pair deletion, its function can be compensated by other isoforms. Investigating the frequency of null allele in Recurrent Miscarriage (RM) subjects could be useful in understanding the relationship between frequency of this allele and RM in a given population. Objective: This study aimed to determine the frequency of HLA-G*0105N null allele and its potential association with down-regulation of HLA-G in subjects with RM. Materials and Methods: Western blotting was used to assess the level of HLA-G protein expression. For investigating the frequency of HLA-G*0105N null allele in RM subjects, PCR-RFLP method was used. Exon 3 of HLA-G gene was amplified by polymerase chain reaction (PCR). Subsequently, PpuM-1 enzyme was employed to digest the PCR products and fragments were analyzed using gel electrophoresis. Results: Digestion using restriction enzyme showed the presence of heterozygous HLA-G*0105N null allele in 10% of the test population. Western blotting results confirmed the decrease in expression of HLA-G in the placental tissue of subjects with RM compared to subjects who could give normal birth. Conclusion: The frequency of heterozygous HLA-G*0105N null allele was high to some extent in subjects with RM. The mutation rate in subjects suggested that there is a significant association between RM and frequency of mutations in this allele. PMID:27525330

  12. 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.

  13. VEX1 controls the allelic exclusion required for antigenic variation in trypanosomes

    PubMed Central

    Glover, Lucy; Hutchinson, Sebastian; Horn, David

    2016-01-01

    Allelic exclusion underpins antigenic variation and immune evasion in African trypanosomes. These bloodstream parasites use RNA polymerase-I (pol-I) to transcribe just one telomeric variant surface glycoprotein (VSG) gene at a time, producing superabundant and switchable VSG coats. We identified trypanosome VSG exclusion-1 (VEX1) using a genetic screen for defects in telomere-exclusive expression. VEX1 was sequestered by the active VSG and silencing of other VSGs failed when VEX1 was either ectopically expressed or depleted, indicating positive and negative regulation, respectively. Positive regulation affected VSGs and nontelomeric pol-I–transcribed genes, whereas negative regulation primarily affected VSGs. Negative regulation by VEX1 also affected telomeric pol-I–transcribed reporter constructs, but only when they contained blocks of sequence sharing homology with a pol-I–transcribed locus. We conclude that restricted positive regulation due to VEX1 sequestration, combined with VEX1-dependent, possibly homology-dependent silencing, drives a “winner-takes-all” mechanism of allelic exclusion. PMID:27226299

  14. VEX1 controls the allelic exclusion required for antigenic variation in trypanosomes.

    PubMed

    Glover, Lucy; Hutchinson, Sebastian; Alsford, Sam; Horn, David

    2016-06-28

    Allelic exclusion underpins antigenic variation and immune evasion in African trypanosomes. These bloodstream parasites use RNA polymerase-I (pol-I) to transcribe just one telomeric variant surface glycoprotein (VSG) gene at a time, producing superabundant and switchable VSG coats. We identified trypanosome VSG exclusion-1 (VEX1) using a genetic screen for defects in telomere-exclusive expression. VEX1 was sequestered by the active VSG and silencing of other VSGs failed when VEX1 was either ectopically expressed or depleted, indicating positive and negative regulation, respectively. Positive regulation affected VSGs and nontelomeric pol-I-transcribed genes, whereas negative regulation primarily affected VSGs. Negative regulation by VEX1 also affected telomeric pol-I-transcribed reporter constructs, but only when they contained blocks of sequence sharing homology with a pol-I-transcribed locus. We conclude that restricted positive regulation due to VEX1 sequestration, combined with VEX1-dependent, possibly homology-dependent silencing, drives a "winner-takes-all" mechanism of allelic exclusion. PMID:27226299

  15. 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

  16. Determination of knockdown resistance allele frequencies in global human head louse populations using the serial invasive signal amplification reaction

    PubMed Central

    Hodgdon, Hilliary E.; Yoon, Kyong Sup; Previte, Domenic J.; Kim, Hyo Jeong; Aboelghar, Gamal E.; Lee, Si Hyeock; Clark, J. Marshall

    2010-01-01

    BACKGROUND Pediculosis is the most prevalent parasitic infestation of humans. Resistance to pyrethrin- and pyrethroid-based pediculicides is due to knockdown (kdr)-type point mutations in the voltage-sensitive sodium channel α-subunit gene. Early detection of resistance is crucial for the selection of effective management strategies. RESULTS Kdr allele frequencies of lice from 14 countries were determined using serial invasive signal amplification reaction. Lice collected from Uruguay, UK and Australia had kdr allele frequencies of 100% while lice from Ecuador, Papua New Guinea, South Korea and Thailand had kdr allele frequencies of 0%. The remaining 7 countries investigated, including seven US populations, two Argentina, Brazil, Denmark, Czech Republic, Egypt and Israel, displayed variable kdr allele frequencies, ranging from 11% to 97%. CONCLUSION The newly developed and validated SISAR method is suitable for accurate monitoring of kdr allele frequencies in head lice. Proactive management is needed where kdr-type resistance is not yet saturated. Based on sodium channel insensitivity and its occurrence in louse populations resistant to pyrethrin- and pyrethroid-based pediculicides, the T917I mutation appears a key marker for resistance. Results from the Egyptian population, however, indicate that phenotypic resistance of lice with single or double mutations (M815I and/or L920F) should also be determined. PMID:20564731

  17. Allelic and haplotype variation of major histocompatibility complex class II DRB1 and DQB loci in the St Lawrence beluga (Delphinapterus leucas).

    PubMed

    1999-07-01

    In order to assess levels of major histocompatibility complex (Mhc) variation within the St Lawrence beluga (Delphinapterus leucas) the variation at the beluga Mhc DRB1 class II locus was assessed by single-strand conformation polymorphism (SSCP) analysis of the peptide-binding region for 313 whales collected from 13 sampling locations across North America. In addition, samples from west Greenland and the St Lawrence were also typed at the DQB locus, allowing comparison to a previous study and assessment of linkage disequilibrium of alleles at the two loci. Comparisons of DRB1 and DQB allele frequencies among all sampling locations indicated genetic structure (alpha < 0.005). Most of this structure resulted from differences between the different wintering groups. Significant genetic structure (alpha = 0.05) exists among each pair of the following groups at both the DRB1 and DQB loci; St Lawrence, Hudson Strait, Bering Sea, Cunningham Inlet, and Davis Strait (minus Cunningham Inlet), except the St Lawrence and Hudson Strait for the DQB locus. In the St Lawrence population, six of the eight DRB1 alleles are present representing all five known allelic lineages. Evidence of linkage disequilibrium between the DRB1 and DQB is present in two sampling locations, the St Lawrence and Nuussuaq (alpha = 0.05). Analysis of probable DRB1-DQB haplotypes among groups of beluga suggests a haplotype reduction in the St Lawrence. PMID:10447854

  18. Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants.

    PubMed

    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

    2014-10-01

    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

  19. 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

  20. Population genetics of nine short tandem repeat loci: allele frequency distribution in a Brazilian population sample.

    PubMed

    Soares-Vieira, José Arnaldo; Billerbeck, Ana Elisa C; Pinto, Emília Modolo; Iwamura, Edna S M; Bilharinho de Mendonça, Berenice; Otto, Paulo A

    2002-06-01

    Gene and genotype frequencies in relation to the D3S1358, vWA, FGA, TH01, TPOX, CSF1PO, D5S818, D13S317, and D7S820 loci were determined in a sample of 290 unrelated individuals (204 Caucasians and 86 mulattoes) living in the city of São Paulo, Brazil. The sex test Amelogenin was also performed in all subjects from our sample, revealing the expected sex in all instances. Allele frequency data obtained from the analysis of these samples were in the usual range of other population groups with similar racial background. In the sample of Caucasian individuals, panmictic proportions were ruled out in relation to TPOX and CSF1PO loci, but only in the latter was the overall frequency of heterozygotes significantly less than expected. In the sample of mulattoes, Hardy-Weinberg proportions were rejected in relation to FGA and CSF1PO loci, but in no instance were the overall numbers of heterozygotes different from the corresponding expected ones under panmixia. Taking into account all this and also the number of tests performed, the degree of genetic heterogeneity of Brazilian populations, and the critical level reached by the significant results (1% < alpha<5%), the departures from panmixia here observed can be considered to be negligible in altering significantly biologic relationship odds calculated under the assumption of random matings. PMID:12040266

  1. Knockdown resistance allele frequencies in North American head louse (Anoplura: Pediculidae) populations.

    PubMed

    Yoon, Kyong Sup; Previte, Domenic J; Hodgdon, Hilliary E; Poole, Bryan C; Kwon, Deok Ho; El-Ghar, Gamal E Abo; Lee, Si Hyeock; Clark, J Marshall

    2014-03-01

    The study examines the extent and frequency of a knockdown-type resistance allele (kdr type) in North American populations of human head lice. Lice were collected from 32 locations in Canada and the United States. DNA was extracted from individual lice and used to determine their zygosity using the serial invasive signal amplification technique to detect the kdr-type T917I (TI) mutation, which is most responsible for nerve insensitivity that results in the kdr phenotype and permethrin resistance. Previously sampled sites were resampled to determine if the frequency of the TI mutation was changing. The TI frequency was also reevaluated using a quantitative sequencing method on pooled DNA samples from selected sites to validate this population genotyping method. Genotyping substantiated that TI occurs at high levels in North American lice (88.4%). Overall, the TI frequency in U.S. lice was 84.4% from 1999 to 2009, increased to 99.6% from 2007 to 2009, and was 97.1% in Canadian lice in 2008. Genotyping results using the serial invasive signal amplification reaction (99.54%) and quantitative sequencing (99.45%) techniques were highly correlated. Thus, the frequencies of TI in North American head louse populations were found to be uniformly high, which may be due to the high selection pressure from the intensive and widespread use of the pyrethrins- or pyrethroid-based pediculicides over many years, and is likely a main cause of increased pediculosis and failure of pyrethrins- or permethrin-based products in Canada and the United States. Alternative approaches to treatment of head lice infestations are critically needed. PMID:24724296

  2. Knockdown Resistance Allele Frequencies in North American Head Louse (Anoplura: Pediculidae) Populations

    PubMed Central

    Yoon, Kyong Sup; Previte, Domenic J.; Hodgdon, Hilliary E.; Poole, Bryan C.; Kwon, Deok Ho; El-Ghar, Gamal E. Abo; Lee, Si Hyeock; Clark, J. Marshall

    2014-01-01

    The study examines the extent and frequency of a knockdown-type resistance allele (kdr type) in North American populations of human head lice. Lice were collected from 32 locations in Canada and the United States. DNA was extracted from individual lice and used to determine their zygosity using the serial invasive signal amplification technique to detect the kdr-type T917I (TI) mutation, which is most responsible for nerve insensitivity that results in the kdr phenotype and permethrin resistance. Previously sampled sites were resampled to determine if the frequency of the TI mutation was changing. The TI frequency was also reevaluated using a quantitative sequencing method on pooled DNA samples from selected sites to validate this population genotyping method. Genotyping substantiated that TI occurs at high levels in North American lice (88.4%). Overall, the TI frequency in U.S. lice was 84.4% from 1999 to 2009, increased to 99.6% from 2007 to 2009, and was 97.1% in Canadian lice in 2008. Genotyping results using the serial invasive signal amplification reaction (99.54%) and quantitative sequencing (99.45%) techniques were highly correlated. Thus, the frequencies of TI in North American head louse populations were found to be uniformly high, which may be due to the high selection pressure from the intensive and widespread use of the pyrethrins- or pyrethroid-based pediculicides over many years, and is likely a main cause of increased pediculosis and failure of pyrethrins- or permethrin-based products in Canada and the United States. Alternative approaches to treatment of head lice infestations are critically needed. PMID:24724296

  3. 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

  4. Evaluation of DNA pooling for the estimation of microsatellite allele frequencies: a case study using striped bass (Morone saxatilis).

    PubMed

    Skalski, Garrick T; Couch, Charlene R; Garber, Amber F; Weir, Bruce S; Sullivan, Craig V

    2006-06-01

    Using striped bass (Morone saxatilis) and six multiplexed microsatellite markers, we evaluated procedures for estimating allele frequencies by pooling DNA from multiple individuals, a method suggested as cost-effective relative to individual genotyping. Using moment-based estimators, we estimated allele frequencies in experimental DNA pools and found that the three primary laboratory steps, DNA quantitation and pooling, PCR amplification, and electrophoresis, accounted for 23, 48, and 29%, respectively, of the technical variance of estimates in pools containing DNA from 2-24 individuals. Exact allele-frequency estimates could be made for pools of sizes 2-8, depending on the locus, by using an integer-valued estimator. Larger pools of size 12 and 24 tended to yield biased estimates; however, replicates of these estimates detected allele frequency differences among pools with different allelic compositions. We also derive an unbiased estimator of Hardy-Weinberg disequilibrium coefficients that uses multiple DNA pools and analyze the cost-efficiency of DNA pooling. DNA pooling yields the most potential cost savings when a large number of loci are employed using a large number of individuals, a situation becoming increasingly common as microsatellite loci are developed in increasing numbers of taxa. PMID:16582444

  5. Detection of MPLW515L/K Mutations and Determination of Allele Frequencies with a Single-Tube PCR Assay

    PubMed Central

    Takei, Hiraku; Morishita, Soji; Araki, Marito; Edahiro, Yoko; Sunami, Yoshitaka; Hironaka, Yumi; Noda, Naohiro; Sekiguchi, Yuji; Tsuneda, Satoshi; Ohsaka, Akimichi; Komatsu, Norio

    2014-01-01

    A gain-of-function mutation in the myeloproliferative leukemia virus (MPL) gene, which encodes the thrombopoietin receptor, has been identified in patients with essential thrombocythemia and primary myelofibrosis, subgroups of classic myeloproliferative neoplasms (MPNs). The presence of MPL gene mutations is a critical diagnostic criterion for these diseases. Here, we developed a rapid, simple, and cost-effective method of detecting two major MPL mutations, MPLW515L/K, in a single PCR assay; we termed this method DARMS (dual amplification refractory mutation system)-PCR. DARMS-PCR is designed to produce three different PCR products corresponding to MPLW515L, MPLW515K, and all MPL alleles. The amplicons are later detected and quantified using a capillary sequencer to determine the relative frequencies of the mutant and wild-type alleles. Applying DARMS-PCR to human specimens, we successfully identified MPL mutations in MPN patients, with the exception of patients bearing mutant allele frequencies below the detection limit (5%) of this method. The MPL mutant allele frequencies determined using DARMS-PCR correlated strongly with the values determined using deep sequencing. Thus, we demonstrated the potential of DARMS-PCR to detect MPL mutations and determine the allele frequencies in a timely and cost-effective manner. PMID:25144224

  6. 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

  7. Allelic frequency and genotypes of prion protein at codon 136 and 171 in Iranian Ghezel sheep breeds

    PubMed Central

    Zadeh, Reza Ashrafi; Omrani, Mir Davood; Ramezani, Fatemeh; Amniattalab, Amir

    2011-01-01

    PrP genotypes at codons 136 and 171 in 120 Iranian Ghezel sheep breeds were studied using allele-specific PCR amplification and compared with the well-known sheep breeds in North America, the United States and Europe. The frequency of V allele and VV genotype at codon 136 of Ghezel sheep breed was significantly lower than AA and AV. At codon 171, the frequency of allele H was significantly lower than Q and R. Despite the similarities of PrP genotypes at codons 136 and 171 between Iranian Ghezel sheep breeds and some of the studied breeds, significant differences were found with others. Planning of effective breeding control and successful eradication of susceptible genotypes in Iranian Ghezel sheep breeds will not be possible unless the susceptibility of various genotypes in Ghezel sheep breeds to natural or experimental scrapie has been elucidated. PMID:21778818

  8. Mapping Bias Overestimates Reference Allele Frequencies at the HLA Genes in the 1000 Genomes Project Phase I Data

    PubMed Central

    Brandt, Débora Y. C.; Aguiar, Vitor R. C.; Bitarello, Bárbara D.; Nunes, Kelly; Goudet, Jérôme; Meyer, Diogo

    2015-01-01

    Next-generation sequencing (NGS) technologies have become the standard for data generation in studies of population genomics, as the 1000 Genomes Project (1000G). However, these techniques are known to be problematic when applied to highly polymorphic genomic regions, such as the human leukocyte antigen (HLA) genes. Because accurate genotype calls and allele frequency estimations are crucial to population genomics analyses, it is important to assess the reliability of NGS data. Here, we evaluate the reliability of genotype calls and allele frequency estimates of the single-nucleotide polymorphisms (SNPs) reported by 1000G (phase I) at five HLA genes (HLA-A, -B, -C, -DRB1, and -DQB1). We take advantage of the availability of HLA Sanger sequencing of 930 of the 1092 1000G samples and use this as a gold standard to benchmark the 1000G data. We document that 18.6% of SNP genotype calls in HLA genes are incorrect and that allele frequencies are estimated with an error greater than ±0.1 at approximately 25% of the SNPs in HLA genes. We found a bias toward overestimation of reference allele frequency for the 1000G data, indicating mapping bias is an important cause of error in frequency estimation in this dataset. We provide a list of sites that have poor allele frequency estimates and discuss the outcomes of including those sites in different kinds of analyses. Because the HLA region is the most polymorphic in the human genome, our results provide insights into the challenges of using of NGS data at other genomic regions of high diversity. PMID:25787242

  9. 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...

  10. 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

  11. 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.

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

    PubMed Central

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

    2010-01-01

    AIM: Distribution of HLA class I and II alleles and haplotype was studied in Pakistani population and compared with the data reported for Caucasoid, Africans, Orientals and Arab populations. MATERIALS AND METHODS: HLA class I and II polymorphisms in 1000 unrelated Pakistani individuals was studied using sequence-specific primers and polymerase chain reaction and assay. RESULTS: The most frequent class I alleles observed were A*02, B*35 and CW*07, with frequencies of 19.2, 13.7 and 20%, respectively. Fifteen distinct HLA-DRB1 alleles and eight HLA-DQB1 alleles were recognized. The most frequently observed DRB1 alleles which represented more than 60% of the subjects were DRB1 *03, *07, *11 and *15. The rare DRB1 alleles detected in this study were HLADRB1 *08 and *09, having frequencies of 0.9 and 1.7%, respectively. In addition, at DRB1-DQB1 loci there were 179 different haplotypes and 285 unique genotypes and the most common haplotype was DRB1*15-DQB1*06 which represented 17% of the total DRB1-DQB1 haplotypes. In our population, haplotype A*33-B*58-Cw*03 comprised 2.8% of the total class I haplotypes observed. This haplotype was seen only in the oriental populations and has not been reported in the African or European Caucasoid. CONCLUSION: Our study showed a close similarity of HLA class I and II alleles with that of European Caucasoid and Orientals. In Pakistani population, two rare loci and three haplotypes were identified, whereas haplotypes characteristic of Caucasians, Africans and Orientals were also found, suggesting an admixture of different races due to migration to and from this region. PMID:21206703

  13. Impact of TP53 mutation variant allele frequency on phenotype and outcomes in myelodysplastic syndromes.

    PubMed

    Sallman, D A; Komrokji, R; Vaupel, C; Cluzeau, T; Geyer, S M; McGraw, K L; Al Ali, N H; Lancet, J; McGinniss, M J; Nahas, S; Smith, A E; Kulasekararaj, A; Mufti, G; List, A; Hall, J; Padron, E

    2016-03-01

    Although next-generation sequencing has allowed for the detection of somatic mutations in myelodysplastic syndromes (MDS), the clinical relevance of variant allele frequency (VAF) for the majority of mutations is unknown. We profiled TP53 and 20 additional genes in our training set of 219 patients with MDS or secondary acute myeloid leukemia with findings confirmed in a validation cohort. When parsed by VAF, TP53 VAF predicted for complex cytogenetics in both the training (P=0.001) and validation set (P<0.0001). MDS patients with a TP53 VAF > 40% had a median overall survival (OS) of 124 days versus an OS that was not reached in patients with VAF <20% (hazard ratio (HR), 3.52; P=0.01) with validation in an independent cohort (HR, 4.94, P=0.01). TP53 VAF further stratified distinct prognostic groups independent of clinical prognostic scoring systems (P=0.0005). In multivariate analysis, only a TP53 VAF >40% was an independent covariate (HR, 1.61; P<0.0001). In addition, SRSF2 VAF predicted for monocytosis (P=0.003), RUNX1 VAF with thrombocytopenia (P=0.01) and SF3B1 with ringed sideroblasts (P=0.001). Together, our study indicates that VAF should be incorporated in patient management and risk stratification in MDS. PMID:26514544

  14. Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies.

    PubMed Central

    Falush, Daniel; Stephens, Matthew; Pritchard, Jonathan K

    2003-01-01

    We describe extensions to the method of Pritchard et al. for inferring population structure from multilocus genotype data. Most importantly, we develop methods that allow for linkage between loci. The new model accounts for the correlations between linked loci that arise in admixed populations ("admixture linkage disequilibium"). This modification has several advantages, allowing (1) detection of admixture events farther back into the past, (2) inference of the population of origin of chromosomal regions, and (3) more accurate estimates of statistical uncertainty when linked loci are used. It is also of potential use for admixture mapping. In addition, we describe a new prior model for the allele frequencies within each population, which allows identification of subtle population subdivisions that were not detectable using the existing method. We present results applying the new methods to study admixture in African-Americans, recombination in Helicobacter pylori, and drift in populations of Drosophila melanogaster. The methods are implemented in a program, structure, version 2.0, which is available at http://pritch.bsd.uchicago.edu. PMID:12930761

  15. Inference of Population Splits and Mixtures from Genome-Wide Allele Frequency Data

    PubMed Central

    Pickrell, Joseph K.; Pritchard, Jonathan K.

    2012-01-01

    Many aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple populations. In our model, the sampled populations in a species are related to their common ancestor through a graph of ancestral populations. Using genome-wide allele frequency data and a Gaussian approximation to genetic drift, we infer the structure of this graph. We applied this method to a set of 55 human populations and a set of 82 dog breeds and wild canids. In both species, we show that a simple bifurcating tree does not fully describe the data; in contrast, we infer many migration events. While some of the migration events that we find have been detected previously, many have not. For example, in the human data, we infer that Cambodians trace approximately 16% of their ancestry to a population ancestral to other extant East Asian populations. In the dog data, we infer that both the boxer and basenji trace a considerable fraction of their ancestry (9% and 25%, respectively) to wolves subsequent to domestication and that East Asian toy breeds (the Shih Tzu and the Pekingese) result from admixture between modern toy breeds and “ancient” Asian breeds. Software implementing the model described here, called TreeMix, is available at http://treemix.googlecode.com. PMID:23166502

  16. 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. PMID:27532632

  17. High Susceptibility to Cry1Ac and Low Resistance Allele Frequency Reduce the Risk of Resistance of Helicoverpa armigers 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

  18. HLA allele and haplotype frequencies in the Albanian population and their relationship with the other European populations.

    PubMed

    Sulcebe, G; Sanchez-Mazas, A; Tiercy, J-M; Shyti, E; Mone, I; Ylli, Z; Kardhashi, V

    2009-12-01

    Human leucocyte antigen (HLA) alleles are very interesting markers in identifying population relationships. Moreover, their frequency distribution data are important in the implementation of donor-recipient registry programs for transplantation purposes and also in determining the genetic predisposition for many diseases. For these reasons, we studied the HLA class I and II allele and haplotype frequencies in 160 healthy, unrelated Albanian individuals originating from all regions of the country. The HLA genotyping was performed through a 2-digit resolution SSOP method. The data were analysed with Arlequin and Phylip programs. No deviation was found from the Hardy-Weinberg equilibrium. A total of 17 A*, 30 B*, 12 Cw*, 13 DRB1* and 5 DQB1* alleles were identified. The six most frequent HLA-A-B-DRB1 haplotypes were A*02-B*18-DRB1*11 (5.60%), A*02-B*51-DRB1*16 (4.74%), A*01-B*08-DRB1*03 (3.48%), A*24-B*35-DRB1*11 (2.77%), A*02-B*51-DRB1*13 (2.21%), A*24-B*35-DRB1*14 (1.89%). Interestingly, 12 HLA-A-B-Cw-DRB1-DQB1 haplotypes occurred at a frequency >1%. When compared with the other populations, a close relationship was found with North Greek, Bulgarian, Macedonian, Romanian, Turkish, Cretan, Serbian, Croatian and Italian populations. A higher differentiation in allele frequency level was found with Western Europe populations. These data are the first report of HLA allele and haplotype distribution in an Albanian population inside this country. When compared with other populations, their distribution frequencies show close similarities with neighbouring populations of the entire Balkan area. PMID:19703234

  19. Allelic variation in the vacuolar TPK1 channel affects its calcium dependence and may impact on stomatal conductance.

    PubMed

    Hartley, Tom N; Maathuis, Frans J M

    2016-01-01

    Natural variation can be exploited to identify allelic variants of proteins. In this study, patch clamp was used to determine transport properties of two AtTPK1 alleles from Landsberg and Kas-2 ecotypes. No difference in conductance or ion selectivity was observed but the Kas version of TPK1 showed different Ca(2+) dependence in its open probability compared to Ler. Leaves from Kas showed lower rates of water loss than those of Ler, in either the absence or presence of ABA, an observation that is consistent with higher TPK1 channel activity at comparable cytoplasmic Ca(2+) concentrations. A model that explains the results is presented. PMID:26765783

  20. 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...

  1. 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...

  2. Major-Effect Alleles at Relatively Few Loci Underlie Distinct Vernalization and Flowering Variation in Arabidopsis Accessions

    PubMed Central

    Lister, Clare; Anderson, Jillian; Warthmann, Norman; Shindo, Chikako; Irwin, Judith; Nordborg, Magnus; Dean, Caroline

    2011-01-01

    We have explored the genetic basis of variation in vernalization requirement and response in Arabidopsis accessions, selected on the basis of their phenotypic distinctiveness. Phenotyping of F2 populations in different environments, plus fine mapping, indicated possible causative genes. Our data support the identification of FRI and FLC as candidates for the major-effect QTL underlying variation in vernalization response, and identify a weak FLC allele, caused by a Mutator-like transposon, contributing to flowering time variation in two N. American accessions. They also reveal a number of additional QTL that contribute to flowering time variation after saturating vernalization. One of these was the result of expression variation at the FT locus. Overall, our data suggest that distinct phenotypic variation in the vernalization and flowering response of Arabidopsis accessions is accounted for by variation that has arisen independently at relatively few major-effect loci. PMID:21625501

  3. Inbreeding of bottlenecked butterfly populations. Estimation using the likelihood of changes in marker allele frequencies.

    PubMed Central

    Saccheri, I J; Wilson, I J; Nichols, R A; Bruford, M W; Brakefield, P M

    1999-01-01

    Polymorphic enzyme and minisatellite loci were used to estimate the degree of inbreeding in experimentally bottlenecked populations of the butterfly, Bicyclus anynana (Satyridae), three generations after founding events of 2, 6, 20, or 300 individuals, each bottleneck size being replicated at least four times. Heterozygosity fell more than expected, though not significantly so, but this traditional measure of the degree of inbreeding did not make full use of the information from genetic markers. It proved more informative to estimate directly the probability distribution of a measure of inbreeding, sigma2, the variance in the number of descendants left per gene. In all bottlenecked lines, sigma2 was significantly larger than in control lines (300 founders). We demonstrate that this excess inbreeding was brought about both by an increase in the variance of reproductive success of individuals, but also by another process. We argue that in bottlenecked lines linkage disequilibrium generated by the small number of haplotypes passing through the bottleneck resulted in hitchhiking of particular marker alleles with those haplotypes favored by selection. In control lines, linkage disequilibrium was minimal. Our result, indicating more inbreeding than expected from demographic parameters, contrasts with the findings of previous (Drosophila) experiments in which the decline in observed heterozygosity was slower than expected and attributed to associative overdominance. The different outcomes may both be explained as a consequence of linkage disequilibrium under different regimes of inbreeding. The likelihood-based method to estimate inbreeding should be of wide applicability. It was, for example, able to resolve small differences in sigma2 among replicate lines within bottleneck-size treatments, which could be related to the observed variation in reproductive viability. PMID:10049922

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

    PubMed

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

    2015-07-01

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

  5. 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.

  6. 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. PMID:24218619

  7. 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. PMID:26755614

  8. 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

  9. 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. PMID:27058239

  10. 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

  11. 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

  12. Case-control study of allele frequencies of 15 short tandem repeat loci in males with impulsive violent behavior

    PubMed Central

    Yang, Chun; Ba, Huajie; Gao, Zhiqin; Zhao, Hanqing; Yu, Haiying; Guo, Wei

    2013-01-01

    Background Analysis of genetic polymorphisms in short tandem repeats (STRs) is an accepted method for detecting associations between genotype and phenotype but it has not previously been used in the study of the genetics of impulsive violent behavior. Objective Compare the prevalence of different polymorphisms in 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) between men with a history of impulsive violence and male control subjects without a history of impulsive violence. Methods The distributions of the alleles of the 15 STR loci were compared between 407 cases with impulsive violent behavior and 415 controls using AmpFlSTR® Identifiler™ kits. Results Compared to controls, the average frequencies of the following alleles were significantly lower in individuals with a history of violent behavior: allele 10 of TH01 (OR=0.29, 95%CI=0.16-0.52, p<0.0001,), allele 8 of TPOX (OR=0.71, 95%CI=0.58-0.86, p=0.0005), allele 9 of TPOX (OR=0.65, 95%CI=0.47-0.89, p=0.0072) and allele 14 of CSF1PO (OR=0.27, 95%CI=0.11-0.68, p=0.0035). One allele was significantly higher in cases than controls: allele 11 of TPOX (OR=1.79, 95%CI=1.45-2.22, p<0.0001). Conclusions To the best of our knowledge, this is the first behavioral genetic study that clearly demonstrates a close relationship between specific genetic markers and impulsive aggression in non-psychiatric offenders. Further prospective work will be needed to determine whether or not the alleles identified can be considered risk factors for impulsive aggression and, if so, the underlying mechanisms that result in this relationship. PMID:24991178

  13. 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

  14. 46 CFR 111.01-17 - Voltage and frequency variations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 4 2014-10-01 2014-10-01 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....

  15. 46 CFR 111.01-17 - Voltage and frequency variations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 4 2011-10-01 2011-10-01 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....

  16. 46 CFR 111.01-17 - Voltage and frequency variations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 4 2010-10-01 2010-10-01 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....

  17. 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....

  18. High Resolution Human Leukocyte Antigen Class I Allele Frequencies and HIV-1 Infection Associations in Chinese Han and Uyghur Cohorts

    PubMed Central

    Liu, Yanhou; Zhao, Zhongfang; Li, Tianyi; Liao, Qi; Kushner, Nicholas; Touzjian, Neal Y.; Shao, Yiming; Sun, Yongtao; Strong, Amie J.; Lu, Yichen

    2012-01-01

    Background Host immunogenetic factors such as HLA class I polymorphism are important to HIV-1 infection risk and AIDS progression. Previous studies using high-resolution HLA class I profile data of Chinese populations appeared insufficient to provide information for HIV-1 vaccine development and clinical trial design. Here we reported HLA class I association with HIV-1 susceptibility in a Chinese Han and a Chinese Uyghur cohort. Methodology/Principal Findings Our cohort included 327 Han and 161 Uyghur ethnic individuals. Each cohort included HIV-1 seropositive and HIV-1 seronegative subjects. Four-digit HLA class I typing was performed by sequencing-based typing and high-resolution PCR-sequence specific primer. We compared the HLA class I allele and inferred haplotype frequencies between HIV-1 seropositive and seronegative groups. A neighbor-joining tree between our cohorts and other populations was constructed based on allele frequencies of HLA-A and HLA-B loci. We identified 58 HLA-A, 75 HLA-B, and 32 HLA-Cw distinct alleles from our cohort and no novel alleles. The frequency of HLA-B*5201 and A*0301 was significantly higher in the Han HIV-1 negative group. The frequency of HLA-B*5101 was significantly higher in the Uyghur HIV-1 negative group. We observed statistically significant increases in expectation-maximization (EM) algorithm predicted haplotype frequencies of HLA-A*0201-B*5101 in the Uyghur HIV-1 negative group, and of Cw*0304-B*4001 in the Han HIV-1 negative group. The B62s supertype frequency was found to be significantly higher in the Han HIV-1 negative group than in the Han HIV-1 positive group. Conclusions At the four-digit level, several HLA class I alleles and haplotypes were associated with lower HIV-1 susceptibility. Homogeneity of HLA class I and Bw4/Bw6 heterozygosity were not associated with HIV-1 susceptibility in our cohort. These observations contribute to the Chinese HLA database and could prove useful in the development of HIV-1 vaccine

  19. 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. PMID:25728575

  20. The role of culture-gene coevolution in morality judgment: examining the interplay between tightness-looseness and allelic variation of the serotonin transporter gene.

    PubMed

    Mrazek, Alissa J; Chiao, Joan Y; Blizinsky, Katherine D; Lun, Janetta; Gelfand, Michele J

    2013-01-01

    This research provides novel insights into the evolutionary basis of cultural norm development and maintenance. We yield evidence for a unique culture-gene coevolutionary model between ecological threat, allelic frequency of the serotonin transporter polymorphism (5-HTTLPR), cultural tightness-looseness-the strength of norms and tolerance for deviance from norms-and moral justifiability. As hypothesized, the results across 21 nations show that: (a) propensity for ecological threat correlates with short (S) allele frequency in the 5-HTTLPR, (b) allelic frequency in the 5-HTTLPR and vulnerability to ecological threat both correlate with cultural tightness-looseness, (c) susceptibility to ecological threat predicts tightness-looseness via the mediation of S allele carriers, and (d) frequency of S allele carriers predicts justifiability of morally relevant behavior via tightness-looseness. This research highlights the importance of studying the interplay between environmental, genetic, and cultural factors underlying contemporary differences in social behavior and presents an empirical framework for future research. PMID:24404439

  1. Frequency of HLA-DRB1 gene alleles in patients with multiple sclerosis in a Lithuanian population.

    PubMed

    Balnytė, Renata; Rastenytė, Daiva; Mickevičienė, Dalia; Vaitkus, Antanas; Skrodenienė, Erika; Vitkauskienė, Astra

    2012-01-01

    The aim of the present study was to investigate the influence of HLA-DRB1 alleles on the genetic susceptibility to multiple sclerosis in the Lithuanian population. MATERIAL AND METHODS. A total of 120 patients with multiple sclerosis and 120 unrelated healthy controls were enrolled in this case-control study. Allelic frequencies were compared between the groups. HLA-DRB1 alleles were genotyped using the polymerase chain reaction. RESULTS. HLA-DRB1*15 was present in 55.8% of the patients with multiple sclerosis and 10.0% of the controls (OR, 5.58; 95% CI, 3.19-9.77; P<0.0001). The protective alleles that were found to be more prevalent among the controls compared with the patients with multiple sclerosis were HLA-DRB1*01 (26.7% vs. 7.5%, P<0.0001), *03 (17.5% vs. 8.3%, P=0.034), and *16 (11.7% vs. 3.3%, P=0.014). HLA-DRB1*15 was more common among the female patients with multiple sclerosis than among the male patients (68.4% vs. 34.1%; OR, 4.18; 95%, CI 1.90-9.22; P=0.001). The heterozygous inheritance of HLA-DRB1*15 allele was more common in the patients with a history of maternal multiple sclerosis than in those with a history of paternal multiple sclerosis (29.4% vs. 9.8%; P=0.045). CONCLUSIONS. HLA-DRB1*15 was found to be associated with multiple sclerosis in the Lithuanian population. This allele was more prevalent among the female patients with multiple sclerosis. Maternal multiple sclerosis was more common than paternal multiple sclerosis, but the relationship with HLA-DRB1*15 allele was not established. HLA-DRB1*01, *03, and *16 appeared to be the protective alleles in this series. PMID:22370504

  2. Huvariome: a web server resource of whole genome next-generation sequencing allelic frequencies to aid in pathological candidate gene selection

    PubMed Central

    2012-01-01

    Background Next generation sequencing provides clinical research scientists with direct read out of innumerable variants, including personal, pathological and common benign variants. The aim of resequencing studies is to determine the candidate pathogenic variants from individual genomes, or from family-based or tumor/normal genome comparisons. Whilst the use of appropriate controls within the experimental design will minimize the number of false positive variations selected, this number can be reduced further with the use of high quality whole genome reference data to minimize false positives variants prior to candidate gene selection. In addition the use of platform related sequencing error models can help in the recovery of ambiguous genotypes from lower coverage data. Description We have developed a whole genome database of human genetic variations, Huvariome, determined by whole genome deep sequencing data with high coverage and low error rates. The database was designed to be sequencing technology independent but is currently populated with 165 individual whole genomes consisting of small pedigrees and matched tumor/normal samples sequenced with the Complete Genomics sequencing platform. Common variants have been determined for a Benelux population cohort and represented as genotypes alongside the results of two sets of control data (73 of the 165 genomes), Huvariome Core which comprises 31 healthy individuals from the Benelux region, and Diversity Panel consisting of 46 healthy individuals representing 10 different populations and 21 samples in three Pedigrees. Users can query the database by gene or position via a web interface and the results are displayed as the frequency of the variations as detected in the datasets. We demonstrate that Huvariome can provide accurate reference allele frequencies to disambiguate sequencing inconsistencies produced in resequencing experiments. Huvariome has been used to support the selection of candidate cardiomyopathy

  3. Fostered and left behind alleles in peanut: interspecific QTL mapping reveals footprints of domestication and useful natural variation for breeding

    PubMed Central

    2012-01-01

    Background Polyploidy can result in genetic bottlenecks, especially for species of monophyletic origin. Cultivated peanut is an allotetraploid harbouring limited genetic diversity, likely resulting from the combined effects of its single origin and domestication. Peanut wild relatives represent an important source of novel alleles that could be used to broaden the genetic basis of the cultigen. Using an advanced backcross population developed with a synthetic amphidiploid as donor of wild alleles, under two water regimes, we conducted a detailed QTL study for several traits involved in peanut productivity and adaptation as well as domestication. Results A total of 95 QTLs were mapped in the two water treatments. About half of the QTL positive effects were associated with alleles of the wild parent and several QTLs involved in yield components were specific to the water-limited treatment. QTLs detected for the same trait mapped to non-homeologous genomic regions, suggesting differential control in subgenomes as a consequence of polyploidization. The noteworthy clustering of QTLs for traits involved in seed and pod size and in plant and pod morphology suggests, as in many crops, that a small number of loci have contributed to peanut domestication. Conclusion In our study, we have identified QTLs that differentiated cultivated peanut from its wild relatives as well as wild alleles that contributed positive variation to several traits involved in peanut productivity and adaptation. These findings offer novel opportunities for peanut improvement using wild relatives. PMID:22340522

  4. 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

  5. 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. PMID:18232402

  6. On variation of word frequencies in Russian literary texts

    NASA Astrophysics Data System (ADS)

    Kargin, Vladislav

    2016-03-01

    We study the variation of word frequencies in Russian literary texts. Our findings indicate that the standard deviation of a word's frequency across texts depends on its average frequency according to a power law with exponent 1/2 < α < 1, which shows that the rarer words have a relatively larger degree of frequency volatility (that is, higher "burstiness"). A latent factor model has been estimated to investigate the structure of the word frequency distribution. The findings suggest that the dependence of a word's frequency volatility on its average frequency can be explained by the asymmetry in the distribution of latent factors.

  7. Allelic frequencies and association with carcass traits of six genes in local subpopulations of Japanese Black cattle.

    PubMed

    Nishimaki, Takahiro; Ibi, Takayuki; Siqintuya; Kobayashi, Naohiko; Matsuhashi, Tamako; Akiyama, Takayuki; Yoshida, Emi; Imai, Kazumi; Matsui, Mayu; Uemura, Keiichi; Eto, Hisayoshi; Watanabe, Naoto; Fujita, Tatsuo; Saito, Yosuke; Komatsu, Tomohiko; Hoshiba, Hiroshi; Mannen, Hideyuki; Sasazaki, Shinji; Kunieda, Tetsuo

    2016-04-01

    Marker-assisted selection (MAS) is expected to accelerate the genetic improvement of Japanese Black cattle. However, verification of the effects of the genes for MAS in different subpopulations is required prior to the application of MAS. In this study, we investigated the allelic frequencies and genotypic effects for carcass traits of six genes, which can be used in MAS, in eight local subpopulations. These genes are SCD, FASN and SREBP1, which are associated with the fatty acid composition of meat, and NCAPG, MC1R and F11, which are associated with carcass weight, coat color and blood coagulation abnormality, respectively. The frequencies of desirable alleles of SCD and FASN were relatively high and that of NCAPG was relatively low, and NCAPG was significantly associated with several carcass traits, including carcass weight. The proportions of genotypic variance explained by NCAPG to phenotypic variance were 4.83 for carcass weight. We thus confirmed that NCAPG is a useful marker for selection of carcass traits in these subpopulations. In addition, we found that the desirable alleles of six genes showed no negative effects on carcass traits. Therefore, selection using these genes to improve target traits should not have negative impacts on carcass traits. PMID:26249527

  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. Allelic Variation of Calsyntenin 2 (CLSTN2) Modulates the Impact of Developmental Tobacco Smoke Exposure on Mnemonic Processing in Adolescents

    PubMed Central

    Jacobsen, Leslie K.; Picciotto, Marina R.; Heath, Christopher J.; Mencl, W. Einar; Gelernter, Joel

    2010-01-01

    Background Exposure to nicotine in tobacco smoke during development has been linked to subsequent deficits in attention and memory. The present study tested for evidence that genetic variation may contribute to individual differences in vulnerability to the effects of developmental exposure to tobacco smoke on memory and medial temporal lobe function in adolescents. Methods Verbal and visuospatial memory were assessed and functional magnetic resonance imaging (fMRI) data were acquired in 101 adolescents systematically characterized for prenatal and adolescent exposure to tobacco smoke, while they performed an encoding and recognition memory task. The impact of allelic variation at loci within CLSTN2 (encoding synaptic protein calsyntenin 2) and KIBRA, shown previously to modulate early and delayed recall of words, on the dependent measures was examined. Results KIBRA genotype did not exert significant main or interacting effects with prenatal or adolescent exposure to tobacco smoke on verbal or visuospatial memory. Previous observations of a beneficial effect of the CLSTN2 C allele on verbal recall were replicated. Adolescent exposure to tobacco smoke reversed this beneficial effect and was associated with increased activation of parahippocampal gyrus during early and delayed recognition in CLTSN2 C allele carriers. While the CLSTN2 C allele conferred enhanced functional connectivity between brain regions subserving accurate verbal recognition, adolescent exposure to tobacco smoke reversed this effect. Conclusions These findings extend previous work demonstrating that calsyntenins play an essential role in learning and indicate that this role is modulated both by CLSTN2 genotype and, during adolescent development, by exposure to tobacco smoke. PMID:19058786

  10. High-Frequency Variation of Purine Biosynthesis Genes Is a Mechanism of Success in Campylobacter jejuni

    PubMed Central

    Cameron, Andrew; Huynh, Steven; Scott, Nichollas E.; Frirdich, Emilisa; Apel, Dmitry; Foster, Leonard J.; Parker, Craig T.

    2015-01-01

    ABSTRACT Phenotypic variation is prevalent in the zoonotic pathogen Campylobacter jejuni, the leading agent of enterocolitis in the developed world. Heterogeneity enhances the survival and adaptive malleability of bacterial populations because variable phenotypes may allow some cells to be protected against future stress. Exposure to hyperosmotic stress previously revealed prevalent differences in growth between C. jejuni strain 81-176 colonies due to resistant or sensitive phenotypes, and these isolated colonies continued to produce progeny with differential phenotypes. In this study, whole-genome sequencing of isolated colonies identified allelic variants of two purine biosynthesis genes, purF and apt, encoding phosphoribosyltransferases that utilize a shared substrate. Genetic analyses determined that purF was essential for fitness, while apt was critical. Traditional and high-depth amplicon-sequencing analyses confirmed extensive intrapopulation genetic variation of purF and apt that resulted in viable strains bearing alleles with in-frame insertion duplications, deletions, or missense polymorphisms. Different purF and apt alleles were associated with various stress survival capabilities under several niche-relevant conditions and contributed to differential intracellular survival in an epithelial cell infection model. Amplicon sequencing revealed that intracellular survival selected for stress-fit purF and apt alleles, as did exposure to oxygen and hyperosmotic stress. Putative protein recognition direct repeat sequences were identified in purF and apt, and a DNA-protein affinity screen captured a predicted exonuclease that promoted the global spontaneous mutation rate. This work illustrates the adaptive properties of high-frequency genetic variation in two housekeeping genes, which influences C. jejuni survival under stress and promotes its success as a pathogen. PMID:26419875

  11. Allelic frequencies for the HLA-DQA1, D1S80, HUMTHO1, HUMTPOX, HUMCSF1PO and HUMVWA loci in Cantabria (middle north Spain).

    PubMed

    Sánchez-Molina, I; Calvet, R

    2000-01-01

    Allele frequencies for six DNA polymorphisms have been studied in a population sample from Cantabria (middle north Spain) using the polymerase chain reaction. The HLA-DQA1 locus was analyzed by the reverse dot-blot technique and the other five by polyacrylamide gel electrophoresis followed by silver staining. Six alleles were found for HLA-DQA1. 15 alleles for D1S80, 6 alleles for HUMTHO1 and HUMCSF1PO, 7 for HUMTPOX and 8 alleles for HUMVWA. The 21 repeat allele in HUMVWA had not previously been reported in a Spanish population. The genotype distributions met Hardy-Weinberg expectations for all the systems and some statistical parameters of forensic interest were calculated. Comparisons with other populations revealed significant differences for HLA-DQA1, HUMVWA and HUMTHO1, with interracial differences being more pronounced than between Spanish populations. The HUMVWA system showed the highest forensic efficiency of the six polymorphisms studied. PMID:10641932

  12. High frequency of the apolipoprotein E *4 allele in African pygmies and most of the African populations in sub-Saharan Africa.

    PubMed

    Zekraoui, L; Lagarde, J P; Raisonnier, A; Gérard, N; Aouizérate, A; Lucotte, G

    1997-08-01

    Apolipoprotein E genotypes (alleles *2, *3, and *4) have been determined in 70 Aka Pygmies and 470 unrelated African sub-Saharan subjects. Allele frequencies for Pygmies are 5.7% for APOE*2, 53.6% for APOE*3, and 40.7% for APOE*4, and the global proportions for sub-Saharan subjects are 11.6% for APOE*2, 70.6% for APOE*3, and 17.8% for APOE*4. The frequencies in some ethnic groups are statistically different from the overall mean in the Afar and the Isa, the Ewe (Togo), the Malinke (Guinea), and the Mossi; three ethnic groups have a higher allele frequency of APOE*4 (Fon, 29.4%; Zairians, 33.3%; Tutsi, 38.5%). The APOE*4 allele is considered the ancestral form because of its high frequency in African Pygmies and other aboriginal populations. PMID:9198315

  13. 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

  14. Skewed allele frequencies of an Mx gene mutation with potential resistance to avian influenza virus in different chicken populations.

    PubMed

    Li, X Y; Qu, L J; Yao, J F; Yang, N

    2006-07-01

    The Mx gene is considered to confer positive antiviral responses to the orthomyxovirus in many organisms. In the chicken, 1 nonsynonymous single nucleotide polymorphism (G to A) at position 2,032 of Mx cDNA was demonstrated to confer positive antiviral activity in vitro to avian influenza virus in a previous study. In the current study, 15 Chinese native chicken breeds, 4 highly selected commercial lines, and the Red Jungle Fowl were selected to detect allele frequencies of the Mx mutation. The frequencies of the favorable allele A in native breeds were 0.7241 to 0.9554, which were much higher than those (0.0565 to 0.2742) found in the commercial populations. Whereas most native breeds were in Hardy-Weinberg equilibrium at this locus (P > 0.01), 3 out of 4 commercial populations were not in Hardy-Weinberg equilibrium (P < 0.01). Selection, environment, and negative correlations between production and disease resistant traits could contribute to highly skewed frequencies of the mutation among native breeds and commercial populations. The results suggested that further studies are needed with regard to the genetic resistance to avian influenza in different populations with various domestication background and selection history. PMID:16830876

  15. Fish scales and SNP chips: SNP genotyping and allele frequency estimation in individual and pooled DNA from historical samples of Atlantic salmon (Salmo salar)

    PubMed Central

    2013-01-01

    Background DNA extracted from historical samples is an important resource for understanding genetic consequences of anthropogenic influences and long-term environmental change. However, such samples generally yield DNA of a lower amount and quality, and the extent to which DNA degradation affects SNP genotyping success and allele frequency estimation is not well understood. We conducted high density SNP genotyping and allele frequency estimation in both individual DNA samples and pooled DNA samples extracted from dried Atlantic salmon (Salmo salar) scales stored at room temperature for up to 35 years, and assessed genotyping success, repeatability and accuracy of allele frequency estimation using a high density SNP genotyping array. Results In individual DNA samples, genotyping success and repeatability was very high (> 0.973 and > 0.998, respectively) in samples stored for up to 35 years; both increased with the proportion of DNA of fragment size > 1000 bp. In pooled DNA samples, allele frequency estimation was highly repeatable (Repeatability = 0.986) and highly correlated with empirical allele frequency measures (Mean Adjusted R2 = 0.991); allele frequency could be accurately estimated in > 95% of pooled DNA samples with a reference group of at least 30 individuals. SNPs located in polyploid regions of the genome were more sensitive to DNA degradation: older samples had lower genotyping success at these loci, and a larger reference panel of individuals was required to accurately estimate allele frequencies. Conclusions SNP genotyping was highly successful in degraded DNA samples, paving the way for the use of degraded samples in SNP genotyping projects. DNA pooling provides the potential for large scale population genetic studies with fewer assays, provided enough reference individuals are also genotyped and DNA quality is properly assessed beforehand. We provide recommendations for future studies intending to conduct high-throughput SNP

  16. 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

  17. Interethnic variation of CYP2C19 alleles, 'predicted' phenotypes and 'measured' metabolic phenotypes across world populations.

    PubMed

    Fricke-Galindo, I; Céspedes-Garro, C; Rodrigues-Soares, F; Naranjo, M E G; Delgado, Á; de Andrés, F; López-López, M; Peñas-Lledó, E; LLerena, A

    2016-04-01

    The present study evaluates the worldwide frequency distribution of CYP2C19 alleles and CYP2C19 metabolic phenotypes ('predicted' from genotypes and 'measured' with a probe drug) among healthy volunteers from different ethnic groups and geographic regions, as well as the relationship between the 'predicted' and 'measured' CYP2C19 metabolic phenotypes. A total of 52 181 healthy volunteers were studied within 138 selected original research papers. CYP2C19*17 was 42- and 24-fold more frequent in Mediterranean-South Europeans and Middle Easterns than in East Asians (P<0.001, in both cases). Contrarily, CYP2C19*2 and CYP2C19*3 alleles were more frequent in East Asians (30.26% and 6.89%, respectively), and even a twofold higher frequency of these alleles was found in Native populations from Oceania (61.30% and 14.42%, respectively; P<0.001, in all cases), which may be a consequence of genetic drift process in the Pacific Islands. Regarding CYP2C19 metabolic phenotype, poor metabolizers (PMs) were more frequent among Asians than in Europeans, contrarily to the phenomenon reported for CYP2D6. A correlation has been found between the frequencies of CYP2C19 poor metabolism 'predicted' from CYP2C19 genotypes (gPMs) and the poor metabolic phenotype 'measured' with a probe drug (mPMs) when subjects are either classified by ethnicity (r=0.94, P<0.001) or geographic region (r=0.99, P=0.002). Nevertheless, further research is needed in African and Asian populations, which are under-represented, and additional CYP2C19 variants and the 'measured' phenotype should be studied. PMID:26503820

  18. [Distribution and frequency of HLA alleles and haplotypes in Brazilians with type 1 diabetes mellitus].

    PubMed

    Alves, Crésio; Meyer, Isadora; Vieira, Nara; Toralles, Maria Betânia P; LeMaire, Denise

    2006-06-01

    The genetic predisposition to type 1 diabetes (DM1) is associated with genes of the human leukocyte antigen (HLA) system, specially the HLA-DR and -DQ. In Caucasians, the HLA-DR3 and -DR4 antigens are associated with susceptibility and the -DR2, with protection. In Brazil, a country with a large miscegenation of European Caucasians, Native Amerindians and African Blacks, the genetic basis of DM1 has not been adequately studied. The aim of this paper is to present a critical review of articles indexed in the MEDLINE and LILACS-BIREME data basis about the association of HLA with DM1 in Brazilians. Eight papers, all of them from the Southeast region, were found. Immunogenetic susceptibility to DM1 in Brazilians was associated with HLA-DRB1*03, -DRB*04, -DQB1*0201, -DQB1*0302 alleles, and protection against DM1 was associated with HLA-DQB1*0602, -DQB1*0301 alleles and -DR2 and -DR7 antigens. Since the Brazilian population is not racially homogeneous, it is not possible to extrapolate studies from a single region to the remainder of the country. It is necessary to study populations from different regions to identify new associations or to strengthen associations with the ones already identified. This knowledge will contribute to future prophylactic or therapeutic interventions in the group of Brazilians at risk of developing DM1. PMID:16936983

  19. Allelic frequencies and statistical data obtained from 15 STR loci in a population of the Goiás State.

    PubMed

    Vieira, T C; Silva, D M; Gigonzac, M A D; Ferreira, V L; Gonçalves, M W; da Cruz, A D

    2013-01-01

    Due to the miscegenation of the Brazilian population, the central region of Brazil was colonized by internal migration of individuals from different origins, who contributed to the genetic diversity existing in this population. The purpose of this study was to estimate population parameters based on the allele frequencies for 15 polymorphic autosomal short-tandem repeat (STR) loci present in the population of the State of Goiás in the central region of Brazil, and to compare the results with those of others from different Brazilian populations. DNA was obtained from a sample of 986 unrelated individuals by a commercial reagent kit and was quantified by spectrometry for later amplification in the thermocycler. These loci, commonly used in forensics and paternity testing, reflected Hardy-Weinberg equilibrium in this population. The D18S51 and Penta E loci had the highest number of alleles, while the observed heterozygosity reached the highest rates in FGA (0.920), D7S820 (0.870), and vWA (0.867) markers. Genetic diversity reached the highest levels in Penta E (0.906), Penta D (0.873), and D18S51 (0.860) markers, and the investigated forensic parameters showed high average values, with 93% power of discrimination, polymorphism information content of 78%, gene diversity of 79%, and observed heterozygosity of 79%. Similar to the other populations of Brazil, the population of the Midwest is derived from the admixture of 3 main parental groups: Amerindian, European, particularly Portuguese, and Africans from sub-Saharan Africa. In this context, the overall distribution of allele frequencies in the STR markers of various Brazilian populations is quite similar to the data obtained in this study. PMID:23359020

  20. Latitudinal variation of chorus frequency observed in the topside ionosphere

    NASA Astrophysics Data System (ADS)

    Ondoh, T.; Nakamura, Y.; Watanabe, S.; Murakami, T.

    1982-07-01

    Latitudinal variations of chorus band frequency have been obtained from frequency-time VLF spectrograms of relatively long ISIS passes received at Syowa station, Antarctica, in 1977 and 1978. The upper and lower limit frequencies of the dayside chorus decrease with L value, and their latitudinal variations roughly agree with a latitudinal variation of one half of the equatorial gyrofrequency. This result is consistent with the dayside magnetospheric chorus model in which the chorus generated near the equatorial magnetosphere propagates along the field lines in the ducted mode or inwards from the original field line in the nonducted model. Nightside choruses were observed in geomagnetically disturbed periods; thus the generation mechanism for the nightside chorus seems to be different from that of the dayside chorus. A new case was found in which the chorus band frequencies at latitudes beyond the plasmapause are higher than those at latitudes inside the plasmapause.

  1. 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

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

    PubMed Central

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

    2012-01-01

    Sequence based typing was used to identify HLA-A,B,C,DRB1 alleles from 558 consecutively recruited U.S. volunteers with Eastern European ancestry for an unrelated hematopoietic stem cell registry. Four of the 31 HLA-A alleles, 29 -C alleles, 59 -B alleles, and 42 -DRB1 alleles identified (A*0325, B*440204, Cw*0332, and *0732N) are novel. The HLA-A*02010101g allele was observed at a frequency of 0.28. Two-, three- and four-locus haplotypes were estimated using the expectation maximization algorithm. The highest-frequency extended haplotypes (A*010101g-Cw*070101g-B*0801g-DRB1*0301 and A*03010101g-Cw*0702-B*0702-DRB1*1501) were observed at frequencies of 0.04 and 0.03, respectively. Linkage disequilibrium values (D’ij) of the constituent 2-locus haplotypes were highly significant for both extended haplotypes (p-values were less than 8 × 10−10), but were consistently higher for the more frequent haplotype. Balancing selection was inferred to be acting on all four loci, with the strongest evidence of balancing selection observed for the HLA-C locus. Comparisons of the A-C-B haplotype and DRB1 frequencies in this population to those for African, European and western Asian populations revealed high degrees of identity with Czech, Polish, and Slovenian populations and significant differences from the general European American population. PMID:19000140

  3. A prospective evaluation of the transthyretin Ile122 allele frequency in an African-American population.

    PubMed

    Yamashita, Taro; Hamidi Asl, Kamran; Yazaki, Masahide; Benson, Merrill D

    2005-06-01

    Transthyretin Val122Ile is one of greater than 80 mutations in transthyretin (TTR) that are associated with hereditary amyloidosis. Retrospective studies have shown a prevalence of this mutation as high as 3.9% in African-Americans. The present study was undertaken to determine in a prospective fashion the prevalence of the TTR Val122Ile allele in African-Americans in a Midwestern American city. DNA was isolated from cord bloods collected at the time of birth in the County hospital of Indianapolis, Indiana. Samples were identified only as to ethnic origin of the mother. Analysis was performed by PCR amplification of TTR exon 4 followed by SSCP and RFLP. Cord bloods from 1,973 children born at the County hospital were analyzed. Thirty of 1,000 DNA samples from African-American newborns were positive for TTR Val122Ile (3%). Two of 453 DNA samples from Caucasian newborns were positive (0.44%). Zero of 490 DNA samples from newborns of Hispanic mothers and 0 of 30 from newborns with mothers classified as other (including Asian) were positive. This prospective study demonstrates that 3% of newborns of African-American women in an urban population have the TTR Val122Ile mutation which is associated with late-onset cardiomyopathy. The degree of penetrance of this mutation at the clinical level has not yet been determined. PMID:16011990

  4. Allelic and copy-number variations of FcγRs affect granulocyte function and susceptibility for autoimmune blistering diseases.

    PubMed

    Recke, Andreas; Vidarsson, Gestur; Ludwig, Ralf J; Freitag, Miriam; Möller, Steffen; Vonthein, Reinhard; Schellenberger, Julia; Haase, Ozan; Görg, Siegfried; Nebel, Almut; Flachsbart, Friederike; Schreiber, Stefan; Lieb, Wolfgang; Gläser, Regine; Benoit, Sandrine; Sárdy, Miklós; Eming, Rüdiger; Hertl, Michael; Zillikens, Detlef; König, Inke R; Schmidt, Enno; Ibrahim, Saleh

    2015-07-01

    Low-affinity Fcγ receptors (FcγR) bridge innate and adaptive immune responses. In many autoimmune diseases, these receptors act as key mediators of the pathogenic effects of autoantibodies. Genes encoding FcγR exhibit frequent variations in sequence and gene copy number that influence their functional properties. FcγR variations also affect the susceptibility to systemic autoimmunity, e.g. systemic lupus erythematosus and rheumatoid arthritis. This raises the question whether FcγR variations are also associated with organ-specific autoimmunity, particularly autoantibody-mediated diseases, such as subepidermal autoimmune blistering diseases (AIBD). A multitude of evidence suggests a pathogenic role of neutrophil granulocyte interaction with autoantibodies via FcγR. In a two-stage study, we analyzed whether the FcγR genotype affects neutrophil function and mRNA expression, and consequently, bullous pemphigoid (BP) disease risk. We compared this to findings in pemphigus vulgaris/foliaceus (PV/PF), two Fc-independent AIBDs. Our results indicate that both allele and copy number variation of FcγR genes affect FcγR mRNA expression and reactive oxygen species (ROS) release by granulocytes. Susceptibility of BP was associated with FcγR genotypes that led to a decreased ROS release by neutrophils, indicating an unexpected protective role for these cells. BP and PV/PF differed substantially regarding the FcγR genotype association patterns, pointing towards different disease etiologies. PMID:26032265

  5. 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. PMID:26329765

  6. Next-generation sequencing analysis of off-ladder alleles due to migration shift caused by sequence variation at D12S391 locus.

    PubMed

    Fujii, Koji; Watahiki, Haruhiko; Mita, Yusuke; Iwashima, Yasuki; Miyaguchi, Hajime; Kitayama, Tetsushi; Nakahara, Hiroaki; Mizuno, Natsuko; Sekiguchi, Kazumasa

    2016-09-01

    In short tandem repeat (STR) analysis, length polymorphisms are detected by capillary electrophoresis (CE). At most STR loci, mobility shift due to sequence variation in the repeat region was thought not to affect the typing results. In our recent population studies of 1501 Japanese individuals, off-ladder calls were observed at the D12S391 locus using PowerPlex Fusion in nine samples for allele 22, one sample for allele 25, and one sample for allele 26. However, these samples were typed as ordinary alleles within the bins using GlobalFiler. In this study, next-generation sequencing analysis using MiSeq was performed for the D12S391 locus from the 11 off-ladder samples and 33 other samples, as well as the allelic ladders of PowerPlex Fusion and GlobalFiler. All off-ladder allele 22 in the nine samples had [AGAT]11[AGAC]11 as a repeat structure, while the corresponding allele was [AGAT]15[AGAC]6[AGAT] for the PowerPlex Fusion ladder, and [AGAT]13[AGAC]9 for the GlobalFiler ladder. Overall, as the number of [AGAT] in the repeat structure decreased at the D12S391 locus, the peak migrated more slowly using PowerPlex Fusion, the reverse strand of which was labeled, and it migrated more rapidly using GlobalFiler, the forward strand of which was labeled. The allelic ladders of both STR kits were reamplified with our small amplicon D12S391 primers and their mobility was also examined. In conclusion, off-ladder observations of allele 22 at the D12S391 locus using PowerPlex Fusion were mainly attributed to a relatively large difference of the repeat structure between its allelic ladder and off-ladder allele 22. PMID:27591542

  7. Determination of the Allelic Frequency in Smith-Lemli-Opitz Syndrome by Analysis of Massively Parallel Sequencing Data Sets

    PubMed Central

    Cross, Joanna L.; Iben, James; Simpson, Claire; Thurm, Audrey; Swedo, Susan; Tierney, Elaine; Bailey-Wilson, Joan; Biesecker, Leslie G.; Porter, Forbes D.; Wassif, Christopher A.

    2014-01-01

    Data from massively parallel sequencing or “Next Generation Sequencing” of the human exome has reached a critical mass in both public and private databases, in that these collections now allow researchers to critically evaluate population genetics in a manner that was not feasible a decade ago. The ability to determine pathogenic allele frequencies by evaluation of the full coding sequences and not merely a single SNP or series of SNPs will lead to more accurate estimations of incidence. For demonstrative purposes we analyzed the causative gene for the disorder Smith-Lemli-Opitz Syndrome (SLOS), the 7-dehydrocholesterol reductase (DHCR7) gene and determined both the carrier frequency for DHCR7 mutations, and predicted an expected incidence of the disorder. Estimations of the incidence of SLOS have ranged widely from 1:10,000 to 1:70,000 while the carrier frequency has been reported as high as 1 in 30. Using four exome data sets with a total of 17,836 chromosomes, we ascertained a carrier frequency of pathogenic DHRC7 mutations of 1.01%, and predict a SLOS disease incidence of 1/39,215 conceptions. This approach highlights yet another valuable aspect of the exome sequencing databases, to inform clinical and health policy decisions related to genetic counseling, prenatal testing and newborn screening. PMID:24813812

  8. Determination of the allelic frequency in Smith-Lemli-Opitz syndrome by analysis of massively parallel sequencing data sets.

    PubMed

    Cross, J L; Iben, J; Simpson, C L; Thurm, A; Swedo, S; Tierney, E; Bailey-Wilson, J E; Biesecker, L G; Porter, F D; Wassif, C A

    2015-06-01

    Data from massively parallel sequencing or 'Next Generation Sequencing' of the human exome has reached a critical mass in both public and private databases, in that these collections now allow researchers to critically evaluate population genetics in a manner that was not feasible a decade ago. The ability to determine pathogenic allele frequencies by evaluation of the full coding sequences and not merely a single nucleotide polymorphism (SNP) or series of SNPs will lead to more accurate estimations of incidence. For demonstrative purposes, we analyzed the causative gene for the disorder Smith-Lemli-Opitz Syndrome (SLOS), the 7-dehydrocholesterol reductase (DHCR7) gene and determined both the carrier frequency for DHCR7 mutations, and predicted an expected incidence of the disorder. Estimations of the incidence of SLOS have ranged widely from 1:10,000 to 1:70,000 while the carrier frequency has been reported as high as 1 in 30. Using four exome data sets with a total of 17,836 chromosomes, we ascertained a carrier frequency of pathogenic DHRC7 mutations of 1.01%, and predict a SLOS disease incidence of 1/39,215 conceptions. This approach highlights yet another valuable aspect of the exome sequencing databases, to inform clinical and health policy decisions related to genetic counseling, prenatal testing and newborn screening. PMID:24813812

  9. 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. PMID:25398792

  10. Preliminary evidence that allelic variation in the LMX1A gene influences training-related working memory improvement.

    PubMed

    Bellander, Martin; Brehmer, Yvonne; Westerberg, Helena; Karlsson, Sari; Fürth, Daniel; Bergman, Olle; Eriksson, Elias; Bäckman, Lars

    2011-06-01

    LMX1A is a transcription factor involved in the development of dopamine (DA)-producing neurons in midbrain. Previous research has shown that allelic variations in three LMX1A single nucleotide polymorphisms (SNPs) were related to risk of Parkinson's disease (PD), suggesting that these SNPs may influence the number of mesencephalic DA neurons. Prompted by the established link between striatal DA functions and working memory (WM) performance, we examined two of these SNPs in relation to the ability to benefit from 4 weeks of WM training. One SNP (rs4657412) was strongly associated with the magnitude of training-related gains in verbal WM. The allele linked to larger gains has previously been suggested to be associated with higher dopaminergic nerve cell density. No differential gains of either SNP were observed for spatial WM, and the genotype groups were also indistinguishable in tests of attention, interference control, episodic memory, perceptual speed, and reasoning for both SNPs. This pattern of data is in agreement with previous findings from our group, suggesting that cognitive effects of DA-related genes may be more easily detected in a training context than for single-assessment performance scores. PMID:21435346

  11. An Analysis of HLA-A, -B, and -DRB1 Allele and Haplotype Frequencies of 21,918 Residents Living in Liaoning, China

    PubMed Central

    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. PMID:24691290

  12. 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

  13. Allelic variations in 5, 10-methylenetetrahydrofolate reductase gene and susceptibility to cervical cancer in Indian women.

    PubMed

    Nandan, Naveen Kumar; Wajid, Saima; Biswas, Shilpie; Juneja, Sominder Singh; Rizvi, Moshahid; Prakash, Raminder; Naqvi, Samar Husain

    2008-01-01

    Methylenetetrahydrofolate reductase (MTHFR) gene located on chromosome 1p36.3 catalyses the conversion of 5,10-methylenetetrahydrofolate to 5,methyltetrahydrofolate, the major methyl donor for the conversion of homocysteine to methionine. Two common polymorphisms in the MTHFR gene have been identified, 677C>T in exon 4, leading to substitution of alanine by valine and 1298A>C in exon 7 which leads to the replacement of glutamic acid by alanine resulting into reduced enzyme activity. The potential influence of MTHFR activity on DNA methylation and on the availability of uridylates and thymidylates for DNA synthesis and repair makes MTHFR an attractive candidate for cancer predisposing gene. In order to elucidate the role of MTHFR polymorphism in cervical cancer, both the exons for 677C>T and 1298A>C mutations were analyzed among 219 females, including 77 females with normal cervical cytology, 80 with cervical dysplasia and 62 with squamous cell carcinoma of uterine cervix. Females with mutant allele at 677 position (CT/TT genotypes) were found to be almost three times the risk of cervical dysplasia than females with CC genotype [OR, 2.9; (CI, 1.5-5.7)], but were less likely to develop squamous cell carcinoma [OR, 1.5 (CI, 0.7-3.2)]. Similar findings were observed for mutation at 1298 position, females with AC/CC genotypes were almost four times the risk of cervical dysplasia [OR, 4.3 (CI, 2.1-9.0)], as compared to AA genotype. Our study lends further support to the hypothesis that the MTHFR polymorphism (677C>T or 1298A>C) is involved in susceptibility to cervical dysplasia. PMID:19356065

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

    PubMed

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

    2008-02-01

    Variation of a VNTR in the DAT1 gene in seven ethnic groups of the Middle East was used to infer the history and affinities of these groups. The populations consisted of Assyrian, Jewish, Zoroastrian, Armenian, Turkmen, and Arab peoples of Iran, Iraq, and Kuwait. Three hundred forty subjects from these seven ethnic groups were screened for DAT1. DAT1 VNTR genotyping showed 3, 6, 7, 8, 9, 10, 11, and 12 alleles in the samples. Analysis of these data revealed differentiation and relationship among the populations. In this region, which covers an area of 2-2.5 million km2, the influence of geography and especially of linguistic characteristics has had potentially major effects on differentiation. Religion also has played a major role in imposing restrictions on some ethnic groups, who as a consequence have maintained their community. Overall, these ethnic groups showed greater heterogeneity compared to other populations. PMID:18505046

  15. Allele frequency for Cystic fibrosis in Indians vis-a/-vis global populations.

    PubMed

    Bepari, Karnajit Kumar; Malakar, Arup Kumar; Paul, Prosenjit; Halder, Binata; Chakraborty, Supriyo

    2015-01-01

    Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. This gene encodes a protein involved in epithelial anion channel. Cystic fibrosis is the most common life-limiting genetic disorder in Caucasians; it also affects other ethnic groups like the Blacks and the Native Americans. Cystic fibrosis is considered to be rare among individuals from the Indian subcontinent. We analyzed a total of 29 world׳s populations for cystic fibrosis on the basis of gene frequency and heterozygosity. Among 29 countries Switzerland revealed the highest gene frequency and heterozygosity for CF (0.022, 0.043) whereas Japan recorded the lowest values (0.002, 0.004) followed by India (0.004, 0.008). Our analysis suggests that the prevalence of cystic fibrosis is very low in India. PMID:26339151

  16. Allelic frequency determination of the 24-bp chitotriosidase duplication in the Portuguese population by real-time PCR.

    PubMed

    Rodrigues, M R; Sá Miranda, M C; Amaral, O

    2004-01-01

    Chitotriosidase is a human chitinase produced by macrophages. Its enzymatic activity is markedly elevated in serum of patients suffering from lysosomal storage disorders, as well as other diseases in which macrophages are activated. Therefore, it is a useful tool as a secondary marker in the diagnosis of several disorders including Gaucher disease type 1 and Niemann-Pick disease. The determination of chitotriosidase levels as a diagnosis complement in some lysosomal storage disorders and in enzyme replacement therapy follow-up of Gaucher disease patients is of great importance. However, the fact that a mutation caused by a 24-bp duplication in the CHIT1 gene resulting in deficiency of plasma chitotriosidase activity is very frequent makes the establishment of the frequency of this mutation in different population groups necessary. Furthermore, in order to validate the use of chitotriosidase activity as a marker, it is indispensable to screen individuals for this particular mutation. In this work, we present the results of a study where the allelic frequency of the above mentioned CHIT1 gene mutation was determined in the Portuguese population by real-time PCR. The frequency of carriers encountered in this sample of Portuguese individuals was of 37%. PMID:15528158

  17. On the variation of interaural time differences with frequency.

    PubMed

    Benichoux, Victor; Rébillat, Marc; Brette, Romain

    2016-04-01

    Interaural time difference (ITD) is a major cue to sound localization in humans and animals. For a given subject and position in space, ITD depends on frequency. This variation is analyzed here using a head related transfer functions (HRTFs) database collected from the literature and comprising human HRTFs from 130 subjects and animal HRTFs from six specimens of different species. For humans, the ITD is found to vary with frequency in a way that shows consistent differences with respect to a spherical head model. Maximal ITD values were found to be about 800 μs in low frequencies and 600 μs in high frequencies. The ITD variation with frequency (up to 200 μs for some positions) occurs within the frequency range where ITD is used to judge the lateral position of a sound source. In addition, ITD varies substantially within the bandwidth of a single auditory filter, leading to systematic differences between envelope and fine-structure ITDs. Because the frequency-dependent pattern of ITD does not display spherical symmetries, it potentially provides cues to elevation and resolves front/back confusion. The fact that the relation between position and ITDs strongly depends on the sound's spectrum in turn suggests that humans and animals make use of this relationship for the localization of sounds. PMID:27106329

  18. Os incae: variation in frequency in major human population groups

    PubMed Central

    HANIHARA, TSUNEHIKO; ISHIDA, HAJIME

    2001-01-01

    The variation in frequency of the Inca bone was examined in major human populations around the world. The New World populations have generally high frequencies of the Inca bone, whereas lower frequencies occur in northeast Asians and Australians. Tibetan/Nepalese and Assam/Sikkim populations in northeast India have more Inca bones than do neighbouring populations. Among modern populations originally derived from eastern Asian population stock, the frequencies are highest in some of the marginal isolated groups. In Central and West Asia as well as in Europe, frequency of the Inca bone is relatively low. The incidence of the complete Inca bone is, moreover, very low in the western hemisphere of the Old World except for Subsaharan Africa. Subsaharan Africans show as a whole a second peak in the occurrence of the Inca bone. Geographical and ethnographical patterns of the frequency variation of the Inca bone found in this study indicate that the possible genetic background for the occurrence of this bone cannot be completely excluded. Relatively high frequencies of the Inca bone in Subsaharan Africans indicate that this trait is not a uniquely eastern Asian regional character. PMID:11273039

  19. Allele Frequencies of Variants in Ultra Conserved Elements Identify Selective Pressure on Transcription Factor Binding

    PubMed Central

    Silla, Toomas; Kepp, Katrin; Tai, E. Shyong; Goh, Liang; Davila, Sonia; Ivkovic, Tina Catela; Calin, George A.; Voorhoeve, P. Mathijs

    2014-01-01

    Ultra-conserved genes or elements (UCGs/UCEs) in the human genome are extreme examples of conservation. We characterized natural variations in 2884 UCEs and UCGs in two distinct populations; Singaporean Chinese (n = 280) and Italian (n = 501) by using a pooled sample, targeted capture, sequencing approach. We identify, with high confidence, in these regions the abundance of rare SNVs (MAF<0.5%) of which 75% is not present in dbSNP137. UCEs association studies for complex human traits can use this information to model expected background variation and thus necessary power for association studies. By combining our data with 1000 Genome Project data, we show in three independent datasets that prevalent UCE variants (MAF>5%) are more often found in relatively less-conserved nucleotides within UCEs, compared to rare variants. Moreover, prevalent variants are less likely to overlap transcription factor binding site. Using SNPfold we found no significant influence of RNA secondary structure on UCE conservation. All together, these results suggest UCEs are not under selective pressure as a stretch of DNA but are under differential evolutionary pressure on the single nucleotide level. PMID:25369454

  20. 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

  1. Gm and Km alleles in two Spanish Pyrenean populations (Andorra and Pallars Sobirà): a review of Gm variation in the Western Mediterranean basin.

    PubMed

    Giraldo, M P; Esteban, E; Aluja, M P; Nogués, R M; Backés-Duró, C; Dugoujon, J M; Moral, P

    2001-11-01

    Two Spanish eastern Pyrenean populations, Andorra and Pallars Sobirà, have been tested for G1m(1,2,3,17), G2m(23), G3m(5,6,10,11,13,14,15,16,21,24,28) and Km(1) immunoglobulin allotypes. Km allele and Gm haplotype frequencies in both samples fit well into the Western Mediterranean and, more strictly, Pyrenean ranges with some peculiarities: Andorra showed an elevated frequency (14.7%) of the typical Asian and European Gm21,28;1,2,17;. haplotype, while Pallars Sobirà was characterized by high values (3.7%) of Gm5*;1,17;., a typical sub-Saharan Gm haplotype. Gm diversity assessed through genetic distance and variance analyses revealed a significant geographic partition (4.3%) of Mediterraneans among south, north-east, and north-west groups. It is interesting to note the relatively low genetic variance (2.1%) found between south and north-western Mediterraneans that could reflect ancient population relationships. More locally, genetic boundaries and diversity analyses failed to indicate any geographic pattern and/or genetic differentiation related with the political border in the Pyrenees. The present pattern of variation in this area is probably the result of genetic isolation processes, in addition to some specific demographic phenomena, in the Pyrenean valleys. PMID:11851984

  2. 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

  3. Frequency of BLAD and CVM alleles in sires and elite heifers of Czech Holstein cattle.

    PubMed

    Cítek, J; Rehout, V; Schröffelová, D; Hradecká, E

    2008-12-01

    In this paper, we analyse the occurrence of BLAD and CVM heterozygous animals in Holstein cattle in the Czech Republic in 1993-2005. The occurrence of BLAD heterozygous sires and heifers (BL) during the period 1993-1998 in Czech Holsteins was 13.9% and 10.7%. Radical measures have been taken to restore the population. Evidently, the measures have been efficient, in 2005 one BLAD heterozygous sire of 101 was found. Continuous testing is necessary, because in commercial herds, the eradication process is not short-term. The found occurrence ofCVM heterozygous sires (CV) decreased from 20% in 2001 to 8% (7 positive of 85) in 2005.This is still quite a high frequency. The occurrence in CV females of 20% remains higher. Therefore, the use of CV sires should be restricted thoroughly. Identification of the molecular basis for inherited diseases, should lead to control measures which would enable the quick recovery of the population. PMID:19113030

  4. 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

  5. The impact of CACNA1C allelic variation on regional gray matter volume in Chinese population.

    PubMed

    Huang, Liang; Mo, Yin; Sun, Xuejin; Yu, Hualin; Li, Hao; Wu, Lichuan; Li, Ming

    2016-04-01

    The SNP rs1006737 in CACNA1C gene has been significantly associated with psychiatric disorders (e.g., schizophrenia and bipolar disorder) in European populations. In Han Chinese, rs1006737 is also strongly associated with schizophrenia, although the effects of the psychosis risk SNP on related brain functions and structures in this population remain unclear. Here, we examined the association of rs1006737 with gray matter volume in a sample of 278 healthy Han Chinese. A whole-brain voxel-based morphometry (VBM) analysis revealed a significant association in the region around right superior occipital gyrus (family-wise error corrected, P = 0.023). Our data provides initial evidence for the involvement of this psychosis genetic risk locus in brain structure variations in Chinese population, and calls for further investigations. PMID:26756527

  6. Allelic Variation in Cell Wall Candidate Genes Affecting Solid Wood Properties in Natural Populations and Land Races of Pinus radiata

    PubMed Central

    Dillon, S. K.; Nolan, M.; Li, W.; Bell, C.; Wu, H. X.; Southerton, S. G.

    2010-01-01

    Forest trees are ideally suited to association mapping due to their high levels of diversity and low genomic linkage disequilibrium. Using an association mapping approach, single-nucleotide polymorphism (SNP) markers influencing quantitative variation in wood quality were identified in a natural population of Pinus radiata. Of 149 sites examined, 10 demonstrated significant associations (P < 0.05, q < 0.1) with one or more traits after accounting for population structure and experimentwise error. Without accounting for marker interactions, phenotypic variation attributed to individual SNPs ranged from 2 to 6.5%. Undesirable negative correlations between wood quality and growth were not observed, indicating potential to break negative correlations by selecting for individual SNPs in breeding programs. Markers that yielded significant associations were reexamined in an Australian land race. SNPs from three genes (PAL1, PCBER, and SUSY) yielded significant associations. Importantly, associations with two of these genes validated associations with density previously observed in the discovery population. In both cases, decreased wood density was associated with the minor allele, suggesting that these SNPs may be under weak negative purifying selection for density in the natural populations. These results demonstrate the utility of LD mapping to detect associations, even when the power to detect SNPs with small effect is anticipated to be low. PMID:20498299

  7. 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. PMID:20445095

  8. Variations and Transmission of QTL Alleles for Yield and Fiber Qualities in Upland Cotton Cultivars Developed in China

    PubMed Central

    Zhang, Tianzhen; Qian, Neng; Zhu, Xiefei; Chen, Hong; Wang, Sen; Mei, Hongxian; Zhang, Yuanming

    2013-01-01

    Cotton is the world’s leading cash crop, and genetic improvement of fiber yield and quality is the primary objective of cotton breeding program. In this study, we used various approaches to identify QTLs related to fiber yield and quality. Firstly, we constructed a four-way cross (4WC) mapping population with four base core cultivars, Stoneville 2B, Foster 6, Deltapine 15 and Zhongmiansuo No.7 (CRI 7), as parents in Chinese cotton breeding history and identified 83 QTLs for 11 agronomic and fiber quality traits. Secondly, association mapping of agronomical and fiber quality traits was based on 121 simple sequence repeat (SSR) markers using a general linear model (GLM). For this, 81 Gossypium hirsutum L. accessions including the four core parents and their derived cultivars were grown in seven diverse environments. Using these approaches, we successfully identified 180 QTLs significantly associated with agronomic and fiber quality traits. Among them were 66 QTLs that were identified via linkage disequilibrium (LD) and 4WC family-based linkage (FBL) mapping and by previously published family-based linkage (FBL) mapping in modern Chinese cotton cultivars. Twenty eight and 44 consistent QTLs were identified by 4WC and LD mapping, and by FBL and LD mapping methods, respectively. Furthermore, transmission and variation of QTL-alleles mapped by LD association in the three breeding periods revealed that some could be detected in almost all Chinese cotton cultivars, suggesting their stable transmission and some identified only in the four base cultivars and not in the modern cultivars, suggesting they were missed in conventional breeding. These results will be useful to conduct genomics-assisted breeding effectively using these existing and novel QTL alleles to improve yield and fiber qualities in cotton. PMID:23468939

  9. 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

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

    2016-04-01

    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

  10. 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

  11. 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. PMID:18048345

  12. 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. PMID:12798016

  13. A new method for studying population genetics of cyst nematodes based on Pool-Seq and genomewide allele frequency analysis.

    PubMed

    Mimee, Benjamin; Duceppe, Marc-Olivier; Véronneau, Pierre-Yves; Lafond-Lapalme, Joël; Jean, Martine; Belzile, François; Bélair, Guy

    2015-11-01

    Cyst nematodes are important agricultural pests responsible for billions of dollars of losses each year. Plant resistance is the most effective management tool, but it requires a close monitoring of population genetics. Current technologies for pathotyping and genotyping cyst nematodes are time-consuming, expensive and imprecise. In this study, we capitalized on the reproduction mode of cyst nematodes to develop a simple population genetic analysis pipeline based on genotyping-by-sequencing and Pool-Seq. This method yielded thousands of SNPs and allowed us to study the relationships between populations of different origins or pathotypes. Validation of the method on well-characterized populations also demonstrated that it was a powerful and accurate tool for population genetics. The genomewide allele frequencies of 23 populations of golden nematode, from nine countries and representing the five known pathotypes, were compared. A clear separation of the pathotypes and fine genetic relationships between and among global populations were obtained using this method. In addition to being powerful, this tool has proven to be very time- and cost-efficient and could be applied to other cyst nematode species. PMID:25846829

  14. Maximum likelihood model based on minor allele frequencies and weighted Max-SAT formulation for haplotype assembly.

    PubMed

    Mousavi, Sayyed R; Khodadadi, Ilnaz; Falsafain, Hossein; Nadimi, Reza; Ghadiri, Nasser

    2014-06-01

    Human haplotypes include essential information about SNPs, which in turn provide valuable information for such studies as finding relationships between some diseases and their potential genetic causes, e.g., for Genome Wide Association Studies. Due to expensiveness of directly determining haplotypes and recent progress in high throughput sequencing, there has been an increasing motivation for haplotype assembly, which is the problem of finding a pair of haplotypes from a set of aligned fragments. Although the problem has been extensively studied and a number of algorithms have already been proposed for the problem, more accurate methods are still beneficial because of high importance of the haplotypes information. In this paper, first, we develop a probabilistic model, that incorporates the Minor Allele Frequency (MAF) of SNP sites, which is missed in the existing maximum likelihood models. Then, we show that the probabilistic model will reduce to the Minimum Error Correction (MEC) model when the information of MAF is omitted and some approximations are made. This result provides a novel theoretical support for the MEC, despite some criticisms against it in the recent literature. Next, under the same approximations, we simplify the model to an extension of the MEC in which the information of MAF is used. Finally, we extend the haplotype assembly algorithm HapSAT by developing a weighted Max-SAT formulation for the simplified model, which is evaluated empirically with positive results. PMID:24491253

  15. Allele frequency-based analyses robustly map sequence sites under balancing selection in a malaria vaccine candidate antigen.

    PubMed Central

    Polley, Spencer D; Chokejindachai, Watcharee; Conway, David J

    2003-01-01

    The Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading candidate for a malaria vaccine. Here, within-population analyses of alleles from 50 Thai P. falciparum isolates yield significant evidence for balancing selection on polymorphisms within the disulfide-bonded domains I and III of the surface accessible ectodomain of AMA1, a result very similar to that seen previously in a Nigerian population. Studying the frequency of nucleotide polymorphisms in both populations shows that the between-population component of variance (F(ST)) is significantly lower in domains I and III compared to the intervening domain II and compared to 11 unlinked microsatellite loci. A nucleotide site-by-site analysis shows that sites with exceptionally high or low F(ST) values cluster significantly into serial runs, with four runs of low values in domain I and one in domain III. These runs may map the sequences that are consistently under the strongest balancing selection from naturally acquired immune responses. PMID:14573469

  16. 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

  17. Regional differences of HFE (C282Y, H63D) allele frequencies in the Netherlands A model case illustrating the significance of genographics and prehistorical population migration.

    PubMed

    Cobbaert, C M; Delanghe, J; Boer, J M A; Feskens, E J M

    2012-01-01

    We investigated HFE C282Y and H63D allele frequencies in three Dutch towns in the Netherlands, as well as their association with cardiovascular disease (CVD) mortality. Study subjects were selected from participants of the Monitoring Project on Cardiovascular Disease Risk Factors in the Netherlands carried out in Amsterdam, Doetinchem and Maastricht among > 35000 subjects, 20-59 years of age. Mortality follow-up lasted 9 to 13 years. A random sample of the cohort (n = 1075) provided information on the total study population. The random sample and all CVD deaths (n = 301) were genotyped for the C282Y and H63D mutation. Adjusted hazard ratios (HR) for CVD mortality were calculated per genotype. C282Y allele frequencies differed significantly between the towns investigated (p = 0.017), whereas the allele frequencies of H63D were similar (p = 0.141) across towns. In Maastricht we found a C282Y allele frequency of 0.086 compared to 0.055 in Amsterdam and 0.054 in Doetinchem. C282Y and H63D heterozygosity did not predict fatal CVD in either men or women, whereas homozygosity for the H63D mutation increased fatal CVD in women (adjusted HR = 8.5; 95% CI = 2.3-31.1). The unexpected high C282Y allele frequency in Maastricht is in line with the recent evidence of a Celtic origin of citizens from the former southern Netherlands and with prehistorical population migrations revealed in the context of the international Genographic Project, a landmark study of prehistorical human migrations around the globe. We recommend that when designing national screening programmes and national registries for genetic disorders, potential regional prevalence differences should be taken into account. PMID:23340149

  18. 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

  19. 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

  20. Association of Allelic Variation in PtoXET16A with Growth and Wood Properties in Populus tomentosa

    PubMed Central

    Wang, Bowen; Zhang, Deqiang

    2014-01-01

    Xyloglucan endo-transglycosylases (XETs) modify the xyloglucan-cellulose framework of plant cell walls and, thus, affect cell wall expansion and strength. Dissecting the mechanism by which natural variation in XETs affects wood properties can inform breeding efforts to improve wood quality and yield traits. To this end, we isolated a full-length PtoXET16A cDNA clone from Populus tomentosa. Real-time PCR analysis showed that PtoXET16A was maximally expressed in the root, followed by phloem, cambium, and developing xylem, suggesting that PtoXET16A plays important roles in the development of vascular tissues. Nucleotide diversity and linkage disequilibrium analysis revealed that PtoXET16A has high single nucleotide polymorphism (SNP) diversity (π = 0.01266 and θw = 0.01392) and low linkage disequilibrium (r2 ≥ 0.1, within 900 bp). SNP- and haplotype-based association analyses of 426 individuals from a natural population indicated that nine SNPs (including two non-synonymous markers and one splicing variant) (p ≤ 0.05, false discovery rate Q ≤ 0.01), and nine haplotypes (p ≤ 0.05) were significantly associated with growth and wood properties, each explaining from 3.40%–10.95% of phenotypic variance. This work shows that examination of allelic variation and linkage disequilibrium by a candidate-gene-based approach can help to decipher the genetic basis of wood formation. Moreover, the SNP markers identified in this study can potentially be applied for marker-assisted selection to improve growth and wood-property traits in Populus. PMID:25250912

  1. 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

  2. MHC class II variation in a rare and ecological specialist mouse lemur reveals lower allelic richness and contrasting selection patterns compared to a generalist and widespread sympatric congener.

    PubMed

    Pechouskova, Eva; Dammhahn, Melanie; Brameier, Markus; Fichtel, Claudia; Kappeler, Peter M; Huchard, Elise

    2015-04-01

    The polymorphism of immunogenes of the major histocompatibility complex (MHC) is thought to influence the functional plasticity of immune responses and, consequently, the fitness of populations facing heterogeneous pathogenic pressures. Here, we evaluated MHC variation (allelic richness and divergence) and patterns of selection acting on the two highly polymorphic MHC class II loci (DRB and DQB) in the endangered primate Madame Berthe's mouse lemur (Microcebus berthae). Using 454 pyrosequencing, we examined MHC variation in a total of 100 individuals sampled over 9 years in Kirindy Forest, Western Madagascar, and compared our findings with data obtained previously for its sympatric congener, the grey mouse lemur (Microcebus murinus). These species exhibit a contrasting ecology and demography that were expected to affect MHC variation and molecular signatures of selection. We found a lower allelic richness concordant with its low population density, but a similar level of allelic divergence and signals of historical selection in the rare feeding specialist M. berthae compared to the widespread generalist M. murinus. These findings suggest that demographic factors may exert a stronger influence than pathogen-driven selection on current levels of allelic richness in M. berthae. Despite a high sequence similarity between the two congeners, contrasting selection patterns detected at DQB suggest its potential functional divergence. This study represents a first step toward unravelling factors influencing the adaptive divergence of MHC genes between closely related but ecologically differentiated sympatric lemurs and opens new questions regarding potential functional discrepancy that would explain contrasting selection patterns detected at DQB. PMID:25687337

  3. 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

  4. 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

    Kohyama, Moeko; Tada, Naomi; Mitsui, Hiroko; Tomioka, Hitomi; Tsutsui, Toshihiko; Yabuki, Akira; Rahman, Mohammad Mahbubur; Kushida, Kazuya; Mizukami, Keijiro; Yamato, Osamu

    2016-03-01

    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

  5. Effects of cigarette smoking on human in vivo somatic mutation: Longitudinal sampling of smokers demonstrates a decrease in glycophorin A (GPA) allele-loss variant cell frequencies following cessation

    SciTech Connect

    Bigbee, W.L.; Langlois, R.G. ); Grant, S.G.; Jensen, R.H. ); Mooney, L.M.; Perera, F.P. )

    1993-01-01

    The human in vivo glycophorin A (GPA) assay uses immunolabeling and flow cytometry to quantitate somatic variation in erythrocytes expressing GPA allele loss and allele-loss and duplication phenotypes in peripheral blood samples. The frequency of these variant erythrocytes (V[sub f]) presumably reflects the level of somatic mutation at this locus in the nucleated hematopoietic precursor cells of the bone marrow. We have previously shown that the GPA assay is a cumulative, integrating biodosimeter of accidental, medical, and occupational exposure to chemical mutagens and ionizing radiation. Surveys of otherwise unexposed populations point to an increased GPA allele loss V[sub f] in cigarette smokers compared to nonsmokers consistent with the induction of somatic mutation by mutagenic components of tobacco smoke. To further test this association, blood samples from active heavy smokers who entered a multi-endpoint Smokender study were obtained at enrollment and at 10 wks and 6 and 12 mo following smoking cessation. Results from the first 109 individuals reveal a decrease in the mean GPA allele loss V[sub f] ranging from 9.0 [+-] 1.0 [times] 10[sup [minus]6] (n = 109) for the active smoking samples, to 9.1 [+-] 1.8 [times] 10[sup [minus]6] (n = 46), 6.0 [+-] 0.7 [times] 10[sup [minus]6] (n = 15), and 5.8 [+-] 1.6 [times] 10[sup [minus]6] (n = 8) for the three postcessation samples, respectively. No change in the GPA allele loss and duplication V[sub f] was observed, thus confining the spectrum of mutational events induced by exposure to cigarette smoke. The observed decrease in the level of somatic mutation in smokers following cessation suggests limited persistence and/or repair of tobacco-smoke-induced genetic alterations consistent with epidemiologic findings of decreased cancer risk in smokers following cessation.

  6. Automated analysis of high-throughput B-cell sequencing data reveals a high frequency of novel immunoglobulin V gene segment alleles

    PubMed Central

    Gadala-Maria, Daniel; Yaari, Gur; Uduman, Mohamed; Kleinstein, Steven H.

    2015-01-01

    Individual variation in germline and expressed B-cell immunoglobulin (Ig) repertoires has been associated with aging, disease susceptibility, and differential response to infection and vaccination. Repertoire properties can now be studied at large-scale through next-generation sequencing of rearranged Ig genes. Accurate analysis of these repertoire-sequencing (Rep-Seq) data requires identifying the germline variable (V), diversity (D), and joining (J) gene segments used by each Ig sequence. Current V(D)J assignment methods work by aligning sequences to a database of known germline V(D)J segment alleles. However, existing databases are likely to be incomplete and novel polymorphisms are hard to differentiate from the frequent occurrence of somatic hypermutations in Ig sequences. Here we develop a Tool for Ig Genotype Elucidation via Rep-Seq (TIgGER). TIgGER analyzes mutation patterns in Rep-Seq data to identify novel V segment alleles, and also constructs a personalized germline database containing the specific set of alleles carried by a subject. This information is then used to improve the initial V segment assignments from existing tools, like IMGT/HighV-QUEST. The application of TIgGER to Rep-Seq data from seven subjects identified 11 novel V segment alleles, including at least one in every subject examined. These novel alleles constituted 13% of the total number of unique alleles in these subjects, and impacted 3% of V(D)J segment assignments. These results reinforce the highly polymorphic nature of human Ig V genes, and suggest that many novel alleles remain to be discovered. The integration of TIgGER into Rep-Seq processing pipelines will increase the accuracy of V segment assignments, thus improving B-cell repertoire analyses. PMID:25675496

  7. Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: comparison with caucasian and asian populations.

    PubMed

    Roco, Angela; 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

  8. 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

  9. Frequency variations of discrete cranial traits in major human populations. I. Supernumerary ossicle variations

    PubMed Central

    HANIHARA, TSUNEHIKO; ISHIDA, HAJIME

    2001-01-01

    Four supernumerary ossicle variations—the ossicle at the lambda, the parietal notch bone, the asterionic bone, and the occipitomastoid bone—were examined for laterality differences, intertrait correlations, sex differences, and between group variations in the samples from around the world. Significant laterality differences were not detected in almost all samples. In some pairs of traits, significant association of occurrence were found. Several geographic samples were sexually dimorphic with respect to the asterionic bone and to a lesser extent for the parietal notch bone. East/Northeast Asians including the Arctic populations in general had lower frequencies of the 4 accessory ossicles. Australians, Melanesians and the majority of the New World peoples, on the other hand, generally had high frequencies. In the western hemisphere of the Old World, Subsaharan Africans had relatively high frequencies. Except for the ossicle at the lambda, the distribution pattern in incidence showed clinal variation from south to north. Any identifiable adaptive value related to environmental or subsistence factors may be expressed in such clinal variation. This may allow us to hypothesise that not only mechanical factors but a founder effect, genetic drift, and population structure could have been the underlying causes for interregional variation and possible clines in the incidences of the accessory ossicles. PMID:11465862

  10. 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

  11. Single molecule molecular inversion probes for targeted, high-accuracy detection of low-frequency variation

    PubMed Central

    Hiatt, Joseph B.; Pritchard, Colin C.; Salipante, Stephen J.; O'Roak, Brian J.; Shendure, Jay

    2013-01-01

    The detection and quantification of genetic heterogeneity in populations of cells is fundamentally important to diverse fields, ranging from microbial evolution to human cancer genetics. However, despite the cost and throughput advances associated with massively parallel sequencing, it remains challenging to reliably detect mutations that are present at a low relative abundance in a given DNA sample. Here we describe smMIP, an assay that combines single molecule tagging with multiplex targeted capture to enable practical and highly sensitive detection of low-frequency or subclonal variation. To demonstrate the potential of the method, we simultaneously resequenced 33 clinically informative cancer genes in eight cell line and 45 clinical cancer samples. Single molecule tagging facilitated extremely accurate consensus calling, with an estimated per-base error rate of 8.4 × 10−6 in cell lines and 2.6 × 10−5 in clinical specimens. False-positive mutations in the single molecule consensus base-calls exhibited patterns predominantly consistent with DNA damage, including 8-oxo-guanine and spontaneous deamination of cytosine. Based on mixing experiments with cell line samples, sensitivity for mutations above 1% frequency was 83% with no false positives. At clinically informative sites, we identified seven low-frequency point mutations (0.2%–4.7%), including BRAF p.V600E (melanoma, 0.2% alternate allele frequency), KRAS p.G12V (lung, 0.6%), JAK2 p.V617F (melanoma, colon, two lung, 0.3%–1.4%), and NRAS p.Q61R (colon, 4.7%). We anticipate that smMIP will be broadly adoptable as a practical and effective method for accurately detecting low-frequency mutations in both research and clinical settings. PMID:23382536

  12. Allele Frequencies of the Single Nucleotide Polymorphisms Related to the Body Burden of Heavy Metals in the Korean Population and Their Ethnic Differences

    PubMed Central

    Eom, Sang-Yong; Lim, Ji-Ae; Kim, Yong-Dae; Choi, Byung-Sun; Hwang, Myung Sil; Park, Jung-Duck; Kim, Heon; Kwon, Ho-Jang

    2016-01-01

    This study was performed to select single nucleotide polymorphisms (SNPs) related to the body burden of heavy metals in Koreans, to provide Korean allele frequencies of selected SNPs, and to assess the difference in allele frequencies with other ethnicities. The candidate-gene approach method and genome-wide association screening were used to select SNPs related to the body burden of heavy metals. Genotyping analysis of the final 192 SNPs selected was performed on 1,483 subjects using the VeraCode Goldengate assay. Allele frequencies differences and genetic differentiations between the Korean population and Chinese (CHB), Japanese (JPT), Caucasian (CEU), and African (YIR) populations were tested by Fisher’s exact test and fixation index (FST), respectively. The Korean population was genetically similar to the CHB and JPT populations (FST < 0.05, for all SNPs in both populations). However, a significant difference in the allele frequencies between the Korean and CEU and YIR populations were observed in 99 SNPs (60.7%) and 120 SNPs (73.6%), respectively. Ten (6.1%) and 26 (16.0%) SNPs had genetic differentiation (FST > 0.05) among the Korean-CEU and Korean-YIR comparisons, respectively. The SNP with the largest FST value between the Korean and African populations was cystathionine-β-synthase rs234709 (FST: KOR-YIR, 0.309; KOR-CEU, 0.064). Our study suggests that interethnic differences exist in SNPs associated with heavy metals of Koreans, and it should be considered in future studies that address ethnic differences in heavy-metal concentrations in the body and genetic susceptibility to the body burden of heavy metals. PMID:27437086

  13. Status of allele frequency and diversity of Plasmodium falciparum msp1, msp2 and glurp before implementation of an artemisinin-based combined therapy in Northwestern Colombia.

    PubMed Central

    Arango, Eliana; Carmona-Fonseca, Jaime

    2013-01-01

    Introduction: The status of msp1, msp2 and glurp allele frequency and the diversity of Plasmodium falciparum in Northwestern Colombia before the implementation of an artemisinin-combined therapy have been explored only by a few authors and in a relatively small number of samples from this highly endemic region. Objective: To evaluate the frequency of msp1, msp2, and glurp alleles and the diversity of P. falciparum in two Colombian regions before the use of an artemisinin-combined therapy. Methods: This study was part of a major anti-malarial efficacy trial designed as a random, clinically-controlled study for which 224 subjects were recruited. Region 2 of msp1 and msp2 (central region) were amplified by a nested PCR; glurp (region R2) was amplified by a semi-nested PCR. Results: For msp1, five genotypes were observed, representing the K1, MAD20, and RO33 allelic families. All samples corresponded to a MAD20 150 bp allele. For msp2 (IC family), two alleles were detected and for glurp, eight were observed. A total 33 haplotypes were detected. Conclusions: Analysis of glurpcan be used to successfully genotype parasite populations in the new studies in Colombia aimed at exploring Plasmodium spp population dynamics. In addition, analysis of msp1 and msp2 can also be of value for comparisons with past studies, but not when the objective is to study parasites obtained from the same patient in a reduced period of time; for instance, during treatment efficacy studies. PMID:24892236

  14. Rapid genotyping assays for the 4-base pair deletion of canine MDR1/ABCB1 gene and low frequency of the mutant allele in Border Collie dogs.

    PubMed

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

    2012-01-01

    P-glycoprotein, encoded by the MDR1 or ABCB1 gene, is an integral component of the blood-brain barrier as an efflux pump for xenobiotics crucial in limiting drug uptake into the central nervous system. Dogs homozygous for a 4-base pair deletion of the canine MDR1 gene show altered expression or function of P-glycoprotein, resulting in neurotoxicosis after administration of the substrate drugs. In the present study, the usefulness of microchip electrophoresis for genotyping assays detecting this deletion mutation was evaluated. Mutagenically separated polymerase chain reaction (MS-PCR) and real-time PCR assays were newly developed and evaluated. Furthermore, a genotyping survey was carried out in a population of Border Collies dogs in Japan to determine the allele frequency in this breed. Microchip electrophoresis showed advantages in detection sensitivity and time saving over other modes of electrophoresis. The MS-PCR assay clearly discriminated all genotypes. Real-time PCR assay was most suitable for a large-scale survey due to its high throughput and rapidity. The genotyping survey demonstrated that the carrier and mutant allele frequencies were 0.49% and 0.25%, respectively, suggesting that the mutant allele frequency in Border Collies is markedly low compared to that in the susceptible dog breeds such as rough and smooth Collies. PMID:22362942

  15. 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. PMID:27352221

  16. Five-year tracking of Plasmodium falciparum allele frequencies in a holoendemic area with indistinct seasonal transitions

    PubMed Central

    Akala, Hoseah M; Achieng, Angela O; Eyase, Fredrick L; Juma, Dennis W; Ingasia, Luiser; Cheruiyot, Agnes C; Okello, Charles; Omariba, Duke; Owiti, Eunice A; Muriuki, Catherine; Yeda, Redemptah; Andagalu, Ben; Johnson, Jacob D; Kamau, Edwin

    2014-01-01

    Background The renewed malaria eradication efforts require an understanding of the seasonal patterns of frequency of polymorphic variants in order to focus limited funds productively. Although cross-sectional studies in holoendemic areas spanning a single year could be useful in describing parasite genotype status at a given point, such information is inadequate in describing temporal trends in genotype polymorphisms. For Plasmodium falciparum isolates from Kisumu District Hospital, Plasmodium falciparum chloroquine-resistance transporter gene (Pfcrt-K76T) and P. falciparum multidrug resistance gene 1 (PfMDR1-N86Y), were analyzed for polymorphisms and parasitemia changes in the 53 months from March 2008 to August 2012. Observations were compared with prevailing climatic factors, including humidity, rainfall, and temperature. Methods Parasitemia (the percentage of infected red blood cells per total red blood cells) was established by microscopy for P. falciparum malaria-positive samples. P. falciparum DNA was extracted from whole blood using a Qiagen DNA Blood Mini Kit. Single nucleotide polymorphism identification at positions Pfcrt-K76T and PfMDR1-N86Y was performed using real-time polymerase chain reaction and/or sequencing. Data on climatic variables were obtained from http://www.tutiempo.net/en/. Results A total of 895 field isolates from 2008 (n=169), 2009 (n=161), 2010 (n=216), 2011 (n=223), and 2012 (n=126) showed large variations in monthly frequency of PfMDR1-N86Y and Pfcrt-K76T as the mutant genotypes decreased from 68.4%±15% and 38.1%±13% to 29.8%±18% and 13.3%±9%, respectively. The mean percentage of parasitemia was 2.61%±1.01% (coefficient of variation 115.86%; n=895). There was no correlation between genotype or parasitemia and climatic factors. Conclusion This study shows variability in the frequency of Pfcrt-K76T and PfMDR1-N86Y polymorphisms during the study period, bringing into focus the role of cross-sectional studies in describing temporal

  17. High Frequency of Pathogenic Rearrangements in SPG11 and Extensive Contribution of Mutational Hotspots and Founder Alleles.

    PubMed

    Günther, Sven; Elert-Dobkowska, Ewelina; Soehn, Anne S; Hinreiner, Sophie; Yoon, Grace; Heller, Raoul; Hellenbroich, Yorck; Hübner, Christian A; Ray, Peter N; Hehr, Ute; Bauer, Peter; Sulek, Anna; Beetz, Christian

    2016-07-01

    Biallelic loss-of-function mutations in SPG11 cause a wide spectrum of recessively inherited, neurodegenerative disorders including hereditary spastic paraplegia (HSP), amyotrophic lateral sclerosis, and Charcot-Marie-Tooth disease. By comprehensive screening of three large cohorts of HSP index patients, we identified 83 alleles with "small" mutations and 13 alleles that carry large genomic rearrangements. Including relevant data from previous studies, we estimate that copy number variants (CNVs) account for ∼19% of pathogenic SPG11 alleles. The breakpoints for all novel and some previously reported CNVs were determined by long-range PCR and sequencing. This revealed several Alu-associated recombination hotspots. We also found evidence for additional mutational mechanisms, including for a two-step event in which an Alu retrotransposition preceded the actual rearrangement. Apparently independent samples with identical breakpoints were analyzed by microsatellite PCRs. The resulting haplotypes suggested the existence of two rearrangement founder alleles. Our findings widen the spectra of mutations and mutational mechanisms in SPG11, underscore the pivotal role played by Alus, and are of high diagnostic relevance for a wide spectrum of clinical phenotypes including the most frequent form of recessive HSP. PMID:27071356

  18. Extreme Recombination Frequencies Shape Genome Variation and Evolution in the Honeybee, Apis mellifera

    PubMed Central

    Wallberg, Andreas; Glémin, Sylvain; Webster, Matthew T.

    2015-01-01

    Meiotic recombination is a fundamental cellular process, with important consequences for evolution and genome integrity. However, we know little about how recombination rates vary across the genomes of most species and the molecular and evolutionary determinants of this variation. The honeybee, Apis mellifera, has extremely high rates of meiotic recombination, although the evolutionary causes and consequences of this are unclear. Here we use patterns of linkage disequilibrium in whole genome resequencing data from 30 diploid honeybees to construct a fine-scale map of rates of crossing over in the genome. We find that, in contrast to vertebrate genomes, the recombination landscape is not strongly punctate. Crossover rates strongly correlate with levels of genetic variation, but not divergence, which indicates a pervasive impact of selection on the genome. Germ-line methylated genes have reduced crossover rate, which could indicate a role of methylation in suppressing recombination. Controlling for the effects of methylation, we do not infer a strong association between gene expression patterns and recombination. The site frequency spectrum is strongly skewed from neutral expectations in honeybees: rare variants are dominated by AT-biased mutations, whereas GC-biased mutations are found at higher frequencies, indicative of a major influence of GC-biased gene conversion (gBGC), which we infer to generate an allele fixation bias 5 – 50 times the genomic average estimated in humans. We uncover further evidence that this repair bias specifically affects transitions and favours fixation of CpG sites. Recombination, via gBGC, therefore appears to have profound consequences on genome evolution in honeybees and interferes with the process of natural selection. These findings have important implications for our understanding of the forces driving molecular evolution. PMID:25902173

  19. Frequency of HLA-DRB1 and HLA-DQB1 Alleles and Haplotype Association in Syrian Population.

    PubMed

    Jazairi, Batoul; Khansaa, Issam; Ikhtiar, Adnan; Murad, Hossam

    2016-02-01

    The study of Human Leukocyte Antigen (HLA) system is very important in health and diseases. As the HLA loci are the most polymorphic in the human genome, it plays a very important role in the immune responses to self and nonself antigens. In the light of the growing importance of typing the HLA alleles in transplantation, autoimmune diseases, cancer, and many other diseases, we studied 225 unrelated healthy Syrian subjects for their HLA class II genotypes in an attempt to reveal the distribution of the HLA (DRB1-DQB1) alleles in the general Syrian population. Our results revealed that the most common alleles for the DRB1 locus were DRB1*11 (26.4%), DRB1*04 (14%), and DRB1*07 (12%). However, the most frequent alleles for the DQB1 locus were DQB1*03 (40.9%) and DQB1*05 (25.1%). The frequent of two-locus haplotypes carry the most frequent alleles at these loci. The most frequently detected class II ''haplotypes'' are DRB1*11-DQB1*03 (8.9%), DRB1*01-DQB1*05 (3.6%), and DRB1*04-DQB1*03 (2.7%). Compared with other populations, our result, deduced from the analysis of genetic distances and the construction of neighbor-joining (NJ) dendrogram, and principal component analysis (PCA) indicates that Syrians are related to Middle Eastern populations. Our data about the Syrian population will aid researchers in studying the relation of HLA class II with different diseases in a Syrian population and will add to the available international literature associated with these loci. PMID:26853713

  20. Vestibular function is associated with residual low-frequency hearing loss in patients with bi-allelic mutations in the SLC26A4 gene.

    PubMed

    Jung, Jinsei; Seo, Young Wook; Choi, Jae Young; Kim, Sung Huhn

    2016-05-01

    DFNB4 is non-syndromic, autosomal recessive type of hearing loss with an enlarged vestibular aqueduct (EVA) caused by mutations in SLC26A4/pendrin. Although the characteristics of hearing loss are well known in DFNB4, vestibular function remains inconclusive. We evaluated the vestibular function of 31 patients with bi-allelic mutations in SLC26A4/pendrin and analyzed genetic, radiological, and audiological correlations with vestibular function. In a caloric test, unilateral and bilateral vestibulopathies were detected in 45.2% and 6.4% of patients, respectively; however, only 22.6% had subjective vertigo symptoms. While vestibular phenotype was not significantly associated with specific mutations in genetic alleles or the sizes of the endolymphatic sac and vestibular aqueduct, a residual hearing threshold at a low frequency (500 Hz) was definitely correlated with vestibular function in DFNB4 (p = 0.005). These findings may indicate that vestibular function in DFNB4 deteriorates unilaterally in ears when hearing loss occurs. In conclusion, DFNB4 shows vestibular dysfunction, which is strongly linked to hearing loss at low frequencies without any allelic or anatomical predisposing factor. PMID:26900070

  1. Frequency of alleles conferring resistance to Bt maize in French and US corn belt populations of the European corn borer, Ostrinia nubilalis.

    PubMed

    Bourguet, D; Chaufaux, J; Séguin, M; Buisson, C; Hinton, J L; Stodola, T J; Porter, P; Cronholm, G; Buschman, L L; Andow, D A

    2003-05-01

    Farmers, industry, governments and environmental groups agree that it would be useful to manage transgenic crops producing insecticidal proteins to delay the evolution of resistance in target pests. The main strategy proposed for delaying resistance to Bacillus thuringiensis ( Bt) toxins in transgenic crops is the high-dose/refuge strategy. This strategy is based on the unverified assumption that resistance alleles are initially rare (<10(-3)). We used an F(2) screen on >1,200 isofemale lines of Ostrinia nubilalis Hübner (Lepidoptera: Crambidae) collected in France and the US corn belt during 1999-2001. In none of the isofemale lines did we detect alleles conferring resistance to Bt maize producing the Cry1Ab toxin. A Bayesian analysis of the data indicates that the frequency of resistance alleles in France was <9.20 x 10(-4) with 95% probability, and a detection probability of >80%. In the northern US corn belt, the frequency of resistance to Bt maize was <4.23 x 10(-4) with 95% probability, and a detection probability of >90%. Only 95 lines have been screened from the southern US corn belt, so these data are still inconclusive. These results suggest that resistance is probably rare enough in France and the northern US corn belt for the high-dose plus refuge strategy to delay resistance to Bt maize. PMID:12748773

  2. HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype frequencies in a population of 432 healthy unrelated individuals from Albania.

    PubMed

    Sulcebe, Genc; Shyti, Erkena

    2016-08-01

    This paper reports the HLA-A, -B, -C, -DRB1 and -DQB1 allele and haplotype polymorphism in a population of 432 healthy individuals from Albania. First-field HLA genotyping was performed by polymerase chain reaction sequence-specific priming and/or oligonucleotide methods. The data were analyzed statistically using gene counting and Arlequin software packages. No deviation from Hardy Weinberg Equilibrium was detected at any of the loci studied. The HLA genotypic data of the population sample reported here are available publicly in the Allele Frequencies Net Database and they can serve as a reference database for further HLA-based population genetics studies including the Albanian population. PMID:27262454

  3. Allele frequencies and population data for 17 Y-STR loci (The AmpFlSTR® Y-filer™) in Casablanca resident population.

    PubMed

    Laouina, Adil; El Houate, Brahim; Yahia, Hakima; Azeddoug, Houssine; Boulouiz, Redouane; Chbel, Faiza

    2011-01-01

    Allele frequencies and population data for 17 Y-STR loci included in the AmpFlSTR® Y-filer™ PCR amplification kit (Applied Biosystems, Foster City, USA), that permit the simultaneous amplification of all the markers included in the actually used European "extended haplotype", DYS19, DYS189I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385I/II, DYS438, DYS439 and also DYS437, DYS448, DYS456, DYS458, DYS635 and Y GATA H4, were obtained from a sample of 166 healthy unrelated males resident in Casablanca (from Morocco). A total of 166 haplotypes were identified, of which 142 were unique. The overall haplotype diversity for the 17 Y-STR loci reached 0.9974, and a discrimination capacity was 0.855. We report some non-standard situations, including duplications and microvariant alleles. PMID:21126935

  4. Variation of herbivore-induced volatile terpenes among Arabidopsis ecotypes depends on allelic differences and subcellular targeting of two terpene synthases, TPS02 and TPS03.

    PubMed

    Huang, Mengsu; Abel, Christian; Sohrabi, Reza; Petri, Jana; Haupt, Ina; Cosimano, John; Gershenzon, Jonathan; Tholl, Dorothea

    2010-07-01

    When attacked by insects, plants release mixtures of volatile compounds that are beneficial for direct or indirect defense. Natural variation of volatile emissions frequently occurs between and within plant species, but knowledge of the underlying molecular mechanisms is limited. We investigated intraspecific differences of volatile emissions induced from rosette leaves of 27 accessions of Arabidopsis (Arabidopsis thaliana) upon treatment with coronalon, a jasmonate mimic eliciting responses similar to those caused by insect feeding. Quantitative variation was found for the emission of the monoterpene (E)-beta-ocimene, the sesquiterpene (E,E)-alpha-farnesene, the irregular homoterpene 4,8,12-trimethyltridecatetra-1,3,7,11-ene, and the benzenoid compound methyl salicylate. Differences in the relative emissions of (E)-beta-ocimene and (E,E)-alpha-farnesene from accession Wassilewskija (Ws), a high-(E)-beta-ocimene emitter, and accession Columbia (Col-0), a trace-(E)-beta-ocimene emitter, were attributed to allelic variation of two closely related, tandem-duplicated terpene synthase genes, TPS02 and TPS03. The Ws genome contains a functional allele of TPS02 but not of TPS03, while the opposite is the case for Col-0. Recombinant proteins of the functional Ws TPS02 and Col-0 TPS03 genes both showed (E)-beta-ocimene and (E,E)-alpha-farnesene synthase activities. However, differential subcellular compartmentalization of the two enzymes in plastids and the cytosol was found to be responsible for the ecotype-specific differences in (E)-beta-ocimene/(E,E)-alpha-farnesene emission. Expression of the functional TPS02 and TPS03 alleles is induced in leaves by elicitor and insect treatment and occurs constitutively in floral tissues. Our studies show that both pseudogenization in the TPS family and subcellular segregation of functional TPS enzymes control the variation and plasticity of induced volatile emissions in wild plant species. PMID:20463089

  5. 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

  6. Allelic variation in a simple sequence repeat element of neisserial pglB2 and its consequences for protein expression and protein glycosylation.

    PubMed

    Viburiene, Raimonda; Vik, Åshild; Koomey, Michael; Børud, Bente

    2013-08-01

    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

  7. Loss of Mhc and Neutral Variation in Peary Caribou: Genetic Drift Is Not Mitigated by Balancing Selection or Exacerbated by Mhc Allele Distributions

    PubMed Central

    Taylor, Sabrina S.; Jenkins, Deborah A.; Arcese, Peter

    2012-01-01

    Theory and empirical results suggest that the rate of loss of variation at Mhc and neutral microsatellite loci may differ because selection influences Mhc genes, and because a high proportion of rare alleles at Mhc loci may result in high rates of loss via drift. Most published studies compare Mhc and microsatellite variation in various contemporary populations to infer the effects of population size on genetic variation, even though different populations are likely to have different demographic histories that may also affect contemporary genetic variation. We directly compared loss of variation at Mhc and microsatellite loci in Peary caribou by comparing historical and contemporary samples. We observed that similar proportions of genetic variation were lost over time at each type of marker despite strong evidence for selection at Mhc genes. These results suggest that microsatellites can be used to estimate genome-wide levels of variation, but also that adaptive potential is likely to be lost following population bottlenecks. However, gene conversion and recombination at Mhc loci may act to increase variation following bottlenecks. PMID:22655029

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

    PubMed

    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

  9. 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

  10. Analysis of the distribution of HLA-A alleles in populations from five continents.

    PubMed

    Middleton, D; Williams, F; Meenagh, A; Daar, A S; Gorodezky, C; Hammond, M; Nascimento, E; Briceno, I; Perez, M P

    2000-10-01

    The variation and frequency of HLA-A genotypes were established by PCR-SSOP typing in diverse geographically distributed populations: Brazilian, Colombian Kogui, Cuban, Mexican, Omani, Singapore Chinese, and South African Zulu. HLA-A allelic families with only one allele were identified for HLA-A*01, -A*23, -A*25, -A*31, -A*32, -A*36, -A*43, -A*69, -A*80; and with two alleles for HLA-A*03, -A*11, -A*26, -A*29, -A*33, -A*34, and -A*66. Greater variation was detected for HLA-A*02, -A*24, and -A*68 allele families. Colombian Kogui and Mexican Seris showed the least diversity with respect to HLA-A alleles, albeit with small numbers tested, with only four and five HLA-A alleles identified, respectively. It would appear by their presence in all populations studied, either rural or indigenous, that certain alleles are very important in pathogen peptide presentation. PMID:11082518

  11. Characterization and allelic variation of the transporters associated with antigen processing (TAP) genes in the domestic dog (Canis lupus familiaris).

    PubMed

    Gojanovich, Gregory S; Ross, Peter; Holmer, Savannah G; Holmes, Jennifer C; Hess, Paul R

    2013-12-01

    The function of the transporters associated with antigen processing (TAP) complex is to shuttle antigenic peptides from the cytosol to the endoplasmic reticulum to load MHC class I molecules for CD8(+) T-cell immunosurveillance. Here we report the promoter and coding regions of the canine TAP1 and TAP2 genes, which encode the homologous subunits forming the TAP heterodimer. By sampling genetically divergent breeds, polymorphisms in both genes were identified, although there were few amino acid differences between alleles. Splice variants were also found. When aligned to TAP genes of other species, functional regions appeared conserved, and upon phylogenetic analysis, canine sequences segregated appropriately with their orthologs. Transfer of the canine TAP2 gene into a murine TAP2-defective cell line rescued surface MHC class I expression, confirming exporter function. This data should prove useful in investigating the association of specific TAP defects or alleles with immunity to intracellular pathogens and cancer in dogs. PMID:23892057

  12. Characterization and allelic variation of the transporters associated with antigen processing (TAP) genes in the domestic dog (Canis lupus familiaris)

    PubMed Central

    Gojanovich, Gregory S.; Ross, Peter; Holmer, Savannah R.; Holmes, Jennifer C.; Hess, Paul R.

    2013-01-01

    The function of the transporters associated with antigen processing (TAP) complex is to shuttle antigenic peptides from the cytosol to the endoplasmic reticulum to load MHC class I molecules for CD8+ T-cell immunosurveillance. Here we report the promoter and coding regions of the canine TAP1 and TAP2 genes, which encode the homologous subunits forming the TAP heterodimer. By sampling genetically divergent breeds, polymorphisms in both genes were identified, although there were few amino acid differences between alleles. Splice variants were also found. When aligned to TAP genes of other species, functional regions appeared conserved, and upon phylogenetic analysis, canine sequences segregated appropriately with their orthologs. Transfer of the canine TAP2 gene into a murine TAP2-defective cell line rescued surface MHC class I expression, confirming exporter function. This data should prove useful in investigating the association of specific TAP defects or alleles with immunity to intracellular pathogens and cancer in dogs. PMID:23892057

  13. 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

  14. 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

  15. 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. PMID:26940567

  16. 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

  17. 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

  18. 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

  19. Dominance variation across six herbicides of the Arabidopsis thaliana csr1-1 and csr1-2 resistance alleles.

    PubMed

    Roux, Fabrice; Matéjicek, Annick; Gasquez, Jacques; Reboud, Xavier

    2005-11-01

    Dominance of a resistance trait can be defined as a measure of the relative position of the phenotype of the heterozygote RS compared with the phenotype of the two corresponding homozygotes, SS and RR. This parameter has been shown to have primary importance in the dynamics of pesticide resistance evolution. Literature on insecticide resistance suggests that dominance levels in the presence of insecticide vary greatly from completely recessive to completely dominant. With insecticides, both the chemical applied and the dosages used have been demonstrated to affect the dominance. By contrast, almost all herbicide resistances have been found to be inherited as partially to totally dominant traits. This discrepancy between weeds and insects may partly result from the methodologies applied to measure the dominance, ie a single dose for herbicide versus several doses for insecticide. Using two well-known resistances (csr1-1 and csr1-2) to acetolactate synthase (ALS) inhibitors in Arabidopsis thaliana (L) Heynh (mouse-ear cress), we used several herbicide doses to determine the dominance level to six ALS-inhibiting herbicides. The dominance level in the presence of herbicide varied from completely dominant to completely recessive, depending on the resistance allele and the herbicide tested. The dominance of the csr1-1 and csr1-2 resistance alleles ranged from 0 (completely recessive) to 1.1 (dominant) and from 0 to 0.3 (partially dominant), respectively. The recessivity of some resistance alleles in the presence of herbicide could lead to the development of improved resistance management in order to delay or avoid herbicide resistance evolution, especially in the control of outcrossing weed species. PMID:16007690

  20. 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

  1. Allelic Variations at Four Major Maturity E Genes and Transcriptional Abundance of the E1 Gene Are Associated with Flowering Time and Maturity of Soybean Cultivars

    PubMed Central

    Wang, Yueqiang; Chen, Xin; Ren, Haixiang; Yang, Jiayin; Cheng, Wen; Zong, Chunmei; Gu, Heping; Qiu, Hongmei; Wu, Hongyan; Zhang, Xingzheng; Cui, Tingting; Xia, Zhengjun

    2014-01-01

    The time to flowering and maturity are ecologically and agronomically important traits for soybean landrace and cultivar adaptation. As a typical short-day crop, long day conditions in the high-latitude regions require soybean cultivars with photoperiod insensitivity that can mature before frost. Although the molecular basis of four major E loci (E1 to E4) have been deciphered, it is not quite clear whether, or to what degree, genetic variation and the expression level of the four E genes are associated with the time to flowering and maturity of soybean cultivars. In this study, we genotyped 180 cultivars at E1 to E4 genes, meanwhile, the time to flowering and maturity of those cultivars were investigated at six geographic locations in China from 2011 to 2012 and further confirmed in 2013. The percentages of recessive alleles at E1, E2, E3 and E4 loci were 38.34%, 84.45%, 36.33%, and 7.20%, respectively. Statistical analysis showed that allelic variations at each of four loci had a significant effect on flowering time as well as maturity. We classified the 180 cultivars into eight genotypic groups based on allelic variations of the four major E loci. The genetic group of e1-nf representing dysfunctional alleles at the E1 locus flowered earliest in all the geographic locations. In contrast, cultivars in the E1E2E3E4 group originated from the southern areas flowered very late or did not flower before frost at high latitude locations. The transcriptional abundance of functional E1 gene was significantly associated with flowering time. However, the ranges of time to flowering and maturity were quite large within some genotypic groups, implying the presence of some other unknown genetic factors that are involved in control of flowering time or maturity. Known genes (e.g. E3 and E4) and other unknown factors may function, at least partially, through regulation of the expression of the E1 gene. PMID:24830458

  2. 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. PMID:26832308

  3. Allelic variations in the CYBA gene of NADPH oxidase and risk of kidney complications in patients with type 1 diabetes.

    PubMed

    Patente, Thiago A; Mohammedi, Kamel; Bellili-Muñoz, Naïma; Driss, Fathi; Sanchez, Manuel; Fumeron, Frédéric; Roussel, Ronan; Hadjadj, Samy; Corrêa-Giannella, Maria Lúcia; Marre, Michel; Velho, Gilberto

    2015-09-01

    Oxidative stress plays a pivotal role in the pathophysiology of diabetic nephropathy, and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system is an important source of reactive oxygen species in hyperglycemic conditions in the kidney. Plasma concentration of advanced oxidation protein products (AOPP), a marker of oxidative stress, is increased in patients with diabetic nephropathy. We investigated associations of variants in the CYBA gene, encoding the regulatory subunit p22(phox) of NADPH oxidase, with diabetic nephropathy and plasma AOPP and myeloperoxidase (MPO) concentrations in type 1 diabetic patients. Seven SNPs in the CYBA region were analyzed in 1357 Caucasian subjects with type 1 diabetes from the SURGENE (n=340), GENEDIAB (n=444), and GENESIS (n=573) cohorts. Duration of follow-up was 10, 9, and 6 years, respectively. Cox proportional hazards and logistic regression analyses were used to estimate hazard ratios (HR) or odds ratios (OR) for incidence and prevalence of diabetic nephropathy. The major G-allele of rs9932581 was associated with the incidence of renal events defined as new cases of microalbuminuria or the progression to a more severe stage of nephropathy during follow-up (HR 1.59, 95% CI 1.17-2.18, P=0.003) in SURGENE. The same allele was associated with established/advanced nephropathy (OR 1.52, 95% CI 1.22-1.92, P=0.0001) and with the incidence of end-stage renal disease (ESRD) (HR 2.01, 95% CI 1.30-3.24, P=0.001) in GENEDIAB/GENESIS pooled studies. The risk allele was also associated with higher plasma AOPP concentration in subsets of SURGENE and GENEDIAB, with higher plasma MPO concentration in a subset of GENEDIAB, and with lower estimated glomerular filtration rate (eGFR) in the three cohorts. In conclusion, a functional variant in the promoter of the CYBA gene was associated with lower eGFR and with prevalence and incidence of diabetic nephropathy and ESRD in type 1 diabetic patients. These results are consistent with

  4. 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

  5. HLA-A, B and DRB1 allele and haplotype frequencies in volunteer bone marrow donors from the north of Parana State

    PubMed Central

    Bardi, Marlene Silva; Jarduli, Luciana Ribeiro; Jorge, Adylson Justino; Camargo, Rossana Batista Oliveira Godoy; Carneiro, Fernando Pagotto; Gelinski, Jair Roberto; Silva, Roseclei Assunção Feliciano; Lavado, Edson Lopes

    2012-01-01

    Background Knowledge of allele and haplotype frequencies of the human leukocyte antigen (HLA) system is important in the search for unrelated bone marrow donors. The Brazilian population is very heterogeneous and the HLA system is highly informative of populations because of the high level of polymorphisms. Aim The aim of this study was to characterize the immunogenetic profile of ethnic groups (Caucasians, Afro-Brazilians and Asians) in the north of Parana State. Methods A study was carried out of 3978 voluntary bone marrow donors registered in the Brazilian National Bone Marrow Donor Registry and typed for the HLA-A, B and DRB1 (low resolution) loci. The alleles were characterized by the polymerase chain reaction sequence-specific oligonucleotides method using the LabType SSO kit (One Lambda, CA, USA). The ARLEQUIN v.3.11 computer program was used to calculate allele and haplotype frequencies Results The most common alleles found in Caucasians were HLA-A*02, 24, 01; HLA-B*35, 44, 51; DRB1*11, 13, 07; for Afro-Brazilians they were HLA-A*02, 03, 30; HLA-B*35, 15, 44; DRB1*13, 11, 03; and for Asians they were: HLA-A*24, 02, 26; HLA-B*40, 51, 52; DRB1*04, 15, 09. The most common haplotype combinations were: HLA-A*01, B*08, DRB1*03 and HLA-A*29, B*44, DRB1*07 for Caucasians; HLA-A*29, B*44, DRB1*07 and HLA-A*01, B*08 and DRB1*03 for Afro-Brazilians; and HLA-A*24, B*52, DRB1*15 and HLA-A*24, B*40 and DRB1*09 for Asians. Conclusion There is a need to target and expand bone marrow donor campaigns in the north of Parana State. The data of this study may be used as a reference by the Instituto Nacional de Cancer/Brazilian National Bone Marrow Donor Registry to evaluate the immunogenetic profile of populations in specific regions and in the selection of bone marrow donors PMID:23049380

  6. alpha1-antitrypsin (PI) alleles as markers of Westeuropean influence in the Baltic Sea region.

    PubMed

    Beckman, L; Sikström, C; Mikelsaar, A; Krumina, A; Kucinskas, V; Beckman, G

    1999-01-01

    The distribution of alpha1-antitrypsin (PI) alleles was studied in an attempt to elucidate migrations and admixture between populations in the Baltic Sea region. The frequency of the PI Z allele, a typically Northwesteuropean marker gene, showed a highly significant regional variation in the Baltic Sea region. The highest frequency (4.5%) was found in the western part of Latvia (Courland). The PI S allele, another marker of Westeuropean influence, also showed an increased frequency in the Courland population. These results indicate that among the populations east of the Baltic Sea the Curonian population has the most pronounced Westeuropean influence. Archaeological data have shown that from the 7th century and for several hundreds of years Courland received immigrations from mainland Sweden and the island of Gotland. We speculate that the increased frequencies of the PI Z alleles and S alleles in Courland may have been caused by these migrations. PMID:9858859

  7. 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…

  8. A further polymorphism of the Gd locus for glucose-6-phosphate dehydrogenase present among blacks (Nigerians) and apparently absent among Caucasoids: the quantitative isoelectrophoretic variation of the Gd+ allele.

    PubMed

    Modiano, G; Ciminelli, B M; Malaspina, P; Santolamazza, P; Sedran, L; Meloni, T; Forteleoni, G; Mela, G

    1991-01-01

    A structural but isoelectrophoretic moderate variation of glucose-6-phosphate dehydrogenase (G6PD) activity is common among Nigerians (a black population exposed to a long-lasting intense Plasmodium falciparum malarial endemia). It had never even been searched for among Caucasoids and Mongoloids. In the present work, we attempted to ascertain whether this polymorphism exists among Caucasoids. With this purpose, two Caucasoid male populations were studied: Sardinians and Romans, who respectively did and did not experience an evolutionarily effective exposure to P. falciparum. The approach adopted here consisted in comparing the variations of G6PD activity observed between brothers who certainly received their Gd gene from the same grandparent (hence Gd genes identical by descent) with those between brothers who received it (in the Roman series) or may have received it (in the Sardinian series) from different grandparents. No evidence for common moderate G6PD activity variations segregating with the Gd gene was found either in Romans or Sardinians, who have both been studied with much larger samples and more sensitive approaches than those which detected such type of polymorphism among Nigerians. The upper 95% confidence limit of such zero estimates for the frequency of the isoelectrophoretic quantitative Gd variant alleles were about 0.04 and 0.025 for Romans and Sardinians, respectively. This is the first example of a genetic region (the Gd gene with its flanking sequences) apparently monomorphic in a major race and with several (four) polymorphic sites in another major race. PMID:1797629

  9. 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.

  10. 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. PMID:22362793

  11. Allelic variations in the vitamin D receptor gene, insulin secretion and parents' heights are independently associated with height in obese children and adolescents.

    PubMed

    Ferrarezi, Daniela A F; Bellili-Muñoz, Naïma; Nicolau, Christiane; Cheurfa, Nadir; Guazzelli, Isabel C; Frazzatto, Eliana; Velho, Gilberto; Villares, Sandra M

    2012-10-01

    Polymorphisms in the VDR gene were reported to be associated with variations in intrauterine and postnatal growth and with adult height, but also with other traits that are strongly correlated such as the BMI, insulin sensitivity, insulin secretion and hyperglycemia. Here, we assessed the impact of VDR polymorphisms on body height and its interactions with obesity- and glucose tolerance-related traits in obese children and adolescents. We studied 173 prepubertal (Tanner's stage 1) and 146 pubertal (Tanner's stages 2-5) obese children who were referred for a weight-loss program. Three single nucleotide polymorphisms were genotyped: rs1544410 (BsmI), rs7975232 (ApaI) and rs731236 (TaqI). BsmI and TaqI genotypes were significantly associated with height in pubertal children, but the associations did not reach statistical significance in prepubertal children. In stepwise regression analyses, the lean body mass, insulin secretion, BsmI or TaqI genotypes and the father's and the mother's height were independently and positively associated with height in pubertal children. These covariables accounted for 46% of the trait variance. The height of homozygous carriers of the minor allele of BsmI was 0.65 z-scores (4cm) higher than the height of homozygous carriers of the major allele (P=.0006). Haplotype analyses confirmed the associations of the minor alleles of BsmI and TaqI with increased height. In conclusion, VDR genotypes were significantly associated with height in pubertal obese children. The associations were independent from the effects of confounding traits, such as the body fat mass, insulin secretion, insulin sensitivity and glucose tolerance. PMID:22551951

  12. Alcelaphine Herpesvirus-1 (Malignant Catarrhal Fever Virus) in Wildebeest Placenta: Genetic Variation of ORF50 and A9.5 Alleles

    PubMed Central

    Lankester, Felix; Lugelo, Ahmed; Mnyambwa, Nicholas; Ndabigaye, Ahab; Keyyu, Julius; Kazwala, Rudovick; Grant, Dawn M.; Relf, Valerie; Haig, David M.; Cleaveland, Sarah; Russell, George C.

    2015-01-01

    Alcelaphine herpesvirus–1 (AlHV-1), a causative agent of malignant catarrhal fever in cattle, was detected in wildebeest (Connochaetes taurinus) placenta tissue for the first time. Although viral load was low, the finding of viral DNA in over 50% of 94 samples tested lends support to the possibility that placental tissue could play a role in disease transmission and that wildebeest calves are infected in utero. Two viral loci were sequenced to examine variation among virus samples obtained from wildebeest and cattle: the ORF50 gene, encoding the lytic cycle transactivator protein, and the A9.5 gene, encoding a novel polymorphic viral glycoprotein. ORF50 was well conserved with six newly discovered alleles differing at only one or two base positions. In contrast, while only three new A9.5 alleles were discovered, these differed by up to 13% at the nucleotide level and up to 20% at the amino acid level. Structural homology searching performed with the additional A9.5 sequences determined in this study adds power to recent analysis identifying the four-helix bundle cytokine interleukin-4 (IL4) as the major homologue. The majority of MCF virus samples obtained from Tanzanian cattle and wildebeest encoded A9.5 polypeptides identical to the previously characterized A9.5 allele present in the laboratory maintained AlHV-1 C500 strain. This supports the view that AlHV-1 C500 is suitable for the development of a vaccine for wildebeest-associated MCF. PMID:25969987

  13. Alcelaphine Herpesvirus-1 (Malignant Catarrhal Fever Virus) in Wildebeest Placenta: Genetic Variation of ORF50 and A9.5 Alleles.

    PubMed

    Lankester, Felix; Lugelo, Ahmed; Mnyambwa, Nicholas; Ndabigaye, Ahab; Keyyu, Julius; Kazwala, Rudovick; Grant, Dawn M; Relf, Valerie; Haig, David M; Cleaveland, Sarah; Russell, George C

    2015-01-01

    Alcelaphine herpesvirus-1 (AlHV-1), a causative agent of malignant catarrhal fever in cattle, was detected in wildebeest (Connochaetes taurinus) placenta tissue for the first time. Although viral load was low, the finding of viral DNA in over 50% of 94 samples tested lends support to the possibility that placental tissue could play a role in disease transmission and that wildebeest calves are infected in utero. Two viral loci were sequenced to examine variation among virus samples obtained from wildebeest and cattle: the ORF50 gene, encoding the lytic cycle transactivator protein, and the A9.5 gene, encoding a novel polymorphic viral glycoprotein. ORF50 was well conserved with six newly discovered alleles differing at only one or two base positions. In contrast, while only three new A9.5 alleles were discovered, these differed by up to 13% at the nucleotide level and up to 20% at the amino acid level. Structural homology searching performed with the additional A9.5 sequences determined in this study adds power to recent analysis identifying the four-helix bundle cytokine interleukin-4 (IL4) as the major homologue. The majority of MCF virus samples obtained from Tanzanian cattle and wildebeest encoded A9.5 polypeptides identical to the previously characterized A9.5 allele present in the laboratory maintained AlHV-1 C500 strain. This supports the view that AlHV-1 C500 is suitable for the development of a vaccine for wildebeest-associated MCF. PMID:25969987

  14. 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...

  15. 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

  16. Multi-allelic major effect genes interact with minor effect QTLs to control adaptive color pattern variation in Heliconius erato.

    PubMed

    Papa, Riccardo; Kapan, Durrell D; Counterman, Brian A; Maldonado, Karla; Lindstrom, Daniel P; Reed, Robert D; Nijhout, H Frederik; Hrbek, Tomas; McMillan, W Owen

    2013-01-01

    Recent studies indicate that relatively few genomic regions are repeatedly involved in the evolution of Heliconius butterfly wing patterns. Although this work demonstrates a number of cases where homologous loci underlie both convergent and divergent wing pattern change among different Heliconius species, it is still unclear exactly how many loci underlie pattern variation across the genus. To address this question for Heliconius erato, we created fifteen independent crosses utilizing the four most distinct color pattern races and analyzed color pattern segregation across a total of 1271 F2 and backcross offspring. Additionally, we used the most variable brood, an F2 cross between H. himera and the east Ecuadorian H. erato notabilis, to perform a quantitative genetic analysis of color pattern variation and produce a detailed map of the loci likely involved in the H. erato color pattern radiation. Using AFLP and gene based markers, we show that fewer major genes than previously envisioned control the color pattern variation in H. erato. We describe for the first time the genetic architecture of H. erato wing color pattern by assessing quantitative variation in addition to traditional linkage mapping. In particular, our data suggest three genomic intervals modulate the bulk of the observed variation in color. Furthermore, we also identify several modifier loci of moderate effect size that contribute to the quantitative wing pattern variation. Our results are consistent with the two-step model for the evolution of mimetic wing patterns in Heliconius and support a growing body of empirical data demonstrating the importance of major effect loci in adaptive change. PMID:23533571

  17. 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. PMID:10646230

  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

    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. PMID:24532702

  19. 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

  20. Diurnal Expression Pattern, Allelic Variation, and Association Analysis Reveal Functional Features of the E1 Gene in Control of Photoperiodic Flowering in Soybean

    PubMed Central

    Wu, Hongyan; Zhang, Yupeng; Zhang, Xingzheng; Yang, Jiayin; Wang, Yaying; Yang, Guang; Qiu, Hongmei; Cui, Tingting; Xia, Zhengjun

    2015-01-01

    Although four maturity genes, E1 to E4, in soybean have been successfully cloned, their functional mechanisms and the regulatory network of photoperiodic flowering remain to be elucidated. In this study, we investigated how the diurnal expression pattern of the E1 gene is related to photoperiodic length; and to what extent allelic variation in the B3-like domain of the E1 gene is associated with flowering time phenotype. The bimodal expression of the E1 gene peaked first at around 2 hours after dawn in long-day condition. The basal expression level of E1 was enhanced by the long light phase, and decreased by duration of dark. We identified a 5bp (3 SNP and 2-bp deletion) mutation, referred to an e1-b3a, which occurs in the middle of B3 domain of the E1 gene in the early flowering cultivar Yanhuang 3. Subcellular localization analysis showed that the putative truncated e1-b3a protein was predominately distributed in nuclei, indicating the distribution pattern of e1-b3a was similar to that of E1, but not to that of e1-as. Furthermore, genetic analysis demonstrated allelic variations at the E1 locus significantly underlay flowering time in three F2 populations. Taken together, we can conclude the legume specific E1 gene confers some special features in photoperiodic control of flowering in soybean. Further characterization of the E1 gene will extend our understanding of the soybean flowering pathway in soybean. PMID:26275311

  1. Cerebellum volume in high-risk offspring from multiplex alcohol dependence families: association with allelic variation in GABRA2 and BDNF.

    PubMed

    Hill, Shirley Y; Wang, Shuhui; Carter, Howard; Tessner, Kevin; Holmes, Brian; McDermott, Michael; Zezza, Nicholas; Stiffler, Scott

    2011-12-30

    Offspring from families with multiple cases of alcohol dependence have a greater likelihood of developing alcohol dependence (AD) and related substance use disorders. Greater susceptibility for developing these disorders may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing and AD susceptibility. We examined the cerebellum of 71 adolescent/young adult high-risk (HR) offspring from families with multiple cases of alcohol dependence (multiplex families), and 60 low-risk (LR) controls with no family history of alcohol or drug dependence who were matched for age, gender, socioeconomic status and IQ, with attention given to possible effects of personal use of substances and maternal use during pregnancy. Magnetic resonance images were acquired on a General Electric 1.5-Tesla scanner and manually traced (BRAINS2) blind to clinical information. GABRA2 and BDNF variation were tested for their association with cerebellar volumes. High-risk offspring from multiplex AD families showed greater total volume of the cerebellum and total gray matter (GM), in comparison with LR controls. An interaction between allelic variation in GABRA2 and BDNF genes was associated with GM volumes, suggesting that inherited variation in these genes may promote early developmental differences in neuronal proliferation of the cerebellum. PMID:22047728

  2. Cerebellum volume in high-risk offspring from multiplex alcohol dependence families: Association with allelic variation in GABRA2 and BDNF

    PubMed Central

    Hill, Shirley Y.; Wang, Shuhui; Carter, Howard; Tessner, Kevin; Holmes, Brian; McDermott, Michael; Zezza, Nicholas; Stiffler, Scott

    2012-01-01

    Offspring from families with multiple cases of alcohol dependence have a greater likelihood of developing alcohol dependence (AD) and related substance use disorders. Greater susceptibility for developing these disorders may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing and AD susceptibility. We examined the cerebellum of 71 adolescent/young adult high-risk (HR) offspring from families with multiple cases of alcohol dependence (multiplex families), and 60 low-risk (LR) controls with no family history of alcohol or drug dependence who were matched for age, gender, socioeconomic status and IQ, with attention given to possible effects of personal use of substances and maternal use during pregnancy. Magnetic resonance images were acquired on a General Electric 1.5-Tesla scanner and manually traced (BRAINS2) blind to clinical information. GABRA2 and BDNF variation were tested for their association with cerebellar volumes. High-risk offspring from multiplex AD families showed greater total volume of the cerebellum and total gray matter (GM), in comparison with LR controls. An interaction between allelic variation in GABRA2 and BDNF genes was associated with GM volumes, suggesting that inherited variation in these genes may promote early developmental differences in neuronal proliferation of the cerebellum. PMID:22047728

  3. 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

  4. 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. PMID:27311063

  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. Allelic Variation in the Perennial Ryegrass FLOWERING LOCUS T Gene Is Associated with Changes in Flowering Time across a Range of Populations1[W

    PubMed Central

    Skøt, Leif; Sanderson, Ruth; Thomas, Ann; Skøt, Kirsten; Thorogood, Danny; Latypova, Galina; Asp, Torben; Armstead, Ian

    2011-01-01

    The Arabidopsis (Arabidopsis thaliana) FLOWERING LOCUS T (FT) gene and its orthologs in other plant species (e.g. rice [Oryza sativa] OsFTL2/Hd3a) have an established role in the photoperiodic induction of flowering response. The genomic and phenotypic variations associated with the perennial ryegrass (Lolium perenne) ortholog of FT, designated LpFT3, was assessed in a diverse collection of nine European germplasm populations, which together constituted an association panel of 864 plants. Sequencing and genotyping of a series of amplicons derived from the nine populations, containing the complete exon and intron sequences as well as 5′ and 3′ noncoding sequences of LpFT3, identified a total of seven haplotypes. Genotyping assays designed to detect the genomic variation showed that three haplotypes were present in approximately equal proportions and represented 84% of the total, with a fourth representing a further 11%. Of the three major haplotypes, two were predicted to code for identical protein products and the third contained two amino acid substitutions. Association analysis using either a mixed model with a relationship matrix to correct for population structure and relatedness or structured association with further correction using genomic control indicated significant associations between LpFT3 and variation in flowering time. These associations were corroborated in a validation population segregating for the same major alleles. The most “diagnostic” region of genomic variation was situated 5′ of the coding sequence. Analysis of this region identified that the interhaplotype variation was closely associated with sequence motifs that were apparently conserved in the 5′ region of orthologs of LpFT3 from other plant species. These may represent cis-regulatory elements involved in influencing the expression of this gene. PMID:21115808

  7. Allelic Variation in a Cellulose Synthase Gene (PtoCesA4) Associated with Growth and Wood Properties in Populus tomentosa

    PubMed Central

    Du, Qingzhang; Xu, Baohua; Pan, Wei; Gong, Chenrui; Wang, Qingshi; Tian, Jiaxing; Li, Bailian; Zhang, Deqiang

    2013-01-01

    Lignocellulosic biomass from trees provides a renewable feedstock for biofuels, lumber, pulp, paper, and other uses. Dissecting the mechanism underlying natural variation of the complex traits controlling growth and lignocellulose biosynthesis in trees can enable marker-assisted breeding to improve wood quality and yield. Here, we combined linkage disequilibrium (LD)-based association analysis with traditional linkage analysis to detect the genetic effect of a Populus tomentosa cellulose synthase gene, PtoCesA4. PtoCesA4 is strongly expressed in developing xylem and leaves. Nucleotide diversity and LD in PtoCesA4, sampled from the P. tomentosa natural distribution, revealed that PtoCesA4 harbors high single nucleotide polymorphism (SNP) diversity (πT = 0.0080 and θw = 0.0098) and low LD (r2 ≥ 0.1, within 1400 bp), demonstrating that the potential of a candidate-gene-based LD approach in understanding the molecular basis underlying quantitative variation in this species. By combining single SNP, multi-SNP, and haplotype-based associations in an association population of 460 individuals with single SNP linkage analysis in a family-based linkage populations (1200 individuals), we identified three strong associations (false discovery rate Q < 0.05) in both populations. These include two nonsynonymous markers (SNP49 associated with α-cellulose content and SNP59 associated with fiber width) and a noncoding marker (SNP18 associated with α-cellulose content). Variation in RNA transcript abundance among genotypic classes of SNP49 was confirmed in these two populations. Therefore, combining different methods allowed us to examine functional PtoCesA4 allelic variation underlying natural variation in complex quantitative traits related to growth and lignocellulosic biosynthesis. PMID:24048648

  8. Identification of Neisseria meningitidis genetic loci involved in the modulation of phase variation frequencies.

    PubMed

    Alexander, Heather L; Rasmussen, Andrew W; Stojiljkovic, Igor

    2004-11-01

    It has been proposed that increased phase variation frequencies in Neisseria meningitidis augment transmissibility and invasiveness. A Himar1 mariner transposon mutant library was constructed in serogroup A N. meningitidis and screened for clones with increased phase variation frequencies. Insertions increasing the frequency of slippage events within mononucleotide repeat tracts were identified in three known phase variation-modulating genes (mutS, mutL, and uvrD), as well as six additional loci (pilP, fbpA, fbpB, NMA1233, and two intergenic regions). The implications of these insertion mutations are discussed. PMID:15501815

  9. 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

  10. 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

  11. Prevalence and allele frequency estimation of bovine leukocyte adhesion deficiency (BLAD) in Holstein-Friesian cattle in Japan.

    PubMed

    Nagahata, H; Miura, T; Tagaki, K; Ohtake, M; Noda, H; Yasuda, T; Nioka, K

    1997-04-01

    Blood samples from 796 Holstein dairy cows in 20 herds from 6 districts in Japan from June 1994 to August 1995 were examined to determine whether they were BLAD-free, BLAD carriers, or BLAD-affected by use of DNA-polymerase chain reaction (PCR) analysis. The usage of semen of confirmed BLAD-carriers for artificial insemination in the Hokkaido district and two selected dairy farms was examined to estimate the gene frequency of BLAD carriers of sires. BLAD-carrier prevalence in 20 herds (796 cows, over 2.5 years old) ranged from 0 to 23.5%, and the mean BLAD-carrier prevalence was 8.1%. The BLAD-carrier prevalence in 10 herds (363 cows) in which the occurrence of BLAD was not detected by the DNA-PCR test ranged from 0 to 12.5% with a mean of 5.4%. The BLAD-carrier prevalence in 10 herds (433 cows) in which the occurrence of BLAD was confirmed by DNA-PCR analysis ranged from 2.6 to 23.5% with a mean of 10.8%, and these values were significantly (P < 0.05) higher than those of dairy herds in which the occurrence of BLAD was not detected. The age distribution in BLAD carriers in these cows ranged from 2.5 to 11 years. The mean gene frequencies of BLAD among 796 cows from 20 herds and 433 cows from 10 herds in which the occurrence of BLAD was detected were 0.041 and 0.054, respectively. The proportional usage of semen of BLAD carriers for artificial insemination in the Hokkaido district in 1992 was 12.6%, and its gene frequency was 0.058. On two selected farms in which higher BLAD-carrier rates were detected, the prevalences were 35.5% and 25.8%, and their gene frequencies were 0.177 and 0.129, respectively. The occurrence of BLAD-affected in Holstein dairy cattle was estimated to be 0.16-0.31% at birth in Japan without genetic control. PMID:9152929

  12. Multiple post-domestication origins of kabuli chickpea through allelic variation in a diversification-associated transcription factor.

    PubMed

    Varma Penmetsa, R; Carrasquilla-Garcia, Noelia; Bergmann, Emily M; Vance, Lisa; Castro, Brenna; Kassa, Mulualem T; Sarma, Birinchi K; Datta, Subhojit; Farmer, Andrew D; Baek, Jong-Min; Coyne, Clarice J; Varshney, Rajeev K; von Wettberg, Eric J B; Cook, Douglas R

    2016-09-01

    Chickpea (Cicer arietinum) is among the founder crops domesticated in the Fertile Crescent. One of two major forms of chickpea, the so-called kabuli type, has white flowers and light-colored seed coats, properties not known to exist in the wild progenitor. The origin of the kabuli form has been enigmatic. We genotyped a collection of wild and cultivated chickpea genotypes with 538 single nucleotide polymorphisms (SNPs) and examined patterns of molecular diversity relative to geographical sources and market types. In addition, we examined sequence and expression variation in candidate anthocyanin biosynthetic pathway genes. A reduction in genetic diversity and extensive genetic admixture distinguish cultivated chickpea from its wild progenitor species. Among germplasm, the kabuli form is polyphyletic. We identified a basic helix-loop-helix (bHLH) transcription factor at chickpea's B locus that conditions flower and seed colors, orthologous to Mendel's A gene of garden pea, whose loss of function is associated invariantly with the kabuli type of chickpea. From the polyphyletic distribution of the kabuli form in germplasm, an absence of nested variation within the bHLH gene and invariant association of loss of function of bHLH among the kabuli type, we conclude that the kabuli form arose multiple times during the phase of phenotypic diversification after initial domestication of cultivated chickpea. PMID:27193699

  13. Next-generation sequencing of ABCA4: High frequency of complex alleles and novel mutations in patients with retinal dystrophies from Central Europe.

    PubMed

    Ścieżyńska, Aneta; Oziębło, Dominika; Ambroziak, Anna M; Korwin, Magdalena; Szulborski, Kamil; Krawczyński, Maciej; Stawiński, Piotr; Szaflik, Jerzy; Szaflik, Jacek P; Płoski, Rafał; Ołdak, Monika

    2016-04-01

    Variation in the ABCA4 locus has emerged as the most prevalent cause of monogenic retinal diseases. The study aimed to discover causative ABCA4 mutations in a large but not previously investigated cohort with ABCA4-related diseases originating from Central Europe and to refine the genetic relevance of all identified variants based on population evidence. Comprehensive clinical studies were performed to identify patients with Stargardt disease (STGD, n = 76) and cone-rod dystrophy (CRD, n = 16). Next-generation sequencing targeting ABCA4 was applied for a widespread screening of the gene. The results were analyzed in the context of exome data from a corresponding population (n = 594) and other large genomic databases. Our data disprove the pathogenic status of p.V552I and provide more evidence against a causal role of four further ABCA4 variants as drivers of the phenotype under a recessive paradigm. The study identifies 12 novel potentially pathogenic mutations (four of them recurrent) and a novel complex allele p.[(R152*; V2050L)]. In one third (31/92) of our cohort we detected the p.[(L541P; A1038V)] complex allele, which represents an unusually high level of genetic homogeneity for ABCA4-related diseases. Causative ABCA4 mutations account for 79% of STGD and 31% of CRD cases. A combination of p.[(L541P; A1038V)] and/or a truncating ABCA4 mutation always resulted in an early disease onset. Identification of ABCA4 retinopathies provides a specific molecular diagnosis and justifies a prompt introduction of simple precautions that may slow disease progression. The comprehensive, population-specific study expands our knowledge on the genetic landscape of retinal diseases. PMID:26593885

  14. 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

  15. Allelic variations in coding regions of the vitamin D receptor gene in dairy cows and potential susceptibility to periparturient hypocalcaemia.

    PubMed

    Deiner, Carolin; Reiche, Maria; Lassner, Dirk; Grienitz, Desirée; Twardziok, Sven; Moesch, Anne; Wenning, Peter; Martens, Holger

    2012-11-01

    Periparturient hypocalcaemia (milk fever) is a disorder of Ca metabolism in dairy cattle primarily affecting multiparous cows. The major reasons for the rapid decrease of blood Ca concentration after calving are the prompt increase of Ca secretion into the colostrum and the delayed activation of Ca regulation mechanisms including calcitriol, a metabolite of vitamin D. In man, vitamin D receptor (VDR) gene polymorphisms are reported to be associated with disturbances of Ca metabolism, whereas data confirming the same in dairy cows are still missing. Moreover, polymorphisms that only affect non-coding regions are sometimes difficult to ascribe to a specific disorder as pathways and unequivocal links remain elusive. Therefore, the idea of the present study was to investigate in a small group of dairy cows with documented clinical records whether polymorphisms in the coding regions of the VDR gene existed and whether these potentially found variations were correlated with the incidence of periparturient hypocalcaemia. For this purpose, blood DNA was isolated from 26 dairy cows in their 4th to 6th lactation, out of which 17 had experienced hypocalcaemia at least once, whereas 9 cows had never undergone periparturient hypocalcaemia in their lifetime. The 10 VDR exons and small parts of adjacent introns were sequenced and compared with the Bos taurus VDR sequence published on NCBI based on the DNA of one Hereford cow. In total, 8 sequence alterations were detected in the fragments, which were primarily heterozygous. However, only 4 of them were really located on exons thereby potentially causing changes of the encoded amino acid of the VDR protein, but were not correlated with the incidence of periparturient hypocalcaemia. Certainly, this lack of statistical correlation could be due to the small number of animals included; anyhow, it was not encouraging enough to initiate a larger study with hundreds of cows and document blood Ca levels post partum for at least four

  16. 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.

  17. Inter- and Intra-Individual Variation in Allele-Specific DNA Methylation and Gene Expression in Children Conceived using Assisted Reproductive Technology

    PubMed Central

    Turan, Nahid; Katari, Sunita; Gerson, Leigh F.; Chalian, Raffi; Foster, Michael W.; Gaughan, John P.; Coutifaris, Christos; Sapienza, Carmen

    2010-01-01

    Epidemiological studies have reported a higher incidence of rare disorders involving imprinted genes among children conceived using assisted reproductive technology (ART), suggesting that ART procedures may be disruptive to imprinted gene methylation patterns. We examined intra- and inter-individual variation in DNA methylation at the differentially methylated regions (DMRs) of the IGF2/H19 and IGF2R loci in a population of children conceived in vitro or in vivo. We found substantial variation in allele-specific methylation at both loci in both groups. Aberrant methylation of the maternal IGF2/H19 DMR was more common in the in vitro group, and the overall variance was also significantly greater in the in vitro group. We estimated the number of trophoblast stem cells in each group based on approximation of the variance of the binomial distribution of IGF2/H19 methylation ratios, as well as the distribution of X chromosome inactivation scores in placenta. Both of these independent measures indicated that placentas of the in vitro group were derived from fewer stem cells than the in vivo conceived group. Both IGF2 and H19 mRNAs were significantly lower in placenta from the in vitro group. Although average birth weight was lower in the in vitro group, we found no correlation between birth weight and IGF2 or IGF2R transcript levels or the ratio of IGF2/IGF2R transcript levels. Our results show that in vitro conception is associated with aberrant methylation patterns at the IGF2/H19 locus. However, very little of the inter- or intra-individual variation in H19 or IGF2 mRNA levels can be explained by differences in maternal DMR DNA methylation, in contrast to the expectations of current transcriptional imprinting models. Extraembryonic tissues of embryos cultured in vitro appear to be derived from fewer trophoblast stem cells. It is possible that this developmental difference has an effect on placental and fetal growth. PMID:20661447

  18. Preservation of Tetherin and CD4 Counter-Activities in Circulating Vpu Alleles despite Extensive Sequence Variation within HIV-1 Infected Individuals

    PubMed Central

    Pickering, Suzanne; Hué, Stephane; Kim, Eun-Young; Reddy, Susheel; Wolinsky, Steven M.; Neil, Stuart J. D.

    2014-01-01

    The HIV-1 Vpu protein is expressed from a bi-cistronic message late in the viral life cycle. It functions during viral assembly to maximise infectious virus release by targeting CD4 for proteosomal degradation and counteracting the antiviral protein tetherin (BST2/CD317). Single genome analysis of vpu repertoires throughout infection in 14 individuals infected with HIV-1 clade B revealed extensive amino acid diversity of the Vpu protein. For the most part, this variation in Vpu increases over the course of infection and is associated with predicted epitopes of the individual's MHC class I haplotype, suggesting CD8+ T cell pressure is the major driver of Vpu sequence diversity within the host. Despite this variability, the Vpu functions of targeting CD4 and counteracting both physical virus restriction and NF-κB activation by tetherin are rigorously maintained throughout HIV-1 infection. Only a minority of circulating alleles bear lesions in either of these activities at any given time, suggesting functional Vpu mutants are heavily selected against even at later stages of infection. Comparison of Vpu proteins defective for one or several functions reveals novel determinants of CD4 downregulation, counteraction of tetherin restriction, and inhibition of NF-κB signalling. These data affirm the importance of Vpu functions for in vivo persistence of HIV-1 within infected individuals, not simply for transmission, and highlight its potential as a target for antiviral therapy. PMID:24465210

  19. Natural selection on marine carnivores elaborated a diverse family of classical MHC class I genes exhibiting haplotypic gene content variation and allelic polymorphism.

    PubMed

    Hammond, John A; Guethlein, Lisbeth A; Norman, Paul J; Parham, Peter

    2012-12-01

    Pinnipeds, marine carnivores, diverged from terrestrial carnivores ~45 million years ago, before their adaptation to marine environments. This lifestyle change exposed pinnipeds to different microbiota and pathogens, with probable impact on their MHC class I genes. Investigating this question, genomic sequences were determined for 71 MHC class I variants: 27 from harbor seal and 44 from gray seal. These variants form three MHC class I gene lineages, one comprising a pseudogene. The second, a candidate nonclassical MHC class I gene, comprises a nonpolymorphic transcribed gene related to dog DLA-79 and giant panda Aime-1906. The third is the diversity lineage, which includes 62 of the 71 seal MHC class I variants. All are transcribed, and they minimally represent six harbor and 12 gray seal MHC class I genes. Besides species-specific differences in gene number, seal MHC class I haplotypes exhibit gene content variation and allelic polymorphism. Patterns of sequence variation, and of positions for positively selected sites, indicate the diversity lineage genes are the seals' classical MHC class I genes. Evidence that expansion of diversity lineage genes began before gray and harbor seals diverged is the presence in both species of two distinctive sublineages of diversity lineage genes. Pointing to further expansion following the divergence are the presence of species-specific genes and greater MHC class I diversity in gray seals than harbor seals. The elaboration of a complex variable family of classical MHC class I genes in pinnipeds contrasts with the single, highly polymorphic classical MHC class I gene of dog and giant panda, terrestrial carnivores. PMID:23001684

  20. 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. PMID:17911381

  1. Natural selection on marine carnivores elaborated a diverse family of classical MHC class I genes exhibiting haplotypic gene content variation and allelic polymorphism

    PubMed Central

    Norman, Paul J.; Parham, Peter

    2012-01-01

    Pinnipeds, marine carnivores, diverged from terrestrial carnivores ~45 million years ago, before their adaptation to marine environments. This lifestyle change exposed pinnipeds to different microbiota and pathogens, with probable impact on their MHC class I genes. Investigating this question, genomic sequences were determined for 71 MHC class I variants: 27 from harbor seal and 44 from gray seal. These variants form three MHC class I gene lineages, one comprising a pseudogene. The second, a candidate nonclassical MHC class I gene, comprises a nonpolymorphic transcribed gene related to dog DLA-79 and giant panda Aime-1906. The third is the diversity lineage, which includes 62 of the 71 seal MHC class I variants. All are transcribed, and they minimally represent six harbor and 12 gray seal MHC class I genes. Besides species-specific differences in gene number, seal MHC class I haplotypes exhibit gene content variation and allelic polymorphism. Patterns of sequence variation, and of positions for positively selected sites, indicate the diversity lineage genes are the seals’ classical MHC class I genes. Evidence that expansion of diversity lineage genes began before gray and harbor seals diverged is the presence in both species of two distinctive sublineages of diversity lineage genes. Pointing to further expansion following the divergence are the presence of species-specific genes and greater MHC class I diversity in gray seals than harbor seals. The elaboration of a complex variable family of classical MHC class I genes in pinnipeds contrasts with the single, highly polymorphic classical MHC class I gene of dog and giant panda, terrestrial carnivores. PMID:23001684

  2. Allele frequency-based and polymorphism-versus-divergence indices of balancing selection in a new filtered set of polymorphic genes in Plasmodium falciparum.

    PubMed

    Ochola, Lynette Isabella; Tetteh, Kevin K A; Stewart, Lindsay B; Riitho, Victor; Marsh, Kevin; Conway, David J

    2010-10-01

    Signatures of balancing selection operating on specific gene loci in endemic pathogens can identify candidate targets of naturally acquired immunity. In malaria parasites, several leading vaccine candidates convincingly show such signatures when subjected to several tests of neutrality, but the discovery of new targets affected by selection to a similar extent has been slow. A small minority of all genes are under such selection, as indicated by a recent study of 26 Plasmodium falciparum merozoite-stage genes that were not previously prioritized as vaccine candidates, of which only one (locus PF10_0348) showed a strong signature. Therefore, to focus discovery efforts on genes that are polymorphic, we scanned all available shotgun genome sequence data from laboratory lines of P. falciparum and chose six loci with more than five single nucleotide polymorphisms per kilobase (including PF10_0348) for in-depth frequency-based analyses in a Kenyan population (allele sample sizes >50 for each locus) and comparison of Hudson-Kreitman-Aguade (HKA) ratios of population diversity (π) to interspecific divergence (K) from the chimpanzee parasite Plasmodium reichenowi. Three of these (the msp3/6-like genes PF10_0348 and PF10_0355 and the surf(4.1) gene PFD1160w) showed exceptionally high positive values of Tajima's D and Fu and Li's F indices and have the highest HKA ratios, indicating that they are under balancing selection and should be prioritized for studies of their protein products as candidate targets of immunity. Combined with earlier results, there is now strong evidence that high HKA ratio (as well as the frequency-independent ratio of Watterson's /K) is predictive of high values of Tajima's D. Thus, the former offers value for use in genome-wide screening when numbers of genome sequences within a species are low or in combination with Tajima's D as a 2D test on large population genomic samples. PMID:20457586

  3. 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. PMID:19449655

  4. 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

  5. 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.

  6. Frequency variations of discrete cranial traits in major human populations. IV. Vessel and nerve related variations

    PubMed Central

    HANIHARA, TSUNEHIKO; ISHIDA, HAJIME

    2001-01-01

    This concludes a series of descriptive statistical reports on discrete cranial traits in 81 human populations from around the world. Four variants classified as vessel and nerve related characters were investigated: patent condylar canal; supraorbital foramen; accessory infraorbital foramen; and accessory mental foramen. A significant asymmetric occurrence without any side preference was detected for the accessory mental foramen. Significant intertrait associations were found between the accessory infraorbital and supraorbital foramina in the panPacific region and Subsaharan African samples. The intertrait associations between the accessory infraorbital foramen and some traits classified as hypostotic were found mainly in the samples from the western part of the Old World, and those as hyperostotic traits in the samples from eastern Asian and the related population samples. With a few exceptions, the occurrence of a patent condylar canal and a supraorbital foramen was predominant in females, but the accessory infraorbital and accessory mental foramina were predominant in males. The frequency distributions of the traits showed interregional clinality and intraregional discontinuity. A temporal trend was found in the Northeast Asian region in the frequencies of the accessory infraorbital and accessory mental foramina. The diversity of modern human discrete cranial traits may at least in part be attributable to differential retention or intensification from an ancestral pattern. PMID:11554505

  7. Observational Evidence for Variations of the Acoustic Cutoff Frequency with Height in the Solar Atmosphere

    NASA Astrophysics Data System (ADS)

    Wiśniewska, A.; Musielak, Z. E.; Staiger, J.; Roth, M.

    2016-03-01

    Direct evidence for the existence of an acoustic cutoff frequency in the solar atmosphere is given by observations performed by using the HELioseismological Large Regions Interferometric DEvice operating on the Vacuum Tower Telescope located on Tenerife. The observational results demonstrate variations of the cutoff with atmospheric heights. The observed variations of the cutoff are compared to theoretical predictions made by using five acoustic cutoff frequencies that have been commonly used in helioseismology and asteroseismology. The comparison shows that none of the theoretical predictions is fully consistent with the observational data. The implication of this finding is far reaching as it urgently requires either major revisions of the existing methods of finding acoustic cutoff frequencies or developing new methods that would much better account for the physical picture underlying the concept of cutoff frequencies in inhomogeneous media.

  8. Global lightning dynamics deduced from Schumann resonance frequency variations at two sites ~ 550 km apart

    NASA Astrophysics Data System (ADS)

    Satori, G.; Mushtak, V.; Neska, M.; Nagy, T.; Barta, V.

    2012-04-01

    Schumann resonance (SR) peak frequencies depend on the lightning source-observer angular distance. The modal phase shift interaction at nodal distances manifests itself as sharp frequency variations: increases or decreases depend on the direction of the source motion with respect to the observer and the mode number. Nagycenk Observatory (47.6° N, 16.7° E), Hungary and Belsk (51.8 ° N, 20.8 ° E), Poland, are relatively close to each other ( ~550 km apart) compared with SR wavelengths. Both stations can approach the nodal position with respect to the African source region for the third Ez mode and to the Asian/American "chimney" regions for the first Ez mode as lightning activity migrates as the seasons change. These two observation sites can be on the different sides of the nodal line region for some weeks twice during a year, indicating the fine seasonal motion of the source regions which causes relatively large frequency variations (some tenth Hz) and different frequency values at the two stations, especially for the third Ez mode. Source-observer distance dependent frequency variations are presented throughout a year by using simultaneous SR observations at Nagycenk (NCK) and Belsk (BLK). The observed frequency changes are supported by the simulation of the distance-dependent frequency variation based on the computed spectra of the vertical electric field components using the Two-Dimensional Telegraph Equation (TDTE) technique (Kirillov, 2002). For the tropical "chimney" regions the diurnal phase of greatest activity has well established spatial-temporal dynamics. Modal peak frequencies are obtained, along with modal intensities and quality factors, by means of the least-squares fitting of "experimental" spectra by the "classic" Lorentzian function (Williams et al., 2006).

  9. Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C

    PubMed Central

    Delvaux, Nathália; da Costa, Vanessa Duarte; da Costa, Maristella Matos; Villar, Livia Melo; Coelho, Henrique Sérgio Moraes; Esberard, Eliane Bordalo Cathalá; Flores, Priscila Pollo; Brandão-Mello, Carlos Eduardo; Villela-Nogueira, Cristiane Alves; de Almeida, Adilson José; Lampe, Elisabeth

    2015-01-01

    Inosine triphosphatase (ITPA) single nucleotide polymorphisms (SNPs) are strongly associated with protection against ribavirin (RBV)-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354) frequency in healthy and hepatitis C virus (HCV)-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb) levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity) was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101) and CC genotypes (rs1127354), respectively. Men with AA (rs7270101) showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475). In women, there was no influence of genotype (p = 0.5295). For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women. PMID:26154744

  10. Allelic Variation of BnaC.TT2.a and Its Association with Seed Coat Color and Fatty Acids in Rapeseed (Brassica napus L.)

    PubMed Central

    Hussain, Nazim; Li, Zhilan; Wu, Dezhi; Jiang, Lixi

    2016-01-01

    Efficient molecular markers for the selection of rapeseed genetic materials with high seed oil content and ideal fatty acid (FA) composition are preferred by rapeseed breeders. Recently, we reported the molecular mechanism of TRANSPARENT TESTA 2 (TT2) in inhibiting seed FA biosynthesis in Arabidopsis. However, evidence showing the association of rapeseed TT2 homologs and seed FA production are still insufficient. In this study, we collected 83 rapeseed (Brassica napus L.) landraces from different geographical backgrounds to conduct association mapping of BnaC.TT2.a in relation to seed coat color and FA biosynthesis. Population background was corrected by 84 pairs of SSR markers that were uniformly distributed among the linkage groups of the Tapidor-Ningyou-7 DH population. A single copy of BnaC.TT2.a for single nucleotide polymorphism (SNP) assay was cloned by a pair of previously reported specific primers. From the analysis of BnaC.TT2.a allelic variations using GLM+Q model, four SNPs on intron 1 of BnaC.TT2.a that were associated with seed FA were discovered. Moreover, an InDel at position 738 on exon 3 of BnaC.TT2.a indicated a change of protein function that was significantly associated with seed coat color, linoleic acid (C18:2), and total FA content. These findings revealed the role of BnaC.TT2.a in regulating the seed color formation and seed FA biosynthesis in rapeseed, thereby suggesting effective molecular markers for rapeseed breeding. PMID:26752200

  11. Low-frequency wave modulations in an electronegative dusty plasma in the presence of charge variations.

    PubMed

    Ghosh, Samiran; Sarkar, Subrata; Khan, Manoranjan; Gupta, M R

    2011-12-01

    The effects of dust charge variations on low-frequency wave modulations in an electronegative dusty plasma are investigated. The dynamics of the modulated wave is governed by a nonlinear Schrödinger equation with a dissipative term. The dissipation arises due to the nonsteady (nonadiabatic) dust charge variations. Theoretical and numerical investigations predict the formation of dissipative bright (envelope) and dark solitons. The nonsteady charge-variation-induced dissipation reduces the modulational instability growth rate and introduces a characteristic time scale to observe bright solitons. Results are discussed in the context of electronegative dusty plasma experiments. PMID:22304202

  12. Negative frequency-dependent preferences and variation in male facial hair

    PubMed Central

    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. PMID:24740903

  13. 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. PMID:24740903

  14. Fundamental Frequency Variation with an Electrolarynx Improves Speech Understanding: A Case Study

    ERIC Educational Resources Information Center

    Watson, Peter J.; Schlauch, Robert S.

    2009-01-01

    Purpose: This study examined the effect of fundamental frequency (F0) variation on the intelligibility of speech in an alaryngeal talker who used an electrolarynx (EL). Method: One experienced alaryngeal talker produced variable F0 and a constant F0 with his EL as he read sentences aloud. As a control, a group of sentences with variable F0 was…

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. High-frequency variations of hydrogen spectral lines in the B3V star η UMa

    NASA Astrophysics Data System (ADS)

    Pokhvala, S. M.

    2015-09-01

    We reported the detection of high-frequency variations in the hydrogen Balmer lines in the hot star η UMa of spectral class B3V. Spectral observations of η UMa were carried out with slitless spectrograph (R˜100) installed on the 60 cm Carl Zeiss telescope in the Andrushivka Observatory. Spectra were obtained with a time resolution in the sub-second range. It has been found that the η UMa shows rapid variations in the hydrogen lines Hα, Hβ, Hγ, as well as variations in the atmospheric oxygen lines. The intensity variations in the hydrogen lines varies from 0.2% to 0.5% , and that of the oxygen lines is approximately 2%.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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).

  5. Distribution of allele frequencies at TTN g.231054C > T, RPL27A g.3109537C > T and AKIRIN2 c.*188G > A between Japanese Black and four other cattle breeds with differing historical selection for marbling

    PubMed Central

    2011-01-01

    Background Marbling defined by the amount and distribution of intramuscular fat, so-called Shimofuri, is an economically important trait of beef cattle in Japan. Our previous study detected 3 single nucleotide polymorphisms (SNPs), g.231054C > T, g.3109537C > T and c.*188G > A, respectively, in the 5' flanking region of the titin (TTN), the 5' flanking region of the ribosomal protein L27a (RPL27A) and the 3' untranslated region of the akirin 2 genes (AKIRIN2), which have been considered as positional functional candidates for the genes responsible for marbling, and showed association of these SNPs with marbling in Japanese Black beef cattle. In the present study, we investigated the allele frequency distribution of the 3 SNPs among the 5 cattle breeds, Japanese Black, Japanese Brown, Japanese Shorthorn, Holstein and Brown Swiss breeds. Findings We genotyped the TTN g.231054C > T, RPL27A g.3109537C > T and AKIRIN2 c.*188G > A SNPs by polymerase chain reaction-restriction fragment length polymorphism method, using 101 sires and 1,705 paternal half sib progeny steers from 8 sires for Japanese Black, 86 sires and 27 paternal half sib progeny steers from 3 sires for Japanese Brown, 79 sires and 264 paternal half sib progeny steers from 14 sires for Japanese Shorthorn, 119 unrelated cows for Holstein, and 118 unrelated cows for Brown Swiss breeds. As compared to the frequencies of the g.231054C > T T, g.3109537C > T T and c.*188G > A A alleles, associated with high marbling, in Japanese Black breed that has been subjected to a strong selection for high marbling, those in the breeds, Japanese Shorthorn, Holstein and Brown Swiss breeds, that have not been selected for high marbling were null or lower. The Japanese Brown breed selected slightly for high marbling showed lower frequency than Japanese Black breed in the g.3109537C > T T allele, whereas no differences were detected between the 2 breeds in the frequencies of the g.231054C > T T and c.*188G > A A alleles

  6. 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

    2015-01-01

    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

  7. 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

  8. 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...

  9. 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...

  10. Collective frequency variation in network synchronization and reverse PageRank.

    PubMed

    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. PMID:27176319

  11. 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

  12. High frequency of allelic imbalance at chromosome region 16q22-23 in human breast cancer: correlation with high PgR and low S phase.

    PubMed

    Skirnisdottir, S; Eiriksdottir, G; Baldursson, T; Barkardottir, R B; Egilsson, V; Ingvarrson, S

    1995-04-21

    The loss of genetic material from a specific chromosome region in tumors suggests that presence of tumor-suppressor genes. Loss of heterozygosity (LOH) or allelic imbalance (AI) on the long arm of chromosome 16 is a known event in sporadic breast cancer. To locate the commonly deleted regions, and therefore (a) candidate tumor-suppressor gene(s), a deletion map of chromosome 16 was made, using 10 microsatellite markers on 150 sporadic breast tumors. The 3 smallest regions of overlap (SRO) were detected on the long arm of chromosome 16. Allelic imbalance was observed with at least one marker in 67% of the tumors. One marker, D16S421, at the 16q22-23 region, showed the highest allelic imbalance, 58%. Tumors with and without AI on 16q were tested for correlation with clinico-pathological features of the tumors such as estrogen- and progesterone-receptor content (ER and PgR), age at diagnosis, tumor size, node status, histological type, S-phase fraction, AI on chromosome 3p, and ploidy. A correlation was found between AI on 16q and high PgR content, also low S-phase fraction (99% confidence limits). A comparison of tumors with and without AI at the D16S421 marker locus revealed a slight correlation with high PgR content. The survival data showed no difference between patients with AI on 16q and those with a normal allele pattern on the long arm of chromosome 16. PMID:7615353

  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. Variation in Cardiac Pulse Frequencies Modulates vSMC Phenotype Switching During Vascular Remodeling.

    PubMed

    Tosun, Zehra; McFetridge, Peter S

    2015-03-01

    In vitro perfusion systems have exposed vascular constructs to mechanical conditions that emulate physiological pulse pressure and found significant improvements in graft development. However, current models maintain constant, or set pulse/shear mechanics that do not account for the natural temporal variation in frequency. With an aim to develop clinically relevant small diameter vascular grafts, these investigations detail a perfusion culture model that incorporates temporal pulse pressure variation. Our objective was to test the hypothesis that short-term variation in heart rate, such as changes in respiratory activity, plays a significant role in vascular remodeling and graft development. The pulse rate of a healthy volunteer was logged to model the effect of daily activities on heart rate. Vascular bioreactors were used to deliver perfusion conditions based on modeled frequencies of temporal pulse variability, termed Physiologically Modeled Pulse Dynamics (PMPD). Acellular scaffolds derived from the human umbilical vein were seeded with human vascular smooth muscle cells and perfused under defined pulsatile conditions. vSMC exposed to constant pulse frequencies expressed a contractile phenotype, while exposure to PMPD drove cells to a synthetic state with continued cell proliferation, increased tensile strength and stiffness as well as diminished vasoactivity. Results show the temporal variation associated with normal heart physiology to have a profound effect on vascular remodeling and vasoactive function. While these models are representative of vascular regeneration further investigation is required to understanding these and other key regulators in vSMC phenotype switching in non-pathological or wound healing states. This understanding has important clinical implications that may lead to improved treatments that enhance vessel regeneration. PMID:26577103

  15. Gate line edge roughness amplitude and frequency variation effects on intra die MOS device characteristics

    NASA Astrophysics Data System (ADS)

    Hamadeh, Emad; Gunther, Norman G.; Niemann, Darrell; Rahman, Mahmud

    2006-06-01

    Random fluctuations in fabrication process outcomes such as gate line edge roughness (LER) give rise to corresponding fluctuations in scaled down MOS device characteristics. A thermodynamic-variational model is presented to study the effects of LER on threshold voltage and capacitance of sub-50 nm MOS devices. Conceptually, we treat the geometric definition of the MOS devices on a die as consisting of a collection of gates. In turn, each of these gates has an area, A, and a perimeter, P, defined by nominally straight lines subject to random process outcomes producing roughness. We treat roughness as being deviations from straightness consisting of both transverse amplitude and longitudinal wavelength each having lognormal distribution. We obtain closed-form expressions for variance of threshold voltage ( Vth), and device capacitance ( C) at Onset of Strong Inversion (OSI) for a small device. Using our variational model, we characterized the device electrical properties such as σ and σC in terms of the statistical parameters of the roughness amplitude and spatial frequency, i.e., inverse roughness wavelength. We then verified our model with numerical analysis of Vth roll-off for small devices and σ due to dopant fluctuation. Our model was also benchmarked against TCAD of σ as a function of LER. We then extended our analysis to predict variations in σ and σC versus average LER spatial frequency and amplitude, and oxide-thickness. Given the intuitive expectation that LER of very short wavelengths must also have small amplitude, we have investigated the case in which the amplitude mean is inversely related to the frequency mean. We compare with the situation in which amplitude and frequency mean are unrelated. Given also that the gate perimeter may consist of different LER signature for each side, we have extended our analysis to the case when the LER statistical difference between gate sides is moderate, as well as when it is significantly large.

  16. Genetic variation in brain-derived neurotrophic factor val66met allele is associated with altered serotonin-1A receptor binding in human brain.

    PubMed

    Lan, Martin J; Ogden, R Todd; Huang, Yung-yu; Oquendo, Maria A; Sullivan, Gregory M; Miller, Jeffrey; Milak, Matthew; Mann, J John; Parsey, Ramin V

    2014-07-01

    Brain Derived Neurotrophic Factor (BDNF) regulates brain synaptic plasticity. BDNF affects serotonin signaling, increases serotonin levels in brain tissue and prevents degeneration of serotonin neurons. These effects have hardly been studied in human brain. We examined the relationship of the functional val66met polymorphism of the BDNF gene to serotonin 1A (5-HT(1A)) receptor binding in vivo. 50 healthy volunteers (HV) and 50 acutely depressed, unmedicated patients with major depressive disorder (MDD) underwent PET scanning with the 5-HT(1A) receptor ligand, [(11)C]WAY-100635 and a metabolite corrected arterial input function. A linear mixed effects model compared 5-HT(1A) receptor binding potential (BP(F), proportional to the number of available receptors) in 13 brain regions of interest between met allele carriers (met/met and val/met) and noncarriers (val/val) using sex and C-1019G genotype of the 5-HT(1A) receptor promoter functional polymorphism as covariates. There was an interaction between diagnosis and allele (F=4.23, df=1, 94, p=0.042), such that met allele carriers had 17.4% lower BP(F) than non-met carriers in the HV group (t=2.6, df=96, p=0.010), but not in the MDD group (t=-0.4, df=96, p=0.58). These data are consistent with a model where the met allele of the val66met polymorphism causes less proliferation of serotonin synapses, and consequently fewer 5-HT(1A) receptors. In MDD, however, the effect of the val66met polymorphism is not detectable, possibly due to a ceiling effect of over-expression of 5-HT(1A) receptors in mood disorders. PMID:24607934

  17. 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

  18. Search for Temporal Variations in Alpha Using a Yb^+ Optical Frequency Standard

    NASA Astrophysics Data System (ADS)

    Peik, Ekkehard

    2008-05-01

    Optical frequency standards based on forbidden transitions of trapped and laser-cooled ions have now achieved significantly higher stability and also greater accuracy than primary cesium clocks. At PTB we investigate an optical clock based on the electric quadrupole transition S1/2- D3/2 at 688 THz in the ^171Yb^+ ion and have shown that the frequencies realized in two independent ion traps agree to within a few parts in 10^16. Results from a sequence of precise measurements of the absolute transition frequency are now available that cover a period of seven years. Combined with data obtained at NIST on the quadrupole transition in Hg^+, this allows to derive a model-independent limit for a temporal drift of the fine structure constant alpha. We prepare to observe the electric-octupole transition S1/2- F7/2 of Yb^+ at 642 THz with sub-hertz resolution. This narrow-linewidth reference transition promises a reduced quantum-noise limited instability of the single-ion optical clock. The ratio of the 688 THz and 642 THz reference frequencies can be measured as a dimensionless number with a femtosecond laser frequency comb, independent from the realization of the SI second with cesium clocks. Repeated measurements of this quantity permit to search for temporal variations of alpha with increased sensitivity.

  19. 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.

  20. Variations in High Degree Acoustic Mode Frequencies of the Sun during Solar Cycles 23 and 24

    NASA Astrophysics Data System (ADS)

    Tripathy, S. C.; Jain, K.; Hill, F.

    2015-10-01

    We examine continuous measurements of the high-degree acoustic mode frequencies of the Sun covering the period from 2001 July to 2014 June. These are obtained through the ring-diagram technique applied to the full-disk Doppler observations made by the Global Oscillation Network Group. The frequency shifts in the degree range of 180 ≤slant {\\ell } ≤slant 1200 are correlated with different proxies of solar activity, e.g., 10.7 cm radio flux, the International Sunspot Number, and the strength of the local magnetic field. In general, a good agreement is found between the shifts and activity indices, and the correlation coefficients are found to be comparable with intermediate-degree mode frequencies. Analyzing the frequency shifts separately for the two cycles, we find that cycle 24 is weaker than cycle 23. Since the magnetic activity is known to be different in the two hemispheres, for the first time, we compute the frequency shifts over the two hemispheres separately and find that the shifts also display hemispheric asymmetry; the amplitude of shifts in the northern hemisphere peaked during late 2011, more than two years earlier than in the south. We further correlate the hemispheric frequency shifts with the hemispheric sunspot number and mean magnetic activity index (MAI). Since the frequency shifts and the hemispheric activity indices are found to be significantly correlated, we suggest that the shifts be used as an indicator of hemispheric activity since not many indices are measured over the two hemispheres separately. We also investigate the variation at different latitudinal bands and conclude that the shifts in active latitudes correlate well with the local MAI.

  1. 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. PMID:20377573

  2. Population Bottlenecks and Nonequilibrium Models in Population Genetics. I. Allele Numbers When Populations Evolve from Zero Variability

    PubMed Central

    Maruyama, Takeo; Fuerst, Paul A.

    1984-01-01

    A simple numerical method was developed for the mean number and average age of alleles in a population that was initiated with no genetic variation following a sudden population expansion. The methods are used to examine the question of whether allele numbers are elevated compared with values seen in equilibrium populations having equivalent gene diversity. Excess allele numbers in expanding populations were found to be the rule. This was true whether the population began with zero variation or with low levels of variation in either of two initial distributions (initially an equilibrium allele frequency distribution or initially with loci occurring in only two classes of variation). Although the increase of alleles may persist for only a short time, when compared with the time which is required for approach to final equilibrium, the increase may be long when measured in absolute generation numbers. The pattern of increase in very rare alleles (those present only once in a sample) and the persistence of the original allele were also investigated. PMID:6500263

  3. 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. PMID:26336243

  4. Limited evidence for adaptive evolution and functional effect of allelic variation at rs702424 in the promoter of the TAS2R16 bitter taste receptor gene in Africa.

    PubMed

    Campbell, Michael C; Ranciaro, Alessia; Zinshteyn, Daniel; Rawlings-Goss, Renata; Hirbo, Jibril; Thompson, Simon; Woldemeskel, Dawit; Froment, Alain; Omar, Sabah A; Bodo, Jean-Marie; Nyambo, Thomas; Belay, Gurja; Drayna, Dennis; Breslin, Paul A S; Tishkoff, Sarah A

    2014-06-01

    Bitter taste perception, mediated by receptors encoded by the TAS2R loci, has important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on the levels of salicin bitter taste perception. Here, we examined alleles at rs702424 for signatures of selection using Extended Haplotype Homozygosity (EHH) and FST statistics in diverse populations from West Central, Central and East Africa. We also performed a genotype-phenotype analysis of salicin sensitivity in a subset of 135 individuals from East Africa. Based on our data, we did not find evidence for positive selection at rs702424 in African populations, suggesting that nucleotide position 516 is likely the site under selection at TAS2R16. Moreover, we did not detect a significant association between rs702424 alleles and salicin bitter taste recognition, implying that this site does not contribute to salicin phenotypic variance. Overall, this study of African diversity provides further information regarding the genetic architecture and evolutionary history of a biologically-relevant trait in humans. PMID:24785689

  5. Limited Evidence for Adaptive Evolution and Functional Effect of Allelic Variation at rs702424 in the Promoter of the TAS2R16 Bitter Taste Receptor Gene in Africa

    PubMed Central

    Campbell, Michael C.; Ranciaro, Alessia; Zinshteyn, Daniel; Rawlings-Goss, Renata; Hirbo, Jibril; Thompson, Simon; Woldemeskel, Dawit; Froment, Alain; Omar, Sabah A.; Bodo, Jean-Marie; Nyambo, Thomas; Belay, Gurja; Drayna, Dennis; Breslin, Paul A.S.; Tishkoff, Sarah A.

    2014-01-01

    Bitter taste perception, mediated by receptors encoded by the TAS2R loci, plays important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on levels of salicin bitter taste perception. Here, we examined alleles at rs702424 for signatures of selection using Extended Haplotype Homozygosity (EHH) and FST statistics in 44 diverse populations from West Central, Central and East Africa. We also performed a genotype-phenotype analysis of salicin sensitivity in a subset of 135 individuals from East Africa. Based on our data, we did not find evidence for positive selection at rs702424 in African populations, suggesting that site 516 is likely the variant under selection at TAS2R16. Additionally, we did not detect a significant association between rs702424 alleles and salicin bitter taste recognition, implying that this site does not contribute to salicin phenotypic variance. Overall, this study of African diversity provides further information regarding the genetic architecture and evolutionary history of a biologically-relevant trait in humans. PMID:24785689

  6. High frequency and founder effect of the CYP3A4*20 loss-of-function allele in the Spanish population classifies CYP3A4 as a polymorphic enzyme.

    PubMed

    Apellániz-Ruiz, M; Inglada-Pérez, L; Naranjo, M E G; Sánchez, L; Mancikova, V; Currás-Freixes, M; de Cubas, A A; Comino-Méndez, I; Triki, S; Rebai, A; Rasool, M; Moya, G; Grazina, M; Opocher, G; Cascón, A; Taboada-Echalar, P; Ingelman-Sundberg, M; Carracedo, A; Robledo, M; Llerena, A; Rodríguez-Antona, C

    2015-06-01

    Cytochrome P450 3A4 (CYP3A4) is a key drug-metabolizing enzyme. Loss-of-function variants have been reported as rare events, and the first demonstration of a CYP3A4 protein lacking functional activity is caused by CYP3A4*20 allele. Here we characterized the world distribution and origin of CYP3A4*20 mutation. CYP3A4*20 was determined in more than 4000 individuals representing different populations, and haplotype analysis was performed using CYP3A polymorphisms and microsatellite markers. CYP3A4*20 allele was present in 1.2% of the Spanish population (up to 3.8% in specific regions), and all CYP3A4*20 carriers had a common haplotype. This is compatible with a Spanish founder effect and classifies CYP3A4 as a polymorphic enzyme. This constitutes the first description of a CYP3A4 loss-of-function variant with high frequency in a population. CYP3A4*20 results together with the key role of CYP3A4 in drug metabolism support screening for rare CYP3A4 functional alleles among subjects with adverse drug events in certain populations. PMID:25348618

  7. Allelic variation of the COMT gene in a despotic primate society: A haplotype is related to cortisol excretion in Macaca fuscata.

    PubMed

    Pflüger, Lena S; Gutleb, Daria R; Hofer, Martin; Fieder, Martin; Wallner, Bernard; Steinborn, Ralf

    2016-02-01

    Sequence variations in genes of the monoamine neurotransmitter system and their common function in human and non-human primate species are an ongoing issue of investigation. However, the COMT gene, coding for the catechol-O-methyltransferase, has not yet attracted much scientific attention regarding its functional role in non-human primates. Considering that a polymorphism of the human COMT gene affects the enzyme activity and cortisol level in response to a social stressor, this study investigated the impact of COMT on endocrine stress and behavioural parameters in Japanese macaques (Macaca fuscata). The species exemplifies a despotic hierarchy in which males' social rank positions require an adaptation of behaviour strategies. During the mating period steroid secretion and the frequency of aggressive encounters between males increase. We addressed i) whether this species exhibits potential functional COMT variants, ii) whether these variants are associated with faecal cortisol excretion of males, iii) how they are distributed among different social rank positions and iv) whether they are associated with behavioural strategies during times of mate competition. By genotyping 26 males we identified three COMT haplotypes (HT), including a putative splice mutant (HT3). This variant was associated with increased cortisol excretion. Given the observed inverse correlation between cortisol and physical aggression, we assume that different COMT haplotypes may predispose individuals to pursue more or less aggressive strategies. How these gene-stress effects might favour a specific social role is discussed. Our study of non-invasive genotyping in combination with behavioural and endocrine parameters represents an important step towards the understanding of gene-stress effects in a hierarchically organised primate society. PMID:26657779

  8. 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.

  9. Variation in effects of non-Hodgkin lymphoma risk factors according to the human leukocyte antigen (HLA)-DRB1*01:01 allele and ancestral haplotype 8.1.

    PubMed

    Wang, Sophia S; Lu, Yani; Rothman, Nathaniel; Abdou, Amr M; Cerhan, James R; De Roos, Anneclaire; Davis, Scott; Severson, Richard K; Cozen, Wendy; Chanock, Stephen J; Bernstein, Leslie; Morton, Lindsay M; Hartge, Patricia

    2011-01-01

    Genetic variations in human leukocyte antigens (HLA) are critical in host responses to infections, transplantation, and immunological diseases. We previously identified associations with non-Hodgkin lymphoma (NHL) and the HLA-DRB1*01:01 allele and extended ancestral haplotype (AH) 8.1 (HLA-A*01-B*08-DR*03-TNF-308A). To illuminate how HLA alleles and haplotypes may influence NHL etiology, we examined potential interactions between HLA-DRB1*01:01 and AH 8.1, and a wide range of NHL risk factors among 685 NHL cases and 646 controls from a United States population-based case-control study. We calculated odds ratios and 95% confidence intervals by HLA allele or haplotype status, adjusted for sex, age, race and study center for NHL and two major subtypes using polychotomous unconditional logistic regression models. The previously reported elevation in NHL risk associated with exposures to termite treatment and polychlorinated biphenyls were restricted to individuals who did not possess HLA-DRB1*01:01. Previous associations for NHL and DLBCL with decreased sun exposure, higher BMI, and autoimmune conditions were statistically significant only among those with AH 8.1, and null among those without AH 8.1. Our results suggest that NHL risk factors vary in their association based on HLA-DRB1*01:01 and AH 8.1 status. Our results further suggest that certain NHL risk factors may act through a common mechanism to alter NHL risk. Finally, control participants with either HLA-DRB1*01:01 or AH 8.1 reported having a family history of NHL twice as likely as those who did not have either allele or haplotype, providing the first empirical evidence that HLA associations may explain some of the well-established relationship between family history and NHL risk. PMID:22096508

  10. Variation in Effects of Non-Hodgkin Lymphoma Risk Factors According to the Human Leukocyte Antigen (HLA)-DRB1*01:01 Allele and Ancestral Haplotype 8.1

    PubMed Central

    Wang, Sophia S.; Lu, Yani; Rothman, Nathaniel; Abdou, Amr M.; Cerhan, James R.; De Roos, Anneclaire; Davis, Scott; Severson, Richard K.; Cozen, Wendy; Chanock, Stephen J.; Bernstein, Leslie; Morton, Lindsay M.; Hartge, Patricia

    2011-01-01

    Genetic variations in human leukocyte antigens (HLA) are critical in host responses to infections, transplantation, and immunological diseases. We previously identified associations with non-Hodgkin lymphoma (NHL) and the HLA-DRB1*01:01 allele and extended ancestral haplotype (AH) 8.1 (HLA-A*01-B*08-DR*03-TNF-308A). To illuminate how HLA alleles and haplotypes may influence NHL etiology, we examined potential interactions between HLA-DRB1*01:01 and AH 8.1, and a wide range of NHL risk factors among 685 NHL cases and 646 controls from a United States population-based case-control study. We calculated odds ratios and 95% confidence intervals by HLA allele or haplotype status, adjusted for sex, age, race and study center for NHL and two major subtypes using polychotomous unconditional logistic regression models. The previously reported elevation in NHL risk associated with exposures to termite treatment and polychlorinated biphenyls were restricted to individuals who did not possess HLA-DRB1*01:01. Previous associations for NHL and DLBCL with decreased sun exposure, higher BMI, and autoimmune conditions were statistically significant only among those with AH 8.1, and null among those without AH 8.1. Our results suggest that NHL risk factors vary in their association based on HLA-DRB1*01:01 and AH 8.1 status. Our results further suggest that certain NHL risk factors may act through a common mechanism to alter NHL risk. Finally, control participants with either HLA-DRB1*01:01 or AH 8.1 reported having a family history of NHL twice as likely as those who did not have either allele or haplotype, providing the first empirical evidence that HLA associations may explain some of the well-established relationship between family history and NHL risk. PMID:22096508

  11. 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.

  12. Vertical normal modes of human ears: Individual variation and frequency estimation from pinna anthropometry.

    PubMed

    Mokhtari, Parham; Takemoto, Hironori; Nishimura, Ryouichi; Kato, Hiroaki

    2016-08-01

    Beyond the first peak of head-related transfer functions or pinna-related transfer functions (PRTFs) human pinnae are known to have two normal modes with "vertical" resonance patterns, involving two or three pressure anti-nodes in cavum, cymba, and fossa. However, little is known about individual variations in these modes, and there is no established model for estimating their center-frequencies from anthropometry. Here, with geometries of 38 pinnae measured, PRTFs were calculated and vertical modes visualized by numerical simulation. Most pinnae were found to have both Cavum-Fossa and Cavum-Cymba modes, with opposite-phase anti-nodes in cavum and either fossa or cymba, respectively. Nevertheless in both modes, fossa involvement varied substantially across pinnae, dependent on scaphoid fossa depth and cymba shallowness. Linear regression models were evaluated in mode frequency estimation, with 3322 measures derived from 31 pinna landmarks. The Cavum-Fossa normal mode frequency was best estimated [correlation coefficient r = 0.89, mean absolute error (MAE) = 257 Hz or 4.4%] by the distance from canal entrance to helix rim, and cymba horizontal depth. The Cavum-Cymba normal mode frequency was best estimated (r = 0.92, MAE = 247 Hz or 3.2%) by the sagittal-plane distance from concha floor to cymba anterior wall, and cavum horizontal depth. PMID:27586714

  13. 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 Central

    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. PMID:25806042

  14. Allelic variation in paralogs of GDP-L-galactose phosphorylase is a major determinant of vitamin C concentrations in apple fruit.

    PubMed

    Mellidou, Ifigeneia; Chagné, David; Laing, William A; Keulemans, Johan; Davey, Mark W

    2012-11-01

    To identify the genetic factors underlying the regulation of fruit vitamin C (L-ascorbic acid [AsA]) concentrations, quantitative trait loci (QTL) studies were carried out in an F1 progeny derived from a cross between the apple (Malus × domestica) cultivars Telamon and Braeburn over three years. QTL were identified for AsA, glutathione, total antioxidant activity in both flesh and skin tissues, and various quality traits, including flesh browning. Four regions on chromosomes 10, 11, 16, and 17 contained stable fruit AsA-QTL clusters. Mapping of AsA metabolic genes identified colocations between orthologs of GDP-L-galactose phosphorylase (GGP), dehydroascorbate reductase (DHAR), and nucleobase-ascorbate transporter within these QTL clusters. Of particular interest are the three paralogs of MdGGP, which all colocated within AsA-QTL clusters. Allelic variants of MdGGP1 and MdGGP3 derived from the cultivar Braeburn parent were also consistently associated with higher fruit total AsA concentrations both within the mapping population (up to 10-fold) and across a range of commercial apple germplasm (up to 6-fold). Striking differences in the expression of the cv Braeburn MdGGP1 allele between fruit from high- and low-AsA genotypes clearly indicate a key role for MdGGP1 in the regulation of fruit AsA concentrations, and this MdGGP allele-specific single-nucleotide polymorphism marker represents an excellent candidate for directed breeding for enhanced fruit AsA concentrations. Interestingly, colocations were also found between MdDHAR3-3 and a stable QTL for browning in the cv Telamon parent, highlighting links between the redox status of the AsA pool and susceptibility to flesh browning. PMID:23001142

  15. 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

  16. An analytical model for Doppler frequency variations of ionospheric HF sounding caused by SSC

    NASA Astrophysics Data System (ADS)

    Pilipenko, V.; Fedorov, E.; Yumoto, K.; Ikeda, A.; Sun, T. R.

    2010-10-01

    A theoretical model to interpret the deviations of the Doppler sounding radio frequency during the SSC is proposed. The Doppler response is composed from long-period deviation with time scale ˜10 min and short-lived (˜1 min) positive spike. For the interpretation of this spike, the variations of Doppler velocity induced by compressional and Alfvén waves are theoretically estimated on the basis of the thin ionosphere approximation. The analytical model developed goes beyond the older numerical model which has been in use thus far to explain certain facets of the correlation between geomagnetic variations and HF Doppler shifts. This new model provides the possibility to easily estimate the Doppler frequency response to either Alfvén or compresssional modes for extraordinary and ordinary radio waves. A theoretical estimate indicates that, for the same amplitude of the ground magnetic disturbances, a large-scale compressional mode produces a larger ionospheric response than an Alfvén mode. The plasma vertical displacement caused by the ULF inductive electric field is shown to be the dominating effect. The magnitudes and waveforms of the simultaneously detected ionospheric and magnetic responses on SSC at a low-latitude site in Japan fit the considered model.

  17. Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14

    PubMed Central

    Letteboer, Tom G. W.; Benzinou, Michael; Merrick, Christopher B.; Quigley, David A.; Zhau, Kechen; Kim, Il-Jin; To, Minh D.; Jablons, David M.; van Amstel, Johannes K. P.; Westermann, Cornelius J. J.; Giraud, Sophie; Dupuis-Girod, Sophie; Lesca, Gaetan; Berg, Jonathan H.; Balmain, Allan; Akhurst, Rosemary J.

    2015-01-01

    HHT shows clinical variability within and between families. Organ site and prevalence of arteriovenous malformations (AVMs) depend on the HHT causative gene and on environmental and genetic modifiers. We tested whether variation in the functional ENG allele, inherited from the unaffected parent, alters risk for pulmonary AVM in HHT1 mutation carriers who are ENG haploinsufficient. Genetic association was found between rs10987746 of the wild type ENG allele and presence of pulmonary AVM [relative risk = 1.3 (1.0018–1.7424)]. The rs10987746-C at-risk allele associated with lower expression of ENG RNA in a panel of human lymphoblastoid cell lines (P = 0.004). Moreover, in angiogenically active human lung adenocarcinoma tissue, but not in uninvolved quiescent lung, rs10987746-C was correlated with expression of PTPN14 (P = 0.004), another modifier of HHT. Quantitative TAQMAN expression analysis in a panel of normal lung tissues from 69 genetically heterogeneous inter-specific backcross mice, demonstrated strong correlation between expression levels of Eng, Acvrl1, and Ptpn14 (r2 = 0.75–0.9, P < 1 × 10−12), further suggesting a direct or indirect interaction between these three genes in lung in vivo. Our data indicate that genetic variation within the single functional ENG gene influences quantitative and/or qualitative differences in ENG expression that contribute to risk of pulmonary AVM in HHT1, and provide correlative support for PTPN14 involvement in endoglin/ALK1 lung biology in vivo. PTPN14 has been shown to be a negative regulator of Yap/Taz signaling, which is implicated in mechanotransduction, providing a possible molecular link between endoglin/ALK1 signaling and mechanical stress. EMILIN2, which showed suggestive genetic association with pulmonary AVM, is also reported to interact with Taz in angiogenesis. Elucidation of the molecular mechanisms regulating these interactions in endothelial cells may ultimately provide more rational choices for HHT

  18. Mismatch correction modulates mutation frequency and pilus phase and antigenic variation in Neisseria gonorrhoeae.

    PubMed

    Criss, Alison K; Bonney, Kevin M; Chang, Rhoda A; Duffin, Paul M; LeCuyer, Brian E; Seifert, H Steven

    2010-01-01

    The mismatch correction (MMC) system repairs DNA mismatches and single nucleotide insertions or deletions postreplication. To test the functions of MMC in the obligate human pathogen Neisseria gonorrhoeae, homologues of the core MMC genes mutS and mutL were inactivated in strain FA1090. No mutH homologue was found in the FA1090 genome, suggesting that gonococcal MMC is not methyl directed. MMC mutants were compared to a mutant in uvrD, the helicase that functions with MMC in Escherichia coli. Inactivation of MMC or uvrD increased spontaneous resistance to rifampin and nalidixic acid, and MMC/uvrD double mutants exhibited higher mutation frequencies than any single mutant. Loss of MMC marginally enhanced the transformation efficiency of DNA carrying a single nucleotide mismatch but not that of DNA with a 1-kb insertion. Unlike the exquisite UV sensitivity of the uvrD mutant, inactivating MMC did not affect survival after UV irradiation. MMC and uvrD mutants exhibited increased PilC-dependent pilus phase variation. mutS-deficient gonococci underwent an increased frequency of pilin antigenic variation, whereas uvrD had no effect. Recombination tracts in the mutS pilin variants were longer than in parental gonococci but utilized the same donor pilS loci. These results show that gonococcal MMC repairs mismatches and small insertion/deletions in DNA and also affects the recombination events underlying pilin antigenic variation. The differential effects of MMC and uvrD in gonococci unexpectedly reveal that MMC can function independently of uvrD in this human-specific pathogen. PMID:19854909

  19. 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]. PMID:27570807

  20. Seasonal variations in the frequency of atmospheric circulation types in European regions

    NASA Astrophysics Data System (ADS)

    Cahynova, Monika; Huth, Radan

    2010-05-01

    We propose two versions of an "index of seasonality" to study the annual course in the relative frequency of circulation types in several objective and subjective classifications from the COST733 database. The objective classifications have been developed for twelve European regions (domains D00-D11) in the period 1957-2002 and have fixed numbers of types (9, 18, and 27). Both indices are based on the long-term monthly relative frequency of individual circulation types. For each type we indicate the months with the highest and the lowest relative frequency and calculate their difference (range). The first index - "average seasonality" - is an average of the ranges of all types within a given classification. It is anti-correlated with the number of types - a higher number of types means a lower average seasonality. The second index - "maximum seasonality" - only takes into account the circulation type with the highest range (that is, the type with the most pronounced annual course). This index removes the dependence on the number of circulation types in some of the used classifications. Seasonal variations in the relative frequency of circulation types based on the two indices are generally the highest in the eastern Mediterranean (D11) and in whole Europe (D00). The lowest seasonality is found over the British Isles (D04) and Iceland (D01). There are large differences in the seasonality in the individual classifications, because the degree to which the classification identifies the natural seasonal circulation patterns strongly depends on the classification algorithm used. The research is conducted within the COST733 Action "Harmonisation and Applications of Weather Types Classifications for European Regions". The Czech participation in it is supported by the Ministry of Education, Youth, and Sports of the Czech Republic, contract OC115.

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

    PubMed

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

    2014-08-22

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

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

    PubMed Central

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

    2014-01-01

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

  3. SLC40A1 Q248H allele frequencies and Q248H-associated risk of non-HFE iron overload in persons of sub-Saharan African descent.

    PubMed

    Barton, James C; Acton, Ronald T; Lee, Pauline L; West, Carol

    2007-01-01

    The ferroportin polymorphism SLC40A1 Q248H (exon 6, cDNA 744G-->T; Gln248His) occurs in persons of sub-Saharan African descent with and without iron overload, and is associated with elevated serum ferritin concentrations (SF). However, the risk of iron overload associated with Q248H has not been defined. We tabulated previously reported Q248H allele frequency estimates in African-Americans and Native Africans, and computed the risk of iron overload associated with Q248H in subjects who lacked HFE C282Y. The aggregate Q248H allele frequency in 1038 African-Americans in two cohorts from Alabama and one cohort each from Washington, DC and California was 0.0525 (95% CI: 0.0451, 0.0652); there was no significant difference in frequencies across these cohorts. The aggregate frequency in 259 Natives from southeast Africa in two cohorts was 0.0946 (95% CI: 0.0694, 0.1198); the difference between the frequencies of these cohorts was not significant. The aggregate Q248H frequencies in African-Americans and Native Africans differed significantly (0.0525 vs. 0.0946, respectively; p=0.0021). There were reports of 24 unrelated African-Americans and 15 unrelated Native Africans without HFE C282Y who had iron overload. In African-Americans, the odds ratio (OR) of Q248H-associated risk of iron overload using 610 C282Y-negative control subjects unselected for SF was 1.57 (95% CI: 0.52, 4.72; p=0.29). In Native Africans, the OR using 208 control subjects unselected for SF was 1.05 (95% CI: 0.28, 3.90; p=0.58). We conclude that the frequency of SLC40A1 Q248H is significantly lower in African-Americans than in Native Africans. Although OR estimates of iron overload in African-Americans and Native Africans with Q248H were greater than unity, the increased OR were not statistically significant. PMID:17490902

  4. Are short-term variations in solar oscillation frequencies the signature of a second solar dynamo?

    NASA Astrophysics Data System (ADS)

    Broomhall, Anne-Marie; Fletcher, Stephen T.; Salabert, David; Basu, Sarbani; Chaplin, William J.; Elsworth, Yvonne; García, Rafael A.; Jiménez, Antonio; New, Roger

    2011-01-01

    In addition to the well-known 11-year solar cycle, the Sun's magnetic activity also shows significant variation on shorter time scales, e.g. between one and two years. We observe a quasi-biennial (2-year) signal in the solar p-mode oscillation frequencies, which are sensitive probes of the solar interior. The signal is visible in Sun-as-a-star data observed by different instruments and here we describe the results obtained using BiSON, GOLF, and VIRGO data. Our results imply that the 2-year signal is susceptible to the influence of the main 11-year solar cycle. However, the source of the signal appears to be separate from that of the 11-year cycle. We speculate as to whether it might be the signature of a second dynamo, located in the region of near-surface rotational shear.

  5. 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.

  6. 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

    2016-06-01

    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.

  7. 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

  8. Nickel-silica nanocomposite: Variation of the blocking temperature with magnetic field and measuring frequency

    NASA Astrophysics Data System (ADS)

    Singh, V.; Seehra, M. S.; Bonevich, J.

    2008-04-01

    The variations of the blocking temperature TB with measuring frequency fm and applied field H are reported for Ni nanoparticles (NPs) embedded in SiO2 matrix with the nominal composition Ni /SiO2 (15/85). Transmission electron microscopy of the sol-gel prepared NPs yielded a log-normal distribution with diameter D =3.8(0.2)nm whereas x-ray diffraction data yielded D ≃3.3nm. The TB versus fm variation for fm=0.1-1000Hz fits the equation TB=Ta/ln(f0/fm) with f0=2.6×109Hz and Ta=270K whereas TB versus H data follows the equation TB(H)=33(1-H/H0)m with H0=3200Oe and m =2(3/2) for lower (higher) H. These results are compared with the predictions of the Néel-Brown model of magnetic relaxation in noninteracting NPs.

  9. 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.

  10. Variation in the interaction between alleles of HvAPETALA2 and microRNA172 determines the density of grains on the barley inflorescence

    PubMed Central

    Houston, Kelly; McKim, Sarah M.; Comadran, Jordi; Bonar, Nicola; Druka, Ilze; Uzrek, Nicola; Cirillo, Elisa; Guzy-Wrobelska, Justyna; Collins, Nicholas C.; Halpin, Claire; Hansson, Mats; Dockter, Christoph; Druka, Arnis; Waugh, Robbie

    2013-01-01

    Within the cereal grasses, variation in inflorescence architecture results in a conspicuous morphological diversity that in crop species influences the yield of cereal grains. Although significant progress has been made in identifying some of the genes underlying this variation in maize and rice, in the temperate cereals, a group that includes wheat, barley, and rye, only the dosage-dependent and highly pleiotropic Q locus in hexaploid wheat has been molecularly characterized. Here we show that the characteristic variation in the density of grains along the inflorescence, or spike, of modern cultivated barley (Hordeum vulgare) is largely the consequence of a perturbed interaction between microRNA172 and its corresponding binding site in the mRNA of an APELATA2 (AP2)-like transcription factor, HvAP2. We used genome-wide association and biparental mapping to identify HvAP2. By comparing inflorescence development and HvAP2 transcript abundance in an extreme dense-spike mutant and its nearly isogenic WT line, we show that HvAP2 turnover driven by microRNA 172 regulates the length of a critical developmental window that is required for elongation of the inflorescence internodes. Our data indicate that this heterochronic change, an altered timing of developmental events caused by specific temporal variation in the efficiency of HvAP2 turnover, leads to the striking differences in the size and shape of the barley spike. PMID:24065816

  11. 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.

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

    SciTech Connect

    Pena, S.D.J.; De Souza, K.T. ); De Andrade, M.; Chakraborty, R. )

    1994-01-18

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

  13. Height and critical frequency variations of the sporadic-E layer at midlatitudes

    NASA Astrophysics Data System (ADS)

    Šauli, P.; Bourdillon, A.

    2008-12-01

    The present study concerns variations in height and critical frequency of sporadic E layer over a wide period range of hours to several days, covering tidal and planetary oscillation domain. Besides periodicities in the tidal and planetary range that are known to occur within time series of critical frequencies (foEs) of sporadic-E layer [Pancheva, D., Haldoupis, C., Meek, C.E., Manson, A.H., Mitchell, N.J., 2003. Evidence of a role for modulated atmospheric tides in the dependence of sporadic E layers on planetary waves. Journal of Geophysical Research 108, Art. No. 1176; Haldoupis, C., Pancheva, D., Michell, N.J., 2004. A study of tidal and planetary wave periodicities present in midlatitude sporadic E layers. Journal of Geophysical Research 109, Art. No. A02302] among others, we evidence the existence of the 4-day planetary wave well developed in the height of sporadic E time serie (hEs). Moreover it is shown that the central-period of the diurnal tidal component of hEs is not exactly 24 h but it varies between 22 and 26 h at the planetary wave period. At a first glance, this is surprising since the origin of the diurnal tide is a forced oscillation with a 24 h period due to the Earth rotation and the periodic heating of the atmosphere by the Sun. Our interpretation is based on the perturbation of the height of the Es layer imposed by the planetary wave. In this mechanism the Es layer is moved up and down by the planetary wave producing a Doppler effect and resulting in a shift of the central-period around 24 h. With this interpretation, the excursion of the central-period is related to the vertical velocity perturbation of the Es layer due to the planetary wave. For a central period varying between 22 and 26 h the peturbation velocities are 0.026 and , respectively.

  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. Adaptive Feedforward Compensation by Specified Step Settling Considering Resonance Frequency Variation and Constraint on Control Input Amplitude

    NASA Astrophysics Data System (ADS)

    Maeda, Yoshihiro; Wada, Masatake; Iwasaki, Makoto; Hirai, Hiromu

    This paper presents an adaptive feedfowad (FF) compensation method based on a deadbeat control framework for fast and precise positioning in mechatronic systems. The conventional FF compensation approach can design a FF compensator by considering both the frequency shaping and amplitude of FF control input, to suppress the response variations due to the perturbations in plant resonance frequency. However, since the conventional approach is not adaptive against frequency variations, an overshoot and/or undershoot response at the settling region would deteriorate the positioning performance. In this research, therefore, the proposed FF compensation approach with an adaptive identification system for the resonance frequency is adopted to achieve the desired positioning performance. The effectiveness of the proposed FF compensation approach has been verified by experiments using a prototype of an industrial positioning device.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. Frequency ratio of two optical clock transitions in 171Yb+ and constraints on the time variation of fundamental constants.

    PubMed

    Godun, R M; Nisbet-Jones, P B R; Jones, J M; King, S A; Johnson, L A M; Margolis, H S; Szymaniec, K; Lea, S N; Bongs, K; Gill, P

    2014-11-21

    Singly ionized ytterbium, with ultranarrow optical clock transitions at 467 and 436 nm, is a convenient system for the realization of optical atomic clocks and tests of present-day variation of fundamental constants. We present the first direct measurement of the frequency ratio of these two clock transitions, without reference to a cesium primary standard, and using the same single ion of 171Yb+. The absolute frequencies of both transitions are also presented, each with a relative standard uncertainty of 6×10(-16). Combining our results with those from other experiments, we report a threefold improvement in the constraint on the time variation of the proton-to-electron mass ratio, μ/μ=0.2(1.1)×10(-16)  yr(-1), along with an improved constraint on time variation of the fine structure constant, α/α=-0.7(2.1)×10(-17)  yr(-1). PMID:25479482

  2. 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.

  3. Complete Haplotype Sequence of the Human Immunoglobulin Heavy-Chain Variable, Diversity, and Joining Genes and Characterization of Allelic and Copy-Number Variation

    PubMed Central

    Watson, Corey T.; Steinberg, Karyn M.; Huddleston, John; Warren, Rene L.; Malig, Maika; Schein, Jacqueline; Willsey, A. Jeremy; Joy, Jeffrey B.; Scott, Jamie K.; Graves, Tina A.; Wilson, Richard K.; Holt, Robert A.; Eichler, Evan E.; Breden, Felix

    2013-01-01

    The immunoglobulin heavy-chain locus (IGH) encodes variable (IGHV), diversity (IGHD), joining (IGHJ), and constant (IGHC) genes and is responsible for antibody heavy-chain biosynthesis, which is vital to the adaptive immune response. Programmed V-(D)-J somatic rearrangement and the complex duplicated nature of the locus have impeded attempts to reconcile its genomic organization based on traditional B-lymphocyte derived genetic material. As a result, sequence descriptions of germline variation within IGHV are lacking, haplotype inference using traditional linkage disequilibrium methods has been difficult, and the human genome reference assembly is missing several expressed IGHV genes. By using a hydatidiform mole BAC clone resource, we present the most complete haplotype of IGHV, IGHD, and IGHJ gene regions derived from a single chromosome, representing an alternate assembly of ∼1 Mbp of high-quality finished sequence. From this we add 101 kbp of previously uncharacterized sequence, including functional IGHV genes, and characterize four large germline copy-number variants (CNVs). In addition to this germline reference, we identify and characterize eight CNV-containing haplotypes from a panel of nine diploid genomes of diverse ethnic origin, discovering previously unmapped IGHV genes and an additional 121 kbp of insertion sequence. We genotype four of these CNVs by using PCR in 425 individuals from nine human populations. We find that all four are highly polymorphic and show considerable evidence of stratification (Fst = 0.3–0.5), with the greatest differences observed between African and Asian populations. These CNVs exhibit weak linkage disequilibrium with SNPs from two commercial arrays in most of the populations tested. PMID:23541343

  4. 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

  5. Radial-femoral concordance in time and frequency domain-based estimates of systemic arterial respiratory variation.

    PubMed

    Thiele, Robert H; Colquhoun, Douglas A; Tucker-Schwartz, Jason M; Gillies, George T; Durieux, Marcel E

    2012-10-01

    Commonly used arterial respiratory variation metrics are based on mathematical analysis of arterial waveforms in the time domain. Because the shape of the arterial waveform is dependent on the site at which it is measured, we hypothesized that analysis of the arterial waveform in the frequency domain might provide a relatively site-independent means of measuring arterial respiratory variation. Radial and femoral arterial blood pressures were measured in nineteen patients undergoing liver transplantation. Systolic pressure variation (SPV), pulse pressure variation (PPV), area under the curve variation (AUCV), and mean arterial pressure variation (MAPV) at radial and femoral sites were calculated off-line. Two metrics, "Spectral Peak Ratio" (SPeR) and "Spectral Power Ratio" (SPoR) based on ratios of the spectral peak and spectral area (power) at the respiratory and cardiac frequencies, were calculated at both radial and femoral sites. Variance among radial-femoral differences was compared and correlation coefficients describing the relationship between respiratory variation at the radial and femoral sites were developed. The variance in radial-femoral differences were significantly different (p < 0.001). The correlation between radial and femoral estimates of respiratory variation were 0.746, 0.658, 0.858, 0.882, 0.941, and 0.925 for SPV, PPV, AUCV, MAPV, SPeR, and SPoR, respectively. Assuming a PPV treatment threshold of 12 % (or equivalent), differences in treatment decisions based on radial or femoral estimates would arise in 12, 14, 5.4, 5.7, 4.8, and 5.5 % of minutes for SPV, PPV, AUCV, MAPV, spectral peak ratio, and spectral power ratio, respectively. As compared to frequency domain-based estimates of respiratory variation, SPV and PPV are relatively dependent on the anatomic site at which they are measured. Spectral peak and power ratios are relatively site-independent means of measuring respiratory variation, and may offer a useful alternative to time

  6. Effects of magnitude and frequency of variations in external power output on simulated cycling time-trial performance.

    PubMed

    Wells, Marc; Atkinson, Greg; Marwood, Simon

    2013-01-01

    Mechanical models of cycling time-trial performance have indicated adverse effects of variations in external power output on overall performance times. Nevertheless, the precise influences of the magnitude and number of these variations over different distances of time trial are unclear. A hypothetical cyclist (body mass 70 kg, bicycle mass 10 kg) was studied using a mathematical model of cycling, which included the effects of acceleration. Performance times were modelled over distances of 4-40 km, mean power outputs of 200-600 W, power variation amplitudes of 5-15% and variation frequencies of 2-32 per time-trial. Effects of a "fast-start" strategy were compared with those of a constant-power strategy. Varying power improved 4-km performance at all power outputs, with the greatest improvement being 0.90 s for ± 15% power variation. For distances of 16.1, 20 and 40 km, varying power by ± 15% increased times by 3.29, 4.46 and 10.43 s respectively, suggesting that in long-duration cycling in constant environmental conditions, cyclists should strive to reduce power variation to maximise performance. The novel finding of the present study is that these effects are augmented with increasing event distance, amplitude and period of variation. These two latter factors reflect a poor adherence to a constant speed. PMID:23711074

  7. 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

  8. Microsatellite frequencies vary with body mass and body temperature in mammals, suggesting correlated variation in mutation rate.

    PubMed

    Amos, William; 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

  9. Anthelmintic resistance in Swedish sheep flocks based on a comparison of the results from the faecal egg count reduction test and resistant allele frequencies of the beta-tubulin gene.

    PubMed

    Höglund, Johan; Gustafsson, Katarina; Ljungström, Britt-Louise; Engström, Annie; Donnan, Alison; Skuce, Philip

    2009-04-01

    A faecal egg count reduction test (FECRT) survey was conducted during the grazing season 2006 and 2007 to provide an updated indication of the prevalence of anthelmintic resistance in sheep flocks in Sweden. A total of 1330 faecal samples from 90 flocks on 45 farms, with a minimum of 20 ewes each, was collected by local sheep veterinarians. Per treatment group, approximately 15 lambs were dewormed either with oral suspensions of ivermectin (Ivomec vet.) or albendazole (Valbazen vet.). The efficacy on each farm was investigated either in 2006 or 2007 by faecal egg counts collected on the day of treatment and in a new sample from the same animals 7-10 days later. Third-stage larvae (L3) were initially identified morphologically from pooled cultures. These were then used as the source of genomic DNA template for two molecular tests. The first was a PCR-based test for specific identification of Haemonchus contortus, and the second was a Pyrosequencing assay for the analysis of benzimidazole (BZ) resistance targeting the P200 mutation in the parasite's beta-tubulin gene. Larval cultures indicated that Teladorsagia and Trichostrongylus were the predominant genera, but Haemonchus was diagnosed in 37% of the flocks. The PCR results revealed an almost 100% agreement with those farms that had previously been shown to have Haemonchus present, even when the % prevalence was low (approximately 3%). Only two (4%) of the surveyed farms showed evidence of BZ-resistant worm populations, with H. contortus being the species implicated according to post-treatment larval culture results. The Pyrosequencing assay detected BZ resistant allele frequencies of >40% in the Haemonchus-positive farms and 100% resistant alleles in the clinically most resistant farms. These preliminary results suggest that the FECRT is less sensitive than the molecular test at detecting BZ resistance. However, both tests need to be interpreted carefully, bearing in mind the relative proportions of species

  10. 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.

  11. 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...

  12. 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.

  13. Characterizing low-frequency oscillation of Hall thrusters by dielectric wall temperature variation

    SciTech Connect

    Ning, Guo; Liqiu, Wei E-mail: weiliqiu@hit.edu.cn; Yongjie, Ding

    2014-05-15

    The low-frequency oscillation characteristics of a Hall thruster were investigated by varying the dielectric wall temperature. Experimental results indicate that increasing the dielectric wall temperature can result in an increase in the amplitude of low-frequency oscillation and a slight decrease in its frequency. Physical analysis revealed that this change is related to the secondary electron emissions at different dielectric wall temperatures. The evidence suggests that this technique can serve as an effective way for future studies to examine how secondary electron emissions affect a discharging thruster.

  14. Variation in viscoelastic properties of bovine articular cartilage below, up to and above healthy gait-relevant loading frequencies

    PubMed Central

    Sadeghi, Hamid; Shepherd, Duncan ET

    2015-01-01

    The aim of this study was to determine the variation in viscoelastic properties of femoral head bovine articular cartilage, on-bone, over five orders of magnitude of loading frequency. These frequencies ranged from below, up to and above healthy gait-relevant frequencies, using<1, 1–5 and 10 Hz, respectively. Dynamic mechanical analysis was used to measure storage and loss stiffness. A maximum compressive force of 36 N was applied through a chamfered-end, 5.2-mm-diameter, indenter. This induced a maximum nominal stress of 1.7 MPa. The ratio of storage to loss stiffness increased from near parity (2.5) at low frequencies to 11.4 at 10 Hz. This was the result of a significant logarithmic increase (p < 0.05) in storage stiffness with frequency, from 367 N/mm (0.001 Hz) up to 1460 N/mm (10 Hz). In contrast, the loss stiffness remained approximately constant. In conclusion, viscoelastic properties of articular cartilage measured at frequencies below those of gait activities are poor predictors of its relevant dynamic mechanical behaviour. PMID:25767149

  15. Variation in viscoelastic properties of bovine articular cartilage below, up to and above healthy gait-relevant loading frequencies.

    PubMed

    Sadeghi, Hamid; Espino, Daniel M; Shepherd, Duncan E T

    2015-02-01

    The aim of this study was to determine the variation in viscoelastic properties of femoral head bovine articular cartilage, on-bone, over five orders of magnitude of loading frequency. These frequencies ranged from below, up to and above healthy gait-relevant frequencies, using<1, 1-5 and 10 Hz, respectively. Dynamic mechanical analysis was used to measure storage and loss stiffness. A maximum compressive force of 36 N was applied through a chamfered-end, 5.2-mm-diameter, indenter. This induced a maximum nominal stress of 1.7 MPa. The ratio of storage to loss stiffness increased from near parity (2.5) at low frequencies to 11.4 at 10 Hz. This was the result of a significant logarithmic increase (p < 0.05) in storage stiffness with frequency, from 367 N/mm (0.001 Hz) up to 1460 N/mm (10 Hz). In contrast, the loss stiffness remained approximately constant. In conclusion, viscoelastic properties of articular cartilage measured at frequencies below those of gait activities are poor predictors of its relevant dynamic mechanical behaviour. PMID:25767149

  16. 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.

  17. 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...

  18. 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

  19. 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...

  20. Genome-wide variation of the somatic mutation frequency in transgenic plants

    PubMed Central

    Kovalchuk, Igor; Kovalchuk, Olga; Hohn, Barbara

    2000-01-01

    In order to analyse the frequency of point mutations in whole plants, several constructs containing single nonsense mutations in the β-glucuronidase (uidA) gene were used to generate transgenic Arabidopsis thaliana plants. Upon histochemical staining of transgenic plants, sectors indicative of transgene reactivation appeared. Reversion frequencies were in the range of 10–7–10–8 events per base pair, exceeding the previous estimates for other eukaryotes at least 100-fold. The frequency was dependent on the position of the mutation substrate within the transgene and the position of the transgene within the Arabidopsis genome. An inverse relationship between the level of transgene transcription and mutation frequency was observed in single-copy lines. DNA-damaging factors induced the mutation frequency by a factor of up to 56 for UV-C, a factor of 3 for X-rays and a factor of 2 for methyl methanesulfonate. This novel plant mutation-monitoring system allowed us to measure the frequencies of point mutation in whole plants and may be used as an alternative or complement to study the mutagenicity of different environmental factors on the higher eukaryote’s genome. PMID:10970837

  1. 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.

  2. Inferring the age of a fixed beneficial allele.

    PubMed

    Ormond, Louise; Foll, Matthieu; Ewing, Gregory B; Pfeifer, Susanne P; Jensen, Jeffrey D

    2016-01-01

    Estimating the age and strength of beneficial alleles is central to understanding how adaptation proceeds in response to changing environmental conditions. Several haplotype-based estimators exist for inferring the age of segregating beneficial mutations. Here, we develop an approximate Bayesian-based approach that rather estimates these parameters for fixed beneficial mutations in single populations. We integrate a range of existing diversity, site frequency spectrum, haplotype- and linkage disequilibrium-based summary statistics. We show that for strong selective sweeps on de novo mutations the method can estimate allele age and selection strength even in nonequilibrium demographic scenarios. We extend our approach to models of selection on standing variation, and co-infer the frequency at which selection began to act upon the mutation. Finally, we apply our method to estimate the age and selection strength of a previously identified mutation underpinning cryptic colour adaptation in a wild deer mouse population, and compare our findings with previously published estimates as well as with geological data pertaining to the presumed shift in selective pressure. PMID:26576754

  3. Comparative analysis of the apo(a) gene, apo(a) glycoprotein, and plasma concentrations of Lp(a) in three ethnic groups. Evidence for no common "null" allele at the apo(a) locus.

    PubMed Central

    Gaw, A; Boerwinkle, E; Cohen, J C; Hobbs, H H

    1994-01-01

    Distributions of plasma lipoprotein(a) (Lp[a]) concentrations exhibit marked interracial differences. Apolipoprotein(a) (apo[a]), the unique constituent of Lp(a), is highly polymorphic in length due to allelic variations in the number of kringle 4(K-4)-encoding sequences. Plasma Lp(a) concentrations are inversely related to the number of K-4 repeats in the apo(a) alleles. To determine the contribution of this length variation to the interracial variation in plasma Lp(a) levels, we compared apo(a) allele size, glycoprotein size, and plasma Lp(a) concentrations in Caucasians, Chinese, and African Americans. Caucasians and African Americans had very different distributions of plasma Lp(a) concentrations yet there was no significant difference in the overall frequency distributions of their apo(a) alleles. Over the entire size spectrum of apo(a) alleles, the plasma Lp(a) levels were higher in African Americans than in Caucasians. Conversely, Caucasians and Chinese had similar plasma Lp(a) concentrations but significantly different apo(a) allele size distributions. Therefore, interracial differences in the plasma concentrations of Lp(a) are not due to differences in the frequency distributions of apo(a) alleles. We also examined the relationship between apo(a) allele size and the presence of detectable plasma apo(a) protein in plasma. Apo(a) alleles associated with no detectable plasma protein were not of uniformly large size, as had been expected, but were distributed over the entire size spectrum. From this analysis, we conclude that there is no common "null" allele at the apo(a) locus. Images PMID:8200989

  4. Glutathione S-transferase GSTT1 and GSTM1 allozymes: beyond null alleles.

    PubMed

    Agúndez, José A G; Ladero, José M

    2008-03-01

    Moyer AM, Salavaggione OE, Hebbring SJ et al.: Glutathione S-transferase T1 and M1: gene sequence variation and functional genomics. Clin. Cancer Res. 13, 7207-7216 (2007). Genetic variations in the glutathione S-transferases GSTT1 and GSTM1 have been studied in many human populations, and association of these variations with environmentally-related cancers, drug-induced hepatotoxicity and even chronification of viral hepatitis has been shown. However, studies carried out to date have been limited to gene deletion, designated as null alleles, and no extensive studies on other types of genetic variations have been carried out. This study is of great importance, as it describes the occurrence and the allele frequencies for 18 SNPs in the GSTT1 gene, including four nonsynonymous SNPs, and 69 SNPs, two of which are nonsynonymous, in the GSTM1 gene. The GSTT1 SNPs leading to the amino acid substitutions Asp43Asn, Thr65Met, Thr104Pro and a single nucleotide deletion in exon 4 cause a decrease in immunoreactive protein. Interestingly, the previously described nonsynonymous GSTT1 SNPs rs2266635 (Ala21Thr), rs11550606 (Leu30Pro), rs17856199 (Phe45Cys), rs11550605 (Thr104Pro), rs2266633 (Asp141Asn) and rs2234953 (Glu173Lys) were not identified in 400 subjects, thus indicating that these variant alleles are expected to occur at extremely low frequencies. This study reinforces the need to combine SNP databases and resequencing. On combining the data reported in this study with SNP databases, the most promising target SNPs for GSTT1 association studies are those causing the amino acid changes Asp43Asn, Thr65Met, Thr104Pro and the single nucleotide deletion in exon 4. These gene variants should be analyzed in African-American and Hispanic subjects to increase the predictive capacity of genetic tests. For Caucasians and Oriental subjects, testing for null alleles seems to be sufficient. PMID:18303971

  5. Two-Point Observations of High- and Low-Frequency Variations of Helium Abundance in the Solar Win

    NASA Astrophysics Data System (ADS)

    Safrankova, J.; Cagas, P.; Nemecek, Z.; Prech, L.; Zastenker, G. N.; Riazantseva, M.

    2014-12-01

    Variations of the abundance of heavy species observed in the solar wind are usually attributed to spacecraft encounters with streams emanating from different places and altitudes in the source region and their further evolution is considered as being negligible. These conclusions are based on an analysis of highly averaged data and much less attention was devoted to variations on the time scale of seconds. The BMSW instrument onboard the Spektr-R spacecraft provides a high-time resolution data of the helium and proton fluxes and proton velocity, density, and temperature that suitable for investigations of rapid variations. The paper compares measurements in two points (Spektr-R and Wind) and focuses on the changes of helium abundance on this middle scale and on their correlations with variations of other parameters. We have found that only a low-frequency part of He abundance variations can be attributed to changes of the source region, whereas a significant portion of them could be generated by in-transit turbulence that is probably driven by the speed difference between the ion species.

  6. Polymorphisms in the cytochrome P450 CYP1A2 gene (CYP1A2) in colorectal cancer patients and controls: allele frequencies, linkage disequilibrium and influence on caffeine metabolism

    PubMed Central

    Sachse, Christoph; Bhambra, Upinder; Smith, Gillian; Lightfoot, Tracy J; Barrett, Jennifer H; Scollay, Jenna; Garner, R Colin; Boobis, Alan R; Wolf, C Roland; Gooderham, Nigel J

    2003-01-01

    Aim Several single nucleotide polymorphisms (SNPs) of the cytochrome P450 enzyme 1A2 gene (CYP1A2) have been reported. Here, frequencies, linkage disequilibrium and phenotypic consequences of six SNPs are described. Methods From genomic DNA, 114 British Caucasians (49 colorectal cancer cases and 65 controls) were genotyped for the CYP1A2 polymorphisms −3858G→A (allele CYP1A2*1C), −2464T→delT (CYP1A2*1D), −740T→G (CYP1A2*1E and *1G), −164A→C (CYP1A2*1F), 63C→G (CYP1A2*2), and 1545T→C (alleles CYP1A2*1B, *1G, *1H and *3), using polymerase chain reaction–restriction fragment length polymorphism assays. All patients and controls were phenotyped for CYP1A2 by h.p.l.c. analysis of urinary caffeine metabolites. Results In 114 samples, the most frequent CYP1A2 SNPs were 1545T→C (38.2% of tested chromosomes), −164A→C (CYP1A2*1F, 33.3%) and −2464T→delT (CYP1A2*1D, 4.82%). The SNPs were in linkage disequilibrium: the most frequent constellations were found to be −3858G/−2464T/−740T/−164A/63C/1545T (61.8%), −3858G/−2464T/−740T/−164C/63C/1545C (33.3%), and −3858G/−2464delT/−740T/−164A/63C/1545C (3.51%), with no significant frequency differences between cases and controls. In the phenotype analysis, lower caffeine metabolic ratios were detected in cases than in controls. This was significant in smokers (n = 14, P = 0.020), and in a subgroup of 15 matched case-control pairs (P = 0.007), but it was not significant in nonsmokers (n = 100, P = 0.39). There was no detectable association between CYP1A2 genotype and caffeine phenotype. Conclusions (i) CYP1A2 polymorphisms are in linkage disequilibrium. Therefore, only −164A→C (CYP1A2*1F) and −2464T→delT (CYP1A2*1D) need to be analysed in the routine assessment of CYP1A2 genotype; (ii) in vivo CYP1A2 activity is lower in colorectal cancer patients than in controls, and (iii) CYP1A2 genotype had no effect on phenotype (based on the caffeine metabolite ratio). However, this

  7. Variation of Magnetic Particle Imaging Tracer Performance With Amplitude and Frequency of the Applied Magnetic Field

    PubMed Central

    Khandhar, Amit P.; Kemp, Scott J.; Ota, Satoshi; Nakamura, Kosuke; Takemura, Yasushi; Krishnan, Kannan M.

    2015-01-01

    The magnetic response of magnetic particle imaging (MPI) tracers varies with the slew rate of the applied magnetic field, as well as with the tracer's average magnetic core size. Currently, 25 kHz and 20 mT/μ0 drive fields are common in MPI, but lower field amplitudes may be necessary for patient safety in future designs. We studied how several different sizes of monodisperse MPI tracers behaved under different drive field amplitude and frequency, using magnetic particle spectrometry and ac hysteresis for drive field conditions at 16, 26, and 40 kHz, with field amplitudes from 5 to 40 mT/μ0. We observed that both field amplitude and frequency can influence the tracer behavior, but that the magnetic behavior is consistent when the slew rate (the product of field amplitude and frequency) is consistent. However, smaller amplitudes provide a correspondingly smaller field of view, sometimes resulting in excitation of a minor hysteresis loop. PMID:26023242

  8. 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.

  9. 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 across the entire frequency band. No statistically significant signal was detected in any of the three searches.

  10. Longitudinal frequency variation of long-lasting EMIC Pc1-Pc2 waves localized in the inner magnetosphere

    NASA Astrophysics Data System (ADS)

    Kim, K.-H.; Shiokawa, K.; Mann, I. R.; Park, J.-S.; Kwon, H.-J.; Hyun, K.; Jin, H.; Connors, M.

    2016-02-01

    Long-lasting (> 20 h) electromagnetic ion cyclotron (EMIC) Pc1-Pc2 waves were observed by the Athabasca (L =˜ 4.6) induction magnetometer and Canadian Array for Realtime Investigations of Magnetic Activity (L =˜ 4-6) fluxgate magnetometers on 5 April 2007. These waves showed a systematic frequency change with local time, the minimum frequency near dusk, and the maximum frequency near dawn. Assuming the plasmapause as a potential source region of the waves, we estimated the plasmapause location from localized proton enhancement (LPE) events observed at NOAA-Polar Orbiting Environmental Satellites and METOP-2 satellites. We found that the longitudinal frequency variation of EMIC waves has a clear correlation with the estimated plasmapause location and that the waves are in the frequency band between the equatorial helium and oxygen gyrofrequencies at the estimated plasmapause. With our analysis results we suggest that the LPE events are caused by wave-particle interaction with the helium band EMIC waves generated near the plasmapause.

  11. Quantitatively analyzing dielectrical properties of resins and mapping permittivity variations in CFRP with high-frequency eddy current device technology

    NASA Astrophysics Data System (ADS)

    Gäbler, Simone; Heuer, Henning; Heinrich, Gert; Kupke, Richard

    2015-03-01

    Eddy current testing is well-established for non-destructive characterization of electrical conductive materials. The development of high-frequency eddy current technology (with frequency ranges up to 100 MHz) made it even possible to extend the classical fields of application towards less conductive materials like CFRP. Maxwell's equations and recent research show that the use of high-frequency eddy current technology is also suitable for non-conductive materials. In that case the change of complex impedance of the probing coil contains information on sample permittivity. This paper shows that even a quantitative measurement of complex permittivity with high-frequency eddy current device technology is possible using an appropriate calibration. Measurement accuracy is comparable to commercial capacitive dielectric analyzers. If the sample material is electrically conductive, both, permittivity and conductivity influence the complex impedance measured with high-frequency eddy current devices. Depending on the measurement setup and the sheet resistance of the sample a parallel characterization of both parameters is possible on isotropic multi-layer materials. On CFRP the permittivity measurement is much more complex due to the capacitive effects between the carbon rovings. However, first results show that at least the local permittivity variations (like those caused by thermal damages) are detectable.

  12. Cell Surface Expression Level Variation between Two Common Human Leukocyte Antigen Alleles, HLA-A2 and HLA-B8, Is Dependent on the Structure of the C Terminal Part of the Alpha 2 and the Alpha 3 Domains

    PubMed Central

    Dellgren, Christoffer; Nehlin, Jan O.; Barington, Torben

    2015-01-01

    Constitutive cell surface expression of Human Leukocyte Antigen (HLA) class I antigens vary extremely from tissue to tissue and individual antigens may differ widely in expression levels. Down-regulation of class I expression is a known immune evasive mechanism used by cancer cells and viruses. Moreover, recent observations suggest that even minor differences in expression levels may influence the course of viral infections and the frequency of complications to stem cell transplantation. We have shown that some human multipotent stem cells have high expression of HLA-A while HLA-B is only weakly expressed, and demonstrate here that this is also the case for the human embryonic kidney cell line HEK293T. Using quantitative flow cytometry and quantitative polymerase chain reaction we found expression levels of endogenous HLA-A3 (median 71,204 molecules per cell) 9.2-fold higher than the expression of-B7 (P = 0.002). Transfection experiments with full-length HLA-A2 and -B8 encoding plasmids confirmed this (54,031 molecules per cell vs. 2,466, respectively, P = 0.001) independently of transcript levels suggesting a post-transcriptional regulation. Using chimeric constructs we found that the cytoplasmic tail and the transmembrane region had no impact on the differential cell surface expression. In contrast, ~65% of the difference could be mapped to the six C-terminal amino acids of the alpha 2 domain and the alpha 3 domain (amino acids 176–284), i.e. amino acids not previously shown to be of importance for differential expression levels of HLA class I molecules. We suggest that the differential cell surface expression of two common HLA-A and–B alleles is regulated by a post-translational mechanism that may involve hitherto unrecognized molecules. PMID:26258424

  13. Vowel Identification by Listeners with Hearing Impairment in Response to Variation in Formant Frequencies

    ERIC Educational Resources Information Center

    Molis, Michelle R.; Leek, Marjorie R.

    2011-01-01

    Purpose: This study examined the influence of presentation level and mild-to-moderate hearing loss on the identification of a set of vowel tokens systematically varying in the frequency locations of their second and third formants. Method: Five listeners with normal hearing (NH listeners) and five listeners with hearing impairment (HI listeners)…

  14. Active noise control using noise source having adaptive resonant frequency tuning through stress 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 an expandable ring embedded in the noise radiating element. Excitation of the ring causes expansion or contraction of the ring, thereby varying the stress in the noise radiating element. The ring is actuated by a controller which receives input of a feedback 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 ring, causing the ring to expand or contract. Instead of a single ring embedded in the noise radiating panel, a first expandable ring can be bonded to one side of the noise radiating element, and a second expandable ring can be bonded to the other side.

  15. Path loss variation of on-body UWB channel in the frequency bands of IEEE 802.15.6 standard.

    PubMed

    Goswami, Dayananda; Sarma, Kanak C; Mahanta, Anil

    2016-06-01

    The wireless body area network (WBAN) has gaining tremendous attention among researchers and academicians for its envisioned applications in healthcare service. Ultra wideband (UWB) radio technology is considered as excellent air interface for communication among body area network devices. Characterisation and modelling of channel parameters are utmost prerequisite for the development of reliable communication system. The path loss of on-body UWB channel for each frequency band defined in IEEE 802.15.6 standard is experimentally determined. The parameters of path loss model are statistically determined by analysing measurement data. Both the line-of-sight and non-line-of-sight channel conditions are considered in the measurement. Variations of parameter values with the size of human body are analysed along with the variation of parameter values with the surrounding environments. It is observed that the parameters of the path loss model vary with the frequency band as well as with the body size and surrounding environment. The derived parameter values are specific to the particular frequency bands of IEEE 802.15.6 standard, which will be useful for the development of efficient UWB WBAN system. PMID:27382482

  16. Corner Frequency Variation in the Southeastern Region of the 1992 Nicaragua Tsunami Earthquake

    NASA Astrophysics Data System (ADS)

    Rotman, H. M. M.; Bilek, S. L.; Phillips, W. S.

    2014-12-01

    At the Nicaragua portion of the Middle America Trench, where the Cocos Plate is subducting at ~85 mm/yr, a tsunami earthquake (mb 5.3, Ms 7.2, Mw 7.6) occurred at 15 km depth on 2 September 1992, causing a tsunami up to 8 m high and >116 deaths. A tsunami earthquake is characterized by deficiency in high frequency radiated energy and large tsunami for its Ms. Tsunami earthquakes are relatively rare, but their occurrence presents a significant hazard to coastal populations, so the potential to identify tsunami earthquake regions has wide-reaching hazard implications. Here we examine the notion that the cause of the dominantly low frequency energy in the 1992 tsunami earthquake may also manifest in small earthquakes in the same area. We examine 241 events within and south of the 1992 rupture limits with hypocenters 8-30 km depth and 1.7 < Mw < 4.6, recorded by land station and ocean bottom seismometers in southern Nicaragua and northern Costa Rica from November 2005 to June 2006. Event source parameters moment, corner frequency, and stress drop are determined using the spectral ratios of S-wave coda. Mean stress drop inside the 1992 rupture area is 3.2 MPa, and immediately south of the 1992 rupture zone mean stress drop is 10.4 MPa. Inside and outside the 1992 rupture zone at similar depths, the increase in stress drop is by a factor of five and occurs abruptly over <50 km. The mean corner frequency of events in the 1992 rupture area is ~45% the mean corner frequency value for events south of the 1992 rupture zone. Therefore, our results demonstrate different source parameter characteristics for microseismicity in the region of a past tsunami earthquake. If this finding can be reproduced at other subduction zones, it may significantly improve subduction zone coastal hazard assessment.

  17. Spatial and Temporal Variation in Selection of Genes Associated with Pearl Millet Varietal Quantitative Traits In situ.

    PubMed

    Mariac, Cédric; Ousseini, Issaka S; Alio, Abdel-Kader; Jugdé, Hélène; Pham, Jean-Louis; Bezançon, Gilles; Ronfort, Joelle; Descroix, Luc; Vigouroux, Yves

    2016-01-01

    Ongoing global climate changes imply new challenges for agriculture. Whether plants and crops can adapt to such rapid changes is still a widely debated question. We previously showed adaptation in the form of earlier flowering in pearl millet at the scale of a whole country over three decades. However, this analysis did not deal with variability of year to year selection. To understand and possibly manage plant and crop adaptation, we need more knowledge of how selection acts in situ. Is selection gradual, abrupt, and does it vary in space and over time? In the present study, we tracked the evolution of allele frequency in two genes associated with pearl millet phenotypic variation in situ. We sampled 17 populations of cultivated pearl millet over a period of 2 years. We tracked changes in allele frequencies in these populations by genotyping more than seven thousand individuals. We demonstrate that several allele frequencies changes are compatible with selection, by correcting allele frequency changes associated with genetic drift. We found marked variation in allele frequencies from year to year, suggesting a variable selection effect in space and over time. We estimated the strength of selection associated with variations in allele frequency. Our results suggest that the polymorphism maintained at the genes we studied is partially explained by the spatial and temporal variability of selection. In response to environmental changes, traditional pearl millet varieties could rapidly adapt thanks to this available functional variability. PMID:27507986

  18. Spatial and Temporal Variation in Selection of Genes Associated with Pearl Millet Varietal Quantitative Traits In situ

    PubMed Central

    Mariac, Cédric; Ousseini, Issaka S.; Alio, Abdel-Kader; Jugdé, Hélène; Pham, Jean-Louis; Bezançon, Gilles; Ronfort, Joelle; Descroix, Luc; Vigouroux, Yves

    2016-01-01

    Ongoing global climate changes imply new challenges for agriculture. Whether plants and crops can adapt to such rapid changes is still a widely debated question. We previously showed adaptation in the form of earlier flowering in pearl millet at the scale of a whole country over three decades. However, this analysis did not deal with variability of year to year selection. To understand and possibly manage plant and crop adaptation, we need more knowledge of how selection acts in situ. Is selection gradual, abrupt, and does it vary in space and over time? In the present study, we tracked the evolution of allele frequency in two genes associated with pearl millet phenotypic variation in situ. We sampled 17 populations of cultivated pearl millet over a period of 2 years. We tracked changes in allele frequencies in these populations by genotyping more than seven thousand individuals. We demonstrate that several allele frequencies changes are compatible with selection, by correcting allele frequency changes associated with genetic drift. We found marked variation in allele frequencies from year to year, suggesting a variable selection effect in space and over time. We estimated the strength of selection associated with variations in allele frequency. Our results suggest that the polymorphism maintained at the genes we studied is partially explained by the spatial and temporal variability of selection. In response to environmental changes, traditional pearl millet varieties could rapidly adapt thanks to this available functional variability. PMID:27507986

  19. Seasonal and regional variations in extreme precipitation event frequency using CMIP5

    NASA Astrophysics Data System (ADS)

    Janssen, E.; Sriver, R. L.; Wuebbles, D. J.; Kunkel, K. E.

    2016-05-01

    Understanding how the frequency and intensity of extreme precipitation events are changing is important for regional risk assessments and adaptation planning. Here we use observational data and an ensemble of climate change model experiments (from the Coupled Model Intercomparison Project Phase 5 (CMIP5)) to examine past and potential future seasonal changes in extreme precipitation event frequency over the United States. Using the extreme precipitation index as a metric for extreme precipitation change, we find key differences between models and observations. In particular, the CMIP5 models tend to overestimate the number of spring events and underestimate the number of summer events. This seasonal shift in the models is amplified in projections. These results provide a basis for evaluating climate model skill in simulating observed seasonality and changes in regional extreme precipitation. Additionally, we highlight key sources of variability and uncertainty that can potentially inform regional impact analyses and adaptation planning.

  20. Monitoring of ULF (ultra-low-frequency) Geomagnetic Variations Associated with Earthquakes

    PubMed Central

    Hayakawa, Masashi; Hattori, Katsumi; Ohta, Kenji

    2007-01-01

    ULF (ultra-low-frequency) electromagnetic emission is recently recognized as one of the most promising candidates for short-term earthquake prediction. This paper reviews previous convincing evidence on the presence of ULF emissions before a few large earthquakes. Then, we present our network of ULF monitoring in the Tokyo area by describing our ULF magnetic sensors and we finally present a few, latest results on seismogenic electromagnetic emissions for recent large earthquakes with the use of sophisticated signal processings.

  1. High-frequency variations in Earth rotation and the planetary momentum budget

    NASA Technical Reports Server (NTRS)

    Rosen, Richard D.

    1995-01-01

    The major focus of the subject contract was on helping to resolve one of the more notable discrepancies still existing in the axial momentum budget of the solid Earth-atmosphere system, namely the disappearance of coherence between length-of-day (l.o.d.) and atmospheric angular momentum (AAM) at periods shorter than about a fortnight. Recognizing the importance of identifying the source of the high-frequency momentum budget anomaly, the scientific community organized two special measurement campaigns (SEARCH '92 and CONT '94) to obtain the best possible determinations of l.o.d. and AAM. An additional goal was to analyze newly developed estimates of the torques that transfer momentum between the atmosphere and its underlying surface to determine whether the ocean might be a reservoir of momentum on short time scales. Discrepancies between AAM and l.o.d. at sub-fortnightly periods have been attributed to either measurement errors in these quantities or the need to incorporate oceanic angular momentum into the planetary budget. Results from the SEARCH '92 and CONT '94 campaigns suggest that when special attention is paid to the quality of the measurements, better agreement between l.o.d. and AAM at high frequencies can be obtained. The mechanism most responsible for the high-frequency changes observed in AAM during these campaigns involves a direct coupling to the solid Earth, i.e, the mountain torque, thereby obviating a significant oceanic role.

  2. Semi-continuous mesophilic anaerobic digester performance under variations in solids retention time and feeding frequency.

    PubMed

    Manser, Nathan D; Mihelcic, James R; Ergas, Sarina J

    2015-08-01

    The goal of this research was to understand the effect of solids retention time (SRT) and feeding frequency on the performance of anaerobic digesters used to recover bioenergy from swine waste. Semi-continuous mesophilic anaerobic digesters were operated at varying SRTs and feeding frequencies. Performance metrics included biogas and methane production rates, biomass robustness and functionality and removals of volatile solids, soluble chemical oxygen demand, the fecal-indicator bacteria Escherichia coli, and the human pathogen Salmonella. Biochemical methane formation potential and specific methanogenic activity assays were used to demonstrate biomass robustness and functionality. Results indicated that anaerobic digesters fed weekly had higher average methane yields (0.20 vs. 0.18m(3)CH4/kg-VSadded), specific methanogenic activities (40 vs. 35ml/day), and fecal indicator bacteria destruction (99.9% vs. 99.4%) than those fed every-other day. Salmonella, soluble COD, and VS destruction did not change with varied feeding frequency; however, higher removals were observed with longer SRT. PMID:25965953

  3. Atomic Transition Frequencies, Isotope Shifts, and Sensitivity to Variation of the Fine Structure Constant for Studies of Quasar Absorption Spectra

    NASA Astrophysics Data System (ADS)

    Berengut, J. C.; Dzuba, V. A.; Flambaum, V. V.; King, J. A.; Kozlov, M. G.; Murphy, M. T.; Webb, J. K.

    Theories unifying gravity with other interactions suggest spatial and temporal variation of fundamental "constants" in the Universe. A change in the fine structure constant, α = {e}2/hslash c , could be detected via shifts in the frequencies of atomic transitions in quasar absorption systems. Recent studies using 140 absorption systems from the Keck telescope and 153 from the Very Large Telescope, suggest that α varies spatially (61). That is, in one direction on the sky α seems to have been smaller at the time of absorption, while in the opposite direction it seems to have been larger.

  4. Greater variation in BCL-2 mutation frequency among lymphocytes of heavy smokers than among those of controls

    SciTech Connect

    Cortopassi, G.A.; Liu, Y.; Bell, D.A.

    1994-12-31

    It is possible that the risk for tumors in specific human individuals might be most usefully estimated by determining the frequency of (rare) somatic mutations at oncogenic loci in their tissue. Using a sensitive nested PCR assay, we have investigated the frequency of rare t(14;18) (q32;q21) translocations at the bcl-2 proto-oncogene locus in peripheral blood lymphocytes of 85 smokers and 36 control non-smokers. The variation in translocation frequencies (plus or minus the variation at the 95% confidence interval) were 1.4 {+-} -0.37 per million lymphocytes among smokers, versus 0.53 {+-} -0.20 among non-smokers, a 2.6-fold excess of such oncogenic translocations among lymphocytes of smokers. Logistic regression analysis including age, race, sex, years of smoking and pack-years indicated that only current smoking was significantly associated with increased frequency of the translocation of bcl-2 occur in 85% of follicular lymphoma tumors, and about 50% of all Non-Hodgkin`s Lymphoma, and are thought to be the result of errors of the V(D)J recombinase. Epidemiological studies by others have shown that there is about a two-fold higher relative risk of Non-Hodgkin`s Lymphoma for heavy smokers vs. non-smokers. We speculate that one reason for excess NHL tumors among heavy smokers may be their increased average burden of t(14;18) mutations, and that smoke-derived substances may induce errors of the V(D)J recombinase by mutagenic or antigenic mechanisms.

  5. Improving Processes of Mechanized Pulsed Arc Welding of Low-Frequency Range Variation of Mode Parameters

    NASA Astrophysics Data System (ADS)

    Saraev, Yu N.; Solodskiy, S. A.; Ulyanova, O. V.

    2016-04-01

    A new technology of low-frequency modulation of the arc current in MAG and MIG welding is presented. The technology provides control of thermal and crystallization processes, stabilizes the time of formation and crystallization of the weld pool. Conducting theoretical studies allowed formulating the basic criteria for obtaining strong permanent joints for high-duty structures, providing conditions for more equilibrium structure of the deposited metal and the smaller width of the HAZ. The stabilization of time of the formation and crystallization of the weld pool improves the formation of the weld and increases productivity in welding thin sheet metal.

  6. Seasonal Variation of Frequency of High Current Lightning Discharges Observed by JLDN

    NASA Astrophysics Data System (ADS)

    Saito, Mikihisa; Ishii, Masaru; Fujii, Fumiyuki; Matsui, Michihiro

    Seasonal variations of number of high current lightning discharges exceeding 100kA observed by JLDN (Japanese Lightning Detection Network) were analyzed. The months with averaged altitudes of -10°C level higher than 5.7km are classified as ordinary summer from the viewpoint of lightning activity. Meanwhile, on the coast of the Sea of Japan, more than 90% of negative high current lightning discharges were -GC (Ground to Cloud) strokes in the months when monthly averaged altitudes of -10°C level are lower than 2.7km. These months are classified as the winter lightning season when upward lightning flashes frequently occur. Months other than winter or summer are classified as spring or autumn. In these seasons, the proportions of positive high current lightning discharges are higher than those of negative discharges like winter. Thus, the charge structure in the thunderclouds of spring and autumn may be similar to that in winter, and high current lightning strokes tend to occur. Since this variation of seasons is different in each area of Japan, relation of seasons, areas, and densities of high current lightning discharges were analyzed.

  7. Variation in low-frequency estimates of sound levels based on different units of analysis.

    PubMed

    Hawkins, Russell S; Miksis-Olds, Jennifer L; Smith, Chad M

    2014-02-01

    The measurement and analysis of underwater sound is a complicated process because of the variable durations of contributing sources and constantly changing water column dynamics. Because the ambient sound distribution does not always follow a Gaussian structure and may be nonstationary in time, analysis over an extended period is required to accurately characterize the data. Utilizing recordings from the Indian Ocean, the temporal variation in ambient sound including transient signals was examined using multiple processing window lengths and subsampling intervals. Results illustrate the degree of uncertainty in sound levels based on different units of analysis. The average difference between sound level estimates in the 10-30 Hz band due to subsampling was 2 dB and as high as 4 dB. The difference in the full band (5-110 Hz) was as high as 6 dB. Longer averaging windows (200 vs 60 s) resulted in larger variations over different subsampling intervals. This work demonstrates how sampling protocols within a single dataset can influence results and acknowledges that comparative studies at the same location but with different sampling protocols can be substantial if signal processing parameters are not statistically accounted for to confirm interpretation of results and observed trends. PMID:25234879

  8. Seasonal variation in phosphorus concentration-discharge hysteresis inferred from high-frequency in situ monitoring

    NASA Astrophysics Data System (ADS)

    Bieroza, M. Z.; Heathwaite, A. L.

    2015-05-01

    High-resolution in situ total phosphorus (TP), total reactive phosphorus (TRP) and turbidity (TURB) time series are presented for a groundwater-dominated agricultural catchment. Meta-analysis of concentration-discharge (c-q) intra-storm signatures for 61 storm events revealed dominant hysteretic patterns with similar frequency of anti-clockwise and clockwise responses; different determinands (TP, TRP, TURB) behaved similarly. We found that the c-q loop direction is controlled by seasonally variable flow discharge and temperature whereas the magnitude is controlled by antecedent rainfall. Anti-clockwise storm events showed lower flow discharge and higher temperature compared to clockwise events. Hydrological controls were more important for clockwise events and TP and TURB responses, whereas in-stream biogeochemical controls were important for anti-clockwise storm events and TRP responses. Based on the best predictors of the direction of the hysteresis loops, we calibrated and validated a simple fuzzy logic inference model (FIS) to determine likely direction of the c-q responses. We show that seasonal and inter-storm succession in clockwise and anti-clockwise responses corroborates the transition in P transport from a chemostatic to an episodic regime. Our work delivers new insights for the evidence base on the complexity of phosphorus dynamics. We show the critical value of high-frequency in situ observations in advancing understanding of freshwater biogeochemical processes.

  9. Population Dynamics of Sex-Determining Alleles in Honey Bees and Self-Incompatibility Alleles in Plants

    PubMed Central

    Yokoyama, Shozo; Nei, Masatoshi

    1979-01-01

    Mathematical theories of the population dynamics of sex-determining alleles in honey bees are developed. It is shown that in an infinitely large population the equilibrium frequency of a sex allele is 1/n, where n is the number of alleles in the population, and the asymptotic rate of approach to this equilibrium is 2/(3n) per generation. Formulae for the distribution of allele frequencies and the effective and actual numbers of alleles that can be maintained in a finite population are derived by taking into account the population size and mutation rate. It is shown that the allele frequencies in a finite population may deviate considerably from 1/n. Using these results, available data on the number of sex alleles in honey bee populations are discussed. It is also shown that the number of self-incompatibility alleles in plants can be studied in a much simpler way by the method used in this paper. A brief discussion about general overdominant selection is presented. PMID:17248901

  10. High Frequency Variations of Arctic Ocean Bottom Pressure and Their Relation to Atmospheric Pressure

    NASA Astrophysics Data System (ADS)

    Peralta Ferriz, A. C.; Morison, J.; Kwok, R.

    2009-12-01

    The ocean bottom pressure (OBP) was measured at the North Pole from 2005 to 2008, as part of the North Pole Environmental Observatory. OBP shows a spectral peak at a period of about 19 days, which is consistent with modeling results of OBP from the PanArctic Ice-Ocean Model Assimilation System, PIOMAS. The OBP measured in the central Beaufort Sea from 2003 to 2008 as part of the Beaufort Gyre Exploration Project shows the same spectral peak. The variations in Beaufort Sea OBP are well correlated with those at the North Pole. This signal is also detected in the sea level pressure (SLP) records from the NCEP/NCAR re-analysis for the same time as the observations of OBP. Similarly, Morison [1990] found a spectral peak at 19 days in OBP observations across the West Spitsbergen Current, in Fram Strait. Here we explore two questions: What is the source of the 19-day period atmospheric signal and how is this signal transferred to the ocean. Based on satellite altimetry, it has been shown that the inverted barometer effect applies in the Arctic Ocean at daily to weekly time-scales [Kwok, et al., 2006]. Indeed, comparison of OBP from PIOMAS, which assumes a perfect inverted barometer, with observed OBP suggests that departures from the inverted barometer response are small. The fact that the PIOMAS OBP without direct atmosphere pressure loading shows a spectral peak that is similar to observed OBP, suggests that these oscillations are wind (pressure gradient) driven rather than due to direct atmospheric loading. The basin-averaged OBP variations from PIOMAS are well correlated with the atmospheric pressure over Scandinavia. This is consistent with a correlation between southerly winds in Fram Strait and the basin-averaged OBP, with the pressure lagging the wind by 1-2 days. Through examination of atmospheric pressure data and ice-ocean model results, we investigate the hypotheses that the SLP variation is related to the passage of planetary waves across the North Atlantic

  11. Modulation of penetrance by the wild-type allele in dominantly inherited erythropoietic protoporphyria and acute hepatic porphyrias.

    PubMed

    Gouya, Laurent; Puy, Hervé; Robreau, Anne-Marie; Lyoumi, Said; Lamoril, Jérome; Da Silva, Vasco; Grandchamp, Bernard; Deybach, Jean-Charles

    2004-02-01

    We have recently demonstrated that in an autosomal dominant porphyria, erythropoietic protoporphyria (EPP), the coinheritance of a ferrochelatase (FECH) gene defect and of a wild-type low-expressed FECH allele is generally involved in the clinical expression of EPP. This mechanism may provide a model for phenotype modulation by minor variations in the expression of the wild-type allele in the other three autosomal dominant porphyrias that exhibit incomplete penetrance: acute intermittent porphyria (AIP), variegata porphyria (VP) and hereditary coproporphyria (HC), which are caused by partial deficiencies of hydroxy-methyl bilane synthase (HMBS), protoporphyrinogen oxidase (PPOX) and coproporphyrinogen oxidase (CPO), respectively. Given the dominant mode of inheritance of EPP, VP, AIP and HC, we first confirmed that the 200 overtly porphyric subjects (55 EPP, 58 AIP, 56 VP; 31 HC) presented a single mutation restricted to one allele (20 novel mutations and 162 known mutations). We then analysed the available single-nucleotide polymorphisms (SNPs) present at high frequencies in the general population and spreading throughout the FECH, HMBS, PPOX and the CPO genes in four case-control association studies. Finally, we explored the functional consequences of polymorphisms on the abundance of wild-type RNA, and used relative allelic mRNA determinations to find out whether low-expressed HMBS, PPOX and the CPO alleles occur in the general population. We confirm that the wild-type low-expressed allele phenomenon is usually operative in the mechanism of variable penetrance in EPP, but conclude that this is not the case in AIP and VP. For HC, the CPO mRNA determinations strongly suggest that normal CPO alleles with low-expression are present, but whether this low-expression of the wild-type allele could modulate the penetrance of a CPO gene defect in HC families remains to be ascertained. PMID:14669009

  12. Allelic Diversity and Geographical Distribution of the Gene Encoding Plasmodium falciparum Merozoite Surface Protein-3 in Thailand

    PubMed Central

    Sawaswong, Vorthon; Simpalipan, Phumin; Siripoon, Napaporn; Harnyuttanakorn, Pongchai; Pattaradilokrat, Sittiporn

    2015-01-01

    Merozoite surface proteins (MSPs) of malaria parasites play critical roles during the erythrocyte invasion and so are potential candidates for malaria vaccine development. However, because MSPs are often under strong immune selection, they can exhibit extensive genetic diversity. The gene encoding the merozoite surface protein-3 (MSP-3) of Plasmodium falciparum displays 2 allelic types, K1 and 3D7. In Thailand, the allelic frequency of the P. falciparum msp-3 gene was evaluated in a single P. falciparum population in Tak at the Thailand and Myanmar border. However, no study has yet looked at the extent of genetic diversity of the msp-3 gene in P. falciparum populations in other localities. Here, we genotyped the msp-3 alleles of 63 P. falciparum samples collected from 5 geographical populations along the borders of Thailand with 3 neighboring countries (Myanmar, Laos, and Cambodia). Our study indicated that the K1 and 3D7 alleles coexisted, but at different proportions in different Thai P. falciparum populations. K1 was more prevalent in populations at the Thailand-Myanmar and Thailand-Cambodia borders, whilst 3D7 was more prevalent at the Thailand-Laos border. Global analysis of the msp-3 allele frequencies revealed that proportions of K1 and 3D7 alleles of msp-3 also varied in different continents, suggesting the divergence of malaria parasite populations. In conclusion, the variation in the msp-3 allelic patterns of P. falciparum in Thailand provides fundamental knowledge for inferring the P. falciparum population structure and for the best design of msp-3 based malaria vaccines. PMID:25925176

  13. Forcing of polar motion in the Chandler frequency band: An opportunity to evaluate interannual climate variations

    NASA Astrophysics Data System (ADS)

    Plag, H.-P.; Chao, B. F.; Gross, R. S.; Van Dam, T.

    The Earth rotates about its axis once per day but does not do so uniformly. The length of the day changes by as much as a millisecond from day to day and the Earth wobbles as it rotates. That the Earth should wobble was predicted by the Swiss mathematician Leonhard Euler in 1765, but it was not until 1891 that the wobbling motion of the Earth was detected by the American astronomer Seth Carlo Chandler, Jr. In fact, Chandler observed that the Earth has two distinct wobbles, one with an annual period and the other with a 14-month period. The annual wobble is a forced motion of the Earth caused by seasonal variations in the atmosphere, oceans, and hydrosphere.

  14. Frequency of close companions among Kepler planets—a transit time variation study

    SciTech Connect

    Xie, Ji-Wei; Wu, Yanqin; Lithwick, Yoram E-mail: wu@astro.utoronto.ca

    2014-07-10

    A transiting planet exhibits sinusoidal transit time variations (TTVs) if perturbed by a companion near a mean-motion resonance. We search for sinusoidal TTVs in more than 2600 Kepler candidates, using the publicly available Kepler light curves (Q0-Q12). We find that the TTV fractions rise strikingly with the transit multiplicity. Systems where four or more planets transit enjoy a TTV fraction that is roughly five times higher than those where a single planet transits, and about twice as high as those for doubles and triples. In contrast, models in which all transiting planets arise from similar dynamical configurations predict comparable TTV fractions among these different systems. One simple explanation for our results is that there are at least two different classes of Kepler systems, one closely packed and one more sparsely populated.

  15. Low-frequency variations in sea level and currents in south San Francisco Bay

    USGS Publications Warehouse

    Walters, Roy A.

    1982-01-01

    In order to examine physical process in the subtidal time range, sea-level and current meter data for south San Francisco Bay (South Bay) were filtered using a low-pass digital filter to remove tidal period variations. and then subjected to an empirical orthogonal function analysis. For the sea-level data, there is one dominant empirical mode that is correlated with nonlocal coastal forcing. A small amount of the variance is associated with local wind setup. For the current meter data, there are two dominant empirical modes that correlate with local wind forcing and tidal forcing over the spring-neap cycle. In general, South Bay is dominated by coastal forcing on sea level during all seasons, and dominated by wind and tidal forcing on the residual currants during the summer.

  16. Can the Tibetan Plateau snow cover influence the interannual variations of Eurasian heat wave frequency?

    NASA Astrophysics Data System (ADS)

    Wu, Zhiwei; Zhang, Peng; Chen, Hua; Li, Yun

    2016-06-01

    The Eurasian continent has experienced significant year-to-year variations of summer heat waves during the past decades. Several possible factors, such as ocean temperature, soil moisture, and changes in land use and greenhouse gases, have been identified in previous studies, but the mechanisms are still unclear. In this study, it is found that the Tibetan Plateau snow cover (TPSC) is closely linked to the interannual variations of summer heat waves over Eurasia. The TPSC variability explains more than 30 % of the total variances of heat wave variability in the southern Europe and northeastern Asia (SENA) region. A set of numerical experiments reveal that the reduced TPSC may induce a distinct teleconnection pattern across the Eurasian continent, with two anomalous high pressure centers in the upper troposphere over the SENA region, which may lead to a reduction of the cloud formation near the surface. The less cloud cover tends to increase the net shortwave radiation and favor a stronger surface sensible heat flux in the dry surface condition over the SENA region, resulting in a deeper, warmer and drier atmospheric boundary layer that would further inhibit the local cloud formation. Such a positive land-atmosphere feedback may dry the surface even further, heat the near-surface atmosphere and thereby intensify the local heat waves. The above dynamical processes also operate on interdecadal time scales. Given the reduction of the TPSC could become more pronounced with increasing levels of greenhouse gases in a warming climate, we infer that the TPSC may play an increasingly important role in shaping the summer heat waves over the SENA region in next decades.

  17. Solar radial velocity variations and the search for Venus enabled by a laser frequency comb

    NASA Astrophysics Data System (ADS)

    Phillips, David F.; Dumusque, Xavier; Li, Chih-Hao; Glenday, Alexander; Sasselov, Dimitar; Szentgyorgyi, Andrew; Walsworth, Ronald L.

    2016-05-01

    We have recently demonstrated 50 cm/s sensitivity in measuring the radial velocity (RV) between the Earth and Sun using a simple, compact solar telescope feeding the HARPS-N spectrograph at the Italian National Telescope calibrated with our green astro-comb. The green astro-comb is a laser frequency comb optimized for calibrating astrophysical spectrographs. We have been operating the solar telescope to detect the RV signal of the Sun as a star for the past year both to study RV jitter associated with stellar (solar) fluctuations and to demonstrate sensitivity of these instruments to detect terrestrial exoplanets. In this talk I will present results from calibrating the HARPS-N exoplanet searcher spectrograph, solar RV stability, and the current status of our search for the signature of Venus.

  18. Air temperature variations on the Atlantic - Arctic boundary since 1802: the low-frequency pattern and ocean teleconnections

    NASA Astrophysics Data System (ADS)

    Wood, K. R.; Overland, J. E.; Jónsson, T.; Smoliak, B. V.

    2010-12-01

    A two-hundred year instrumental record of annual surface air temperature (SAT) in the Atlantic - Arctic boundary region was reconstructed from four station-based composite time series (Fig. 1). Credibility is supported by ice core records, other temperature proxies, and historical evidence. This record (designated TNA) provides new perspective on past climate fluctuations in a region where pivotal climate system processes occur and where unexplained low-frequency variations were observed during the 20th century. TNA shows that the low-frequency pattern of the 20th century does not have a clear analog in the previous century. During the 19th century decadal-scale climate fluctuations occurred in irregular episodes; none were as distinctive as the early 20th century warming event (~1920 to mid-century), which is the most striking historical feature in the record. Evidence of a strong teleconnection between TNA and SST anomalies in the western boundary current - southern recirculation gyre (WBC) region of the North Atlantic Ocean provides an opportunity to reframe the problem of low-frequency variability in the region in terms tractable to theory and empirical investigation. Positive fluctuations in both TNA (and by extension other climate variables associated with it) and SST in the WBC region could be initiated by persistent variations in the large-scale atmospheric circulation that promote the advection of warm maritime air into the Atlantic - Arctic region and simultaneously limit flux-induced cooling in the Nordic Seas and the WBC/recirculation gyre region. This leads to enhanced ocean heat storage in both regions and may consequently reinforce anomalous atmospheric circulation patterns like those observed during the early 20th century warming event. Figure 1. Extended annual mean SAT record for the Atlantic - Arctic boundary region (TNA). The early 20th century warming (ETCW) episode is marked. Regions represented by station-based composite SAT records used in

  19. Telomere Length Affects the Frequency and Mechanism of Antigenic Variation in Trypanosoma brucei

    PubMed Central

    Hovel-Miner, Galadriel A.; Boothroyd, Catharine E.; Mugnier, Monica; Dreesen, Oliver; Cross, George A. M.; Papavasiliou, F. Nina

    2012-01-01

    Trypanosoma brucei is a master of antigenic variation and immune response evasion. Utilizing a genomic repertoire of more than 1000 Variant Surface Glycoprotein-encoding genes (VSGs), T. brucei can change its protein coat by “switching” from the expression of one VSG to another. Each active VSG is monoallelically expressed from only one of approximately 15 subtelomeric sites. Switching VSG expression occurs by three predominant mechanisms, arguably the most significant of which is the non-reciprocal exchange of VSG containing DNA by duplicative gene conversion (GC). How T. brucei orchestrates its complex switching mechanisms remains to be elucidated. Recent work has demonstrated that an exogenous DNA break in the active site could initiate a GC based switch, yet the source of the switch-initiating DNA lesion under natural conditions is still unknown. Here we investigated the hypothesis that telomere length directly affects VSG switching. We demonstrate that telomerase deficient strains with short telomeres switch more frequently than genetically identical strains with long telomeres and that, when the telomere is short, switching preferentially occurs by GC. Our data supports the hypothesis that a short telomere at the active VSG expression site results in an increase in subtelomeric DNA breaks, which can initiate GC based switching. In addition to their significance for T. brucei and telomere biology, the findings presented here have implications for the many diverse pathogens that organize their antigenic genes in subtelomeric regions. PMID:22952449

  20. Associations of HLA-A, HLA-B and HLA-C alleles frequency with prevalence of herpes simplex virus infections and diseases across global populations: implication for the development of an universal CD8+ T-cell epitope-based vaccine.

    PubMed

    Samandary, Sarah; Kridane-Miledi, Hédia; Sandoval, Jacqueline S; Choudhury, Zareen; Langa-Vives, Francina; Spencer, Doran; Chentoufi, Aziz A; Lemonnier, François A; BenMohamed, Lbachir

    2014-08-01

    A significant portion of the world's population is infected with herpes simplex virus type 1 and/or type 2 (HSV-1 and/or HSV-2), that cause a wide range of diseases including genital herpes, oro-facial herpes, and the potentially blinding ocular herpes. While the global prevalence and distribution of HSV-1 and HSV-2 infections cannot be exactly established, the general trends indicate that: (i) HSV-1 infections are much more prevalent globally than HSV-2; (ii) over a half billion people worldwide are infected with HSV-2; (iii) the sub-Saharan African populations account for a disproportionate burden of genital herpes infections and diseases; (iv) the dramatic differences in the prevalence of herpes infections between regions of the world appear to be associated with differences in the frequencies of human leukocyte antigen (HLA) alleles. The present report: (i) analyzes the prevalence of HSV-1 and HSV-2 infections across various regions of the world; (ii) analyzes potential associations of common HLA-A, HLA-B and HLA-C alleles with the prevalence of HSV-1 and HSV-2 infections in the Caucasoid, Oriental, Hispanic and Black major populations; and (iii) discusses how our recently developed HLA-A, HLA-B, and HLA-C transgenic/H-2 class I null mice will help validate HLA/herpes prevalence associations. Overall, high prevalence of herpes infection and disease appears to be associated with high frequency of HLA-A(∗)24, HLA-B(∗)27, HLA-B(∗)53 and HLA-B(∗)58 alleles. In contrast, low prevalence of herpes infection and disease appears to be associated with high frequency of HLA-B(∗)44 allele. The finding will aid in developing a T-cell epitope-based universal herpes vaccine and immunotherapy. PMID:24798939

  1. Associations of HLA-A, HLA-B and HLA-C Alleles Frequency with Prevalence of Herpes Simplex Virus Infections and Diseases Across Global Populations: Implication for the Development of an Universal CD8+ T-Cell Epitope-Based Vaccine

    PubMed Central

    Samandary, Sarah; Kridane-Miledi, Hédia; Sandoval, Jacqueline S.; Choudhury, Zareen; Langa-Vives, Francina; Spencer, Doran; Chentoufi, Aziz A.; Lemonnier, François A.; BenMohamed, Lbachir

    2014-01-01

    A significant portion of the world’s population is infected with herpes simplex virus type 1 and/or type 2 (HSV-1 and/or HSV-2), that cause a wide range of diseases including genital herpes, oro-facial herpes, and the potentially blinding ocular herpes. While the global prevalence and distribution of HSV-1 and HSV-2 infections cannot be exactly established, the general trends indicate that: (i) HSV-1 infections are much more prevalent globally than HSV-2; (ii) Over half billion people worldwide are infected with HSV-2; (iii) the sub-Saharan African populations account for a disproportionate burden of genital herpes infections and diseases; (iv) the dramatic differences in the prevalence of herpes infections between regions of the world appear to be associated with differences in the frequencies of human leukocyte antigen (HLA) alleles. The present report: (i) analyzes the prevalence of HSV-1 and HSV-2 infections across various regions of the world; (ii) analyzes potential associations of common HLA-A, HLA-B and HLA-C alleles with the prevalence of HSV-1 and HSV-2 infections in the Caucasoid, Oriental, Hispanic and Black major populations; and (iii) discusses how our recently developed HLA-A, HLA-B, and HLA-C transgenic/H-2 class I null mice will help validate HLA/herpes prevalence associations. Overall, high prevalence of herpes infection and disease appears to be associated with high frequency of HLA-A*24, HLA-B*27, HLA-B*53 and HLA-B*58 alleles. In contrast, low prevalence of herpes infection and disease appears to be associated with high frequency of HLA-B*44 allele. The finding will aid in developing a T-cell epitope-based universal herpes vaccine and immunotherapy. PMID:24798939

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

    SciTech Connect

    Garber, T.L.; Butler, L.M.; Watkins, D.I.

    1995-05-01

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

  3. Spatial variations in the frequency-magnitude distribution of earthquakes in the southwestern Okinawa Trough

    NASA Astrophysics Data System (ADS)

    Lin, J.-Y.; Sibuet, J.-C.; Lee, C.-S.; Hsu, S.-K.; Klingelhoefer, F.

    2007-04-01

    The relations between the frequency of occurrence and the magnitude of earthquakes are established in the southern Okinawa Trough for 2823 relocated earthquakes recorded during a passive ocean bottom seismometer experiment. Three high b-values areas are identified: (1) for an area offshore of the Ilan Plain, south of the andesitic Kueishantao Island from a depth of 50 km to the surface, thereby confirming the subduction component of the island andesites; (2) for a body lying along the 123.3°E meridian at depths ranging from 0 to 50 km that may reflect the high temperature inflow rising up from a slab tear; (3) for a third cylindrical body about 15 km in diameter beneath the Cross Backarc Volcanic Trail, at depths ranging from 0 to 15 km. This anomaly might be related to the presence of a magma chamber at the base of the crust already evidenced by tomographic and geochemical results. The high b-values are generally linked to magmatic and geothermal activities, although most of the seismicity is linked to normal faulting processes in the southern Okinawa Trough.

  4. Spatial-temporal variation of low-frequency earthquake bursts near Parkfield, California

    NASA Astrophysics Data System (ADS)

    Wu, Chunquan; Guyer, Robert; Shelly, David; Trugman, Daniel; Frank, William; Gomberg, Joan; Johnson, Paul

    2015-08-01

    Tectonic tremor (TT) and low-frequency earthquakes (LFEs) have been found in the deeper crust of various tectonic environments globally in the last decade. The spatial-temporal behaviour of LFEs provides insight into deep fault zone processes. In this study, we examine recurrence times from a 12-yr catalogue of 88 LFE families with ˜730 000 LFEs in the vicinity of the Parkfield section of the San Andreas Fault (SAF) in central California. We apply an automatic burst detection algorithm to the LFE recurrence times to identify the clustering behaviour of LFEs (LFE bursts) in each family. We find that the burst behaviours in the northern and southern LFE groups differ. Generally, the northern group has longer burst duration but fewer LFEs per burst, while the southern group has shorter burst duration but more LFEs per burst. The southern group LFE bursts are generally more correlated than the northern group, suggesting more coherent deep fault slip and relatively simpler deep fault structure beneath the locked section of SAF. We also found that the 2004 Parkfield earthquake clearly increased the number of LFEs per burst and average burst duration for both the northern and the southern groups, with a relatively larger effect on the northern group. This could be due to the weakness of northern part of the fault, or the northwesterly rupture direction of the Parkfield earthquake.

  5. Spatial variations in the frequency-magnitude distribution of earthquakes at Mount Pinatubo volcano

    USGS Publications Warehouse

    Sanchez, J.J.; McNutt, S.R.; Power, J.A.; Wyss, M.

    2004-01-01

    The frequency-magnitude distribution of earthquakes measured by the b-value is mapped in two and three dimensions at Mount Pinatubo, Philippines, to a depth of 14 km below the summit. We analyzed 1406 well-located earthquakes with magnitudes MD ???0.73, recorded from late June through August 1991, using the maximum likelihood method. We found that b-values are higher than normal (b = 1.0) and range between b = 1.0 and b = 1.8. The computed b-values are lower in the areas adjacent to and west-southwest of the vent, whereas two prominent regions of anomalously high b-values (b ??? 1.7) are resolved, one located 2 km northeast of the vent between 0 and 4 km depth and a second located 5 km southeast of the vent below 8 km depth. The statistical differences between selected regions of low and high b-values are established at the 99% confidence level. The high b-value anomalies are spatially well correlated with low-velocity anomalies derived from earlier P-wave travel-time tomography studies. Our dataset was not suitable for analyzing changes in b-values as a function of time. We infer that the high b-value anomalies around Mount Pinatubo are regions of increased crack density, and/or high pore pressure, related to the presence of nearby magma bodies.

  6. Genetic variation frequencies in Wilms' tumor: A meta-analysis and systematic review.

    PubMed

    Deng, Changkai; Dai, Rong; Li, Xuliang; Liu, Feng

    2016-05-01

    Over the last few decades, numerous biomarkers in Wilms' tumor have been confirmed and shown variations in prevalence. Most of these studies were based on small sample sizes. We carried out a meta-analysis of the research published from 1992 to 2015 to obtain more precise and comprehensive outcomes for genetic tests. In the present study, 70 out of 5175 published reports were eligible for the meta-analysis, which was carried out using Stata 12.0 software. Pooled prevalence for gene mutations WT1, WTX, CTNNB1, TP53, MYCN, DROSHA, and DGCR8 was 0.141 (0.104, 0.178), 0.147 (0.110, 0.184), 0.140 (0.100, 0.190), 0.410 (0.214, 0.605), 0.071 (0.041, 0.100), 0.082 (0.048, 0.116), and 0.036 (0.026, 0.046), respectively. Pooled prevalence of loss of heterozygosity at 1p, 11p, 11q, 16q, and 22q was 0.109 (0.084, 0.133), 0.334 (0.295, 0.373), 0.199 (0.146, 0.252), 0.151 (0.129, 0.172), and 0.148 (0.108, 0.189), respectively. Pooled prevalence of 1q and chromosome 12 gain was 0.218 (0.161, 0.275) and 0.273 (0.195, 0.350), respectively. The limited prevalence of currently known genetic alterations in Wilms' tumors indicates that significant drivers of initiation and progression remain to be discovered. Subgroup analyses indicated that ethnicity may be one of the sources of heterogeneity. However, in meta-regression analyses, no study-level characteristics of indicators were found to be significant. In addition, the findings of our sensitivity analysis and possible publication bias remind us to interpret results with caution. PMID:26892980

  7. Allele-specific expression assays using Solexa

    PubMed Central

    Main, Bradley J; Bickel, Ryan D; McIntyre, Lauren M; Graze, Rita M; Calabrese, Peter P; Nuzhdin, Sergey V

    2009-01-01

    Background Allele-specific expression (ASE) assays can be used to identify cis, trans, and cis-by-trans regulatory variation. Understanding the source of expression variation has important implications for disease susceptibility, phenotypic diversity, and adaptation. While ASE is commonly measured via relative fluorescence at a SNP, next generation sequencing provides an opportunity to measure ASE in an accurate and high-throughput manner using read counts. Results We introduce a Solexa-based method to perform large numbers of ASE assays using only a single lane of a Solexa flowcell. In brief, transcripts of interest, which contain a known SNP, are PCR enriched and barcoded to enable multiplexing. Then high-throughput sequencing is used to estimate allele-specific expression using sequencing counts. To validate this method, we measured the allelic bias in a dilution series and found high correlations between measured and expected values (r>0.9, p < 0.001). We applied this method to a set of 5 genes in a Drosophila simulans parental mix, F1 and introgression and found that for these genes the majority of expression divergence can be explained by cis-regulatory variation. Conclusion We present a new method with the capacity to measure ASE for large numbers of assays using as little as one lane of a Solexa flowcell. This will be a valuable technique for molecular and population genetic studies, as well as for verification of genome-wide data sets. PMID:19740431

  8. Variations in Dream Recall Frequency and Dream Theme Diversity by Age and Sex

    PubMed Central

    Nielsen, Tore

    2012-01-01

    We assessed dream recall frequency (DRF) and dream theme diversity (DTD) with an internet questionnaire among a cohort of 28,888 male and female participants aged 10–79 years in a cross-sectional design. DRF increased from adolescence (ages 10–19) to early adulthood (20–29) and then decreased again for the next 20 years. The nature of this decrease differed for males and females. For males, it began earlier (30–39), proceeded more gradually, and reached a nadir earlier (40–49) than it did for females. For females, it began later (40–49), dropped more abruptly, and reached nadir later (50–59). Marked sex differences were observed for age strata 10–19 through 40–49 and year-by-year analyses estimated the window for these differences to be more precisely from 14 to 44 years. DTD decreased linearly with age for both sexes up to 50–59 and then dropped even more sharply for 60–79. There was a sex difference favoring males on this measure but only for ages 10–19. Findings replicate, in a single sample, those from several previous studies showing an increase in DRF from adolescence to early adulthood, a subsequent decrease primarily in early and middle adulthood, and different patterns of age-related decrease in the two sexes. Age-related changes in sleep structure, such as decreasing %REM sleep which parallel the observed dream recall changes, might help explain these findings, but these sleep changes are much smaller and more gradual in nature. Changes in the phase and amplitude of circadian rhythms of REM propensity and generational differences in life experiences may also account for some part of the findings. That decreases in DTD parallel known age-related decreases in episodic and autobiographical memory may signify that this new diversity measure indexes an aspect of autobiographical memory that also influences dream recall. PMID:22783222

  9. 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 geneti