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Sample records for allele frequency variation

  1. Developments in FINDbase worldwide database for clinically relevant genomic variation allele frequencies.

    PubMed

    Papadopoulos, Petros; Viennas, Emmanouil; Gkantouna, Vassiliki; Pavlidis, Cristiana; Bartsakoulia, Marina; Ioannou, Zafeiria-Marina; Ratbi, Ilham; Sefiani, Abdelaziz; Tsaknakis, John; Poulas, Konstantinos; Tzimas, Giannis; Patrinos, George P

    2014-01-01

    FINDbase (http://www.findbase.org) aims to document frequencies of clinically relevant genomic variations, namely causative mutations and pharmacogenomic markers, worldwide. Each database record includes the population, ethnic group or geographical region, the disorder name and the related gene, accompanied by links to any related databases and the genetic variation together with its frequency in that population. Here, we report, in addition to the regular data content updates, significant developments in FINDbase, related to data visualization and querying, data submission, interrelation with other resources and a new module for genetic disease summaries. In particular, (i) we have developed new data visualization tools that facilitate data querying and comparison among different populations, (ii) we have generated a new FINDbase module, built around Microsoft's PivotViewer (http://www.getpivot.com) software, based on Microsoft Silverlight technology (http://www.silverlight.net), that includes 259 genetic disease summaries from five populations, systematically collected from the literature representing the documented genetic makeup of these populations and (iii) the implementation of a generic data submission tool for every module currently available in FINDbase.

  2. Haemoglobin polymorphism in atlantic cod (Gadus morhua): Allele frequency variation between yearclasses in a Norwegian fjord stock

    NASA Astrophysics Data System (ADS)

    Mork, J.; Sundnes, G.

    1985-03-01

    A total of 262 specimens (0-, and 1-group) of Atlantic cod (Gadus morhua) representing 4 different yearclasses were caught in Trondheimsfjorden, Norway, during 1977 1984. They were genotyped by agar gel electrophoresis for the polymorphic haemoglobin locus HbI (Sick, 1961). The analyses revealed a highly significant (P=0.0003) heterogeneity of HbI allele frequencies between yearclasses. The difference in the frequency of the HbI-1 allele between the first (1977) and the last (1983) yearclass amounted to 0.18 (±0.07). The results appear to support recent reports on considerable selection effects at HbI, and stress the unreliability of allele frequencies at this locus for use in studies of the genetic population structure of cod.

  3. Variation in Meiotic Recombination Frequencies Between Allelic Transgenes Inserted at Different Sites in the Drosophila melanogaster Genome

    PubMed Central

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

    2013-01-01

    Meiotic crossovers are distributed nonrandomly across the genome. Classic studies in Drosophila suggest that the position of a gene along a chromosome arm can affect the outcome of the recombination process, with proximity to the centromere being associated with lower crossing over. To examine this phenomenon molecularly, we developed an assay that measures meiotic crossovers and noncrossover gene conversions between allelic transgenes inserted into different genomic positions. To facilitate collecting a large number of virgin females, we developed a useful genetic system that kills males and undesired classes of females. We found that the recombination frequency at a site in the middle of the X chromosome, where crossovers are normally frequent, was similar to the frequency at the centromere-proximal end of the euchromatin, where crossovers are normally infrequent. In contrast, we recovered no recombinants—crossovers or noncrossovers—at a site on chromosome 4 and at a site toward the distal end of the X chromosome. These results suggest that local sequence or chromatin features have a stronger impact on recombination rates in this transgene assay than position along the chromosome arm. PMID:23797104

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

    PubMed

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

    2014-04-22

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

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

    PubMed

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

    2013-01-01

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

  6. Frequencies of Null Alleles at Enzyme Loci in Natural Populations of Ponderosa and Red Pine

    PubMed Central

    Allendorf, Fred W.; Knudsen, Kathy L.; Blake, George M.

    1982-01-01

    Pinus ponderosa and P. resinosa population samples have mean frequencies of enzymatically inactive alleles of 0.0031 and 0.0028 at 29 and 27 enzyme loci, respectively. Such alleles are rare and are apparently maintained by selection-mutation balance. Ponderosa pine have much higher amounts of allozymic and polygenic phenotypic variation than red pine, yet both species have similar frequencies of null alleles. Thus, null alleles apparently do not contribute to polygenic variation, as has been suggested. The concordance between allozymic and polygenic variation adds support to the view that allozyme studies may be valuable in predicting the relative amount of polygenic variation in populations. PMID:17246067

  7. 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

  8. Allelic variation contributes to bacterial host specificity

    SciTech Connect

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

    2015-10-30

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

  9. Allelic variation contributes to bacterial host specificity

    DOE PAGES

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

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

    PubMed Central

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

    1980-01-01

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

  13. ALFRED: an allele frequency resource for research and teaching

    PubMed Central

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

    2012-01-01

    ALFRED (http://alfred.med.yale.edu) is a free, web accessible, curated compilation of allele frequency data on DNA sequence polymorphisms in anthropologically defined human populations. Currently, ALFRED has allele frequency tables on over 663 400 polymorphic sites; 170 of them have frequency tables for more than 100 different population samples. In ALFRED, a population may have multiple samples with each ‘sample’ consisting of many individuals on which an allele frequency is based. There are 3566 population samples from 710 different populations with allele frequency tables on at least one polymorphism. Fifty of those population samples have allele frequency data for over 650 000 polymorphisms. Records also have active links to relevant resources (dbSNP, PharmGKB, OMIM, Ethnologue, etc.). The flexible search options and data display and download capabilities available through the web interface allow easy access to the large quantity of high-quality data in ALFRED. PMID:22039151

  14. Ethical guideposts for allelic variation databases.

    PubMed

    Knoppers, B M; Laberge, C M

    2000-01-01

    Basically, a mutation database (MDB) is a repository where allelic variations are described and assigned within a specific gene locus. The purposes of an MDB may vary greatly and have different content and structure. The curator of an electronic and computer-based MDB will provide expert feedback (clinical and research). This requires ethical guideposts. Going to direct on-line public access for the content of an MDB or to interactive communication also raises other considerations. Currently, HUGO's MDI (Mutation Database Initiative) is the only integrated effort supporting and guiding the coordinated deployment of MDBs devoted to genetic diversity. Thus, HUGO's ethical "Statements" are applicable. Among the ethical principles, the obligation of preserving the confidentiality of information transferred by a collaborator to the curator is particularly important. Thus, anonymization of such data prior to transmission is essential. The 1997 Universal Declaration on the Human Genome and Human Rights of UNESCO addresses the participation of vulnerable persons. Researchers in charge of MDBs should ensure that information received on the testing of children or incompetent adults is subject to ethical review and approval in the country of origin. Caution should be taken against the involuntary consequences of public disclosure of results without complete explanation. Clear and enforceable regulations must be developed to protect the public against misuse of genetic databanks. Interaction with a databank could be seen as creating a "virtual" physician-patient relationship. However, interactive public MDBs should not give medical advice. We have identified new social ethical principles to govern different levels of complexity of genetic information. They are: reciprocity, mutuality, solidarity, and universality. Finally, precaution and prudence at this early stage of the MDI may not only avoid ethically inextricable conundrums but also provide for the respect for the rights

  15. 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...

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

    PubMed

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

    2015-04-01

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

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

    PubMed

    Haasl, Ryan J; Payseur, Bret A

    2010-12-01

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

  18. Robust identification of local adaptation from allele frequencies.

    PubMed

    Günther, Torsten; Coop, Graham

    2013-09-01

    Comparing allele frequencies among populations that differ in environment has long been a tool for detecting loci involved in local adaptation. However, such analyses are complicated by an imperfect knowledge of population allele frequencies and neutral correlations of allele frequencies among populations due to shared population history and gene flow. Here we develop a set of methods to robustly test for unusual allele frequency patterns and correlations between environmental variables and allele frequencies while accounting for these complications based on a Bayesian model previously implemented in the software Bayenv. Using this model, we calculate a set of "standardized allele frequencies" that allows investigators to apply tests of their choice to multiple populations while accounting for sampling and covariance due to population history. We illustrate this first by showing that these standardized frequencies can be used to detect nonparametric correlations with environmental variables; these correlations are also less prone to spurious results due to outlier populations. We then demonstrate how these standardized allele frequencies can be used to construct a test to detect SNPs that deviate strongly from neutral population structure. This test is conceptually related to FST and is shown to be more powerful, as we account for population history. We also extend the model to next-generation sequencing of population pools-a cost-efficient way to estimate population allele frequencies, but one that introduces an additional level of sampling noise. The utility of these methods is demonstrated in simulations and by reanalyzing human SNP data from the Human Genome Diversity Panel populations and pooled next-generation sequencing data from Atlantic herring. An implementation of our method is available from http://gcbias.org. PMID:23821598

  19. Robust Identification of Local Adaptation from Allele Frequencies

    PubMed Central

    Günther, Torsten; Coop, Graham

    2013-01-01

    Comparing allele frequencies among populations that differ in environment has long been a tool for detecting loci involved in local adaptation. However, such analyses are complicated by an imperfect knowledge of population allele frequencies and neutral correlations of allele frequencies among populations due to shared population history and gene flow. Here we develop a set of methods to robustly test for unusual allele frequency patterns and correlations between environmental variables and allele frequencies while accounting for these complications based on a Bayesian model previously implemented in the software Bayenv. Using this model, we calculate a set of “standardized allele frequencies” that allows investigators to apply tests of their choice to multiple populations while accounting for sampling and covariance due to population history. We illustrate this first by showing that these standardized frequencies can be used to detect nonparametric correlations with environmental variables; these correlations are also less prone to spurious results due to outlier populations. We then demonstrate how these standardized allele frequencies can be used to construct a test to detect SNPs that deviate strongly from neutral population structure. This test is conceptually related to FST and is shown to be more powerful, as we account for population history. We also extend the model to next-generation sequencing of population pools—a cost-efficient way to estimate population allele frequencies, but one that introduces an additional level of sampling noise. The utility of these methods is demonstrated in simulations and by reanalyzing human SNP data from the Human Genome Diversity Panel populations and pooled next-generation sequencing data from Atlantic herring. An implementation of our method is available from http://gcbias.org. PMID:23821598

  20. 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.

  1. 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

  2. ApoE allele frequencies in Italian sporadic and familial Alzheimer's disease.

    PubMed

    Sorbi, S; Nacmias, B; Forleo, P; Latorraca, S; Gobbini, I; Bracco, L; Piacentini, S; Amaducci, L

    1994-08-15

    Recent studies have provided evidence of association of apolipoprotein E (ApoE) epsilon 4 allele and late onset familial and sporadic Alzheimer's disease (AD). Epidemiological studies have established allelic variation at the ApoE locus. We have analyzed the ApoE gene polymorphism in a sample of 446 Italian subjects. Our data confirm a significant association between epsilon 4 allele and sporadic AD. The frequency of epsilon 4 allele in early onset familial AD patients was comparable to control values suggesting that epsilon 4 allele does not represent a risk factor for early onset familial AD (EOFAD). Moreover, we found a not previously reported association between ApoE epsilon 2 allele and sporadic AD and EOFAD. PMID:7824157

  3. 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.

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

    PubMed

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

    2012-07-01

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

  5. Disentangling the Roles of History and Local Selection in Shaping Clinal Variation of Allele Frequencies and Gene Expression in Norway Spruce (Picea abies)

    PubMed Central

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

    2012-01-01

    Understanding the genetic basis of local adaptation is challenging due to the subtle balance among conflicting evolutionary forces that are involved in its establishment and maintenance. One system with which to tease apart these difficulties is clines in adaptive characters. Here we analyzed genetic and phenotypic variation in bud set, a highly heritable and adaptive trait, among 18 populations of Norway spruce (Picea abies), arrayed along a latitudinal gradient ranging from 47°N to 68°N. We confirmed that variation in bud set is strongly clinal, using a subset of five populations. Genotypes for 137 single-nucleotide polymorphisms (SNPs) chosen from 18 candidate genes putatively affecting bud set and 308 control SNPs chosen from 264 random genes were analyzed for patterns of genetic structure and correlation to environment. Population genetic structure was low (FST = 0.05), but latitudinal patterns were apparent among Scandinavian populations. Hence, part of the observed clinal variation should be attributable to population demography. Conditional on patterns of genetic structure, there was enrichment of SNPs within candidate genes for correlations with latitude. Twenty-nine SNPs were also outliers with respect to FST. The enrichment for clinal variation at SNPs within candidate genes (i.e., SNPs in PaGI, PaPhyP, PaPhyN, PaPRR7, and PaFTL2) indicated that local selection in the 18 populations, and/or selection in the ancestral populations from which they were recently derived, shaped the observed cline. Validation of these genes using expression studies also revealed that PaFTL2 expression is significantly associated with latitude, thereby confirming the central role played by this gene in the control of phenology in plants. PMID:22542968

  6. Models of Frequency-Dependent Selection with Mutation from Parental Alleles

    PubMed Central

    Trotter, Meredith V.; Spencer, Hamish G.

    2013-01-01

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

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

    PubMed

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

    2006-01-01

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

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

    PubMed

    Lachance, Joseph; Tishkoff, Sarah A

    2014-10-01

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

  9. 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...

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. The impact of library preparation protocols on the consistency of allele frequency estimates in Pool-Seq data.

    PubMed

    Kofler, Robert; Nolte, Viola; Schlötterer, Christian

    2016-01-01

    Sequencing pools of individuals (Pool-Seq) is a cost-effective method to determine genome-wide allele frequency estimates. Given the importance of meta-analyses combining data sets, we determined the influence of different genomic library preparation protocols on the consistency of allele frequency estimates. We found that typically no more than 1% of the variation in allele frequency estimates could be attributed to differences in library preparation. Also read length had only a minor effect on the consistency of allele frequency estimates. By far, the most pronounced influence could be attributed to sequence coverage. Increasing the coverage from 30- to 50-fold improved the consistency of allele frequency estimates by at least 27%. We conclude that Pool-Seq data can be easily combined across different library preparation methods, but sufficient sequence coverage is key to reliable results.

  16. 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

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

    PubMed

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

    2015-04-30

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

  18. The Joint Allele-Frequency Spectrum in Closely Related Species

    PubMed Central

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

    2007-01-01

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

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

    PubMed

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

    2014-04-01

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

  20. 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

  1. Allele frequency distribution of CYP2C9 2 and CYP2C9 3 polymorphisms in six Mexican populations.

    PubMed

    Castelán-Martínez, Osvaldo D; Hoyo-Vadillo, Carlos; Sandoval-García, Emmanuel; Sandoval-Ramírez, Lucila; González-Ibarra, Miriam; Solano-Solano, Gloria; Gómez-Díaz, Rita A; Parra, Esteban J; Cruz, Miguel; Valladares-Salgado, Adán

    2013-07-10

    Allele frequency differences of functional CYP2C9 polymorphisms are responsible for some of the variation in drug response observed in human populations. The most relevant CYP2C9 functional variants are CYP2C9*2 (rs1799853) and CYP2C9 3 (rs1057910). These polymorphisms show variation in allele frequencies among different population groups. The present study aimed to analyze these polymorphisms in 947 Mexican-Mestizo from Mexico City and 483 individuals from five indigenous Mexican populations: Nahua, Teenek, Tarahumara, Purepecha and Huichol. The CYP2C9*2 allele frequencies in the Mestizo, Nahua and Teenek populations were 0.051, 0.007 and 0.005, respectively. As for CYP2C9 3, the allelic frequencies in the Mestizo, Nahua and Teenek populations were 0.04, 0.005 and 0.005, respectively. The CYP2C9 2 and CYP2C9 3 alleles were not observed in the Tarahumara, Purepecha and Huichol populations. These findings are in agreement with previous studies reporting very low allele frequencies for these polymorphisms in American Indigenous populations.

  2. 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.

  3. 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

  4. Increased TNFA*2, but not TNFB*1, allele frequency in Spanish atopic patients.

    PubMed

    Castro, J; Tellería, J J; Linares, P; Blanco-Quirós, A

    2000-01-01

    Tumor necrosis factor (TNF) is a potent proinflammatory cytokine involved in asthma and atopy. Increased TNF-alpha levels have been found in airway biopsies and bronchoalveolar lavage fluids from asthmatic patients. Constitutional variations in the TNF-alpha secretion levels in vitro are associated with molecular polymorphisms located within and around the TNF loci. Our study objective was to investigate the association between atopy and two described di-allelic polymorphisms in the TNF locus: a G to A transition at position -308 in the 5'-promoter region of the TNFA gene (TNFA*1 and TNFA*2 alleles) and an Ncol restriction fragment length polymorphism (RFLP) in the first intron of the TNFB gene (TNFB*1 and TNFB*2 alleles). The genetic study was performed in 65 unrelated atopic patients and 60 healthy controls. The regions of interest were amplified from genomic DNA using specific primers and polymerase chain reaction. SSP-PCR analysis for TNFA -308 polymorphism genotyping and endonuclease digestion analysis for the TNFB Ncol RFLP were used. The frequency of the TNFA*2 allele was significantly higher in atopic subjects compared to the control group (38.5% vs. 10.5%; chi2 = 32.06; p <0.0001). The TNFA*2 allele is associated with a higher risk for the development of atopy (risk ratio = 9.44; EF = 0.65; chi2 = 30.06 p <0.0005). On the other hand, no significant association between the TNFB alleles and atopy was found. In conclusion, the TNFA*2 allele could be also a genetic risk marker for the predisposition to atopy in our population, as has been reported in other studies. Either the TNFA gene itself or a linked gene on chromosome region 6p21, which has yet to be identified, is a candidate gene for susceptibility to atopy. PMID:10923589

  5. Non-Equilibrium Allele Frequency Spectra Via Spectral Methods

    PubMed Central

    Hey, Jody; Chen, Kevin

    2011-01-01

    A major challenge in the analysis of population genomics data consists of isolating signatures of natural selection from background noise caused by random drift and gene flow. Analyses of massive amounts of data from many related populations require high-performance algorithms to determine the likelihood of different demographic scenarios that could have shaped the observed neutral single nucleotide polymorphism (SNP) allele frequency spectrum. In many areas of applied mathematics, Fourier Transforms and Spectral Methods are firmly established tools to analyze spectra of signals and model their dynamics as solutions of certain Partial Differential Equations (PDEs). When spectral methods are applicable, they have excellent error properties and are the fastest possible in high dimension; see [15]. In this paper we present an explicit numerical solution, using spectral methods, to the forward Kolmogorov equations for a Wright-Fisher process with migration of K populations, influx of mutations, and multiple population splitting events. PMID:21376069

  6. Linkage disequilibrium in the insulin gene region: size variation at the 5' flanking polymorphism and bimodality among "class I" alleles.

    PubMed Central

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

    1994-01-01

    The 5' flanking polymorphism (5'FP), a hypervariable region at the 5' end of the insulin gene, has "class 1" alleles (650-900 bp long) that are in positive linkage disequilibrium with insulin-dependent diabetes mellitus (IDDM). We report that precise sizing of the 5'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. We also examined 5'FP length variation in relation to allelic variation at nearby polymorphisms. At biallelic RFLPs on both sides of the 5'FP, we found that one allele exhibits near-total association with the upper component of the 5'FP class 1 distribution. Such associations represent a little-known but potentially widespread 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. PMID:7915880

  7. Allele frequency net: a database and online repository for immune gene frequencies in worldwide populations.

    PubMed

    Gonzalez-Galarza, Faviel F; Christmas, Stephen; Middleton, Derek; Jones, Andrew R

    2011-01-01

    The allele frequency net database (http://www.allelefrequencies.net) is an online repository that contains information on the frequencies of immune genes and their corresponding alleles in different populations. The extensive variability observed in genes and alleles related to the immune system response and its significance in transplantation, disease association studies and diversity in populations led to the development of this electronic resource. At present, the system contains data from 1133 populations in 608,813 individuals on the frequency of genes from different polymorphic regions such as human leukocyte antigens, killer-cell immunoglobulin-like receptors, major histocompatibility complex Class I chain-related genes and a number of cytokine gene polymorphisms. The project was designed to create a central source for the storage of frequency data and provide individuals with a set of bioinformatics tools to analyze the occurrence of these variants in worldwide populations. The resource has been used in a wide variety of contexts, including clinical applications (histocompatibility, immunology, epidemiology and pharmacogenetics) and population genetics. Demographic information, frequency data and searching tools can be freely accessed through the website.

  8. 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)

  9. 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.

  10. 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

  11. 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

  12. 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).

  13. Confidence intervals for population allele frequencies: the general case of sampling from a finite diploid population of any size.

    PubMed

    Fung, Tak; Keenan, Kevin

    2014-01-01

    The estimation of population allele frequencies using sample data forms a central component of studies in population genetics. These estimates can be used to test hypotheses on the evolutionary processes governing changes in genetic variation among populations. However, existing studies frequently do not account for sampling uncertainty in these estimates, thus compromising their utility. Incorporation of this uncertainty has been hindered by the lack of a method for constructing confidence intervals containing the population allele frequencies, for the general case of sampling from a finite diploid population of any size. In this study, we address this important knowledge gap by presenting a rigorous mathematical method to construct such confidence intervals. For a range of scenarios, the method is used to demonstrate that for a particular allele, in order to obtain accurate estimates within 0.05 of the population allele frequency with high probability (> or = 95%), a sample size of > 30 is often required. This analysis is augmented by an application of the method to empirical sample allele frequency data for two populations of the checkerspot butterfly (Melitaea cinxia L.), occupying meadows in Finland. For each population, the method is used to derive > or = 98.3% confidence intervals for the population frequencies of three alleles. These intervals are then used to construct two joint > or = 95% confidence regions, one for the set of three frequencies for each population. These regions are then used to derive a > or = 95%% confidence interval for Jost's D, a measure of genetic differentiation between the two populations. Overall, the results demonstrate the practical utility of the method with respect to informing sampling design and accounting for sampling uncertainty in studies of population genetics, important for scientific hypothesis-testing and also for risk-based natural resource management. PMID:24465792

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2014-10-01

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

  16. 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

  17. 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

  18. Allele frequency distributions of D1S80 in the Polish population.

    PubMed

    Ciesielka, M; Kozioł, P; Krajka, A

    1996-08-15

    The polymorphism of the D1S80 locus has been analyzed in a population sample of 208 unrelated individuals in the Southeast Poland and 103 mother/child pairs. PCR amplified alleles were separated by a vertical discontinuous polyacrylamide gel electrophoresis system. Nineteen different alleles and 52 phenotypes could be distinguished. The alleles 18 (f = 0.267) and 24 (f = 0.300) were most common in Poland. D1S80 genotype frequencies of Poland population do not deviate from Hardy-Weinberg equilibrium. All mother/child pairs shared at least one D1S80 allele.

  19. Power of IRT in GWAS: successful QTL mapping of sum score phenotypes depends on interplay between risk allele frequency, variance explained by the risk allele, and test characteristics.

    PubMed

    van den Berg, Stéphanie M; Service, Susan K

    2012-12-01

    As data from sequencing studies in humans accumulate, rare genetic variants influencing liability to disease and disorders are expected to be identified. Three simulation studies show that characteristics and properties of diagnostic instruments interact with risk allele frequency to affect the power to detect a quantitative trait locus (QTL) based on a test score derived from symptom counts or questionnaire items. Clinical tests, that is, tests that show a positively skewed phenotypic sum score distribution in the general population, are optimal to find rare risk alleles of large effect. Tests that show a negatively skewed sum score distribution are optimal to find rare protective alleles of large effect. For alleles of small effect, tests with normally distributed item parameters give best power for a wide range of allele frequencies. The item-response theory framework can help understand why an existing measurement instrument has more power to detect risk alleles with either low or high frequency, or both kinds.

  20. Worldwide allele frequencies of the human apolipoprotein E gene: climate, local adaptations, and evolutionary history.

    PubMed

    Eisenberg, Dan T A; Kuzawa, Christopher W; Hayes, M Geoffrey

    2010-09-01

    The epsilon4 allele of the apolipoprotein E (APOE) gene is associated with increased cholesterol levels and heart disease. Population allele frequencies of APOE have previously been shown to vary, with epsilon4 frequencies generally increasing with latitude. We hypothesize that this trend resulted from natural selection protecting against low-cholesterol levels. In high-latitude cold environments and low-latitude hot environments, metabolic rate is elevated, which could require higher cholesterol levels. To explore this hypothesis, we compiled APOE allele frequencies, latitude, temperature, and elevation from populations around the world. epsilon4 allele frequencies show a curvilinear relationship with absolute latitude, with lowest frequencies found in the mid-latitudes where temperatures generally require less expenditure on cooling/thermogenesis. Controlling for population structure in a subset of populations did not appreciably change this pattern of association, consistent with selection pressures that vary by latitude shaping epsilon4 allele frequencies. Temperature records also predict APOE frequency in a curvilinear fashion, with lowest epsilon4 frequencies at moderate temperatures. The model fit between historical temperatures and epsilon4 is less than between latitude and epsilon4, but strengthened after correcting for estimated temperature differences during the Paleolithic. Contrary to our hypothesis, we find that elevation did not improve predictive power, and an integrated measure of the cholesterol effect of multiple APOE alleles was less related to latitude than was epsilon4 alone. Our results lend mixed support for a link between past temperature and human APOE allele distribution and point to the need to develop better models of past climate in future analyses.

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

    PubMed

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

    2007-10-01

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

  2. 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.

  3. 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

  4. Analysis and frequency of bovine lymphocyte antigen DRB3.2 alleles in Jersey cows.

    PubMed

    Gilliespie, B E; Jayarao, B M; Dowlen, H H; Oliver, S P

    1999-09-01

    Jersey cows (n = 172) were genotyped for the bovine lymphocyte antigen (BoLA)-DRB3.2 allele by polymerase chain reaction and restriction fragment length polymorphism analysis. Bovine DNA was isolated from aliquots of whole blood. A two-step polymerase chain reaction followed by digestion with restriction endonucleases RsaI, BstyI, and HaeIII was conducted on the DNA from Jersey cattle. Twenty-four BoLA-DRB3.2 alleles were identified with frequencies ranging from 0.3 to 22.9%. Thirteen allele types were similar to those reported previously; and 11 were new allele types that have not been reported previously. Allele types reported previously include: BoLA-DRB3.2*2, *8, *10, *15, *17, *20, *21, *22, *23, *25, *28, *36, and *37. Their frequencies were 0.3, 11.3, 22.9, 13.6, 5.5, 3.7, 10.7, 3.5, 0.9, 0.3, 4.7, 9.3, and 0.9%, respectively. Of the new allele types detected, *ibe occurred at the highest frequency (6.1%) in Jersey cows from this herd. The six most frequently isolated alleles (BoLA-DRB3.2*8, *10, *15, *21, *36, and *ibe) accounted for 73.9% of the alleles in the population of this herd. Results of this study demonstrate that the BoLA-DRB3.2 locus is highly polymorphic in Jersey cattle.

  5. 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.

  6. 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

  7. [RHD 1227A allele frequency among Rh negative population and random population].

    PubMed

    Wu, Jun-Jie; Hong, Xiao-Zhen; Xu, Xian-Guo; Ma, Kai-Rong; Zhu, Fa-Ming; Yan, Li-Xing

    2006-12-01

    To investigate the frequency of RHD 1227A allele in Rh negative population and random population, an AS-PCR (allele specific-polymerase chain reaction) method was employed to detect RHD 1227A allele. RHD gene copy was determined by D zygosity test and RHD exon 9 nucleotide sequence analysis. The results showed that among 143 Rh negative donors, forty-one RHD 1227A allele carriers were detected, and 8 (19.51%) out of which were RhCCdee, 32 (78.05%) were RhCcdee, and 1 (2.44%) was RhCcdEe. Thirty-five Rh negative RHD 1227A carriers had RHD gene deletion, and the remaining carriers were RHD 1227A homozygous. Seven (1.43%) individuals were detected with RHD 1227A allele among 489 random donors. They were all G/A heterozygous at RHD 1227 site. Serological test indicated that they were normal Rh positive phenotype. It is concluded that the frequency of RHD 1227A allele is 16.43% among Rh negative population and 0.72% among the random population.

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

    PubMed Central

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

    2009-01-01

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

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

    SciTech Connect

    Shriver, M.D.; Jin, L.; Chakraborty, R.; Boerwinkle, E. )

    1993-07-01

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

  10. 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

  11. Natural allelic variations in glutathione peroxidase-1 affect its subcellular localization and function.

    PubMed

    Bera, Soumen; Weinberg, Frank; Ekoue, Dede N; Ansenberger-Fricano, Kristine; Mao, Mao; Bonini, Marcelo G; Diamond, Alan M

    2014-09-15

    Glutathione peroxidase 1 (GPx-1) has been implicated in the etiology of several common diseases due to the association between specific allelic variations and cancer risk. The most common among these variations are the codon 198 polymorphism that results in either a leucine or proline and the number of alanine repeat codons in the coding sequence. The molecular and biologic consequences of these variations remain to be characterized. Toward achieving this goal, we have examined the cellular location of GPx-1 encoded by allelic variants by ectopically expressing these genes in MCF-7 human breast carcinoma cells that produce undetectable levels of GPx-1, thus achieving exclusive expression in the same cellular environment. A differential distribution between the cytoplasm and mitochondria was observed, with the allele expressing the leucine-198 polymorphism and 7 alanine repeats being more cytoplasmically located than the other alleles examined. To assess whether the distribution of GPx-1 between the cytoplasm and mitochondria had a biologic consequence, we engineered derivative GPx-1 proteins that were targeted to the mitochondria by the addition of a mitochondria targeting sequence and expressed these proteins in MCF-7 cells. These cells were examined for their response to oxidative stress, energy metabolism, and impact on cancer-associated signaling molecules. The results obtained indicated that both primary GPx-1 sequence and cellular location have a profound impact on cellular biology and offer feasible hypotheses about how expression of distinct GPx-1 alleles can affect cancer risk. Cancer Res; 74(18); 5118-26. ©2014 AACR.

  12. Allelic variation of the β-, γ- and δ-kafirin genes in diverse Sorghum genotypes.

    PubMed

    Laidlaw, H K C; Mace, E S; Williams, S B; Sakrewski, K; Mudge, A M; Prentis, P J; Jordan, D R; Godwin, I D

    2010-11-01

    The β-, γ- and δ-kafirin genes were sequenced from 35 Sorghum genotypes to investigate the allelic diversity of seed storage proteins. A range of grain sorghums, including inbred parents from internationally diverse breeding programs and landraces, and three wild Sorghum relatives were selected to encompass an extensive array of improved and unimproved germplasm in the Eusorghum. A single locus exists for each of the expressed kafirin-encoding genes, unlike the multigenic α-kafirins. Significant diversity was found for each locus, with the cysteine-rich β-kafirin having four alleles, including the first natural null mutant reported for this prolamin subfamily. This allele contains a frame shift insertion at +206 resulting in a premature stop codon. SDS-PAGE revealed that lines with this allele do not produce β-kafirin. An analysis of flour viscosity reveals that these β-kafirin null lines have a difference in grain quality, with significantly lower viscosity observed over the entire Rapid ViscoAnalyser time course. There was less diversity at the protein level within the cysteine-rich γ-kafirin, with only two alleles in the cultivated sorghums. There were only two alleles for the δ-kafirin locus among the S. bicolor germplasm, with one allele encoding ten extra amino acids, of which five were methionine residues, with an additional methionine resulting from a nucleotide substitution. This longer allele encodes a protein with 19.1% methionine. The Asian species, S. propinquum, had distinct alleles for all three kafirin genes. We found no evidence for selection on the three kafirin genes during sorghum domestication even though the δ-kafirin locus displayed comparatively low genetic variation. This study has identified genetic diversity in all single copy seed storage protein genes, including a null mutant for β-kafirin in Sorghum.

  13. Frequency of CCR5Δ32 allele in healthy Bosniak population.

    PubMed

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

    2014-08-28

    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 lower 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 Hercegovina 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 subjects from Bosnia and Herzegovina (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.

  14. 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

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

    PubMed

    Usher, Christina L; McCarroll, Steven A

    2015-09-01

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

  16. 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.

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

    PubMed

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

    2012-05-01

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

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

    PubMed Central

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

    1981-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-03-01

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

  1. 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

  2. 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

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

    PubMed

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

    2016-10-01

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

  4. 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

  5. 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

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

    PubMed

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

    2014-12-22

    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.

  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. Genotype and allele frequency of CYP2C19*17 in a healthy Iranian population

    PubMed Central

    Payan, Maryam; Tajik, Nader; Rouini, Mohammad Reza; Ghahremani, Mohammad Hossein

    2015-01-01

    Background: Cytochrome P450 2C19 (CYP2C19) is important in metabolism of wide range of drugs. CYP2C19*17 is a novel variant allele which increases gene transcription and therefore results in ultra-rapid metabolizer phenotype (URM). Distribution of this variant allele has not been well studied worldwide. The aim of present study was to investigate allele and genotype frequencies of CYP2C19*17 in a healthy Iranian population and compare them with other ethnic groups. Methods: One hundred eighty healthy unrelated Iranian volunteer took part in this study and were genotyped for CYP2C19 *2, *3, *17 (-3402) by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and CYP2C19*17 (-806) by a nested-PCR assays. The distribution of CYP2C19*17 polymorphism in Iranian population was then compared with other ethnic groups. Results: The CYP2C19*17 allele frequency was 21.6% in Iranian population. Among studied subjects 5.5% were homozygous for CYP2C19*17 and phenotyped as ultra-rapid metabolizers; 28.8% were genotyped as CYP2C19*1*17 (extensive metabolizers) and 3.3% as CYP2C19*2*17 (intermediate metabolizers). Conclusion: The CYP2C19*17 genetic distribution in Iranian population is similar to Middle East or European countries. The high frequency of CYP2C19*17 in Iranian population highlights the importance of this new variant allele in metabolism of CYP2C19 substrates. Thus, future association studies are required to reveal clinical consequence of this genetic polymorphism in carrier individuals. PMID:26793660

  9. A method for estimating the intensity of overdominant selection from the distribution of allele frequencies.

    PubMed Central

    Slatkin, M; Muirhead, C A

    2000-01-01

    A method is proposed for estimating the intensity of overdominant selection scaled by the effective population size, S = 2Ns, from allele frequencies. The method is based on the assumption that, with strong overdominant selection, allele frequencies are nearly at their deterministic equilibrium values and that, to a first approximation, deviations depend only on S. Simulations verify that reasonably accurate estimates of S can be obtained for realistic sample sizes. The method is applied to data from several loci in the major histocompatibility complex (Mhc) in numerous human populations. For alleles distinguished by both serological typing and the sequence of the peptide-binding region, our estimates of S are comparable to those obtained by analysis of DNA sequences in showing that selection is strongest on HLA-B and weaker on HLA-A, HLA-DRB1, and HLA-DQA1. The intensity of selection on HLA-B varied considerably among populations. Two populations, Native American and Inuit, showed an excess rather than a deficiency in homozygosity. Comparable estimates of S were obtained for alleles at Mhc class II loci distinguished by serological reactions (serotyping) and by differences in the amino acid sequences of the peptide-binding region (molecular typing). A comparison of two types of data for DQA1 and DRB1 showed that serotyping led to generally lower estimates of S. PMID:11102400

  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.

  11. 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

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

    SciTech Connect

    Kermicle, J.L.

    1980-01-01

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

  13. Allele frequencies of 14 STR loci in the population of Malta.

    PubMed

    Cassar, M; Farrugia, C; Vidal, C

    2008-05-01

    Allele frequencies of 14 STR loci (D13S317, D16S539, D2S1338, vWA, TPOX, D18S51, D5S818, FGA, D8S1179, D21S11, D7S820, CSF1PO, TH01 and D3S1358) observed in the population of Malta are being reported. Polymerase chain reaction (PCR) amplification using the AmpFl STR Identifiler kit was performed in a random sample of 157 subjects (314 chromosomes). Markers D2S1338, D18S51 and FGA had the highest power of discrimination (PD) values while TPOX was the least informative marker. Allele frequencies observed in the Maltese population were also compared with those of other populations from the Mediterranean region, Europe and Africa. Our data is useful for anthropological and other comparative studies of populations and is powerful for forensic and paternity testing in the Maltese islands.

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

    PubMed Central

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

    2016-01-01

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

  15. 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

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

    PubMed

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

    2014-11-01

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

  17. HLA class II allele and haplotype frequencies in Ethiopian Amhara and Oromo populations.

    PubMed

    Fort, M; de Stefano, G F; Cambon-Thomsen, A; Giraldo-Alvarez, P; Dugoujon, J M; Ohayon, E; Scano, G; Abbal, M

    1998-04-01

    HLA class II alleles were identified in 181 healthy unrelated Ethiopian children of both sexes and in 350 European controls from the South of France. The Ethiopian individuals belonged to the two major ethnic groups of the country: Oromo (N=83) and Amhara (N=98). In both panels, genetic polymorphism of HLA class II alleles was analysed for the first time by molecular typing of DRB1, DQA1 and DQB1 loci. Allelic and phenotypic frequencies were compared with those of European controls and other African populations. Construction of HLA class II three-locus haplotypes was also performed. The study revealed some differences between the two groups. Characteristic features of Central and North African populations appeared on the Ethiopian HLA genotypes. Surprisingly, DRB1*11 presented one of the lowest gene frequencies in both Ethiopian ethnic groups in contrast to Europeans and West Africans. Furthermore, this decrease was more marked than those observed using serological techniques in other geographically close East African countries. Oromo and Amhara only showed minor differences in spite of their different origins and histories. One significant difference consisted of a lower DRB1*01 gene frequency in Oromo as reported in most West African people. Some new or rare haplotypes were also observed in the Oromo group. Our results underline the distinctive features of the Ethiopian populations among the few HLA genotyping data available for East African groups and emphasise the major interest of such investigations in this region of Africa.

  18. 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

  19. HLA-A, -B and -DR allele and haplotype frequencies in Malays.

    PubMed

    Dhaliwal, J S; Shahnaz, M; Too, C L; Azrena, A; Maiselamah, L; Lee, Y Y; Irda, Y A; Salawati, M

    2007-03-01

    One thousand four hundreds and forty-five Malays registered with the Malaysian Marrow Donor Registry were typed for HLA-A, HLA-B and HLA-DR. Fifteen HLA-A, twenty nine HLA-B and fourteen HLA-DR alleles were detected. The most common HLA-A alleles and their frequencies were HLA-A24 (0.35), HLA-A11 (0.21) and HLA-A2 (0.15). The most common HLA-B alleles were HLA-B15 (0.26), HLA-B35 (0.11) and HLA-B18 (0.10) while the most common HLA-DR alleles were HLA-DR15 (0.28), HLA-DR12 (0.27) and HLA-DR7 (0.10). A24-B15-DR12 (0.047), A24-B15-DR15 (0.03) and the A24-B35-DR12 (0.03) were the most frequent haplotypes. This data may be useful in determining the probability of finding a matched donor and for estimating the incidence of HLA associated diseases.

  20. 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.

  1. 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.

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

    PubMed

    Fazeli, Zahra; Vallian, Sadeq

    2012-12-01

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

  3. 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

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

    PubMed Central

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

    2015-01-01

    GIGANTEA (GI) was originally identified by a late-flowering mutant in Arabidopsis, but subsequently has been shown to act in circadian period determination, light inhibition of hypocotyl elongation, and responses to multiple abiotic stresses, including tolerance to high salt and cold (freezing) temperature. Genetic mapping and analysis of families of heterogeneous inbred lines showed that natural variation in GI is responsible for a major quantitative trait locus in circadian period in Brassica rapa. We confirmed this conclusion by transgenic rescue of an Arabidopsis gi-201 loss of function mutant. The two B. rapa GI alleles each fully rescued the delayed flowering of Arabidopsis gi-201 but showed differential rescue of perturbations in red light inhibition of hypocotyl elongation and altered cold and salt tolerance. The B. rapa R500 GI allele, which failed to rescue the hypocotyl and abiotic stress phenotypes, disrupted circadian period determination in Arabidopsis. Analysis of chimeric B. rapa GI alleles identified the causal nucleotide polymorphism, which results in an amino acid substitution (S264A) between the two GI proteins. This polymorphism underlies variation in circadian period, cold and salt tolerance, and red light inhibition of hypocotyl elongation. Loss-of-function mutations of B. rapa GI confer delayed flowering, perturbed circadian rhythms in leaf movement, and increased freezing and increased salt tolerance, consistent with effects of similar mutations in Arabidopsis. Collectively, these data suggest that allelic variation of GI—and possibly of clock genes in general—offers an attractive target for molecular breeding for enhanced stress tolerance and potentially for improved crop yield. PMID:25775524

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

    PubMed

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

    2015-03-24

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

  6. Intracellular Population Genetics: Evidence for Random Drift of Mitochondrial Allele Frequencies in SACCHAROMYCES CEREVISIAE and SCHIZOSACCHAROMYCES POMBE

    PubMed Central

    Thrailkill, Kathryn M.; Birky, C. William; Lückemann, Gudrun; Wolf, Klaus

    1980-01-01

    We report evidence for random drift of mitochondrial allele frequencies in zygote clones of Saccharomyces cerevisiae and Schizosaccharomyces pombe. Monofactorial and bifactorial crosses were done, using strains resistant or sensitive to erythromycin (alleles ER, ES), oligomycin (OR, OS), or diuron (DR, DS). The frequencies of resistant and sensitive cells (and thus the frequencies of the resistant and sensitive alleles) were determined for each of a number of clones of diploid cells arising from individual zygotes. Allele frequencies were extremely variable among these zygote clones; some clones were "uniparental," with mitochondrial alleles from only one parent present. These observations suggest random drift of the allele frequencies in the population of mitochondrial genes within an individual zygote and its diploid progeny. Drift would cease when all the cells in a clone become homoplasmic, due to segregation of the mitochondrial genomes during vegetative cell divisions. To test this, we delayed cell division (and hence segregation) for varying times by starving zygotes in order to give drift more time to operate. As predicted, delaying cell division resulted in an increase in the variance of allele frequencies among the zygote clones and an increase in the proportion of uniparental zygote clones. The changes in form of the allele frequency distributions resembled those seen during random drift in finite Mendelian populations. In bifactorial crosses, genotypes as well as individual alleles were fixed or lost in some zygote clones. However, the mean recombination frequency for a large number of clones did not increase when cell division was delayed. Several possible molecular mechanisms for intracellular random drift are discussed. PMID:7009322

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

    PubMed

    Kaj, Ingemar; Mugal, Carina F

    2016-10-01

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

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

    PubMed

    Kaj, Ingemar; Mugal, Carina F

    2016-10-01

    In population genetic studies, the allele frequency spectrum (AFS) efficiently summarizes genome-wide polymorphism data and shapes a variety of allele frequency-based summary statistics. While existing theory typically features equilibrium conditions, emerging methodology requires an analytical understanding of the build-up of the allele frequencies over time. In this work, we use the framework of Poisson random fields to derive new representations of the non-equilibrium AFS for the case of a Wright-Fisher population model with selection. In our approach, the AFS is a scaling-limit of the expectation of a Poisson stochastic integral and the representation of the non-equilibrium AFS arises in terms of a fixation time probability distribution. The known duality between the Wright-Fisher diffusion process and a birth and death process generalizing Kingman's coalescent yields an additional representation. The results carry over to the setting of a random sample drawn from the population and provide the non-equilibrium behavior of sample statistics. Our findings are consistent with and extend a previous approach where the non-equilibrium AFS solves a partial differential forward equation with a non-traditional boundary condition. Moreover, we provide a bridge to previous coalescent-based work, and hence tie several frameworks together. Since frequency-based summary statistics are widely used in population genetics, for example, to identify candidate loci of adaptive evolution, to infer the demographic history of a population, or to improve our understanding of the underlying mechanics of speciation events, the presented results are potentially useful for a broad range of topics. PMID:27378747

  9. Allelic variation in the dihydrofolate reductase gene at amino acid position 95 contributes to antifolate resistance in Chinese hamster cells.

    PubMed

    Yu, M; Melera, P W

    1993-12-15

    The Chinese hamster lung cell line DC-3F contains two polymorphic dihydrofolate reductase (DHFR) alleles that are defined by an Asp-Asn amino acid sequence difference at position 95 in protein. Previously, we reported that the antifolate-resistant subline DC-3F/A3 overexpressed a Leu22-->Phe mutant of the Asp95 (21k) allele and that this was the basis of its resistance to methotrexate (MTX) and methasquin [P. W. Melera, J. P. Davide, C. A. Hession, and K. W. Scotto, Mol. Cell. Biol., 4: 38-48, 1984]. We now show that another independently selected antifolate-resistant subline of DC-3F, DC-3F8/A55, in addition to being severely compromised in its ability to accumulate MTX, overexpresses a Leu22-->Phe mutant form of the Asn95 (20k) allele. Characterization of purified DHFR from these cells showed that the enzyme displayed a 6-fold higher Kd for MTX (3.92 +/- 0.17 pM) than the wild type (0.58 +/- 0.10 pM), thus explaining its lowered sensitivity to drug. Unexpectedly, however, this value was 4-fold lower than that displayed by the DC-3F/A3 enzyme even though both contain the same (Leu22-->Phe) mutation and differ only at position 95. Indeed, we have also shown that the 21k and 20k wild type enzymes, both containing Leu at position 22, in fact differ by 3-fold (1.58 +/- 0.08 and 0.58 +/- 0.10 pM, respectively) in their Kd's for MTX. This demonstrates that the amino acid at position 95 has an effect on the ability of DHFR to bind MTX. On the other hand, these allelic variants are indistinguishable from each other in their catalytic properties and in their respective Kd's for dihydrofolate. Taken together, these characteristics are consistent with the observation that it is the wild type 21k allele which is preferentially overexpressed at a frequency of 3:1 in MTX-resistant Chinese hamster lung sublines derived by long-term selection in MTX. The results of these studies are novel in that they establish a role for allelic variation in the DHFR gene as a contributor to

  10. 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.

  11. 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

  12. Inference in two dimensions: allele frequencies versus lengths of shared sequence blocks.

    PubMed

    Barton, N H; Etheridge, A M; Kelleher, J; Véber, A

    2013-08-01

    We outline two approaches to inference of neighbourhood size, N, and dispersal rate, σ(2), based on either allele frequencies or on the lengths of sequence blocks that are shared between genomes. Over intermediate timescales (10-100 generations, say), populations that live in two dimensions approach a quasi-equilibrium that is independent of both their local structure and their deeper history. Over such scales, the standardised covariance of allele frequencies (i.e. pairwise FST) falls with the logarithm of distance, and depends only on neighbourhood size, N, and a 'local scale', κ; the rate of gene flow, σ(2), cannot be inferred. We show how spatial correlations can be accounted for, assuming a Gaussian distribution of allele frequencies, giving maximum likelihood estimates of N and κ. Alternatively, inferences can be based on the distribution of the lengths of sequence that are identical between blocks of genomes: long blocks (>0.1 cM, say) tell us about intermediate timescales, over which we assume a quasi-equilibrium. For large neighbourhood size, the distribution of long blocks is given directly by the classical Wright-Malécot formula; this relationship can be used to infer both N and σ(2). With small neighbourhood size, there is an appreciable chance that recombinant lineages will coalesce back before escaping into the distant past. For this case, we show that if genomes are sampled from some distance apart, then the distribution of lengths of blocks that are identical in state is geometric, with a mean that depends on N and σ(2).

  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.

  14. 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

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

    PubMed

    Sala, A; Penacino, G; Corach, D

    1998-10-01

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

  16. Frequency of CYP2C9 alleles in Koreans and their effects on losartan pharmacokinetics

    PubMed Central

    Bae, Jung-woo; Choi, Chang-ik; Kim, Mi-jeong; Oh, Da-hee; Keum, Seul-ki; Park, Jung-in; Kim, Bo-hye; Bang, Hye-kyoung; Oh, Sung-gon; Kang, Byung-sung; Park, Hyun-joo; Kim, Hae-deun; Ha, Ji-hey; Shin, Hee-jung; Kim, Young-hoon; Na, Han-sung; Chung, Myeon-woo; Jang, Choon-gon; Lee, Seok-yong

    2011-01-01

    Aim: CYP2C9 enzyme metabolizes numerous clinically important drugs. The aim of this study is to investigate the frequencies of CYP2C9 genotypes and the effects of selected alleles on losartan pharmacokinetics in a large sample of the Korean population. Methods: The CYP2C9 gene was genotyped in 1796 healthy Korean subjects. CYP2C9 alleles (CYP2C9*1, *2, *3 and *13 alleles) were measured using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and direct sequencing assay. The enzymatic activity of each CYP2C9 genotype was evaluated using losartan as the substrate. Results: The frequencies of CYP2C9*1, *3 and *13 allele were 0.952 (95% confidence interval 0.945–0.959), 0.044 (95% CI 0.037–0.051) and 0.005 (95% CI 0.003–0.007), respectively. The frequencies of the CYP2C9*1/*1, *1/*3, *1/*13 and *3/*3 genotypes were 0.904 (95% CI 0.890–0.918), 0.085 (95% CI 0.072–0.098), 0.009 (95% CI 0.005–0.013) and 0.001 (95% CI 0.000–0.002), respectively. In the pharmacokinetics studies, the AUC0–∞ of losartan in CYP2C9*3/*3 subjects was 1.42-fold larger than that in CYP2C9*1/*1 subjects, and the AUC0–∞ of E-3174, a more active metabolite of losartan, in CYP2C9*3/*3 subjects was only 12% of that in CYP2C9*1/*1 subjects. Conclusion: The results confirmed the frequencies of CYP2C9 genotypes in a large cohort of Koreans, and detected the CYP2C9*3/*3 genotype. CYP2C9*3/*3 subjects metabolized much less losartan into E-3174 than CYP2C9*1/*1 subjects. PMID:21841812

  17. 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

  18. 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

  19. 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

  20. Influence of HLA-DRB1 Alleles on the Variations of Antibody Response to Tuberculosis Serodiagnostic Antigens in Active Tuberculosis Patients

    PubMed Central

    Zhou, Fangbin; Xu, Xindong; Wu, Sijia; Cui, Xiaobing; Fan, Lin; Pan, Weiqing

    2016-01-01

    Serology-based tests for tuberculosis (TB) diagnosis, though rapid, efficient and easily implemented, have so far shown unsatisfactory levels of sensitivity and specificity, probably due to variations of the antibody response in TB patients. The number and types of seropositive antigens vary from individual to individual. The person-to-person variations of antigen recognition may be linked to genetic polymorphisms of the human leukocyte antigen (HLA) class II alleles. In the present study, we find that there is a significant increase in the frequency of HLA-DRB1*14 (P = 2.5×10−4) among subjects with high antibody response levels compared to those with low antibody levels. HLA-DRB1*15, the most frequent allelic group in the studied active TB population, positively correlates with subjects with low antibody response levels rather than subjects with high antibody response levels (P = 0.005), which indicates the loss of relevant antigens for screening of patients with this allelic group. The potential association between HLA-DRB1 allelic group and individual antigens implies that TB diagnostic yield could be improved by the addition of antigens screened at the proteome scale in infected subjects from the HLA-DRB1*15 allelic group. PMID:27788190

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

    PubMed

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

    2007-02-20

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

  2. 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.

  3. D9S1120, a simple STR with a common Native American-specific allele: forensic optimization, locus characterization and allele frequency studies.

    PubMed

    Phillips, C; Rodriguez, A; Mosquera-Miguel, A; Fondevila, M; Porras-Hurtado, L; Rondon, F; Salas, A; Carracedo, A; Lareu, M V

    2008-12-01

    The simple tetrameric STR D9S1120 exhibits a common population-specific allele of 9 repeats (9RA) reported to have an average frequency of 0.36 in Native Americans from both North and South of the continent. Apart from the presence of 9RA in two northeast Siberian populations, D9S1120 shows variability exclusive to, and universal in all American populations studied to date. This STR therefore provides an informative forensic marker applicable in countries with significant proportions of Native American populations or ancestry. We have re-designed PCR primers that reduce the amplified product sizes reported in NCBI UniSTS by more than a third and have characterized the repeat structure of D9S1120. The 9RA allele shares the same repeat structure as the majority of other D9S1120 alleles and so originates from a slippage-diminution mutation rather than an independent deletion. We confirm the previously reported allele frequencies from a range of populations indicating a global heterozygosity range for D9S1120 of 66-75% and estimate the proportion of Native American-diagnostic genotypes to average 53%, underlining the potential usefulness of this STR in both forensic identification and in population genetics studies of the Americas.

  4. 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

  5. Cluster B personality disorders are associated with allelic variation of monoamine oxidase A activity.

    PubMed

    Jacob, Christian P; Müller, Johannes; Schmidt, Michael; Hohenberger, Katrin; Gutknecht, Lise; Reif, Andreas; Schmidtke, Armin; Mössner, Rainald; Lesch, Klaus Peter

    2005-09-01

    Genetic variants of the monoamine oxidase A (MAOA) have been associated with aggression-, anxiety-, and addiction-related behavior in several nonclinical and clinical populations. Here, we investigated the influence of allelic variation of MAOA activity on aggression-related personality traits and disease risk in patients with personality disorders. Personality disorders were diagnosed with the Structured Clinical Interview of DSM-IV and were allocated to cluster A, B, and C. Personality features were assessed by the revised NEO Personality Inventory and the Tridimensional Personality Questionnaire. The genotype of the MAOA gene-linked polymorphic region (MAOA-LPR) was determined in 566 patients with personality disorders and in 281 healthy controls. MAOA genotype was significantly associated with cluster B personality disorders (chi2=7.77, p=0.005, df=1) but not with cluster C personality disorders. In total, 26.0% of cluster B patients were hemi- or homozygous for the low-activity variant of the MAOA genotype, compared to 16.4% in the control group. Associations between MAOA variants and personality domains related to impulsivity and aggressiveness were inconsistent. Our findings further support the notion that allelic variation of MAOA activity contributes modestly to the balance of hyper- (impulsive-aggressive) and hyporeactive (anxious-depressive) traits.

  6. 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

  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. 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.

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

    PubMed

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

    2012-06-01

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

  10. 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

  11. Allele frequency distribution of 10 MiniSTRs in the Pashtun population of Pakistan.

    PubMed

    Shafique, Muhammad; Shahzad, Muhammad Saqib; Perveen, Uzma; Parveen, Rukhsana; Ali, Azam; Hussain, Manzoor; Rehman, Ziaur; Shahid, Ahmad Ali; Husnain, Tayyab

    2015-05-01

    Two hundred individual samples of Pashtun population from Khyber Pakhtunkhwa province of Pakistan were randomly evaluated through 10 MiniSTR loci (CSF1PO, D7S820, TPOX, D18S51, D2S1338, D13S317, FGA, D5S818, D21S11, and D16S539). The PCR product size was reduced in the range of 65 to 280 bp. A total of 112 alleles were observed containing allelic frequency ranging from 0.0025 to 0.4325. Statistical values for forensic and parentage analysis were calculated including combined power of discrimination (PD), combined power of exclusion (PE), and cumulative probability of matching (PM) and equaled to 0.99999999999768, 0.99984944, and 2.33 × 10(-12), respectively. These MiniSTRs show a high degree of polymorphism information content and discriminatory power which would be helpful to resolve forensic cases and establish DNA database for major population groups of Pakistan. In contrast to different populations, significant differences were also observed on these loci. PMID:25821203

  12. 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

  13. 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

  14. Segregating YKU80 and TLC1 alleles underlying natural variation in telomere properties in wild yeast.

    PubMed

    Liti, Gianni; Haricharan, Svasti; Cubillos, Francisco A; Tierney, Anna L; Sharp, Sarah; Bertuch, Alison A; Parts, Leopold; Bailes, Elizabeth; Louis, Edward J

    2009-09-01

    In yeast, as in humans, telomere length varies among individuals and is controlled by multiple loci. In a quest to define the extent of variation in telomere length, we screened 112 wild-type Saccharomyces sensu stricto isolates. We found extensive telomere length variation in S. paradoxus isolates. This phenotype correlated with their geographic origin: European strains were observed to have extremely short telomeres (<150 bp), whereas American isolates had telomeres approximately three times as long (>400 bp). Insertions of a URA3 gene near telomeres allowed accurate analysis of individual telomere lengths and telomere position effect (TPE). Crossing the American and European strains resulted in F1 spores with a continuum of telomere lengths consistent with what would be predicted if many quantitative trait loci (QTLs) were involved in length maintenance. Variation in TPE is similarly quantitative but only weakly correlated with telomere length. Genotyping F1 segregants indicated several QTLs associated with telomere length and silencing variation. These QTLs include likely candidate genes but also map to regions where there are no known genes involved in telomeric properties. We detected transgressive segregation for both phenotypes. We validated by reciprocal hemizygosity that YKU80 and TLC1 are telomere-length QTLs in the two S. paradoxus subpopulations. Furthermore, we propose that sequence divergence within the Ku heterodimer generates negative epistasis within one of the allelic combinations (American-YKU70 and European-YKU80) resulting in very short telomeres. PMID:19763176

  15. 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

  16. 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

  17. 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

  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. 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

  20. 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

  1. 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

  2. Structural Basis of Allele Variation of Human Thiopurine-S-Methyltransferase

    PubMed Central

    Wu, Hong; Horton, John R.; Battaile, Kevin; Allali-Hassani, Abdellah; Martin, Fernando; Zeng, Hong; Loppnau, Peter; Vedadi, Masoud; Bochkarev, Alexey; Plotnikov, Alexander N.; Cheng, Xiaodong

    2009-01-01

    Human thiopurine S-methyltransferase (TPMT) exhibits considerable person-to-person variation in activity to thiopurine drugs. We have produced an N-terminal truncation of human TPMT protein, crystallized the protein in complex with the methyl donor product S-adenosyl-L-homocysteine, and determined the atomic structure to the resolution of 1.58 and 1.89 Å, respectively, for the seleno-methionine incorporated and wild type proteins. The structure of TPMT indicates that the naturally occurring amino acid polymorphisms scatter throughout the structure, and that the amino acids whose alteration have the most influence on function are those that form intra-molecular stabilizing interactions (mainly van der Waals contacts). Furthermore, we have produced four TPMT mutant proteins containing variant alleles of TPMT*2, *3A, *3B, and *3C and examined the structure-function relationship of the mutant proteins based on their expression and solubility in bacteria and their thermostability profile. PMID:17243178

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

    PubMed

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

    2011-01-01

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

  4. 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

  5. Determinants of echolocation call frequency variation in the Formosan lesser horseshoe bat (Rhinolophus monoceros)

    PubMed Central

    Chen, Shiang-Fan; Jones, Gareth; Rossiter, Stephen J.

    2009-01-01

    The origin and maintenance of intraspecific variation in vocal signals is important for population divergence and speciation. Where vocalizations are transmitted by vertical cultural inheritance, similarity will reflect co-ancestry, and thus vocal divergence should reflect genetic structure. Horseshoe bats are characterized by echolocation calls dominated by a constant frequency component that is partly determined by maternal imprinting. Although previous studies showed that constant frequency calls are also influenced by some non-genetic factors, it is not known how frequency relates to genetic structure. To test this, we related constant frequency variation to genetic and non-genetic variables in the Formosan lesser horseshoe bat (Rhinolophus monoceros). Recordings of bats from across Taiwan revealed that females called at higher frequencies than males; however, we found no effect of environmental or morphological factors on call frequency. By comparison, variation showed clear population structure, with frequencies lower in the centre and east, and higher in the north and south. Within these regions, frequency divergence was directional and correlated with geographical distance, suggesting that call frequencies are subject to cultural drift. However, microsatellite clustering analysis showed that broad differences in constant frequency among populations corresponded to discontinuities in allele frequencies resulting from vicariant events. Our results provide evidence that the processes shaping genetic subdivision have concomitant consequences for divergence in echolocation call frequency. PMID:19692399

  6. Protein variation in Adh and Adh-related in Drosophila pseudoobscura. Linkage disequilibrium between single nucleotide polymorphisms and protein alleles.

    PubMed Central

    Schaeffer, S W; Walthour, C S; Toleno, D M; Olek, A T; Miller, E L

    2001-01-01

    A 3.5-kb segment of the alcohol dehydrogenase (Adh) region that includes the Adh and Adh-related genes was sequenced in 139 Drosophila pseudoobscura strains collected from 13 populations. The Adh gene encodes four protein alleles and rejects a neutral model of protein evolution with the McDonald-Kreitman test, although the number of segregating synonymous sites is too high to conclude that adaptive selection has operated. The Adh-related gene encodes 18 protein haplotypes and fails to reject an equilibrium neutral model. The populations fail to show significant geographic differentiation of the Adh-related haplotypes. Eight of 404 single nucleotide polymorphisms (SNPs) in the Adh region were in significant linkage disequilibrium with three ADHR protein alleles. Coalescent simulations with and without recombination were used to derive the expected levels of significant linkage disequilibrium between SNPs and 18 protein haplotypes. Maximum levels of linkage disequilibrium are expected for protein alleles at moderate frequencies. In coalescent models without recombination, linkage disequilibrium decays between SNPs and high frequency haplotypes because common alleles mutate to haplotypes that are rare or that reach moderate frequency. The implication of this study is that linkage disequilibrium mapping has the highest probability of success with disease-causing alleles at frequencies of 10%. PMID:11606543

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

    PubMed Central

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

    2016-01-01

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

  8. Sleep, diurnal preference, health, and psychological well-being: a prospective single-allelic-variation study.

    PubMed

    Lázár, Alpár S; Slak, Ana; Lo, June Chi-Yan; Santhi, Nayantara; von Schantz, Malcolm; Archer, Simon N; Groeger, John A; Dijk, Derk-Jan

    2012-03-01

    Individual differences in sleep and diurnal preference associate with physical and mental health characteristics, but few genetic determinants of these differences have been identified. A variable number tandem repeat (VNTR) polymorphism in the PERIOD3 (PER3) gene (rs57875989) has been reported to associate with diurnal preference, i.e., preferred timing of waking and sleep. Here, the authors investigate in a prospective single-candidate genetic variant study whether allelic variation for this polymorphism associates also with reported actual sleep timing and sleep duration, as well as psychological and health measures. Six hundred and seventy-five subjects, aged 20 to 35 yrs, completed questionnaires to assess sleep and psychological and health characteristics and were genotyped for the PER3 VNTR. Homozygosity for the longer allele (PER3(5/5)) of the VNTR was associated with increased morning preference, earlier wake time and bedtime, and reduced daytime sleepiness. Separate analyses of work and rest days demonstrated that the increase in time in bed during rest days was greatest in PER3(5/5) homozygotes. PER3 genotype modified the effects of sleep timing and duration on fluid intelligence and body mass index. Genotype was not associated with physical or psychological characteristics as assessed by the SF-36 Health Questionnaire, the General Health Questionnaire, the Big Five Inventory, the Behavioral Inhibition System-Behavioral Activation System scales, and the Positive and Negative Affect Scale, even though these measures varied significantly with diurnal preference as assessed by the Morningness-Eveningness Questionnaire. Whereas diurnal preference also predicts mental health and psychological characteristics, as well as sleep timing, the PER3 VNTR specifically affects measures of sleep timing and may also modify the effects of sleep on health outcome measures. PMID:22324552

  9. 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.

  10. Determination of the allelic frequencies of an L-myc and a p53 polymorphism in human lung cancer.

    PubMed

    Weston, A; Ling-Cawley, H M; Caporaso, N E; Bowman, E D; Hoover, R N; Trump, B F; Harris, C C

    1994-04-01

    The L-myc and p53 genes have been implicated in lung cancer. Both of these genes have restriction fragment length polymorphisms (RFLPs) that could account for differential expression or activity of variant forms. An EcoRI restriction site in the L-myc gene was previously reported to be a predictor of poor prognosis in Japanese lung cancer patients. There are several RFLPs in the p53 gene. In exon 4 there is a polymorphism that codes for either an arginine or proline residue at codon 72. We previously reported the frequency of DNA-RFLPs at these gene loci revealed by EcoRI and AccII respectively. Here we report results from a study comparing lung cancer cases (n = 31) with chronic obstructive pulmonary disease controls (n = 49). No association was found between these RFLPs and disease status. Previous observations that the frequencies of these RFLPs varied by race were confirmed. The p53 arginine allele was found to be more common in Caucasians (0.71) than African-Americans (0.50). The EcoRI restriction site present allele in L-myc was more frequent in African-Americans (0.71) than Caucasians (0.49). Thus, the allelic frequency for L-myc was similar in African-Americans to that reported for Japanese, and the allelic frequency for p53 was similar in Caucasians to that reported for Japanese.

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

    PubMed

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

    2015-01-01

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

  12. Reducing bias of allele frequency estimates by modeling SNP genotype data with informative missingness.

    PubMed

    Lin, Wan-Yu; Liu, Nianjun

    2012-01-01

    The presence of missing single-nucleotide polymorphism (SNP) genotypes is common in genetic studies. For studies with low-density SNPs, the most commonly used approach to dealing with genotype missingness is to simply remove the observations with missing genotypes from the analyses. This naïve method is straightforward but is valid only when the missingness is random. However, a given assay often has a different capability in genotyping heterozygotes and homozygotes, causing the phenomenon of "differential dropout" in the sense that the missing rates of heterozygotes and homozygotes are different. In practice, differential dropout among genotypes exists in even carefully designed studies, such as the data from the HapMap project and the Wellcome Trust Case Control Consortium. Under the assumption of Hardy-Weinberg equilibrium and no genotyping error, we here propose a statistical method to model the differential dropout among different genotypes. Compared with the naïve method, our method provides more accurate allele frequency estimates when the differential dropout is present. To demonstrate its practical use, we further apply our method to the HapMap data and a scleroderma data set. PMID:22719749

  13. Exome sequencing can detect pathogenic mosaic mutations present at low allele frequencies.

    PubMed

    Pagnamenta, Alistair T; Lise, Stefano; Harrison, Victoria; Stewart, Helen; Jayawant, Sandeep; Quaghebeur, Gerardine; Deng, Alexander T; Murphy, Valerie Elizabeth; Sadighi Akha, Elham; Rimmer, Andy; Mathieson, Iain; Knight, Samantha J L; Kini, Usha; Taylor, Jenny C; Keays, David A

    2012-01-01

    The development of next generation sequencing (NGS) has radically transformed the scientific landscape, making it possible to sequence the exome of any given individual in a cost-effective way. The power of this approach has been demonstrated by a number of groups who have identified pathogenic mutations in small pedigrees that have been resistant to traditional genetic mapping. Recently it has become clear that exome sequencing has great potential with respect to sporadic disease and the identification of de novo mutations. This is highlighted by studies reporting whole-exome sequencing of patient-parental trios affected by learning disability, autism and schizophrenia. It is widely anticipated that the introduction of this technique into a clinical setting will revolutionise genetic diagnosis. However, the sensitivity of NGS exome sequencing is currently unclear. Here, we describe the exome sequencing of DNA samples from a patient with double cortex syndrome and her parents, resulting in the detection of a mosaic splicing mutation in LIS1. This variant was found at an allele frequency of just 18%, demonstrating that NGS methods have the capacity to identify pathogenic mosaic mutations present at a low level. PMID:22129557

  14. Inference of population splits and mixtures from genome-wide allele frequency data.

    PubMed

    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

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

    PubMed

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

    2009-01-01

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

  17. 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...

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

    PubMed Central

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

    2016-01-01

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

  19. 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

  20. 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

  1. 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

  2. Assortative human pair-bonding for partner ancestry and allelic variation of the dopamine receptor D4 (DRD4) gene

    PubMed Central

    Apicella, Coren L.; Campbell, Benjamin C.; Dreber, Anna; Garcia, Justin R.; Lum, J. Koji

    2010-01-01

    The 7 repeat (7R) allele of the dopamine receptor D4 gene has been associated with attention deficit hyperactivity disorder and risk taking. On the cross-population scale, 7R allele frequencies have been shown to be higher in populations with more of a history of long-term migrations. It has also been shown that the 7R allele is associated with individuals having multiple ancestries. Here, we conduct a replication of this latter finding with two independent samples. Measures of subjects’ ancestry are used to examine past reproductive bonds. The individuals’ history of interracial/ancestral dating and their feelings about this are also assessed. Tentative support for an association between multiple ancestries and the 7R allele was found. These results are dependent upon the method of questioning subjects about their ancestries, with only finer-scale measures of ancestry being associated with 7R. Interracial dating and feelings about interracial pairing were not related to the presence of the 7R allele. This study provides continued support for a role for the 7R allele in migration and/or mate choice patterns. However, replications and extensions of this study are needed and the way ancestry/race is assessed must be carefully considered. PMID:19713452

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

    PubMed

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

    2016-03-01

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

  4. Influence of admixture components on CYP2C9*2 allele frequency in eight indigenous populations from Northwest Mexico.

    PubMed

    Sosa-Macías, M; Lazalde-Ramos, B P; Galaviz-Hernández, C; Rangel-Villalobos, H; Salazar-Flores, J; Martínez-Sevilla, V M; Martínez-Fierro, M L; Dorado, P; Wong, M L; Licinio, J; LLerena, A

    2013-12-01

    We previously documented the lowest frequency of CYP2C9*2 in Mexican indigenous Tepehuanos followed by Mestizos and Mexican-Americans populations, suggesting a negative correlation between the CYP2C9*2 frequency and the degree of Asian ancestry in indigenous Americans. We determined the influence of ethnic admixture components on the CYP2C9 allele distribution in 505 Amerindian from eight indigenous populations through genotyping CYP2C9*2, *3 and *6 alleles by real-time PCR and molecular evaluation of ancestry. The frequencies for CYP2C9*2 were 0.026 in Seris and 0.057 in Mayos, being higher than in Asians (P<0.001). CYP2C9*3 was found in Tarahumaras (0.104), Mayos (0.091), Tepehuanos (0.075), Guarijíos (0.067), Huicholes (0.033) and Coras (0.037), with East Asians having lower frequencies than the former three groups (P<0.001). CYP2C9*6 was not found. The frequency of CYP2C9*2 was lower in Amerindians than in European populations, and higher than their Asian ancestors. The presence of this allele in ethnic groups in Mexico can be explained by European admixture.

  5. 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...

  6. 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

  7. Frequency of the apolipoprotein E epsilon 4 allele in a case-control study of early onset Parkinson's disease.

    PubMed Central

    Whitehead, A S; Bertrandy, S; Finnan, F; Butler, A; Smith, G D; Ben-Shlomo, Y

    1996-01-01

    OBJECTIVES: It has been suggested that Parkinson's disease and Alzheimer's disease may share a common or at least overlapping aetiology. The prevalence of dementia among cases of Parkinson's disease is known to be greater than expected in the general population. The frequency of the apolipoprotein epsilon 4 allele in a large case-control study of early onset Parkinson's disease has been examined. METHODS: 215 patients and 212 population based controls were recruited from the Republic of Ireland between 1992 and 1994. Cases had to have disease onset at 55 years or younger and be born after 1925. RESULTS: The frequency of the epsilon 4 allele was almost identical between cases of Parkinson's disease (14.6%) and healthy controls (13.3%). There was no relation between epsilon 4 status and disease onset, disease duration, Hoehn and Yahr score, and disease progression. The frequency of the epsilon 4 allele was not increased among 10 patients with Parkinson's disease with dementia (10.0%) compared with the other patients without dementia (14.8%). There was no association between epsilon 4 allele status and either a history of smoking, family history of dementia, or Parkinson's disease, or being born in a rural area. The odds ratio for the ApoE epsilon 4 allele associated with Parkinson's disease was 1.10 (95% confidence interval (95% CI) 0.68-1.79), adjusting for age group, sex, and residential status. The pooled odds ratio from a meta-analysis of six studies of ApoE epsilon 4 status and Parkinson's disease was 0.94 (95% CI 0.69-1.27). CONCLUSIONS: The results from our study as well as the pooled meta-analysis exclude any important role for ApoE epsilon 4 status in the development of Parkinson's disease. Our results similarly do not support its role either in dementia associated with Parkinson's disease or disease prognosis. PMID:8890771

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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

  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.

  20. 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

  1. 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

  2. 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

  3. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2002-11-01

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

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

    PubMed

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

    2015-07-03

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

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

    PubMed

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

    2008-05-01

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

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

    PubMed Central

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

    2015-01-01

    It has been 12 years since the Allele Frequency Net Database (AFND; http://www.allelefrequencies.net) was first launched, providing the scientific community with an online repository for the storage of immune gene frequencies in different populations across the world. There have been a significant number of improvements from the first version, making AFND a primary resource for many clinical and scientific areas including histocompatibility, immunogenetics, pharmacogenetics and anthropology studies, among many others. The most widely used part of AFND stores population frequency data (alleles, genes or haplotypes) related to human leukocyte antigens (HLA), killer-cell immunoglobulin-like receptors (KIR), major histocompatibility complex class I chain-related genes (MIC) and a number of cytokine gene polymorphisms. AFND now contains >1400 populations from more than 10 million healthy individuals. Here, we report how the main features of AFND have been updated to include a new section on ‘HLA epitope’ frequencies in populations, a new section capturing the results of studies identifying HLA associations with adverse drug reactions (ADRs) and one for the examination of infectious and autoimmune diseases associated with KIR polymorphisms—thus extending AFND to serve a new user base in these growing areas of research. New criteria on data quality have also been included. PMID:25414323

  8. 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

  9. 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

  10. A hyperactive quantitative trait locus allele of Arabidopsis BRX contributes to natural variation in root growth vigor

    PubMed Central

    Beuchat, Julien; Ragni, Laura; Shindo, Chikako; Kohn, Michael H.; Hardtke, Christian S.

    2010-01-01

    Quantitative trait loci analysis of natural Arabidopsis thaliana accessions is increasingly exploited for gene isolation. However, to date this has mostly revealed deleterious mutations. Among them, a loss-of-function allele identified the root growth regulator BREVIS RADIX (BRX). Here we present evidence that BRX and the paralogous BRX-LIKE (BRXL) genes are under selective constraint in monocotyledons as well as dicotyledons. Unexpectedly, however, whereas none of the Arabidopsis orthologs except AtBRXL1 could complement brx null mutants when expressed constitutively, nearly all monocotyledon BRXLs tested could. Thus, BRXL proteins seem to be more diversified in dicotyledons than in monocotyledons. This functional diversification was correlated with accelerated rates of sequence divergence in the N-terminal regions. Population genetic analyses of 30 haplotypes are suggestive of an adaptive role of AtBRX and AtBRXL1. In two accessions, Lc-0 and Lov-5, seven amino acids are deleted in the variable region between the highly conserved C-terminal, so-called BRX domains. Genotyping of 42 additional accessions also found this deletion in Kz-1, Pu2-7, and Ws-0. In segregating recombinant inbred lines, the Lc-0 allele (AtBRXLc-0) conferred significantly enhanced root growth. Moreover, when constitutively expressed in the same regulatory context, AtBRXLc-0 complemented brx mutants more efficiently than an allele without deletion. The same was observed for AtBRXL1, which compared with AtBRX carries a 13 amino acid deletion that encompasses the deletion found in AtBRXLc-0. Thus, the AtBRXLc-0 allele seems to contribute to natural variation in root growth vigor and provides a rare example of an experimentally confirmed, hyperactive allelic variant. PMID:20404146

  11. PAH Mutation Analysis Consortium Database: a database for disease-producing and other allelic variation at the human PAH locus.

    PubMed

    Hoang, L; Byck, S; Prevost, L; Scriver, C R

    1996-01-01

    The PAH Mutation Analysis Consortium (81 investigators, 26 countries) is engaged in mutation detection at the human PAH locus. Ascertainment of probands occurs largely through newborn screening for hyperphenylalaninemia. A relational database records allelic variation (disease-producing and polymorphic) at the locus. Information is distributed by Newsletter, diskette (WINPAHDB software stand-alone executable on IBM compatible hardware), and at a 'real' site on the Worldwide Web (http://www.mcgill.ca/pahdb). The database presently records (Sept. 27, 1995) 248 alleles in 798 different associations (with polymorphic haplotype, geographic region and population) along with additional information. The database, as a record of human genetic diversity, at a particular locus, contributes to the study of human evolution and demic expansion; it also has medical relevance.

  12. 46 CFR 111.01-17 - Voltage and frequency variations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  13. 46 CFR 111.01-17 - Voltage and frequency variations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

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

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

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

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

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

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  17. Mamu-DQA1 allele and genotype frequencies in a randomly sampled breeding colony of rhesus macaques (Macaca mulatta).

    PubMed

    Rolfs, B K; Lorenz, J G; Wu, C C; Lerche, N W; Smith, D G

    2001-04-01

    We studied the allelic and genotypic distribution of the major histocompatibility class-II locus DQA1 observed in a random sample of Indian rhesus macaques (Macaca mulatta) from a major breeding facility in the United States. The DNA was isolated from whole blood samples collected between 1991 and 1994 from 65 Indian rhesus monkeys. Polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP), which involves use of specific amplification of DQA1 exon 2 and subsequent restriction digestion of the 242-base pair fragment, was used to genotype the animals for the 20 known macaque (Mamu)-DQA1 alleles. Frequencies for four alleles (DQA1*240x, *2502, *2503 and *0102) differed significantly from those reported in a smaller sample of rhesus macaques from the German Primate Center. The modest genetic survey of Mamu-DQA1 genotypes presented here will be particularly useful in designing epidemiologic studies that investigate associations between immunogenetic background and disease susceptibility in macaque models of human disease.

  18. Allele frequencies of BRAFV600 mutations in primary melanomas and matched metastases and their relevance for BRAF inhibitor therapy in metastatic melanoma

    PubMed Central

    Satzger, Imke; Marks, Lena; Kerick, Martin; Klages, Sven; Berking, Carola; Herbst, Rudolf; Völker, Bernward; Schacht, Vivien; Timmermann, Bernd; Gutzmer, Ralf

    2015-01-01

    Background The detection of BRAFV600 mutations in patients with metastatic melanoma is important because of the availability of BRAF inhibitor therapy. However, the clinical relevance of the frequency of BRAFV600 mutant alleles is unclear. Patients and Methods Allele frequencies of BRAFV600 mutations were analyzed by ultra-deep next-generation sequencing in formalin-fixed, paraffin-embedded melanoma tissue (75 primary melanomas and 88 matched metastases). In a second study, pretreatment specimens from 76 patients who received BRAF inhibitors were retrospectively analyzed, and BRAFV600 allele frequencies were correlated with therapeutic results. Results Thirty-five patients had concordantly BRAF-positive and 36 (48%) patients had concordantly BRAF-negative primary melanomas and matched metastases, and four patients had discordant samples with low allele frequencies (3.4–5.2%). Twenty-six of 35 patients with concordant samples had BRAFV600E mutations, three of whom had additional mutations (V600K in two patients and V600R in one) and nine patients had exclusively non-V600E mutations (V600K in eight patients and V600E -c.1799_1800TG > AA- in one patient). The frequency of mutated BRAFV600 alleles was similar in the primary melanoma and matched metastasis in 27/35 patients, but differed by >3-fold in 8/35 of samples. BRAFV600E allele frequencies in pretreatment tumor specimens were not significantly correlated with treatment outcomes in 76 patients with metastatic melanoma who were treated with BRAF inhibitors. Conclusions BRAFV600 mutation status and allele frequency is consistent in the majority of primary melanomas and matched metastases. A small subgroup of patients has double mutations. BRAFV600 allele frequencies are not correlated with the response to BRAF inhibitors. PMID:26498143

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

    PubMed

    Joly, Simon; Bruneau, Anne

    2006-08-01

    Allelic variation within individuals holds information regarding the relationships of organisms, which is expected to be particularly important for reconstructing the evolutionary history of closely related taxa. However, little effort has been committed to incorporate such information for reconstructing the phylogeny of organisms. Haplotype trees represent a solution when one nonrecombinant marker is considered, but there is no satisfying method when multiple genes are to be combined. In this paper, we propose an algorithm that converts a distance matrix of alleles to a distance matrix among organisms. This algorithm allows the incorporation of allelic variation for reconstructing the phylogeny of organisms from one or more genes. The method is applied to reconstruct the phylogeny of the seven native diploid species of Rosa sect. Cinnamomeae in North America. The glyceralgehyde 3-phosphate dehydrogenase (GAPDH), the triose phosphate isomerase (TPI), and the malate synthase (MS) genes were sequenced for 40 individuals from these species. The three genes had little genetic variation, and most species showed incomplete lineage sorting, suggesting these species have a recent origin. Despite these difficulties, the networks (NeighborNet) of organisms reconstructed from the matrix obtained with the algorithm recovered groups that more closely match taxonomic boundaries than did the haplotype trees. The combined network of individuals shows that species west of the Rocky Mountains, Rosa gymnocarpa and R. pisocarpa, form exclusive groups and that together they are distinct from eastern species. In the east, three groups were found to be exclusive: R. nitida-R. palustris, R. foliolosa, and R. blanda-R. woodsii. These groups are congruent with the morphology and the ecology of species. The method is also useful for representing hybrid individuals when the relationships are reconstructed using a phylogenetic network. PMID:16969938

  20. Allele and haplotype frequencies for HLA-DQ in Iranian celiac disease patients

    PubMed Central

    Rostami-Nejad, Mohammad; Romanos, Jihane; Rostami, Kamran; Ganji, Azita; Ehsani-Ardakani, Mohammad Javad; Bakhshipour, Ali-Reza; Zojaji, Homayoun; Mohebbi, Seyed Reza; Zali, Mohammad-Reza; Wijmenga, Cisca

    2014-01-01

    AIM: To assess the distribution of human leukocyte antigen (HLA)-DQ2 and -DQ8 in Iranian celiac disease (CD) patients and compare them to healthy Iranian controls. METHODS: To predict the HLA-DQA1 and -DQB1 genes, we used six previously reported HLA-tagging single nucleotide polymorphism to determine HLA genotypes in 59 Iranian patients with ‘biopsy-confirmed’ CD and in 151 healthy Iranian individuals. To test the transferability of the method, 50 cases and controls were also typed using a commercial kit that identifies individual carriers of DQ2, DQ7 and DQ8 alleles. RESULTS: In this pilot study 97% of CD cases (n = 57) and 58% of controls (n = 87) were carriers of HLA-DQ2 and/or HLA-DQ8 heterodimers, either in the homozygous or heterozygous state. The HLA-DQ pattern of these 57 CD patients: heterozygous DQ2.2 (n = 14) and homozygous DQ2.2 (n = 1), heterozygous DQ2.5 (n = 33) and homozygous DQ2.5 (n = 8), heterozygous DQ8 (n = 13) and homozygous DQ8 (n = 2). Two CD patients were negative for both DQ2 and DQ8 (3%). CONCLUSION: The prevalence of DQ8 in our CD population was higher than that reported in other populations (25.4%). As reported in other populations, our results underline the primary importance of HLA-DQ alleles in the Iranian population’s susceptibility to CD. PMID:24876751

  1. 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

  2. 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

  3. 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.

  4. Solution of high frequency variations of ERP from VLBI observations

    NASA Astrophysics Data System (ADS)

    Zhang, B.; Li, J. L.; Wang, G. L.; Zhao, M.

    2005-01-01

    In the astrometric and geodetic VLBI data analysis software CALC/SOLVE, the high frequency variations of the Earth Rotation Parameters (ERP) are determined by a constrained continuous piecewise linear model. The ERP rate within two epoch nodes is constrained to be smaller than a limitation setting, and the ERP is forced to be continuous at epoch nodes. Observation analysis shows that when the data points are not very dense the constraint and the continuation requirement are helpful to the improvement in the stability of the solution, but degrade the independence of ERP solutions at epoch nodes as well. By using the Userpartial entry of CALC/SOLVE a direct solution module of the high frequency variations of ERP is realized without any constraint on the rate nor the requirement of continuation at nodes. It is shown from real observation reduction that the direct solution mode is feasible. In the solution of high frequency variations of ERP from VLBI observations with long period coverage, the model errors of the precession and nutation (celestial pole offset) should be taken into consideration. A corresponding module is realized and global solutions of the high frequency variation of ERP are successfully performed on the VLBI observations from 1979 to 2003. Comparison of the solutions shows that with the consideration of the pole offsets the precision of parameters could be improved obviously. In the solution of high frequency variation of ERP from VLBI observations, the direct solution mode with the consideration of the pole offsets is accordingly recommended.

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

    PubMed

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

    2014-01-01

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

  6. 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

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

    PubMed

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

    2014-08-01

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

  8. 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

  9. 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

  10. 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.

  11. Gene Expression Variation in Drosophila melanogaster Due to Rare Transposable Element Insertion Alleles of Large Effect

    PubMed Central

    Cridland, Julie M.; Thornton, Kevin R.; Long, Anthony D.

    2015-01-01

    Transposable elements are a common source of genetic variation that may play a substantial role in contributing to gene expression variation. However, the contribution of transposable elements to expression variation thus far consists of a handful of examples. We used previously published gene expression data from 37 inbred Drosophila melanogaster lines from the Drosophila Genetic Reference Panel to perform a genome-wide assessment of the effects of transposable elements on gene expression. We found thousands of transcripts with transposable element insertions in or near the transcript and that the presence of a transposable element in or near a transcript is significantly associated with reductions in expression. We estimate that within this example population, ∼2.2% of transcripts have a transposable element insertion, which significantly reduces expression in the line containing the transposable element. We also find that transcripts with insertions within 500 bp of the transcript show on average a 0.67 standard deviation decrease in expression level. These large decreases in expression level are most pronounced for transposable element insertions close to transcripts and the effect diminishes for more distant insertions. This work represents the first genome-wide analysis of gene expression variation due to transposable elements and suggests that transposable elements are an important class of mutation underlying expression variation in Drosophila and likely in other systems, given the ubiquity of these mobile elements in eukaryotic genomes. PMID:25335504

  12. 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

  13. Estimating Copy Number and Allelic Variation at the Immunoglobulin Heavy Chain Locus Using Short Reads.

    PubMed

    Luo, Shishi; Yu, Jane A; Song, Yun S

    2016-09-01

    The study of genomic regions that contain gene copies and structural variation is a major challenge in modern genomics. Unlike variation involving single nucleotide changes, data on the variation of copy number is difficult to collect and few tools exist for analyzing the variation between individuals. The immunoglobulin heavy variable (IGHV) locus, which plays an integral role in the adaptive immune response, is an example of a complex genomic region that varies in gene copy number. Lack of standard methods to genotype this region prevents it from being included in association studies and is holding back the growing field of antibody repertoire analysis. Here we develop a method that takes short reads from high-throughput sequencing and outputs a genetic profile of the IGHV locus with the read coverage depth and a putative nucleotide sequence for each operationally defined gene cluster. Our operationally defined gene clusters aim to address a major challenge in studying the IGHV locus: the high sequence similarity between gene segments in different genomic locations. Tests on simulated data demonstrate that our approach can accurately determine the presence or absence of a gene cluster from reads as short as 70 bp. More detailed resolution on the copy number of gene clusters can be obtained from read coverage depth using longer reads (e.g., ≥ 100 bp). Detail at the nucleotide resolution of single copy genes (genes present in one copy per haplotype) can be determined with 250 bp reads. For IGHV genes with more than one copy, accurate nucleotide-resolution reconstruction is currently beyond the means of our approach. When applied to a family of European ancestry, our pipeline outputs genotypes that are consistent with the family pedigree, confirms existing multigene variants and suggests new copy number variants. This study paves the way for analyzing population-level patterns of variation in IGHV gene clusters in larger diverse datasets and for quantitatively

  14. Estimating Copy Number and Allelic Variation at the Immunoglobulin Heavy Chain Locus Using Short Reads

    PubMed Central

    Luo, Shishi; Song, Yun S.

    2016-01-01

    The study of genomic regions that contain gene copies and structural variation is a major challenge in modern genomics. Unlike variation involving single nucleotide changes, data on the variation of copy number is difficult to collect and few tools exist for analyzing the variation between individuals. The immunoglobulin heavy variable (IGHV) locus, which plays an integral role in the adaptive immune response, is an example of a complex genomic region that varies in gene copy number. Lack of standard methods to genotype this region prevents it from being included in association studies and is holding back the growing field of antibody repertoire analysis. Here we develop a method that takes short reads from high-throughput sequencing and outputs a genetic profile of the IGHV locus with the read coverage depth and a putative nucleotide sequence for each operationally defined gene cluster. Our operationally defined gene clusters aim to address a major challenge in studying the IGHV locus: the high sequence similarity between gene segments in different genomic locations. Tests on simulated data demonstrate that our approach can accurately determine the presence or absence of a gene cluster from reads as short as 70 bp. More detailed resolution on the copy number of gene clusters can be obtained from read coverage depth using longer reads (e.g., ≥ 100 bp). Detail at the nucleotide resolution of single copy genes (genes present in one copy per haplotype) can be determined with 250 bp reads. For IGHV genes with more than one copy, accurate nucleotide-resolution reconstruction is currently beyond the means of our approach. When applied to a family of European ancestry, our pipeline outputs genotypes that are consistent with the family pedigree, confirms existing multigene variants and suggests new copy number variants. This study paves the way for analyzing population-level patterns of variation in IGHV gene clusters in larger diverse datasets and for quantitatively

  15. 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

  16. POPTREEW: web version of POPTREE for constructing population trees from allele frequency data and computing some other quantities.

    PubMed

    Takezaki, Naoko; Nei, Masatoshi; Tamura, Koichiro

    2014-06-01

    POPTREE software, including the command line (POPTREE) and the Windows (POPTREE2) versions, is available to perform evolutionary analyses of allele frequency data, computing distance measures for constructing population trees and average heterozygosity (H) (measure of genetic diversity within populations) and G(ST) (measure of genetic differentiation among subdivided populations). We have now developed a web version POPTREEW (http://www.med.kagawa-u.ac.jp/∼genomelb/takezaki/poptreew/) to provide cross-platform access to all POPTREE functions including interactive tree editing. Furthermore, new POPTREE software (POPTREE, POPTREE2, and POPTREEW) computes standardized G(ST) and Jost's D, which may be appropriate for data with high variability, and accepts genotype data in GENEPOP format as an input.

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

    PubMed

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

    2007-05-24

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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. Lower frequency of sister chromatid exchanges and altered frequency of HLA B-region alleles among individuals with sporadic dysplastic nevi.

    PubMed

    Illeni, M T; Rovini, D; Di Lernia, M; Cascinelli, N; Ghidoni, A

    1997-01-01

    Sister chromatid exchanges (SCE) were analyzed in peripheral blood lymphocytes of 24 individuals, following diagnosis, and prior to surgical removal, of a sporadic dysplastic nevus (DN). Lower SCE values and variability were found in 23 sporadic DN individuals compared with controls (2.52 +/- 0.12 and 3.76 +/- 0.22 SCE/cell, respectively). These DN individuals, contrarily to healthy controls and some types of tumor patients whose cells are hypersensitive to mutagenic agents, did not show increased SCE rates as a consequence of cigarette smoking, alcohol consumption and diagnostic radiation treatments. These observations are in contrast with clinical evidence that similar lesions are both markers or risk and precursors of malignancy in individuals with multiple nevi, affected by the dysplastic nevus syndrome (DNS) or belonging to FMM (familial malignant melanoma) families. Three HLA class I alleles out of 72 tested were found more frequently in sporadic DN individuals compared with controls: B37 (p < 0.05), B52 (p < 0.01) and B70 (p < 0.01). Whether the greater chromosomal stability (as shown by the SCE analysis), and/or the altered frequency of some HLA alleles could influence the chance of developing cutaneous malignancy in DN individuals is yet to be evaluated.

  4. 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

  5. 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

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

    PubMed

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

    2014-05-01

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

  7. Gene frequencies of ABO and Rh (D) blood group alleles in a healthy infant population in Ibadan, Nigeria.

    PubMed

    Omotade, O O; Adeyemo, A A; Kayode, C M; Falade, S L; Ikpeme, S

    1999-01-01

    The ABO and Rhesus blood group systems remain the most important blood group systems clinically. In order to provide gene frequency values for the ABO and Rh (D) alleles in a healthy infant population in south west Nigeria, 4748 healthy infants were typed for ABO and Rh (D) blood groups over a five year period (1988-1992). Overall, 2575 (54.2%) were blood group O, 1023 (21.6%) were blood group A, 1017 (21.4%) were blood group B and 133 (2.8%) were blood group AB. The distribution of the ABO blood groups did not differ significantly from those expected under the Hardy Weinberg equilibrium (Goodness-of-fit X2 = 6.09, df = 3, p = 0.1075). The proportions of the infants belonging to the various ABO blood groups did not vary significantly over the period of the study (X2 = 14.53, df = 12, p = 0.268). Overall gene frequencies for the O, A and B genes were 0.7398, 0.1305 and 0.1298 respectively. For the Rh (D) gene, 4520 (95.2%) were Rh-positive while 228 (4.8%) were Rh-negative. However, the proportions of Rh (D) negative infants varied significantly over the period of the study, with a particular year (1991) having nearly twice the usual frequency of Rh-negative individuals (X2 = 31.17, df =, p < 0.001). The frequency of the Rh (D) gene was 0.7809. These figures are reported in the hope that they may find some use as reference for studies of ABO blood groups in health and disease, especially since they were obtained in an infant population in which it is expected that selection pressures should not have started to act to any significant extent.

  8. Apolipoprotein E Allelic Frequency Altered in Women with Early-onset Breast Cancer.

    PubMed

    Porrata-Doria, Tirtsa; Matta, Jaime L; Acevedo, Summer F

    2010-05-24

    Among women, the most prevalent type of cancer is breast cancer, affecting 1 out of every 8 women in the United States; in Puerto Rico, 70 out of every 100,000 will develop some type of breast cancer. Therefore, a better understand of the potential risk factors for breast cancer could lead to the development of early detection tools. A gene that has been proposed as a risk factor in several populations around the world is Apolipoprotein E (apoE). ApoE functions as a mechanism of transport for lipoproteins and cholesterol throughout the body, with 3 main isoforms present in humans (apoE2, apoE3, and apoE4). Whether or not apoE4 is a risk factor for breast cancer remains controversial. Previous studies have either included test subjects of all ages (20-80) or have focused on late-onset (after age 50) breast cancer; none has concentrated specifically on early-onset (aged 50 and younger) breast cancer. The objectives of this study was to examine (in a Puerto Rican population) the differences in the relative frequency of occurrence of apoE4 in non-breast cancer versus breast cancer patients and to examine, as well, the potential differences of same in early- versus late-onset patients. We found an increased frequency of apoE4 (odds ratio 2.15) only in early-onset breast cancer survivors, which is similar to the findings of those studies that combined or adjusted for age as well as for an association between apoE4 and decreased tumor size. ApoE is also a potential risk factor for long-term cognitive effects after chemotherapy and affects response to hormone replacement. Our data supports the theory that knowing the apoE genotype of women who are at risk of developing breast cancer may be beneficial, as such knowledge would aid in the prediction of tumor size and the development of treatment regimens.

  9. Allele and genotype frequencies of CYP2C9, CYP2C19 and CYP2D6 in an Italian population.

    PubMed

    Scordo, Maria Gabriella; Caputi, Achille P; D'Arrigo, Concetta; Fava, Giuseppina; Spina, Edoardo

    2004-08-01

    The polymorphic cytochrome P450 isoenzymes (CYPs) 2C9, 2C19 and 2D6 metabolise many important drugs, as well as other xenobiotics. Their polymorphism gives rise to important interindividual and interethnic variability in the metabolism and disposition of several therapeutic agents and may cause differences in the clinical response to these drugs. In this study, we determined the genotype profile of a random Italian population in order to compare the CYP2C9, CYP2C19 and CYP2D6 allele frequencies among Italians with previous findings in other Caucasian populations. Frequencies for the major CYP2C9, CYP2C19 and CYP2D6 mutated alleles and genotypes have been evaluated in 360 unrelated healthy Italian volunteers (210 males and 150 females, aged 19-52 years). Genotyping has been carried out on peripheral leukocytes DNA by molecular biology techniques (PCR, RFLP, long-PCR). CYP2C9, CYP2C19 and CYP2D6 allele and genotype frequencies resulted in equilibrium with the Hardy-Weinberg equation. One hundred and fourteen subjects (31.7%) carried one and 23 subjects (6.4%) carried two CYP2C9 mutated alleles. Sixty-eight (18.9%) volunteers were found to be heterozygous and six (1.7%) homozygous for the CYP2C19*2, while no CYP2C19*3 was detected in the evaluated population. Volunteers could be divided into four CYP2D6 genotypes groups: 192 subjects (53.3%) with no mutated alleles (homozygous extensive metabolisers, EM), 126 (35.0%) with one mutated allele (heterozygous EM), 12 (3.4%) with two mutated alleles (poor metabolisers, PM) and 30 (8.3%) with extracopies of a functional gene (ultrarapid metabolisers, UM). Frequencies of both CYP2C9 and CYP2C19 allelic variants, as well as CYP2D6 detrimental alleles, in Italian subjects were similar to those of other Caucasian populations. Conversely, the prevalence of CYP2D6 gene duplication among Italians resulted very high, confirming the higher frequency of CYP2D6 UM in the Mediterranean area compared to Northern Europe. PMID:15177309

  10. Ultra-deep Illumina sequencing accurately identifies MHC class IIb alleles and provides evidence for copy number variation in the guppy (Poecilia reticulata).

    PubMed

    Lighten, Jackie; van Oosterhout, Cock; Paterson, Ian G; McMullan, Mark; Bentzen, Paul

    2014-07-01

    We address the bioinformatic issue of accurately separating amplified genes of the major histocompatibility complex (MHC) from artefacts generated during high-throughput sequencing workflows. We fit observed ultra-deep sequencing depths (hundreds to thousands of sequences per amplicon) of allelic variants to expectations from genetic models of copy number variation (CNV). We provide a simple, accurate and repeatable method for genotyping multigene families, evaluating our method via analyses of 209 b of MHC class IIb exon 2 in guppies (Poecilia reticulata). Genotype repeatability for resequenced individuals (N = 49) was high (100%) within the same sequencing run. However, repeatability dropped to 83.7% between independent runs, either because of lower mean amplicon sequencing depth in the initial run or random PCR effects. This highlights the importance of fully independent replicates. Significant improvements in genotyping accuracy were made by greatly reducing type I genotyping error (i.e. accepting an artefact as a true allele), which may occur when using low-depth allele validation thresholds used by previous methods. Only a small amount (4.9%) of type II error (i.e. rejecting a genuine allele as an artefact) was detected through fully independent sequencing runs. We observed 1-6 alleles per individual, and evidence of sharing of alleles across loci. Variation in the total number of MHC class II loci among individuals, both among and within populations was also observed, and some genotypes appeared to be partially hemizygous; total allelic dosage added up to an odd number of allelic copies. Collectively, observations provide evidence of MHC CNV and its complex basis in natural populations.

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-06-01

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

  13. 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.

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

    PubMed Central

    Kiesler, Kevin M.; Vallone, Peter M.

    2013-01-01

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

  15. 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.

  16. 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

  17. Variant allele frequency enrichment analysis in vitro reveals sonic hedgehog pathway to impede sustained temozolomide response in GBM

    PubMed Central

    Biswas, Nidhan K.; Chandra, Vikas; Sarkar-Roy, Neeta; Das, Tapojyoti; Bhattacharya, Rabindra N.; Tripathy, Laxmi N.; Basu, Sunandan K.; Kumar, Shantanu; Das, Subrata; Chatterjee, Ankita; Mukherjee, Ankur; Basu, Pryiadarshi; Maitra, Arindam; Chattopadhyay, Ansuman; Basu, Analabha; Dhara, Surajit

    2015-01-01

    Neoplastic cells of Glioblastoma multiforme (GBM) may or may not show sustained response to temozolomide (TMZ) chemotherapy. We hypothesize that TMZ chemotherapy response in GBM is predetermined in its neoplastic clones via a specific set of mutations that alter relevant pathways. We describe exome-wide enrichment of variant allele frequencies (VAFs) in neurospheres displaying contrasting phenotypes of sustained versus reversible TMZ-responses in vitro. Enrichment of VAFs was found on genes ST5, RP6KA1 and PRKDC in cells showing sustained TMZ-effect whereas on genes FREM2, AASDH and STK36, in cells showing reversible TMZ-effect. Ingenuity pathway analysis (IPA) revealed that these genes alter cell-cycle, G2/M-checkpoint-regulation and NHEJ pathways in sustained TMZ-effect cells whereas the lysine-II&V/phenylalanine degradation and sonic hedgehog (Hh) pathways in reversible TMZ-effect cells. Next, we validated the likely involvement of the Hh-pathway in TMZ-response on additional GBM neurospheres as well as on GBM patients, by extracting RNA-sequencing-based gene expression data from the TCGA-GBM database. Finally, we demonstrated TMZ-sensitization of a TMZ non-responder neurosphere in vitro by treating them with the FDA-approved pharmacological Hh-pathway inhibitor vismodegib. Altogether, our results indicate that the Hh-pathway impedes sustained TMZ-response in GBM and could be a potential therapeutic target to enhance TMZ-response in this malignancy. PMID:25604826

  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. 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

  20. 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

  1. Allele variation of DYS19 and Y-Alu insertion (YAP) polymorphisms in Basques: an insight into the peopling of Europe and the Mediterranean region.

    PubMed

    Calderón, R; Carrion, M; Perez-Miranda, A; Peña, J A; Dugoujon, J M; Crouau-Roy, B

    2003-02-01

    Two Y-chromosome DNA polymorphisms, the DYS19 microsatellite and the YAP (at locus DYS287), were tested in males from two autochthonous Basque populations from France and northern Navarre (Spain). The results are compared to those obtained for the same genetic markers in 32 populations from Europe, northern Africa, and western Asia. The high predominance of the DYS19*11 (190-base-pair) allele in Basques indicates that their genetic diversity for microsatellite DYS19 is around half that observed in Europeans, North Africans, and western Asians. The Y-Alu insertion (YAP+) was not detected in the Basque samples. This study attempts to throw some light on the importance of historically recent migratory movements, the main corridors of gene flow, and demographic sizes and their variations in shaping gene frequency patterns in contemporary human populations, particularly in the Mediterranean region. Historical processes may have had more significant effects on the genetic make-up of current human populations than those of prehistoric times.

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

    PubMed

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

    2015-06-01

    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.

  3. 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

  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. 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

  6. 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

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

    PubMed

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

    2016-01-01

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

  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. 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.

  10. Identification of the Variations in the CPT1B and CHKB Genes Along with the HLA-DQB1*06:02 Allele in Turkish Narcolepsy Patients and Healthy Persons

    PubMed Central

    Agilkaya, Sinem; Oztura, Ibrahim; Eroglu, Secil; Karadeniz, Derya; Evlice, Ahmet; Altungoz, Oguz; Yilmaz, Hikmet; Baklan, Baris

    2014-01-01

    Background: The HLA-DQB1*06:02 allele across all ethnic groups and the rs5770917 variation between CPT1B and CHKB genes in Japanese and Koreans are common genetic susceptibility factors for narcolepsy. This comprehensive genetic study sought to assess variations in CHKB and CPT1B susceptibility genes and HLA-DQB1*06:02 allele status in Turkish patients with narcolepsy and healthy persons. Methods: CHKB/CPT1B genes were sequenced in patients with narcolepsy (n=37) and healthy persons (n=100) to detect variations. The HLA-DQB1*06:02 allele status was determined by sequence specific polymerase chain reaction. Results: The HLA-DQB1*06:02 allele was significantly more frequent in narcoleptic patients than in healthy persons (p=2×10−7) and in patients with narcolepsy and cataplexy than in those without (p=0.018). The mean of the multiple sleep latency test, sleep-onset rapid eye movement periods, and frequency of sleep paralysis significantly differed in the HLA-DQB1*06:02–positive patients. rs5770917, rs5770911, rs2269381, and rs2269382 were detected together as a haplotype in three patients and 11 healthy persons. In addition to this haplotype, the indel variation (rs144647670) was detected in the 5′ upstream region of the human CHKB gene in the patients and healthy persons carrying four variants together. Conclusion: This study identified a novel haplotype consisting of the indel variation, which had not been detected in previous studies in Japanese and Korean populations, and observed four single-nucleotide polymorphisms in CHKB/CPT1B. The study confirmed the association of the HLA-DQB1*06:02 allele with narcolepsy and cataplexy susceptibility. The findings suggest that the presence of HLA-DQB1*06:02 may be a predictor of cataplexy in narcoleptic patients and could therefore be used as an additional diagnostic marker alongside hypocretin. PMID:24571861

  11. Increased frequency of co-existing JAK2 exon-12 or MPL exon-10 mutations in patients with low JAK2(V617F) allelic burden.

    PubMed

    Nussenzveig, Roberto H; Pham, Ha T; Perkins, Sherrie L; Prchal, Josef T; Agarwal, Archana M; Salama, Mohamed E

    2016-01-01

    The frequency of co-existing JAK2(V617F)/MPL and JAK2(V617F)/JAK2 exon-12 mutations has not been previously investigated in MPNs. Poor survival was reported in primary myelofibrosis with low JAK2(V617F) allelic burden. However, mutational status of JAK2 exon-12 or MPL were not reported in these patients. This study developed a cost-effective multiplex high resolution melt assay that screens for mutations in JAK2 gene exons-12 and -14 ((V617F)) and MPL gene exon-10. Co-existing mutations with JAK2(V617F) were detected in 2.9% (6/208; two JAK2 exon-12 and four MPL exon-10) patient specimens with known JAK2(V617F) (allelic-burden range: 0.1-96.8%). Co-existing mutations were detected in specimens with < 12% JAK2(V617F) allelic burden. Current WHO guidelines do not recommend further testing once JAK2(V617F) mutation is detected in MPNs. The findings, however, indicate that quantification of JAK2(V617F) allele burden may be clinically relevant in MPNs and in those with low allelic burden additional testing for JAK2 exon-12 and MPL exon-10 mutation should be pursued.

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

    SciTech Connect

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

    1994-03-01

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

  13. A microsatellite polymorphism in the von Willebrand factor gene: comparison of allele frequencies in different population samples and evaluation for forensic medicine.

    PubMed

    Sajantila, A; Pacek, P; Lukka, M; Syvänen, A C; Nokelainen, P; Sistonen, P; Peltonen, L; Budowle, B

    1994-09-16

    The allele frequencies at the tetranucleotide repeat (TCTA) vWA locus in the vWF gene were determined in the general Finnish population, in a population representing an internal isolate of Finland, in the Vologda-Russian population, and in US Black population samples. The allele and genotype frequencies from these population samples were compared with each other and with those reported from Spanish and British population samples. Statistically significant differences were demonstrated between most of the different groups (Finns vs. Vologda-Russians, Finns vs. US Blacks, Finns vs. Spanish, Vologda-Russians vs. US Blacks, Vologda-Russians vs. Spanish, US Blacks vs. Spanish and US Blacks vs. British Caucasians), but not between the two Caucasoid population samples from Finland and Great Britain, nor between or within the subpopulation samples from Finland and those from Vologda-Russia. In addition, the vWA marker was evaluated and demonstrated to be reliable for forensic purposes and paternity testing.

  14. 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

  15. 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

  16. 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

  17. Allele frequencies of the major milk proteins in the Finnish Ayrshire and detection of a new kappa-casein variant.

    PubMed

    Ikonen, T; Ruottinen, O; Erhardt, G; Ojala, M

    1996-06-01

    A total of 20990 Finnish Ayrshire cows were phenotyped for the major milk proteins by isoelectric focusing in polyacrylamide gels. The predominant alleles in the Finnish Ayrshire were alpha S1-casein B (0.999), alpha S2-casein A (0.991), beta-casein A1 (0.509) and alpha 2 (0.490), kappa-casein A (0.612) and beta-lactoglobulin B (0.716). The kappa-casein E allele (0.307) was also rather common in the Finnish Ayrshire. A new kappa-casein variant (kappa-casein F) was demonstrated in two Finnish Ayrshire cows, a dam and a daughter.

  18. Frequency variations of discrete cranial traits in major human populations. II. Hypostotic variations

    PubMed Central

    HANIHARA, TSUNEHIKO; ISHIDA, HAJIME

    2001-01-01

    Five discrete hypostotic cranial traits, tympanic dehiscence, ovale-spinosum confluence, metopism, transverse zygomatic suture vestige, and biasterionic suture, were investigated in 81 human population samples. Except for ovale-spinosum confluence, marked asymmetric occurrences of the bilateral traits were not detected in the majority of the samples. Significant intertrait association was observed mainly between the biasterionic suture and other sutural variations including accessory ossicles. The traits showing relatively consistent sex differences across diverse populations were tympanic dehiscence, which is predominant in females, and biasterionic suture in males. On a world scale, the 5 hypostotic cranial traits showed distinctive patterns of geographical variation. Different clinal variations within and between macrogeographical areas such as western and eastern parts of the Old World were found for the frequencies of the traits. The Ainu may be the most distinct outlier in the eastern Asian region on the basis of the incidence of the traits, especially the transverse zygomatic suture vestige. The interregional variation without reasonable adaptive value and nonadaptive shift of the possible outliers presented in this study suggest that the genetic background for the occurrence of these traits cannot be excluded completely. PMID:11465863

  19. 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

  20. The frequency of the mitochondrial aldehyde dehydrogenase I2 (atypical) allele in Caucasian, Oriental and African black populations determined by the restriction profile of PCR-amplified DNA.

    PubMed

    Dandré, F; Cassaigne, A; Iron, A

    1995-06-01

    The aldehyde dehydrogenase I (ALDH I) gene codes for a mitochondrial enzyme which plays a major role in hepatic alcohol detoxication. It has been related to alcohol flushing in Orientals bearing the atypical ALDH I2 gene. The variant protein results from a lysine for glutamate substitution at position 487 (G-->A change in exon 12). A procedure for ALDH I2 detection consisting in a differentiation between the 'atypical' allele and the 'wild' allele has been improved through PCR and subsequent MboII digestion. Blood samples collected on anticoagulant or directly absorbed on blotting paper were used for DNA amplification in the presence of two specific oligonucleotidic primers, each one able to incorporate a restriction site in the amplimer. After MboII digestion, PCR products were separated by polyacrylamide gel electrophoresis and then visualized with ethidium bromide. This technique permits a rapid and non-radioactive detection of atypical ALDH I2 on a PCR product without the use of allele specific oligonucleotides. It was applied to the study of ALDH I2 allele frequency in random population samples of three ethnic groups: Caucasians, Orientals and African blacks.

  1. Allele-related variation in minisatellite repeats involved in the transcription of the blood group ABO gene.

    PubMed

    Irshaid, N M; Chester, M A; Olsson, M L

    1999-09-01

    Since the cloning in 1990 of cDNA corresponding to mRNA transcribed at the blood group ABO locus, polymorphisms at the ABO locus and phenotype-genotype correlation have been analysed by several investigators. An enhancer-active minisatellite motif reported to contain four 43-bp repeats has been analysed by PCR in blood samples from 160 random Swedish blood donors. Different sizes of the DNA fragments obtained led to further analysis by direct sequencing. Fragments with either one or four 43-bp repeats were identified. A nucleotide substitution (G-->A) at nt. 41 of 43 was found in all alleles with only one repeat. Correlation with the ABO genotypes of the samples, as determined by a panel of ABO genotyping techniques, revealed an allele-related variable number of tandem repeats (VNTR). The A1 and the infrequent O2 allele had only one repeat whilst A2, B, O1 and O1v had four repeats and thus generated longer (by 129 bp) fragments. A further 74 samples obtained from various geographical areas/ethnic groups indicated a widespread correlation with few exceptions. In conclusion, a novel ABO polymorphism located in the 5'-nontranslated region involved in transcriptional regulation of the ABO gene is reported and its relationship to common alleles at this locus defined.

  2. 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

  3. 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

  4. Allele and Haplotype Frequencies of Human Leukocyte Antigen-A, -B, -C, -DRB1, and -DQB1 From Sequence-Based DNA Typing Data in Koreans

    PubMed Central

    In, Ji Won; Roh, Eun Youn; Oh, Sohee; Shin, Sue; Park, Kyoung Un

    2015-01-01

    Background Data on allele frequencies (AFs) and haplotype frequencies (HFs) of HLA-C and -DQB1 are limited in Koreans. We investigated AFs and HFs of HLA-A, -B, -C, -DRB1, and -DQB1 in Koreans by high-resolution sequence-based typing (SBT). Methods Hematopoietic stem cells were obtained from 613 healthy, unrelated donors to analyze HLA-A, -B, -C, -DRB1, and -DQB1 genotypes by using AlleleSEQR HLA-A, -B, -C, -DRB1, and -DQB1 SBT kits (Abbott Molecular, USA), respectively. Alleles belonging to HLA-C*07:01/07:06 group were further discriminated by using PCR-sequence specific primer analysis. AFs and HFs were calculated by direct counting and maximum likelihood method, respectively. Results In all, 24 HLA-A, 46 HLA-B, 24 HLA-C, 29 HLA-DRB1, and 15 HLA-DQB1 alleles were identified. AFs and HFs of HLA-A, -B, and -DRB1 were similar to those reported previously. For the HLA-C locus, C*01:02 was the most common allele, followed by C*03:03, C*03:04, C*14:02, C*03:02, and C*07:02 (AF ≥7%). AFs of C*07:01 and C*07:06 were 0.16% and 3.18%, respectively. For the HLA-DQB1 locus, DQB1*03:01 was the most common allele, followed by DQB1*03:03, *03:02, *06:01, *05:01, *04:01, and *06:02 (AF ≥7%). AFs of DQB1*02:01 and DQB1*02:02 were 2.12% and 6.69%, respectively. HFs of A*33:03-C*07:06 and C*07:06-B*44:03 were 3.09% and 3.10%, respectively, while those of DRB1*07:01-DQB1*02:02 and DRB1*03:01-DQB1*02:01 were 6.61% and 2.04%, respectively. Conclusions This study reported AFs and HFs of HLA, including HLA-C and -DQB1, in Koreans by using high-resolution SBT. These data can be used to resolve ambiguous results of HLA typing for organ and hematopoietic stem cell transplantations. PMID:26131415

  5. 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

  6. 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

  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. Loss of MHC and neutral variation in Peary caribou: genetic drift is not mitigated by balancing selection or exacerbated by MHC allele distributions.

    PubMed

    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.

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

    PubMed

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

    2010-07-01

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

  10. 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

  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. 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

  13. Association between allelic variation at the Phytoene synthase 1 gene and yellow pigment content in the wheat grain.

    PubMed

    Zhang, W; Dubcovsky, J

    2008-03-01

    A better understanding of the genetic factors controlling grain yellow pigment content (GYPC) is important for both pasta (high GYPC) and bread wheat (low GYPC) quality improvement. Quantitative trait loci (QTL) for GYPC have been mapped repeatedly on the distal regions of chromosome arms 7AL and 7BL in wheat, and the Phytoene synthase 1 (PSY-1) gene located in this region has been proposed as a candidate gene. We show here that PSY-E1, the tall wheatgrass orthologue, is completely linked to differences in GYPC, and that selection for white endosperm mutants in recombinant lines carrying this gene resulted in the identification of a mutation in a conserved amino acid of PSY-E1. These results, together with the association between GYPC and allelic differences in PSY-1 in hexaploid wheat, suggest that this gene plays an important role in the determination of GYPC. However, a second white endosperm mutant previously mapped to chromosome arm 7EL showed no mutations in PSY-E1 suggesting the existence of additional gene(s) affecting GYPC in this chromosome region. This hypothesis was further supported by the mapping of QTL for GYPC on 7AL proximal to PSY-1 in a cross between pasta wheat varieties UC1113 and Kofa. Interestingly, the Kofa PSY-B1 allele showed unusually high levels of polymorphisms as a result of a conversion event involving the PSY-A1 allele. In summary, our results support the hypothesis that allelic differences in PSY-1 and at least one additional gene in the distal region of the long arm of homoeologous group 7L are associated with differences in GYPC. PMID:18193186

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

    PubMed

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

    2014-01-01

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

  15. Allelic frequency of the MCP-1 promoter -2518 polymorphism in the Turkish population and in Turkish patients with juvenile rheumatoid arthritis.

    PubMed

    Ozyürek, A Ruhi; Gürses, Dolunay; Ulger, Zülal; Levent, Ertürk; Bakiler, A Rahmi; Berdeli, Afig

    2007-04-01

    Although genetic and environmental factors contribute to the pathogenesis of juvenile rheumathoid arthritis (JRA), the etiology and pathogenesis remain controversial. The objective of this study was to investigate genotypic and allelic frequencies of monocyte chemoattractant protein-1 (MCP-1) gene -2518 (G/A) polymorphism in the healthy Turkish population and patients with JRA. Genomic DNA was collected from 66 JRA patients and 150 healthy individuals. To evaluate the association of the -2518 (G/A) MCP-1 gene polymorphism with the outcome of JRA, we analyzed the types of JRA and the score on the childhood health assessment questionnaire (C-HAQ score). In the healthy Turkish population, the frequencies of A and G alleles were 71 and 29%, respectively. No significant difference was observed between the JRA patients and healthy subjects in the distribution allelic and genotypic frequencies of the -2518 (G/A) MCP-1 gene polymorphism (p>0.05). However, the AG genotype was found to be higher and the AA genotype was found to be lower in the patients with systemic type JRA compared to those with the other types of JRA (p=0.019). When the JRA patients were evaluated according to the C-HAQ score, we found that the -2518 (G/A) MCP-1 gene polymorphism did not relate the prognosis (p>0.05). AG genotype was found to be higher in the systemic type of JRA. The results indicate that MCP-1 gene polymorphism might slightly associate with patients with systemic JRA. Further studies are needed to elucidate the role of this polymorphism in the pathogenesis of JRA in various populations because this polymorphism has a functional significance and an ethnic difference.

  16. 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

  17. 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

  18. 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.

  19. Allele and haplotype frequencies of HLA-A, B, C, DRB1 and DQB1 genes in polytransfused patients in ethnically diverse populations from Brazil.

    PubMed

    Rodrigues, C; Macedo, L C; Bruder, A V; Quintero, F d C; de Alencar, J B; Sell, A M; Visentainer, J E L

    2015-10-01

    The red blood transfusion is a practice often used in patients with haematological and oncological diseases. However, the investigation of human leucocyte antigen (HLA) system frequency in these individuals is of great importance because multiple transfusions may lead to HLA alloimmunization. Brazil is a country that was colonized by many other ethnicities, leading to a mixed ethnicity and regionalized population. In view of the importance of HLA typing in these patients, the aim of this study was to investigate the allele and haplotype frequencies from polytransfused patients from three different regions from Brazil. HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 genotyping of 366 patients was performed by PCR-SSO, based on the Luminex technology (One Lambda(®) ), and the anti-HLA class I and class II antibodies were analysed using LabScreen Single Antigen Antibody Detection (One Lambda, Inc.). Allele and haplotype frequencies of polytransfused patients of three regions from Brazil were obtained using the Arlequin program. The most frequent allele frequencies observed were HLA-A*02, A*03, B*15, B*35, B*51, C*07, C*04, C*03, DRB1*13, DRB1*11, DRB1*07, DRB1*03, DRB1*01, DQB1*03, DQB1*02, DQB1*06 and DQB1*05. There were differences between the groups for allele variants HLA-B*57 (between Group 1 and Group 2) and HLA-C*12 (between Group 1 and Group 3). The most frequent haplotypes found in the sample were HLA-A*01B*08DRB1*03, DRBI*07DQB1*02, DRB1*01DQB1*05, DRB1*13DQB1*06 and A*02B*35. HLA class I and II antibodies were detected in 77.9% and 63.9% patients, respectively, while the both alloantibodies were detected in 62 (50.9%) patients. In conclusion, the HLA typing for polytransfused patients in each region has a great importance, as seen in this study; individuals from different regions from Brazil have HLA distribution not completely homogeneous.

  20. 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

  1. 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.

  2. 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.

  3. 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…

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Allelic frequencies of the HLA-B17 antigen group: comparative analysis by serology, IEF and PCR-SSOP typing.

    PubMed

    Levine, J E; Yang, S Y

    1995-11-01

    Current typing technology for class I HLA antigens uses serological and/or isoelectric focusing gel electrophoresis. DNA typing for the HLA class I antigens can accurately identify the class I genotype of individuals and cell lines. Here, we report correlation of DNA typing results with serological and IEF results for the B17 group. The B17 antigens are relatively common, being carried by almost 9% of Caucasians and 28% of blacks. In this study, five 10th International Histocompatibility Workshop cell lines carrying B17 and 106 individuals in 61 families carrying B17 were DNA typed for B17 using B17-allele-specific amplification and sequence specific oligonucleotide probe hybridization pattern analysis. 38 (55.07%) out of 69 unrelated haplotypes had B*5701, 23 (33.33%) had B*5801, 6 (8.70%) had B*5702, and 2 (2.90%) had B*5802. DNA typing results correlated well with serological and isoelectric focusing results. In general, there was high degree of agreement between all three methods, although heterozygosity for B17 poses a particular problem for serological and IEF methodology. Both B*5701 and B*5801 have the same electrophoretic mobility on IEF gel, corresponding to B17.2, B*5702 corresponds to B17.1, while B*5802 corresponds to B17.3.

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

    PubMed Central

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

    2002-01-01

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

  10. Allelic Diversity and Its Implications for the Rate of Adaptation

    PubMed Central

    Caballero, Armando; García-Dorado, Aurora

    2013-01-01

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

  11. Allelic variation at the interleukin 1β gene is associated with decreased bone mass in patients with inflammatory bowel diseases

    PubMed Central

    Nemetz, A; Toth, M; Garcia-Gonzalez, M; Zagoni, T; Feher, J; Pena, A; Tulassay, Z

    2001-01-01

    BACKGROUND—Interleukin 1β (IL-1β) and its natural antagonist have been implicated in the pathogenesis of inflammatory bowel disease (IBD). Both cytokines influence bone formation. IL-1β stimulates osteoclast activity while interleukin 1 receptor antagonist (IL-1ra) enhances bone formation.
AIMS—To determine whether the decreased bone mass in IBD is related to gene polymorphisms coding for IL-1β and IL-1ra, and thus identify patients with an increased risk.
METHODS—Bone mineral densitometry was performed at the femoral neck, lumbar spine, and the distal third of the radius in 75 IBD patients (34 men/41 women; 40.3 (1.6) years) and in 58 healthy controls (HC; 28 men/30 women; 32.4 (1.2) years). Values were correlated with the TaqI and AvaI gene polymorphisms in the IL1B and the variable number of tandem repeats gene polymorphism in the IL1RN gene.
RESULTS—In IBD patients, but not in HC, carriers of allele 2 at the AvaI gene polymorphism (IL1B-511*2) had significantly lower Z scores at the lumbar spine (−0.82 (0.13) v −0.29 (0.21) p=0.03) and the femoral neck (−0.59 (0.14) v 0.15 (0.19); p=0.003) than non-carriers. These patients also had a higher risk for osteopenia or osteoporosis at the femoral neck (odds ratio 3.63 (95% confidence interval 0.95-13.93)). No association was found between bone mass and the other gene polymorphisms analysed in IBD patients or in HC.
CONCLUSIONS—Our results suggest that genetic variability may be a major determinant of bone loss in IBD. Carriers of IL1B-511*2, who are hypersecretors of IL-1β, have a higher risk of presenting with low bone mass in IBD. Screening for this allele may contribute to determination of the risk of bone loss at the time of disease onset.


Keywords: inflammatory bowel diseases; ulcerative colitis; Crohn's disease; osteoporosis; bone density; genetic polymorphisms; interleukin 1 PMID:11600466

  12. 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

  13. 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

  14. Multi-Allelic Major Effect Genes Interact with Minor Effect QTLs to Control Adaptive Color Pattern Variation in Heliconius erato

    PubMed Central

    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

  15. 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

  16. 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...

  17. 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

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

    PubMed

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

    2014-07-01

    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.

  19. Variation in ion leakage parameters of two wheat genotypes with different Rht-B1 alleles in response to drought.

    PubMed

    Kocheva, Konstantina V; Landjeva, Svetlana P; Georgiev, Georgi I

    2014-12-01

    The reaction to soil drying was evaluated in two Triticum aestivum near-isogenic lines carrying different alleles of the height-reducing gene Rht-B1 based on an improved method for assessment of electrolyte leakage. The two lines were previously shown to differ in their physiological responses to induced water deficit stress. Drought was imposed for 6 days on 10-day-old seedlings. Ion efflux from leaves was measured conductometrically in multiple time points during the 24 h incubation period, and the obtained biphasic kinetics was interpreted according to a previously developed theoretical model proposing different leakage rates through the apoplast and the symplast. Most of the model parameters were able to properly differentiate the two closely related genotypes. The mutant Rht-B1c displayed lower and slower electrolyte leakage in comparison with the wild-type Rht-B1a. It was speculated that the Rht genes expressing defective DELLA proteins might be involved in water stress response through modulation of cell wall stiffness, which influences its capacity for ions retention, and also by their contribution to ROS detoxification, thus indirectly stabilizing cellular membranes. The presented analytical approach relating processes of ion and water flow in and out of the cell could be used for characterization of membrane and cell wall properties of different genotypes under normal and stress conditions.

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. High Frequency Variations in Earth Orientation Derived From GNSS Observations

    NASA Astrophysics Data System (ADS)

    Weber, R.; Englich, S.; Snajdrova, K.; Boehm, J.

    2006-12-01

    Current observations gained by the space geodetic techniques, especially VLBI, GPS and SLR, allow for the determination of Earth Orientation Parameters (EOPs - polar motion, UT1/LOD, nutation offsets) with unprecedented accuracy and temporal resolution. This presentation focuses on contributions to the EOP recovery provided by satellite navigation systems (primarily GPS). The IGS (International GNSS Service), for example, currently provides daily polar motion with an accuracy of less than 0.1mas and LOD estimates with an accuracy of a few microseconds. To study more rapid variations in polar motion and LOD we established in a first step a high resolution (hourly resolution) ERP-time series from GPS observation data of the IGS network covering the period from begin of 2005 till March 2006. The calculations were carried out by means of the Bernese GPS Software V5.0 considering observations from a subset of 79 fairly stable stations out of the IGb00 reference frame sites. From these ERP time series the amplitudes of the major diurnal and semidiurnal variations caused by ocean tides are estimated. After correcting the series for ocean tides the remaining geodetic observed excitation is compared with variations of atmospheric excitation (AAM). To study the sensitivity of the estimates with respect to the applied mapping function we applied both the widely used NMF (Niell Mapping Function) and the VMF1 (Vienna Mapping Function 1). In addition, based on computations covering two months in 2005, the potential improvement due to the use of additional GLONASS data will be discussed. Finally, satellite techniques are also able to provide nutation offset rates with respect to the most recent nutation model. Based on GPS observations from 2005 we established nutation rate time series and subsequently derived the amplitudes of several nutation waves with periods less than 30 days. The results are compared to VLBI estimates processed by means of the OCCAM 6.1 software.

  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

    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. 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

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

    PubMed

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

    2014-01-01

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

  8. 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

  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. 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

  11. 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.

  12. 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

  13. 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

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

    SciTech Connect

    Vitug, A.C.; Goldman, J.M.

    1985-03-01

    Recent reports suggest that 14% to 23% of thyrotoxic patients have silent (painless) thyroiditis, a newly described syndrome characterized by transient thyrotoxicosis with a low radioactive iodine uptake. A three-year review at a Brooklyn (NY) hospital showed only one definite and three possible cases of silent thyroiditis among 86 thyrotoxic patients. At most, 4% to 5% of thyrotoxic patients had silent thyroiditis. The authors suggest a geographic variation in this syndrome. Most cases and the largest series are from Japan and the Great Lakes area of North America. The latter may be related to increased iodine intake over many years in a previously endemic area of hypoiodidism and goiter, although other local factors may also be involved.

  15. 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

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

    PubMed Central

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

    2010-01-01

    High resolution DNA sequencing was used to identify the HLA-A, -B, -C, and -DRB1 alleles found in 552 individuals from the United States indicating Southern European (Italian or Spanish) heritage. A total of 46 HLA-A, 80 HLA-B, 32 HLA-C, and 50 DRB1 alleles were identified. Frequent alleles included A*02:01:01G (allele frequency = 0.26 in Italian Americans; 0.22 in Spanish Americans); B*07:02:01G (Italian Americans allele frequency = 0.11); B*44:03 (Spanish Americans allele frequency = 0.07); C*04:01:01G and C*07:01:01G (allele frequency = 0.13 and 0.16, respectively, in Italian Americans; 0.15 and 0.12, respectively, in Spanish Americans); and DRB1*07:01:01 (allele frequency = 0.12 in each population). The action of balancing selection was inferred at the HLA-B and -C loci in both populations. The A*01:01:01G-C*07:01:01G-B*08:01:01G-DRB1*03:01:01 haplotype was the most frequent A-C-B-DRB1 haplotype in Italian Americans (haplotype frequency = 0.049), and was the second most frequent haplotype in Spanish Americans (haplotype frequency = 0.021). A*29:02:01-C*16:01:01-B*44:03-DRB1*07:01:01 was the most frequent A-C-B-DRB1 haplotype in Spanish Americans (haplotype frequency = 0.023), and was observed at a frequency of 0.015 in Italian Americans. Pairwise F’st values measuring the degree of differentiation between these Southern European-American populations and European and European-American populations suggest that Spanish Americans constitute a distinct subset of the European-American population, most similar to Mexican Americans, whereas Italian Americans cannot be distinguished from the larger European-American population. PMID:20974205

  17. 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.

  18. 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

  19. 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.

  20. Identification of a member of the catalase multigene family on wheat chromosome 7A associated with flour b* colour and biological significance of allelic variation.

    PubMed

    Li, Dora A; Walker, Esther; Francki, Michael G

    2015-12-01

    Carotenoids (especially lutein) are known to be the pigment source for flour b* colour in bread wheat. Flour b* colour variation is controlled by a quantitative trait locus (QTL) on wheat chromosome 7AL and one gene from the carotenoid pathway, phytoene synthase, was functionally associated with the QTL on 7AL in some, but not all, wheat genotypes. A SNP marker within a sequence similar to catalase (Cat3-A1snp) derived from full-length (FL) cDNA (AK332460), however, was consistently associated with the QTL on 7AL and implicated in regulating hydrogen peroxide (H2O2) to control carotenoid accumulation affecting flour b* colour. The number of catalase genes on chromosome 7AL was investigated in this study to identify which gene may be implicated in flour b* variation and two were identified through interrogation of the draft wheat genome survey sequence consisting of five exons and a further two members having eight exons identified through comparative analysis with the single catalase gene on rice chromosome 6, PCR amplification and sequencing. It was evident that the catalase genes on chromosome 7A had duplicated and diverged during evolution relative to its counterpart on rice chromosome 6. The detection of transcripts in seeds, the co-location with Cat3-A1snp marker and maximised alignment of FL-cDNA (AK332460) with cognate genomic sequence indicated that TaCat3-A1 was the member of the catalase gene family associated with flour b* colour variation. Re-sequencing identified three alleles from three wheat varieties, TaCat3-A1a, TaCat3-A1b and TaCat3-A1c, and their predicted protein identified differences in peroxisomal targeting signal tri-peptide domain in the carboxyl terminal end providing new insights into their potential role in regulating cellular H2O2 that contribute to flour b* colour variation.

  1. Flowering time variation in oilseed rape (Brassica napus L.) is associated with allelic variation in the FRIGIDA homologue BnaA.FRI.a.

    PubMed

    Wang, Nian; Qian, Wei; Suppanz, Ida; Wei, Lijuan; Mao, Bizeng; Long, Yan; Meng, Jinling; Müller, Andreas E; Jung, Christian

    2011-11-01

    Oilseed rape (Brassica napus L.) is a major oil crop which is grown worldwide. Adaptation to different environments and regional climatic conditions involves variation in the regulation of flowering time. Winter types have a strong vernalization requirement whereas semi-winter and spring types have a low vernalization requirement or flower without exposure to cold, respectively. In Arabidopsis thaliana, FRIGIDA (FRI) is a key regulator which inhibits floral transition through activation of FLOWERING LOCUS C (FLC), a central repressor of flowering which controls vernalization requirement and response. Here, four FRI homologues in B. napus were identified by BAC library screening and PCR-based cloning. While all homologues are expressed, two genes were found to be differentially expressed in aerial plant organs. One of these, BnaA.FRI.a, was mapped to a region on chromosome A03 which co-localizes with a major flowering time quantitative trait locus in multiple environments in a doubled-haploid mapping population. Association analysis of BnaA.FRI.a revealed that six SNPs, including at least one at a putative functional site, and one haplotype block, respectively, are associated with flowering time variation in 248 accessions, with flowering times differing by 13-19 d between extreme haplotypes. The results from both linkage analysis and association mapping indicate that BnaA.FRI.a is a major determinant of flowering time in oilseed rape, and suggest further that this gene also contributes to the differentiation between growth types. The putative functional polymorphisms identified here may facilitate adaptation of this crop to specific environments through marker-assisted breeding. PMID:21862478

  2. 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.

  3. 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

  4. Frequency of radial artery anatomic variations in patients undergoing transradial heart catheterization.

    PubMed

    Ostojić, Zvonimir; Bulum, Joško; Ernst, Aleksander; Strozzi, Maja; Marić-Bešić, Kristina

    2015-03-01

    Over the last ten years, transradial cardiac catheterization has been increasingly applied, primarily because of its lower incidence of complications compared to the femoral approach. However, one of the greatest flaws of the transradial approach is a relatively high incidence of catheterization failure (1%-5%). Anatomic variations of radial artery are ranked second among the reasons for this. Previous studies have not provided unambiguous data on the frequency of these anomalies. It was therefore the aim of this study to determine the frequency of anatomic variations using routine angiographies of radial artery during left heart catheterization. This was a retrospective study involving examination of 602 images of routine angiographies of radial artery performed during cardiac catheterization. The frequency of anatomic variations of radial artery was 8.8%, exclusive of tortuosities with a frequency of 12.7%. The most frequent anatomic variation was the high origin of radial artery, found in 31 (5.1%) subjects. Radioulnar loops, being one of the potential contraindications for the procedure, were reported in 2% of cases. Regression analysis revealed that age (p < 0.001), female sex (p = 0.015) and high origin (p = 0.034) considerably contributed to the development of tortuosity. The results indicated the incidence of tortuosity to increase linearly with age. Although it is not a contraindication for continuing with the procedure, we recommend that elderly patients have angiography of radial artery performed at the beginning of the procedure due to the higher frequency of tortuosity. PMID:26058245

  5. 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

  6. 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

  7. Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6-Tas1r3 congenic mice

    PubMed Central

    Inoue, Masashi; Glendinning, John I.; Theodorides, Maria L.; Harkness, Sarah; Li, Xia; Bosak, Natalia; Beauchamp, Gary K.; Bachmanov, Alexander A.

    2008-01-01

    The Tas1r3 gene encodes the T1R3 receptor protein, which is involved in sweet taste transduction. To characterize ligand specificity of the T1R3 receptor and the genetic architecture of sweet taste responsiveness, we analyzed taste responses of 129.B6-Tas1r3 congenic mice to a variety of chemically diverse sweeteners and glucose polymers with three different measures: consumption in 48-h two-bottle preference tests, initial licking responses, and responses of the chorda tympani nerve. The results were generally consistent across the three measures. Allelic variation of the Tas1r3 gene influenced taste responsiveness to nonnutritive sweeteners (saccharin, acesulfame-K, sucralose, SC-45647), sugars (sucrose, maltose, glucose, fructose), sugar alcohols (erythritol, sorbitol), and some amino acids (d-tryptophan, d-phenylalanine, l-proline). Tas1r3 genotype did not affect taste responses to several sweet-tasting amino acids (l-glutamine, l-threonine, l-alanine, glycine), glucose polymers (Polycose, maltooligosaccharide), and nonsweet NaCl, HCl, quinine, monosodium glutamate, and inosine 5′-monophosphate. Thus Tas1r3 polymorphisms affect taste responses to many nutritive and nonnutritive sweeteners (all of which must interact with a taste receptor involving T1R3), but not to all carbohydrates and amino acids. In addition, we found that the genetic architecture of sweet taste responsiveness changes depending on the measure of taste response and the intensity of the sweet taste stimulus. Variation in the T1R3 receptor influenced peripheral taste responsiveness over a wide range of sweetener concentrations, but behavioral responses to higher concentrations of some sweeteners increasingly depended on mechanisms that could override input from the peripheral taste system. PMID:17911381

  8. 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

  9. Observation of a 100-MHz frequency variation across the output of a frequency-doubled injection-seeded unstable-resonator Q-switched Nd:YAG laser.

    PubMed

    Forkey, J N; Lempert, W R; Miles, R B

    1997-02-15

    We report high-resolution measurements of the spatial variation of the optical frequency of an injection-seeded unstable-resonator Q-switched Nd:YAG laser. Images of the second harmonic taken through a molecular-iodine notch filter show frequency variations of as much as 100 MHz (second harmonic) between the center and the edge of the beam. PMID:18183159

  10. 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.

  11. Sensitivity of Conditional-Discrimination Performance to Within-Session Variation of Reinforcer Frequency

    ERIC Educational Resources Information Center

    Ward, Ryan D.; Odum, Amy L.

    2008-01-01

    The present experiment developed a methodology for assessing sensitivity of conditional-discrimination performance to within-session variation of reinforcer frequency. Four pigeons responded under a multiple schedule of matching-to-sample components in which the ratio of reinforcers for correct S[subscript 1] and S[subscript 2] responses was…

  12. 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…

  13. Rare HLA drive additional HIV evolution compared to more frequent alleles.

    PubMed

    Rousseau, Christine M; 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

    2009-03-01

    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 < or = 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.

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

    PubMed

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

    2015-02-01

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

  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. 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

  17. Solar-cycle variation of oscillation frequencies and surface magnetic field

    NASA Astrophysics Data System (ADS)

    Tan, S.; Thompson, M. J.; Centeno, R.

    2011-12-01

    We investigate the relationship between solar oscillation frequencies and surface magnetic fields over the course of the last solar cycle. Using MDI and GONG data, we study the variation in the even frequency-splitting coefficients ak (describing solar asphericity and effects of the magnetic field), and the variation in the coefficients Bk of the latitudinal Lengendre decomposition of the surface magnetic field, during the period 1996 - 2010. We find a strong linear correlation between the a and B coefficients, during both the rising and declining phases of the solar cycle, consistent with results published in 2001 (Antia et al.). We also investigated different ways to handle the magnetic field decomposition at the poles, and find that the linear correlation persists, though with varying intercepts. The variation of slope with coefficient index that we find is non-monotonic, which disagrees with the previous study by Antia et al. (2001).

  18. 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.

  19. Solution of the high-frequency variations of ERP from VLBI observations

    NASA Astrophysics Data System (ADS)

    Zhang, Bo; Li, Jin-ling; Wang, Guang-li; Zhao, Ming

    2005-07-01

    In the software CALC/SOLVE for the analysis of VLBI astrometric and geodetic data, the high-frequency variations of earth rotation parameters (ERP) are estimated by segmented linear fittings with additional constraints. That is, the rates of ERP between two epoch nodes are constrained to agree to within some preset value, and the ERP are required to be continuous at the nodes. Our analysis shows that when the data points are not very dense, the constraint and continuity requirement help to improve the stability of the solution, while at the same time they degrade the objectivity of the solution and make the solutions of ERP at different epoch nodes correlated. For this reason, based on the user partial entry of CALC/SOLVE, we have developed a module for the direct solution of the high-frequency variations of ERP, without the constraint on the ERP rate, nor the continuity requirement at the epoch nodes. It is shown by our reduction of real data that the direct solution mode is preferable. To derive the high-frequency variations of ERP from VLBI observations with a long time span, the error in the precession/nutation models (the celestial pole offset) should be taken into consideration and a corresponding module is developed. The global solutions of the high-frequency variations of ERP are successfully performed on the VLBI observations in the period from 1979 to 2003. It is demonstrated that when the errors in precession/nutation models are taken into consideration, the accuracy of the solution is noticeably improved. So, when seeking the high-frequency variations of ERP from VLBI observations, we recommend this direct solution mode, while taking the pole offset into consideration.

  20. Genetic heterogeneity within electrophoretic "alleles" of xanthine dehydrogenase in Drosophila pseudoobscura.

    PubMed

    Singh, R S; Lewontin, R C; Felton, A A

    1976-11-01

    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 head 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 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.

  1. 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.

  2. 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.

  3. 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

  4. 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%.

  5. 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.

  6. 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

  7. Frequency-independent approach to calculate physical optics radiations with the quadratic concave phase variations

    NASA Astrophysics Data System (ADS)

    Wu, Yu Mao; Teng, Si Jia

    2016-11-01

    In this work, we develop the numerical steepest descent path (NSDP) method to calculate the physical optics (PO) radiations with the quadratic concave phase variations. With the surface integral equation method, the physical optics (PO) scattered fields are formulated and further reduced to the surface integrals. The high frequency physical critical points contributions, including the stationary phase points, the boundary resonance points and the vertex points are comprehensively studied via the proposed NSDP method. The key contributions of this work are twofold. One is that together with the PO integrals taking the quadratic parabolic and hyperbolic phase terms, this work makes the NSDP theory be complete for treating the PO integrals with quadratic phase variations. Another is that, in order to illustrate the transition effect of the high frequency physical critical points, in this work, we consider and further extend the NSDP method to calculate the PO integrals with the coalescence of the high frequency critical points. Numerical results for the highly oscillatory PO integral with the coalescence of the critical points are given to verify the efficiency of the proposed NSDP method. The NSDP method could achieve the frequency independent computational workload and error controllable accuracy in all the numerical experiments, especially for the case of the coalescence of the high frequency critical points.

  8. Top down and bottom up selection drives variations in frequency and form of a visual signal.

    PubMed

    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.

  9. 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).

  10. 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).

  11. High frequency variations of Earth Rotation Parameters from GPS and GLONASS observations.

    PubMed

    Wei, Erhu; Jin, Shuanggen; Wan, Lihua; Liu, Wenjie; Yang, Yali; Hu, Zhenghong

    2015-01-28

    The Earth's rotation undergoes changes with the influence of geophysical factors, such as Earth's surface fluid mass redistribution of the atmosphere, ocean and hydrology. However, variations of Earth Rotation Parameters (ERP) are still not well understood, particularly the short-period variations (e.g., diurnal and semi-diurnal variations) and their causes. In this paper, the hourly time series of Earth Rotation Parameters are estimated using Global Positioning System (GPS), Global Navigation Satellite System (GLONASS), and combining GPS and GLONASS data collected from nearly 80 sites from 1 November 2012 to 10 April 2014. These new observations with combining different satellite systems can help to decorrelate orbit biases and ERP, which improve estimation of ERP. The high frequency variations of ERP are analyzed using a de-trending method. The maximum of total diurnal and semidiurnal variations are within one milli-arcseconds (mas) in Polar Motion (PM) and 0.5 milli-seconds (ms) in UT1-UTC. The semidiurnal and diurnal variations are mainly related to the ocean tides. Furthermore, the impacts of satellite orbit and time interval used to determinate ERP on the amplitudes of tidal terms are analyzed. We obtain some small terms that are not described in the ocean tide model of the IERS Conventions 2010, which may be caused by the strategies and models we used or the signal noises as well as artifacts. In addition, there are also small differences on the amplitudes between our results and IERS convention. This might be a result of other geophysical excitations, such as the high-frequency variations in atmospheric angular momentum (AAM) and hydrological angular momentum (HAM), which needs more detailed analysis with more geophysical data in the future.

  12. 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

  13. 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

  14. The role of low-frequency variation in the manifestation of warming trend and ENSO amplitude

    NASA Astrophysics Data System (ADS)

    Yeo, Sae-Rim; Yeh, Sang-Wook; Kim, Kwang-Yul; Kim, WonMoo

    2016-10-01

    Despite the increase in greenhouse gas concentration, the sea surface temperature (SST) over the tropical eastern Pacific during the period of 1999-2014 exhibits less warming trend compared to the earlier decades. It has been noted that this warming hiatus is accompanied by a negative phase of the Pacific Decadal Oscillation (PDO), which represents low-frequency variability over the Pacific. On the other hand, the 2015/2016 El Niño is among the strongest comparable to the 1997/1998 event, which coincides with the recently altered PDO phase from negative to positive. These observational evidences have generated substantial interest in the role of low-frequency variations in modulating El Niño-Southern Oscillation amplitude as well as manifestation of warming signal in the tropical Pacific. Therefore, it is necessary to appropriately separate low-frequency variability and global warming signal from SST records. Here, we present three primary modes of global SST that include secular warming trend, low-frequency variability, and biennial oscillation. Based on the independent behavior of these three modes, global warming is clearly continuing but its manifestation is enhanced (depressed) when the low-frequency variation is in the positive (negative) phase. Further, possibility of strong El Niño increases under the positive phase of the low-frequency mode, which amplifies warming over the tropical eastern Pacific. Indeed, the strong 2015/2016 El Niño is largely attributed to the positive phase of the low-frequency mode. In order to examine the climate models' ability to simulate the three SST modes as obtained in the observational record, the Coupled Model Intercomparison Project phase 5 (CMIP5) datasets are also analyzed. The spatial and temporal characteristics of the three modes have been replicated closely by the selected CMIP5 models forced by the historical condition, which provides an analogy of the interplay of three modes in the observed tropical Pacific SST.

  15. 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

  16. PULSAR TIMING ERRORS FROM ASYNCHRONOUS MULTI-FREQUENCY SAMPLING OF DISPERSION MEASURE VARIATIONS

    SciTech Connect

    Lam, M. T.; Cordes, J. M.; Chatterjee, S.; Dolch, T.

    2015-03-10

    Free electrons in the interstellar medium cause frequency-dependent delays in pulse arrival times due to both scattering and dispersion. Multi-frequency measurements are used to estimate and remove dispersion delays. In this paper, we focus on the effect of any non-simultaneity of multi-frequency observations on dispersive delay estimation and removal. Interstellar density variations combined with changes in the line of sight from pulsar and observer motions cause dispersion measure (DM) variations with an approximately power-law power spectrum, augmented in some cases by linear trends. We simulate time series, estimate the magnitude and statistical properties of timing errors that result from non-simultaneous observations, and derive prescriptions for data acquisition that are needed in order to achieve a specified timing precision. For nearby, highly stable pulsars, measurements need to be simultaneous to within about one day in order for the timing error from asynchronous DM correction to be less than about 10 ns. We discuss how timing precision improves when increasing the number of dual-frequency observations used in DM estimation for a given epoch. For a Kolmogorov wavenumber spectrum, we find about a factor of two improvement in precision timing when increasing from two to three observations but diminishing returns thereafter.

  17. 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

  18. 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...

  19. 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

  20. 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

  1. Studies on metatherian sex chromosomes. I. Inheritance and inactivation of sex-linked allelic genes determining glucose-6-phosphate dehydrogenase variation in kangaroos.

    PubMed

    Johnston, P G; Sharman, G B

    1975-12-01

    Wallaroos (Macropus robustus robustus), which have the G6PD-F electrophoretic phenotype, crossed with euros (M.r.erubescens), of G6PD-S phenotype, produced F1 animals which had only the maternal G6PD type regardless of the direction of the cross. When F1 hybrids were backcrossed to wallaroos or euros, backcross progeny of either perental phenotype resulted. Sex-linked inheritance of allelic G6PD genes is shown to occur in wallaroos, euros and red kangaroos (M. rufus). Dose compensation for X chromosomes at the G6PD locus in kangaroow is achieved by inactivation of the allele of male parental origin.

  2. Allelic association between marker loci.

    PubMed

    Lonjou, C; Collins, A; Morton, N E

    1999-02-16

    Allelic association has proven useful to refine the location of major genes prior to positional cloning, but it is of uncertain value for genome scans in complex inheritance. We have extended kinship theory to give information content for linkage and allelic association. Application to pairs of closely linked markers as a surrogate for marker x oligogene pairs indicates that association is largely determined by regional founders, with little effect of subsequent demography. Sub-Saharan Africa has the least allelic association, consistent with settlement of other regions by small numbers of founders. Recent speculation about substantial advantages of isolates over large populations, of constant size over expansion, and of F1 hybrids over incrosses is not supported by theory or data. On the contrary, fewer affected cases, less opportunity for replication, and more stochastic variation tend to make isolates less informative for allelic association, as they are for linkage.

  3. 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

  4. 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.

  5. Frequency of t(14;18) in follicular lymphoma patients: geographical or technical variation.

    PubMed

    Ismail, S I; Sughayer, M A; Al-Quadan, T F; Qaqish, B M; Tarawneh, M S

    2009-10-01

    The t(14;18) translocation is the most distinguishing molecular finding in follicular lymphoma (FL). However, the reported frequencies of t(14;18) in FL show significant variation, which is often attributed to geographical and/or methodological factors. The methods used to detect t(14;18) include Southern blotting, conventional cytogenetics, fluorescent in situ hybridization, and polymerized chain reaction (PCR). Because of its practicality and superior sensitivity, PCR is becoming the more commonly used method in clinical laboratories. The identification of the main breakpoint regions on chromosome 18, including the major breakpoint region (MBR), the minor cluster region (mcr), and the newly defined intermediate cluster region (icr), increased the detection frequency of PCR. In our study, using a highly sensitive nested PCR strategy with primers for MBR, mcr and icr regions, we were able to detect t(14;18) in 95% of FL patients, which is one of the highest reported frequencies using PCR. We screened 58 FL patient samples collected retrospectively from different hospitals in Jordan. DNA was extracted from archival paraffin-embedded samples, some of which were >10 years old. The respective breakpoint distributions were, 47 for MBR (81%), two for mcr (3.5%) and six for icr (10.3%). In this report, we analyze this high frequency of t(14;18) detection in a general review of the recent literature, in an attempt to assess the geographical vs. methodological influences on the reported frequencies.

  6. 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.

  7. 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...

  8. Allelic variation of LMW-GS composition in Chinese wheat landraces of the Yangtze-River region detected by MALDI-TOF-MS

    PubMed Central

    Peng, Yanchun; Yu, Zitong; Islam, Shahidul; Zhang, Yujuan; Wang, Xiaolong; Lei, Zhensheng; Yu, Kan; Sun, Dongfa; Ma, Wujun

    2016-01-01

    Low molecular weight glutenin subunits are important components of wheat storage proteins, which play an important role in determining end-use quality of common wheat. A newly established matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) procedure was used to analyze 478 landraces of bread wheat collected from the Yangtze-River region in China. Results indicated that 17 alleles at three loci: Glu-A3, Glu-B3 and Glu-D3 were identified, resulting in 87 different allele combinations. Of the 17 alleles detected at all the Glu-3 loci, five belonged to Glu-A3, seven to Glu-B3 and five to Glu-D3 locus. MALDI-TOF-MS indicated Glu-A3a/c was present in 72.8%, Glu-A3b in 8.4%, Glu-A3d in 8.4%, Glu-A3f in 5.2% and Glu-A3e in 3.6% lines. Seven types of alleles were identified at the Glu-B3 locus: Glu-B3d/i (25.5%), Glu-B3b (21.3%), Glu-B3c (16.9%), Glu-B3h (13.8%), Glu-B3f (8.4%), Glu-B3a (8.2%), and Glu-B3g (5.2%). Five types of Glu-D3 alleles were detected: Glu-D3a (58.4%), Glu-D3c (22.6%), Glu-D3d (15.5%), Glu-D3b (3.3%) and Glu-D3f (0.2%). Four new alleles that showed abnormal MALDI-TOF spectrum patterns were identified at the Glu-A3 and Glu-B3 loci. A detailed study is needed to further characterize these alleles and their potential usage for wheat improvement. PMID:27795690

  9. Frequency of sternal foramen evaluated by MDCT: a minor variation of great relevance.

    PubMed

    Babinski, Marcio A; de Lemos, Leandro; Babinski, Monique S D; Gonçalves, Marianna V T; De Paula, Rafael C; Fernandes, Rodrigo M P

    2015-04-01

    Due to inadvertent cardiac or great vessel injury, sternal foramina may pose as a great hazard during sternal puncture. They can also be misinterpreted as osteolytic lesions in cross-sectional imaging of the sternum. The distribution of these variations differs between populations, but data from Brazilians are scarcely reported. Therefore, this study aimed to verify the frequency of midline sternal foramen and double-ended xiphoid process, as developmental variations, in order to avoid fatal complications following sternal puncture of sternal acupuncture treatment. A total of 114 chest computed tomograms were evaluated. The frequency of midline sternal foramen in a complication risk bearing feature is of approximately 10.5%. The double-ended xiphoid process was present in 17.5%. We conclude that sternal acupuncture should be planned in the region of corpus-previous CT should be done to rule out this variation. Furthermore, we strongly recommend the acupuncture technique which prescribes a safe superficial-oblique approach to the sternum. PMID:25023390

  10. Variation of Herbivore-Induced Volatile Terpenes among Arabidopsis Ecotypes Depends on Allelic Differences and Subcellular Targeting of Two Terpene Synthases, TPS02 and TPS031[W][OA

    PubMed Central

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

    2010-01-01

    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)-β-ocimene, the sesquiterpene (E,E)-α-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)-β-ocimene and (E,E)-α-farnesene from accession Wassilewskija (Ws), a high-(E)-β-ocimene emitter, and accession Columbia (Col-0), a trace-(E)-β-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)-β-ocimene and (E,E)-α-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)-β-ocimene/(E,E)-α-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

  11. 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.

  12. Seasonal and Regional Variations of U.S. Trends in Extreme Precipitation Frequency

    NASA Astrophysics Data System (ADS)

    Kunkel, K. E.; Krisotovich, D.; Smith, R.; Ensor, L.; Easterling, D.

    2008-12-01

    Numerous studies have documented increases in U.S. heavy precipitation during the latter part of the 20th Century. Recent studies have also revealed that event frequencies were quite high early in the 20th Century, nearly as high as in the 1980s and 1990s. This suggests that natural variability may be quite large and perhaps the recent increases in the U.S. have a large natural component. The meteorological reasons behind the observed major decadal-scale variations in heavy precipitation have not been investigated. Have there been secular changes in the frequency, intensity, and other characteristics of the meteorological phenomena producing heavy precipitation? Can we attribute these changes to hemispheric or global trends in circulation, SSTs, etc.? Are the recent increases primarily a result of increases in atmospheric water vapor concentrations? Heavy precipitation events occur in a variety of meteorological situations/types that are seasonally and regionally variable. The seasonal and regional differences in trends can provide important insights into possible causes of decadal-scale variations in the frequency and intensity of extreme events. An investigation of such variations has revealed that in those cases where regional monthly trends are statistically significant, the trends are overwhelmingly upward. The great majority of these statistically significant upward monthly trends occur in the warm season (May-October), with the most widespread increases occurring in August. The central part of the U.S. from the Gulf Coast northward into the Great Lakes in particular has experienced statistically significant increases in many warm season months. The timing and locations of the observed increases suggest that a variety of phenomena could be contributing, including tropical cyclones, mesoscale convective systems, extratropical cyclones, and increased water vapor transport from the Gulf of Mexico/western Atlantic. More detailed investigation is required to

  13. Origin of terminal voltage variations due to self-mixing in terahertz frequency quantum cascade lasers.

    PubMed

    Grier, Andrew; Dean, Paul; Valavanis, Alexander; Keeley, James; Kundu, Iman; Cooper, Jonathan D; Agnew, Gary; Taimre, Thomas; Lim, Yah Leng; Bertling, Karl; Rakić, Aleksandar D; Li, Lianhe H; Harrison, Paul; Linfield, Edmund H; Ikonić, Zoran; Davies, A Giles; Indjin, Dragan

    2016-09-19

    We explain the origin of voltage variations due to self-mixing in a terahertz (THz) frequency quantum cascade laser (QCL) using an extended density matrix (DM) approach. Our DM model allows calculation of both the current-voltage (I-V) and optical power characteristics of the QCL under optical feedback by changing the cavity loss, to which the gain of the active region is clamped. The variation of intra-cavity field strength necessary to achieve gain clamping, and the corresponding change in bias required to maintain a constant current density through the heterostructure is then calculated. Strong enhancement of the self-mixing voltage signal due to non-linearity of the (I-V) characteristics is predicted and confirmed experimentally in an exemplar 2.6 THz bound-to-continuum QCL.

  14. Origin of terminal voltage variations due to self-mixing in terahertz frequency quantum cascade lasers.

    PubMed

    Grier, Andrew; Dean, Paul; Valavanis, Alexander; Keeley, James; Kundu, Iman; Cooper, Jonathan D; Agnew, Gary; Taimre, Thomas; Lim, Yah Leng; Bertling, Karl; Rakić, Aleksandar D; Li, Lianhe H; Harrison, Paul; Linfield, Edmund H; Ikonić, Zoran; Davies, A Giles; Indjin, Dragan

    2016-09-19

    We explain the origin of voltage variations due to self-mixing in a terahertz (THz) frequency quantum cascade laser (QCL) using an extended density matrix (DM) approach. Our DM model allows calculation of both the current-voltage (I-V) and optical power characteristics of the QCL under optical feedback by changing the cavity loss, to which the gain of the active region is clamped. The variation of intra-cavity field strength necessary to achieve gain clamping, and the corresponding change in bias required to maintain a constant current density through the heterostructure is then calculated. Strong enhancement of the self-mixing voltage signal due to non-linearity of the (I-V) characteristics is predicted and confirmed experimentally in an exemplar 2.6 THz bound-to-continuum QCL. PMID:27661929

  15. Variations in fundamental frequency peak position in Japanese macaque (Macaca fuscata) coo calls.

    PubMed

    Owren, M J; Casale, T M

    1994-09-01

    Japanese macaques (Macaca fuscata) produce coo calls whose use in various contexts is correlated with differences in the relative temporal position of the peak value of a call's fundamental frequency (Green, 1975). Studies have produced conflicting results about both the location of the category boundary between smooth early high and smooth late high coo subtypes and macaques' perceptual sensitivity to variations in peak position. In this study, fundamental frequency peak positions were measured in 578 coos produced by 8 captive adult female Japanese macaques in order to test whether calls with peak positions close to either of 2 hypothesized boundaries occurred at low rates. Overall, such calls were found to occur at rate equal to or higher than predicted by chance. Peak position varied more consistently between animals than by behavioral context. The results may indicate that peak position in coos does not form 2 distinct categories.

  16. Variation in drug injection frequency among out-of-treatment drug users in a national sample.

    PubMed

    Singer, M; Himmelgreen, D; Dushay, R; Weeks, M R

    1998-05-01

    This article analyzes data on drug injection frequency in a sample of more than 13,000 out-of-treatment drug injectors interviewed across 21 U.S. cities and Puerto Rico through the National Institute on Drug Abuse (NIDA) Cooperative Agreement for AIDS Community-Based Outreach/Intervention Research Program. The goals of the article are to present findings on injection frequency and to predict variation in terms of a set of variables suggested by previous research, including location, ethnicity, gender, age, educational attainment, years since first use of alcohol and marijuana, income, living arrangement, homelessness, drugs injected, and duration of injection across drugs. Three models were tested. Significant intersite differences were identified in injection frequency, although most of the other predictor variables we tested accounted for little of the variance. Ethnicity and drugs injected, however, were found to be significant. Taken together, location, ethnicity, and type of drug injected provide a configuration that differentiated and (for the variables available for the analysis) best predicted injection frequency. The public health implications of these findings are presented.

  17. 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.

  18. 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

  19. Allelic asymmetry of the Lethal hybrid rescue (Lhr) gene expression in the hybrid between Drosophila melanogaster and D. simulans: confirmation by using genetic variations of D. melanogaster.

    PubMed

    Shirata, Mika; Araye, Quenta; Maehara, Kazunori; Enya, Sora; Takano-Shimizu, Toshiyuki; Sawamura, Kyoichi

    2014-02-01

    In the cross between Drosophila melanogaster females and D. simulans males, hybrid males die at the late larval stage, and the sibling females also die at later stages at high temperatures. Removing the D. simulans allele of the Lethal hybrid rescue gene (Lhr (sim) ) improves the hybrid incompatibility phenotypes. However, the loss-of-function mutation of Lhr (sim) (Lhr (sim0) ) does not rescue the hybrid males in crosses with several D. melanogaster strains. We first describe the genetic factor possessed by the D. melanogaster strains. It has been suggested that removing the D. melanogaster allele of Lhr (Lhr (mel) ), that is Lhr (mel0) , does not have the hybrid male rescue effect, contrasting to Lhr (sim0) . Because the expression level of the Lhr gene is known to be Lhr (sim) > Lhr (mel) in the hybrid, Lhr (mel0) may not lead to enough of a reduction in total Lhr expression. Then, there is a possibility that the D. melanogaster factor changes the expression level to Lhr (sim) < Lhr (mel) . But in fact, the expression level was Lhr (sim) > Lhr (mel) in the hybrid irrespectively of the presence of the factor. At last, we showed that Lhr (mel0) slightly improves the viability of hybrid females, which was not realized previously. All of the present results are consistent with the allelic asymmetry model of the Lhr gene expression in the hybrid.

  20. 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...

  1. 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

  2. Frequencies of immune hypersensitivity reaction-associated HLA class I alleles in healthy South African Indian and mixed ancestry populations determined by a novel real-time PCR assay.

    PubMed

    Loubser, S; Paximadis, M; Gentle, N; Puren, A; Gray, C M; Tiemessen, C T

    2014-10-01

    We have determined the frequencies of human leucocyte antigen (HLA)-B*57:01, HLA-B*35:05, HLA-C*04 and HLA-C*08 in healthy individuals of South African Indian (SAI) ethnicity (n = 50) and South African mixed (SAM) ancestry (n = 50) using real-time allele-specific polymerase chain reaction (AS-PCR) assay. HLA-B*57:01 associates with immune hypersensitivity reaction (IHR) in individuals exposed to abacavir (ABC), while nevirapine (NVP) IHR associates with HLA-B*35:05, HLA-C*04 and HLA-C*08. Real-time AS-PCR assays typically use less DNA, are more cost-effective and rapid compared with conventional genotyping methods, such as sequence-based typing (SBT). The assay was developed using samples of known HLA class I genotype and subsequently applied to the SAI and SAM samples. HLA-B*57:01 was detected in SAM and SAI populations at frequencies of 8.0% and 12.0%, respectively, while HLA-B*35:05 was not found in SAI individuals, but was present in 6.0% of SAM individuals. HLA-C*04 was detected in 22.0% and 24.0% of SAM and SAI individuals, respectively, while 10.0% and 8.0% of SAM and SAI individuals, respectively, were HLA-C*08 positive. This study reports the development of a novel real-time AS-PCR assay to identify HLA class I alleles associated with ABC and NVP IHR and has established the frequencies of these alleles present in healthy SAI and SAM populations. Using South African demographic data, our hypothetical analysis suggests that a substantial number of individuals would benefit from the assay.

  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.

  4. 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

  5. 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

  6. A comparison of intrasubject variation across sessions of three vocal frequency perturbation indices.

    PubMed

    Higgins, M B; Saxman, J H

    1989-09-01

    Within-subject variation of three vocal frequency perturbation indices was compared across multiple sessions. The magnitude of jitter factor (JF), pitch perturbation quotient (PPQ), and directional perturbation quotient (DPF) was measured every other day for 33 consecutive days for ten female and five male normal young adult speakers. Perturbation measures were calculated using a zero-crossing analysis of taped [i] and [u] productions. Pearson product-moment correlations among the three perturbation indices were calculated to examine their relation over time. Coefficients of variation for JF, PPQ, and DPF were considered indicative of the temporal stability of the three measures. JF and PPQ provided redundant information about laryngeal behaviors in steady-state productions. DPF, however, appeared to measure different laryngeal behaviors. Also, JF and PPQ varied considerably within individuals across sessions while DPF was the more temporally stable measure. Multiple sampling sessions and measurement of both the magnitude and direction of period differences are advised for future investigations of vocal frequency perturbation.

  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.

  8. 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

  9. 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

  10. Regional frequency analysis to asses wind resource spatial and temporal variations in Washington State

    NASA Astrophysics Data System (ADS)

    Mortuza, M.; Demissie, D.

    2013-12-01

    According to the U.S. Department of Energy's annual wind technologies market report, the wind power capacity in the country grew from 2.5 gigawatts in early 2000 to 60 gigawatts in 2012, making it one of the largest new sources of electric capacity additions in the U.S. in recent years. With over 2.8 gigawatts of current capacity (eighth largest in the nation), Washington State plays a significant role in this rapidly increasing energy resource. To further expand and/or optimize these capacities, assessment of wind resource and its spatial and temporal variations are important. However, since at-site frequency analysis using meteorological data is not adequate for extending wind frequency to locations with no data, longer return period, and heterogeneous topography and surface, a regional frequency analysis based on L-moment method is adopted in this study to estimate regional wind speed patterns and return periods in Washington State using hourly mean wind speed data from 1979 - 2010. The analysis applies the k-means, hierarchical and self-organizing map clustering techniques to explore potential clusters or regions; statistical tests are then applied to identify homogeneous regions and appropriate probability distribution models. The result from the analysis is expected to provide essential knowledge about the areas with potential capacity of constructing wind power plants, which can also be readily extended to assist decisions on their daily operations.

  11. 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

  12. Examining Spatio-Temporal Intensity-Frequency Variations in Extreme Monsoon Rainfall using High Resolution Data

    NASA Astrophysics Data System (ADS)

    Devak, M.; Rajendran, V.; C T, D.

    2015-12-01

    The study of extreme events has gained the attention of hydrologists in recent times. Though these events are rare, the effects are catastrophic. It is reported that the frequency of the occurrence of these events has increased in recent decades, and is attributed to the recent revelation of climate change. Numerous studies have pointed out significant changes in extremely heavy precipitation over India, using coarse resolution data. Though there are disagreements in the results and its spatial uniformity, all these studies emphasize the need of fine resolution analysis. Fine resolution analysis is necessary mainly due to the highly heterogeneous characteristics of Indian monsoon, and for the proper employment in flood hazard preparedness and water resources management. The present study aims to analyse the spatio-temporal variation and trends in the intensity and frequency of heavy precipitation during Indian monsoon using 0.25°×0.25° resolution gridded data for a period of 113 years (1901-2013). The exceedance threshold is fixed at 90th percentile of rainfall over 113 years and parameters are defined accordingly. The maximum intensity of each extreme rainfall episode of 30 year moving window has been modelled using Peak Over Threshold based Extreme Value Theory to compute return level (considered for intensity). In addition, the number of such episodes in a particular year has been termed as frequency. Non-parametric Mann-Kendall test has been carried out for both intensity and frequency, to compute the statistical trend. In addition, moving block bootstrap approach has been used to incorporate the serial correlation. The significance of the trend has been evaluated at different significance levels and finally, change in trend over last century has been examined.

  13. 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

  14. 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.

  15. 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.

  16. High-frequency Earth rotation variations deduced from altimetry-based ocean tides

    NASA Astrophysics Data System (ADS)

    Madzak, Matthias; Schindelegger, Michael; Böhm, Johannes; Bosch, Wolfgang; Hagedoorn, Jan

    2016-11-01

    A model of diurnal and semi-diurnal variations in Earth rotation parameters (ERP) is constructed based on altimetry-measured tidal heights from a multi-mission empirical ocean tide solution. Barotropic currents contributing to relative angular momentum changes are estimated for nine major tides in a global inversion algorithm that solves the two-dimensional momentum equations on a regular 0.5° grid with a heavily weighted continuity constraint. The influence of 19 minor tides is accounted for by linear admittance interpolation of ocean tidal angular momentum, although the assumption of smooth admittance variations with frequency appears to be a doubtful concept for semi-diurnal mass terms in particular. A validation of the newly derived model based on post-fit corrections to polar motion and universal time (Δ UT1) from the analysis of Very Long Baseline Interferometry (VLBI) observations shows a variance reduction for semi-diurnal Δ UT1 residuals that is significant at the 0.05 level with respect to the conventional ERP model. Improvements are also evident for the explicitly modeled K_1, Q_1, and K_2 tides in individual ERP components, but large residuals of more than 15 μ as remain at the principal lunar frequencies of O_1 and M_2. We attribute these shortcomings to uncertainties in the inverted relative angular momentum changes and, to a minor extent, to violation of mass conservation in the empirical ocean tide solution. Further dedicated hydrodynamic modeling efforts of these anomalous constituents are required to meet the accuracy standards of modern space geodesy.

  17. RHD allele distribution in Africans of Mali

    PubMed Central

    Wagner, Franz F; Moulds, Joann M; Tounkara, Anatole; Kouriba, Bourema; Flegel, Willy A

    2003-01-01

    Background Aberrant and non-functional RHD alleles are much more frequent in Africans than in Europeans. The DAU cluster of RHD alleles exemplifies that the alleles frequent in Africans have evaded recognition until recently. A comprehensive survey of RHD alleles in any African population was lacking. Results We surveyed the molecular structure and frequency of RHD alleles in Mali (West Africa) by evaluating 116 haplotypes. Only 69% could be attributed to standard RHD (55%) or the RHD deletion (14%). The aberrant RHD allele DAU-0 was predicted for 19%, RHDΨ for 7% and Ccdes for 4% of all haplotypes. DAU-3 and the new RHD allele RHD(L207F), dubbed DMA, were found in one haplotype each. A PCR-RFLP for the detection of the hybrid Rhesus box diagnostic for the RHD deletion in Europeans was false positive in 9 individuals, including all carriers of RHDΨ . Including two silent mutations and the RHD deletion, a total of 9 alleles could be differentiated. Conclusion Besides standard RHD and the RHD deletion, DAU-0, RHDΨ and Ccdes are major alleles in Mali. Our survey proved that the most frequent alleles of West Africans have been recognized allowing to devise reliable genotyping and phenotyping strategies. PMID:14505497

  18. 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.

  19. Variation in humpback whale (Megaptera novaeangliae) song length in relation to low-frequency sound broadcasts.

    PubMed

    Fristrup, Kurt M; Hatch, Leila T; Clark, Christopher W

    2003-06-01

    Humpback whale song lengths were measured from recordings made off the west coast of the island of Hawai'i in March 1998 in relation to acoustic broadcasts ("pings") from the U.S. Navy SURTASS Low Frequency Active sonar system. Generalized additive models were used to investigate the relationships between song length and time of year, time of day, and broadcast factors. There were significant seasonal and diurnal effects. The seasonal factor was associated with changes in the density of whales sighted near shore. The diurnal factor was associated with changes in surface social activity. Songs that ended within a few minutes of the most recent ping tended to be longer than songs sung during control periods. Many songs that were overlapped by pings, and songs that ended several minutes after the most recent ping, did not differ from songs sung in control periods. The longest songs were sung between 1 and 2 h after the last ping. Humpbacks responded to louder broadcasts with longer songs. The fraction of variation in song length that could be attributed to broadcast factors was low. Much of the variation in humpback song length remains unexplained.

  20. 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.

  1. Allelic Variation and Differential Expression of the mSIN3A Histone Deacetylase Complex Gene Arid4b Promote Mammary Tumor Growth and Metastasis

    PubMed Central

    Winter, Scott F.; Lukes, Luanne; Walker, Renard C.; Welch, Danny R.; Hunter, Kent W.

    2012-01-01

    Accumulating evidence suggests that breast cancer metastatic progression is modified by germline polymorphism, although specific modifier genes have remained largely undefined. In the current study, we employ the MMTV-PyMT transgenic mouse model and the AKXD panel of recombinant inbred mice to identify AT–rich interactive domain 4B (Arid4b; NM_194262) as a breast cancer progression modifier gene. Ectopic expression of Arid4b promoted primary tumor growth in vivo as well as increased migration and invasion in vitro, and the phenotype was associated with polymorphisms identified between the AKR/J and DBA/2J alleles as predicted by our genetic analyses. Stable shRNA–mediated knockdown of Arid4b caused a significant reduction in pulmonary metastases, validating a role for Arid4b as a metastasis modifier gene. ARID4B physically interacts with the breast cancer metastasis suppressor BRMS1, and we detected differential binding of the Arid4b alleles to histone deacetylase complex members mSIN3A and mSDS3, suggesting that the mechanism of Arid4b action likely involves interactions with chromatin modifying complexes. Downregulation of the conserved Tpx2 gene network, which is comprised of many factors regulating cell cycle and mitotic spindle biology, was observed concomitant with loss of metastatic efficiency in Arid4b knockdown cells. Consistent with our genetic analysis and in vivo experiments in our mouse model system, ARID4B expression was also an independent predictor of distant metastasis-free survival in breast cancer patients with ER+ tumors. These studies support a causative role of ARID4B in metastatic progression of breast cancer. PMID:22693453

  2. 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.

  3. Periodic Variations in the O - C Diagrams of Five Pulsation Frequencies of the DB White Dwarf EC 20058-5234

    NASA Astrophysics Data System (ADS)

    Dalessio, J.; Sullivan, D. J.; Provencal, J. L.; Shipman, H. L.; Sullivan, T.; Kilkenny, D.; Fraga, L.; Sefako, R.

    2013-03-01

    Variations in the pulsation arrival time of five independent pulsation frequencies of the DB white dwarf EC 20058-5234 individually imitate the effects of reflex motion induced by a planet or companion but are inconsistent when considered in unison. The pulsation frequencies vary periodically in a 12.9 year cycle and undergo secular changes that are inconsistent with simple neutrino plus photon-cooling models. The magnitude of the periodic and secular variations increases with the period of the pulsations, possibly hinting that the corresponding physical mechanism is located near the surface of the star. The phase of the periodic variations appears coupled to the sign of the secular variations. The standards for pulsation-timing-based detection of planetary companions around pulsating white dwarfs, and possibly other variables such as subdwarf B stars, should be re-evaluated. The physical mechanism responsible for this surprising result may involve a redistribution of angular momentum or a magnetic cycle. Additionally, variations in a supposed combination frequency are shown to match the sum of the variations of the parent frequencies to remarkable precision, an expected but unprecedented confirmation of theoretical predictions. Based on observations obtained at the Southern Astrophysical Research (SOAR) telescope, which is a joint project of the Ministério da Ciência, Tecnologia, e Inovação (MCTI) da República Federativa do Brasil, the US National Optical Astronomy Observatory (NOAO), the University of North Carolina at Chapel Hill (UNC), and Michigan State University (MSU).

  4. The tRNA-Tyr gene family of Saccharomyces cerevisiae: agents of phenotypic variation and position effects on mutation frequency.

    PubMed Central

    Ito-Harashima, Sayoko; Hartzog, Phillip E; Sinha, Himanshu; McCusker, John H

    2002-01-01

    Extensive phenotypic diversity or variation exists in clonal populations of microorganisms and is thought to play a role in adaptation to novel environments. This phenotypic variation or instability, which occurs by multiple mechanisms, may be a form of cellular differentiation and a stochastic means for modulating gene expression. This work dissects a case of phenotypic variation in a clinically derived Saccharomyces cerevisiae strain involving a cox15 ochre mutation, which acts as a reporter. The ochre mutation reverts to sense at a low frequency while tRNA-Tyr ochre suppressors (SUP-o) arise at a very high frequency to produce this phenotypic variation. The SUP-o mutations are highly pleiotropic. In addition, although all SUP-o mutations within the eight-member tRNA-Tyr gene family suppress the ochre mutation reporter, there are considerable phenotypic differences among the different SUP-o mutants. Finally, and of particular interest, there is a strong position effect on mutation frequency within the eight-member tRNA-Tyr gene family, with one locus, SUP6, mutating at a much higher than average frequency and two other loci, SUP2 and SUP8, mutating at much lower than average frequencies. Mechanisms for the position effect on mutation frequency are evaluated. PMID:12196388

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

    PubMed

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

    2014-01-01

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

  6. 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

  7. 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.

  8. Dielectric properties of porcine cerebrospinal tissues at microwave frequencies: in vivo, in vitro and systematic variation with age

    NASA Astrophysics Data System (ADS)

    Peyman, A.; Holden, S. J.; Watts, S.; Perrott, R.; Gabriel, C.

    2007-04-01

    The dielectric properties of pig cerebrospinal tissues were measured in vivo and in vitro, in the frequency range of 50 MHz-20 GHz. The total combined measurement uncertainty was calculated at each frequency point and is reported over representative frequency regions. Comparisons were made for each tissue between the two sets of data and with the literature of the past decade. The in vitro study was extended to include tissue from pigs weighing approximately 10, 50 and 250 kg to re-visit the question of the variation of dielectric properties with age. White matter and spinal chord showed significant variation as function of animal age, no age-related variations were recorded for grey matter.

  9. Quantitative resistance affects the speed of frequency increase but not the diversity of the virulence alleles overcoming a major resistance gene to Leptosphaeria maculans in oilseed rape.

    PubMed

    Delourme, R; Bousset, L; Ermel, M; Duffé, P; Besnard, A L; Marquer, B; Fudal, I; Linglin, J; Chadœuf, J; Brun, H

    2014-10-01

    Quantitative resistance mediated by multiple genetic factors has been shown to increase the potential for durability of major resistance genes. This was demonstrated in the Leptosphaeria maculans/Brassica napus pathosystem in a 5year recurrent selection field experiment on lines harboring the qualitative resistance gene Rlm6 combined or not with quantitative resistance. The quantitative resistance limited the size of the virulent isolate population. In this study we continued this recurrent selection experiment in the same way to examine whether the pathogen population could adapt and render the major gene ineffective in the longer term. The cultivars Eurol, with a susceptible background, and Darmor, with quantitative resistance, were used. We confirmed that the combination of qualitative and quantitative resistance is an effective approach for controlling the pathogen epidemics over time. This combination did not prevent isolates virulent against the major gene from amplifying in the long term but the quantitative resistance significantly delayed for 5years the loss of effectiveness of the qualitative resistance and disease severity was maintained at a low level on the genotype with both types of resistance after the fungus population had adapted to the major gene. We also showed that diversity of AvrLm6 virulence alleles was comparable in isolates recovered after the recurrent selection on lines carrying either the major gene alone or in combination with quantitative resistance: a single repeat-induced point mutation and deletion events were observed in both situations. Breeding varieties which combine qualitative and quantitative resistance can effectively contribute to disease control by increasing the potential for durability of major resistance genes.

  10. 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.

  11. 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.

  12. Process controls on regional flood frequency: Coefficient of variation and basin scale

    NASA Astrophysics Data System (ADS)

    BlöSchl, Günter; Sivapalan, Murugesu

    1997-12-01

    The coefficient of variation (CV) of maximum annual floods is examined to understand the effects of process controls and catchment size. A derived flood frequency model is used to interpret data from 489 catchments in Austria. At the core of process controls appears to be the interaction of catchment response time and storm duration, but the magnitude is not large, and often this interaction is hidden by other processes. The dependence of rainfall intensity and duration is clearly very important and reduces CV significantly. Increasing channel travel times with catchment scale tend to translate into decreasing CVs with area for small catchments while they tend to translate into increasing CVs with area for larger catchments. Nonlinear runoff processes, including threshold effects, is the main mechanism for increasing CV. They give rise to complex patterns in the relationship between CV and area. Base flow has been used as a surrogate for a number of processes, such as seasonality of streamflow. It always decreases CV and, in particular, leads to a significant decrease of CV with area. Both the observed tendency of CV to decrease with area and the scatter in the data are the result of a complex interplay of a number of processes which allows various alternative interpretations. Depending on which processes dominate under a particular hydrologic regime, different patterns arise. It appears that the explanations of the relationship between CV and catchment scale suggested in the literature are too simplistic. The case is made for using the concept of hydrologic regimes and process studies of the type presented here to help delineate homogeneous regions for regional flood frequency analyses in a physically consistent way.

  13. 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

  14. 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

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

    PubMed Central

    Stanciu, Florin; Vladu, Simona; Cuţăr, Veronica; Cocioabă, Daniela; Iancu, Florentina; Cotolea, Adnana; Stoian, Ionel Marius

    2013-01-01

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

  16. 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

  17. Allele frequencies for 15 autosomal STRs in a population sample from the Federal District (Brazil)-a territory that arose from nothing.

    PubMed

    Barra, Gustavo Barcelos; Santa Rita, Ticiane Henriques; Chianca, Camilla Figueiredo; Velasco, Lara Franciele Ribeiro; de Souza, Claudia Ferreira

    2014-09-01

    The Federal District (Brazil) was created in 1960 in the Central-West Region of Brazil in a previously unpopulated area. In 2010, this artificially founded district was populated by 2,562,963 inhabitants. In this study, the genetic variations of the 15 Next Generation Multiplex (NGM(TM)) short tandem repeat loci were analyzed. The results indicate that the NGM(TM) is a highly informative genetic system in this population, which is more similar to the southeastern, northeastern, and overall Brazil populations. This conclusion agrees with the population composition reported in the 2010 National Survey Inquiries, in which most of the immigrants were from the northeast and the southeast.

  18. 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.

  19. Dynamics of Adaptive Alleles in Divergently Selected Body Weight Lines of Chickens

    PubMed Central

    Pettersson, Mats E.; Johansson, Anna M.; Siegel, Paul B.; Carlborg, Örjan

    2013-01-01

    By studying genomic changes over time in populations subjected to strong artificial directional selection, we can gain insights to the dynamics of beneficial alleles originating from the founder population or emerging as novel mutations undergoing ongoing selection. The Virginia lines are a chicken resource population generated by long-term bi-directional, single-trait selection for juvenile body weight. We studied genome-wide allele frequency changes from generation 40 to 53 using genome-wide genotypes from directional and relaxed selection lines. Overall, there were small changes in allele frequencies at individual loci over the studied time period; but, on average, the changes were greater in lines with larger phenotypic changes. This is consistent with previous findings that much of the response to selection over the first 40 years of selection was attributable to utilization of standing genetic variation at many loci in the genome, indicating a mostly polygenic architecture for body weight. Over the course of the selection experiment, the largest phenotypic response to selection was observed in the high-weight selected line, and in this line we detected a single locus where the allele frequency changed rapidly during a late stage of the experiment. This locus likely contains a novel, beneficial mutation that appeared between generations 40 and 45 and was driven to fixation in 5 to 10 generations. This result illustrates the dependence of continued long-term selection response on standing genetic variation at many loci as well as strong, novel, beneficial mutations. PMID:24170737

  20. High-frequency variations in Earth rotation from Global Positioning System data

    NASA Astrophysics Data System (ADS)

    Rothacher, M.; Beutler, G.; Weber, R.; Hefty, J.

    2001-01-01

    Using the data of the global, dense Global Positioning System (GPS) network established by the International GPS Service a continuous, uninterrupted series of subdaily Earth rotation parameters (ERPs) with a time resolution of 2 hours has been generated at the Center for Orbit Determination in Europe. The series starts in January 1995 and has a length of more than 3 years. Starting from the 2-hour ERP values of this, to our knowledge, unique time series, the high-frequency variations in Universal Time (UT1) and polar motion (PM) due to ocean tides are studied and a set of sine and cosine coefficients is estimated for all the major tidal terms at nearly diurnal and semidiurnal frequencies. The GPS series is not very homogeneous (various processing changes during the 3 years) and still short compared to the length of very long baseline interferometry (VLBI) and satellite laser ranging (SLR) data sets. However, the results derived from this series are already of the same quality as the results from VLBI and SLR. A comparison of the tidal coefficients stemming from all three space-geodetic techniques shows an agreement on the 1 μs level for UT1 and 10 microarc seconds (μas) for PM, respectively. The RMS difference between the ocean tide amplitudes estimated from GPS data and from TOPEX/Poseidon altimeter data amounts to 0.7-0.9 μs in UT1 and 9-13 μas in PM. The residual spectrum that remains after the removal of all tidal terms has a noise level of ˜5-10 μas in PM and 0.5-1 μs in UT1 and contains nontidal signals (up to 55 μas in PM and 3 μs in UT1) that might be due to the impact of the satellite orbit modeling (12-hour revolution period of the satellites) or, alternatively, due to atmospheric or oceanic normal modes.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. HLA-A, HLA-B, HLA-DRB1 allele and haplotype frequencies in 6384 umbilical cord blood units and transplantation matching and engraftment statistics in the Zhejiang cord blood bank of China.

    PubMed

    Wang, F; He, J; Chen, S; Qin, F; Dai, B; Zhang, W; Zhu, F M; Lv, H J

    2014-02-01

    Umbilical cord blood (UCB) is a widely accepted source of progenitor cells, and now, many cord blood banks were established. Here, we analysed the HLA-A, HLA-B and HLA-DRB1 allele and haplotype frequencies, HLA matching possibilities for searching potential donors and outcome of UCB transplantations in Zhejiang cord blood bank of China. A total of 6384 UCB units were characterized for 17 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles at the first field resolution level. Additionally, B*14, B*15 and B*40 were typed to the second field level. A total of 1372 distinct A-B-DRB1 haplotypes were identified. The frequencies of 7 haplotypes were more than 1%, and 439 haplotypes were <0.01%. A*02-B*46-DRB1*09, A*33-B*58-DRB1*03 and A*30-B*13-DRB1*07 were the most common haplotypes, with frequencies of 4.4%, 3.3%, and 2.9%, respectively. Linkage disequilibrium(LD) analysis showed that there were 83 A-B, 106 B-DRB1, 54 A-DRB1 haplotypes with positive LD, in which 51 A-B, 60 B-DRB1, 32 A-DRB1 haplotypes exhibited a significant LD (P < 0.05). In 682 search requests, 12.9%, 40.0% and 42.7% of patients were found to have 6 of 6, 5 of 6 and 4 of 6 HLA-A, HLA-B and HLA-DRB1 matching donors, respectively. A total of 30 UCB units were transplanted to 24 patients (3 patients not evaluated due to early death); 14 of 21 patients (66.7%) engrafted. This study reveals the HLA distribution and its transplantation application in the cord blood bank of Zhejiang province. These data can help to select potential UCB donors for transplantation and used to assess the scale of new cord blood banking endeavours.

  7. High frequency and allele-specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus.

    PubMed

    Bogdanova, N V; Antonenkova, N N; Rogov, Y I; Karstens, J H; Hillemanns, P; Dörk, T

    2010-10-01

    Breast cancer and ovarian cancer are common malignancies in Belarus accounting for about 3500 and 800 new cases per year, respectively. For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. We assessed the frequency and distribution of three BRCA1 founder mutations 5382insC, 4153delA and Cys61Gly in two hospital-based series of 1945 unselected breast cancer patients and of 201 unselected ovarian cancer patients from Belarus as well as in 1019 healthy control females from the same population. Any of these mutations were identified in 4.4% of the breast cancer patients, 26.4% of the ovarian cancer patients and 0.5% of the controls. In the breast cancer patients, BRCA1 mutations were strongly associated with earlier age at diagnosis, with oestrogen receptor (ER) negative tumours and with a first-degree family history of breast cancer, although only 35% of the identified BRCA1 mutation carriers had such a family history. There were no marked differences in the regional distribution of BRCA1 mutations, so that the significant differences in age at diagnosis and family history of breast cancer patients from areas afflicted by the Chernobyl accident could not be explained by BRCA1. We next observed a higher impact and a shifted mutational spectrum of BRCA1 in the series of Byelorussian ovarian cancer patients where the three founder mutations accounted for 26.4% (53/201). While the Cys61Gly mutation appeared underrepresented in ovarian cancer as compared with breast cancer cases from the same population (p = 0.01), the 4153delA mutation made a higher contribution to ovarian cancer than to breast cancer (p < 0.01). BRCA1 mutations were significantly enriched among ovarian cancer cases with a first-degree family history of breast or ovarian cancer, whereas the median age at ovarian cancer diagnosis was not different between mutation carriers and non-carriers. Taken together, these results

  8. Esterase variation at three loci in meat ants.

    PubMed

    Halliday, R B

    1979-01-01

    The meat ant (Iridomyrmex purpureus) occurs in a number of color forms, with uncertain taxonomic status. Gel electrophresis of meat ant extracts, followed by nonspecific esterase staining, reveals several zones of activity. Allelic variation at three loci is proposed to account for variation in some of these zones. Two of the loci (Es-1, Es-2) appear to have recessive null alleles, whose frequencies have been estimated by the method of maximum likelihood. Geographic variation in allele frequency is attributed to behavioral and geographic subdivision of the population. Apparent disturbances in segregation ratios and deviations from Hardy-Weinberg equilibrium can be accounted for if it is argued that some nests contain more than one queen. Differences in gene frequency between sympatric populations of the red and blue forms of I. purpureus are observed, confirming their reproductive is isolation and sibling species status.

  9. 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.

  10. Variation in the resting frequency of Rhinolophus pusillus in Mainland China: effect of climate and implications for conservation.

    PubMed

    Jiang, Tinglei; Metzner, Walter; You, Yuyan; Liu, Sen; Lu, Guanjun; Li, Shi; Wang, Lei; Feng, Jiang

    2010-10-01

    This study describes variation patterns in the constant frequency of echolocation calls emitted at rest and when not flying ("resting frequency" RF) of the least horseshoe bat, Rhinolophus pusillus, on a broad geographical scale and in response to local climatic variables. Significant differences in RF were observed among populations throughout the species range in Mainland China, and this variation was positively and significantly related to climate conditions, especially environmental humidity, but the variability was only weakly associated with geographical distance. Sex dimorphism in the RF of R. pusillus may imply that female and male might keep their frequencies within a narrow range for sex recognition. Moreover, bats adjusted resting frequency to humidity, which may imply partitioning diet by prey size or the influence of rainfall noise. The results indicate that bats adjust echolocation call frequency to adapt to environmental conditions. Therefore, environmental selection shape the diversity of echolocation call structure of R. pusillus in geographically separated populations, and conservation efforts should focus on changes in local climate and effects of environmental noise.

  11. Variation in high-frequency wave radiation from small repeating earthquakes as revealed by cross-spectral analysis

    NASA Astrophysics Data System (ADS)

    Hatakeyama, Norishige; Uchida, Naoki; Matsuzawa, Toru; Okada, Tomomi; Nakajima, Junichi; Matsushima, Takeshi; Kono, Toshio; Hirahara, Satoshi; Nakayama, Takashi

    2016-11-01

    We examined the variation in the high-frequency wave radiation for three repeating earthquake sequences (M = 3.1-4.1) in the northeastern Japan subduction zone by waveform analyses. Earthquakes in each repeating sequence are located at almost the same place and show low-angle thrust type focal mechanisms, indicating that they represent repeated ruptures of a seismic patch on the plate boundary. We calculated cross-spectra of the waveforms and obtained the phases and coherences for pairs of events in the respective repeating sequences in order to investigate the waveform differences. We used waveform data sampled at 1 kHz that were obtained from temporary seismic observations we conducted immediately after the 2011 Tohoku earthquake near the source area. For two repeating sequences, we found that the interevent delay times for the two waveforms in a frequency band higher than the corner frequencies are different from those in a lower frequency band for particular event pairs. The phases and coherences show that there are coherent high-frequency waves for almost all the repeaters regardless of the high-frequency delays. These results indicate that high-frequency waves are always radiated from the same vicinity (subpatch) for these events but the time intervals between the ruptures of the subpatch and the centroid times can vary. We classified events in the sequence into two subgroups according to the high-frequency band interevent delays relative to the low-frequency band. For one sequence, we found that all the events that occurred just after (within 11 days) larger nearby earthquakes belong to one subgroup while other events belong to the other subgroup. This suggests that the high-frequency wave differences were caused by stress perturbations due to the nearby earthquakes. In summary, our observations suggest that high-frequency waves from the repeating sequence are radiated not from everywhere but from a long-duration subpatch within the seismic slip area. The

  12. 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

  13. 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

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

    PubMed

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

    2015-05-01

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

  15. 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.

  16. 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...

  17. Parameterizing both path amplitude and delay variations of underwater acoustic channels for block decoding of orthogonal frequency division multiplexing.

    PubMed

    Xu, Xiaoka; Wang, Zhaohui; Zhou, Shengli; Wan, Lei

    2012-06-01

    There are no commonly-agreed mathematical models for the input-output relationship of underwater acoustic channels. For each path in a time-varying multipath channel within a short period of time (e.g., one short data block), this paper proposes to use one polynomial to approximate the amplitude variation and another polynomial up to the first order to approximate the delay variation within a block duration. Under such a channel parameterization, the discrete-time channel input- output relationship tailored to zero-padded orthogonal-frequency-division-multiplexing (OFDM) transmissions is then derived, based on which an OFDM receiver is validated using experimental data collected during the 2008 Surface Processes and Acoustic Communications Experiment. For channels with a short coherence time, the numerical results show that incorporating both the amplitude and delay variations improves the system performance.

  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. Variation in the frequency and extent of hybridization between Leucosceptrum japonicum and L. stellipilum (Lamiaceae) in the Central Japanese Mainland.

    PubMed

    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

  20. Variation in the resting frequency of Rhinolophus pusillus in Mainland China: Effect of climate and implications for conservation

    PubMed Central

    Jiang, Tinglei; Metzner, Walter; You, Yuyan; Liu, Sen; Lu, Guanjun; Li, Shi; Wang, Lei; Feng, Jiang

    2010-01-01

    This study describes variation patterns in the constant frequency of echolocation calls emitted at rest and when not flying (“resting frequency” RF) of the least horseshoe bat, Rhinolophus pusillus, on a broad geographical scale and in response to local climatic variables. Significant differences in RF were observed among populations throughout the species range in Mainland China, and this variation was positively and significantly related to climate conditions, especially environmental humidity, but the variability was only weakly associated with geographical distance. Sex dimorphism in the RF of R. pusillus may imply that female and male might keep their frequencies within a narrow range for sex recognition. Moreover, bats adjusted resting frequency to humidity, which may imply partitioning diet by prey size or the influence of rainfall noise. The results indicate that bats adjust echolocation call frequency to adapt to environmental conditions. Therefore, environmental selection shape the diversity of echolocation call structure of R. pusillus in geographically separated populations, and conservation efforts should focus on changes in local climate and effects of environmental noise. PMID:20968390

  1. 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...

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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)…

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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...

  13. 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

  14. 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 Stat