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Sample records for linkage disequilibrium estimation

  1. Effective population size of an indigenous Swiss cattle breed estimated from linkage disequilibrium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Effective population size is an important parameter for the assessment of genetic diversity within a livestock population and its development over time. If pedigree information is not available, linkage disequilibrium (LD) analysis might offer an alternative perspective for the estimation of effecti...

  2. Exploring linkage disequilibrium.

    PubMed

    Baird, Stuart J E

    2015-09-01

    Linkage disequilibrium (LD, association of allelic states across loci) is poorly understood by many evolutionary biologists, but as technology for multilocus sampling improves, we ignore LD at our peril. If we sample variation at 10 loci in an organism with 20 chromosomes, we can reasonably treat them as 10 'independent witnesses' of the evolutionary process. If instead, we sample variation at 1000 loci, many are bound to be close together on a chromosome. With only one or two crossovers per meiosis, associations between close neighbours decay so slowly that even LD created far in the past will not have dissipated, so we cannot treat the 1000 loci as independent witnesses (Barton ). This means that as marker density on genomes increases classic analyses assuming independent loci become mired in the problem of overconfidence: if 1000 independent witnesses are assumed, and that number should be much lower, any conclusion will be overconfident. This is of special concern because our literature suffers from a strong publication bias towards confident answers, even when they turn out to be wrong (Knowles ). In contrast, analyses that take into account associations across loci both control for overconfidence and can inform us about LD generating events far in the past, for example human/Neanderthal admixture (Fu et al. ). With increased marker density, biologists must increase their awareness of LD and, in this issue of Molecular Ecology Resources, Kemppainen et al. () make software available that can only help in this process: LDna allows patterns of LD in a data set to be explored using tools borrowed from network analysis. This has great potential, but realizing that potential requires understanding LD. PMID:26261040

  3. Linkage Disequilibrium Estimation of Chinese Beef Simmental Cattle Using High-density SNP Panels

    PubMed Central

    Zhu, M.; Zhu, B.; Wang, Y. H.; Wu, Y.; Xu, L.; Guo, L. P.; Yuan, Z. R.; Zhang, L. P.; Gao, X.; Gao, H. J.; Xu, S. Z.; Li, J. Y.

    2013-01-01

    Linkage disequilibrium (LD) plays an important role in genomic selection and mapping quantitative trait loci (QTL). In this study, the pattern of LD and effective population size (Ne) were investigated in Chinese beef Simmental cattle. A total of 640 bulls were genotyped with IlluminaBovinSNP50BeadChip and IlluminaBovinHDBeadChip. We estimated LD for each autosomal chromosome at the distance between two random SNPs of <0 to 25 kb, 25 to 50 kb, 50 to 100 kb, 100 to 500 kb, 0.5 to 1 Mb, 1 to 5 Mb and 5 to 10 Mb. The mean values of r2 were 0.30, 0.16 and 0.08, when the separation between SNPs ranged from 0 to 25 kb to 50 to 100 kb and then to 0.5 to 1 Mb, respectively. The LD estimates decreased as the distance increased in SNP pairs, and increased with the increase of minor allelic frequency (MAF) and with the decrease of sample sizes. Estimates of effective population size for Chinese beef Simmental cattle decreased in the past generations and Ne was 73 at five generations ago. PMID:25049849

  4. Effects of overlapping generations on linkage disequilibrium estimates of effective population size.

    PubMed

    Waples, Robin S; Antao, Tiago; Luikart, Gordon

    2014-06-01

    Use of single-sample genetic methods to estimate effective population size has skyrocketed in recent years. Although the underlying models assume discrete generations, they are widely applied to age-structured species. We simulated genetic data for 21 iteroparous animal and plant species to evaluate two untested hypotheses regarding performance of the single-sample method based on linkage disequilibrium (LD): (1) estimates based on single-cohort samples reflect the effective number of breeders in one reproductive cycle (Nb), and (2) mixed-age samples reflect the effective size per generation (Ne). We calculated true Ne and Nb, using the model species' vital rates, and verified these with individual-based simulations. We show that single-cohort samples should be equally influenced by Nb and Ne and confirm this with simulated results: [Formula: see text] was a linear (r(2) = 0.98) function of the harmonic mean of Ne and Nb. We provide a quantitative bias correction for raw [Formula: see text] based on the ratio Nb/Ne, which can be estimated from two or three simple life history traits. Bias-adjusted estimates were within 5% of true Nb for all 21 study species and proved robust when challenged with new data. Mixed-age adult samples produced downwardly biased estimates in all species, which we attribute to a two-locus Wahlund effect (mixture LD) caused by combining parents from different cohorts in a single sample. Results from this study will facilitate interpretation of rapidly accumulating genetic estimates in terms of both Ne (which influences long-term evolutionary processes) and Nb (which is more important for understanding eco-evolutionary dynamics and mating systems). PMID:24717176

  5. Effects of Overlapping Generations on Linkage Disequilibrium Estimates of Effective Population Size

    PubMed Central

    Waples, Robin S.; Antao, Tiago; Luikart, Gordon

    2014-01-01

    Use of single-sample genetic methods to estimate effective population size has skyrocketed in recent years. Although the underlying models assume discrete generations, they are widely applied to age-structured species. We simulated genetic data for 21 iteroparous animal and plant species to evaluate two untested hypotheses regarding performance of the single-sample method based on linkage disequilibrium (LD): (1) estimates based on single-cohort samples reflect the effective number of breeders in one reproductive cycle (Nb), and (2) mixed-age samples reflect the effective size per generation (Ne). We calculated true Ne and Nb, using the model species’ vital rates, and verified these with individual-based simulations. We show that single-cohort samples should be equally influenced by Nb and Ne and confirm this with simulated results: N^b was a linear (r2 = 0.98) function of the harmonic mean of Ne and Nb. We provide a quantitative bias correction for raw N^b based on the ratio Nb/Ne, which can be estimated from two or three simple life history traits. Bias-adjusted estimates were within 5% of true Nb for all 21 study species and proved robust when challenged with new data. Mixed-age adult samples produced downwardly biased estimates in all species, which we attribute to a two-locus Wahlund effect (mixture LD) caused by combining parents from different cohorts in a single sample. Results from this study will facilitate interpretation of rapidly accumulating genetic estimates in terms of both Ne (which influences long-term evolutionary processes) and Nb (which is more important for understanding eco-evolutionary dynamics and mating systems). PMID:24717176

  6. Estimating contemporary effective population size on the basis of linkage disequilibrium in the face of migration.

    PubMed

    Waples, Robin S; England, Phillip R

    2011-10-01

    Effective population size (Ne) is an important genetic parameter because of its relationship to loss of genetic variation, increases in inbreeding, accumulation of mutations, and effectiveness of selection. Like most other genetic approaches that estimate contemporary Ne, the method based on linkage disequilibrium (LD) assumes a closed population and (in the most common applications) randomly recombining loci. We used analytical and numerical methods to evaluate the absolute and relative consequences of two potential violations of the closed-population assumption: (1) mixture LD caused by occurrence of more than one gene pool, which would downwardly bias Ne and (2) reductions in drift LD (and hence upward bias in Ne) caused by an increase in the number of parents responsible for local samples. The LD method is surprisingly robust to equilibrium migration. Effects of mixture LD are small for all values of migration rate (m), and effects of additional parents are also small unless m is high in genetic terms. LD estimates of Ne therefore accurately reflect local (subpopulation) Ne unless m>∼5-10%. With higher m, Ne converges on the global (metapopulation) Ne. Two general exceptions were observed. First, equilibrium migration that is rare and hence episodic can occasionally lead to substantial mixture LD, especially when sample size is small. Second, nonequilibrium, pulse migration of strongly divergent individuals can also create strong mixture LD and depress estimates of local Ne. In both cases, assignment tests, Bayesian clustering, and other methods often will allow identification of recent immigrants that strongly influence results. In simulations involving equilibrium migration, the standard LD method performed better than a method designed to jointly estimate Ne and m. The above results assume loci are not physically linked; for tightly linked loci, the LD signal from past migration events can persist for many generations, with consequences for Ne estimates

  7. Genetic Characterization and Linkage Disequilibrium Estimation of a Global Maize Collection Using SNP Markers

    PubMed Central

    Yan, Jianbing; Shah, Trushar; Warburton, Marilyn L.; Buckler, Edward S.; McMullen, Michael D.; Crouch, Jonathan

    2009-01-01

    A newly developed maize Illumina GoldenGate Assay with 1536 SNPs from 582 loci was used to genotype a highly diverse global maize collection of 632 inbred lines from temperate, tropical, and subtropical public breeding programs. A total of 1229 informative SNPs and 1749 haplotypes within 327 loci was used to estimate the genetic diversity, population structure, and familial relatedness. Population structure identified tropical and temperate subgroups, and complex familial relationships were identified within the global collection. Linkage disequilibrium (LD) was measured overall and within chromosomes, allelic frequency groups, subgroups related by geographic origin, and subgroups of different sample sizes. The LD decay distance differed among chromosomes and ranged between 1 to 10 kb. The LD distance increased with the increase of minor allelic frequency (MAF), and with smaller sample sizes, encouraging caution when using too few lines in a study. The LD decay distance was much higher in temperate than in tropical and subtropical lines, because tropical and subtropical lines are more diverse and contain more rare alleles than temperate lines. A core set of inbreds was defined based on haplotypes, and 60 lines capture 90% of the haplotype diversity of the entire panel. The defined core sets and the entire collection can be used widely for different research targets. PMID:20041112

  8. Linkage Disequilibrium Estimation of Effective Population Size with Immigrants from Divergent Populations: A Case Study on Spanish Mackerel (Scomberomorus commerson).

    PubMed

    Macbeth, Gilbert Michael; Broderick, Damien; Buckworth, Rik C; Ovenden, Jennifer R

    2013-03-11

    Estimates of genetic effective population size (Ne) using molecular markers are a potentially useful tool for the management of endangered through to commercial species. But, pitfalls are predicted when the effective size is large, as estimates require large numbers of samples from wild populations for statistical validity. Our simulations showed that linkage disequilibrium estimates of Ne up to 10,000 with finite confidence limits can be achieved with sample sizes around 5000. This was deduced from empirical allele frequencies of seven polymorphic microsatellite loci in a commercially harvested fisheries species, the narrow barred Spanish mackerel (Scomberomorus commerson). As expected, the smallest standard deviation of Ne estimates occurred when low frequency alleles were excluded. Additional simulations indicated that the linkage disequilibrium method was sensitive to small numbers of genotypes from cryptic species or conspecific immigrants. A correspondence analysis algorithm was developed to detect and remove outlier genotypes that could possibly be inadvertently sampled from cryptic species or non-breeding immigrants from genetically separate populations. Simulations demonstrated the value of this approach in Spanish mackerel data. When putative immigrants were removed from the empirical data, 95% of the Ne estimates from jacknife resampling were above 24,000. PMID:23550119

  9. Linkage Disequilibrium Estimation of Effective Population Size with Immigrants from Divergent Populations: A Case Study on Spanish Mackerel (Scomberomorus commerson)

    PubMed Central

    Macbeth, Gilbert Michael; Broderick, Damien; Buckworth, Rik C.; Ovenden, Jennifer R.

    2013-01-01

    Estimates of genetic effective population size (Ne) using molecular markers are a potentially useful tool for the management of endangered through to commercial species. However, pitfalls are predicted when the effective size is large because estimates require large numbers of samples from wild populations for statistical validity. Our simulations showed that linkage disequilibrium estimates of Ne up to 10,000 with finite confidence limits can be achieved with sample sizes of approximately 5000. This number was deduced from empirical allele frequencies of seven polymorphic microsatellite loci in a commercially harvested fisheries species, the narrow-barred Spanish mackerel (Scomberomorus commerson). As expected, the smallest SD of Ne estimates occurred when low-frequency alleles were excluded. Additional simulations indicated that the linkage disequilibrium method was sensitive to small numbers of genotypes from cryptic species or conspecific immigrants. A correspondence analysis algorithm was developed to detect and remove outlier genotypes that could possibly be inadvertently sampled from cryptic species or nonbreeding immigrants from genetically separate populations. Simulations demonstrated the value of this approach in Spanish mackerel data. When putative immigrants were removed from the empirical data, 95% of the Ne estimates from jacknife resampling were greater than 24,000. PMID:23550119

  10. Estimating Effective Population Size from Linkage Disequilibrium between Unlinked Loci: Theory and Application to Fruit Fly Outbreak Populations

    PubMed Central

    Sved, John A; Cameron, Emilie C.; Gilchrist, A. Stuart

    2013-01-01

    There is a substantial literature on the use of linkage disequilibrium (LD) to estimate effective population size using unlinked loci. The estimates are extremely sensitive to the sampling process, and there is currently no theory to cope with the possible biases. We derive formulae for the analysis of idealised populations mating at random with multi-allelic (microsatellite) loci. The ‘Burrows composite index’ is introduced in a novel way with a ‘composite haplotype table’. We show that in a sample of diploid size , the mean value of or from the composite haplotype table is biased by a factor of , rather than the usual factor for a conventional haplotype table. But analysis of population data using these formulae leads to estimates that are unrealistically low. We provide theory and simulation to show that this bias towards low estimates is due to null alleles, and introduce a randomised permutation correction to compensate for the bias. We also consider the effect of introducing a within-locus disequilibrium factor to , and find that this factor leads to a bias in the estimate. However this bias can be overcome using the same randomised permutation correction, to yield an altered with lower variance than the original , and one that is also insensitive to null alleles. The resulting formulae are used to provide estimates on 40 samples of the Queensland fruit fly, Bactrocera tryoni, from populations with widely divergent expectations. Linkage relationships are known for most of the microsatellite loci in this species. We find that there is little difference in the estimated values from using known unlinked loci as compared to using all loci, which is important for conservation studies where linkage relationships are unknown. PMID:23894410

  11. Positional Cloning by Linkage Disequilibrium

    PubMed Central

    Maniatis, Nikolas; Collins, Andrew; Gibson, Jane; Zhang, Weihua; Tapper, William; Morton, Newton E.

    2004-01-01

    Recently, metric linkage disequilibrium (LD) maps that assign an LD unit (LDU) location for each marker have been developed (Maniatis et al. 2002). Here we present a multiple pairwise method for positional cloning by LD within a composite likelihood framework and investigate the operating characteristics of maps in physical units (kb) and LDU for two bodies of data (Daly et al. 2001; Jeffreys et al. 2001) on which current ideas of blocks are based. False-negative indications of a disease locus (type II error) were examined by selecting one single-nucleotide polymorphism (SNP) at a time as causal and taking its allelic count (0, 1, or 2, for the three genotypes) as a pseudophenotype, Y. By use of regression and correlation, association between every pseudophenotype and the allelic count of each SNP locus (X) was based on an adaptation of the Malecot model, which includes a parameter for location of the putative gene. By expressing locations in kb or LDU, greater power for localization was observed when the LDU map was fitted. The efficiency of the kb map, relative to the LDU map, to describe LD varied from a maximum of 0.87 to a minimum of 0.36, with a mean of 0.62. False-positive indications of a disease locus (type I error) were examined by simulating an unlinked causal SNP and the allele count was used as a pseudophenotype. The type I error was in good agreement with Wald’s likelihood theorem for both metrics and all models that were tested. Unlike tests that select only the most significant marker, haplotype, or haploset, these methods are robust to large numbers of markers in a candidate region. Contrary to predictions from tagging SNPs that retain haplotype diversity, the sample with smaller size but greater SNP density gave less error. The locations of causal SNPs were estimated with the same precision in blocks and steps, suggesting that block definition may be less useful than anticipated for mapping a causal SNP. These results provide a guide to

  12. Linkage Disequilibrium Mapping of Meat Quality QTL

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies based on linkage analysis have identified broad areas in the bovine genome associated with meat quality. Linkage disequilibrium (LD) analyses have the potential to identify narrower regions and point towards candidate genes. Tenderness and marbling were chosen to be evaluated in a ...

  13. Whole genome linkage disequilibrium maps in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine whole genome linkage disequilibrium maps were constructed for eight breeds of cattle. These data provide fundamental information concerning bovine genome organization which will allow the design of studies to associate genetic variation with economically important traits and also provides bac...

  14. Linkage disequilibrium in Theobroma cacao L. populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although the potential of Linkage Disequilibrium (LD) mapping to associate markers to agronomic and horticultural traits has been already recognized in cacao, its real efficiency depends on the nature and structure of the LD in the genome of the populations under study. LD is dependent on several fa...

  15. How Population Growth Affects Linkage Disequilibrium

    PubMed Central

    Rogers, Alan R.

    2014-01-01

    The “LD curve” relates the linkage disequilibrium (LD) between pairs of nucleotide sites to the distance that separates them along the chromosome. The shape of this curve reflects natural selection, admixture between populations, and the history of population size. This article derives new results about the last of these effects. When a population expands in size, the LD curve grows steeper, and this effect is especially pronounced following a bottleneck in population size. When a population shrinks, the LD curve rises but remains relatively flat. As LD converges toward a new equilibrium, its time path may not be monotonic. Following an episode of growth, for example, it declines to a low value before rising toward the new equilibrium. These changes happen at different rates for different LD statistics. They are especially slow for estimates of σd2, which therefore allow inferences about ancient population history. For the human population of Europe, these results suggest a history of population growth. PMID:24907258

  16. Linkage disequilibrium in the neurofibromatosis 1 (NF1) region: implications for gene mapping.

    PubMed Central

    Jorde, L B; Watkins, W S; Viskochil, D; O'Connell, P; Ward, K

    1993-01-01

    To test the usefulness of linkage disequilibrium for gene mapping, we compared physical distances and linkage disequilibrium among eight RFLPs in the neurofibromatosis 1 (NF1) region. Seven of the polymorphisms span most of the NF1 gene, while the remaining polymorphism lies approximately 70 kb 3' to a stop codon in exon 49. By using Centre d'Etude du Polymorphisme Humain (CEPH) kindreds, 91-110 unrelated parents were genotyped. A high degree of disequilibrium is maintained among the seven intragenic polymorphisms (r > .82, P < 10(-7)), even though they are separated by as much as 340 kb. The 3' polymorphism is only 68 kb distal to the next polymorphism, but disequilibrium between the 3' polymorphism and all others is comparatively low (magnitude of 4 < .33, P values .27-.001). This result was replicated in three sets of unrelated kindreds: the Utah CEPH families, the non-Utah CEPH families, and an independent set of NF1 families. Trigenic, quadrigenic, three-locus, and four-locus disequilibrium measures were also estimated. There was little evidence of higher-order linkage disequilibrium. As expected for a disease with multiple mutations, no disequilibrium was observed between the disease gene and any of the RFLPs. The observed pattern of high disequilibrium within the gene and a loss of disequilibrium 3' to the stop codon could have implications for gene mapping studies. These are discussed, and guidelines for linkage disequilibrium studies are suggested. PMID:8105688

  17. Constructing Linkage Disequilibrium Map with Iterative Approach

    NASA Astrophysics Data System (ADS)

    Ao, S. I.

    2008-05-01

    With recent advance of the genotyping single nucleotide polymorphisms (SNPs) in mass scale of high density in a candidate region of the human genome, the linkage disequilibrium analysis can offer a much higher resolution of the biological samples than the traditional linkage maps. We have formulated this LD mapping problem as a constrained unidimensional scaling problem. Our method, which is directly based on the measurement of LD among SNPs, is non-parametric. Therefore it is different from LD maps derived from the given Malecot model. We have formulated with the quadratic programming approach for solving this constrained unidimensional scaling problem. Different from the classical metric unidimensional scaling problem, the constrained problem is not an NP-hard combinatorial problem. The optimal solution is determined by using the quadratic programming solver. Nevertheless, because of the large requirement for memory during the running time that may cause the out of memory problems, and the high computational time of the quadratic programming algorithm, the iterative algorithm has been developed for solving this LD constrained unidimensional scaling problem.

  18. Linkage disequilibrium estimates of contemporary N e using highly variable genetic markers: a largely untapped resource for applied conservation and evolution.

    PubMed

    Waples, Robin S; Do, Chi

    2010-05-01

    Genetic methods are routinely used to estimate contemporary effective population size (N e) in natural populations, but the vast majority of applications have used only the temporal (two-sample) method. We use simulated data to evaluate how highly polymorphic molecular markers affect precision and bias in the single-sample method based on linkage disequilibrium (LD). Results of this study are as follows: (1) Low-frequency alleles upwardly bias [Formula: see text], but a simple rule can reduce bias to estimates can be obtained for relatively small populations (N e < 200), and small populations are not likely to be mistaken for large ones. However, it is very difficult to obtain reliable estimates for large populations. (3) With 'microsatellite' data, the LD method has greater precision than the temporal method, unless the latter is based on samples taken many generations apart. Our results indicate the LD method has widespread applicability to conservation (which typically focuses on small populations) and the study of evolutionary processes in local populations. Considerable opportunity exists to extract more information about N e in nature by wider use of single-sample estimators and by combining estimates from different methods. PMID:25567922

  19. Estimates of Selection and Gene Flow from Measures of Cline Width and Linkage Disequilibrium in Heliconius Hybrid Zones

    PubMed Central

    Mallet, J.; Barton, N.; Gerardo, L. M.; Jose, S. C.; Manuel, M. M.; Eeley, H.

    1990-01-01

    Hybrid zones can yield estimates of natural selection and gene flow. The width of a cline in gene frequency is approximately proportional to gene flow (σ) divided by the square root of per-locus selection ( &s). Gene flow also causes gametic correlations (linkage disequilibria) between genes that differ across hybrid zones. Correlations are stronger when the hybrid zone is narrow, and rise to a maximum roughly equal to s. Thus cline width and gametic correlations combine to give estimates of gene flow and selection. These indirect measures of σ and s are especially useful because they can be made from collections, and require no field experiments. The method was applied to hybrid zones between color pattern races in a pair of Peruvian Heliconius butterfly species. The species are Mullerian mimics of one another, and both show the same changes in warning color pattern across their respective hybrid zones. The expectations of cline width and gametic correlation were generated using simulations of clines stabilized by strong frequency-dependent selection. In the hybrid zone in Heliconius erato, clines at three major color pattern loci were between 8.5 and 10.2 km wide, and the pairwise gametic correlations peaked at R & 0.35. These measures suggest that s & 0.23 per locus, and that σ & 2.6 km. In erato, the shapes of the clines agreed with that expected on the basis of dominance. Heliconius melpomene has a nearly coincident hybrid zone. In this species, cline widths at four major color pattern loci varied between 11.7 and 13.4 km. Pairwise gametic correlations peaked near R & 1.00 for tightly linked genes, and at R & 0.40 for unlinked genes, giving s & 0.25 per locus and σ & 3.7 km. In melpomene, cline shapes did not perfectly fit theoretical shapes based on dominance; this deviation might be explained by long-distance migration and/or strong epistasis. Compared with erato, sample sizes in melpomene are lower and the genetics of its color patterns are less well

  20. Linkage disequilibrium predicts physical distance in the adenomatous polyposis coli region

    SciTech Connect

    Jorde, L.B.; Watkins, W.S.; Carlson, M.; Albertsen, H.; Thliveris, A.; Leppert, M. )

    1994-05-01

    To test the reliability of linkage-disequilibrium analysis for gene mapping, the authors compared physical distance and linkage disequilibrium among seven polymorphisms in the adenomatous polyposis coli (APC) region on chromosome 5. Three of them lie within the APC gene, and two lie within the nearby MCC (mutated in colon cancer) gene. One polymorphism lies between the two genes, and one is likely to be 5' of MCC. Five of these polymorphisms are newly reported. All polymorphisms were typed in the CEPH kindreds, yielding 179-205 unrelated two-locus haplotypes. Linkage disequilibrium between each pair of polymorphisms is highly correlated with physical distance in this 550-kb region (correlation coefficient [minus].80, P < .006). This result is replicated in both the Utah and non-Utah CEPH kindreds. There is a tendency for greater disequilibrium among pairs of polymorphisms located within the same gene than among other pairs of polymorphisms. Trigenic, quadrigenic, three-locus, and four-locus disequilibrium measures were also estimated, but these measures revealed much less disequilibrium than did the two-locus disequilibrium measures. A review of 19 published disequilibrium studies, including this one, shows that linkage disequilibrium nearly always correlates significantly with physical distance in genomic regions >50-60 kb but that it does not do so in smaller genomic regions. The authors show that this agrees with theoretical predictions. This finding helps to resolve controversies regarding the use of disequilibrium for inferring gene order. Disequilibrium mapping is unlikely to predict gene order correctly in regions <50-60 kb in size but can often be applied successfully in regions of 50-500 kb or so in size. It is convenient that this is the range in which other mapping techniques, including chromosome walking and linkage mapping, become difficult. 81 refs., 3 figs., 5 tabs.

  1. A comparison of genetic map distance and linkage disequilibrium between 15 polymorphic dinucleotide repeat loci in two populations

    SciTech Connect

    Urbanek, M.; Goldman, D.; Long, J.C.

    1994-09-01

    Linkage disequilibrium has recently been used to map the diastrophic dysplasia gene in a Finnish sample. One advantage of this method is that the large pedigrees required by some other methods are unnecessary. Another advantage is that linkage disequilibrium mapping capitalizes on the cumulative history of recombination events, rather than those occurring within the sampled individuals. A potential limitation of linkage disequilibrium mapping is that linkage equilibrium is likely to prevail in all but the most isolated populations, e.g., those which have recently experienced founder effects or severe population bottlenecks. In order to test the method`s generality, we examined patterns of linkage disequilibrium between pairs of loci within a known genetic map. Two populations were analyzed. The first population, Navajo Indians (N=45), is an isolate that experienced a severe bottleneck in the 1860`s. The second population, Maryland Caucasians (N=45), is cosmopolitan. We expected the Navajo sample to display more linkage disequilibrium than the Caucasian sample, and possibly that the Navajo disequilibrium pattern would reflect the genetic map. Linkage disequilibrium coefficients were estimated between pairs of alleles at different loci using maximum likelihood. The genetic isolate structure of Navajo Indians is confirmed by the DNA typings. Heterozygosity is lower than in the Caucasians, and fewer different alleles are observed. However, a relationship between genetic map distance and linkage disequilibrium could be discerned in neither the Navajo nor the Maryland samples. Slightly more linkage disequilibrium was observed in the Navajos, but both data sets were characterized by very low disequilibrium levels. We tentatively conclude that linkage disequilibrium mapping with dinucleotide repeats will only be useful with close linkage between markers and diseases, even in very isolated populations.

  2. The Structure of Linkage Disequilibrium Around a Selective Sweep

    PubMed Central

    McVean, Gil

    2007-01-01

    The fixation of advantageous mutations by natural selection has a profound impact on patterns of linked neutral variation. While it has long been appreciated that such selective sweeps influence the frequency spectrum of nearby polymorphism, it has only recently become clear that they also have dramatic effects on local linkage disequilibrium. By extending previous results on the relationship between genealogical structure and linkage disequilibrium, I obtain simple expressions for the influence of a selective sweep on patterns of allelic association. I show that sweeps can increase, decrease, or even eliminate linkage disequilibrium (LD) entirely depending on the relative position of the selected and neutral loci. I also show the importance of the age of the neutral mutations in predicting their degree of association and describe the consequences of such results for the interpretation of empirical data. In particular, I demonstrate that while selective sweeps can eliminate LD, they generate patterns of genetic variation very different from those expected from recombination hotspots. PMID:17194788

  3. Linkage disequilibrium interval mapping of quantitative trait loci

    PubMed Central

    Boitard, Simon; Abdallah, Jihad; de Rochambeau, Hubert; Cierco-Ayrolles, Christine; Mangin, Brigitte

    2006-01-01

    Background For many years gene mapping studies have been performed through linkage analyses based on pedigree data. Recently, linkage disequilibrium methods based on unrelated individuals have been advocated as powerful tools to refine estimates of gene location. Many strategies have been proposed to deal with simply inherited disease traits. However, locating quantitative trait loci is statistically more challenging and considerable research is needed to provide robust and computationally efficient methods. Results Under a three-locus Wright-Fisher model, we derived approximate expressions for the expected haplotype frequencies in a population. We considered haplotypes comprising one trait locus and two flanking markers. Using these theoretical expressions, we built a likelihood-maximization method, called HAPim, for estimating the location of a quantitative trait locus. For each postulated position, the method only requires information from the two flanking markers. Over a wide range of simulation scenarios it was found to be more accurate than a two-marker composite likelihood method. It also performed as well as identity by descent methods, whilst being valuable in a wider range of populations. Conclusion Our method makes efficient use of marker information, and can be valuable for fine mapping purposes. Its performance is increased if multiallelic markers are available. Several improvements can be developed to account for more complex evolution scenarios or provide robust confidence intervals for the location estimates. PMID:16542433

  4. Highly Variable Patterns of Linkage Disequilibrium in Multiple Soybean Populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Prospects for utilizing whole genome association analysis in autogamous plant populations appear promising due to the reported high levels of linkage disequilibrium (LD). To determine the optimal strategies for implementing association analysis in soybean (Glycine max L. Merr.), we analyzed the str...

  5. The genetic structure of natural populations of Drosophila melanogaster XIII. Further studies on linkage disequilibrium.

    PubMed

    Mukai, T; Voelker, R A

    1977-05-01

    The Raleigh, North Carolina, population of Drosophila melanogaster was examined for linkage disequilibrium in 1974, several years after previous analyses in 1968, 1969, and 1970. alphaglycerol-3-phosphate dehydrogenase-1 (alphaGpdh-1), malate dehydrogenase-1 (Mdh-1), alcohol dehydrogenase (Adh), and hexokinase-C (Hex-C, tentative name, F. M. Johnson, unpublished; position determined by the present authors to be 2-74.5) were assayed for 617 second chromosomes, and esterase-C (Est-C) and octanol dehydrogenase (Odh) were assayed for 526 third chromosomes. In addition, two polymorphic inversions in the second chromosomes [In(2L)t and In(2R)NS] were examined, and the following findings were obtained: (1) No linkage disequilibrium between isozyme genes was detected. Significant linkage disequilibria were found only between the polymorphic inversions and isozyme genes [In(2L)t vs. Adh, and In(2R)NS vs. Hex-C]. Significant disequilibrium was not detected between In(2L)t and alphaGpdh-1, which is included in the inversion, but a tendency toward disequilibrium was consistently found from 1968 to 1974. The frequency of two-strand double crossovers within inversion In(2L)t involving a single crossover on each side of alphaGpdh-1 was estimated to be 0.00022. Thus, the consistent but not significant linkage disequilibrium between the two factors can be explained by recombination after the inversion occurred. (2) Previously existing linkage disequilibrium between Adh and In(2R)NS (the distance is about 30 cM, but the effective recombination value is about 1.75%) was found to have disappeared. (3) No higher-order linkage disequilibrium was detected. (4) Linkage disequilibrium between Odh and Est-C (the distance of which was estimated to be 0.0058 +/- 0.002) could not be detected (chi(2) (df=1) = 0.9).-From the above results, it was concluded that linkage disequilibria among isozyme genes are very rare in D. melanogaster, so that the Franklin-Lewontin model (Franklin and Lewontin

  6. Constructing a linkage-linkage disequilibrium map using dominant-segregating markers.

    PubMed

    Zhu, Xuli; Dong, Leiming; Jiang, Libo; Li, Huan; Sun, Lidan; Zhang, Hui; Yu, Weiwu; Liu, Haokai; Dai, Wensheng; Zeng, Yanru; Wu, Rongling

    2016-02-01

    The relationship between linkage disequilibrium (LD) and recombination fraction can be used to infer the pattern of genetic variation and evolutionary process in humans and other systems. We described a computational framework to construct a linkage-LD map from commonly used biallelic, single-nucleotide polymorphism (SNP) markers for outcrossing plants by which the decline of LD is visualized with genetic distance. The framework was derived from an open-pollinated (OP) design composed of plants randomly sampled from a natural population and seeds from each sampled plant, enabling simultaneous estimation of the LD in the natural population and recombination fraction due to allelic co-segregation during meiosis. We modified the framework to infer evolutionary pasts of natural populations using those marker types that are segregating in a dominant manner, given their role in creating and maintaining population genetic diversity. A sophisticated two-level EM algorithm was implemented to estimate and retrieve the missing information of segregation characterized by dominant-segregating markers such as single methylation polymorphisms. The model was applied to study the relationship between linkage and LD for a non-model outcrossing species, a gymnosperm species, Torreya grandis, naturally distributed in mountains of the southeastern China. The linkage-LD map constructed from various types of molecular markers opens a powerful gateway for studying the history of plant evolution. PMID:26622063

  7. Detecting Recombination Hotspots from Patterns of Linkage Disequilibrium

    PubMed Central

    Wall, Jeffrey D.; Stevison, Laurie S.

    2016-01-01

    With recent advances in DNA sequencing technologies, it has become increasingly easy to use whole-genome sequencing of unrelated individuals to assay patterns of linkage disequilibrium (LD) across the genome. One type of analysis that is commonly performed is to estimate local recombination rates and identify recombination hotspots from patterns of LD. One method for detecting recombination hotspots, LDhot, has been used in a handful of species to further our understanding of the basic biology of recombination. For the most part, the effectiveness of this method (e.g., power and false positive rate) is unknown. In this study, we run extensive simulations to compare the effectiveness of three different implementations of LDhot. We find large differences in the power and false positive rates of these different approaches, as well as a strong sensitivity to the window size used (with smaller window sizes leading to more accurate estimation of hotspot locations). We also compared our LDhot simulation results with comparable simulation results obtained from a Bayesian maximum-likelihood approach for identifying hotspots. Surprisingly, we found that the latter computationally intensive approach had substantially lower power over the parameter values considered in our simulations. PMID:27226166

  8. Detecting Recombination Hotspots from Patterns of Linkage Disequilibrium.

    PubMed

    Wall, Jeffrey D; Stevison, Laurie S

    2016-01-01

    With recent advances in DNA sequencing technologies, it has become increasingly easy to use whole-genome sequencing of unrelated individuals to assay patterns of linkage disequilibrium (LD) across the genome. One type of analysis that is commonly performed is to estimate local recombination rates and identify recombination hotspots from patterns of LD. One method for detecting recombination hotspots, LDhot, has been used in a handful of species to further our understanding of the basic biology of recombination. For the most part, the effectiveness of this method (e.g., power and false positive rate) is unknown. In this study, we run extensive simulations to compare the effectiveness of three different implementations of LDhot. We find large differences in the power and false positive rates of these different approaches, as well as a strong sensitivity to the window size used (with smaller window sizes leading to more accurate estimation of hotspot locations). We also compared our LDhot simulation results with comparable simulation results obtained from a Bayesian maximum-likelihood approach for identifying hotspots. Surprisingly, we found that the latter computationally intensive approach had substantially lower power over the parameter values considered in our simulations. PMID:27226166

  9. A haplotype-based algorithm for multilocus linkage disequilibrium mapping of quantitative trait loci with epistasis.

    PubMed Central

    Lou, Xiang-Yang; Casella, George; Littell, Ramon C; Yang, Mark C K; Johnson, Julie A; Wu, Rongling

    2003-01-01

    For tightly linked loci, cosegregation may lead to nonrandom associations between alleles in a population. Because of its evolutionary relationship with linkage, this phenomenon is called linkage disequilibrium. Today, linkage disequilibrium-based mapping has become a major focus of recent genome research into mapping complex traits. In this article, we present a new statistical method for mapping quantitative trait loci (QTL) of additive, dominant, and epistatic effects in equilibrium natural populations. Our method is based on haplotype analysis of multilocus linkage disequilibrium and exhibits two significant advantages over current disequilibrium mapping methods. First, we have derived closed-form solutions for estimating the marker-QTL haplotype frequencies within the maximum-likelihood framework implemented by the EM algorithm. The allele frequencies of putative QTL and their linkage disequilibria with the markers are estimated by solving a system of regular equations. This procedure has significantly improved the computational efficiency and the precision of parameter estimation. Second, our method can detect marker-QTL disequilibria of different orders and QTL epistatic interactions of various kinds on the basis of a multilocus analysis. This can not only enhance the precision of parameter estimation, but also make it possible to perform whole-genome association studies. We carried out extensive simulation studies to examine the robustness and statistical performance of our method. The application of the new method was validated using a case study from humans, in which we successfully detected significant QTL affecting human body heights. Finally, we discuss the implications of our method for genome projects and its extension to a broader circumstance. The computer program for the method proposed in this article is available at the webpage http://www.ifasstat.ufl.edu/genome/~LD. PMID:12702696

  10. Linkage disequilibrium in Angus, Charolais, and Crossbred beef cattle

    PubMed Central

    Lu, Duc; Sargolzaei, Mehdi; Kelly, Matthew; Li, Changxi; Vander Voort, Gordon; Wang, Zhiquan; Plastow, Graham; Moore, Stephen; Miller, Stephen P.

    2012-01-01

    Linkage disequilibrium (LD) and the persistence of its phase across populations are important for genomic selection as well as fine scale mapping of quantitative trait loci (QTL). However, knowledge of LD in beef cattle, as well as the persistence of LD phase between crossbreds (C) and purebreds, is limited. The objective of this study was to understand the patterns of LD in Angus (AN), Charolais (CH), and C beef cattle based on 31,073, 32,088, and 33,286 SNP in each population, respectively. Amount of LD decreased rapidly from 0.29 to 0.23 to 0.19 in AN, 0.22 to 0.16 to 0.12 in CH, 0.21 to 0.15 to 0.11 in C, when the distance range between markers changed from 0–30 kb to 30–70 kb and then to 70–100 kb, respectively. Breeds and chromosomes had significant effects (P < 0.001) on LD decay. There was significant interaction between breeds and chromosomes (P < 0.001). Correlations of LD phase were high between C and AN (0.84), C and CH (0.81), as well as between AN and CH (0.77) for distances less than or equal to 70 kb. These dropped when the distance increased. Estimated effective population sizes for AN and CH were 207 and 285, respectively, for 10 generations ago. Given a useful LD of at least 0.3 between pairs of SNPs, the LD phase between any pair of the three breed groups was highly persistent. The current SNP density would allow the capture of approximately 49% of useful LD between SNP and marker QTL in AN, and 38% in CH. A higher density SNP panel or redesign of the current panel is needed to achieve more of useful LD for the purpose of genomic selection beef cattle. PMID:22912646

  11. Linkage and Linkage Disequilibrium Scan for Autism Loci in an Extended Pedigree from Finland

    PubMed Central

    Kilpinen, Helena; Ylisaukko-oja, Tero; Rehnström, Karola; Gaál, Emilia; Turunen, Joni A.; Kempas, Elli; von Wendt, Lennart; Varilo, Teppo; Peltonen, Leena

    2009-01-01

    Population isolates, such as Finland, have proved beneficial in mapping rare causative genetic variants due to a limited number of founders resulting in reduced genetic heterogeneity and extensive linkage disequilibrium. We have here used this special opportunity to identify rare alleles in autism by genealogically tracing 20 autism families into one extended pedigree with verified genealogical links reaching back to the 17th century. In this unique pedigree we performed a dense microsatellite marker genome-wide scan of linkage and linkage disequilibrium, and followed initial findings with extensive fine-mapping. We identified a putative autism susceptibility locus at 19p13.3, and obtained further evidence for previously identified loci at 1q23 and 15q11-13. Most promising candidate genes were TLE2 and TLE6 genes clustered at 19p13 and ATP1A2 at 1q23. PMID:19454485

  12. Population structure and its effect on haplotype diversity and linkage disequilibrium surrounding the xa5 locus of rice (Oryza sativa L.).

    PubMed Central

    Garris, Amanda J; McCouch, Susan R; Kresovich, Stephen

    2003-01-01

    To assess the usefulness of linkage disequilibrium mapping in an autogamous, domesticated species, we have characterized linkage disequilibrium in the candidate region for xa5, a recessive gene conferring race-specific resistance to bacterial blight in rice. This trait and locus have good mapping information, a tractable phenotype, and available sequence data, but no cloned gene. We sampled 13 short segments from the 70-kb candidate region in 114 accessions of Oryza sativa. Five additional segments were sequenced from the adjacent 45-kb region in resistant accessions to estimate the distance at which linkage disequilibrium decays. The data show significant linkage disequilibrium between sites 100 kb apart. The presence of the xa5 resistant reaction in two ecotypes and in accessions with different haplotypes in the candidate region may indicate multiple origins or genetic heterogeneity for resistance. In addition, genetic differentiation between ecotypes emphasizes the need for controlling for population structure in the design of linkage disequilibrium studies in rice. PMID:14573486

  13. AUTOGSCAN: powerful tools for automated genome-wide linkage and linkage disequilibrium analysis.

    PubMed

    Hiekkalinna, Tero; Terwilliger, Joseph D; Sammalisto, Sampo; Peltonen, Leena; Perola, Markus

    2005-02-01

    Genome-wide linkage analysis using multiple traits and statistical software packages is a tedious process which requires a significant amount of manual file manipulation. Different linkage analysis programs require different input file formats, making the task of analyzing data with multiple methods even more time-consuming. We have developed a software tool, AUTOGSCAN, that automates file formatting, the running of statistical analyses, and the summarizing of resulting statistics for whole genome scans with a push of a button, using several independent, and often idiosyncratic, statistical software packages such as MERLIN, SOLAR and GENEHUNTER. We also describe a program, ANALYZE, designed to run qualitative linkage analysis with several different statistical strategies and programs to efficiently screen for linkage and linkage disequilibrium for a given discrete trait. The ANALYZE program can also be used by AUTOGSCAN in a genome-wide sense. PMID:15836805

  14. Novel measures of linkage disequilibrium that correct the bias due to population structure and relatedness

    PubMed Central

    Mangin, B; Siberchicot, A; Nicolas, S; Doligez, A; This, P; Cierco-Ayrolles, C

    2012-01-01

    Among the several linkage disequilibrium measures known to capture different features of the non-independence between alleles at different loci, the most commonly used for diallelic loci is the r2 measure. In the present study, we tackled the problem of the bias of r2 estimate, which results from the sample structure and/or the relatedness between genotyped individuals. We derived two novel linkage disequilibrium measures for diallelic loci that are both extensions of the usual r2 measure. The first one, rS2, uses the population structure matrix, which consists of information about the origins of each individual and the admixture proportions of each individual genome. The second one, rV2, includes the kinship matrix into the calculation. These two corrections can be applied together in order to correct for both biases and are defined either on phased or unphased genotypes. We proved that these novel measures are linked to the power of association tests under the mixed linear model including structure and kinship corrections. We validated them on simulated data and applied them to real data sets collected on Vitis vinifera plants. Our results clearly showed the usefulness of the two corrected r2 measures, which actually captured ‘true' linkage disequilibrium unlike the usual r2 measure. PMID:21878986

  15. Novel measures of linkage disequilibrium that correct the bias due to population structure and relatedness.

    PubMed

    Mangin, B; Siberchicot, A; Nicolas, S; Doligez, A; This, P; Cierco-Ayrolles, C

    2012-03-01

    Among the several linkage disequilibrium measures known to capture different features of the non-independence between alleles at different loci, the most commonly used for diallelic loci is the r(2) measure. In the present study, we tackled the problem of the bias of r(2) estimate, which results from the sample structure and/or the relatedness between genotyped individuals. We derived two novel linkage disequilibrium measures for diallelic loci that are both extensions of the usual r(2) measure. The first one, r(S)(2), uses the population structure matrix, which consists of information about the origins of each individual and the admixture proportions of each individual genome. The second one, r(V)(2), includes the kinship matrix into the calculation. These two corrections can be applied together in order to correct for both biases and are defined either on phased or unphased genotypes.We proved that these novel measures are linked to the power of association tests under the mixed linear model including structure and kinship corrections. We validated them on simulated data and applied them to real data sets collected on Vitis vinifera plants. Our results clearly showed the usefulness of the two corrected r(2) measures, which actually captured 'true' linkage disequilibrium unlike the usual r(2) measure. PMID:21878986

  16. Linkage disequilibrium patterns vary with chromosomal location: A case study from the von Willebrand factor region

    SciTech Connect

    Watkins, W.S.; Zenger, R.; O'Brien, E.; Jorde, L.B. ); Nyman, D. ); Eriksson, A.W. ); Renlund, M.

    1994-08-01

    Linkage disequilibrium analysis has been used as a tool for analyzing marker order and locating disease genes. Under appropriate circumstances, disequilibrium patterns reflect recombination events that have occurred throughput a population's history. As a result, disequilibrium mapping may be useful in genomic regions of <1 cM where the number of informative meioses needed to detect recombinant individuals within pedigrees is exceptionally high. Its utility for refining target areas for candidate disease genes before initiating chromosomal walks and cloning experiments will be enhanced as the relationship between linkage disequilibrium and physical distance is better understood. To address this issue, the authors have characterized linkage disequilibrium in a 144-kb region of the von Willebrand factor gene on chromosome 12. Sixty CEPH and 12 von Willebrand disease families were genotypes for five PCR-based markers, which include two microsatellite repeats and three single-base-pair substitutions. Linkage disequilibrium and physical distance between polymorphisms are highly correlated (r[sub m] = -.76; P<.05) within this region. None of the five markers showed significant disequilibrium with the von Willebrand disease phenotype. The linkage disequilibrium/physical distance relationship was also analyzed as a function of chromosomal location for this and eight previously characterized regions. This analysis revealed a general trend in which linkage disequilibrium dissipates more rapidly with physical distance in telomeric regions than in centromeric regions. This trend is consistent with higher recombination rates near telomeres. 52 refs., 3 figs., 4 tabs.

  17. Linkage Disequilibrium Under Skewed Offspring Distribution Among Individuals in a Population

    PubMed Central

    Eldon, Bjarki; Wakeley, John

    2008-01-01

    Correlations in coalescence times between two loci are derived under selectively neutral population models in which the offspring of an individual can number on the order of the population size. The correlations depend on the rates of recombination and random drift and are shown to be functions of the parameters controlling the size and frequency of these large reproduction events. Since a prediction of linkage disequilibrium can be written in terms of correlations in coalescence times, it follows that the prediction of linkage disequilibrium is a function not only of the rate of recombination but also of the reproduction parameters. Low linkage disequilibrium is predicted if the offspring of a single individual frequently replace almost the entire population. However, high linkage disequilibrium can be predicted if the offspring of a single individual replace an intermediate fraction of the population. In some cases the model reproduces the standard Wright–Fisher predictions. Contrary to common intuition, high linkage disequilibrium can be predicted despite frequent recombination, and low linkage disequilibrium under infrequent recombination. Simulations support the analytical results but show that the variance of linkage disequilibrium is very large. PMID:18245371

  18. Peach genetic resources: diversity, population structure and linkage disequilibrium

    PubMed Central

    2013-01-01

    Background Peach (Prunus persica (L.) Batsch) is one of the most important model fruits in the Rosaceae family. Native to the west of China, where peach has been domesticated for more than 4,000 years, its cultivation spread from China to Persia, Mediterranean countries and to America. Chinese peach has had a major impact on international peach breeding programs due to its high genetic diversity. In this research, we used 48 highly polymorphic SSRs, distributed over the peach genome, to investigate the difference in genetic diversity, and linkage disequilibrium (LD) among Chinese cultivars, and North American and European cultivars, and the evolution of current peach cultivars. Results In total, 588 alleles were obtained with 48 SSRs on 653 peach accessions, giving an average of 12.25 alleles per locus. In general, the average value of observed heterozygosity (0.47) was lower than the expected heterozygosity (0.60). The separate analysis of groups of accessions according to their origin or reproductive strategies showed greater variability in Oriental cultivars, mainly due to the high level of heterozygosity in Chinese landraces. Genetic distance analysis clustered the cultivars into two main groups: one included four wild related Prunus, and the other included most of the Oriental and Occidental landraces and breeding cultivars. STRUCTURE analysis assigned 469 accessions to three subpopulations: Oriental (234), Occidental (174), and Landraces (61). Nested STRUCTURE analysis divided the Oriental subpopulation into two different subpopulations: ‘Yu Lu’ and ‘Hakuho’. The Occidental breeding subpopulation was also subdivided into nectarine and peach subpopulations. Linkage disequilibrium (LD) analysis in each of these subpopulations showed that the percentage of linked (r2 > 0.1) intra-chromosome comparisons ranged between 14% and 47%. LD decayed faster in Oriental (1,196 Kbp) than in Occidental (2,687 Kbp) samples. In the ‘Yu Lu’ subpopulation there

  19. Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores.

    PubMed

    Vilhjálmsson, Bjarni J; Yang, Jian; Finucane, Hilary K; Gusev, Alexander; Lindström, Sara; Ripke, Stephan; Genovese, Giulio; Loh, Po-Ru; Bhatia, Gaurav; Do, Ron; Hayeck, Tristan; Won, Hong-Hee; Kathiresan, Sekar; Pato, Michele; Pato, Carlos; Tamimi, Rulla; Stahl, Eli; Zaitlen, Noah; Pasaniuc, Bogdan; Belbin, Gillian; Kenny, Eimear E; Schierup, Mikkel H; De Jager, Philip; Patsopoulos, Nikolaos A; McCarroll, Steve; Daly, Mark; Purcell, Shaun; Chasman, Daniel; Neale, Benjamin; Goddard, Michael; Visscher, Peter M; Kraft, Peter; Patterson, Nick; Price, Alkes L

    2015-10-01

    Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R(2) increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase. PMID:26430803

  20. Modeling Linkage Disequilibrium Increases Accuracy of Polygenic Risk Scores

    PubMed Central

    Vilhjálmsson, Bjarni J.; Yang, Jian; Finucane, Hilary K.; Gusev, Alexander; Lindström, Sara; Ripke, Stephan; Genovese, Giulio; Loh, Po-Ru; Bhatia, Gaurav; Do, Ron; Hayeck, Tristan; Won, Hong-Hee; Ripke, Stephan; Neale, Benjamin M.; Corvin, Aiden; Walters, James T.R.; Farh, Kai-How; Holmans, Peter A.; Lee, Phil; Bulik-Sullivan, Brendan; Collier, David A.; Huang, Hailiang; Pers, Tune H.; Agartz, Ingrid; Agerbo, Esben; Albus, Margot; Alexander, Madeline; Amin, Farooq; Bacanu, Silviu A.; Begemann, Martin; Belliveau, Richard A.; Bene, Judit; Bergen, Sarah E.; Bevilacqua, Elizabeth; Bigdeli, Tim B.; Black, Donald W.; Bruggeman, Richard; Buccola, Nancy G.; Buckner, Randy L.; Byerley, William; Cahn, Wiepke; Cai, Guiqing; Campion, Dominique; Cantor, Rita M.; Carr, Vaughan J.; Carrera, Noa; Catts, Stanley V.; Chambert, Kimberly D.; Chan, Raymond C.K.; Chen, Ronald Y.L.; Chen, Eric Y.H.; Cheng, Wei; Cheung, Eric F.C.; Chong, Siow Ann; Cloninger, C. Robert; Cohen, David; Cohen, Nadine; Cormican, Paul; Craddock, Nick; Crowley, James J.; Curtis, David; Davidson, Michael; Davis, Kenneth L.; Degenhardt, Franziska; Del Favero, Jurgen; DeLisi, Lynn E.; Demontis, Ditte; Dikeos, Dimitris; Dinan, Timothy; Djurovic, Srdjan; Donohoe, Gary; Drapeau, Elodie; Duan, Jubao; Dudbridge, Frank; Durmishi, Naser; Eichhammer, Peter; Eriksson, Johan; Escott-Price, Valentina; Essioux, Laurent; Fanous, Ayman H.; Farrell, Martilias S.; Frank, Josef; Franke, Lude; Freedman, Robert; Freimer, Nelson B.; Friedl, Marion; Friedman, Joseph I.; Fromer, Menachem; Genovese, Giulio; Georgieva, Lyudmila; Gershon, Elliot S.; Giegling, Ina; Giusti-Rodrguez, Paola; Godard, Stephanie; Goldstein, Jacqueline I.; Golimbet, Vera; Gopal, Srihari; Gratten, Jacob; Grove, Jakob; de Haan, Lieuwe; Hammer, Christian; Hamshere, Marian L.; Hansen, Mark; Hansen, Thomas; Haroutunian, Vahram; Hartmann, Annette M.; Henskens, Frans A.; Herms, Stefan; Hirschhorn, Joel N.; Hoffmann, Per; Hofman, Andrea; Hollegaard, Mads V.; Hougaard, David M.; Ikeda, Masashi; Joa, Inge; Julia, Antonio; Kahn, Rene S.; Kalaydjieva, Luba; Karachanak-Yankova, Sena; Karjalainen, Juha; Kavanagh, David; Keller, Matthew C.; Kelly, Brian J.; Kennedy, James L.; Khrunin, Andrey; Kim, Yunjung; Klovins, Janis; Knowles, James A.; Konte, Bettina; Kucinskas, Vaidutis; Kucinskiene, Zita Ausrele; Kuzelova-Ptackova, Hana; Kahler, Anna K.; Laurent, Claudine; Keong, Jimmy Lee Chee; Lee, S. Hong; Legge, Sophie E.; Lerer, Bernard; Li, Miaoxin; Li, Tao; Liang, Kung-Yee; Lieberman, Jeffrey; Limborska, Svetlana; Loughland, Carmel M.; Lubinski, Jan; Lnnqvist, Jouko; Macek, Milan; Magnusson, Patrik K.E.; Maher, Brion S.; Maier, Wolfgang; Mallet, Jacques; Marsal, Sara; Mattheisen, Manuel; Mattingsdal, Morten; McCarley, Robert W.; McDonald, Colm; McIntosh, Andrew M.; Meier, Sandra; Meijer, Carin J.; Melegh, Bela; Melle, Ingrid; Mesholam-Gately, Raquelle I.; Metspalu, Andres; Michie, Patricia T.; Milani, Lili; Milanova, Vihra; Mokrab, Younes; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Murphy, Kieran C.; Murray, Robin M.; Myin-Germeys, Inez; Mller-Myhsok, Bertram; Nelis, Mari; Nenadic, Igor; Nertney, Deborah A.; Nestadt, Gerald; Nicodemus, Kristin K.; Nikitina-Zake, Liene; Nisenbaum, Laura; Nordin, Annelie; O’Callaghan, Eadbhard; O’Dushlaine, Colm; O’Neill, F. Anthony; Oh, Sang-Yun; Olincy, Ann; Olsen, Line; Van Os, Jim; Pantelis, Christos; Papadimitriou, George N.; Papiol, Sergi; Parkhomenko, Elena; Pato, Michele T.; Paunio, Tiina; Pejovic-Milovancevic, Milica; Perkins, Diana O.; Pietilinen, Olli; Pimm, Jonathan; Pocklington, Andrew J.; Powell, John; Price, Alkes; Pulver, Ann E.; Purcell, Shaun M.; Quested, Digby; Rasmussen, Henrik B.; Reichenberg, Abraham; Reimers, Mark A.; Richards, Alexander L.; Roffman, Joshua L.; Roussos, Panos; Ruderfer, Douglas M.; Salomaa, Veikko; Sanders, Alan R.; Schall, Ulrich; Schubert, Christian R.; Schulze, Thomas G.; Schwab, Sibylle G.; Scolnick, Edward M.; Scott, Rodney J.; Seidman, Larry J.; Shi, Jianxin; Sigurdsson, Engilbert; Silagadze, Teimuraz; Silverman, Jeremy M.; Sim, Kang; Slominsky, Petr; Smoller, Jordan W.; So, Hon-Cheong; Spencer, Chris C.A.; Stahl, Eli A.; Stefansson, Hreinn; Steinberg, Stacy; Stogmann, Elisabeth; Straub, Richard E.; Strengman, Eric; Strohmaier, Jana; Stroup, T. Scott; Subramaniam, Mythily; Suvisaari, Jaana; Svrakic, Dragan M.; Szatkiewicz, Jin P.; Sderman, Erik; Thirumalai, Srinivas; Toncheva, Draga; Tooney, Paul A.; Tosato, Sarah; Veijola, Juha; Waddington, John; Walsh, Dermot; Wang, Dai; Wang, Qiang; Webb, Bradley T.; Weiser, Mark; Wildenauer, Dieter B.; Williams, Nigel M.; Williams, Stephanie; Witt, Stephanie H.; Wolen, Aaron R.; Wong, Emily H.M.; Wormley, Brandon K.; Wu, Jing Qin; Xi, Hualin Simon; Zai, Clement C.; Zheng, Xuebin; Zimprich, Fritz; Wray, Naomi R.; Stefansson, Kari; Visscher, Peter M.; Adolfsson, Rolf; Andreassen, Ole A.; Blackwood, Douglas H.R.; Bramon, Elvira; Buxbaum, Joseph D.; Børglum, Anders D.; Cichon, Sven; Darvasi, Ariel; Domenici, Enrico; Ehrenreich, Hannelore; Esko, Tonu; Gejman, Pablo V.; Gill, Michael; Gurling, Hugh; Hultman, Christina M.; Iwata, Nakao; Jablensky, Assen V.; Jonsson, Erik G.; Kendler, Kenneth S.; Kirov, George; Knight, Jo; Lencz, Todd; Levinson, Douglas F.; Li, Qingqin S.; Liu, Jianjun; Malhotra, Anil K.; McCarroll, Steven A.; McQuillin, Andrew; Moran, Jennifer L.; Mortensen, Preben B.; Mowry, Bryan J.; Nthen, Markus M.; Ophoff, Roel A.; Owen, Michael J.; Palotie, Aarno; Pato, Carlos N.; Petryshen, Tracey L.; Posthuma, Danielle; Rietschel, Marcella; Riley, Brien P.; Rujescu, Dan; Sham, Pak C.; Sklar, Pamela; St. Clair, David; Weinberger, Daniel R.; Wendland, Jens R.; Werge, Thomas; Daly, Mark J.; Sullivan, Patrick F.; O’Donovan, Michael C.; Kraft, Peter; Hunter, David J.; Adank, Muriel; Ahsan, Habibul; Aittomäki, Kristiina; Baglietto, Laura; Berndt, Sonja; Blomquist, Carl; Canzian, Federico; Chang-Claude, Jenny; Chanock, Stephen J.; Crisponi, Laura; Czene, Kamila; Dahmen, Norbert; Silva, Isabel dos Santos; Easton, Douglas; Eliassen, A. Heather; Figueroa, Jonine; Fletcher, Olivia; Garcia-Closas, Montserrat; Gaudet, Mia M.; Gibson, Lorna; Haiman, Christopher A.; Hall, Per; Hazra, Aditi; Hein, Rebecca; Henderson, Brian E.; Hofman, Albert; Hopper, John L.; Irwanto, Astrid; Johansson, Mattias; Kaaks, Rudolf; Kibriya, Muhammad G.; Lichtner, Peter; Lindström, Sara; Liu, Jianjun; Lund, Eiliv; Makalic, Enes; Meindl, Alfons; Meijers-Heijboer, Hanne; Müller-Myhsok, Bertram; Muranen, Taru A.; Nevanlinna, Heli; Peeters, Petra H.; Peto, Julian; Prentice, Ross L.; Rahman, Nazneen; Sánchez, María José; Schmidt, Daniel F.; Schmutzler, Rita K.; Southey, Melissa C.; Tamimi, Rulla; Travis, Ruth; Turnbull, Clare; Uitterlinden, Andre G.; van der Luijt, Rob B.; Waisfisz, Quinten; Wang, Zhaoming; Whittemore, Alice S.; Yang, Rose; Zheng, Wei; Kathiresan, Sekar; Pato, Michele; Pato, Carlos; Tamimi, Rulla; Stahl, Eli; Zaitlen, Noah; Pasaniuc, Bogdan; Belbin, Gillian; Kenny, Eimear E.; Schierup, Mikkel H.; De Jager, Philip; Patsopoulos, Nikolaos A.; McCarroll, Steve; Daly, Mark; Purcell, Shaun; Chasman, Daniel; Neale, Benjamin; Goddard, Michael; Visscher, Peter M.; Kraft, Peter; Patterson, Nick; Price, Alkes L.

    2015-01-01

    Polygenic risk scores have shown great promise in predicting complex disease risk and will become more accurate as training sample sizes increase. The standard approach for calculating risk scores involves linkage disequilibrium (LD)-based marker pruning and applying a p value threshold to association statistics, but this discards information and can reduce predictive accuracy. We introduce LDpred, a method that infers the posterior mean effect size of each marker by using a prior on effect sizes and LD information from an external reference panel. Theory and simulations show that LDpred outperforms the approach of pruning followed by thresholding, particularly at large sample sizes. Accordingly, predicted R2 increased from 20.1% to 25.3% in a large schizophrenia dataset and from 9.8% to 12.0% in a large multiple sclerosis dataset. A similar relative improvement in accuracy was observed for three additional large disease datasets and for non-European schizophrenia samples. The advantage of LDpred over existing methods will grow as sample sizes increase. PMID:26430803

  1. Inferring admixture histories of human populations using linkage disequilibrium.

    PubMed

    Loh, Po-Ru; Lipson, Mark; Patterson, Nick; Moorjani, Priya; Pickrell, Joseph K; Reich, David; Berger, Bonnie

    2013-04-01

    Long-range migrations and the resulting admixtures between populations have been important forces shaping human genetic diversity. Most existing methods for detecting and reconstructing historical admixture events are based on allele frequency divergences or patterns of ancestry segments in chromosomes of admixed individuals. An emerging new approach harnesses the exponential decay of admixture-induced linkage disequilibrium (LD) as a function of genetic distance. Here, we comprehensively develop LD-based inference into a versatile tool for investigating admixture. We present a new weighted LD statistic that can be used to infer mixture proportions as well as dates with fewer constraints on reference populations than previous methods. We define an LD-based three-population test for admixture and identify scenarios in which it can detect admixture events that previous formal tests cannot. We further show that we can uncover phylogenetic relationships among populations by comparing weighted LD curves obtained using a suite of references. Finally, we describe several improvements to the computation and fitting of weighted LD curves that greatly increase the robustness and speed of the calculations. We implement all of these advances in a software package, ALDER, which we validate in simulations and apply to test for admixture among all populations from the Human Genome Diversity Project (HGDP), highlighting insights into the admixture history of Central African Pygmies, Sardinians, and Japanese. PMID:23410830

  2. Intrahaplotypic Variants Differentiate Complex Linkage Disequilibrium within Human MHC Haplotypes

    PubMed Central

    Lam, Tze Hau; Tay, Matthew Zirui; Wang, Bei; Xiao, Ziwei; Ren, Ee Chee

    2015-01-01

    Distinct regions of long-range genetic fixation in the human MHC region, known as conserved extended haplotypes (CEHs), possess unique genomic characteristics and are strongly associated with numerous diseases. While CEHs appear to be homogeneous by SNP analysis, the nature of fine variations within their genomic structure is unknown. Using multiple, MHC-homozygous cell lines, we demonstrate extensive sequence conservation in two common Asian MHC haplotypes: A33-B58-DR3 and A2-B46-DR9. However, characterization of phase-resolved MHC haplotypes revealed unique intra-CEH patterns of variation and uncovered 127 single nucleotide variants (SNVs) which are missing from public databases. We further show that the strong linkage disequilibrium structure within the human MHC that typically confounds precise identification of genetic features can be resolved using intra-CEH variants, as evidenced by rs3129063 and rs448489, which affect expression of ZFP57, a gene important in methylation and epigenetic regulation. This study demonstrates an improved strategy that can be used towards genetic dissection of diseases. PMID:26593880

  3. Genome-wide linkage-disequilibrium profiles from single individuals.

    PubMed

    Lynch, Michael; Xu, Sen; Maruki, Takahiro; Jiang, Xiaoqian; Pfaffelhuber, Peter; Haubold, Bernhard

    2014-09-01

    Although the analysis of linkage disequilibrium (LD) plays a central role in many areas of population genetics, the sampling variance of LD is known to be very large with high sensitivity to numbers of nucleotide sites and individuals sampled. Here we show that a genome-wide analysis of the distribution of heterozygous sites within a single diploid genome can yield highly informative patterns of LD as a function of physical distance. The proposed statistic, the correlation of zygosity, is closely related to the conventional population-level measure of LD, but is agnostic with respect to allele frequencies and hence likely less prone to outlier artifacts. Application of the method to several vertebrate species leads to the conclusion that >80% of recombination events are typically resolved by gene-conversion-like processes unaccompanied by crossovers, with the average lengths of conversion patches being on the order of one to several kilobases in length. Thus, contrary to common assumptions, the recombination rate between sites does not scale linearly with distance, often even up to distances of 100 kb. In addition, the amount of LD between sites separated by <200 bp is uniformly much greater than can be explained by the conventional neutral model, possibly because of the nonindependent origin of mutations within this spatial scale. These results raise questions about the application of conventional population-genetic interpretations to LD on short spatial scales and also about the use of spatial patterns of LD to infer demographic histories. PMID:24948778

  4. Inferring outcrossing in the homothallic fungus Sclerotinia sclerotiorum using linkage disequilibrium decay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The occurrence and frequency of outcrossing in homothallic fungal species in nature is an unresolved question. Here we report detection of frequent outcrossing in the homothallic fungus Sclerotinia sclerotiorum. In using multilocus linkage disequilibrium (LD) to infer recombination among microsatell...

  5. Linkage disequilibrium analysis of G-olf{sub {alpha}} (GNAL) in bipolar affective disorder

    SciTech Connect

    Tsiouris, S.J.; Breschel, T.S.; Xu, J.

    1996-09-20

    This study examines G-olf{sub {alpha}} as a possible candidate gene for susceptibility to bipolar affective disorder (BPAD) using the Transmission Disequilibrium Test (TDT). G-olf{sub {alpha}}, which encodes a subunit of a G-protein involved in intracellular signaling, maps within a region of chromosome 18 that has been implicated by two different linkage studies as a potential site of BPAD susceptibility loci. The expression pattern of G-olf{sub {alpha}} in the brain, its coupling to dopamine receptors, and the effects of lithium salts on G-proteins all support G-olf{sub {alpha}} as a candidate gene for BPAD. Our study population consisted of 106 probands and sibs with bipolar I disorder, with a median age-at-onset of 21.5 years ascertained from the United States. There was no evidence of linkage disequilibrium between BPAD and any of the observed G-olf{sub {alpha}} alleles in our sample. Division of families based on sex of the transmitting parent did not significantly change the results. This sample had good power (78%) to detect linkage disequilibrium with alleles conferring a relative risk equal to that estimated for the putative 18p locus (2.58). Our results do not support a major role for G-olf{sub {alpha}} as a susceptibility locus for BPAD in a substantial portion of our sample. Other genes lying near G-olf{sub {alpha}} within the linked region on chromosome 18 cannot be excluded by our data. This study illustrates the use of the TDT in evaluating candidate genes within linked chromosome regions. 24 refs., 1 tab.

  6. Linkage-Disequilibrium-Based Binning Affects the Interpretation of GWASs

    PubMed Central

    Christoforou, Andrea; Dondrup, Michael; Mattingsdal, Morten; Mattheisen, Manuel; Giddaluru, Sudheer; Nöthen, Markus M.; Rietschel, Marcella; Cichon, Sven; Djurovic, Srdjan; Andreassen, Ole A.; Jonassen, Inge; Steen, Vidar M.; Puntervoll, Pål; Le Hellard, Stéphanie

    2012-01-01

    Genome-wide association studies (GWASs) are critically dependent on detailed knowledge of the pattern of linkage disequilibrium (LD) in the human genome. GWASs generate lists of variants, usually SNPs, ranked according to the significance of their association to a trait. Downstream analyses generally focus on the gene or genes that are physically closest to these SNPs and ignore their LD profile with other SNPs. We have developed a flexible R package (LDsnpR) that efficiently assigns SNPs to genes on the basis of both their physical position and their pairwise LD with other SNPs. We used the positional-binning and LD-based-binning approaches to investigate whether including these “LD-based” SNPs would affect the interpretation of three published GWASs on bipolar affective disorder (BP) and of the imputed versions of two of these GWASs. We show how including LD can be important for interpreting and comparing GWASs. In the published, unimputed GWASs, LD-based binning effectively “recovered” 6.1%–8.3% of Ensembl-defined genes. It altered the ranks of the genes and resulted in nonnegligible differences between the lists of the top 2,000 genes emerging from the two binning approaches. It also improved the overall gene-based concordance between independent BP studies. In the imputed datasets, although the increases in coverage (>0.4%) and rank changes were more modest, even greater concordance between the studies was observed, attesting to the potential of LD-based binning on imputed data as well. Thus, ignoring LD can result in the misinterpretation of the GWAS findings and have an impact on subsequent genetic and functional studies. PMID:22444669

  7. Performance of random forest when SNPs are in linkage disequilibrium

    PubMed Central

    Meng, Yan A; Yu, Yi; Cupples, L Adrienne; Farrer, Lindsay A; Lunetta, Kathryn L

    2009-01-01

    Background Single nucleotide polymorphisms (SNPs) may be correlated due to linkage disequilibrium (LD). Association studies look for both direct and indirect associations with disease loci. In a Random Forest (RF) analysis, correlation between a true risk SNP and SNPs in LD may lead to diminished variable importance for the true risk SNP. One approach to address this problem is to select SNPs in linkage equilibrium (LE) for analysis. Here, we explore alternative methods for dealing with SNPs in LD: change the tree-building algorithm by building each tree in an RF only with SNPs in LE, modify the importance measure (IM), and use haplotypes instead of SNPs to build a RF. Results We evaluated the performance of our alternative methods by simulation of a spectrum of complex genetics models. When a haplotype rather than an individual SNP is the risk factor, we find that the original Random Forest method performed on SNPs provides good performance. When individual, genotyped SNPs are the risk factors, we find that the stronger the genetic effect, the stronger the effect LD has on the performance of the original RF. A revised importance measure used with the original RF is relatively robust to LD among SNPs; this revised importance measure used with the revised RF is sometimes inflated. Overall, we find that the revised importance measure used with the original RF is the best choice when the genetic model and the number of SNPs in LD with risk SNPs are unknown. For the haplotype-based method, under a multiplicative heterogeneity model, we observed a decrease in the performance of RF with increasing LD among the SNPs in the haplotype. Conclusion Our results suggest that by strategically revising the Random Forest method tree-building or importance measure calculation, power can increase when LD exists between SNPs. We conclude that the revised Random Forest method performed on SNPs offers an advantage of not requiring genotype phase, making it a viable tool for use in the

  8. Genetic Diversity, Population Structure, and Linkage Disequilibrium in Bread Wheat (Triticum aestivum L.).

    PubMed

    Tascioglu, Tulin; Metin, Ozge Karakas; Aydin, Yildiz; Sakiroglu, Muhammet; Akan, Kadir; Uncuoglu, Ahu Altinkut

    2016-08-01

    Bread wheat (Triticum aestivum L.) gene pool was analyzed with 117 microsatellite markers scattered throughout A, B, and D genomes. Ninety microsatellite markers were giving 1620 polymorphic alleles in 55 different bread wheat genotypes. These genotypes were found to be divided into three subgroups based on Bayesian model and Principal component analysis. The highest polymorphism information content value for the markers resides on A genome was estimated for wmc262 marker located on 4A chromosome with the polymorphism information content value of 0.960. The highest polymorphism information content value (0.954) among the markers known to be located on B genome was realized for wmc44 marker located on 1B chromosome. The highest polymorphism information content value for the markers specific to D genome was found in gwm174 marker located on 5D chromosome with the polymorphism information content value of 0.948. The presence of linkage disequilibrium between 81 pairwise SSR markers reside on the same chromosome was tested and very limited linkage disequilibrium was observed. The results confirmed that the most distant genotype pairs were as follows Ceyhan-99-Behoth 6, Gerek 79-Douma 40989, and Karahan-99-Douma 48114. PMID:27048293

  9. Linkage disequilibrium fine mapping of quantitative trait loci: A simulation study

    PubMed Central

    Abdallah, Jihad M; Goffinet, Bruno; Cierco-Ayrolles, Christine; Pérez-Enciso, Miguel

    2003-01-01

    Recently, the use of linkage disequilibrium (LD) to locate genes which affect quantitative traits (QTL) has received an increasing interest, but the plausibility of fine mapping using linkage disequilibrium techniques for QTL has not been well studied. The main objectives of this work were to (1) measure the extent and pattern of LD between a putative QTL and nearby markers in finite populations and (2) investigate the usefulness of LD in fine mapping QTL in simulated populations using a dense map of multiallelic or biallelic marker loci. The test of association between a marker and QTL and the power of the test were calculated based on single-marker regression analysis. The results show the presence of substantial linkage disequilibrium with closely linked marker loci after 100 to 200 generations of random mating. Although the power to test the association with a frequent QTL of large effect was satisfactory, the power was low for the QTL with a small effect and/or low frequency. More powerful, multi-locus methods may be required to map low frequent QTL with small genetic effects, as well as combining both linkage and linkage disequilibrium information. The results also showed that multiallelic markers are more useful than biallelic markers to detect linkage disequilibrium and association at an equal distance. PMID:12939203

  10. Polymorphism, recombination, and linkage disequilibrium within the HLA class II region

    SciTech Connect

    Begovich, A.B.; McClure, G.R.; Suraj, V.C.; Helmuth, R.C.; Fildes, N.; Bugawan, T.L.; Erlich, H.A. ); Klitz, W. )

    1992-01-01

    Thirty-nine CEPH families, comprised of 502 individuals, have been typed for the HLA class II genes DRB1, DQA1, DQB1, and DPB1 using nonradioactive sequence-specific oligonucleotide probes to analyze polymerase chain reaction amplified DNA. This population, which consists of 266 independent chromosomes, contains 27 DRB1, 7 DQA1, 12 DQB1, and 17 DPB1 alleles. Analysis of the distribution of allele frequencies using the homozygosity statistic, which gives an indication of past selection pressures, suggests that balancing selection has acted on the DRB1, DQA1, and DQB1 loci. The distribution of DPB1 alleles, however, suggests a different evolutionary past. Family data permits the estimation of recombination rates and the unambiguous assignment of haplotypes. No recombinants were found between DRB1, DQA1, and DQB1; however, recombinants were detected between DQB1 and DPB1, resulting in an estimated recombination fraction of [ge]0.008 [+-] 0.004. Only 33 distinct DRB1-DQA1-DQB1 haplotypes were found in this population which illustrates the extreme nonrandom haplotypic association of alleles at these loci. A few of these haplotypes are unusual (previously unreported) for a Caucasian population and most likely result from past recombination events between the DR and DQ subregions. Examination of disequilibrium across the HLA region using these data and the available serologic HLA-A and HLA-B types of these samples shows that global disequilibrium between these loci declines with the recombination fraction, approaching statistic nonsignificance at the most distant interval, HLA-A and HLA-DP. DR-DQ haplotypes in linkage disequilibrium with DPB1 and B are noted and, finally, the evolutionary origin of certain class II haplotypes is addressed. 63 refs., 3 figs., 8 tabs.

  11. Linkage disequilibrium patterns across a recombination gradient in African Drosophila melanogaster.

    PubMed Central

    Andolfatto, Peter; Wall, Jeffrey D

    2003-01-01

    Previous multilocus surveys of nucleotide polymorphism have documented a genome-wide excess of intralocus linkage disequilibrium (LD) in Drosophila melanogaster and D. simulans relative to expectations based on estimated mutation and recombination rates and observed levels of diversity. These studies examined patterns of variation from predominantly non-African populations that are thought to have recently expanded their ranges from central Africa. Here, we analyze polymorphism data from a Zimbabwean population of D. melanogaster, which is likely to be closer to the standard population model assumptions of a large population with constant size. Unlike previous studies, we find that levels of LD are roughly compatible with expectations based on estimated rates of crossing over. Further, a detailed examination of genes in different recombination environments suggests that markers near the telomere of the X chromosome show considerably less linkage disequilibrium than predicted by rates of crossing over, suggesting appreciable levels of exchange due to gene conversion. Assuming that these populations are near mutation-drift equilibrium, our results are most consistent with a model that posits heterogeneity in levels of exchange due to gene conversion across the X chromosome, with gene conversion being a minor determinant of LD levels in regions of high crossing over. Alternatively, if levels of exchange due to gene conversion are not negligible in regions of high crossing over, our results suggest a marked departure from mutation-drift equilibrium (i.e., toward an excess of LD) in this Zimbabwean population. Our results also have implications for the dynamics of weakly selected mutations in regions of reduced crossing over. PMID:14668383

  12. An assessment of linkage disequilibrium in Holstein cattle using a Bayesian network.

    PubMed

    Morota, G; Valente, B D; Rosa, G J M; Weigel, K A; Gianola, D

    2012-12-01

    Linkage disequilibrium (LD) is defined as a non-random association of the distributions of alleles at different loci within a population. This association between loci is valuable in prediction of quantitative traits in animals and plants and in genome-wide association studies. A question that arises is whether standard metrics such as D' and r(2) reflect complex associations in a genetic system properly. It seems reasonable to take the view that loci associate and interact together as a system or network, as opposed to in a simple pairwise manner. We used a Bayesian network (BN) as a representation of choice for an LD network. A BN is a graphical depiction of a probability distribution and can represent sets of conditional independencies. Moreover, it provides a visual display of the joint distribution of the set of random variables in question. The usefulness of BN for linkage disequilibrium was explored and illustrated using genetic marker loci found to have the strongest effects on milk protein in Holstein cattle based on three strategies for ranking marker effect estimates: posterior means, standardized posterior means and additive genetic variance. Two different algorithms, Tabu search (a local score-based algorithm) and incremental association Markov blanket (a constraint-based algorithm), coupled with the chi-square test, were used for learning the structure of the BN and were compared with the reference r(2) metric represented as an LD heat map. The BN captured several genetic markers associated as clusters, implying that markers are inter-related in a complicated manner. Further, the BN detected conditionally dependent markers. The results confirm that LD relationships are of a multivariate nature and that r(2) gives an incomplete description and understanding of LD. Use of an LD Bayesian network enables inferring associations between loci in a systems framework and provides a more accurate picture of LD than that resulting from the use of pairwise

  13. Constructing a linkage–linkage disequilibrium map using dominant-segregating markers

    PubMed Central

    Zhu, Xuli; Dong, Leiming; Jiang, Libo; Li, Huan; Sun, Lidan; Zhang, Hui; Yu, Weiwu; Liu, Haokai; Dai, Wensheng; Zeng, Yanru; Wu, Rongling

    2016-01-01

    The relationship between linkage disequilibrium (LD) and recombination fraction can be used to infer the pattern of genetic variation and evolutionary process in humans and other systems. We described a computational framework to construct a linkage–LD map from commonly used biallelic, single-nucleotide polymorphism (SNP) markers for outcrossing plants by which the decline of LD is visualized with genetic distance. The framework was derived from an open-pollinated (OP) design composed of plants randomly sampled from a natural population and seeds from each sampled plant, enabling simultaneous estimation of the LD in the natural population and recombination fraction due to allelic co-segregation during meiosis. We modified the framework to infer evolutionary pasts of natural populations using those marker types that are segregating in a dominant manner, given their role in creating and maintaining population genetic diversity. A sophisticated two-level EM algorithm was implemented to estimate and retrieve the missing information of segregation characterized by dominant-segregating markers such as single methylation polymorphisms. The model was applied to study the relationship between linkage and LD for a non-model outcrossing species, a gymnosperm species, Torreya grandis, naturally distributed in mountains of the southeastern China. The linkage–LD map constructed from various types of molecular markers opens a powerful gateway for studying the history of plant evolution. PMID:26622063

  14. Assessing signatures of selection through variation in linkage disequilibrium between taurine and indicine cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Signatures of selection are regions in the genome that have been preferentially maintained because of their functional importance in specific processes. These regions can be detected because of their lower genetic variability and specific regional linkage disequilibrium patterns. The varLD methodol...

  15. Extensive genetic diversity and low linkage disequilibrium within the COMT locus in maize exotic populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Caffeic acid 3-O-methytransferase (COMT) gene is a prime candidate for cell wall digestibility improvement based on the characterization of brown midrib-3 mutants. We compared the genetic diversity and linkage disequilibrium at COMT locus between populations sampled within the Germplasm Enhance...

  16. Map-based molecular diversity, linkage disequilibrium and association mapping of fruit traits in melon

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The wide phenotypic diversity, in melon fruits, is the result of consumer preferences combined with genotype fitness to the different agro-climatic zones. There is no sufficient information with respect to the extent of genetic divergence, population structure and linkage disequilibrium (LD) in mel...

  17. Population-Specific Patterns of Linkage Disequilibrium and SNP Variation in Spring and Winter Polyploid Wheat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Single nucleotide polymorphisms (SNPs) are ideally suited for the construction of high-resolution genetic maps, studying population evolutionary history and performing genome-wide association mapping experiments. Here we used a genome-wide set of 1536 SNPs to study linkage disequilibrium (LD) and po...

  18. An Initial Assessment of Genome-wide Linkage Disequilibrium in Soybean

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Linkage disequilibrium (LD) is the "non-random association of alleles" and can be utilized through association analysis to discover quantitative trait loci (QTLs). The largest resource of soybean germplasm is the Asian landraces that are the most immediate result of domestication. Previously it ha...

  19. Linkage disequilibrium based association mapping of fiber quality traits in G. hirsutum L. variety germplasm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cotton is the world’s leading cash crop, but it lags behind other major crops for marker-assisted breeding due to limited polymorphisms and a genetic bottleneck through historic domestication. Linkage disequilibrium (LD)-mapping using nonrandom associations of loci in haplotypes is a powerful high-r...

  20. Revealing misassembled segments in the bovine reference genome by high resolution linkage disequilibrium scan

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Misassembly signatures, created by shuffling the order of sequences while assembling a genome, can be easily seen by analyzing the unexpected behaviour of the linkage disequilibrium (LD) decay. A heuristic process was proposed to identify those misassembly signatures and presented the ones found in ...

  1. Extent of linkage disequilibrium in large breed dogs: chromosomal and breed variation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: Understanding extent of linkage disequilibrium (LD) is a crucial component for successful utilization of genome-wide association studies (GWAS). The extent of LD in the dog has been described based upon small marker sets in multiple breeds and studies. Understanding variation in LD on a per...

  2. A first insight into population structure and linkage disequilibrium in the US peanut minicore collection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Knowledge of genetic diversity, population structure, and degree of linkage disequilibrium (LD) in target association mapping populations is of great importance and is a prerequisite for LD-based mapping. In the present study, 96 genotypes comprising 92 accessions of the US peanut minicore collectio...

  3. A rapid method of haplotyping HFE mutations and linkage disequilibrium in a Caucasoid population

    PubMed Central

    Mullighan, C; Bunce, M; Fanning, G; Marshall, S; Welsh, K

    1998-01-01

    Background—HFE mutations are associated with hereditary haemochromatosis. However, a simple method capable of demonstrating the cis/trans arrangement of alleles is lacking, and linkage disequilibrium between HFE alleles and classic HLA loci is unknown. These are important issues as the pathogenic role of the mutations is not known. 
Aims—To develop a simple method of genotyping HFE mutations suitable for clinical use in addition to large disease studies. 
Patients—A total of 330 Caucasoid cadaveric organ donor controls were examined. Ten individuals previously HLA-H genotyped by polymerase chain reaction using restriction fragment length polymorphism (PCR-RFLP) were also examined to validate the method. 
Methods—A simple polymerase chain reaction using sequence specific primers (PCR-SSP) capable of haplotyping the mutations was developed. HFE allele and haplotype frequencies and linkage disequilibrium with eight HLA class I and II loci were examined in the control population. 
Results—27% and 19.7% of patients were positive for the 63D and 282Y alleles, respectively. No chromosome carried both 63D and 282Y. Linkage disequilibrium between 282Y and HLA-A*03 was confirmed, but was not straightforward: some A*03-associated alleles (DRB1*15, DQB1*06), but not all (B*07, Cw*0702), were associated with 282Y. 
Conclusions—Linkage disequilibrium data suggest that an HLA-B*07 containing haplotype contains an element affording protection from haemochromatosis and may suggest the timing of the founder 282Y mutation. 

 Keywords: HFE; haemochromatosis; PCR-SSP; linkage disequilibrium PMID:9616322

  4. Does probabilistic modelling of linkage disequilibrium evolution improve the accuracy of QTL location in animal pedigree?

    PubMed Central

    2010-01-01

    Background Since 2001, the use of more and more dense maps has made researchers aware that combining linkage and linkage disequilibrium enhances the feasibility of fine-mapping genes of interest. So, various method types have been derived to include concepts of population genetics in the analyses. One major drawback of many of these methods is their computational cost, which is very significant when many markers are considered. Recent advances in technology, such as SNP genotyping, have made it possible to deal with huge amount of data. Thus the challenge that remains is to find accurate and efficient methods that are not too time consuming. The study reported here specifically focuses on the half-sib family animal design. Our objective was to determine whether modelling of linkage disequilibrium evolution improved the mapping accuracy of a quantitative trait locus of agricultural interest in these populations. We compared two methods of fine-mapping. The first one was an association analysis. In this method, we did not model linkage disequilibrium evolution. Therefore, the modelling of the evolution of linkage disequilibrium was a deterministic process; it was complete at time 0 and remained complete during the following generations. In the second method, the modelling of the evolution of population allele frequencies was derived from a Wright-Fisher model. We simulated a wide range of scenarios adapted to animal populations and compared these two methods for each scenario. Results Our results indicated that the improvement produced by probabilistic modelling of linkage disequilibrium evolution was not significant. Both methods led to similar results concerning the location accuracy of quantitative trait loci which appeared to be mainly improved by using four flanking markers instead of two. Conclusions Therefore, in animal half-sib designs, modelling linkage disequilibrium evolution using a Wright-Fisher model does not significantly improve the accuracy of the

  5. Heritability and Familiality of Temperament and Character Dimensions in Korean Families with Schizophrenic Linkage Disequilibrium

    PubMed Central

    Lee, Byung Dae; Park, Je Min; Lee, Young Min; Moon, Eunsoo; Jeong, Hee Jeong; Chung, Young In; Yi, Young Mi

    2016-01-01

    Objective Categorical syndromes such as schizophrenia may represent complexes of many continuous psychological structural phenotypes along several dimensions of personality development/degeneration. The present study investigated the heritability and familiality of personality dimensions in Korean families with schizophrenic linkage disequilibrium (LD). Methods We recruited 179 probands (with schizophrenia) as well as, whenever possible, their parents and siblings. We used the Temperament and Character Inventory (TCI) to measure personality and symptomatic dimensions. The heritability of personality dimensions in a total of 472 family members was estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR). To measure familiality, we compared the personality dimensions of family members with those of 336 healthy unrelated controls using analysis of variance (ANOVA) analysis. Results Three of the seven TCI variables were significantly heritable and were included in subsequent analyses. The three groups (control, unaffected first-degree relative, case) were found to significantly differ from one another, with the expected order of average group scores, for all heritable dimensions. Conclusion Despite several study limitations with respect to family recruitment and phenotyping, our results show that aberrations in several personality dimensions related to genetic-environment coactions or interactions may underlie the complexity of the schizophrenic syndrome. PMID:27121432

  6. Temporal dynamics of linkage disequilibrium in two populations of bighorn sheep

    PubMed Central

    Miller, Joshua M; Poissant, Jocelyn; Malenfant, René M; Hogg, John T; Coltman, David W

    2015-01-01

    Linkage disequilibrium (LD) is the nonrandom association of alleles at two markers. Patterns of LD have biological implications as well as practical ones when designing association studies or conservation programs aimed at identifying the genetic basis of fitness differences within and among populations. However, the temporal dynamics of LD in wild populations has received little empirical attention. In this study, we examined the overall extent of LD, the effect of sample size on the accuracy and precision of LD estimates, and the temporal dynamics of LD in two populations of bighorn sheep (Ovis canadensis) with different demographic histories. Using over 200 microsatellite loci, we assessed two metrics of multi-allelic LD, D′, and χ′2. We found that both populations exhibited high levels of LD, although the extent was much shorter in a native population than one that was founded via translocation, experienced a prolonged bottleneck post founding, followed by recent admixture. In addition, we observed significant variation in LD in relation to the sample size used, with small sample sizes leading to depressed estimates of the extent of LD but inflated estimates of background levels of LD. In contrast, there was not much variation in LD among yearly cross-sections within either population once sample size was accounted for. Lack of pronounced interannual variability suggests that researchers may not have to worry about interannual variation when estimating LD in a population and can instead focus on obtaining the largest sample size possible. PMID:26380673

  7. Linkage Disequilibrium Decay and Past Population History in the Human Genome

    PubMed Central

    Park, Leeyoung

    2012-01-01

    The fluctuation of population size has not been well studied in the previous studies of theoretical linkage disequilibrium (LD) expectation. In this study, an improved theoretical prediction of LD decay was derived to account for the effects of changes in effective population sizes. The equation was used to estimate effective population size (Ne) assuming a constant Ne and LD at equilibrium, and these Ne estimates implied the past changes of Ne for a certain number of generations until equilibrium, which differed based on recombination rate. As the influence of recent population history on the Ne estimates is larger than old population history, recent changes in population size can be inferred more accurately than old changes. The theoretical predictions based on this improved expression showed accurate agreement with the simulated values. When applied to human genome data, the detailed recent history of human populations was obtained. The inferred past population history of each population showed good correspondence with historical studies. Specifically, four populations (three African ancestries and one Mexican ancestry) showed population growth that was significantly less than that of other populations, and two populations originated from China showed prominent exponential growth. During the examination of overall LD decay in the human genome, a selection pressure on chromosome 14, the gephyrin gene, was observed in all populations. PMID:23056365

  8. High-resolution linkage-disequilibrium mapping of the cartilage-hair hypoplasia gene

    SciTech Connect

    Sulisalo, T.; Klockars, J.; Chapelle, A. de la; Kaitila, I. |; Maekitie, O.; Sistonen, P.; Francomano, C.A.

    1994-11-01

    We recently assigned the gene for an autosomal recessive skeletal dysplasia, cartilage-hair hypoplasia (CHH), to 9p21-p13 in Finnish and Amish families. An association was observed between CHH and alleles at D9S163 in both family series, suggesting that these loci are in linkage disequilibrium and close to each other. Here we extended these studies by exploiting the linkage-disequilibrium information that can be obtained from families with a single affected child, and we studied 66 Finnish CHH families with seven microsatellite markers. The analysis based on the Luria and Delbrueck (1943) method and adapted to the study of human founder populations suggests that the distance between CHH and D9S163 is {approximately}0.3 cM. An eight-point linkage analysis modified to take advantage of all possible information in 15 Finnish and 17 Amish families was capable of narrowing the likely location of CHH to within an interval of 1.7 cM on a male map. The peak lod score of 54.92 was attained 0.03 and 0.1 cM proximal to D9S163 on the male and female maps, respectively. These results confirm the power of genetic resolution, that lies in the study of linkage disequilibrium in well-defined founder populations with one major ancestral disease mutation. 21 refs., 4 figs., 3 tabs.

  9. Transmission test for linkage disequilibrium: The insulin gene region and insulin-dependent diabetes mellitus (IDDM)

    SciTech Connect

    Spielman, R.S.; McGinnis, R.E. ); Ewens, W.J. )

    1993-03-01

    A population association has consistently been observed between insulin-dependent diabetes mellitus (IDDM) and the class 1 alleles of the region of tandem-repeat DNA (5[prime] flanking polymorphism [5[prime]FP])adjacent to the insulin gene on chromosome 11p. This finding suggests that the insulin gene region contains a gene or genes contributing to IDDM susceptibility. However, several studies that have sought to show linkage with IDDM by testing for cosegregation in affected sib pairs have failed to find evidence for linkage. As means for identifying genes for complex diseases, both the association and the affected-sib-pairs approaches have limitations. It is well known that population association between a disease and a genetic marker can arise as an artifact of population structure, even in the absence of linkage. On the other hand, linkage studies with modest numbers of affected sib pairs may fail to detect linkage, especially if there is linkage heterogeneity. The authors consider an alternative method to test for linkage with a genetic marker when population association has been found. Using data from families with at least one affected child, they evaluate the transmission of the associated marker allele from a heterozygous parent to an affected offspring. This approach has been used by several investigators, but the statistical properties of the method as a test for linkage have not been investigated. In the present paper they describe the statistical basis for this transmission test for linkage disequilibrium (transmission/disequilibrium test [TDT]). They then show the relationship of this test to tests of cosegregation that are based on the proportion of haplotypes or genes identical by descent in affected sibs. The TDT provides strong evidence for linkage between the 5[prime]FP and susceptibility to IDDM. 27 refs., 6 tabs.

  10. Effective Population Size, Extended Linkage Disequilibrium and Signatures of Selection in the Rare Dog Breed Lundehund

    PubMed Central

    Pfahler, Sophia; Distl, Ottmar

    2015-01-01

    The Lundehund is an old dog breed with remarkable anatomical features including polydactyly in all four limbs and extraordinary flexibility of the spine. We genotyped 28 Lundehund using the canine Illumina high density beadchip to estimate the effective population size (Ne) and inbreeding coefficients as well as to identify potential regions of positive selection. The decay of linkage disequilibrium was slow with r2 = 0.95 in 50 kb distance. The last 7-200 generations ago, Ne was at 10-13. An increase of Ne was noted in the very recent generations with a peak value of 19 for Ne at generation 4. The FROH estimated for 50-, 65- and 358-SNP windows were 0.87, 087 and 0.81, respectively. The most likely estimates for FROH after removing identical-by-state segments due to linkage disequilibria were at 0.80-0.81. The extreme loss of heterozygosity has been accumulated through continued inbreeding over 200 generations within a probably closed population with a small effective population size. The mean inbreeding coefficient based on pedigree data for the last 11 generations (FPed = 0.10) was strongly biased downwards due to the unknown coancestry of the founders in this pedigree data. The long-range haplotype test identified regions with genes involved in processes of immunity, olfaction, woundhealing and neuronal development as potential targets of selection. The genes QSOX2, BMPR1B and PRRX2 as well as MYOM1 are candidates for selection on the Lundehund characteristics small body size, increased number of digits per paw and extraordinary mobility, respectively. PMID:25860808

  11. Linkage disequilibrium between the beta frequency of the human EEG and a GABAA receptor gene locus

    PubMed Central

    Porjesz, Bernice; Almasy, Laura; Edenberg, Howard J.; Wang, Kongming; Chorlian, David B.; Foroud, Tatiana; Goate, Alison; Rice, John P.; O'Connor, Sean J.; Rohrbaugh, John; Kuperman, Samuel; Bauer, Lance O.; Crowe, Raymond R.; Schuckit, Marc A.; Hesselbrock, Victor; Conneally, P. Michael; Tischfield, Jay A.; Li, Ting-Kai; Reich, Theodore; Begleiter, Henri

    2002-01-01

    Human brain oscillations represent important features of information processing and are highly heritable. A common feature of beta oscillations (13–28 Hz) is the critical involvement of networks of inhibitory interneurons as pacemakers, gated by γ-aminobutyric acid type A (GABAA) action. Advances in molecular and statistical genetics permit examination of quantitative traits such as the beta frequency of the human electroencephalogram in conjunction with DNA markers. We report a significant linkage and linkage disequilibrium between beta frequency and a set of GABAA receptor genes. Uncovering the genes influencing brain oscillations provides a better understanding of the neural function involved in information processing. PMID:11891318

  12. Mapping by admixture linkage disequilibrium in human populations: limits and guidelines.

    PubMed Central

    Stephens, J. C.; Briscoe, D.; O'Brien, S. J.

    1994-01-01

    Certain human hereditary conditions, notably those with low penetrance and those which require an environmental event such as infectious disease exposure, are difficult to localize in pedigree analysis, because of uncertainty in the phenotype of an affected patient's relatives. An approach to locating these genes in human cohort studies would be to use association analysis, which depends on linkage disequilibrium of flanking polymorphic DNA markers. In theory, a high degree of linkage disequilibrium between genes separated by 10-20 cM will be generated and persist in populations that have a history of recent (3-20 generations ago) admixture between genetically differentiated racial groups, such as has occurred in African Americans and Hispanic populations. We have conducted analytic and computer simulations to quantify the effect of genetic, genomic, and population parameters that affect the amount and ascertainment of linkage disequilibrium in populations with a history of genetic admixture. Our goal is to thoroughly explore the ranges of all relevant parameters or factors (e.g., sample size and degree of genetic differentiation between populations) that may be involved in gene localization studies, in hopes of prescribing guidelines for an efficient mapping strategy. The results provide reasonable limits on sample size (200-300 patients), marker number (200-300 in 20-cM intervals), and allele differentiation (loci with allele frequency difference of > or = .3 between admixed parent populations) to produce an efficient approach (> 95% ascertainment) for locating genes not easily tracked in human pedigrees. PMID:7942858

  13. Characterization of Linkage Disequilibrium in a Rainbow Trout Broodstock Population

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The development of selective breeding strategies employing marker assisted selection in species with low to medium density genetic maps must account for the non-random association of alleles between linked loci. To conduct efficient association studies and estimate the average size of haplotypes ge...

  14. Fine mapping of the congenital chloride diarrhea gene by linkage disequilibrium

    SciTech Connect

    Hoeglund, P.; de la Chapelle, A.; Kere, J.

    1995-07-01

    Congenital chloride diarrhea is a recessively inherited intestinal disorder affecting electrolyte transportation. The clinical presentation is a life-threatening watery diarrhea with a high chloride content. Recently, the congenital chloride diarrhea gene (CLD) was assigned to chromosome 7 by linkage in eight Finnish families. In the present study, refined mapping of CLD was performed by studying linkage and linkage disequilibrium in 24 Finnish and 4 Swedish families. Recombination mapping assigned CLD to an {approximately}10-cM region flanked by D7S515 and D7S799. Linkage disequilibrium was detected over this large genetic region, with the strongest allelic association at D7S496. Application of the Luria and Delbrueck-derived analysis allowed for a further narrowing of the CLD region to {approximately}.37 cM from the marker D7S496. Haplotype analysis placed CLD unequivocally between D7S501 and D7S692, very close to D7S496 and most likely on the distal side of D7S496. This combined analytical approach allowed highly accurate mapping of CLD, each component adding complementary and consistent mapping information. 32 refs., 4 figs., 4 tabs.

  15. Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds.

    PubMed

    Alhaddad, Hasan; Khan, Razib; Grahn, Robert A; Gandolfi, Barbara; Mullikin, James C; Cole, Shelley A; Gruffydd-Jones, Timothy J; Häggström, Jens; Lohi, Hannes; Longeri, Maria; Lyons, Leslie A

    2013-01-01

    Domestic cats have a unique breeding history and can be used as models for human hereditary and infectious diseases. In the current era of genome-wide association studies, insights regarding linkage disequilibrium (LD) are essential for efficient association studies. The objective of this study is to investigate the extent of LD in the domestic cat, Felis silvestris catus, particularly within its breeds. A custom illumina GoldenGate Assay consisting of 1536 single nucleotide polymorphisms (SNPs) equally divided over ten 1 Mb chromosomal regions was developed, and genotyped across 18 globally recognized cat breeds and two distinct random bred populations. The pair-wise LD descriptive measure (r(2)) was calculated between the SNPs in each region and within each population independently. LD decay was estimated by determining the non-linear least-squares of all pair-wise estimates as a function of distance using established models. The point of 50% decay of r(2) was used to compare the extent of LD between breeds. The longest extent of LD was observed in the Burmese breed, where the distance at which r(2) ≈ 0.25 was ∼380 kb, comparable to several horse and dog breeds. The shortest extent of LD was found in the Siberian breed, with an r(2) ≈ 0.25 at approximately 17 kb, comparable to random bred cats and human populations. A comprehensive haplotype analysis was also conducted. The haplotype structure of each region within each breed mirrored the LD estimates. The LD of cat breeds largely reflects the breeds' population history and breeding strategies. Understanding LD in diverse populations will contribute to an efficient use of the newly developed SNP array for the cat in the design of genome-wide association studies, as well as to the interpretation of results for the fine mapping of disease and phenotypic traits. PMID:23308248

  16. Extent of Linkage Disequilibrium in the Domestic Cat, Felis silvestris catus, and Its Breeds

    PubMed Central

    Alhaddad, Hasan; Khan, Razib; Grahn, Robert A.; Gandolfi, Barbara; Mullikin, James C.; Cole, Shelley A.; Gruffydd-Jones, Timothy J.; Häggström, Jens; Lohi, Hannes; Longeri, Maria; Lyons, Leslie A.

    2013-01-01

    Domestic cats have a unique breeding history and can be used as models for human hereditary and infectious diseases. In the current era of genome-wide association studies, insights regarding linkage disequilibrium (LD) are essential for efficient association studies. The objective of this study is to investigate the extent of LD in the domestic cat, Felis silvestris catus, particularly within its breeds. A custom illumina GoldenGate Assay consisting of 1536 single nucleotide polymorphisms (SNPs) equally divided over ten 1 Mb chromosomal regions was developed, and genotyped across 18 globally recognized cat breeds and two distinct random bred populations. The pair-wise LD descriptive measure (r2) was calculated between the SNPs in each region and within each population independently. LD decay was estimated by determining the non-linear least-squares of all pair-wise estimates as a function of distance using established models. The point of 50% decay of r2 was used to compare the extent of LD between breeds. The longest extent of LD was observed in the Burmese breed, where the distance at which r2 ≈ 0.25 was ∼380 kb, comparable to several horse and dog breeds. The shortest extent of LD was found in the Siberian breed, with an r2 ≈ 0.25 at approximately 17 kb, comparable to random bred cats and human populations. A comprehensive haplotype analysis was also conducted. The haplotype structure of each region within each breed mirrored the LD estimates. The LD of cat breeds largely reflects the breeds’ population history and breeding strategies. Understanding LD in diverse populations will contribute to an efficient use of the newly developed SNP array for the cat in the design of genome-wide association studies, as well as to the interpretation of results for the fine mapping of disease and phenotypic traits. PMID:23308248

  17. Genetic diversity and linkage disequilibrium in Drosophila melanogaster with different rates of development

    SciTech Connect

    Marinkovic, D.; Tucic, N.; Moya, A.; Ayala, F.J.

    1987-11-01

    The authors examined eight enzyme polymorphisms in groups of Drosophila melanogaster flies with fast, intermediate and slow development. The allelic frequencies are similar in all three developmental classes, but the distribution of the genotypes among the class is significantly heterogeneous for the three loci on the second chromosome. When the total sample of 300 individuals is examined, significant gametic disequilibrium appears in 3 out of 13 pairs of genes located on the same chromosome and in 4 out of 15 pairs of genes located on different chromosomes. This 25% incidence of disequilibrium between pairs of genes is larger than previously observed in other natural populations (but similar to the incidence observed in laboratory populations). The greater frequency of significant gametic disequilibrium in our study is probably due to the large number of genomes sampled. Some models specifically predict that individuals with faster rates of development (i.e., greater fitness) should be more heterozygous (and exhibit more linkage disequilibrium) than individuals with slower development. This hypothesis is not supported by our results.

  18. Markers for Mapping by Admixture Linkage Disequilibrium in African American and Hispanic Populations

    PubMed Central

    Smith, Michael W.; Lautenberger, James A.; Shin, Hyoung Doo; Chretien, Jean-Paul; Shrestha, Sadeep; Gilbert, Dennis A.; O’Brien, Stephen J.

    2001-01-01

    Population linkage disequilibrium occurs as a consequence of mutation, selection, genetic drift, and population substructure produced by admixture of genetically distinct ethnic populations. African American and Hispanic ethnic groups have a history of significant gene flow among parent groups, which can be of value in affecting genome scans for disease-gene discovery in the case-control and transmission/disequilibrium test designs. Disease-gene discovery using mapping by admixture linkage disequilibrium (MALD) requires a map of polymorphic markers that differentiate between the founding populations, along with differences in disease-gene allele frequencies. We describe markers appropriate for MALD mapping by assessing allele frequencies of 744 short tandem repeats (STRs) in African Americans, Hispanics, European Americans, and Asians, by choosing STR markers that have large differences in composite δ, log-likelihood ratios, and/or I*(2) for MALD. Additional markers can be added to this MALD map by utilization of the rapidly growing single-nucleotide–polymorphism databases and the literature, to achieve a 3–10-cM scanning scale. The map will be useful for studies of diseases, including prostate and breast cancer, diabetes, hypertension, and end-stage renal disease, that have large differences in incidence between the founding populations of either Hispanics or African Americans. PMID:11590548

  19. Multiple Linkage Disequilibrium Mapping Methods to Validate Additive Quantitative Trait Loci in Korean Native Cattle (Hanwoo)

    PubMed Central

    Li, Yi; Kim, Jong-Joo

    2015-01-01

    The efficiency of genome-wide association analysis (GWAS) depends on power of detection for quantitative trait loci (QTL) and precision for QTL mapping. In this study, three different strategies for GWAS were applied to detect QTL for carcass quality traits in the Korean cattle, Hanwoo; a linkage disequilibrium single locus regression method (LDRM), a combined linkage and linkage disequilibrium analysis (LDLA) and a BayesCπ approach. The phenotypes of 486 steers were collected for weaning weight (WWT), yearling weight (YWT), carcass weight (CWT), backfat thickness (BFT), longissimus dorsi muscle area, and marbling score (Marb). Also the genotype data for the steers and their sires were scored with the Illumina bovine 50K single nucleotide polymorphism (SNP) chips. For the two former GWAS methods, threshold values were set at false discovery rate <0.01 on a chromosome-wide level, while a cut-off threshold value was set in the latter model, such that the top five windows, each of which comprised 10 adjacent SNPs, were chosen with significant variation for the phenotype. Four major additive QTL from these three methods had high concordance found in 64.1 to 64.9Mb for Bos taurus autosome (BTA) 7 for WWT, 24.3 to 25.4Mb for BTA14 for CWT, 0.5 to 1.5Mb for BTA6 for BFT and 26.3 to 33.4Mb for BTA29 for BFT. Several candidate genes (i.e. glutamate receptor, ionotropic, ampa 1 [GRIA1], family with sequence similarity 110, member B [FAM110B], and thymocyte selection-associated high mobility group box [TOX]) may be identified close to these QTL. Our result suggests that the use of different linkage disequilibrium mapping approaches can provide more reliable chromosome regions to further pinpoint DNA makers or causative genes in these regions. PMID:26104396

  20. Multiple Linkage Disequilibrium Mapping Methods to Validate Additive Quantitative Trait Loci in Korean Native Cattle (Hanwoo).

    PubMed

    Li, Yi; Kim, Jong-Joo

    2015-07-01

    The efficiency of genome-wide association analysis (GWAS) depends on power of detection for quantitative trait loci (QTL) and precision for QTL mapping. In this study, three different strategies for GWAS were applied to detect QTL for carcass quality traits in the Korean cattle, Hanwoo; a linkage disequilibrium single locus regression method (LDRM), a combined linkage and linkage disequilibrium analysis (LDLA) and a BayesCπ approach. The phenotypes of 486 steers were collected for weaning weight (WWT), yearling weight (YWT), carcass weight (CWT), backfat thickness (BFT), longissimus dorsi muscle area, and marbling score (Marb). Also the genotype data for the steers and their sires were scored with the Illumina bovine 50K single nucleotide polymorphism (SNP) chips. For the two former GWAS methods, threshold values were set at false discovery rate <0.01 on a chromosome-wide level, while a cut-off threshold value was set in the latter model, such that the top five windows, each of which comprised 10 adjacent SNPs, were chosen with significant variation for the phenotype. Four major additive QTL from these three methods had high concordance found in 64.1 to 64.9Mb for Bos taurus autosome (BTA) 7 for WWT, 24.3 to 25.4Mb for BTA14 for CWT, 0.5 to 1.5Mb for BTA6 for BFT and 26.3 to 33.4Mb for BTA29 for BFT. Several candidate genes (i.e. glutamate receptor, ionotropic, ampa 1 [GRIA1], family with sequence similarity 110, member B [FAM110B], and thymocyte selection-associated high mobility group box [TOX]) may be identified close to these QTL. Our result suggests that the use of different linkage disequilibrium mapping approaches can provide more reliable chromosome regions to further pinpoint DNA makers or causative genes in these regions. PMID:26104396

  1. Use of linkage disequilibrium approaches to map genes for bipolar disorder in the Costa Rican population

    SciTech Connect

    Escamilla, M.A.; Reus, V.I.; Smith, L.B.; Freimer, N.B.

    1996-05-31

    Linkage disequilibrium (LD) analysis provides a powerful means for screening the genome to map the location of disease genes, such as those for bipolar disorder (BP). As described in this paper, the population of the Central Valley of Costa Rica, which is descended from a small number of founders, should be suitable for LD mapping; this assertion is supported by reconstruction of extended haplotypes shared by distantly related individuals in this population suffering low-frequency hearing loss (LFHL1), which has previously been mapped by linkage analysis. A sampling strategy is described for applying LD methods to map genes for BP, and clinical and demographic characteristics of an initially collected sample are discussed. This sample will provide a complement to a previously collected set of Costa Rican BP families which is under investigation using standard linkage analysis. 42 refs., 4 figs., 2 tabs.

  2. Short Communication Mendelian inheritance, linkage, and genotypic disequilibrium in microsatellite loci of Hymenaea stigonocarpa Mart. ex Hayne (Fabaceae-Caesalpinioideae).

    PubMed

    Moraes, M A; Kubota, T Y K; Silva, E C B; Silva, A M; Cambuim, J; Moraes, M L T; Furlani Junior, E; Sebbenn, A M

    2016-01-01

    Hymenaea stigonocarpa is a deciduous and monoecious Neotropical tree species pollinated by bats. Due to overexploitation and habitat destruction, the population size has drastically diminished in nature. No previous study has investigated Mendelian inheritance, linkage, and genotypic disequilibrium in the available microsatellite markers in this species. So, our aim was to estimate these parameters using six microsatellite loci in a sample of 470 adults and 219 juveniles from two populations of H. stigonocarpa. In addition, 30 seeds per tree from 35 seed-trees were collected. Each seed was kept record of the seed-trees and fruit origin. Based on the six microsatellite loci, we found that only 10.6% of the cases showed significant deviations from Mendelian segregation and 15.3% showed linkage. We detected no evidence of genotypic disequilibrium between the loci in the adult trees or juveniles. Thus, our results suggest that these loci can be used with great accuracy in future genetic analyses of H. stigonocarpa populations. PMID:27525897

  3. Linkage disequilibrium mapping of the cornea plana congenita gene CNA2

    SciTech Connect

    Tahvanainen, E.; Karila, E.; Kolehmainen, J.

    1995-12-10

    We recently assigned a gene for autosomal recessive cornea plana congenita (CNA2; MIM No. 217300) by linkage analysis to the approximately 3-cM interval between markers D12S82 and D12S327. Here, we extended these studies by exploiting the haplotype and linkage disequilibrium information that can be derived from the genetically isolated Finnish population and its subpopulations. By testing 32 independent families with 10 polymorphic markers in the CNA2 interval, strong allelic association between CNA2 and a set of markers with a peak at marker D12S351 was detected. Based on linkage disequilibrium analysis, the critical region for CNA2 could be narrowed to only 0.04-0.3 cM from marker D12S351, thus defining a critical interval 0.08-0.60 cM in length. These results provide a basis for highly focused positional cloning of CNA2. 18 refs., 5 figs., 1 tab.

  4. Linkage disequilibrium in wild and cultured populations of Pacific oyster ( Crassostrea gigas)

    NASA Astrophysics Data System (ADS)

    Guo, Xiang; Li, Qi; Kong, Lingfeng; Yu, Hong

    2016-04-01

    Linkage disequilibrium (LD) can be applied for mapping the actual genes responsible for variation of economically important traits through association mapping. The feasibility and efficacy of association studies are strongly dependent on the extent of LD which determines the number and density of markers in the studied population, as well as the experimental design for an association analysis. In this study, we first characterized the extent of LD in a wild population and a cultured mass-selected line of Pacific oyster ( Crassostrea gigas). A total of 88 wild and 96 cultured individuals were selected to assess the level of genome-wide LD with 53 microsatellites, respectively. For syntenic marker pairs, no significant association was observed in the wild population; however, three significant associations occurred in the cultured population, and the significant LD extended up to 12.7 cM, indicating that strong artificial selection is a key force for substantial increase of genome-wide LD in cultured population. The difference of LD between wild and cultured populations showed that association studies in Pacific oyster can be achieved with reasonable marker densities at a relatively low cost by choosing an association mapping population. Furthermore, the frequent occurrence of LD between non-syntenic loci and rare alleles encourages the joint application of linkage analysis and LD mapping when mapping genes in oyster. The information on the linkage disequilibrium in the cultured population is useful for future association mapping in oyster.

  5. Ethnic-Difference Markers for Use in Mapping by Admixture Linkage Disequilibrium

    PubMed Central

    Collins-Schramm, Heather E.; Phillips, Carolyn M.; Operario, Darwin J.; Lee, Jane S.; Weber, James L.; Hanson, Robert L.; Knowler, William C.; Cooper, Richard; Li, Hongzhe; Seldin, Michael F.

    2002-01-01

    Mapping by admixture linkage disequilibrium (MALD) is a potentially powerful technique for the mapping of complex genetic diseases. The practical requirements of this method include (a) a set of markers spanning the genome that have large allele-frequency differences between the parental ethnicities contributing to the admixed population and (b) an understanding of the extent of admixture in the study population. To this end, a DNA-pooling technique was used to screen microsatellite and diallelic insertion/deletion markers for allele-frequency differences between putative representatives of the parental populations of the admixed Mexican American (MA) and African American (AA) populations. Markers with promising pooled differences were then confirmed by individual genotyping in both the parental and admixed populations. For the MA population, screening of >600 markers identified 151 ethnic-difference markers (EDMs) with δ>0.30 (where δ is the absolute value of each allele-frequency difference between two populations, summed over all marker alleles and divided by two) that are likely to be useful for MALD analysis. For the AA population, analysis of >400 markers identified 97 EDMs. In addition, individual genotyping of these markers in Pima Amerindians, Yavapai Amerindians, European American (EA) individuals, Africans from Zimbabwe, MA individuals, and AA individuals, as well as comparison to the CEPH genotyping set, suggests that the differences between subpopulations of an ethnicity are small for many markers with large interethnic differences. Estimates of admixture that are based on individual genotyping of these markers are consistent with a 60% EA:40% Amerindian contribution to MA populations and with a 20% EA:80% African contribution to AA populations. Taken together, these data suggest that EDMs with large interpopulation and small intrapopulation differences can be readily identified for MALD studies in both AA and MA populations. PMID:11845411

  6. Genomewide linkage disequilibrium mapping of severe bipolar disorder in a population isolate.

    PubMed

    Ophoff, Roel A; Escamilla, Michael A; Service, Susan K; Spesny, Mitzi; Meshi, Dar B; Poon, Wingman; Molina, Julio; Fournier, Eduardo; Gallegos, Alvaro; Mathews, Carol; Neylan, Thomas; Batki, Steven L; Roche, Erin; Ramirez, Margarita; Silva, Sandra; De Mille, Melissa C; Dong, Penny; Leon, Pedro E; Reus, Victor I; Sandkuijl, Lodewijk A; Freimer, Nelson B

    2002-09-01

    Genomewide association studies may offer the best promise for genetic mapping of complex traits. Such studies in outbred populations require very densely spaced single-nucleotide polymorphisms. In recently founded population isolates, however, extensive linkage disequilibrium (LD) may make these studies feasible with currently available sets of short tandem repeat markers, spaced at intervals as large as a few centimorgans. We report the results of a genomewide association study of severe bipolar disorder (BP-I), using patients from the isolated population of the central valley of Costa Rica. We observed LD with BP-I on several chromosomes; the most striking results were in proximal 8p, a region that has previously shown linkage to schizophrenia. This region could be important for severe psychiatric disorders, rather than for a specific phenotype. PMID:12119601

  7. A general model for likelihood computations of genetic marker data accounting for linkage, linkage disequilibrium, and mutations.

    PubMed

    Kling, Daniel; Tillmar, Andreas; Egeland, Thore; Mostad, Petter

    2015-09-01

    Several applications necessitate an unbiased determination of relatedness, be it in linkage or association studies or in a forensic setting. An appropriate model to compute the joint probability of some genetic data for a set of persons given some hypothesis about the pedigree structure is then required. The increasing number of markers available through high-density SNP microarray typing and NGS technologies intensifies the demand, where using a large number of markers may lead to biased results due to strong dependencies between closely located loci, both within pedigrees (linkage) and in the population (allelic association or linkage disequilibrium (LD)). We present a new general model, based on a Markov chain for inheritance patterns and another Markov chain for founder allele patterns, the latter allowing us to account for LD. We also demonstrate a specific implementation for X chromosomal markers that allows for computation of likelihoods based on hypotheses of alleged relationships and genetic marker data. The algorithm can simultaneously account for linkage, LD, and mutations. We demonstrate its feasibility using simulated examples. The algorithm is implemented in the software FamLinkX, providing a user-friendly GUI for Windows systems (FamLinkX, as well as further usage instructions, is freely available at www.famlink.se ). Our software provides the necessary means to solve cases where no previous implementation exists. In addition, the software has the possibility to perform simulations in order to further study the impact of linkage and LD on computed likelihoods for an arbitrary set of markers. PMID:25425094

  8. Linkage Disequilibrium on the Bovine X Chromosome: Characterization and Use in Quantitative Trait Locus Mapping

    PubMed Central

    Sandor, Cynthia; Farnir, Frédéric; Hansoul, Sarah; Coppieters, Wouter; Meuwissen, Théo; Georges, Michel

    2006-01-01

    We herein demonstrate that in the Holstein–Friesian dairy cattle population, microsatellites are as polymorphic on the X chromosome as on the autosomes but that the level of linkage disequilibrium between these markers is higher on the X chromosome than on the autosomes. The latter observation is not compatible with the small male-to-female ratio that prevails in this population and results in a higher gonosomal than autosomal effective population size. It suggests that the X chromosome undergoes distinct selective or mutational forces. We describe and characterize a novel Markovian approach to exploit this linkage disequilibrium to compute the probability that two chromosomes are identical-by-descent conditional on flanking marker data. We use the ensuing probabilities in a restricted maximum-likelihood approach to search for quantitative trait loci (QTL) affecting 48 traits of importance to the dairy industry and provide evidence for the presence of QTL affecting 5 of these traits on the bovine X chromosome. PMID:16648641

  9. Genome Scan for Selection in Structured Layer Chicken Populations Exploiting Linkage Disequilibrium Information

    PubMed Central

    Gholami, Mahmood; Reimer, Christian; Erbe, Malena; Preisinger, Rudolf; Weigend, Annett; Weigend, Steffen; Servin, Bertrand; Simianer, Henner

    2015-01-01

    An increasing interest is being placed in the detection of genes, or genomic regions, that have been targeted by selection because identifying signatures of selection can lead to a better understanding of genotype-phenotype relationships. A common strategy for the detection of selection signatures is to compare samples from distinct populations and to search for genomic regions with outstanding genetic differentiation. The aim of this study was to detect selective signatures in layer chicken populations using a recently proposed approach, hapFLK, which exploits linkage disequilibrium information while accounting appropriately for the hierarchical structure of populations. We performed the analysis on 70 individuals from three commercial layer breeds (White Leghorn, White Rock and Rhode Island Red), genotyped for approximately 1 million SNPs. We found a total of 41 and 107 regions with outstanding differentiation or similarity using hapFLK and its single SNP counterpart FLK respectively. Annotation of selection signature regions revealed various genes and QTL corresponding to productions traits, for which layer breeds were selected. A number of the detected genes were associated with growth and carcass traits, including IGF-1R, AGRP and STAT5B. We also annotated an interesting gene associated with the dark brown feather color mutational phenotype in chickens (SOX10). We compared FST, FLK and hapFLK and demonstrated that exploiting linkage disequilibrium information and accounting for hierarchical population structure decreased the false detection rate. PMID:26151449

  10. Assessing signatures of selection through variation in linkage disequilibrium between taurine and indicine cattle

    PubMed Central

    2014-01-01

    Background Signatures of selection are regions in the genome that have been preferentially increased in frequency and fixed in a population because of their functional importance in specific processes. These regions can be detected because of their lower genetic variability and specific regional linkage disequilibrium (LD) patterns. Methods By comparing the differences in regional LD variation between dairy and beef cattle types, and between indicine and taurine subspecies, we aim at finding signatures of selection for production and adaptation in cattle breeds. The VarLD method was applied to compare the LD variation in the autosomal genome between breeds, including Angus and Brown Swiss, representing taurine breeds, and Nelore and Gir, representing indicine breeds. Genomic regions containing the top 0.01 and 0.1 percentile of signals were characterized using the UMD3.1 Bos taurus genome assembly to identify genes in those regions and compared with previously reported selection signatures and regions with copy number variation. Results For all comparisons, the top 0.01 and 0.1 percentile included 26 and 165 signals and 17 and 125 genes, respectively, including TECRL, BT.23182 or FPPS, CAST, MYOM1, UVRAG and DNAJA1. Conclusions The VarLD method is a powerful tool to identify differences in linkage disequilibrium between cattle populations and putative signatures of selection with potential adaptive and productive importance. PMID:24592996

  11. Evidence of linkage disequilibrium in the Spanish polycystic kidney disease 1 population

    SciTech Connect

    Peral, B.; Ward, C.J.; Thomas, S.; Harris, P.C. ); Stallings, R.L. ); San Millan, J.L.; Moreno, F.

    1994-05-01

    Forty-one Spanish families with polycystic kidney disease 1 (PKD1) were studied for evidence of linkage disequilibrium between the disease locus and six closely linked markers. Four of these loci - three highly polymorphic microsatellites (SM6, CW3, and CW2) and a RFLP marker (BLu24) - are described for the first time in this report. Overall the results reveal many different haplotypes on the disease-carrying chromosome, suggesting a variety of independent PKD1 mutations. However, linkage disequilibrium was found between BLu24 and PKD1, and this was corroborated by haplotype analysis including the microsatellite polymorphisms. From this analysis a group of closely related haplotypes, consisting of four markers, was found on 40% of PKD1 chromosomes, although markers flanking this homogeneous region showed greater variability. This study has highlighted an interesting subpopulation of Spanish PKD1 chromosomes, many of which have a common origin, that may be useful for localizing the PKD1 locus more precisely. 37 refs., 1 fig., 4 tabs.

  12. Linkage disequilibrium on the bovine X chromosome: characterization and use in quantitative trait locus mapping.

    PubMed

    Sandor, Cynthia; Farnir, Frédéric; Hansoul, Sarah; Coppieters, Wouter; Meuwissen, Théo; Georges, Michel

    2006-07-01

    We herein demonstrate that in the Holstein-Friesian dairy cattle population, microsatellites are as polymorphic on the X chromosome as on the autosomes but that the level of linkage disequilibrium between these markers is higher on the X chromosome than on the autosomes. The latter observation is not compatible with the small male-to-female ratio that prevails in this population and results in a higher gonosomal than autosomal effective population size. It suggests that the X chromosome undergoes distinct selective or mutational forces. We describe and characterize a novel Markovian approach to exploit this linkage disequilibrium to compute the probability that two chromosomes are identical-by-descent conditional on flanking marker data. We use the ensuing probabilities in a restricted maximum-likelihood approach to search for quantitative trait loci (QTL) affecting 48 traits of importance to the dairy industry and provide evidence for the presence of QTL affecting 5 of these traits on the bovine X chromosome. PMID:16648641

  13. Accounting for linkage disequilibrium in genome-wide association studies: A penalized regression method.

    PubMed

    Liu, Jin; Wang, Kai; Ma, Shuangge; Huang, Jian

    2013-01-01

    Penalized regression methods are becoming increasingly popular in genome-wide association studies (GWAS) for identifying genetic markers associated with disease. However, standard penalized methods such as LASSO do not take into account the possible linkage disequilibrium between adjacent markers. We propose a novel penalized approach for GWAS using a dense set of single nucleotide polymorphisms (SNPs). The proposed method uses the minimax concave penalty (MCP) for marker selection and incorporates linkage disequilibrium (LD) information by penalizing the difference of the genetic effects at adjacent SNPs with high correlation. A coordinate descent algorithm is derived to implement the proposed method. This algorithm is efficient in dealing with a large number of SNPs. A multi-split method is used to calculate the p-values of the selected SNPs for assessing their significance. We refer to the proposed penalty function as the smoothed MCP and the proposed approach as the SMCP method. Performance of the proposed SMCP method and its comparison with LASSO and MCP approaches are evaluated through simulation studies, which demonstrate that the proposed method is more accurate in selecting associated SNPs. Its applicability to real data is illustrated using heterogeneous stock mice data and a rheumatoid arthritis. PMID:25258655

  14. Haplotype Analysis and Linkage Disequilibrium at Five Loci in Eragrostis tef.

    PubMed

    Smith, Shavannor M; Yuan, Yinan; Doust, Andrew N; Bennetzen, Jeffrey L

    2012-03-01

    Eragrostis tef (Zucc.), a member of the Chloridoideae subfamily of grasses, is one of the most important food crops in Ethiopia. Lodging is the most important production problem in tef. The rht1 and sd1 dwarfing genes have been useful for improving lodging resistance in wheat and rice, respectively, in what has been known as the "Green Revolution." All homologs of rht1 and sd1 were cloned and sequenced from 31 tef accessions collected from across Ethiopia. The allotetraploid tef genome was found to carry two rht1 homologs. From sequence variation between these two putative homologs, an approximate ancestral divergence date of 6.4 million years ago was calculated for the two genomes within tef. Three sd1 homologs were identified in tef, with unknown orthologous/paralogous relationships. The genetic diversity in the 31 studied accessions was organized into a relatively small number of haplotypes (2-4) for four of these genes, whereas one rht1 homeologue exhibited 10 haplotypes. A low level of nucleotide diversity was observed at all loci. Linkage disequilibrium analysis demonstrated strong linkage disequilibrium, extending the length of the five genes investigated (2-4 kb), with no significant decline. There was no significant correlation between haplotypes of any of these genes and their recorded site of origin. PMID:22413094

  15. Nonlinear Analysis of Time Series in Genome-Wide Linkage Disequilibrium Data

    NASA Astrophysics Data System (ADS)

    Hernández-Lemus, Enrique; Estrada-Gil, Jesús K.; Silva-Zolezzi, Irma; Fernández-López, J. Carlos; Hidalgo-Miranda, Alfredo; Jiménez-Sánchez, Gerardo

    2008-02-01

    The statistical study of large scale genomic data has turned out to be a very important tool in population genetics. Quantitative methods are essential to understand and implement association studies in the biomedical and health sciences. Nevertheless, the characterization of recently admixed populations has been an elusive problem due to the presence of a number of complex phenomena. For example, linkage disequilibrium structures are thought to be more complex than their non-recently admixed population counterparts, presenting the so-called ancestry blocks, admixed regions that are not yet smoothed by the effect of genetic recombination. In order to distinguish characteristic features for various populations we have implemented several methods, some of them borrowed or adapted from the analysis of nonlinear time series in statistical physics and quantitative physiology. We calculate the main fractal dimensions (Kolmogorov's capacity, information dimension and correlation dimension, usually named, D0, D1 and D2). We also have made detrended fluctuation analysis and information based similarity index calculations for the probability distribution of correlations of linkage disequilibrium coefficient of six recently admixed (mestizo) populations within the Mexican Genome Diversity Project [1] and for the non-recently admixed populations in the International HapMap Project [2]. Nonlinear correlations showed up as a consequence of internal structure within the haplotype distributions. The analysis of these correlations as well as the scope and limitations of these procedures within the biomedical sciences are discussed.

  16. High nucleotide diversity and limited linkage disequilibrium in Helicoverpa armigera facilitates the detection of a selective sweep.

    PubMed

    Song, S V; Downes, S; Parker, T; Oakeshott, J G; Robin, C

    2015-11-01

    Insecticides impose extreme selective pressures on populations of target pests and so insecticide resistance loci of these species may provide the footprints of 'selective sweeps'. To lay the foundation for future genome-wide scans for selective sweeps and inform genome-wide association study designs, we set out to characterize some of the baseline population genomic parameters of one of the most damaging insect pests in agriculture worldwide, Helicoverpa armigera. To this end, we surveyed nine Z-linked loci in three Australian H. armigera populations. We find that estimates of π are in the higher range among other insects and linkage disequilibrium decays over short distances. One of the surveyed loci, a cytochrome P450, shows an unusual haplotype configuration with a divergent allele at high frequency that led us to investigate the possibility of an adaptive introgression around this locus. PMID:26174024

  17. The decay of linkage disequilibrium under random union of gametes: how to calculate Bennett's principal components.

    PubMed

    Dawson, K J

    2000-08-01

    How rapidly does an arbitrary pattern of statistical association among a set of loci decay under meiosis and random union of gametes? This problem is non-trivial, even in the case of an infinitely large population where selection and other forces are absent. J. H. Bennett (1954, Ann. Hum. Genet. 18, 311-317) found that, for an arbitrary number of loci with an arbitrary linkage map, it is possible to define measures of linkage disequilibrium that decay geometrically with time. He found a recursive method for deriving expressions for these variables in terms of "allelic moments" (the factorial moments about the origin of the "allelic indicators"), and expressions for the allelic moments in terms of his new variables. However, Bennett no where stated his recursive algorithm explicitly, nor did he give a general formula for his measures of linkage disequilibrium, for an arbitrary number of loci. Recursive definitions of Bennett's variables were obtained by Lyubich. However, the expressions generated by these recursions are not the same as those found by Bennett. (They do not express Bennett's variables as functions of the allelic moments.) Lyubich's derivations employ genetic algebras. Here, I present a method for obtaining explicit expressions for Bennett's variables in terms of the allelic moments. I show that the transformation from the allelic moments to Bennett's variables and the inverse transformation always have the form that Bennett claimed. (This transformation and its inverse have essentially the same form.) I present general recursions for calculating the coefficients in the forward transformation and the coefficients in the inverse transformation. My derivations involve combinatorial arguments and ordinary algebra only. The special case of unlinked loci is briefly discussed. PMID:10944472

  18. Genome-wide distribution of genetic diversity and linkage disequilibrium in a mass-selected population of maritime pine

    PubMed Central

    2014-01-01

    Background The accessibility of high-throughput genotyping technologies has contributed greatly to the development of genomic resources in non-model organisms. High-density genotyping arrays have only recently been developed for some economically important species such as conifers. The potential for using genomic technologies in association mapping and breeding depends largely on the genome wide patterns of diversity and linkage disequilibrium in current breeding populations. This study aims to deepen our knowledge regarding these issues in maritime pine, the first species used for reforestation in south western Europe. Results Using a new map merging algorithm, we first established a 1,712 cM composite linkage map (comprising 1,838 SNP markers in 12 linkage groups) by bringing together three already available genetic maps. Using rigorous statistical testing based on kernel density estimation and resampling we identified cold and hot spots of recombination. In parallel, 186 unrelated trees of a mass-selected population were genotyped using a 12k-SNP array. A total of 2,600 informative SNPs allowed to describe historical recombination, genetic diversity and genetic structure of this recently domesticated breeding pool that forms the basis of much of the current and future breeding of this species. We observe very low levels of population genetic structure and find no evidence that artificial selection has caused a reduction in genetic diversity. By combining these two pieces of information, we provided the map position of 1,671 SNPs corresponding to 1,192 different loci. This made it possible to analyze the spatial pattern of genetic diversity (H e ) and long distance linkage disequilibrium (LD) along the chromosomes. We found no particular pattern in the empirical variogram of H e across the 12 linkage groups and, as expected for an outcrossing species with large effective population size, we observed an almost complete lack of long distance LD. Conclusions These

  19. Novel microsatellite repeats (MSRs) and linkage disequilibrium analysis in the SMA region of 5q13.1

    SciTech Connect

    Yaraghi, Z.; Roy, N.; MacKenzie, A.E.

    1994-09-01

    The spinal muscular atrophies (SMA) are characterized by degeneration of the anterior horn cells of the spinal cord, leading to muscular atrophy associated with progressive paralysis. The gene involved in SMA has been mapped by linkage analysis to a region of 5q13.1 flanked centromerically by D5S435 and telomerically by D5S557. We are in the process of identifying new microsatellite repeats to further define the genetic map of the SMA region. A contiguous array of YAC clones covering the SMA containing D5S435-D56S112 interval of 5q13.1 was established. From this contig, a 700 kb clone 76C1, which contains the 200 kb CMS-1/CATT-1 critical region, was used to generate a partial Sau3A1 phage library. We have previously shown that 2 CATT-1 subloci are in linkage disequilibrium with type I SMA. The 76C1 subloci are in linkage disequilibrium with type I SMA. The 76C1 phage library has been screened for human MSRs. To date we have identified two novel polymorphic microsatellites and four further candidates are being characterized. Results of linkage disequilibrium studies currently underway will be presented. The identification of a linkage disequilibrium maximum will be helpful in the further narrowing of the SMA region.

  20. Dosage Transmission Disequilibrium Test (dTDT) for Linkage and Association Detection

    PubMed Central

    Zhang, Zhehao; Wang, Jen-Chyong; Howells, William; Lin, Peng; Agrawal, Arpana; Edenberg, Howard J.; Tischfield, Jay A.; Schuckit, Marc A.; Bierut, Laura J.; Goate, Alison; Rice, John P.

    2013-01-01

    Both linkage and association studies have been successfully applied to identify disease susceptibility genes with genetic markers such as microsatellites and Single Nucleotide Polymorphisms (SNPs). As one of the traditional family-based studies, the Transmission/Disequilibrium Test (TDT) measures the over-transmission of an allele in a trio from its heterozygous parents to the affected offspring and can be potentially useful to identify genetic determinants for complex disorders. However, there is reduced information when complete trio information is unavailable. In this study, we developed a novel approach to “infer” the transmission of SNPs by combining both the linkage and association data, which uses microsatellite markers from families informative for linkage together with SNP markers from the offspring who are genotyped for both linkage and a Genome-Wide Association Study (GWAS). We generalized the traditional TDT to process these inferred dosage probabilities, which we name as the dosage-TDT (dTDT). For evaluation purpose, we developed a simulation procedure to assess its operating characteristics. We applied the dTDT to the simulated data and documented the power of the dTDT under a number of different realistic scenarios. Finally, we applied our methods to a family study of alcohol dependence (COGA) and performed individual genotyping on complete families for the top signals. One SNP (rs4903712 on chromosome 14) remained significant after correcting for multiple testing Methods developed in this study can be adapted to other platforms and will have widespread applicability in genomic research when case-control GWAS data are collected in families with existing linkage data. PMID:23691058

  1. A linkage disequilibrium perspective on the genetic mosaic of speciation in two hybridizing Mediterranean white oaks

    PubMed Central

    Goicoechea, P G; Herrán, A; Durand, J; Bodénès, C; Plomion, C; Kremer, A

    2015-01-01

    We analyzed the genetic mosaic of speciation in two hybridizing Mediterranean white oaks from the Iberian Peninsula (Quercus faginea Lamb. and Quercus pyrenaica Willd.). The two species show ecological divergence in flowering phenology, leaf morphology and composition, and in their basic or acidic soil preferences. Ninety expressed sequence tag-simple sequence repeats (EST-SSRs) and eight nuclear SSRs were genotyped in 96 trees from each species. Genotyping was designed in two steps. First, we used 69 markers evenly distributed over the 12 linkage groups (LGs) of the oak linkage map to confirm the species genetic identity of the sampled genotypes, and searched for differentiation outliers. Then, we genotyped 29 additional markers from the chromosome bins containing the outliers and repeated the multilocus scans. We found one or two additional outliers within four saturated bins, thus confirming that outliers are organized into clusters. Linkage disequilibrium (LD) was extensive; even for loosely linked and for independent markers. Consequently, score tests for association between two-marker haplotypes and the ‘species trait' showed a broad genomic divergence, although substantial variation across the genome and within LGs was also observed. We discuss the influence of several confounding effects on neutrality tests and review the evolutionary processes leading to extensive LD. Finally, we examine how LD analyses within regions that contain outlier clusters and quantitative trait loci can help to identify regions of divergence and/or genomic hitchhiking in the light of predictions from ecological speciation theory. PMID:25515016

  2. An investigation of genetic heterogeneity and linkage disequilibrium in 161 families with spinal muscular atrophy

    SciTech Connect

    Merette, C.; Gilliam, T.C.; Brzustowicz, L.M. ); Daniels, R.J.; Davies, K.E. ); Melki, J.; Munnich, A. ); Pericak-Vance, M.A. ); Siddique, T. ); Voosen, B. )

    1994-05-01

    The authors performed linkage analysis of 161 families with spinal muscular atrophy (SMA) in which affected individuals suffer from the intermediate or mild form of the disease (Types II or III). Markers for six loci encompassing the chromosome 5q11.2-q13.3 region were typed. The best map location for the disease locus was found to be between D5S6 and MAP1B. The corresponding 1 lod unit support interval is confined to this interval and spans 0.5 cM. The data strongly support the hypothesis of linkage heterogeneity (likelihood ratio, 1.14 [times] 10[sup 4]), with 5% of the families unlinked. Four families have a probability of less than 50% of segregating the SMA gene linked to the region 5q11.2-q13.3. A likelihood approach to test for linkage disequilibrium revealed no significant departure from Hardy-Weinberg equilibrium with any marker under study. 28 refs., 4 figs., 3 tabs.

  3. Linkage disequilibrium and population-structure analysis among Capsicum annuum L. cultivars for use in association mapping.

    PubMed

    Nimmakayala, Padma; Abburi, Venkata L; Abburi, Lavanya; Alaparthi, Suresh Babu; Cantrell, Robert; Park, Minkyu; Choi, Doil; Hankins, Gerald; Malkaram, Sridhar; Reddy, Umesh K

    2014-08-01

    Knowledge of population structure and linkage disequilibrium among the worldwide collections of peppers currently classified as hot, mild, sweet and ornamental types is indispensable for applying association mapping and genomic selection to improve pepper. The current study aimed to resolve the genetic diversity and relatedness of Capsicum annuum germplasm by use of simple sequence repeat (SSR) loci across all chromosomes in samples collected in 2011 and 2012. The physical distance covered by the entire set of SSRs used was 2,265.9 Mb from the 3.48-Gb hot-pepper genome size. The model-based program STRUCTURE was used to infer five clusters, which was further confirmed by classical molecular-genetic diversity analysis. Mean heterozygosity of various loci was estimated to be 0.15. Linkage disequilibrium (LD) was used to identify 17 LD blocks across various chromosomes with sizes from 0.154 Kb to 126.28 Mb. CAMS-142 of chromosome 1 was significantly associated with both capsaicin (CA) and dihydrocapsaicin (DCA) levels. Further, CAMS-142 was located in an LD block of 98.18 Mb. CAMS-142 amplified bands of 244, 268, 283 and 326 bp. Alleles 268 and 283 bp had positive effects on both CA and DCA levels, with an average R(2) of 12.15 % (CA) and 12.3 % (DCA). Eight markers from seven different chromosomes were significantly associated with fruit weight, contributing an average effect of 15 %. CAMS-199, HpmsE082 and CAMS-190 are the three major quantitative trait loci located on chromosomes 8, 9, and 10, respectively, and were associated with fruit weight in samples from both years of the study. This research demonstrates the effectiveness of using genome-wide SSR-based markers to assess features of LD and genetic diversity within C. annuum. PMID:24585251

  4. Patterns of cyto-nuclear linkage disequilibrium in Silene latifolia: genomic heterogeneity and temporal stability

    PubMed Central

    Fields, P D; McCauley, D E; McAssey, E V; Taylor, D R

    2014-01-01

    Non-random association of alleles in the nucleus and cytoplasmic organelles, or cyto-nuclear linkage disequilibrium (LD), is both an important component of a number of evolutionary processes and a statistical indicator of others. The evolutionary significance of cyto-nuclear LD will depend on both its magnitude and how stable those associations are through time. Here, we use a longitudinal population genetic data set to explore the magnitude and temporal dynamics of cyto-nuclear disequilibria through time. We genotyped 135 and 170 individuals from 16 and 17 patches of the plant species Silene latifolia in Southwestern VA, sampled in 1993 and 2008, respectively. Individuals were genotyped at 14 highly polymorphic microsatellite markers and a single-nucleotide polymorphism (SNP) in the mitochondrial gene, atp1. Normalized LD (D′) between nuclear and cytoplasmic loci varied considerably depending on which nuclear locus was considered (ranging from 0.005–0.632). Four of the 14 cyto-nuclear associations showed a statistically significant shift over approximately seven generations. However, the overall magnitude of this disequilibrium was largely stable over time. The observed origin and stability of cyto-nuclear LD is most likely caused by the slow admixture between anciently diverged lineages within the species' newly invaded range, and the local spatial structure and metapopulation dynamics that are known to structure genetic variation in this system. PMID:24002238

  5. Refining the position of Wilson disease by linkage disequilibrium with polymorphic microsatellites.

    PubMed Central

    Bowcock, A. M.; Tomfohrde, J.; Weissenbach, J.; Bonne-Tamir, B.; St George-Hyslop, P.; Giagheddu, M.; Cavalli-Sforza, L. L.; Farrer, L. A.

    1994-01-01

    Wilson disease (WND) is an autosomal recessive disorder that is due to an inability of the liver to eliminate copper. Copper buildup in the liver, brain, kidney, and other tissues can result in liver cirrhosis, neurologic and psychiatric defects, and other problems. We have localized the disease-containing region to between D13S31 and D13S59, with > 70 multiply affected families, and have constructed a YAC contig of > 4.5 Mb that spans these loci and orders nine highly polymorphic microsatellites. Here we present an analysis of disequilibrium with markers in this interval and provide evidence for strong allelic associations between AFM084xc5 alleles and WND alleles in European, Middle Eastern, and East Asian populations. Significant but weaker allelic associations were also observed between WND alleles and alleles at D13S137 and D13S169. The strength of the association between AFM084xc5 and WND in all non-Sardinian populations combined (linkage-disequilibrium coefficient [phi] = .61) suggests that the number of mutations accounting for WND is less than expected on the basis of the variety of clinical symptoms that are observed. PMID:8279473

  6. Refining the position of Wilson disease by linkage disequilibrium with polymorphic microsatellites

    SciTech Connect

    Bowcock, A.M.; Tomfohrde, J. ); Weissenbach, J. ); Bonne-Tamir, B.; George-Hyslop, P.; Giagheddu, M.; Cavalli-Sforza, L.L.; Farrer, L.A.

    1994-01-01

    Wilson disease (WND) is an autosomal recessive disorder that is due to an inability to the liver to eliminate copper. Copper buildup in the liver, brain, kidney, and other tissues can result in liver cirrhosis, neurologic and psychiatric defects, and other problems. The authors have localized the disease-containing region to between D13S31 and D13S59, with >70 multiply affected families, and have constructed a YAC contig of >4.5 Mb that spans these loci and orders nine highly polymorphic microsatellites. Here, the authors present an analysis of disequilibrium with markers in this interval and provide evidence for strong allelic associations between AFM084[times]c5 alleles and WND allels in European, Middle Eastern, and East Asian populations. Significant but weaker allelic associations were also observed between WND alleles and alleles at D13S137 and D13S169. The strength of the association between AFM084[times]c5 and WND in all non-Sardinian populations combined (linkage-disequilibrium coefficient [[theta

  7. Nucleotide Sequence Diversity and Linkage Disequilibrium of Four Nuclear Loci in Foxtail Millet (Setaria italica)

    PubMed Central

    He, Shui-lian; Yang, Yang; Morrell, Peter L.; Yi, Ting-shuang

    2015-01-01

    Foxtail millet (Setaria italica (L.) Beauv) is one of the earliest domesticated grains, which has been cultivated in northern China by 8,700 years before present (YBP) and across Eurasia by 4,000 YBP. Owing to a small genome and diploid nature, foxtail millet is a tractable model crop for studying functional genomics of millets and bioenergy grasses. In this study, we examined nucleotide sequence diversity, geographic structure, and levels of linkage disequilibrium at four nuclear loci (ADH1, G3PDH, IGS1 and TPI1) in representative samples of 311 landrace accessions across its cultivated range. Higher levels of nucleotide sequence and haplotype diversity were observed in samples from China relative to other sampled regions. Genetic assignment analysis classified the accessions into seven clusters based on nucleotide sequence polymorphisms. Intralocus LD decayed rapidly to half the initial value within ~1.2 kb or less. PMID:26325578

  8. Genome-wide distribution of genetic diversity and linkage disequilibrium in elite sugar beet germplasm

    PubMed Central

    2011-01-01

    Background Characterization of population structure and genetic diversity of germplasm is essential for the efficient organization and utilization of breeding material. The objectives of this study were to (i) explore the patterns of population structure in the pollen parent heterotic pool using different methods, (ii) investigate the genome-wide distribution of genetic diversity, and (iii) assess the extent and genome-wide distribution of linkage disequilibrium (LD) in elite sugar beet germplasm. Results A total of 264 and 238 inbred lines from the yield type and sugar type inbreds of the pollen parent heterotic gene pools, respectively, which had been genotyped with 328 SNP markers, were used in this study. Two distinct subgroups were detected based on different statistical methods within the elite sugar beet germplasm set, which was in accordance with its breeding history. MCLUST based on principal components, principal coordinates, or lapvectors had high correspondence with the germplasm type information as well as the assignment by STRUCTURE, which indicated that these methods might be alternatives to STRUCTURE for population structure analysis. Gene diversity and modified Roger's distance between the examined germplasm types varied considerably across the genome, which might be due to artificial selection. This observation indicates that population genetic approaches could be used to identify candidate genes for the traits under selection. Due to the fact that r2 >0.8 is required to detect marker-phenotype association explaining less than 1% of the phenotypic variance, our observation of a low proportion of SNP loci pairs showing such levels of LD suggests that the number of markers has to be dramatically increased for powerful genome-wide association mapping. Conclusions We provided a genome-wide distribution map of genetic diversity and linkage disequilibrium for the elite sugar beet germplasm, which is useful for the application of genome-wide association

  9. Extensive genetic diversity and low linkage disequilibrium within the COMT locus in Germplasm Enhancement of Maize populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Caffeic acid 3-O-methytransferase (COMT) gene is a prime candidate for cell wall digestibility improvement based on the characterization of brown midrib-3 mutants. We compared the genetic diversity and linkage disequilibrium at COMT locus between populations sampled within the Germplasm Enhance...

  10. Genetic structure and linkage disequilibrium in a diverse, representative collection of the C4 model plant, Sorghum bicolor

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To facilitate the mapping of genes in sorghum [Sorghum bicolor (L.) Moench] underlying economically important traits, we analyzed the genetic structure and linkage disequilibrium in a sorghum mini core collection of 242 landraces with 14,739 SNPs. The SNPs were produced using a highly multiplexed g...

  11. A First Insight into Population Structure and Linkage Disequilibrium in the US Peanut Mini-core Collection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Knowledge of genetic diversity, population structure, and degree of linkage disequilibrium (LD) in target association mapping populations is of great importance and is a prerequisite for LD-based mapping. In the present study, 96 genotypes comprising 92 accessions of the U.S. peanut mini-core colle...

  12. Population structure and linkage disequilibrium in oat (Avena sativa L.): implications for genome-wide association studies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The level of population structure and the extent of linkage disequilibrium (LD) can have large impacts on the power, resolution, and design of genome-wide association studies (GWAS) in plants. Until recently, the topics of LD and population structure have not been explored in oat due to the lack of...

  13. Assessing microsatellite linkage disequilibrium in wild, cultivated, and mapping populations of Theobroma cacao L and its impact on association mapping

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Linkage disequilibrium (LD) is the nonrandom association of alleles and loci within sets of genetic data and when measured over the genomes of a species can provide important indications for how future association analyses should proceed. This information can be advantageous especially for slow-gro...

  14. Detection of linkage disequilibrium between the myotonic dystrophy locus and a new polymorphic DNA marker.

    PubMed Central

    Harley, H G; Brook, J D; Floyd, J; Rundle, S A; Crow, S; Walsh, K V; Thibault, M C; Harper, P S; Shaw, D J

    1991-01-01

    We have examined the linkage of two new polymorphic DNA markers (D19S62 and D19S63) and a previously unreported polymorphism with an existing DNA marker (ERCC1) to the myotonic dystrophy (DM) locus. In addition, we have used pulsed-field gel electrophoresis to obtain a fine-structure map of this region. The detection of linkage disequilibrium between DM and one of these markers (D19S63) is the first demonstration of this phenomenon in a heterogeneous DM population. The results suggest that at least 58% of DM patients in the British population, as well as those in a French-Canadian subpopulation, are descended from the same ancestral DM mutation. We discuss the implications of this finding in terms of strategies for cloning the DM gene, for a possible role in modification of risk for prenatal and presymptomatic testing, and we speculate on the origin and number of existing mutations which may result in a DM phenotype. PMID:2063878

  15. Long distance linkage disequilibrium and limited hybridization suggest cryptic speciation in atlantic cod.

    PubMed

    Bradbury, Ian R; Bowman, Sharen; Borza, Tudor; Snelgrove, Paul V R; Hutchings, Jeffrey A; Berg, Paul R; Rodríguez-Ezpeleta, Naiara; Lighten, Jackie; Ruzzante, Daniel E; Taggart, Christopher; Bentzen, Paul

    2014-01-01

    Hybrid zones provide unprecedented opportunity for the study of the evolution of reproductive isolation, and the extent of hybridization across individuals and genomes can illuminate the degree of isolation. We examine patterns of interchromosomal linkage disequilibrium (ILD) and the presence of hybridization in Atlantic cod, Gadus morhua, in previously identified hybrid zones in the North Atlantic. Here, previously identified clinal loci were mapped to the cod genome with most (∼70%) occurring in or associated with (<5 kb) coding regions representing a diverse array of possible functions and pathways. Despite the observation that clinal loci were distributed across three linkage groups, elevated ILD was observed among all groups of clinal loci and strongest in comparisons involving a region of low recombination along linkage group 7. Evidence of ILD supports a hypothesis of divergence hitchhiking transitioning to genome hitchhiking consistent with reproductive isolation. This hypothesis is supported by Bayesian characterization of hybrid classes present and we find evidence of common F1 hybrids in several regions consistent with frequent interbreeding, yet little evidence of F2 or backcrossed individuals. This work suggests that significant barriers to hybridization and introgression exist among these co-occurring groups of cod either through strong selection against hybrid individuals, or genetic incompatibility and intrinsic barriers to hybridization. In either case, the presence of strong clinal trends, and little gene flow despite extensive hybridization supports a hypothesis of reproductive isolation and cryptic speciation in Atlantic cod. Further work is required to test the degree and nature of reproductive isolation in this species. PMID:25259573

  16. Long Distance Linkage Disequilibrium and Limited Hybridization Suggest Cryptic Speciation in Atlantic Cod

    PubMed Central

    Bradbury, Ian R.; Bowman, Sharen; Borza, Tudor; Snelgrove, Paul V. R.; Hutchings, Jeffrey A.; Berg, Paul R.; Rodríguez-Ezpeleta, Naiara; Lighten, Jackie; Ruzzante, Daniel E.; Taggart, Christopher; Bentzen, Paul

    2014-01-01

    Hybrid zones provide unprecedented opportunity for the study of the evolution of reproductive isolation, and the extent of hybridization across individuals and genomes can illuminate the degree of isolation. We examine patterns of interchromosomal linkage disequilibrium (ILD) and the presence of hybridization in Atlantic cod, Gadus morhua, in previously identified hybrid zones in the North Atlantic. Here, previously identified clinal loci were mapped to the cod genome with most (∼70%) occurring in or associated with (<5 kb) coding regions representing a diverse array of possible functions and pathways. Despite the observation that clinal loci were distributed across three linkage groups, elevated ILD was observed among all groups of clinal loci and strongest in comparisons involving a region of low recombination along linkage group 7. Evidence of ILD supports a hypothesis of divergence hitchhiking transitioning to genome hitchhiking consistent with reproductive isolation. This hypothesis is supported by Bayesian characterization of hybrid classes present and we find evidence of common F1 hybrids in several regions consistent with frequent interbreeding, yet little evidence of F2 or backcrossed individuals. This work suggests that significant barriers to hybridization and introgression exist among these co-occurring groups of cod either through strong selection against hybrid individuals, or genetic incompatibility and intrinsic barriers to hybridization. In either case, the presence of strong clinal trends, and little gene flow despite extensive hybridization supports a hypothesis of reproductive isolation and cryptic speciation in Atlantic cod. Further work is required to test the degree and nature of reproductive isolation in this species. PMID:25259573

  17. Identification and Replication of Three Novel Myopia Common Susceptibility Gene Loci on Chromosome 3q26 using Linkage and Linkage Disequilibrium Mapping

    PubMed Central

    Carbonaro, Francis; Liew, S. H. Melissa; Lau, Winston; Spector, Tim D.; Hammond, Christopher J.

    2008-01-01

    Refractive error is a highly heritable quantitative trait responsible for considerable morbidity. Following an initial genome-wide linkage study using microsatellite markers, we confirmed evidence for linkage to chromosome 3q26 and then conducted fine-scale association mapping using high-resolution linkage disequilibrium unit (LDU) maps. We used a preliminary discovery marker set across the 30-Mb region with an average SNP density of 1 SNP/15 kb (Map 1). Map 1 was divided into 51 LDU windows and additional SNPs were genotyped for six regions (Map 2) that showed preliminary evidence of multi-marker association using composite likelihood. A total of 575 cases and controls selected from the tails of the trait distribution were genotyped for the discovery sample. Malecot model estimates indicate three loci with putative common functional variants centred on MFN1 (180,566 kb; 95% confidence interval 180,505–180, 655 kb), approximately 156 kb upstream from alternate-splicing SOX2OT (182,595 kb; 95% CI 182,533–182,688 kb) and PSARL (184,386 kb; 95% CI 184,356–184,411 kb), with the loci showing modest to strong evidence of association for the Map 2 discovery samples (p<10−7, p<10−10, and p = 0.01, respectively). Using an unselected independent sample of 1,430 individuals, results replicated for the MFN1 (p = 0.006), SOX2OT (p = 0.0002), and PSARL (p = 0.0005) gene regions. MFN1 and PSARL both interact with OPA1 to regulate mitochondrial fusion and the inhibition of mitochondrial-led apoptosis, respectively. That two mitochondrial regulatory processes in the retina are implicated in the aetiology of myopia is surprising and is likely to provide novel insight into the molecular genetic basis of common myopia. PMID:18846214

  18. Selection of Genetic Markers for Association Analyses, Using Linkage Disequilibrium and Haplotypes

    PubMed Central

    Meng, Zhaoling; Zaykin, Dmitri V.; Xu, Chun-Fang; Wagner, Michael; Ehm, Margaret G.

    2003-01-01

    The genotyping of closely spaced single-nucleotide polymorphism (SNP) markers frequently yields highly correlated data, owing to extensive linkage disequilibrium (LD) between markers. The extent of LD varies widely across the genome and drives the number of frequent haplotypes observed in small regions. Several studies have illustrated the possibility that LD or haplotype data could be used to select a subset of SNPs that optimize the information retained in a genomic region while reducing the genotyping effort and simplifying the analysis. We propose a method based on the spectral decomposition of the matrices of pairwise LD between markers, and we select markers on the basis of their contributions to the total genetic variation. We also modify Clayton’s “haplotype tagging SNP” selection method, which utilizes haplotype information. For both methods, we propose sliding window–based algorithms that allow the methods to be applied to large chromosomal regions. Our procedures require genotype information about a small number of individuals for an initial set of SNPs and selection of an optimum subset of SNPs that could be efficiently genotyped on larger numbers of samples while retaining most of the genetic variation in samples. We identify suitable parameter combinations for the procedures, and we show that a sample size of 50–100 individuals achieves consistent results in studies of simulated data sets in linkage equilibrium and LD. When applied to experimental data sets, both procedures were similarly effective at reducing the genotyping requirement while maintaining the genetic information content throughout the regions. We also show that haplotype-association results that Hosking et al. obtained near CYP2D6 were almost identical before and after marker selection. PMID:12796855

  19. Linkage disequilibrium based association mapping of fiber quality traits in G. hirsutum L. variety germplasm.

    PubMed

    Abdurakhmonov, Ibrokhim Y; Saha, Sukumar; Jenkins, Jonnie N; Buriev, Zabardast T; Shermatov, Shukhrat E; Scheffler, Brain E; Pepper, Alan E; Yu, John Z; Kohel, Russell J; Abdukarimov, Abdusattor

    2009-07-01

    Cotton is the world's leading cash crop, but it lags behind other major crops for marker-assisted breeding due to limited polymorphisms and a genetic bottleneck through historic domestication. This underlies a need for characterization, tagging, and utilization of existing natural polymorphisms in cotton germplasm collections. Here we report genetic diversity, population characteristics, the extent of linkage disequilibrium (LD), and association mapping of fiber quality traits using 202 microsatellite marker primer pairs in 335 G. hirsutum germplasm grown in two diverse environments, Uzbekistan and Mexico. At the significance threshold (r (2) >or= 0.1), a genome-wide average of LD extended up to genetic distance of 25 cM in assayed cotton variety accessions. Genome wide LD at r (2) >or= 0.2 was reduced to approximately 5-6 cM, providing evidence of the potential for association mapping of agronomically important traits in cotton. Results suggest linkage, selection, inbreeding, population stratification, and genetic drift as the potential LD-generating factors in cotton. In two environments, an average of ~20 SSR markers was associated with each main fiber quality traits using a unified mixed liner model (MLM) incorporating population structure and kinship. These MLM-derived significant associations were confirmed in general linear model and structured association test, accounting for population structure and permutation-based multiple testing. Several common markers, showing the significant associations in both Uzbekistan and Mexican environments, were determined. Between 7 and 43% of the MLM-derived significant associations were supported by a minimum Bayes factor at 'moderate to strong' and 'strong to very strong' evidence levels, suggesting their usefulness for marker-assisted breeding programs and overall effectiveness of association mapping using cotton germplasm resources. PMID:19067183

  20. Linkage disequilibrium and population structure in wild and domesticated populations of Phaseolus vulgaris L.

    PubMed Central

    Rossi, Monica; Bitocchi, Elena; Bellucci, Elisa; Nanni, Laura; Rau, Domenico; Attene, Giovanna; Papa, Roberto

    2009-01-01

    Together with the knowledge of the population structure, a critical aspect for the planning of association and/or population genomics studies is the level of linkage disequilibrium (LD) that characterizes the species and the population used for such an analysis. We have analyzed the population structure and LD in wild and domesticated populations of Phaseolus vulgaris L. using amplified fragment length polymorphism markers, most of which were genetically mapped in two recombinant inbred populations. Our results reflect the previous knowledge of the occurrence of two major wild gene pools of P. vulgaris, from which two independent domestication events originated, one in the Andes and one in Mesoamerica. The high level of LD in the whole sample was mostly due to the gene pool structure, with a much higher LD in domesticated compared to wild populations. In relation to association studies, our results also suggest that whole-genome-scan approaches are feasible in the common bean. Interestingly, an excess of inter-chromosomal LD was found in the domesticated populations, which suggests an important role for epistatic selection during domestication. Moreover, our results indicate the occurrence of a strong bottleneck in the Andean wild population before domestication, suggesting a Mesoamerican origin of P. vulgaris. Finally, our data support the occurrence of a single domestication event in Mesoamerica, and the same scenario in the Andes. PMID:25567895

  1. Selecting a Maximally Informative Set of Single-Nucleotide Polymorphisms for Association Analyses Using Linkage Disequilibrium

    PubMed Central

    Carlson, Christopher S.; Eberle, Michael A.; Rieder, Mark J.; Yi, Qian; Kruglyak, Leonid; Nickerson, Deborah A.

    2004-01-01

    Common genetic polymorphisms may explain a portion of the heritable risk for common diseases. Within candidate genes, the number of common polymorphisms is finite, but direct assay of all existing common polymorphism is inefficient, because genotypes at many of these sites are strongly correlated. Thus, it is not necessary to assay all common variants if the patterns of allelic association between common variants can be described. We have developed an algorithm to select the maximally informative set of common single-nucleotide polymorphisms (tagSNPs) to assay in candidate-gene association studies, such that all known common polymorphisms either are directly assayed or exceed a threshold level of association with a tagSNP. The algorithm is based on the r2 linkage disequilibrium (LD) statistic, because r2 is directly related to statistical power to detect disease associations with unassayed sites. We show that, at a relatively stringent r2 threshold (r2>0.8), the LD-selected tagSNPs resolve >80% of all haplotypes across a set of 100 candidate genes, regardless of recombination, and tag specific haplotypes and clades of related haplotypes in nonrecombinant regions. Thus, if the patterns of common variation are described for a candidate gene, analysis of the tagSNP set can comprehensively interrogate for main effects from common functional variation. We demonstrate that, although common variation tends to be shared between populations, tagSNPs should be selected separately for populations with different ancestries. PMID:14681826

  2. Accuracy of Genomic Prediction in Switchgrass (Panicum virgatum L.) Improved by Accounting for Linkage Disequilibrium

    PubMed Central

    Ramstein, Guillaume P.; Evans, Joseph; Kaeppler, Shawn M.; Mitchell, Robert B.; Vogel, Kenneth P.; Buell, C. Robin; Casler, Michael D.

    2016-01-01

    Switchgrass is a relatively high-yielding and environmentally sustainable biomass crop, but further genetic gains in biomass yield must be achieved to make it an economically viable bioenergy feedstock. Genomic selection (GS) is an attractive technology to generate rapid genetic gains in switchgrass, and meet the goals of a substantial displacement of petroleum use with biofuels in the near future. In this study, we empirically assessed prediction procedures for genomic selection in two different populations, consisting of 137 and 110 half-sib families of switchgrass, tested in two locations in the United States for three agronomic traits: dry matter yield, plant height, and heading date. Marker data were produced for the families’ parents by exome capture sequencing, generating up to 141,030 polymorphic markers with available genomic-location and annotation information. We evaluated prediction procedures that varied not only by learning schemes and prediction models, but also by the way the data were preprocessed to account for redundancy in marker information. More complex genomic prediction procedures were generally not significantly more accurate than the simplest procedure, likely due to limited population sizes. Nevertheless, a highly significant gain in prediction accuracy was achieved by transforming the marker data through a marker correlation matrix. Our results suggest that marker-data transformations and, more generally, the account of linkage disequilibrium among markers, offer valuable opportunities for improving prediction procedures in GS. Some of the achieved prediction accuracies should motivate implementation of GS in switchgrass breeding programs. PMID:26869619

  3. Sequence variation and linkage disequilibrium in the human T-cell receptor beta (TCRB) locus.

    PubMed

    Subrahmanyan, L; Eberle, M A; Clark, A G; Kruglyak, L; Nickerson, D A

    2001-08-01

    The T-cell receptor (TCR) plays a central role in the immune system, and > 90% of human T cells present a receptor that consists of the alpha TCR subunit (TCRA) and the beta subunit (TCRB). Here we report an analysis of 63 variable genes (BV), spanning 553 kb of TCRB that yielded 279 single-nucleotide polymorphisms (SNPs). Samples were drawn from 10 individuals and represent four populations-African American, Chinese, Mexican, and Northern European. We found nine variants that produce nonfunctional BV segments, removing those genes from the TCRB genomic repertoire. There was significant heterogeneity among population samples in SNP frequency (including the BV-inactivating sites), indicating the need for multiple-population samples for adequate variant discovery. In addition, we observed considerable linkage disequilibrium (LD) (r(2) > 0.1) over distances of approximately 30 kb in TCRB, and, in general, the distribution of r(2) as a function of physical distance was in close agreement with neutral coalescent simulations. LD in TCRB showed considerable spatial variation across the locus, being concentrated in "blocks" of LD; however, coalescent simulations of the locus illustrated that the heterogeneity of LD we observed in TCRB did not differ markedly from that expected from neutral processes. Finally, examination of the extended genotypes for each subject demonstrated homozygous stretches of >100 kb in the locus of several individuals. These results provide the basis for optimization of locuswide SNP typing in TCRB for studies of genotype-phenotype association. PMID:11438886

  4. Sequence Variation and Linkage Disequilibrium in the Human T-Cell Receptor β (TCRB) Locus

    PubMed Central

    Subrahmanyan, Lakshman; Eberle, Michael A.; Clark, Andrew G.; Kruglyak, Leonid; Nickerson, Deborah A.

    2001-01-01

    The T-cell receptor (TCR) plays a central role in the immune system, and >90% of human T cells present a receptor that consists of the α TCR subunit (TCRA) and the β subunit (TCRB). Here we report an analysis of 63 variable genes (BV), spanning 553 kb of TCRB that yielded 279 single-nucleotide polymorphisms (SNPs). Samples were drawn from 10 individuals and represent four populations—African American, Chinese, Mexican, and Northern European. We found nine variants that produce nonfunctional BV segments, removing those genes from the TCRB genomic repertoire. There was significant heterogeneity among population samples in SNP frequency (including the BV-inactivating sites), indicating the need for multiple-population samples for adequate variant discovery. In addition, we observed considerable linkage disequilibrium (LD) (r2>0.1) over distances of ∼30 kb in TCRB, and, in general, the distribution of r2 as a function of physical distance was in close agreement with neutral coalescent simulations. LD in TCRB showed considerable spatial variation across the locus, being concentrated in “blocks” of LD; however, coalescent simulations of the locus illustrated that the heterogeneity of LD we observed in TCRB did not differ markedly from that expected from neutral processes. Finally, examination of the extended genotypes for each subject demonstrated homozygous stretches of >100 kb in the locus of several individuals. These results provide the basis for optimization of locuswide SNP typing in TCRB for studies of genotype-phenotype association. PMID:11438886

  5. Shades of gray: A comparison of linkage disequilibrium between Hutterites and Europeans

    PubMed Central

    Thompson, Emma E; Sun, Ying; Nicolae, Dan; Ober, Carole

    2014-01-01

    Founder or isolated populations have advantages for genetic studies due to decreased genetic and environmental heterogeneity. However, whereas longer range linkage disequilibrium (LD) in these populations is expected to facilitate gene localization, extensive LD may actually limit the ability for gene discovery. The North American Hutterite population is one of the best characterized young founder populations and members of this isolate have been the subjects of our studies of complex traits, including fertility, asthma and cardiovascular disease, for >20 years. Here, we directly assess the patterns and extent of global LD using single nucleotide polymorphism (SNP) genotypes with minor allele frequencies (MAFs) ≥5% from the Affymetrix GeneChip® Mapping 500K array in 60 relatively unrelated Hutterites and 60 unrelated Europeans (HapMap CEU). Although LD among some marker pairs extends further in the Hutterites than in Europeans, the pattern of LD and minor allele frequencies are surprisingly similar. These results indicate that 1) identifying disease genes should be no more difficult in the Hutterites than in outbred European populations, 2) the same common susceptibility alleles for complex diseases should be present in the Hutterites and outbred European populations, and 3) imputation algorithms based on HapMap CEU should be applicable to the Hutterites. PMID:19697328

  6. Experimental Designs for Reliable Detection of Linkage Disequilibrium in Unstructured Random Population Association Studies

    PubMed Central

    Ball, Roderick D.

    2005-01-01

    A method is given for design of experiments to detect associations (linkage disequilibrium) in a random population between a marker and a quantitative trait locus (QTL), or gene, with a given strength of evidence, as defined by the Bayes factor. Using a version of the Bayes factor that can be linked to the value of an F-statistic with an existing deterministic power calculation makes it possible to rapidly evaluate a comprehensive range of scenarios, demonstrating the feasibility, or otherwise, of detecting genes of small effect. The Bayes factor is advocated for use in determining optimal strategies for selecting candidate genes for further testing or applications. The prospects for fine-scale mapping of QTL are reevaluated in this framework. We show that large sample sizes are needed to detect small-effect genes with a respectable-sized Bayes factor, and to have good power to detect a QTL allele at low frequency it is necessary to have a marker with similar allele frequency near the gene. PMID:15781715

  7. Species Discrimination, Population Structure and Linkage Disequilibrium in Eucalyptus camaldulensis and Eucalyptus tereticornis Using SSR Markers

    PubMed Central

    Arumugasundaram, Shanmugapriya; Ghosh, Modhumita; Veerasamy, Sivakumar; Ramasamy, Yasodha

    2011-01-01

    Eucalyptus camaldulensis and E. tereticornis are closely related species commonly cultivated for pulp wood in many tropical countries including India. Understanding the genetic structure and linkage disequilibrium (LD) existing in these species is essential for the improvement of industrially important traits. Our goal was to evaluate the use of simple sequence repeat (SSR) loci for species discrimination, population structure and LD analysis in these species. Investigations were carried out with the most common alleles in 93 accessions belonging to these two species using 62 SSR markers through cross amplification. The polymorphic information content (PIC) ranged from 0.44 to 0.93 and 0.36 to 0.93 in E. camaldulensis and E. tereticornis respectively. A clear delineation between the two species was evident based on the analysis of population structure and species-specific alleles. Significant genotypic LD was found in E. camaldulensis, wherein out of 135 significant pairs, 17 pairs showed r2≥0.1. Similarly, in E. tereticornis, out of 136 significant pairs, 18 pairs showed r2≥0.1. The extent of LD decayed rapidly showing the significance of association analyses in eucalypts with higher resolution markers. The availability of whole genome sequence for E. grandis and the synteny and co-linearity in the genome of eucalypts, will allow genome-wide genotyping using microsatellites or single nucleotide polymorphims. PMID:22163287

  8. Exploiting Linkage Disequilibrium for Ultrahigh-Dimensional Genome-Wide Data with an Integrated Statistical Approach.

    PubMed

    Carlsen, Michelle; Fu, Guifang; Bushman, Shaun; Corcoran, Christopher

    2016-02-01

    Genome-wide data with millions of single-nucleotide polymorphisms (SNPs) can be highly correlated due to linkage disequilibrium (LD). The ultrahigh dimensionality of big data brings unprecedented challenges to statistical modeling such as noise accumulation, the curse of dimensionality, computational burden, spurious correlations, and a processing and storing bottleneck. The traditional statistical approaches lose their power due to [Formula: see text] (n is the number of observations and p is the number of SNPs) and the complex correlation structure among SNPs. In this article, we propose an integrated distance correlation ridge regression (DCRR) approach to accommodate the ultrahigh dimensionality, joint polygenic effects of multiple loci, and the complex LD structures. Initially, a distance correlation (DC) screening approach is used to extensively remove noise, after which LD structure is addressed using a ridge penalized multiple logistic regression (LRR) model. The false discovery rate, true positive discovery rate, and computational cost were simultaneously assessed through a large number of simulations. A binary trait of Arabidopsis thaliana, the hypersensitive response to the bacterial elicitor AvrRpm1, was analyzed in 84 inbred lines (28 susceptibilities and 56 resistances) with 216,130 SNPs. Compared to previous SNP discovery methods implemented on the same data set, the DCRR approach successfully detected the causative SNP while dramatically reducing spurious associations and computational time. PMID:26661113

  9. Accuracy of Genomic Prediction in Switchgrass (Panicum virgatum L.) Improved by Accounting for Linkage Disequilibrium.

    PubMed

    Ramstein, Guillaume P; Evans, Joseph; Kaeppler, Shawn M; Mitchell, Robert B; Vogel, Kenneth P; Buell, C Robin; Casler, Michael D

    2016-01-01

    Switchgrass is a relatively high-yielding and environmentally sustainable biomass crop, but further genetic gains in biomass yield must be achieved to make it an economically viable bioenergy feedstock. Genomic selection (GS) is an attractive technology to generate rapid genetic gains in switchgrass, and meet the goals of a substantial displacement of petroleum use with biofuels in the near future. In this study, we empirically assessed prediction procedures for genomic selection in two different populations, consisting of 137 and 110 half-sib families of switchgrass, tested in two locations in the United States for three agronomic traits: dry matter yield, plant height, and heading date. Marker data were produced for the families' parents by exome capture sequencing, generating up to 141,030 polymorphic markers with available genomic-location and annotation information. We evaluated prediction procedures that varied not only by learning schemes and prediction models, but also by the way the data were preprocessed to account for redundancy in marker information. More complex genomic prediction procedures were generally not significantly more accurate than the simplest procedure, likely due to limited population sizes. Nevertheless, a highly significant gain in prediction accuracy was achieved by transforming the marker data through a marker correlation matrix. Our results suggest that marker-data transformations and, more generally, the account of linkage disequilibrium among markers, offer valuable opportunities for improving prediction procedures in GS. Some of the achieved prediction accuracies should motivate implementation of GS in switchgrass breeding programs. PMID:26869619

  10. Fine-scale genetic mapping based on linkage disequilibrium: theory and applications.

    PubMed

    Xiong, M; Guo, S W

    1997-06-01

    Linkage-disequilibrium mapping (LDM) recently has been hailed as a powerful statistical method for fine-scale mapping of disease genes. After reviewing its historical background and methodological development, we present a general, mathematical, and conceptually coherent framework for LDM that incorporates multilocus and multiallelic markers and mutational processes at the marker and disease loci. With this framework, we address several issues relevant to fine-scale mapping and propose some efficient computational methods for LDM. We implement various LDM methods that incorporate population growth, recurrent mutation, and marker mutations, on the basis of a general framework. We demonstrate these methods by applying them to published data on cystic fibrosis, Huntington disease, Friedreich ataxia, and progressive myoclonus epilepsy. Since the genes responsible for these diseases all have been cloned, we can evaluate the performance of our methods and can compare ours with that of other methods. Using the proposed methods, we successfully and accurately predicted the locations of genes responsible for these diseases, on the basis of published data only. PMID:9199574

  11. Linkage disequilibrium and diversity for three genomic regions in Azoreans and mainland Portuguese

    PubMed Central

    2009-01-01

    Studies on linkage disequilibrium (LD) across the genome and populations have been used in recent years with the main objective of improving gene mapping of complex traits. Here, we characterize the patterns of genetic diversity of HLA loci and evaluate LD (D') extent in three genomic regions: Xq13.3, NRY and HLA. In addition, we examine the distribution of DXS1225-DXS8082 haplotype diversity in Azoreans and mainland Portuguese. Allele distribution has demonstrated that the São Miguel population is genetically very diverse; haplotype analysis revealed 100% discriminatory power for X- and Y-markers and 94.3% for HLA markers. Standardized multiallelic D' in these three genomic regions shows values lower than 0.33, thereby suggesting there is no extensive LD in the São Miguel population. Data regarding the distribution of DXS1225-DXS8082 haplotypes indicate that there are no significant differences among all the populations studied, (Azorean geographical groups, the Azores archipelago and mainland Portugal). Moreover, in these as well as in other European populations, the most frequent DXS1225-DXS8082 haplotype is 210-219. Even though São Miguel islanders and Azoreans do not constitute isolated populations and show LD for only very short physical distances, certain characteristics, such as the absence of genetic structure, the same environment and the possibility of constructing extensive pedigrees through church and civil records, offer an opportunity for dissecting the genetic background of complex diseases in these populations. PMID:21637671

  12. Linkage disequilibrium analysis of case-control data: an application to generalized aggressive periodontitis.

    PubMed

    Scapoli, C; Trombelli, L; Mamolini, E; Collins, A

    2005-02-01

    Several studies have shown a role for the involvement of interleukin (IL)-1 gene cluster polymorphisms in the risk of periodontal diseases. In the present study, we tested polymorphisms, derived from genes of the IL-1 cluster, for association with generalized aggressive periodontitis (GAP) through both allelic association and by constructing a linkage disequilibrium (LD) map of the 2q13-14 disease candidate region. The IL-1RN (VNTR) genotype distribution observed was significantly different in GAP and control subjects (P=0.019). We also observed some evidence for an association between GAP and the IL-1B(+3953) polymorphism (P=0.039). The pattern of association in the region, represented as an LD map, identifies a recombination hot area between the IL-1B(+3953) and IL-1B(-511) polymorphisms. Multilocus modelling of association with disease gives a location for the peak association at the IL-1B(+3953) marker, although support for the peak is not significant. Haplotype analysis identifies a IL-1B(+3953)-IL-1B(-511) haplotype as having the lowest P-value in the region. Recognition of the presence of a recombination hot area between the IL-1B(+3953) and IL-1B(-511) polymorphisms will have an important bearing on future efforts to develop higher resolution SNP analysis in this region for both this and other diseases for which this cluster is implicated. PMID:15602586

  13. Extensive Long-Range and Nonsyntenic Linkage Disequilibrium in Livestock Populations: Deconstruction of a Conundrum

    PubMed Central

    Lipkin, E.; Straus, K.; Stein, R. Tal; Bagnato, A.; Schiavini, F.; Fontanesi, L.; Russo, V.; Medugorac, I.; Foerster, M.; Sölkner, J.; Dolezal, M.; Medrano, J. F.; Friedmann, A.; Soller, M.

    2009-01-01

    Great interest was aroused by reports, based on microsatellite markers, of high levels of statistically significant long-range and nonsyntenic linkage disequilibrium (LD) in livestock. Simulation studies showed that this could result from population family structure. In contrast, recent SNP-based studies of livestock populations report much lower levels of LD. In this study we show, on the basis of microsatellite data from four cattle populations, that high levels of long-range LD are indeed obtained when using the multi-allelic D′ measure of LD. Long-range and nonsyntenic LD are exceedingly low, however, when evaluated by the standardized chi-square measure of LD, which stands in relation to the predictive ability of LD. Furthermore, specially constructed study populations provided no evidence for appreciable LD resulting from family structure at the grandparent level. We propose that the high statistical significance and family structure effects observed in the earlier studies are due to the use of large sample sizes, which accord high statistical significance to even slight deviations from asymptotic expectations under the null hypothesis. Nevertheless, even after taking sample size into account, our results indicate that microsatellites testify to the presence of usable LD at considerably wider separation distances than SNPs, suggesting that use of SNP haplotypes may considerably increase the usefulness of a given fixed SNP array. PMID:19087960

  14. Linkage Disequilibrium and Genome-Wide Association Mapping in Tetraploid Wheat (Triticum turgidum L.)

    PubMed Central

    Laidò, Giovanni; Marone, Daniela; Russo, Maria A.; Colecchia, Salvatore A.; Mastrangelo, Anna M.; De Vita, Pasquale; Papa, Roberto

    2014-01-01

    Association mapping is a powerful tool for the identification of quantitative trait loci through the exploitation of the differential decay of linkage disequilibrium (LD) between marker loci and genes of interest in natural and domesticated populations. Using a sample of 230 tetraploid wheat lines (Triticum turgidum ssp), which included naked and hulled accessions, we analysed the pattern of LD considering 26 simple sequence repeats and 970 mostly mapped diversity array technology loci. In addition, to validate the potential for association mapping in durum wheat, we evaluated the same genotypes for plant height, heading date, protein content, and thousand-kernel weight. Molecular and phenotypic data were used to: (i) investigate the genetic and phenotypic diversity; (ii) study the dynamics of LD across the durum wheat genome, by investigating the patterns of LD decay; and (iii) test the potential of our panel to identify marker–trait associations through the analysis of four quantitative traits of major agronomic importance. Moreover, we compared and validated the association mapping results with outlier detection analysis based on population divergence. Overall, in tetraploid wheat, the pattern of LD is extremely population dependent and is related to the domestication and breeding history of durum wheat. Comparing our data with several other studies in wheat, we confirm the position of many major genes and quantitative trait loci for the traits considered. Finally, the analysis of the selection signature represents a very useful complement to validate marker–trait associations. PMID:24759998

  15. Linkage disequilibrium and haplotype analysis among Polish families with spinal muscular atrophy

    SciTech Connect

    Brzustowicz, L.M.; Wang, C.H.; Matseoane, D.; Kleyn, P.W.; Vitale, E.; Das, K.; Penchaszadeh, G.K.; Gilliam, T.C.; Munsat, T.L.; Hausmanowa-Petrusewicz, I.

    1995-01-01

    Spinal muscular atrophy (SMA) is an inherited degenerative disorder of anterior horn cells that results in progressive muscle weakness and atrophy. The autosomal recessive forms of childhood-onset SMA have been mapped to chromosome 5q11.2-13.3, in a number of studies examining different populations. A total of 9 simple sequence repeat markers were genotyped against 32 Polish families with SMA. The markers span an {approximately}0.7 cM region defined by the SMA flanking markers D5S435 and MAP1B. Significant linkage disequilibrium (corrected P<0.5) was detected at four of these markers, with D/D{sub max} values of {le}.89. Extended haplotype analysis revealed a predominant haplotype associated with SMA. The apparently high mutation rate of some of the markers has resulted in a number of haplotypes that vary slightly from this predominant haplotype. The predominant haplotype and these closely related patterns represent 25% of the disease chromosomes and none of the nontransmitted parental chromosomes. This predominant haplotype is present both in patients with acute (type I) and in chronic (types II and III) forms of SMA and occurs twice in a homozygous state, both times in children with chronic SMA. 34 refs., 2 figs., 2 tabs.

  16. An empiric comparison of linkage disequilibrium parameters in disease gene localizations; the myotonic dystrophy experience

    SciTech Connect

    Podolsky, L.; Baird, S.; Korneluk, R.G.

    1994-09-01

    Analyses of linkage disequilibrium (LD) between markers of known location and disease phenotypes often provide valuable information in efforts to clone the causative genes. However, there exist a number of factors which may attenuate a consistent inverse relationship between physical distance and LD for a given pairing of a genetic marker and a human disease gene. Chief among these is the effect of the general population frequency of an allele which demonstrates LD with a disease gene. Possibly as a result of this, a number of methods of calculating LD has been proposed. We have calculated seven such LD parameters for twelve physically mapped RFLP`s from a 1.3 Mb DM gene containing region of 19q13.3 using 107 DM and 213 non-DM chromosomes. Correlation of the DM-marker physical distance with LD for the 12 loci reveals the Yule coefficient and Dij{prime} parameter to give the most consistent relationship. The D{prime} parameter shown to have a relative allele frequency independence gave only a weak correlation. A similar analysis is being carried out on published cystic fibrosis genetic and physical mapping data. The parameters identified in this study may be the most appropriate for future LD based localizations of disease genes.

  17. Molecular diversity, population structure, and linkage disequilibrium in a worldwide collection of tobacco (Nicotiana tabacum L.) germplasm

    PubMed Central

    2012-01-01

    Background The goals of our study were to assess the phylogeny and the population structure of tobacco accessions representing a wide range of genetic diversity; identify a subset of accessions as a core collection capturing most of the existing genetic diversity; and estimate, in the tobacco core collection, the extent of linkage disequilibrium (LD) in seven genomic regions using simple sequence repeat (SSR) markers. To this end, a collection of accessions were genotyped with SSR markers. Molecular diversity was evaluated and LD was analyzed across seven regions of the genome. Results A genotyping database for 312 tobacco accessions was profiled with 49 SSR markers. Principal Coordinate Analysis (PCoA) and Bayesian cluster analysis revealed structuring of the tobacco population with regard to commercial classes and six main clades were identified, which correspond to "Oriental", Flue-Cured", "Burley", "Dark", "Primitive", and "Other" classes. Pairwise kinship was calculated between accessions, and an overall low level of co-ancestry was observed. A set of 89 genotypes was identified that captured the whole genetic diversity detected at the 49 loci. LD was evaluated on these genotypes, using 422 SSR markers mapping on seven linkage groups. LD was estimated as squared correlation of allele frequencies (r2). The pattern of intrachromosomal LD revealed that in tobacco LD extended up to distances as great as 75 cM with r2 > 0.05 or up to 1 cM with r2 > 0.2. The pattern of LD was clearly dependent on the population structure. Conclusions A global population of tobacco is highly structured. Clustering highlights the accessions with the same market class. LD in tobacco extends up to 75 cM and is strongly dependent on the population structure. PMID:22435796

  18. Potential linkage disequilibrium between schizophrenia and locus D22S278 on the long arm of chromosome 22

    SciTech Connect

    Moises, H.W.; Yang, L.; Havsteen, B.

    1995-10-09

    Locus D22S278 at 22q12 has been implicated in schizophrenia by sib-pair analysis. In order to replicate these results, we performed the transmission test for linkage disequilibrium (TDT) in 113 unrelated schizophrenic patients and their 226 parents. Evidence for potential linkage disequilibrium was obtained between schizophrenia and allele 243 of the marker AFM 182xd12 at the locus D22S278 (P = 0.02). The results of our study suggest a detectable oligogenic gene in a multigene system for schizophrenia closely linked to D22S278 on the long arm of chromosome 22. If confirmed by others, this finding could lead to the identification of a schizophrenia susceptibility gene. 12 refs., 1 tab.

  19. Population genomic structure and linkage disequilibrium analysis of South African goat breeds using genome-wide SNP data.

    PubMed

    Mdladla, K; Dzomba, E F; Huson, H J; Muchadeyi, F C

    2016-08-01

    The sustainability of goat farming in marginal areas of southern Africa depends on local breeds that are adapted to specific agro-ecological conditions. Unimproved non-descript goats are the main genetic resources used for the development of commercial meat-type breeds of South Africa. Little is known about genetic diversity and the genetics of adaptation of these indigenous goat populations. This study investigated the genetic diversity, population structure and breed relations, linkage disequilibrium, effective population size and persistence of gametic phase in goat populations of South Africa. Three locally developed meat-type breeds of the Boer (n = 33), Savanna (n = 31), Kalahari Red (n = 40), a feral breed of Tankwa (n = 25) and unimproved non-descript village ecotypes (n = 110) from four goat-producing provinces of the Eastern Cape, KwaZulu-Natal, Limpopo and North West were assessed using the Illumina Goat 50K SNP Bead Chip assay. The proportion of SNPs with minor allele frequencies >0.05 ranged from 84.22% in the Tankwa to 97.58% in the Xhosa ecotype, with a mean of 0.32 ± 0.13 across populations. Principal components analysis, admixture and pairwise FST identified Tankwa as a genetically distinct population and supported clustering of the populations according to their historical origins. Genome-wide FST identified 101 markers potentially under positive selection in the Tankwa. Average linkage disequilibrium was highest in the Tankwa (r(2)  = 0.25 ± 0.26) and lowest in the village ecotypes (r(2) range = 0.09 ± 0.12 to 0.11 ± 0.14). We observed an effective population size of <150 for all populations 13 generations ago. The estimated correlations for all breed pairs were lower than 0.80 at marker distances >100 kb with the exception of those in Savanna and Tswana populations. This study highlights the high level of genetic diversity in South African indigenous goats as well as the utility of the genome-wide SNP marker panels in

  20. A powerful likelihood method for the analysis of linkage disequilibrium between trait loci and one or more polymorphic marker loci

    SciTech Connect

    Terwilliger, J.D.

    1995-03-01

    Historically, most methods for detecting linkage disequilibrium were designed for use with diallelic marker loci, for which the analysis is straightforward. With the advent of polymorphic markers with many alleles, the normal approach to their analysis has been either to extend the methodology for two-allele systems (leading to an increase in df and to a corresponding loss of power) or to select the allele believed to be associated and then collapse the other alleles, reducing, in a biased way, the locus to a diallelic system. I propose a likelihood-based approach to testing for linkage disequilibrium, an approach that becomes more conservative as the number of alleles increases, and as the number of markers considered jointly increases in a multipoint test for linkage disequilibrium, while maintaining high power. Properties of this method for detecting associations and fine mapping the location of disease traits are investigated. It is found to be, in general, more powerful than conventional methods, and it provides a tractable framework for the fine mapping of new disease loci. Application to the cystic fibrosis data of Kerem et al. is included to illustrate the method. 12 refs., 4 figs., 4 tabs.

  1. Comparative population genetics of the panicoid grasses: sequence polymorphism, linkage disequilibrium and selection in a diverse sample of sorghum bicolor.

    PubMed Central

    Hamblin, Martha T; Mitchell, Sharon E; White, Gemma M; Gallego, Javier; Kukatla, Rakesh; Wing, Rod A; Paterson, Andrew H; Kresovich, Stephen

    2004-01-01

    Levels of genetic variation and linkage disequilibrium (LD) are critical factors in association mapping methods as well as in identification of loci that have been targets of selection. Maize, an outcrosser, has a high level of sequence variation and a limited extent of LD. Sorghum, a closely related but largely self-pollinating panicoid grass, is expected to have higher levels of LD. As a first step in estimation of population genetic parameters in sorghum, we surveyed 27 diverse S. bicolor accessions for sequence variation at a total of 29,186 bp in 95 short regions derived from genetically mapped RFLPs located throughout the genome. Consistent with its higher level of inbreeding, the extent of LD is at least severalfold greater in sorghum than in maize. Total sequence variation in sorghum is about fourfold lower than that in maize, while synonymous variation is fivefold lower, suggesting a smaller effective population size in sorghum. Because we surveyed a species-wide sample, the mating system, which primarily affects population-level diversity, may not be primarily responsible for this difference. Comparisons of polymorphism and divergence suggest that both directional and diversifying selection have played important roles in shaping variation in the sorghum genome. PMID:15166170

  2. A Scale-Corrected Comparison of Linkage Disequilibrium Levels between Genic and Non-Genic Regions

    PubMed Central

    Berger, Swetlana; Schlather, Martin; de los Campos, Gustavo; Weigend, Steffen; Preisinger, Rudolf; Erbe, Malena; Simianer, Henner

    2015-01-01

    The understanding of non-random association between loci, termed linkage disequilibrium (LD), plays a central role in genomic research. Since causal mutations are generally not included in genomic marker data, LD between those and available markers is essential for capturing the effects of causal loci on localizing genes responsible for traits. Thus, the interpretation of association studies requires a detailed knowledge of LD patterns. It is well known that most LD measures depend on minor allele frequencies (MAF) of the considered loci and the magnitude of LD is influenced by the physical distances between loci. In the present study, a procedure to compare the LD structure between genomic regions comprising several markers each is suggested. The approach accounts for different scaling factors, namely the distribution of MAF, the distribution of pair-wise differences in MAF, and the physical extent of compared regions, reflected by the distribution of pair-wise physical distances. In the first step, genomic regions are matched based on similarity in these scaling factors. In the second step, chromosome- and genome-wide significance tests for differences in medians of LD measures in each pair are performed. The proposed framework was applied to test the hypothesis that the average LD is different in genic and non-genic regions. This was tested with a genome-wide approach with data sets for humans (Homo sapiens), a highly selected chicken line (Gallus gallus domesticus) and the model plant Arabidopsis thaliana. In all three data sets we found a significantly higher level of LD in genic regions compared to non-genic regions. About 31% more LD was detected genome-wide in genic compared to non-genic regions in Arabidopsis thaliana, followed by 13.6% in human and 6% chicken. Chromosome-wide comparison discovered significant differences on all 5 chromosomes in Arabidopsis thaliana and on one third of the human and of the chicken chromosomes. PMID:26517830

  3. Extent and Distribution of Linkage Disequilibrium in the Old Order Amish

    PubMed Central

    Van Hout, Cristopher V; Levin, Albert M; Rampersaud, Evadnie; Shen, Haiqing; O'Connell, Jeffrey R; Mitchell, Braxton D; Shuldiner, Alan R; Douglas, Julie A

    2010-01-01

    Knowledge of the extent and distribution of linkage disequilibrium (LD) is critical to the design and interpretation of gene mapping studies. Because the demographic history of each population varies and is often not accurately known, it is necessary to empirically evaluate LD on a population-specific basis. Here we present the first genome-wide survey of LD in the Old Order Amish (OOA) of Lancaster County Pennsylvania, a closed population derived from a modest number of founders. Specifically, we present a comparison of LD between OOA individuals and US Utah participants in the International HapMap project (abbreviated CEU) using a high-density single nucleotide polymorphism (SNP) map. Overall, the allele (and haplotype) frequency distributions and LD profiles were remarkably similar between these two populations. For example, the median absolute allele frequency difference for autosomal SNPs was 0.05, with an inter-quartile range of 0.02–0.09, and for autosomal SNPs 10–20 kb apart with common alleles (minor allele frequency≥0.05), the LD measure r2 was at least 0.8 for 15 and 14% of SNP pairs in the OOA and CEU, respectively. Moreover, tag SNPs selected from the HapMap CEU sample captured a substantial portion of the common variation in the OOA (∼88%) at r2≥0.8. These results suggest that the OOA and CEU may share similar LD profiles for other common but untyped SNPs. Thus, in the context of the common variant-common disease hypothesis, genetic variants discovered in gene mapping studies in the OOA may generalize to other populations. PMID:19697356

  4. High rates of phasing errors in highly polymorphic species with low levels of linkage disequilibrium.

    PubMed

    Bukowicki, Marek; Franssen, Susanne U; Schlötterer, Christian

    2016-07-01

    Short read sequencing of diploid individuals does not permit the direct inference of the sequence on each of the two homologous chromosomes. Although various phasing software packages exist, they were primarily tailored for and tested on human data, which differ from other species in factors that influence phasing, such as SNP density, amounts of linkage disequilibrium (LD) and sample sizes. Despite becoming increasingly popular for other species, the reliability of phasing in non-human data has not been evaluated to a sufficient extent. We scrutinized the phasing accuracy for Drosophila melanogaster, a species with high polymorphism levels and reduced LD relative to humans. We phased two D. melanogaster populations and compared the results to the known haplotypes. The performance increased with size of the reference panel and was highest when the reference panel and phased individuals were from the same population. Full genomic SNP data and inclusion of sequence read information also improved phasing. Despite humans and Drosophila having similar switch error rates between polymorphic sites, the distances between switch errors were much shorter in Drosophila with only fragments <300-1500 bp being correctly phased with ≥95% confidence. This suggests that the higher SNP density cannot compensate for the higher recombination rate in D. melanogaster. Furthermore, we show that populations that have gone through demographic events such as bottlenecks can be phased with higher accuracy. Our results highlight that statistically phased data are particularly error prone in species with large population sizes or populations lacking suitable reference panels. PMID:26929272

  5. Nucleotide diversity and linkage disequilibrium in 11 expressed resistance candidate genes in Lolium perenne

    PubMed Central

    Xing, Yongzhong; Frei, Uschi; Schejbel, Britt; Asp, Torben; Lübberstedt, Thomas

    2007-01-01

    Background Association analysis is an alternative way for QTL mapping in ryegrass. So far, knowledge on nucleotide diversity and linkage disequilibrium in ryegrass is lacking, which is essential for the efficiency of association analyses. Results 11 expressed disease resistance candidate (R) genes including 6 nucleotide binding site and leucine rich repeat (NBS-LRR) like genes and 5 non-NBS-LRR genes were analyzed for nucleotide diversity. For each of the genes about 1 kb genomic fragments were isolated from 20 heterozygous genotypes in ryegrass. The number of haplotypes per gene ranged from 9 to 27. On average, one single nucleotide polymorphism (SNP) was present per 33 bp between two randomly sampled sequences for the 11 genes. NBS-LRR like gene fragments showed a high degree of nucleotide diversity, with one SNP every 22 bp between two randomly sampled sequences. NBS-LRR like gene fragments showed very high non-synonymous mutation rates, leading to altered amino acid sequences. Particularly LRR regions showed very high diversity with on average one SNP every 10 bp between two sequences. In contrast, non-NBS LRR resistance candidate genes showed a lower degree of nucleotide diversity, with one SNP every 112 bp. 78% of haplotypes occurred at low frequency (<5%) within the collection of 20 genotypes. Low intragenic LD was detected for most R genes, and rapid LD decay within 500 bp was detected. Conclusion Substantial LD decay was found within a distance of 500 bp for most resistance candidate genes in this study. Hence, LD based association analysis is feasible and promising for QTL fine mapping of resistance traits in ryegrass. PMID:17683574

  6. Population Structure, Genetic Variation, and Linkage Disequilibrium in Perennial Ryegrass Populations Divergently Selected for Freezing Tolerance

    PubMed Central

    Kovi, Mallikarjuna Rao; Fjellheim, Siri; Sandve, Simen R.; Larsen, Arild; Rudi, Heidi; Asp, Torben; Kent, Matthew Peter; Rognli, Odd Arne

    2015-01-01

    Low temperature is one of the abiotic stresses seriously affecting the growth of perennial ryegrass (Lolium perenne L.), and freezing tolerance is a complex trait of major agronomical importance in northern and central Europe. Understanding the genetic control of freezing tolerance would aid in the development of cultivars of perennial ryegrass with improved adaptation to frost. The plant material investigated in this study was an experimental synthetic population derived from pair-crosses among five European perennial ryegrass genotypes, representing adaptations to a range of climatic conditions across Europe. A total number of 80 individuals (24 of High frost [HF]; 29 of Low frost [LF], and 27 of Unselected [US]) from the second generation of the two divergently selected populations and an unselected (US) control population were genotyped using 278 genome-wide SNPs derived from perennial ryegrass transcriptome sequences. Our studies investigated the genetic diversity among the three experimental populations by analysis of molecular variance and population structure, and determined that the HF and LF populations are very divergent after selection for freezing tolerance, whereas the HF and US populations are more similar. Linkage disequilibrium (LD) decay varied across the seven chromosomes and the conspicuous pattern of LD between the HF and LF population confirmed their divergence in freezing tolerance. Furthermore, two Fst outlier methods; finite island model (fdist) by LOSITAN and hierarchical structure model using ARLEQUIN, both detected six loci under directional selection. These outlier loci are most probably linked to genes involved in freezing tolerance, cold adaptation, and abiotic stress. These six candidate loci under directional selection for freezing tolerance might be potential marker resources for breeding perennial ryegrass cultivars with improved freezing tolerance. PMID:26617611

  7. The heterogeneous levels of linkage disequilibrium in white spruce genes and comparative analysis with other conifers.

    PubMed

    Pavy, N; Namroud, M-C; Gagnon, F; Isabel, N; Bousquet, J

    2012-03-01

    In plants, knowledge about linkage disequilibrium (LD) is relevant for the design of efficient single-nucleotide polymorphism arrays in relation to their use in population and association genomics studies. Previous studies of conifer genes have shown LD to decay rapidly within gene limits, but exceptions have been reported. To evaluate the extent of heterogeneity of LD among conifer genes and its potential causes, we examined LD in 105 genes of white spruce (Picea glauca) by sequencing a panel of 48 haploid megagametophytes from natural populations and further compared it with LD in other conifer species. The average pairwise r(2) value was 0.19 (s.d.=0.19), and LD dropped quickly with a half-decay being reached at a distance of 65 nucleotides between sites. However, LD was significantly heterogeneous among genes. A first group of 29 genes had stronger LD (mean r(2)=0.28), and a second group of 38 genes had weaker LD (mean r(2)=0.12). While a strong relationship was found with the recombination rate, there was no obvious relationship between LD and functional classification. The level of nucleotide diversity, which was highly heterogeneous across genes, was also not significantly correlated with LD. A search for selection signatures highlighted significant deviations from the standard neutral model, which could be mostly attributed to recent demographic changes. Little evidence was seen for hitchhiking and clear relationships with LD. When compared among conifer species, on average, levels of LD were similar in genes from white spruce, Norway spruce and Scots pine, whereas loblolly pine and Douglas fir genes exhibited a significantly higher LD. PMID:21897435

  8. Accuracy of genomic prediction in switchgrass (Panicum virgatum L.) improved by accounting for linkage disequilibrium

    DOE PAGESBeta

    Ramstein, Guillaume P.; Evans, Joseph; Kaeppler, Shawn M.; Mitchell, Robert B.; Vogel, Kenneth P.; Buell, C. Robin; Casler, Michael D.

    2016-02-11

    Switchgrass is a relatively high-yielding and environmentally sustainable biomass crop, but further genetic gains in biomass yield must be achieved to make it an economically viable bioenergy feedstock. Genomic selection (GS) is an attractive technology to generate rapid genetic gains in switchgrass, and meet the goals of a substantial displacement of petroleum use with biofuels in the near future. In this study, we empirically assessed prediction procedures for genomic selection in two different populations, consisting of 137 and 110 half-sib families of switchgrass, tested in two locations in the United States for three agronomic traits: dry matter yield, plant height,more » and heading date. Marker data were produced for the families’ parents by exome capture sequencing, generating up to 141,030 polymorphic markers with available genomic-location and annotation information. We evaluated prediction procedures that varied not only by learning schemes and prediction models, but also by the way the data were preprocessed to account for redundancy in marker information. More complex genomic prediction procedures were generally not significantly more accurate than the simplest procedure, likely due to limited population sizes. Nevertheless, a highly significant gain in prediction accuracy was achieved by transforming the marker data through a marker correlation matrix. Our results suggest that marker-data transformations and, more generally, the account of linkage disequilibrium among markers, offer valuable opportunities for improving prediction procedures in GS. Furthermore, some of the achieved prediction accuracies should motivate implementation of GS in switchgrass breeding programs.« less

  9. Extent of Linkage Disequilibrium and Effective Population Size in Four South African Sanga Cattle Breeds

    PubMed Central

    Makina, Sithembile O.; Taylor, Jeremy F.; van Marle-Köster, Este; Muchadeyi, Farai C.; Makgahlela, Mahlako L.; MacNeil, Michael D.; Maiwashe, Azwihangwisi

    2015-01-01

    Knowledge on the extent of linkage disequilibrium (LD) in livestock populations is essential to determine the minimum distance between markers required for effective coverage when conducting genome-wide association studies (GWAS). This study evaluated the extent of LD, persistence of allelic phase and effective population size (Ne) for four Sanga cattle breeds in South Africa including the Afrikaner (n = 44), Nguni (n = 54), Drakensberger (n = 47), and Bonsmara breeds (n = 46), using Angus (n = 31) and Holstein (n = 29) as reference populations. We found that moderate LD extends up to inter-marker distances of 40–60 kb in Angus (0.21) and Holstein (0.21) and up to 100 kb in Afrikaner (0.20). This suggests that genomic selection and association studies performed within these breeds using an average inter-marker r2≥ 0.20 would require about 30,000–50,000 SNPs. However, r2≥ 0.20 extended only up to 10–20 kb in the Nguni and Drakensberger and 20–40 kb in the Bonsmara indicating that 75,000 to 150,000 SNPs would be necessary for GWAS in these breeds. Correlation between alleles at contiguous loci indicated that phase was not strongly preserved between breeds. This suggests the need for breed-specific reference populations in which a much greater density of markers should be scored to identify breed specific haplotypes which may then be imputed into multi-breed commercial populations. Analysis of effective population size based on the extent of LD, revealed Ne = 95 (Nguni), Ne = 87 (Drakensberger), Ne = 77 (Bonsmara), and Ne = 41 (Afrikaner). Results of this study form the basis for implementation of genomic selection programs in the Sanga breeds of South Africa. PMID:26648975

  10. Improving power in contrasting linkage-disequilibrium patterns between cases and controls.

    PubMed

    Wang, Tao; Zhu, Xiaofeng; Elston, Robert C

    2007-05-01

    Genetic association studies offer an opportunity to find genetic variants underlying complex human diseases. The success of this approach depends on the linkage disequilibrium (LD) between markers and the disease variant(s) in a local region of the genome. Because, in the region with a disease mutation, the LD pattern among markers may differ between cases and controls, in some scenarios, it is useful to compare a measure of this LD, to map disease mutations. For example, using the composite correlation to characterize the LD among markers, Zaykin et al. recently suggested an "LD contrast" test and showed that it has high power under certain haplotype-driven disease models. Furthermore, it is likely that individual variants observed at different positions in a gene act jointly with each other to influence the phenotype, and the LD contrast test is also a useful method to detect such joint action. However, the LD among markers introduced by mutations and their joint action is usually confounded by background LD, which is measured at the population level, especially in a local region with disease mutations. Because the measures of LD that are usually used, such as the composite correlation, represent both effects, they may not be optimal for the purpose of detecting association when high background LD exists. Here, we describe a test that improves the LD contrast test by taking into account the background LD. Because the proposed test is developed in a regression framework, it is very flexible and can be extended to continuous traits and to incorporate covariates. Our simulation results demonstrate the validity and substantially higher power of the proposed method over current methods. Finally, we illustrate our new method by applying it to real data from the International Collaborative Study on Hypertension in Blacks. PMID:17436245

  11. Efficient Genome-Wide TagSNP Selection Across Populations via the Linkage Disequilibrium Criterion

    PubMed Central

    Wu, Yonghui; Lonardi, Stefano; Jiang, Tao

    2010-01-01

    Abstract In this article, we studied the tag single-nucleotide polymorphism (tagSNP) selection problem on multiple populations using the pairwise r2 linkage disequilibrium criterion. We proposed a novel combinatorial optimization model for the tagSNP selection problem, called the minimum common tagSNP selection (MCTS) problem, and presented efficient solutions for MCTS. Our approach consists of the following three main steps: (i) partitioning the SNP markers into small disjoint components, (ii) applying some data reduction rules to simplify the problem, and (iii) applying either a fast greedy algorithm or a Lagrangian relaxation algorithm to solve the remaining (general) MCTS. These algorithms also provide lower bounds on tagging (i.e., the minimum number of tagSNPs needed). The lower bounds allow us to evaluate how far our solution is from the optimum. To the best of our knowledge, it is the first time the tagging lower bounds are discussed in the literature. We assessed the performance of our algorithms on real HapMap data for genome-wide tagging. The experiments demonstrated that our algorithms run 3–4 orders of magnitude faster than the existing single-population tagging programs such as FESTA, LD-Select, and the multiple-population tagging method MultiPop-TagSelect. Our method also greatly reduced the required tagSNPs compared with LD-Select on a single population and MultiPop-TagSelect on multiple populations. Moreover, the numbers of tagSNPs selected by our algorithms are almost optimal because they are very close to the corresponding lower bounds obtained by our method. PMID:20078395

  12. The extent of linkage disequilibrium in beef cattle breeds using high-density SNP genotypes

    PubMed Central

    2014-01-01

    Background The extent of linkage disequilibrium (LD) between molecular markers impacts genome-wide association studies and implementation of genomic selection. The availability of high-density single nucleotide polymorphism (SNP) genotyping platforms makes it possible to investigate LD at an unprecedented resolution. In this work, we characterised LD decay in breeds of beef cattle of taurine, indicine and composite origins and explored its variation across autosomes and the X chromosome. Findings In each breed, LD decayed rapidly and r2 was less than 0.2 for marker pairs separated by 50 kb. The LD decay curves clustered into three groups of similar LD decay that distinguished the three main cattle types. At short distances between markers (< 10 kb), taurine breeds showed higher LD (r2 = 0.45) than their indicine (r2 = 0.25) and composite (r2 = 0.32) counterparts. This higher LD in taurine breeds was attributed to a smaller effective population size and a stronger bottleneck during breed formation. Using all SNPs on only the X chromosome, the three cattle types could still be distinguished. However for taurine breeds, the LD decay on the X chromosome was much faster and the background level much lower than for indicine breeds and composite populations. When using only SNPs that were polymorphic in all breeds, the analysis of the X chromosome mimicked that of the autosomes. Conclusions The pattern of LD mirrored some aspects of the history of breed populations and showed a sharp decay with increasing physical distance between markers. We conclude that the availability of the HD chip can be used to detect association signals that remained hidden when using lower density genotyping platforms, since LD dropped below 0.2 at distances of 50 kb. PMID:24661366

  13. Assessing the patterns of linkage disequilibrium in genic regions of the human genome.

    PubMed

    Sun, Peng; Zhang, Ruijie; Jiang, Yongshuai; Wang, Xing; Li, Jin; Lv, Hongchao; Tang, Guoping; Guo, Xiaodan; Meng, Xianwen; Zhang, Haikun; Zhang, Ruimin

    2011-10-01

    We used the genotyping data generated by the International HapMap Project to study the patterns of linkage disequilibrium (LD) in human genic regions. LD patterns for 11,998 genes from 11 HapMap populations were identified by analyzing the distribution of haplotype blocks. The genes were prioritized using LD levels. The results showed that there were significant differences in the degree of LD between genes. Genes with high or low LD (the upper and lower quartiles of the LD levels) fell into different Gene Ontology functional categories. The high LD genes clustered preferentially in the metabolic process, macromolecule localization and cell-cycle categories, whereas the low LD genes clustered in the developmental process, ion transport, and immune and regulation system categories. Furthermore, we subdivided the genic region into 3'-UTR, 5'-UTR and CDS (coding region), and compared the different LD patterns in these subregions. We found that the LD patterns in low LD genes had a more interspersed block structure compared with the high LD genes. This was especially true in the CDS and 5'-UTR. The extent of LD was somewhat higher in 5'-UTRs compared with 3'-UTRs for both high and low LD genes. In addition, we assessed the overlap for the intragenic LD regions and found that the LD regions in high LD genes were more consistent among populations. Comprehensive information about the distribution of LD patterns in gene regions in populations may provide insights into the evolutionary history of humans and help in the selection of biomarkers for disease association studies. PMID:21824289

  14. Geographic stratification of linkage disequilibrium: a worldwide population study in a region of chromosome 22

    PubMed Central

    2004-01-01

    Recent studies of haplotype diversity in a number of genomic regions have suggested that long stretches of DNA are preserved in the same chromosome, with little evidence of recombination events. The knowledge of the extent and strength of these haplotypes could become a powerful tool for future genetic analysis of complex traits. Different patterns of linkage disequilibrium (LD) have been found when comparing individuals of African and European descent, but there is scarce knowledge about the worldwide population stratification. Thus, the study of haplotype composition and the pattern of LD from a global perspective are relevant for elucidating their geographical stratification, as it may have implications in the future analysis of complex traits. We have typed 12 single nucleotide polymorphisms in a chromosome 22 region--previously described as having high LD levels in European populations -- in 39 different world populations. Haplotype structure has a clear continental structure with marked heterogeneity within some continents (Africa, America). The pattern of LD among neighbouring markers exhibits a strong clustering of all East Asian populations on the one hand and of Western Eurasian populations (including Europe) on the other, revealing only two major LD patterns, but with some very specific outliers due to specific demographic histories. Moreover, it should be taken into account that African populations are highly heterogeneous. The present results support the existence of a wide (but not total) communality in LD patterns in human populations from different continental regions, despite differences in their demographic histories, as population factors seem to be less relevant compared with genomic forces in shaping the patterns of LD. PMID:15606995

  15. Linkage disequilibrium at the APA insecticidal seed protein locus of common bean (Phaseolus vulgaris L.)

    PubMed Central

    2010-01-01

    Background An interesting seed protein family with a role in preventing insect herbivory is the multi-gene, APA family encoding the α-amylase inhibitor, phytohemagglutinin and arcelin proteins of common bean (Phaseolus vulgaris). Variability for this gene family exists and has been exploited to breed for insect resistance. For example, the arcelin locus has been successfully transferred from wild to cultivated common bean genotypes to provide resistance against the bruchid species Zabrotes subfasciatus although the process has been hampered by a lack of genetic tools for and understanding about the locus. In this study, we analyzed linkage disequilibrium (LD) between microsatellite markers at the APA locus and bruchid resistance in a germplasm survey of 105 resistant and susceptible genotypes and compared this with LD in other parts of the genome. Results Microsatellite allele diversity was found to vary with each of the eight APA-linked markers analyzed, and two markers within the APA locus were found to be diagnostic for bruchid resistance or susceptibility and for the different arcelin alleles inherited from the wild accessions. Arc1 was found to provide higher levels of resistance than Arc5 and the markers in the APA locus were highly associated with resistance showing that introgression of this gene-family from wild beans provides resistance in cultivated beans. LD around the APA locus was found to be intermediate compared to other regions of the genome and the highest LD was found within the APA locus itself for example between the markers PV-atct001 and PV-ag004. Conclusions We found the APA locus to be an important genetic determinant of bruchid resistance and also found that LD existed mostly within the APA locus but not beyond it. Moderate LD was also found for some other regions of the genome perhaps related to domestication genes. The LD pattern may reflect the introgression of arcelin from the wild into the cultivated background through breeding. LD

  16. Linkage disequilibrium between an allele at the dopamine D4 receptor locus and Tourette syndrome, by the transmission-disequilibrium test

    SciTech Connect

    Grice, D.E.; Gelernter, J.; Leckman, J.F.; Pauls, D.L.

    1996-09-01

    Dopaminergic abnormalities are implicated in the pathogenesis of Tourette syndrome (TS) and chronic multiple tics. We used the transmission-disequilibrium test (TDT) method to test for linkage disequilibrium between a specific allele (the seven-repeat allele (DRD4*7R) of the exon 3 VNTR polymorphic site) at the D4 dopamine receptor locus (DRD4) and expression of chronic multiple tics and TS. This particular allele had been shown in functional studies to have different binding properties compared with the other common alleles in this DRD4 polymorphic system. We studied 64 family trios (consisting of an affected person and two parents, at least one heterozygous for DRD4*7R), including 12 nuclear family trios and 52 trios from four large TS kindreds. The DRD4*7R allele was transmitted significantly more frequently than expected ({chi}{sup 2}{sub TDT} ranging from 8.47 [P < .004] to 10.80 [P = .001], depending on breadth of disease definition and inclusion or exclusion of inferred genotypes). Confirmation of this finding will depend on either replication in other samples or the identification of a transmitted functional mutation within this sample. 56 refs., 2 figs., 3 tabs.

  17. Genome-wide patterns of segregation and linkage disequilibrium: the construction of a linkage genetic map of the poplar rust fungus Melampsora larici-populina

    PubMed Central

    Pernaci, Michaël; De Mita, Stéphane; Andrieux, Axelle; Pétrowski, Jérémy; Halkett, Fabien; Duplessis, Sébastien; Frey, Pascal

    2014-01-01

    The poplar rust fungus Melampsora larici-populina causes significant yield reduction and severe economic losses in commercial poplar plantations. After several decades of breeding for qualitative resistance and subsequent breakdown of the released resistance genes, breeders now focus on quantitative resistance, perceived to be more durable. But quantitative resistance also can be challenged by an increase of aggressiveness in the pathogen. Thus, it is of primary importance to better understand the genetic architecture of aggressiveness traits. To this aim, our goal is to build a genetic linkage map for M. larici-populina in order to map quantitative trait loci related to aggressiveness. First, a large progeny of M. larici-populina was generated through selfing of the reference strain 98AG31 (which genome sequence is available) on larch plants, the alternate host of the poplar rust fungus. The progeny's meiotic origin was validated through a segregation analysis of 115 offspring with 14 polymorphic microsatellite markers, of which 12 segregated in the expected 1:2:1 Mendelian ratio. A microsatellite-based linkage disequilibrium analysis allowed us to identify one potential linkage group comprising two scaffolds. The whole genome of a subset of 47 offspring was resequenced using the Illumina HiSeq 2000 technology at a mean sequencing depth of 6X. The reads were mapped onto the reference genome of the parental strain and 144,566 SNPs were identified across the genome. Analysis of distribution and polymorphism of the SNPs along the genome led to the identification of 2580 recombination blocks. A second linkage disequilibrium analysis, using the recombination blocks as markers, allowed us to group 81 scaffolds into 23 potential linkage groups. These preliminary results showed that a high-density linkage map could be constructed by using high-quality SNPs based on low-coverage resequencing of a larger number of M. larici-populina offspring. PMID:25309554

  18. Refined positioning of a quantitative trait locus affecting somatic cell score on chromosome 18 in the German Holstein using linkage disequilibrium.

    PubMed

    Baes, C; Brand, B; Mayer, M; Kühn, C; Liu, Z; Reinhardt, F; Reinsch, N

    2009-08-01

    Combined linkage and linkage disequilibrium analysis (LALD) was conducted to more accurately map a previously reported quantitative trait locus (QTL) affecting somatic cell score on bovine chromosome 18. A grand-daughter design consisting of 6 German Holstein grandsire families with 1,054 progeny-tested genotyped sons was used in this study. Twenty microsatellite markers, 5 single nucleotide polymorphisms, and an erythrocyte antigen marker with an average marker spacing of 1.95 cM were analyzed along a chromosomal segment of 50.80 cM. Variance components were estimated and restricted maximum likelihood test statistics were calculated at the midpoint of each marker interval. The test statistics calculated in single-QTL linkage analysis exceeded the genome-wide significance threshold at several putative QTL positions. Using LALD, we were successful in assigning a genome-wide significant QTL to a confidence interval of 10.8 cM between the markers ILSTS002 and BMS833. The QTL in this marker interval was estimated to be responsible for between 5.89 and 13.86% of the genetic variation in somatic cell score. In contrast to the single-QTL linkage analysis model, LALD analyses with a 2-QTL model confirmed the position of one QTL, but gave no conclusive evidence for the existence or position of a second QTL. Ultimately, the QTL position was narrowed down considerably compared with previous results with a refined confidence interval of less than 11 cM. PMID:19620688

  19. Anonymous marker loci within 400 kb of HLA-A generate haplotypes in linkage disequilibrium with the hemochromatosis gene (HFE)

    SciTech Connect

    Yaouanq, J.; Perichon, M.; Treut, A.L.; Kahloun, A.E.; Mauvieux, V.; Blayau, M.; Jouanolle, A.M.; Chauvel, B.; Le Gall, J.Y.; David, V. )

    1994-02-01

    The hemochromatosis gene (HFE) maps to 6p21.3 and is less than 1 cM from the HLA class I gene; however, the precise physical location of the gene has remained elusive and controversial. The unambiguous identification of a crossover event within hemochromatosis families is very difficult; it is particularly hampered by the variability of the phenotypic expression as well as by the sex- and age-related penetrance of the disease. For these considerations, traditional linkage analysis could prove of limited value in further refining the extrapolated physical position of HFE. The authors therefore embarked upon a linkage-disequilibrium analysis of HFE and normal chromosomes for the Brittany population. In this report, 66 hemochromatosis families yielding 151 hemochromatosis chromosomes and 182 normal chromosomes were RFLP-typed with a battery of probes, including two newly derived polymorphic markers from the 6.7 and HLA-F loci located 150 and 250 kb telomeric to HLA-A, respectively. The results suggest a strong peak of existing linkage disequilibrium focused within the i82-to-6.7 interval (approximately 250 kb). The zone of linkage disequilibrium is flanked by the i97 locus, positioned 30 kb proximal to i82, and the HLA-F gene, found 250 kb distal to HLA-A, markers of which display no significant association with HFE. These data support the possibility that HFE resides within the 400-kb expanse of DNA between i97 and HLA-F. Alternatively, the very tight association of HLA-A3 and allele 1 of the 6.7 locus, both of which are comprised by the major ancestral or founder HFE haplotype in Brittany, supports the possibility that the disease gene may reside immediately telomeric to the 6.7 locus within the linkage-disequilibrium zone. Additionally, hemochromatosis haplotypes possessing HLA-A11 and the low-frequency HLA-F polymorphism (allele 2) are supportive of a separate founder chromosome containing a second, independently arising mutant allele. 69 refs., 1 fig., 5 tabs.

  20. MICA, MICB Polymorphisms and Linkage Disequilibrium with HLA-B in a Chinese Mongolian Population.

    PubMed

    Wang, W Y; Tian, W; Zhu, F M; Liu, X X; Li, L X; Wang, F

    2016-06-01

    In this study, polymorphisms of major histocompatibility complex class I chain-related genes A and B (MICA and MICB) and human leucocyte antigen (HLA)-B gene were investigated for 158 unrelated Chinese Mongolian subjects recruited from central Inner Mongolia Autonomous Region, northern China, by polymerase chain reaction-sequence-based typing (PCR-SBT) and cloning. Collectively, 79 alleles, including 20 MICA, 12 MICB and 47 HLA-B alleles, were identified. MICA*008:01 (21.2%), MICB*005:02 (48.1%) and HLA-B*51:01 (7.91%) were the most common alleles. Significant global linkage disequilibrium (LD) was detected between HLA-B and MICA, HLA-B and MICB, and MICA and MICB loci (all P < 0.000001). The most frequent haplotypes were HLA-B*51:01-MICA*009:01 (7.28%), HLA-B*58:01-MICB*008 (6.96%), MICA*010-MICB*005:02 (13.92%) and HLA-B*58:01-MICA*002:01-MICB*008 (6.96%). HLA-B-MICA haplotypes such as HLA-B*50:01-MICA*009:02 were associated with single MICB allele. Some HLA-B-MICA haplotypes were associated with multiple MICB alleles, including HLA-B*51:01-MICA*009:01. One novel MICB allele, MICB*031, was identified, which has possibly arisen from MICB*002:01 through single mutation event. We also confirmed the existence of a recently recognized MICA allele, MICA*073, whose ethnic origin has not been previously described. Genotype distributions at MICA, MICB and HLA-B were consistent with a neutrality model. Our results provide new insight into MIC genetic polymorphisms in Chinese ethnic groups. Findings shown here are important from an anthropologic perspective and will inform future studies of the potential role of MIC genes in allogeneic organ transplantation and HLA-linked disease association in populations of related ancestry. PMID:27028549

  1. Microsatellites haplotyping of CF chromosomes shows linkage disequilibrium and several founder effects in Brittany (France)

    SciTech Connect

    Raguenes, O.; Ferec, C.; Mercier, B.

    1994-09-01

    A large study on cystic fibrosis (CF) is underway in Brittany (France). It is based on 902 CF patients distributed in 795 families who were or are still followed at the {open_quotes}Centre Helio-Marin{close_quotes} in Roscoff and/or were subjected to a molecular analysis at the {open_quotes}Centre de Biogenetique{close_quotes} in Brest. At present, the CF mutations have been identified in 309 patients born in Brittany, most of them of Celtic origin. A microsatellite (MS) study using IVS 17b TA, IVS 17b CA and IVS 8 CA was also completed in 63 CF patients and their parents (carriers of the {Delta}F508 mutation or the G551D mutation or the 1078delT mutation or the W846X mutation). All the 21 chromosomes carrying the 1078delT mutation had the same MS haplotype (16-21-13), which was also found on 9 of the 83 non-CF chromosomes analyzed. All the 16 chromosomes with the G551D mutation carried another MS haplotype (16-7-17), which was also found on 13.3% of the non-CF chromosomes. All the 6 chromosomes with the W846X mutation carried the 16-32-13 haplotype, also found on 6.0% of the non-CF chromosomes. Sixteen different MS haplotypes were found among the 74 chromosomes carrying the{Delta}F508 mutation, three of them representing 74.3% (55/74) of the chromosomes. These were the 23-31-13 haplotype (31/74 - 41.9%), the 17-31-13 haplotype (11/74 - 14.9%), and the 17-32-13 haplotype (13/74 - 17.6%). These results show that the CF mutations observed in Brittany are in linkage disequilibrium with the MS haplotypes. They also suggest that their presence in Brittany is the consequence of several founder effects.

  2. Power of QTL mapping experiments in commercial Atlantic salmon populations, exploiting linkage and linkage disequilibrium and effect of limited recombination in males.

    PubMed

    Hayes, B J; Gjuvsland, A; Omholt, S

    2006-07-01

    Whereas detection and positioning of genes that affect quantitative traits (quantitative trait loci (QTL)) using linkage mapping uses only information from recombinants in the genotyped generations, linkage disequilibrium (LD) mapping uses historical recombinants. Thus, whereas linkage mapping requires large family sizes to detect and accurately position QTL, LD mapping is more dependent on the number of families sampled from the population. In commercial Atlantic salmon breeding programmes, only a small number of individuals per family are routinely phenotyped for traits such as disease resistance and meat colour. In this paper, we assess the power and accuracy of combined linkage disequilibrium linkage analysis (LDLA) to detect QTL in the commercial population using simulation. When 15 half-sib sire families (each sire mated to 30 dams, each dam with 10 progeny) were sampled from the population for genotyping, we were able to detect a QTL explaining 10% of the phenotypic variance in 85% of replicates and position this QTL within 3 cM of the true position in 70% of replicates. When recombination was absent in males, a feature of the salmon genome, power to detect QTL increased; however, the accuracy of positioning the QTL was decreased. By increasing the number of sire families sampled from the population to be genotyped to 30, we were able to increase both the proportion of QTL detected and correctly positioned (even with no recombination in males). QTL with much smaller effect could also be detected. The results suggest that even with the existing recording structure in commercial salmon breeding programmes, there is considerable power to detect and accurately position QTL using LDLA. PMID:16685283

  3. The age of human mutation: genealogical and linkage disequilibrium analysis of the CLN5 mutation in the Finnish population.

    PubMed Central

    Varilo, T.; Savukoski, M.; Norio, R.; Santavuori, P.; Peltonen, L.; Järvelä, I.

    1996-01-01

    Variant late infantile neuronal ceroid lipofuscinosis (vLINCL) is an autosomal recessive progressive encephalopathy of childhood enriched in the western part of Finland, with a local incidence of 1 in 1500. We recently assigned the locus for vLINCL, CLN5, to 13q21.1-q32. In the present study, the haplotype analysis of Finnish CLN5 chromosomes provides evidence that one single mutation causes vLINCL in the Finnish population. Eight microsatellite markers closely linked to the CLN5 gene on chromosome 13q were analyzed, to study identity by descent by shared haplotype analysis. One single haplotype formed by flanking markers D13S160 and D13S162 in strong linkage disequilibrium (P < .0001) was present in 81% of disease-bearing chromosomes. Allele 4 at the marker locus D13S162 was detected in 94% of disease-bearing chromosomes. To evaluate the age of the CLN5 mutation by virtue of its restricted geographical distribution, church records were used to identify the common ancestors for 18 vLINCL families diagnosed in Finland. The pedigrees of the vLINCL ancestors merged on many occasions, which also supports a single founder mutation that obviously happened 20 to 30 generations ago (i.e., approximately 500 years ago) in this isolated population. Linkage disequilibrium was detected with seven markers covering an extended genetic distance of 11 cM, which further supports the young age of the CLN5 mutation. When the results of genealogical and linkage disequilibrium studies were combined, the CLN5 gene was predicted to lie approximately 200 - 400 kb (total range 30 - 1360 kb) from the closest marker D13S162. Images Figure 1 PMID:8644710

  4. A tetranucleotide repeat (D4S1652) is linked to facioscapulohumeral dystrophy and shows no linkage disequilibrium with the disease

    SciTech Connect

    Mathews, K.D.; Bailey, H.L.; Mills, K.A.

    1994-09-01

    Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant dystrophy which is associated with a deletion in a subtelomeric repeat element on 4q35. The gene has not yet been identified. The probe detecting this deletion (D4F104S1) is not chromosome 4-specific, and at least one large family has been identified which is not linked to chromosome 4. Thus, persymptomatic/prenatal diagnosis can only be provided to families that are proven to be chromosome 4-linked or where a new mutation is demonstrated. The markers available to demonstrate linkage to chromosome 4, D4S139, D4S163, and D4F35S1, are VNTRs. We have used D4S1652, a tetranucleotide repeat recently identified by the Cooperative Human Linkage Center, in our FSHD families. We found it is completely linked to the 4q35 VNTRs and to the disease phenotype. Physical mapping, using radiation hybrids and somatic cell hybrids, places D4S1652 between D4S139, an interval of approximately 1 Mb. We have used D4S1652 to look for linkage disequilibrium in our FSHD patient population. This result is of interest because of our hypothesis that the deletion in the subtelomeric repeat element alters transcription of a more proximal gene through a position effect. Previously available markers have been unsatisfactory for this experiment because of difficulty comparing numerous VNTR alleles across families. We observed 4, easily distinguished, D4S1652 alleles in our families. We studied 14 chromosomes associated with disease phenotype and 55 chromosomes from nontransmitting parents. We found no evidence for linkage disequilibrium ({chi}{sup 2}=1.313, nonsignificant). This result will need confirmation with a larger patient population, but is consistent with the clinical observation that there is a high rate of a new mutation in this disorder.

  5. Linkage disequilibrium network analysis (LDna) gives a global view of chromosomal inversions, local adaptation and geographic structure.

    PubMed

    Kemppainen, Petri; Knight, Christopher G; Sarma, Devojit K; Hlaing, Thaung; Prakash, Anil; Maung Maung, Yan Naung; Somboon, Pradya; Mahanta, Jagadish; Walton, Catherine

    2015-09-01

    Recent advances in sequencing allow population-genomic data to be generated for virtually any species. However, approaches to analyse such data lag behind the ability to generate it, particularly in nonmodel species. Linkage disequilibrium (LD, the nonrandom association of alleles from different loci) is a highly sensitive indicator of many evolutionary phenomena including chromosomal inversions, local adaptation and geographical structure. Here, we present linkage disequilibrium network analysis (LDna), which accesses information on LD shared between multiple loci genomewide. In LD networks, vertices represent loci, and connections between vertices represent the LD between them. We analysed such networks in two test cases: a new restriction-site-associated DNA sequence (RAD-seq) data set for Anopheles baimaii, a Southeast Asian malaria vector; and a well-characterized single nucleotide polymorphism (SNP) data set from 21 three-spined stickleback individuals. In each case, we readily identified five distinct LD network clusters (single-outlier clusters, SOCs), each comprising many loci connected by high LD. In A. baimaii, further population-genetic analyses supported the inference that each SOC corresponds to a large inversion, consistent with previous cytological studies. For sticklebacks, we inferred that each SOC was associated with a distinct evolutionary phenomenon: two chromosomal inversions, local adaptation, population-demographic history and geographic structure. LDna is thus a useful exploratory tool, able to give a global overview of LD associated with diverse evolutionary phenomena and identify loci potentially involved. LDna does not require a linkage map or reference genome, so it is applicable to any population-genomic data set, making it especially valuable for nonmodel species. PMID:25573196

  6. Linkage disequilibrium network analysis (LDna) gives a global view of chromosomal inversions, local adaptation and geographic structure

    PubMed Central

    Kemppainen, Petri; Knight, Christopher G; Sarma, Devojit K; Hlaing, Thaung; Prakash, Anil; Maung Maung, Yan Naung; Somboon, Pradya; Mahanta, Jagadish; Walton, Catherine

    2015-01-01

    Recent advances in sequencing allow population-genomic data to be generated for virtually any species. However, approaches to analyse such data lag behind the ability to generate it, particularly in nonmodel species. Linkage disequilibrium (LD, the nonrandom association of alleles from different loci) is a highly sensitive indicator of many evolutionary phenomena including chromosomal inversions, local adaptation and geographical structure. Here, we present linkage disequilibrium network analysis (LDna), which accesses information on LD shared between multiple loci genomewide. In LD networks, vertices represent loci, and connections between vertices represent the LD between them. We analysed such networks in two test cases: a new restriction-site-associated DNA sequence (RAD-seq) data set for Anopheles baimaii, a Southeast Asian malaria vector; and a well-characterized single nucleotide polymorphism (SNP) data set from 21 three-spined stickleback individuals. In each case, we readily identified five distinct LD network clusters (single-outlier clusters, SOCs), each comprising many loci connected by high LD. In A. baimaii, further population-genetic analyses supported the inference that each SOC corresponds to a large inversion, consistent with previous cytological studies. For sticklebacks, we inferred that each SOC was associated with a distinct evolutionary phenomenon: two chromosomal inversions, local adaptation, population-demographic history and geographic structure. LDna is thus a useful exploratory tool, able to give a global overview of LD associated with diverse evolutionary phenomena and identify loci potentially involved. LDna does not require a linkage map or reference genome, so it is applicable to any population-genomic data set, making it especially valuable for nonmodel species. PMID:25573196

  7. Linkage Disequilibrium Mapping of the Chromosome 6q21–22.31 Bipolar I Disorder Susceptibility Locus

    PubMed Central

    Fan, Jinbo; Ionita-Laza, Iuliana; McQueen, Matthew B.; Devlin, Bernie; Purcell, Shaun; Faraone, Stephen V.; Allen, Michael H.; Bowden, Charles L.; Calabrese, Joseph R.; Fossey, Mark D.; Friedman, Edward S.; Gyulai, Laszlo; Hauser, Peter; Ketter, Terence B.; Marangell, Lauren B.; Miklowitz, David J.; Nierenberg, Andrew A.; Patel, Jayendra K.; Sachs, Gary S.; Thase, Michael E.; Molay, Francine B.; Escamilla, Michael A.; Nimgaonkar, Vishwajit L.; Sklar, Pamela; Laird, Nan M.; Smoller, Jordan W.

    2014-01-01

    We previously reported genome-wide significant evidence for linkage between chromosome 6q and bipolar I disorder (BPI) by performing a meta-analysis of original genotype data from 11 genome scan linkage studies. We now present follow-up linkage disequilibrium mapping of the linked region utilizing 3,047 single nucleotide polymorphism (SNP) markers in a case–control sample (N = 530 cases, 534 controls) and family-based sample (N = 256 nuclear families, 1,301 individuals). The strongest single SNP result (rs6938431, P=6.72× 10−5) was observed in the case–control sample, near the solute carrier family 22, member 16 gene (SLC22A16). In a replication study, we genotyped 151 SNPs in an independent sample (N = 622 cases, 1,181 controls) and observed further evidence of association between variants at SLC22A16 and BPI. Although consistent evidence of association with any single variant was not seen across samples, SNP-wise and gene-based test results in the three samples provided convergent evidence for association with SLC22A16, a carnitine transporter, implicating this gene as a novel candidate for BPI risk. Further studies in larger samples are warranted to clarify which, if any, genes in the 6q region confer risk for bipolar disorder. PMID:19308960

  8. Linkage disequilibrium and haplotype studies of chromosome 8p 11. 1-21. 1 markers and Werner syndrome

    SciTech Connect

    Yu, Chang-En; Schellenberg, G.D.; Oshima, Junko; Martin, G.M.; Goddard, K.A.B.; Wijsman, E.M. ); Miki, Tetsuro; Nakura, Jun; Ogihara, Toshio ); Poot, M.; Hoehn, H. )

    1994-08-01

    Werner syndrome (WS) is an autosomal recessive disorder, characterized as a progeroid syndrome, previously mapped to the 8p 11.2-21.1 region. Because WS is so rare, and because many patients are from consanguineous marriages, fine localization of the gene by traditional meiotic mapping methods is unlikely to succeed. Here the authors present the results of a search for a region that exhibits linkage disequilibrium with the disorder, under the assumption that identification of such a region may provide an alternative method of narrowing down the location of WRN, the gene responsible for WS. They present allele frequencies in Japanese and Caucasian cases and controls for D8S137, D8S131, D8S87, D8S278, D8S259, D8S283, fibroblast growth factor receptor 1, ankyrin 1, D8S339, and two polymorphisms in glutathione reductase (GSR), covering [approximately] 16.5 cM in total. They show that three of the markers examined - D8S339 and both polymorphisms in the GSR locus - show strong statistically significant evidence of disequilibrium with WRN in the Japanese population but not in the Caucasian population. In addition, they show that a limited number of haplotypes are associated with the disease in both populations and that these haplotypes define clusters of apparently related haplotypes that may identify as many as eight or nine independent WRN mutations in these two populations. 36 refs., 1 fig., 4 tabs.

  9. EVALUATION OF GENETIC DIVERSITY AND GENOME-WIDE LINKAGE DISEQUILIBRIUM AMOUNG US WHEAT (TRITICUM AETIVUM L.) GERMPLASM REPRESENTING DIFFERENT MARKET CLASSES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic diversity and genome-wide linkage disequilibrium (LD) were investigated among forty-three US wheat (Triticum aestivum L.) elite cultivars and breeding lines representing seven US wheat market classes using 242 wheat genomic simple sequence repeat (SSR) markers distributed throughout the whea...

  10. Single nucleotide polymorphisms generated by genotyping by sequencing to characterize genome-wide diversity, linkage disequilibrium, and selective sweeps in cultivated watermelon

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Large datasets containing single nucleotide polymorphisms (SNPs) are used to analyze genome-wide diversity in a robust collection of cultivars from representative accessions, across the world. The extent of linkage disequilibrium (LD) within a population determines the number of markers required fo...

  11. 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...

  12. Evaluation of genetic diversity and genome-wide linkage disequilibrium among US wheat (Triticum aestivum L.) germplasm representing different market classes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic diversity and genome-wide linkage disequilibrium (LD) were investigated among forty-three U.S. wheat (Triticum aestivum L.) elite cultivars and breeding lines representing seven U.S. wheat market classes using 242 wheat genomic simple sequence repeat (SSR) markers distributed throughout the ...

  13. HLA class II linkage disequilibrium and haplotype evolution in the Cayapa Indians of Ecuador

    SciTech Connect

    Trachtenberg, E.A.; Erlich, H.A.; Klitz, W.

    1995-08-01

    DNA-based typing of the HLA class II loci in a sample of the Cayapa Indians of Ecuador reveals several lines of evidence that selection has operated to maintain and to diversify the existing level of polymorphism in the class II region. As has been noticed for other Native American groups, the overall level of polymorphism at the DRB1, DQA1, DQB1, and DPB1 loci is reduced relative to that found in other human populations. Nonetheless, the relative eveness in the distribution of allele frequencies at each of the four loci points to the role of balancing selection in the maintenance of the polymorphism. The DQA1 and DQB1 loci, in particular, have near-maximum departures from the neutrality model, which suggests that balancing selection has been especially strong in these cases. Several novel DQA1-DQB1 haplotypes and the discovery of a new DRB1 allele demonstrate an evolutionary tendency favoring the diversification of class II alleles and haplotypes. The recombination interval between the centromeric DPB1 locus and the other class II loci will, in the absence of other forces such as selection, reduce disequilibrium across this region. However, nearly all common alleles were found to be part of DR-DP haplotypes in strong disequilibrium, consistent with the recent action of selection acting on these haplotypes in the Cayapa. 50 refs., 3 figs., 3 tabs.

  14. Linkage disequilibrium with linkage analysis of multiline crosses reveals different multiallelic QTL for hybrid performance in the flint and dent heterotic groups of maize.

    PubMed

    Giraud, Héloïse; Lehermeier, Christina; Bauer, Eva; Falque, Matthieu; Segura, Vincent; Bauland, Cyril; Camisan, Christian; Campo, Laura; Meyer, Nina; Ranc, Nicolas; Schipprack, Wolfgang; Flament, Pascal; Melchinger, Albrecht E; Menz, Monica; Moreno-González, Jesús; Ouzunova, Milena; Charcosset, Alain; Schön, Chris-Carolin; Moreau, Laurence

    2014-12-01

    Multiparental designs combined with dense genotyping of parents have been proposed as a way to increase the diversity and resolution of quantitative trait loci (QTL) mapping studies, using methods combining linkage disequilibrium information with linkage analysis (LDLA). Two new nested association mapping designs adapted to European conditions were derived from the complementary dent and flint heterotic groups of maize (Zea mays L.). Ten biparental dent families (N = 841) and 11 biparental flint families (N = 811) were genotyped with 56,110 single nucleotide polymorphism markers and evaluated as test crosses with the central line of the reciprocal design for biomass yield, plant height, and precocity. Alleles at candidate QTL were defined as (i) parental alleles, (ii) haplotypic identity by descent, and (iii) single-marker groupings. Between five and 16 QTL were detected depending on the model, trait, and genetic group considered. In the flint design, a major QTL (R(2) = 27%) with pleiotropic effects was detected on chromosome 10, whereas other QTL displayed milder effects (R(2) < 10%). On average, the LDLA models detected more QTL but generally explained lower percentages of variance, consistent with the fact that most QTL display complex allelic series. Only 15% of the QTL were common to the two designs. A joint analysis of the two designs detected between 15 and 21 QTL for the five traits. Of these, between 27 for silking date and 41% for tasseling date were significant in both groups. Favorable allelic effects detected in both groups open perspectives for improving biomass production. PMID:25271305

  15. Using the variability of linkage disequilibrium between subpopulations to infer sweeps and epistatic selection in a diverse panel of chickens.

    PubMed

    Beissinger, T M; Gholami, M; Erbe, M; Weigend, S; Weigend, A; de Leon, N; Gianola, D; Simianer, H

    2016-02-01

    A whole-genome scan for identifying selection acting on pairs of linked loci is proposed and implemented. The scan is based on , one of Ohta's 1982 measures of between-population linkage disequilibrium (LD). An approximate empirical null distribution for the statistic is suggested. Although the partitioning of LD into between-population components was originally used to investigate epistatic selection, we demonstrate that values of may also be influenced by single-locus selective sweeps with linkage but no epistasis. The proposed scan is implemented in a diverse panel of chickens including 72 distinct breeds genotyped at 538 298 single-nucleotide polymorphisms. In all, 1723 locus pairs are identified as putatively corresponding to a selective sweep or epistatic selection. These pairs of loci generally cluster to form overlapping or neighboring signals of selection. Known variants that were expected to have been under selection in the panel are identified, as well as an assortment of novel regions that have putatively been under selection in chickens. Notably, a promising pair of genes located 8 MB apart on chromosome 9 are identified based on as demonstrating strong evidence of dispersive epistatic selection between populations. PMID:26350629

  16. Evaluation of Linkage Disequilibrium Pattern and Association Study on Seed Oil Content in Brassica napus Using ddRAD Sequencing

    PubMed Central

    Wu, Zhikun; Wang, Bo; Chen, Xun; Wu, Jiangsheng; King, Graham J.; Xiao, Yingjie; Liu, Kede

    2016-01-01

    High-density genetic markers are the prerequisite for understanding linkage disequilibrium (LD) and genome-wide association studies (GWASs) of complex traits in crops. To evaluate the LD pattern in oilseed rape, we sequenced a previous association panel containing 189 B. napus inbred lines using double-digested restriction-site associated DNA (ddRAD) and genotyped 19,327 RAD tags. A total of 15,921 RAD tags were assigned to a published genetic linkage map and the majority (71.1%) of these tags was uniquely mapped to the draft reference genome “Darmor-bzh.” The distance of LD decay was 1,214 kb across the genome at the background level (r2 = 0.26), with the distances of LD decay being 405 kb and 2,111 kb in the A and C subgenomes, respectively. A total of 361 haplotype blocks with length > 100 kb were identified in the entire genome. The association panel could be classified into two groups, P1 and P2, which are essentially consistent with the geographical origins of varieties. A large number of group-specific haplotypes were identified, reflecting that varieties in the P1 and P2 groups experienced distinct selection in breeding programs to adapt their different growth habitats. GWAS repeatedly detected two loci significantly associated with oil content of seeds based on the developed SNPs, suggesting that the high-density SNPs were useful for understanding the genetic determinants of complex traits in GWAS. PMID:26730738

  17. Evaluation of Linkage Disequilibrium Pattern and Association Study on Seed Oil Content in Brassica napus Using ddRAD Sequencing.

    PubMed

    Wu, Zhikun; Wang, Bo; Chen, Xun; Wu, Jiangsheng; King, Graham J; Xiao, Yingjie; Liu, Kede

    2016-01-01

    High-density genetic markers are the prerequisite for understanding linkage disequilibrium (LD) and genome-wide association studies (GWASs) of complex traits in crops. To evaluate the LD pattern in oilseed rape, we sequenced a previous association panel containing 189 B. napus inbred lines using double-digested restriction-site associated DNA (ddRAD) and genotyped 19,327 RAD tags. A total of 15,921 RAD tags were assigned to a published genetic linkage map and the majority (71.1%) of these tags was uniquely mapped to the draft reference genome "Darmor-bzh." The distance of LD decay was 1,214 kb across the genome at the background level (r2 = 0.26), with the distances of LD decay being 405 kb and 2,111 kb in the A and C subgenomes, respectively. A total of 361 haplotype blocks with length > 100 kb were identified in the entire genome. The association panel could be classified into two groups, P1 and P2, which are essentially consistent with the geographical origins of varieties. A large number of group-specific haplotypes were identified, reflecting that varieties in the P1 and P2 groups experienced distinct selection in breeding programs to adapt their different growth habitats. GWAS repeatedly detected two loci significantly associated with oil content of seeds based on the developed SNPs, suggesting that the high-density SNPs were useful for understanding the genetic determinants of complex traits in GWAS. PMID:26730738

  18. Toward localization of the Werner syndrome gene by linkage disequilibrium and ancestral haplotyping: Lessons learned from analysis of 35 chromosome 8p11.1-21.1 markers

    SciTech Connect

    Goddard, K.A.B.; Wijsman, E.M.; Martin, G.M.

    1996-06-01

    Werner syndrome (WS) is an autosomal recessive disorder characterized by premature onset of a number of age-related diseases. The gene for WS, WRN, has been mapped to the 8p11.1-21.1 region with further localization through linkage disequilibrium mapping. Here we present the results of linkage disequilibrium and ancestral haplotype analyses of 35 markers to further refine the location of WRN. We identified an interval in this region in which 14 of 18 markers tested show significant evidence of linkage disequilibrium in at least one of the two populations tested. Analysis of extended and partial haplotypes covering 21 of the markers studied supports the existence of both obligate and probable ancestral recombinant events which localize WRN almost certainly to the interval between DSS2196 and D8S2186, and most likely to the narrower interval between D8S2168 and D8S2186. These haplotype analyses also suggest that there are multiple WRN mutations in each of the two populations under study. We also present a comparison of approaches to performing disequilibrium tests with multiallelic markers, and show that some commonly used approximations for such tests perform poorly in comparison to exact probability tests. Finally, we discuss some of the difficulties introduced by the high mutation rate at microsatellite markers which influence our ability to use ancestral haplotype analysis to localize disease genes. 51 refs., 6 figs., 7 tabs.

  19. A Novel Method for Estimating Linkage Maps

    PubMed Central

    Tan, Yuan-De; Fu, Yun-Xin

    2006-01-01

    The goal of linkage mapping is to find the true order of loci from a chromosome. Since the number of possible orders is large even for a modest number of loci, the problem of finding the optimal solution is known as a NP-hard problem or traveling salesman problem (TSP). Although a number of algorithms are available, many either are low in the accuracy of recovering the true order of loci or require tremendous amounts of computational resources, thus making them difficult to use for reconstructing a large-scale map. We developed in this article a novel method called unidirectional growth (UG) to help solve this problem. The UG algorithm sequentially constructs the linkage map on the basis of novel results about additive distance. It not only is fast but also has a very high accuracy in recovering the true order of loci according to our simulation studies. Since the UG method requires n − 1 cycles to estimate the ordering of n loci, it is particularly useful for estimating linkage maps consisting of hundreds or even thousands of linked codominant loci on a chromosome. PMID:16783016

  20. Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy

    SciTech Connect

    Othmane, K.B.; Speer, M.C.; Stauffer, J.

    1995-09-01

    Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive Limb Girdle muscular dystrophy (LGMD2C) characterized by late age of onset, proximal muscle weakness leading to disability, high creatine kinase values, normal intelligence and normal dystrophin in muscle biopsy. We have shown previously that three DLMD families from Tunisia are linked to chromosome 13q12. To further localize the LGMD2C gene, we have investigated seven additional families (119 individuals). Both genotyping and two-point linkage analysis were performed as described elsewhere. 7 refs., 1 fig., 1 tab.

  1. Linkage disequilibrium between the juvenile neuronal ceroid lipofuscinosis gene and marker loci on chromosome 16p12. 1

    SciTech Connect

    Lerner, T.J.; MacCormack, K.; Gleitsman, J.; Schlumpf, K.; Breakefield, X.O.; Gusella, J.F.; Haines, J.L. )

    1994-01-01

    The neuronal ceroid lipofuscinoses (NCL; Batten disease) are a collection of autosomal recessive disorders characterized by the accumulation of autofluorescent lipopigments in the neurons and other cell types. Clinically, these disorders are characterized by progressive encephalopathy, loss of vision, and seizures. CLN3, the gene responsible for juvenile NCL, has been mapped to a 15-cM region flanked by the marker loci D16S148 and D16S150 on human chromosome 16. CLN2, the gene causing the late-infantile form of NCL (LNCL), is not yet mapped. The authors have used highly informative dinucleoide repeat markers mapping between D16S148 and D16S150 to refine the localization of CLN3 and to test for linkage to CLN2. The authors find significant linkage disequilibrium between CLN3 and the dinucleotide repeat marker loci D16S288 (X[sup 2](7) = 46.5, P < .005), D16S298 (X[sup 2](6) = 36.6, P < .005), and D16S299 (X[sup 2](7) = 73.8, P < .005), and also a novel RFLP marker at the D16S272 locus (X[sup 2](1) = 5.7, P = .02). These markers all map to 16p12.1. The D16S298/D16S299 haplotype [open quotes]5/4[close quotes] is highly overrepresented, accounting for 54% of CLN3 chromosomes as compared with 8% of control chromosomes (X[sup 2] = 117, df = 1, P < .001). Examination of the haplotypes suggests that the CLN3 locus can be narrowed to the region immediately surrounding these markers in 16p12.1. Analysis of D16S299 in LNCL pedigrees supports the previous finding that CLN3 and CLN2 are different genetic loci. This study also indicates that dinucleotide repeat markers play a valuable role in disequilibrium studies. 23 refs., 1 fig., 4 tabs.

  2. Sexual antagonism and meiotic drive cause stable linkage disequilibrium and favour reduced recombination on the X chromosome.

    PubMed

    Rydzewski, W T; Carioscia, S A; Liévano, G; Lynch, V D; Patten, M M

    2016-06-01

    Sexual antagonism and meiotic drive are sex-specific evolutionary forces with the potential to shape genomic architecture. Previous theory has found that pairing two sexually antagonistic loci or combining sexual antagonism with meiotic drive at linked autosomal loci augments genetic variation, produces stable linkage disequilibrium (LD) and favours reduced recombination. However, the influence of these two forces has not been examined on the X chromosome, which is thought to be enriched for sexual antagonism and meiotic drive. We investigate the evolution of the X chromosome under both sexual antagonism and meiotic drive with two models: in one, both loci experience sexual antagonism; in the other, we pair a meiotic drive locus with a sexually antagonistic locus. We find that LD arises between the two loci in both models, even when the two loci freely recombine in females and that driving haplotypes will be enriched for male-beneficial alleles, further skewing sex ratios in these populations. We introduce a new measure of LD, Dz', which accounts for population allele frequencies and is appropriate for instances where these are sex specific. Both models demonstrate that natural selection favours modifiers that reduce the recombination rate. These results inform observed patterns of congealment found on driving X chromosomes and have implications for patterns of natural variation and the evolution of recombination rates on the X chromosome. PMID:26999777

  3. Linkage disequilibrium analysis in young populations: pseudo-vitamin D-deficiency rickets and the founder effect in French Canadians.

    PubMed

    Labuda, M; Labuda, D; Korab-Laskowska, M; Cole, D E; Zietkiewicz, E; Weissenbach, J; Popowska, E; Pronicka, E; Root, A W; Glorieux, F H

    1996-09-01

    Pseudo-vitamin D-deficiency rickets (PDDR) was mapped close to D12S90 and between proximal D12S312 and distal (D12S305, D12S104) microsatellites that were subsequently found on a single YAC clone. Analysis of a complex haplotype in linkage disequilibrium (LD) with the disease discriminated among distinct founder effects in French Canadian populations in Acadia and in Charlevoix-Saguenay-Lac-Saint-Jean (Ch-SLSJ), as well as an earlier one in precolonial Europe. A simple demographic model suggested the historical age of the founder effect in Ch-SLSJ to be approximately 12 generations. The corresponding LD data are consistent with this figure when they are analyzed within the framework of Luria-Delbrück model, which takes into account the population growth. Population sampling due to a limited number of first settlers and the rapid demographic expansion appear to have played a major role in the founding of PDDR in Ch-SLSJ and, presumably, other genetic disorders endemic to French Canada. Similarly, the founder effect in Ashkenazim, coinciding with their early settlement in medieval Poland and subsequent expansion eastward, could explain the origin of frequent genetic diseases in this population. PMID:8751865

  4. Linkage disequilibrium analysis of polymorphisms in the gene for myelin oligodendrocyte glycoprotein in Tourette's syndrome patients from a Chinese sample.

    PubMed

    Huang, Yi; Li, Tao; Wang, Yun; Ansar, Jawaid; Lanting, Guo; Liu, Xiehe; Zhao, Jing Hua; Hu, Xun; Sham, Pak C; Collier, David

    2004-01-01

    Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterised by multiple motor and phonic tics, which wax and wane. Recently, evidence has accumulated supporting the role of autoimmune mechanisms in the aetiology of GTS, suggesting that it is within the paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) spectrum of childhood neurobehavioural disorders. An immunopathogenic role of antibodies against myelin oligodendrocyte glycoprotein (MOG) has been suggested in this syndrome. In this study, we investigate the association of three microsatellite polymorphisms (MOGa, MOGb, MOGc) in the gene for MOG with GTS in 197 family trios collected from southwest China. Linkage disequilibrium between these three markers was observed with the strongest between MOGa and MOGc (D' = 0.541, P = 0.000). We did not find overall significant evidence for distorted transmission of any of these three markers of MOG gene in GTS, although we observed a weak preferential transmission of the 148 bp allele of MOGc (chi(2) = 4.000, P = 0.046) which did not survive correction for multiple testing. Our results suggest that there is no association between the MOG gene polymorphisms we tested and GTS. PMID:14681920

  5. Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits

    PubMed Central

    Paes, Geísa Pinheiro; Viana, José Marcelo Soriano; Silva, Fabyano Fonseca e; Mundim, Gabriel Borges

    2016-01-01

    Abstract The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kernel weight, kernel sphericity, and kernel density. The LD statistics were the difference between the observed and expected haplotype frequencies (D), the proportion of D relative to the expected maximum value in the population, and the square of the correlation between the values of alleles at two loci. Association mapping was based on least squares and Bayesian approaches. In the tropical populations, D-values greater than 0.10 were observed for SNPs separated by 100-150 Mb, while most of the D-values in the temperate populations were less than 0.05. Selection for expansion volume indirectly led to increase in LD values, population differentiation, and significant changes in SNP frequency. Some associations were observed for expansion volume and the other quality traits. The candidate genes are involved with starch, storage protein, lipid, and cell wall polysaccharides synthesis. PMID:27007903

  6. The association between type 1 diabetes and the ITPR3 gene polymorphism due to linkage disequilibrium with HLA class II.

    PubMed

    Qu, H-Q; Marchand, L; Szymborski, A; Grabs, R; Polychronakos, C

    2008-04-01

    A fine mapping study of the MHC region in a Swedish case-control population sample reported a novel type 1 diabetes (T1D) association from the inositol 1-, 4-, 5-trisphosphate receptor type 3 gene (ITPR3) in a case-control study, reportedly independent of the HLA class II effect. We attempted to replicate this novel association in a family-based study of 1120 T1D families with at least one affected child, an approach immune to population stratification. We found association of the ITPR3 single nucleotide polymorphisms (SNPs) rs2296336 with T1D but in a direction opposite to that reported. Moreover, rs2296336 was in linkage disequilibrium (LD) with specific alleles of the HLA DQB1 gene. Conditional regression showed that all of the ITPR3 SNP T1D association could be accounted for by the DQB1 effect. Therefore, our findings do not support an obvious role of genetic variation of the ITPR3 gene in T1D risk. PMID:18340361

  7. Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits.

    PubMed

    Corradin, Olivia; Saiakhova, Alina; Akhtar-Zaidi, Batool; Myeroff, Lois; Willis, Joseph; Cowper-Sal lari, Richard; Lupien, Mathieu; Markowitz, Sanford; Scacheri, Peter C

    2014-01-01

    DNA variants (SNPs) that predispose to common traits often localize within noncoding regulatory elements such as enhancers. Moreover, loci identified by genome-wide association studies (GWAS) often contain multiple SNPs in linkage disequilibrium (LD), any of which may be causal. Thus, determining the effect of these multiple variant SNPs on target transcript levels has been a major challenge. Here, we provide evidence that for six common autoimmune disorders (rheumatoid arthritis, Crohn's disease, celiac disease, multiple sclerosis, lupus, and ulcerative colitis), the GWAS association arises from multiple polymorphisms in LD that map to clusters of enhancer elements active in the same cell type. This finding suggests a "multiple enhancer variant" hypothesis for common traits, where several variants in LD impact multiple enhancers and cooperatively affect gene expression. Using a novel method to delineate enhancer-gene interactions, we show that multiple enhancer variants within a given locus typically target the same gene. Using available data from HapMap and B lymphoblasts as a model system, we provide evidence at numerous loci that multiple enhancer variants cooperatively contribute to altered expression of their gene targets. The effects on target transcript levels tend to be modest and can be either gain- or loss-of-function. Additionally, the genes associated with multiple enhancer variants encode proteins that are often functionally related and enriched in common pathways. Overall, the multiple enhancer variant hypothesis offers a new paradigm by which noncoding variants can confer susceptibility to common traits. PMID:24196873

  8. Effects of Introgression and Recombination on Haplotype Structure and Linkage Disequilibrium Surrounding a Locus Encoding Bymovirus Resistance in Barley

    PubMed Central

    Stracke, Silke; Presterl, Thomas; Stein, Nils; Perovic, Dragan; Ordon, Frank; Graner, Andreas

    2007-01-01

    We present a detailed analysis of linkage disequilibrium (LD) in the physical and genetic context of the barley gene Hv-eIF4E, which confers resistance to the barley yellow mosaic virus (BYMV) complex. Eighty-three SNPs distributed over 132 kb of Hv-eIF4E and six additional fragments genetically mapped to its flanking region were used to derive haplotypes from 131 accessions. Three haplogroups were recognized, discriminating between the alleles rym4 and rym5, which each encode for a spectrum of resistance to BYMV. With increasing map distance, haplotypes of susceptible genotypes displayed diverse patterns driven mainly by recombination, whereas haplotype diversity within the subgroups of resistant genotypes was limited. We conclude that the breakdown of LD within 1 cM of the resistance gene was generated mainly by susceptible genotypes. Despite the LD decay, a significant association between haplotype and resistance to BYMV was detected up to a distance of 5.5 cM from the resistance gene. The LD pattern and the haplotype structure of the target chromosomal region are the result of interplay between low recombination and recent breeding history. PMID:17151251

  9. Linkage disequilibrium, SNP frequency change due to selection, and association mapping in popcorn chromosome regions containing QTLs for quality traits.

    PubMed

    Paes, Geísa Pinheiro; Viana, José Marcelo Soriano; Silva, Fabyano Fonseca E; Mundim, Gabriel Borges

    2016-03-01

    The objectives of this study were to assess linkage disequilibrium (LD) and selection-induced changes in single nucleotide polymorphism (SNP) frequency, and to perform association mapping in popcorn chromosome regions containing quantitative trait loci (QTLs) for quality traits. Seven tropical and two temperate popcorn populations were genotyped for 96 SNPs chosen in chromosome regions containing QTLs for quality traits. The populations were phenotyped for expansion volume, 100-kernel weight, kernel sphericity, and kernel density. The LD statistics were the difference between the observed and expected haplotype frequencies (D), the proportion of D relative to the expected maximum value in the population, and the square of the correlation between the values of alleles at two loci. Association mapping was based on least squares and Bayesian approaches. In the tropical populations, D-values greater than 0.10 were observed for SNPs separated by 100-150 Mb, while most of the D-values in the temperate populations were less than 0.05. Selection for expansion volume indirectly led to increase in LD values, population differentiation, and significant changes in SNP frequency. Some associations were observed for expansion volume and the other quality traits. The candidate genes are involved with starch, storage protein, lipid, and cell wall polysaccharides synthesis. PMID:27007903

  10. Refined mapping of a gene responsible for Fukuyama-type congenital muscular dystrophy: Evidence for strong linkage disequilibrium

    SciTech Connect

    Toda, Tatsushi; Ikegawa, Shiro; Okui, Keiko; Nakamura, Yusuke; Kanazawa, Ichiro; Kondo, Eri; Saito, Kayoko; Fukuyama, Yukio; Yoshioka, Mieko; Kumagai, Toshiyuki

    1994-11-01

    Fukuyama-type congenital muscular dystrophy (FCMD), the second most common form of childhood muscular dystrophy in Japan, is an autosomal recessive severe muscular dystrophy associated with an anomaly of the brain. After our initial mapping of the FCMD locus to chromosome 9q31-33, we further defined the locus within a region of {approximately}5 cM between loci D9S127 and CA246, by homozygosity mapping in patients born to consanguineous marriages and by recombination analyses in other families. We also found evidence for strong linkage disequilibrium between FCMD and a polymorphic microsatellite marker, mfd220, which showed no recombination and a lod score of (Z) 17.49. A {open_quotes}111-bp{close_quotes} allele for the mfd220 was observed in 22 (34%) of 64 FCMD chromosomes, but it was present in only 1 of 120 normal chromosomes. This allelic association with FCMD was highly significant ({chi}{sup 2} = 50.7; P < .0001). Hence, we suspect that the FCMD gene could lie within a few hundred kilobases of the mfd220 locus. 32 refs., 2 figs., 2 tabs.

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

    PubMed Central

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

    2009-01-01

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

  12. 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.

  13. Using Sequence Variants in Linkage Disequilibrium with Causative Mutations to Improve Across-Breed Prediction in Dairy Cattle: A Simulation Study.

    PubMed

    van den Berg, Irene; Boichard, Didier; Guldbrandtsen, Bernt; Lund, Mogens S

    2016-01-01

    Sequence data are expected to increase the reliability of genomic prediction by containing causative mutations directly, especially in cases where low linkage disequilibrium between markers and causative mutations limits prediction reliability, such as across-breed prediction in dairy cattle. In practice, the causative mutations are unknown, and prediction with only variants in perfect linkage disequilibrium with the causative mutations is not realistic, leading to a reduced reliability compared to knowing the causative variants. Our objective was to use sequence data to investigate the potential benefits of sequence data for the prediction of genomic relationships, and consequently reliability of genomic breeding values. We used sequence data from five dairy cattle breeds, and a larger number of imputed sequences for two of the five breeds. We focused on the influence of linkage disequilibrium between markers and causative mutations, and assumed that a fraction of the causative mutations was shared across breeds and had the same effect across breeds. By comparing the loss in reliability of different scenarios, varying the distance between markers and causative mutations, using either all genome wide markers from commercial SNP chips, or only the markers closest to the causative mutations, we demonstrate the importance of using only variants very close to the causative mutations, especially for across-breed prediction. Rare variants improved prediction only if they were very close to rare causative mutations, and all causative mutations were rare. Our results show that sequence data can potentially improve genomic prediction, but careful selection of markers is essential. PMID:27317779

  14. Using Sequence Variants in Linkage Disequilibrium with Causative Mutations to Improve Across-Breed Prediction in Dairy Cattle: A Simulation Study

    PubMed Central

    van den Berg, Irene; Boichard, Didier; Guldbrandtsen, Bernt; Lund, Mogens S.

    2016-01-01

    Sequence data are expected to increase the reliability of genomic prediction by containing causative mutations directly, especially in cases where low linkage disequilibrium between markers and causative mutations limits prediction reliability, such as across-breed prediction in dairy cattle. In practice, the causative mutations are unknown, and prediction with only variants in perfect linkage disequilibrium with the causative mutations is not realistic, leading to a reduced reliability compared to knowing the causative variants. Our objective was to use sequence data to investigate the potential benefits of sequence data for the prediction of genomic relationships, and consequently reliability of genomic breeding values. We used sequence data from five dairy cattle breeds, and a larger number of imputed sequences for two of the five breeds. We focused on the influence of linkage disequilibrium between markers and causative mutations, and assumed that a fraction of the causative mutations was shared across breeds and had the same effect across breeds. By comparing the loss in reliability of different scenarios, varying the distance between markers and causative mutations, using either all genome wide markers from commercial SNP chips, or only the markers closest to the causative mutations, we demonstrate the importance of using only variants very close to the causative mutations, especially for across-breed prediction. Rare variants improved prediction only if they were very close to rare causative mutations, and all causative mutations were rare. Our results show that sequence data can potentially improve genomic prediction, but careful selection of markers is essential. PMID:27317779

  15. A Consensus Genetic Map for Pinus taeda and Pinus elliottii and Extent of Linkage Disequilibrium in Two Genotype-Phenotype Discovery Populations of Pinus taeda.

    PubMed

    Westbrook, Jared W; Chhatre, Vikram E; Wu, Le-Shin; Chamala, Srikar; Neves, Leandro Gomide; Muñoz, Patricio; Martínez-García, Pedro J; Neale, David B; Kirst, Matias; Mockaitis, Keithanne; Nelson, C Dana; Peter, Gary F; Davis, John M; Echt, Craig S

    2015-08-01

    A consensus genetic map for Pinus taeda (loblolly pine) and Pinus elliottii (slash pine) was constructed by merging three previously published P. taeda maps with a map from a pseudo-backcross between P. elliottii and P. taeda. The consensus map positioned 3856 markers via genotyping of 1251 individuals from four pedigrees. It is the densest linkage map for a conifer to date. Average marker spacing was 0.6 cM and total map length was 2305 cM. Functional predictions of mapped genes were improved by aligning expressed sequence tags used for marker discovery to full-length P. taeda transcripts. Alignments to the P. taeda genome mapped 3305 scaffold sequences onto 12 linkage groups. The consensus genetic map was used to compare the genome-wide linkage disequilibrium in a population of distantly related P. taeda individuals (ADEPT2) used for association genetic studies and a multiple-family pedigree used for genomic selection (CCLONES). The prevalence and extent of LD was greater in CCLONES as compared to ADEPT2; however, extended LD with LGs or between LGs was rare in both populations. The average squared correlations, r(2), between SNP alleles less than 1 cM apart were less than 0.05 in both populations and r(2) did not decay substantially with genetic distance. The consensus map and analysis of linkage disequilibrium establish a foundation for comparative association mapping and genomic selection in P. taeda and P. elliottii. PMID:26068575

  16. A Consensus Genetic Map for Pinus taeda and Pinus elliottii and Extent of Linkage Disequilibrium in Two Genotype-Phenotype Discovery Populations of Pinus taeda

    PubMed Central

    Westbrook, Jared W.; Chhatre, Vikram E.; Wu, Le-Shin; Chamala, Srikar; Neves, Leandro Gomide; Muñoz, Patricio; Martínez-García, Pedro J.; Neale, David B.; Kirst, Matias; Mockaitis, Keithanne; Nelson, C. Dana; Peter, Gary F.; Echt, Craig S.

    2015-01-01

    A consensus genetic map for Pinus taeda (loblolly pine) and Pinus elliottii (slash pine) was constructed by merging three previously published P. taeda maps with a map from a pseudo-backcross between P. elliottii and P. taeda. The consensus map positioned 3856 markers via genotyping of 1251 individuals from four pedigrees. It is the densest linkage map for a conifer to date. Average marker spacing was 0.6 cM and total map length was 2305 cM. Functional predictions of mapped genes were improved by aligning expressed sequence tags used for marker discovery to full-length P. taeda transcripts. Alignments to the P. taeda genome mapped 3305 scaffold sequences onto 12 linkage groups. The consensus genetic map was used to compare the genome-wide linkage disequilibrium in a population of distantly related P. taeda individuals (ADEPT2) used for association genetic studies and a multiple-family pedigree used for genomic selection (CCLONES). The prevalence and extent of LD was greater in CCLONES as compared to ADEPT2; however, extended LD with LGs or between LGs was rare in both populations. The average squared correlations, r2, between SNP alleles less than 1 cM apart were less than 0.05 in both populations and r2 did not decay substantially with genetic distance. The consensus map and analysis of linkage disequilibrium establish a foundation for comparative association mapping and genomic selection in P. taeda and P. elliottii. PMID:26068575

  17. Evidence, from family studies, for linkage disequilibrium between TGFA and a gene for nonsyndromic cleft lip with or without cleft palate

    SciTech Connect

    Feng, Hongshu; Lee, A.; Gasser, D.L.; Sassani, R.; Bartlett, S.P.; Buetow, K.H.; Hecht, J.T.; Malcolm, S.; Winter, R.M.; Vintiner, G.M.

    1994-11-01

    The inheritance of alleles of the transforming growth factor alpha (TGFA) locus has been studied in families affected with cleft lip with or without cleft palate (CL/P), by using the transmission/disequilibrium test described by Spielman and colleagues. Only heterozygous parents with an affected child can be included in this test, but within such families a significantly greater frequency of C2 alleles were transmitted to affected children than would be expected by chance. There was no evidence that the total number of C2 alleles transmitted to affected and unaffected children differed significantly from random segregation. These data provide evidence from within families that a gene for susceptibility to CL/P is in significant linkage disequilibrium with the C2 allele of the TGFA locus. 30 refs., 1 fig., 2 tabs.

  18. Population genetic structure, linkage disequilibrium and effective population size of conserved and extensively raised village chicken populations of Southern Africa

    PubMed Central

    Khanyile, Khulekani S.; Dzomba, Edgar F.; Muchadeyi, Farai C.

    2015-01-01

    Extensively raised village chickens are considered a valuable source of biodiversity, with genetic variability developed over thousands of years that ought to be characterized and utilized. Surveys that can reveal a population's genetic structure and provide an insight into its demographic history will give valuable information that can be used to manage and conserve important indigenous animal genetic resources. This study reports population diversity and structure, linkage disequilibrium and effective population sizes of Southern African village chickens and conservation flocks from South Africa. DNA samples from 312 chickens from South African village and conservation flocks (n = 146), Malawi (n = 30) and Zimbabwe (n = 136) were genotyped using the Illumina iSelect chicken SNP60K BeadChip. Population genetic structure analysis distinguished the four conservation flocks from the village chicken populations. Of the four flocks, the Ovambo clustered closer to the village chickens particularly those sampled from South Africa. Clustering of the village chickens followed a geographic gradient whereby South African chickens were closer to those from Zimbabwe than to chickens from Malawi. Different conservation flocks seemed to have maintained different components of the ancestral genomes with a higher proportion of village chicken diversity found in the Ovambo population. Overall population LD averaged over chromosomes ranged from 0.03 ± 0.07 to 0.58 ± 0.41 and averaged 0.15 ± 0.16. Higher LD, ranging from 0.29 to 0.36, was observed between SNP markers that were less than 10 kb apart in the conservation flocks. LD in the conservation flocks steadily decreased to 0.15 (PK) and 0.24 (VD) at SNP marker interval of 500 kb. Genomewide LD decay in the village chickens from Malawi, Zimbabwe and South Africa followed a similar trend as the conservation flocks although the mean LD values for the investigated SNP intervals were lower. The results suggest low effective

  19. Conservative Extensions of Linkage Disequilibrium Measures from Pairwise to Multi-loci and Algorithms for Optimal Tagging SNP Selection

    NASA Astrophysics Data System (ADS)

    Tarpine, Ryan; Lam, Fumei; Istrail, Sorin

    We present results on two classes of problems. The first result addresses the long standing open problem of finding unifying principles for Linkage Disequilibrium (LD) measures in population genetics (Lewontin 1964 [10], Hedrick 1987 [8], Devlin and Risch 1995 [5]). Two desirable properties have been proposed in the extensive literature on this topic and the mutual consistency between these properties has remained at the heart of statistical and algorithmic difficulties with haplotype and genome-wide association study analysis. The first axiom is (1) The ability to extend LD measures to multiple loci as a conservative extension of pairwise LD. All widely used LD measures are pairwise measures. Despite significant attempts, it is not clear how to naturally extend these measures to multiple loci, leading to a "curse of the pairwise". The second axiom is (2) The Interpretability of Intermediate Values. In this paper, we resolve this mutual consistency problem by introducing a new LD measure, directed informativeness overrightarrow{I} (the directed graph theoretic counterpart of the informativeness measure introduced by Halldorsson et al. [6]) and show that it satisfies both of the above axioms. We also show the maximum informative subset of tagging SNPs based on overrightarrow{I} can be computed exactly in polynomial time for realistic genome-wide data. Furthermore, we present polynomial time algorithms for optimal genome-wide tagging SNPs selection for a number of commonly used LD measures, under the bounded neighborhood assumption for linked pairs of SNPs. One problem in the area is the search for a quality measure for tagging SNPs selection that unifies the LD-based methods such as LD-select (implemented in Tagger, de Bakker et al. 2005 [4], Carlson et al. 2004 [3]) and the information-theoretic ones such as informativeness. We show that the objective function of the LD-select algorithm is the Minimal Dominating Set (MDS) on r 2-SNP graphs and show that we can

  20. FastTagger: an efficient algorithm for genome-wide tag SNP selection using multi-marker linkage disequilibrium

    PubMed Central

    2010-01-01

    Background Human genome contains millions of common single nucleotide polymorphisms (SNPs) and these SNPs play an important role in understanding the association between genetic variations and human diseases. Many SNPs show correlated genotypes, or linkage disequilibrium (LD), thus it is not necessary to genotype all SNPs for association study. Many algorithms have been developed to find a small subset of SNPs called tag SNPs that are sufficient to infer all the other SNPs. Algorithms based on the r2 LD statistic have gained popularity because r2 is directly related to statistical power to detect disease associations. Most of existing r2 based algorithms use pairwise LD. Recent studies show that multi-marker LD can help further reduce the number of tag SNPs. However, existing tag SNP selection algorithms based on multi-marker LD are both time-consuming and memory-consuming. They cannot work on chromosomes containing more than 100 k SNPs using length-3 tagging rules. Results We propose an efficient algorithm called FastTagger to calculate multi-marker tagging rules and select tag SNPs based on multi-marker LD. FastTagger uses several techniques to reduce running time and memory consumption. Our experiment results show that FastTagger is several times faster than existing multi-marker based tag SNP selection algorithms, and it consumes much less memory at the same time. As a result, FastTagger can work on chromosomes containing more than 100 k SNPs using length-3 tagging rules. FastTagger also produces smaller sets of tag SNPs than existing multi-marker based algorithms, and the reduction ratio ranges from 3%-9% when length-3 tagging rules are used. The generated tagging rules can also be used for genotype imputation. We studied the prediction accuracy of individual rules, and the average accuracy is above 96% when r2 ≥ 0.9. Conclusions Generating multi-marker tagging rules is a computation intensive task, and it is the bottleneck of existing multi-marker based tag

  1. Linkage Disequilibrium for Two X-Linked Genes in Sardinia and Its Bearing on the Statistical Mapping of the Human X Chromosome

    PubMed Central

    Filippi, G.; Rinaldi, A.; Palmarino, R.; Seravalli, E.; Siniscalco, M.

    1977-01-01

    The distribution of four X-linked mutants (G6PD, Deutan, Protan and Xg) among lowland and once highly malarial populations of Sardinia discloses a clear-cut example of linkage disequilibrium between two of them (G6PD and Protan). In the same populations the distribution of G6PD-deficiency versus colorblindness of the Deutan type and the Xg blood-group is not significantly different from that expected at equilibrium. These data suggest indirectly that the loci for G6PD and Protan may be nearer to one another than those for G6PD and Deutan. PMID:301840

  2. Extensive Linkage Disequilibrium, a Common 16.7-Kilobase Deletion, and Evidence of Balancing Selection in the Human Protocadherin α Cluster

    PubMed Central

    Noonan, James P.; Li, Jun; Nguyen, Loan; Caoile, Chenier; Dickson, Mark; Grimwood, Jane; Schmutz, Jeremy; Feldman, Marcus W.; Myers, Richard M.

    2003-01-01

    Regions of extensive linkage disequilibrium (LD) appear to be a common feature of the human genome. However, the mechanisms that maintain these regions are unknown. In an effort to understand whether gene density contributes to LD, we determined the degree of promoter sequence variation in a large tandem-arrayed gene family, the human protocadherin α cluster, on chromosome 5. These genes are expressed at synaptic junctions in the developing brain and the adult brain and may be involved in the determination of synaptic complexity. We sequenced the promoters of all 13 α protocadherin genes in 96 European Americans and identified polymorphisms in the promoters α1, α3, α4, α5, α7, α9, α11, and α13. In these promoters, 11 common SNPs are in extensive LD, forming two 48-kb haplotypes of equal frequency, in this population, that extend from the α1 through α7 genes. We sequenced these promoters in East Asians and African Americans, and we estimated haplotype frequencies and calculated LD statistics for all three populations. Our results indicate that, although extensive LD is an ancient feature of the α cluster, it has eroded over time. SNPs 3′ of α7 are involved in ancestral recombination events in all populations, and overall α-cluster LD is reduced in African Americans. We obtained significant positive values for Tajima's D test for all α promoter SNPs in Europeans (D=3.03) and East Asians (D=2.64), indicating an excess of intermediate-frequency variants, which is a signature of balancing selection. We also discovered a 16.7-kb deletion that truncates the α8 gene and completely removes the α9 and α10 genes. This deletion appears in unaffected individuals from multiple populations, suggesting that a reduction in protocadherin gene number is not obviously deleterious. PMID:12577201

  3. Refined assignment of the infantile neuronal ceroid lipofuscinosis (INCL, CLN1) locus at 1p32: Incorporation of linkage disequilibrium in multipoint analysis

    SciTech Connect

    Hellsten, E.; Vesa, J.; Peltonen, L.; Jaervela, I. ); Speer, M.C.; Ott, J. New York State Psychiatric Institute, New York ); Maekelae, T.P.; Alitalo, K. )

    1993-06-01

    Infantile neuronal ceroid lipofuscinosis, INCL, CLN1, is an autosomally inherited progressive neuro-generative disorder. The disease results in the massive death of cortical neurons, suggesting an essential role for the CLN1 gene product in the normal neuronal maturation during the first years of life. Identification of new multiallelic markers has now made possible the construction of a refined genetic map encompassing the CLN1 locus at 1p32. Strong allelic association was detected with a new, highly polymorphic HY-TM1 marker. The authors incorporated this observed linkage disequilibrium into multipoint linkage analysis, which significantly increased the informativeness of the limited family material and facilitated refined assignment of the CLN1 locus. 23 refs., 2 figs., 4 tabs.

  4. MIDAS: software for analysis and visualisation of interallelic disequilibrium between multiallelic markers

    PubMed Central

    Gaunt, Tom R; Rodriguez, Santiago; Zapata, Carlos; Day, Ian NM

    2006-01-01

    Background Various software tools are available for the display of pairwise linkage disequilibrium across multiple single nucleotide polymorphisms. The HapMap project also presents these graphics within their website. However, these approaches are limited in their use of data from multiallelic markers and provide limited information in a graphical form. Results We have developed a software package (MIDAS – Multiallelic Interallelic Disequilibrium Analysis Software) for the estimation and graphical display of interallelic linkage disequilibrium. Linkage disequilibrium is analysed for each allelic combination (of one allele from each of two loci), between all pairwise combinations of any type of multiallelic loci in a contig (or any set) of many loci (including single nucleotide polymorphisms, microsatellites, minisatellites and haplotypes). Data are presented graphically in a novel and informative way, and can also be exported in tabular form for other analyses. This approach facilitates visualisation of patterns of linkage disequilibrium across genomic regions, analysis of the relationships between different alleles of multiallelic markers and inferences about patterns of evolution and selection. Conclusion MIDAS is a linkage disequilibrium analysis program with a comprehensive graphical user interface providing novel views of patterns of linkage disequilibrium between all types of multiallelic and biallelic markers. Availability Available from and PMID:16643648

  5. HLA-A-B-C-DRB1-DQB1 phased haplotypes in 124 Nigerian families indicate extreme HLA diversity and low linkage disequilibrium in Central-West Africa.

    PubMed

    Testi, M; Battarra, M; Lucarelli, G; Isgro, A; Morrone, A; Akinyanju, O; Wakama, T; Nunes, J M; Andreani, M; Sanchez-Mazas, A

    2015-10-01

    The simultaneous typing of five-HLA loci at high resolution and the availability of pedigree data allowed us to characterize extended five-locus phased haplotypes in 124 Nigerian families and to compare the observed frequencies with those expected by an expectation-maximization algorithm for unphased data. Despite the occurrence of some frequent alleles at each locus (e.g. B*53:01, which is assumed to protect against Plasmodium falciparum), as many as 82% of the sampled individuals carry two unique five-locus haplotypes and only three extended haplotypes with frequency above 1% exhibit significant linkage disequilibrium. Although preliminary, these results reveal an extreme level of HLA diversity in the Nigerian population, which reflects both its multi-ethnic composition and the very ancient demographic history of African populations. PMID:26300115

  6. Estimating parental relationship in linkage analysis of recessive traits

    SciTech Connect

    Merette, C.; Ott, J.

    1996-05-17

    In linkage analysis of recessive traits, parental relationship is important. For the case that it is unknown, the question is investigated as to whether estimating parental relationship and using the estimated relationship in linkage analysis is beneficial. Results show that estimating parental relationship can reliably be carried out on the basis of 50-100 genetic marker loci (analysis based on theory by Thompson). Misspecification of parental relationship leads to a loss of linkage informativeness, but not to false-positive evidence for linkage. An asymptotic bias in the recombination fraction estimate occurs when parents are unrelated and falsely taken to be related, but no such bias is seen when related parents are taken to be unrelated. Results from this investigation suggest that an estimated parental relationship may be used in linkage analysis as if it were the correct relationship, when evidence for the estimated relationship is supported by a likelihood ratio of at least 10:1 against the parents being unrelated. 9 refs., 2 figs., 5 tabs.

  7. Linkage disequilibrium in the insulin gene region is related to the exact number of repeat units present at the 5{prime} flanking polymorphism

    SciTech Connect

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

    1994-09-01

    Tandem DNA repeat units (RUs) located 5{prime} to the insulin (INS) gene give rise to a {open_quotes}5{prime} flanking polymorphism{close_quotes} (5{prime}FP) with minisatellite alleles belonging to 3 size classes. The shortest or {open_quotes}class 1{close_quotes} alleles (mean length of {approximately}40 RUs) are associated with insulin-dependent diabetes mellitus (IDDM), and the 5{prime}FP is one of several INS region loci in strong linkage disequilibrium with IDDM. We have amplified class 1 alleles and have determined the exact number of RUs in individual class 1 alleles found in parents of 50 IDDM families. We also obtained INS region haplotypes by typing two loci near tyrosine hydroxylase (TH) and two loci near insulin-like growth factor II (IGF2). We obtained these results: (1) Class 1 alleles (n=101) were found at every integer length from 30 to 44 RUs, the lengths of smallest and largest class 1 alleles observed. The allele frequency distribution was trimodal with peaks at 31, 40 and 42 RUs; 18%, 34% and 48% of the alleles belonged to the three components, respectively. (2) Allelic variation at each flanking locus was highly associated with the exact number of RUs present at the 5{prime}FP. Our results suggest that creation of new 5{prime}FP or other minisatellite haplotypes may be {open_quotes}constrained{close_quotes} in that flanking alleles usually become associated with a new minisatellite length different by only one or two RUs. Furthermore, since many flanking alleles were associated with a single narrow range of class 1 integer lengths, determining exact RU length may aid in visualizing linkage disequilibrium and allelic associations involving other minisatellite loci.

  8. Evidence of linkage disequilibrium between schizophrenia and the SCA1 CAG repeat on chromosome 6p23

    SciTech Connect

    Wang, S.; Sun, Cui-E; Diehl, S.R.

    1996-09-01

    Schizophrenia and the closely related phenotype schizoaffective disorder are severe mental illnesses that affect >1.0% of the population. The major role that genetic factors contribute to disease susceptibility is very well established. Schizophrenia appears to be a highly complex and heterogeneous disorder, however, and gene-mapping efforts also face challenges in assigning diagnoses and in delineating the disease`s phenotypic boundary. Several recently reported studies indicate that a schizophrenia-susceptibility gene may reside on the distal short arm of chromosome 6. Wang et al. reported a strong suggestion of linkage to chromosome 6pter-p22, using a resource based on 186 Irish families that was developed by K. S, Kendler, D. Walsh and colleagues, and one of us (S.R.D.), as described elsewhere. In that study, locus D6S260 gave the highest pairwise LOD score, 3.5, allowing for locus heterogeneity. Analysis with D6S260 and the distal locus F13A1 yielded a multipoint LOD score of 3.9, which maximized by allowing for locus heterogeneity and assuming that 50% of families are linked to this region. Nonparametric affected-pedigree-member analyses also supported this finding. Several other groups have recently reported additional evidence suggesting linkage to this region, both in an expanded collection of Irish families and in families from a variety of other geographic locations. However, none of these studies succeed in narrowing the location of the putative disease gene beyond the {approximately}30-cM region first identified by Wang et al. 44 refs., 1 fig., 1 tab.

  9. Genetic association between intronic variants in AS3MT and arsenic methylation efficiency is focused on a large linkage disequilibrium cluster in chromosome 10

    PubMed Central

    Gomez-Rubio, Paulina; Meza-Montenegro, Maria M.; Cantu-Soto, Ernesto; Klimecki, Walter T.

    2009-01-01

    Differences in arsenic metabolism are known to play a role in individual variability in arsenic-induced disease susceptibility. Genetic variants in genes relevant to arsenic metabolism are considered to be partially responsible for the variation in arsenic metabolism. Specifically, variants in arsenic (3+ oxidation state) methyltransferase (AS3MT), the key gene in the metabolism of arsenic, have been associated with increased arsenic methylation efficiency. Of particular interest is the fact that different studies have reported that several of the AS3MT single nucleotide polymorphisms (SNPs) are in strong linkage-disequilibrium (LD), which also extends to a nearby gene, CYP17A1. In an effort to characterize the extent of the region in LD, we genotyped 46 SNPs in a 347,000 base region of chromosome 10 that included AS3MT in arsenic-exposed subjects from Mexico. Pairwise LD analysis showed strong LD for these polymorphisms, represented by a mean r2 of 0.82, spanning a region that includes 5 genes. Genetic association analysis with arsenic metabolism confirmed the previously observed association between AS3MT variants, including this large cluster of linked polymorphisms, and arsenic methylation efficiency. The existence of a large genomic region sharing strong LD with polymorphisms associated with arsenic metabolism presents a predicament because the observed phenotype cannot be unequivocally assigned to a single SNP or even a single gene. The results reported here should be carefully considered for future genomic association studies involving AS3MT and arsenic metabolism. PMID:20014157

  10. Genome-wide distribution of linkage disequilibrium in the population of Palau and its implications for gene flow in Remote Oceania.

    PubMed

    Devlin, B; Roeder, K; Otto, C; Tiobech, S; Byerley, W

    2001-06-01

    Linkage disequilibrium (LD) between alleles on the same human chromosome results from various evolutionary processes and is thus telling about the history of populations. Recently, LD has garnered substantial interest for its value to map and fine-map disease genes. We examine the distribution of LD between short tandem repeat alleles on autosomes and sex chromosomes in the Remote Oceanic population of Palau to evaluate whether the data are consistent with a recent hypothesis about the origins of genetic variation in Palau, specifically that the population experienced extensive male-biased gene flow following initial settlement. Consistent with evolutionary theory based on effective population size, LD between X-linked alleles is stochastically greater than LD between autosomal alleles, however, small but detectable LD occurs for autosomal markers separated by substantial distances. By contrast, while Y-linked alleles experience only one-third the effective population size of X-linked alleles, their mean value for pairwise LD is only slightly larger than X-linked alleles. For a small population known to experience at least two extreme bottlenecks, 56 six-locus Y haplotypes exhibit remarkable diversity (0.96), comparable to Y diversity of Europeans, however, autosomal and X-linked markers display significantly less diversity, as measured by heterozygosity (4.1% less). Palauan Y haplotypes also fall into distinct clusters, again unlike that of Europe. We argue these data are consistent with waves of male-biased gene flow. PMID:11499679

  11. Linkage Disequilibrium Mapping in Domestic Dog Breeds Narrows the Progressive Rod-Cone Degeneration (prcd) Interval and Identifies Ancestral Disease Transmitting Chromosome

    PubMed Central

    Goldstein, Orly; Zangerl, Barbara; Pearce-Kelling, Sue; Sidjanin, Duska J.; Kijas, James W.; Felix, Jeanette; Acland, Gregory M; Aguirre, Gustavo D.

    2014-01-01

    Canine progressive rod-cone degeneration (prcd) is a retinal disease previously mapped to a broad, gene-rich centromeric region of canine chromosome 9. As allelic disorders are present in multiple breeds, we used linkage disequilibrium (LD) to narrow the ∼6.4 Mb interval candidate region. Multiple dog breeds, each representing genetically isolated populations, were typed for SNPs and other polymorphisms identified from BACs. The candidate region was initially localized to a 1.5 Mb zero recombination interval between growth factor receptor-bound protein 2 (GRB2) and SEC14-like 1 (SEC14L). A fine-scale haplotype of the region was developed which reduced the LD interval to 106 Kb, and identified a conserved haplotype of 98 polymorphisms present in all prcd-affected chromosomes from 14 different dog breeds. The findings strongly suggest that a common ancestor transmitted the prcd disease allele to many of the modern dog breeds, and demonstrate the power of LD approach in the canine model. PMID:16859891

  12. A High-Resolution Linkage-Disequilibrium Map of the Human Major Histocompatibility Complex and First Generation of Tag Single-Nucleotide Polymorphisms

    PubMed Central

    Miretti, Marcos M.; Walsh, Emily C.; Ke, Xiayi; Delgado, Marcos; Griffiths, Mark; Hunt, Sarah; Morrison, Jonathan; Whittaker, Pamela; Lander, Eric S.; Cardon, Lon R.; Bentley, David R.; Rioux, John D.; Beck, Stephan; Deloukas, Panos

    2005-01-01

    Autoimmune, inflammatory, and infectious diseases present a major burden to human health and are frequently associated with loci in the human major histocompatibility complex (MHC). Here, we report a high-resolution (1.9 kb) linkage-disequilibrium (LD) map of a 4.46-Mb fragment containing the MHC in U.S. pedigrees with northern and western European ancestry collected by the Centre d'Etude du Polymorphisme Humain (CEPH) and the first generation of haplotype tag single-nucleotide polymorphisms (tagSNPs) that provide up to a fivefold increase in genotyping efficiency for all future MHC-linked disease-association studies. The data confirm previously identified recombination hotspots in the class II region and allow the prediction of numerous novel hotspots in the class I and class III regions. The region of longest LD maps outside the classic MHC to the extended class I region spanning the MHC-linked olfactory-receptor gene cluster. The extended haplotype homozygosity analysis for recent positive selection shows that all 14 outlying haplotype variants map to a single extended haplotype, which most commonly bears HLA-DRB1*1501. The SNP data, haplotype blocks, and tagSNPs analysis reported here have been entered into a multidimensional Web-based database (GLOVAR), where they can be accessed and viewed in the context of relevant genome annotation. This LD map allowed us to give coordinates for the extremely variable LD structure underlying the MHC. PMID:15747258

  13. Distinct Linkage Disequilibrium (LD) Runs of Single Nucleotide Polymorphisms and Microsatellite Markers; Implications for Use of Mixed Marker Haplotypes in LD-based Mapping

    PubMed Central

    Lee, Kyung-A; Sohn, Kwang-Min; Cho, Seung-Hee; Hwang, Hyokkee; Kim, Sun Woo; Won, Hong-Hee; Kim, Hee-Jin; Kim, Min Ji; Cho, Sang Sun; Park, Jun Hee

    2007-01-01

    It has been suggested that the haplotypic relationship between microsatellite markers and single nucleotide polymorphisms (SNPs) is of considerable importance, as microsatellite markers can potentially be incorporated into haplotypes containing SNPs to increase marker density across a region of interest. However, SNPs and microsatellite markers have different mutation rates and durations, and it is conceivable that the linkage disequilibrium (LD) patterns between the genetic markers may considerably differ. We assessed the LD patterns using 1,661 SNPs and 65 microsatellite markers along chromosome 22 and investigated whether common patterns of LD between the two genetic markers are deduced from the results. The results demonstrated that the patterns of LD among microsatellite markers varied considerably and the LD runs of SNPs and microsatellite markers showed distinct patterns. Microsatellite markers have a much higher mutation rate and the evolution of microsatellite markers is a more complex process which has distinct mutation properties from those of SNPs. We consider that these might contribute to the different LD patterns between the two genetic markers. Therefore, it would seem inadvisable to make assumptions about persistence of LD across even a relatively small genetic distance among microsatellite markers and to construct mixed marker haplotypes/LD maps employing microsatellite markers. PMID:17596648

  14. Genetic Characterization and Linkage Disequilibrium Estimation of a Global Maize Collection Using SNP Markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A newly developed maize Illumina GoldenGate Assay with 1536 SNPs from 582 candidate genes was used to genotype a highly diverse global maize collection of 632 inbred lines from temperate, tropical, and subtropical public breeding programs. A total of 1229 informative SNPs and 1785 haplotypes were ...

  15. Estimates of linkage disequilibrium and effective population size in rainbow trout

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of molecular genetic technologies for broodstock management and selective breeding of aquaculture species is becoming increasingly more common with the continued development of genome tools and reagents. Several laboratories have produced genetic maps for rainbow trout to aid in the identif...

  16. Does a central MHC gene in linkage disequilibrium with HLA-DRB1*0401 affect susceptibility to type 1 diabetes?

    PubMed

    Windsor, L; Puschendorf, M; Allcock, R; Scott, A; Sayer, D; Kucharzak, R; Gut, I; McCann, V; Davis, E; Witt, C; Christiansen, F; Price, P

    2005-06-01

    Subtypes of HLA-DR4 are associated with susceptibility or protection against type 1 diabetes (T1DM). We addressed whether this reflects linkage disequilibrium with the true susceptibility locus by studying broader MHC haplotypes marked by alleles of HLA-B, IKBL (adjacent to TNFA) and complement C4. The study used a largely Caucasian cohort from Western Australia. HLA-DRB1*0401 and HLA-DRB1*0405 marked susceptibility to T1DM. In Caucasians, DRB1*0401 occurs predominantly in the 44.1 ancestral haplotype (AH; HLA-A2,B44, DRB1*0401,DQB1*0301) and the 62.1AH (HLA-A2,B15(62),DRB1*0401,DQB1*0302). HLA-B15 marked susceptibility and HLA-B44 marked with resistance to T1DM in patients and controls preselected for HLA-DRB1*0401. A gene between TNFA and HLA-B on the 8.1AH (HLA-A1,B8,;DR3,DQ2) modifies the effects of the class II alleles. Here, alleles characteristic of the 62.1AH (C4B3, IKBL+446*T and HLA-A2,B15) were screened in donors preselected for HLA-DRB1*0401. C4B3 was associated with diabetes, consistent with a diabetes gene telomeric of MHC class II. However, increases in carriage of IKBL+446*T and HLA-A2,B15 were marginal, as too few control subjects were available with the diabetogenic alleles. However, with these tools, selection of HLA-DRB1*0401, DQB1*0302 donors who are positive and negative for C4B3 will allow bidirectional mapping of diabetes genes in the central MHC. PMID:15858601

  17. MHC microsatellite diversity and linkage disequilibrium among common HLA-A, HLA-B, DRB1 haplotypes: implications for unrelated donor hematopoietic transplantation and disease association studies.

    PubMed

    Malkki, M; Single, R; Carrington, M; Thomson, G; Petersdorf, E

    2005-08-01

    Twenty-two human major histocompatibility complex (MHC) region microsatellite (Msat) markers were studied for diversity and linkage disequilibrium (LD) with HLA loci in hematopoietic cell transplant recipients and their HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 allele-matched unrelated donors. These Msats showed highly significant LD over much of the MHC region. The Msat diversity of five common Caucasian haplotypes (HLA-A1-B8-DR3, A3-B7-DR15, A2-B44-DR4, A29-B44-DR7, and A2-B7-DR15) was examined using a new measure called 'haplotype specific heterozygosity' (HSH). Each of the five haplotypes had at least one Msat marker with an HSH value of zero indicating that only one Msat allele was observed for the particular HLA haplotype. In addition, the ability of Msats to predict HLA-A-B-DRB1 haplotypes was studied. Over 90% prediction probability of two common haplotypes (HLA-A1-B8-DR3 and HLA-A3-B7-DR15) was achieved with information from three Msats (D6S265/D6S2787/D6S2894 and D6S510/D6S2810/D6S2876, respectively). We demonstrate how the HSH index can be used in the selection of informative Msats for transplantation and disease association studies. Markers with low HSH values can be used to predict specific HLA haplotypes or multilocus genotypes to supplement the screening of HLA-matched donors for transplantation. Markers with high HSH values will be most informative in studies investigating MHC region disease-susceptibility genes where HLA haplotypic effects are known to exist. PMID:16029431

  18. Linkage Disequilibrium between Two High-Frequency Deletion Polymorphisms: Implications for Association Studies Involving the glutathione-S transferase (GST) Genes

    PubMed Central

    Zhao, Yongzhong; Marotta, Michael; Eichler, Evan E.; Eng, Charis; Tanaka, Hisashi

    2009-01-01

    Copy number variations (CNVs) represent a large source of genetic variation in humans and have been increasingly studied for disease association. A deletion polymorphism of the gene encoding the cytosolic detoxification enzyme glutathione S-transferase theta 1 (GSTT1) has been extensively studied for cancer susceptibility (919 studies, from HuGE navigator, http://www.hugenavigator.net/). However, clear conclusions have not been reached. Since the GSTT1 gene is located within a genomic region of segmental duplications (SD), there may be a confounding effect from another, yet-uncharacterized CNV at the same locus. Here we describe a previously uncharacterized 38-kilo-base (kb) long deletion polymorphism of GSTT2B located within a 61-kb DNA inverted repeat. GSTT2B is a duplicated copy of GSTT2, the only paralogue of GSTT1 in humans. A newly developed PCR assay revealed that a microhomology-mediated breakpoint appears to be shared among individuals at high frequency. The GSTT2B deletion polymorphism was in strong linkage disequilibrium (LD) (D′ = 0.841) with the neighboring GSTT1 deletion polymorphism in the Caucasian population. Alleles harboring a single deletion were significantly overrepresented (p = 2.22×10−16), suggesting a selection against alleles with both deletions. The deletion alleles are almost certainly the derived ones, because the GSTT2B-GSTT2-GSTT1 genes were strictly retained in chimpanzees. Extremely low GSTT2 mRNA expression was associated with the GSTT2B deletion, suggesting an influence of the deletion on the flanking region and loss of GSTT2 function. Genome-wide LD analysis between deletion polymorphisms further points to the uniqueness of two deletions, because strong LD between deletion polymorphisms might be very rare in humans. These results show a complex genomic organization and unexpected biological functions of CNVs within segmental duplications and emphasize the importance of detailed structural characterization for disease

  19. Subtyping of phosphoglucomutase locus 1 (PGM1) polymorphism in some populations of Rwanda: description of variant phenotypes, "haplotype" frequencies, and linkage disequilibrium data.

    PubMed

    Santachiara-Benerecetti, A S; Ranzani, G N; Antonini, G; Beretta, M

    1982-03-01

    Some populations of Rwanda (South Twa Pygmies, Hutu, and Tutsi) have been analyzed by acid starch gel electrophoresis for the subtyping of PGM1 polymorphism. The new polymorphic third PGM11 allele, the PGM1(1Twa), which we recently detected in Twa Pygmies from North Rwanda, has not been found in this survey, whereas the rare PGM1(6) allele attains subpolymorphic frequencies in all groups. Comparison between the various populations of Rwanda shows that they differ significantly from each other with the exception of South Twa Pygmies and Tutsi. A relatively low frequency (9.6%) of the PGM1(2S) allele appears to be typical of North Twa Pygmies; a low frequency of PGM1(2F) (1.2%-3.6%) has been found in all these groups but not in the Hutu (6.4%); and a particularly high incidence of the PGM1(1F) allele (the highest so far reported) has been observed in the South Twa Pygmies (20%) and in the Tutsi (18%). The PGM1(1Twa) and PGM1(6) enzymes, which in acid starch gel are not distinguishable, can be clearly differentiated by isoelectric focusing. In addition, the same technique has shown that the rare PGM1(7) allele observed in one Hutu is different from that found at polymorphic frequency in the Japanese and from a rare PGM1(7) allele found in Germany. On the very likely hypothesis that the PGM1(1S), PGM1(1F), PGM1(2S), and PGM1(2F) result from variations at two different polymorphic sites, 1/2 and F/S, within the PGM1 structural gene, all the available population data have been analyzed to investigate whether preferential combinations (haplotypes) were identifiable. Whereas Caucasians show a prevalence of 2F and 1S combination with an 8.02% mean value of linkage disequilibrium expressed as % Dmax, from the very few and scattered African data, it is impossible to draw any inference at present. PMID:6462057

  20. Disequilibrium mapping: Composite likelihood for pairwise disequilibrium

    SciTech Connect

    Devlin, B.; Roeder, K.; Risch, N.

    1996-08-15

    The pattern of linkage disequilibrium between a disease locus and a set of marker loci has been shown to be a useful tool for geneticists searching for disease genes. Several methods have been advanced to utilize the pairwise disequilibrium between the disease locus and each of a set of marker loci. However, none of the methods take into account the information from all pairs simultaneously while also modeling the variability in the disequilibrium values due to the evolutionary dynamics of the population. We propose a Composite Likelihood CL model that has these features when the physical distances between the marker loci are known or can be approximated. In this instance, and assuming that there is a single disease mutation, the CL model depends on only three parameters, the recombination fraction between the disease locus and an arbitrary marker locus, {theta}, the age of the mutation, and a variance parameter. When the CL is maximized over a grid of {theta}, it provides a graph that can direct the search for the disease locus. We also show how the CL model can be generalized to account for multiple disease mutations. Evolutionary simulations demonstrate the power of the analyses, as well as their potential weaknesses. Finally, we analyze the data from two mapped diseases, cystic fibrosis and diastrophic dysplasia, finding that the CL method performs well in both cases. 28 refs., 6 figs., 4 tabs.

  1. Estimation of Hardy-Weinberg and pairwise disequilibrium in the apolipoprotein AI-CIII-AIV gene cluster.

    PubMed Central

    Haviland, M B; Kessling, A M; Davignon, J; Sing, C F

    1991-01-01

    Departures from Hardy-Weinberg (HW) equilibria and pairwise disequilibria were estimated in a sample of unrelated healthy individuals typed for six RFLPs in the apo AI-CIII-AIV gene region. The sample was composed of males and females, selected for health, from two populations, those of exclusively French-Canadian (FC) and those of some non-French-Canadian (NFC) ancestry. An approach suggested by Weir and Cockerham, which includes estimates of nonrandom association (disequilibria) between three and four alleles at two loci as well as the traditional associations between two alleles, at two loci was used. The pattern of departures from HW equilibria suggested that the genetic structures of the FC and NFC are different. Departure from HW equilibrium at an RFLP locus could not be predicted from information about other loci in the same gene region. Nonrandom associations were also evident from the pairwise analyses. Two pairs of loci had significant diallelic disequilibria, while two other pairs had significant triallelic disequilibria. All of the RFLP pairs had at least one measure of disequilibrium at its maximum value determined by allele frequencies. Inferences about pairwise disequilibria depended on the statistical approach used. Sizes of the pairwise disequilibria were not correlated with the physical distance between loci. The impact of these disequilibria on RFLP-phenotype association studies is discussed. PMID:1678249

  2. Informative-Transmission Disequilibrium Test (i-TDT):Combined Linkage and Association Mapping That Includes Unaffected Offspring as Well as Affected Offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To date, there is no test valid for the composite null hypothesis of no linkage or no association that utilizes transmission information from heterozygous parents to their unaffected offspring as well as the affected offspring from ascertained nuclear families. Since the unaffected siblings also pro...

  3. Refined localization of the Batten disease gene (CL3) by haplotype and linkage disequilibrium mapping to D16S288-D16S383 and exclusion from this region of a variant form of Batten disease with granular osmiophilic deposits

    SciTech Connect

    Mitchison, H.M.; O`Rawe, A.M.; Gormally, E.

    1995-06-05

    Haplotype analysis in a collaborative collection of 143 families with juvenile-onset neuronal ceroid lipofuscinosis (JNCL) or Batten (Spielmeyer-Vogt-Sjoegren) disease has permitted refined localization of the disease gene, CLN3, which was assigned to chromosome 16 in 1989. Recombination events in four maternal meioses delimit new flanking genetic markers for CLN3 which localize the gene to the chromosome interval 16p12.1-11.2 between microsatellite markers D16S288 and D16S383. This narrows the position of CLN3 to a region of 2.1 cM, a significant reduction from the previous best interval. Using haplotypes, analysis of the strong linkage disequilibrium that exists between genetic markers within the D16S288-D16S383 interval and CLN3 shows that CLN3 is in closest proximity to loci D16S299 and D16S298. Analysis of markers across the D16S288-D16S383 region in four families with a variant form of JNCL characterized histologically by cytosomal granular osmiophilic deposits (GROD) has excluded linkage of the gene locus to the CLN3 region of chromosome 16, suggesting that JNCL with GROD is not an allelic form of JNCL. 8 refs., 2 figs., 2 tabs.

  4. Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM interval on chromosome 1q42-43.

    PubMed Central

    Parvari, R; Hershkovitz, E; Kanis, A; Gorodischer, R; Shalitin, S; Sheffield, V C; Carmi, R

    1998-01-01

    The syndrome of hypoparathyroidism associated with growth retardation, developmental delay, and dysmorphism (HRD) is a newly described, autosomal recessive, congenital disorder with severe, often fatal consequences. Since the syndrome is very rare, with all parents of affected individuals being consanguineous, it is presumed to be caused by homozygous inheritance of a single recessive mutation from a common ancestor. To localize the HRD gene, we performed a genomewide screen using DNA pooling and homozygosity mapping for apparently unlinked kindreds. Analysis of a panel of 359 highly polymorphic markers revealed linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination fraction of 0. Analysis of three additional markers-GGAA6F06, D1S2678, and D1S179-in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of additional chromosome 1 markers revealed evidence of genetic linkage disequilibrium and place the HRD locus within an approximately 1-cM interval defined by D1S1540 and D1S2678 on chromosome 1q42-43. PMID:9634513

  5. Mapping of the gene for Machado-Joseph disease within a 3.6-cM interval flanked by D14S291/D14S280 and D14S81, on the basis of studies of linkage and linkage disequilibrium in 24 Japanese families

    SciTech Connect

    Sasaki, Hidenao; Ihara, Tatsuo; Wakisaka, Akemi; Takada, Akio; Yoshiki, Takashi; Hamada, Takeshi; Suzuki, Yoshihiro; Iwabuchi, Kiyoshi; Onari, Keiko; Tada, Jyoji

    1995-01-01

    The gene locus of Machado-Joseph disease (MJD) has recently been mapped within a 29-cM subregion of 14q chromosome. We did a linkage study of 24 multigenerational MJD Japanese pedigrees, in an attempt to narrow the candidate region of this gene. Pairwise and multipoint linkage analysis, together with haplotype segregation analysis, led to the conclusion that the MJD gene is located at the 6.8-cM interval between D14S256 and D14S81 (Z{sub max} = 24.78, multipoint linkage analysis). D14S291 and D14S280, located at the center of this interval, showed no obligate recombination with the MJD gene (Z{sub max} = 5.93 for D14S291 and 9.99 for D14S280). A weak, but significant, linkage disequilibrium of MJD gene was noted with D14S81 (P<.05) but not with D14S291 or D14S280. These results suggest that a 3.6-cM interval flanked by D14S291/D14S280 and D14S81 is the most likely location of the MJD gene and that it is closest to D14S81. 33 refs., 4 figs., 6 tabs.

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

    PubMed Central

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

    2003-01-01

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

  7. Linkage disequilibrium for two X-linked genes in Sardinia and its bearing on the statistical mapping of the human X chromosome.

    PubMed

    Filippi, G; Rinaldi, A; Palmarino, R; Seravalli, E; Siniscalco, M

    1977-05-01

    The distribution of four X-linked mutants (G6PD, Deutan, Protan and Xg) among lowland and once highly malarial populations of Sardinia discloses a clear-cut example of linkage disequiligrium between two of them (G6PD and Protan). In the same populations the distribution of G6PD-deficiency versus colorblindness of the Deutan type and the Xg blood-group is not significantly different from that expected at equilibrium. These data suggest indirectly that the loci for G6PD and Protan may be nearer to one another than those for G6PD and Deutan. PMID:301840

  8. Incidence and Estimated Prevalence of Endometriosis and Adenomyosis in Northeast Italy: A Data Linkage Study.

    PubMed

    Morassutto, Caterina; Monasta, Lorenzo; Ricci, Giuseppe; Barbone, Fabio; Ronfani, Luca

    2016-01-01

    Despite being quite frequent and having serious implications in terms of symptomatology and fertility, data on incidence and prevalence of endometriosis and adenomyosis following gold standard definitions are dramatically lacking. The average time from onset of symptoms to diagnosis in industrialized countries still ranges from five to ten years. Using the regional centralized data linkage system, we calculated incidence and prevalence of endometriosis and adenomyosis in the female population of Friuli Venezia Giulia region, Italy, for the years 2011-2013. Cases were defined as new diagnoses from hospital discharge records, following procedures allowing direct visualization for endometriosis and hysterectomy for adenomyosis, with or without histological confirmation. Diagnoses were considered "new" after verifying women had not been diagnosed in the previous ten years. Incidence of endometriosis and adenomyosis in women aged 15-50 years is 0.14%. Prevalence, estimated from incidence, is 2.00%. Adenomyosis, representing 28% of all diagnoses, becomes increasingly prevalent after the age of 50 years. Our results shows how the study of both endometriosis and adenomyosis should not be limited to women of premenopausal age. Further efforts are needed to sensitize women and health professional, and to find new data linkage possibilities to identify undiagnosed cases. PMID:27101396

  9. Incidence and Estimated Prevalence of Endometriosis and Adenomyosis in Northeast Italy: A Data Linkage Study

    PubMed Central

    Ricci, Giuseppe; Barbone, Fabio; Ronfani, Luca

    2016-01-01

    Despite being quite frequent and having serious implications in terms of symptomatology and fertility, data on incidence and prevalence of endometriosis and adenomyosis following gold standard definitions are dramatically lacking. The average time from onset of symptoms to diagnosis in industrialized countries still ranges from five to ten years. Using the regional centralized data linkage system, we calculated incidence and prevalence of endometriosis and adenomyosis in the female population of Friuli Venezia Giulia region, Italy, for the years 2011–2013. Cases were defined as new diagnoses from hospital discharge records, following procedures allowing direct visualization for endometriosis and hysterectomy for adenomyosis, with or without histological confirmation. Diagnoses were considered “new” after verifying women had not been diagnosed in the previous ten years. Incidence of endometriosis and adenomyosis in women aged 15–50 years is 0.14%. Prevalence, estimated from incidence, is 2.00%. Adenomyosis, representing 28% of all diagnoses, becomes increasingly prevalent after the age of 50 years. Our results shows how the study of both endometriosis and adenomyosis should not be limited to women of premenopausal age. Further efforts are needed to sensitize women and health professional, and to find new data linkage possibilities to identify undiagnosed cases. PMID:27101396

  10. Thermal disequilibrium at the top of volcanic clouds and its effect on estimates of the column height

    NASA Technical Reports Server (NTRS)

    Woods, Andrew W.; Self, Stephen

    1992-01-01

    Satellite images of large volcanic explosions reveal that the tops of volcanic eruptions columns are much cooler than the surrounding atmosphere. It is proposed that this effect occurs whenever a mixture of hot volcanic ash and entrained air ascends sufficiently high into a stably stratified atmosphere. Although the mixture is initially very hot, it expands and cools as the ambient pressure decreases. It is shown that cloud-top undercoolings in excess of 20 C may develop in clouds that penetrate the stratosphere, and it is predicted that, for a given cloud-top temperature, variations in the initial temperature of 100-200 C may correspond to variations in the column height of 5-10 km. It is deduced that the present practice of converting satellite-based measurements of the temperature at the top of volcanic eruptions columns to estimates of the column height will produce rather inaccurate results and should therefore be discontinued.

  11. Modified distance in average linkage based on M-estimator and MADn criteria in hierarchical cluster analysis

    NASA Astrophysics Data System (ADS)

    Muda, Nora; Othman, Abdul Rahman

    2015-10-01

    The process of grouping a set of objects into classes of similar objects is called clustering. It divides a large group of observations into smaller groups so that the observations within each group are relatively similar and the observations in different groups are relatively dissimilar. In this study, an agglomerative method in hierarchical cluster analysis is chosen and clusters were constructed by using an average linkage technique. An average linkage technique requires distance between clusters, which is calculated based on the average distance between all pairs of points, one group with another group. In calculating the average distance, the distance will not be robust when there is an outlier. Therefore, the average distance in average linkage needs to be modified in order to overcome the problem of outlier. Therefore, the criteria of outlier detection based on MADn criteria is used and the average distance is recalculated without the outlier. Next, the distance in average linkage is calculated based on a modified one step M-estimator (MOM). The groups of cluster are presented in dendrogram graph. To evaluate the goodness of a modified distance in the average linkage clustering, the bootstrap analysis is conducted on the dendrogram graph and the bootstrap value (BP) are assessed for each branch in dendrogram that formed the group, to ensure the reliability of the branches constructed. This study found that the average linkage technique with modified distance is significantly superior than the usual average linkage technique, if there is an outlier. Both of these techniques are said to be similar if there is no outlier.

  12. Analgesia dose prescribing and estimated glomerular filtration rate decline: a general practice database linkage cohort study

    PubMed Central

    Nderitu, Paul; Doos, Lucy; Strauss, Vicky Y; Lambie, Mark; Davies, Simon J; Kadam, Umesh T

    2014-01-01

    Objective We aimed to quantify the short-term effect of non-steroidal anti-inflammatory drugs (NSAIDs), aspirin and paracetamol analgesia dose prescribing on estimated glomerular filtration rate (eGFR) decline in the general practice population. Design A population-based longitudinal clinical data linkage cohort study. Setting Two large general practices in North Staffordshire, UK. Participants Patients aged 40 years and over with ≥2 eGFR measurements spaced ≥90 days apart between 1 January 2009 and 31 December 2010 were selected. Exposure Using WHO Defined Daily Dose standardised cumulative analgesia prescribing, patients were categorised into non-user, normal and high-dose groups. Outcome measure The primary outcome was defined as a >5 mL/min/1.73 m2/year eGFR decrease between the first and last eGFR. Logistic regression analyses were used to estimate risk, adjusting for sociodemographics, comorbidity, baseline chronic kidney disease (CKD) status, renin-angiotensin-system inhibitors and other analgesia prescribing. Results There were 4145 patients (mean age 66 years, 55% female) with an analgesia prescribing prevalence of 17.2% for NSAIDs, 39% for aspirin and 22% for paracetamol and stage 3–5 CKD prevalence was 16.1% (n=667). Normal or high-dose NSAID and paracetamol prescribing was not significantly associated with eGFR decline. High-dose aspirin prescribing was associated with a reduced risk of eGFR decline in patients with a baseline (first) eGFR ≥60 mL/min/1.73 m2; OR=0.52 (95% CI 0.35 to 0.77). Conclusions NSAID, aspirin and paracetamol prescribing over 2 years did not significantly affect eGFR decline with a reduced risk of eGFR decline in high-dose aspirin users with well-preserved renal function. However, the long-term effects of analgesia use on eGFR decline remain to be determined. PMID:25138808

  13. THREaD Mapper Studio: a novel, visual web server for the estimation of genetic linkage maps.

    PubMed

    Cheema, Jitender; Ellis, T H Noel; Dicks, Jo

    2010-07-01

    The estimation of genetic linkage maps is a key component in plant and animal research, providing both an indication of the genetic structure of an organism and a mechanism for identifying candidate genes associated with traits of interest. Because of this importance, several computational solutions to genetic map estimation exist, mostly implemented as stand-alone software packages. However, the estimation process is often largely hidden from the user. Consequently, problems such as a program crashing may occur that leave a user baffled. THREaD Mapper Studio (http://cbr.jic.ac.uk/threadmapper) is a new web site that implements a novel, visual and interactive method for the estimation of genetic linkage maps from DNA markers. The rationale behind the web site is to make the estimation process as transparent and robust as possible, while also allowing users to use their expert knowledge during analysis. Indeed, the 3D visual nature of the tool allows users to spot features in a data set, such as outlying markers and potential structural rearrangements that could cause problems with the estimation procedure and to account for them in their analysis. Furthermore, THREaD Mapper Studio facilitates the visual comparison of genetic map solutions from third party software, aiding users in developing robust solutions for their data sets. PMID:20494977

  14. Backward disequilibrium in elderly subjects

    PubMed Central

    Manckoundia, Patrick; Mourey, France; Pérennou, Dominic; Pfitzenmeyer, Pierre

    2008-01-01

    Backward disequilibrium is observed frequently in daily clinical practice. However, there are no epidemiological data concerning this postural disorder. Defined by a posterior position of the centre of mass with respect to the base of support, backward disequilibrium is abnormal postural behavior, usually characterized by a posterior trunk tilt in standing and sitting positions, which predisposes subjects to backward falls. Many afflictions whether they are somatic (degenerative, ischemic and traumatic brain lesions), psychosomatic (psychomotor disadaptation syndrome, confinement to bed, nonuse situations) or psychological (depression) can cause backward disequilibrium. A vicious circle of falls, and loss of autonomy can arise and this is the main consequence of backward disequilibrium. Thus, in this paper, we review backward disequilibrium in elderly subjects with regard to the causes, consequences, assessment, and management. PMID:19281059

  15. Admixture and linkage disequilibrium analysis of meat goat breeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding the population structure and variation within the genome will assist with efforts to make genetic gains for meat goat production. A recently developed Illumina Goat 50K SNP panel containing 52,295 SNP loci was created primarily from SNPs identified in European dairy goat breeds and Asi...

  16. River Capture in Disequilibrium Landscapes

    NASA Astrophysics Data System (ADS)

    McCoy, S. W.; Perron, J.; Willett, S.; Goren, L.

    2013-12-01

    The process of river piracy or river capture has long drawn interest as a potential mechanism by which drainage basins large and small evolve towards an equilibrium state. River capture transfers both drainage area and drainage lines from one river basin to another, which can cause large, abrupt shifts in network topology, drainage divide positions, and river incision rates. Despite numerous case studies in which river capture has been proposed to have occurred, there is no general, mechanistic framework for understanding the controls on river capture, nor are there quantitative criteria for determining if capture has occurred. Here we use new metrics of landscape disequilibrium to first identify landscapes in which drainage reorganization is occurring. These metrics are based on a balance between an integral of the contributing drainage area and elevation. In an analysis of rivers in the Eastern United States we find that many rivers are in a state of disequilibrium and are experiencing recent or ongoing area exchange between basins. In these disequilibrium basins we find widespread evidence for network rearrangement via river capture at multiple scales. We then conduct numerical experiments with a 2-D landscape evolution model to explore the conditions in which area exchange among drainage basins is likely to occur as discrete capture events as opposed to continuous divide migration. These experiments indicate that: (1) capture activity increases with the degree of disequilibrium induced by persistent spatial gradients in tectonic forcing or by temporal changes in climate or tectonic forcing; (2) capture activity is strongly controlled by the initial planform drainage network geometry; and (3) capture activity scales with the fluvial incision rate constant in the river power erosion law.

  17. Geographic Differences in Genetic Locus Linkages for Borrelia burgdorferi

    PubMed Central

    Travinsky, Bridgit; Bunikis, Jonas

    2010-01-01

    Borrelia burdorferi genotype in the northeastern United States is associated with Lyme borreliosis severity. Analysis of DNA sequences of the outer surface protein C gene and rrs-rrlA intergenic spacer from extracts of Ixodes spp. ticks in 3 US regions showed linkage disequilibrium between the 2 loci within a region but not consistently between regions. PMID:20587192

  18. Demonstrating Cost-Effective Marker Assisted Selection for Biomass Yield in Red Clover (Trifolium pratense L.) – Part 2: Nested Within-Family Linkage Based Selection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many linkage and linkage-disequilibrium based marker assisted selection (MAS) methodologies have been proposed. To achieve success, most require mapping populations and/or very high marker genome coverage. Presented is a MAS scheme that requires no mapping populations or known linkage group configur...

  19. Ancestry inference in complex admixtures via variable-length Markov chain linkage models.

    PubMed

    Rodriguez, Jesse M; Bercovici, Sivan; Elmore, Megan; Batzoglou, Serafim

    2013-03-01

    Inferring the ancestral origin of chromosomal segments in admixed individuals is key for genetic applications, ranging from analyzing population demographics and history, to mapping disease genes. Previous methods addressed ancestry inference by using either weak models of linkage disequilibrium, or large models that make explicit use of ancestral haplotypes. In this paper we introduce ALLOY, an efficient method that incorporates generalized, but highly expressive, linkage disequilibrium models. ALLOY applies a factorial hidden Markov model to capture the parallel process producing the maternal and paternal admixed haplotypes, and models the background linkage disequilibrium in the ancestral populations via an inhomogeneous variable-length Markov chain. We test ALLOY in a broad range of scenarios ranging from recent to ancient admixtures with up to four ancestral populations. We show that ALLOY outperforms the previous state of the art, and is robust to uncertainties in model parameters. PMID:23421795

  20. Ancestry Inference in Complex Admixtures via Variable-length Markov Chain Linkage Models

    PubMed Central

    Bercovici, Sivan; Elmore, Megan; Batzoglou, Serafim

    2013-01-01

    Abstract Inferring the ancestral origin of chromosomal segments in admixed individuals is key for genetic applications, ranging from analyzing population demographics and history, to mapping disease genes. Previous methods addressed ancestry inference by using either weak models of linkage disequilibrium, or large models that make explicit use of ancestral haplotypes. In this paper we introduce ALLOY, an efficient method that incorporates generalized, but highly expressive, linkage disequilibrium models. ALLOY applies a factorial hidden Markov model to capture the parallel process producing the maternal and paternal admixed haplotypes, and models the background linkage disequilibrium in the ancestral populations via an inhomogeneous variable-length Markov chain. We test ALLOY in a broad range of scenarios ranging from recent to ancient admixtures with up to four ancestral populations. We show that ALLOY outperforms the previous state of the art, and is robust to uncertainties in model parameters. PMID:23421795

  1. A high-resolution linkage map for the Z chromosome in chicken reveals hot spots for recombination.

    PubMed

    Wahlberg, P; Strömstedt, L; Tordoir, X; Foglio, M; Heath, S; Lechner, D; Hellström, A R; Tixier-Boichard, M; Lathrop, M; Gut, I G; Andersson, L

    2007-01-01

    A comprehensive linkage map for chicken chromosome Z was constructed as the result of a large-scale screening of single nucleotide polymorphisms (SNPs). A total of 308 SNPs were assigned to Z based on the genotype distribution among 182 birds representing several populations. A linkage map comprising 210 markers and spanning 200.9 cM was established by analyzing a small Red junglefowl/White Leghorn intercross. There was excellent agreement between the linkage map for Z and a recently released assembly of the chicken genome (May 2006). Almost all SNPs assigned to chromosome Z in the present study are on Z in the new genome assembly. The remaining 12 loci are all found on unassigned contigs that can now be assigned to Z. The average recombination rate was estimated at 2.7 cM/Mb but there was a very uneven distribution of recombination events with both cold and hot spots of recombination. The existence of one of the major hot spots of recombination, located around position 39.4 Mb, was supported by the observed pattern of linkage disequilibrium. Thirteen markers from unassigned contigs were shown to be located on chromosome W. Three of these contigs included genes that have homologues on chromosome Z. The preliminary assignment of three more genes to the gene-poor W chromosome may be important for studies on the mechanism of sex determination and dosage compensation in birds. PMID:17675841

  2. Linkage map integration

    SciTech Connect

    Collins, A.; Teague, J.; Morton, N.E.; Keats, B.J.

    1996-08-15

    The algorithms that drive the map+ program for locus-oriented linkage mapping are presented. They depend on the enhanced location database program ldb+ to specify an initial comprehensive map that includes all loci in the summary lod file. Subsequently the map may be edited or order constrained and is automatically improved by estimating the location of each locus conditional on the remainder, beginning with the most discrepant loci. Operating characteristics permit rapid and accurate construction of linkage maps with several hundred loci. The map+ program also performs nondisjunction mapping with tests of nonstandard recombination. We have released map+ on Internet as a source program in the C language together with the location database that now includes the LODSOURCE database. 28 refs., 5 tabs.

  3. The Impact of the Choice of Data Source in Record Linkage Studies Estimating Mortality in Venous Thromboembolism.

    PubMed

    Gallagher, Arlene M; Williams, Tim; Leufkens, Hubert G M; de Vries, Frank

    2016-01-01

    Linked electronic healthcare databases are increasingly being used in observational research. The objective of this study was to investigate the impact of the choice of data source in estimating mortality following VTE, with a secondary aim to investigate the influence of the denominator definition. We used the UK Clinical Practice Research Datalink (CPRD) to identify patients aged 18+ with venous thromboembolism (VTE). Multiple cohorts were identified in order to assess how mortality rates differed with a range of data sources. For each of the cohorts, incidence rates per 1,000 person years (/1000py) and relative rates (RRs) of all-cause mortality were calculated. The lowest mortality rate was found when only primary care data were used for both the exposure (VTE) and the outcome (death) (108.4/1000py). The highest mortality rate was found for patients diagnosed in secondary care (237.2/1000py). When linked primary and secondary care data were included for eligible patients and for the overlapping period of data collection, a mortality rate of 173.2/1000py was found. Sensitivity analyses varying the denominator definition provided a range of results (140.6-164.3/1000py). The relative rates of mortality by gender and age were comparable across all cohorts. Depending on the choice of data source, the population studied may be different. This may have substantial impact on the main findings, in particular on incidence rates of mortality following VTE. PMID:26863417

  4. The Impact of the Choice of Data Source in Record Linkage Studies Estimating Mortality in Venous Thromboembolism

    PubMed Central

    Gallagher, Arlene M.; Williams, Tim; Leufkens, Hubert G. M.; de Vries, Frank

    2016-01-01

    Linked electronic healthcare databases are increasingly being used in observational research. The objective of this study was to investigate the impact of the choice of data source in estimating mortality following VTE, with a secondary aim to investigate the influence of the denominator definition. We used the UK Clinical Practice Research Datalink (CPRD) to identify patients aged 18+ with venous thromboembolism (VTE). Multiple cohorts were identified in order to assess how mortality rates differed with a range of data sources. For each of the cohorts, incidence rates per 1,000 person years (/1000py) and relative rates (RRs) of all-cause mortality were calculated. The lowest mortality rate was found when only primary care data were used for both the exposure (VTE) and the outcome (death) (108.4/1000py). The highest mortality rate was found for patients diagnosed in secondary care (237.2/1000py). When linked primary and secondary care data were included for eligible patients and for the overlapping period of data collection, a mortality rate of 173.2/1000py was found. Sensitivity analyses varying the denominator definition provided a range of results (140.6–164.3/1000py). The relative rates of mortality by gender and age were comparable across all cohorts. Depending on the choice of data source, the population studied may be different. This may have substantial impact on the main findings, in particular on incidence rates of mortality following VTE. PMID:26863417

  5. Reporting Errors in Siblings’ Survival Histories and Their Impact on Adult Mortality Estimates: Results From a Record Linkage Study in Senegal

    PubMed Central

    Helleringer, Stéphane; Pison, Gilles; Kanté, Almamy M.; Duthé, Géraldine; Andro, Armelle

    2014-01-01

    Estimates of adult mortality in countries with limited vital registration (e.g., sub-Saharan Africa) are often derived from information about the survival of a respondent’s siblings. We evaluated the completeness and accuracy of such data through a record linkage study conducted in Bandafassi, located in southeastern Senegal. We linked at the individual level retrospective siblings’ survival histories (SSH) reported by female respondents (n = 268) to prospective mortality data and genealogies collected through a health and demographic surveillance system (HDSS). Respondents often reported inaccurate lists of siblings. Additions to these lists were uncommon, but omissions were frequent: respondents omitted 3.8 % of their live sisters, 9.1 % of their deceased sisters, and 16.6 % of their sisters who had migrated out of the DSS area. Respondents underestimated the age at death of the siblings they reported during the interview, particularly among siblings who had died at older ages (≥45 years). Restricting SSH data to person-years and events having occurred during a recent reference period reduced list errors but not age and date errors. Overall, SSH data led to a 20 % underestimate of 45q15 relative to HDSS data. Our study suggests new quality improvement strategies for SSH data and demonstrates the potential use of HDSS data for the validation of “unconventional” demographic techniques. PMID:24493063

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

    PubMed Central

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

    1999-01-01

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

  7. Linkage analysis: Inadequate for detecting susceptibility loci in complex disorders?

    SciTech Connect

    Field, L.L.; Nagatomi, J.

    1994-09-01

    Insulin-dependent diabetes mellitus (IDDM) may provide valuable clues about approaches to detecting susceptibility loci in other oligogenic disorders. Numerous studies have demonstrated significant association between IDDM and a VNTR in the 5{prime} flanking region of the insulin (INS) gene. Paradoxically, all attempts to demonstrate linkage of IDDM to this VNTR have failed. Lack of linkage has been attributed to insufficient marker locus information, genetic heterogeneity, or high frequency of the IDDM-predisposing allele in the general population. Tyrosine hydroxylase (TH) is located 2.7 kb from INS on the 5` side of the VNTR and shows linkage disequilibrium with INS region loci. We typed a highly polymorphic microsatellite within TH in 176 multiplex families, and performed parametric (lod score) linkage analysis using various intermediate reduced penetrance models for IDDM (including rare and common disease allele frequencies), as well as non-parametric (affected sib pair) linkage analysis. The scores significantly reject linkage for recombination values of .05 or less, excluding the entire 19 kb region containing TH, the 5{prime} VNTR, the INS gene, and IGF2 on the 3{prime} side of INS. Non-parametric linkage analysis also provided no significant evidence for linkage (mean TH allele sharing 52.5%, P=.12). These results have important implications for efforts to locate genes predisposing to complex disorders, strongly suggesting that regions which are significantly excluded by linkage methods may nevertheless contain predisposing genes readily detectable by association methods. We advocate that investigators routinely perform association analyses in addition to linkage analyses.

  8. Linear models for joint association and linkage QTL mapping

    PubMed Central

    2009-01-01

    Background Populational linkage disequilibrium and within-family linkage are commonly used for QTL mapping and marker assisted selection. The combination of both results in more robust and accurate locations of the QTL, but models proposed so far have been either single marker, complex in practice or well fit to a particular family structure. Results We herein present linear model theory to come up with additive effects of the QTL alleles in any member of a general pedigree, conditional to observed markers and pedigree, accounting for possible linkage disequilibrium among QTLs and markers. The model is based on association analysis in the founders; further, the additive effect of the QTLs transmitted to the descendants is a weighted (by the probabilities of transmission) average of the substitution effects of founders' haplotypes. The model allows for non-complete linkage disequilibrium QTL-markers in the founders. Two submodels are presented: a simple and easy to implement Haley-Knott type regression for half-sib families, and a general mixed (variance component) model for general pedigrees. The model can use information from all markers. The performance of the regression method is compared by simulation with a more complex IBD method by Meuwissen and Goddard. Numerical examples are provided. Conclusion The linear model theory provides a useful framework for QTL mapping with dense marker maps. Results show similar accuracies but a bias of the IBD method towards the center of the region. Computations for the linear regression model are extremely simple, in contrast with IBD methods. Extensions of the model to genomic selection and multi-QTL mapping are straightforward. PMID:19788745

  9. On Detecting Biospheres from Chemical Thermodynamic Disequilibrium in Planetary Atmospheres.

    PubMed

    Krissansen-Totton, Joshua; Bergsman, David S; Catling, David C

    2016-01-01

    Atmospheric chemical disequilibrium has been proposed as a method for detecting extraterrestrial biospheres from exoplanet observations. Chemical disequilibrium is potentially a generalized biosignature since it makes no assumptions about particular biogenic gases or metabolisms. Here, we present the first rigorous calculations of the thermodynamic chemical disequilibrium in Solar System atmospheres, in which we quantify the available Gibbs energy: the Gibbs free energy of an observed atmosphere minus that of atmospheric gases reacted to equilibrium. The purely gas phase disequilibrium in Earth's atmosphere is mostly attributable to O2 and CH4. The available Gibbs energy is not unusual compared to other Solar System atmospheres and smaller than that of Mars. However, Earth's fluid envelope contains an ocean, allowing gases to react with water and requiring a multiphase calculation with aqueous species. The disequilibrium in Earth's atmosphere-ocean system (in joules per mole of atmosphere) ranges from ∼20 to 2 × 10(6) times larger than the disequilibria of other atmospheres in the Solar System, where Mars is second to Earth. Only on Earth is the chemical disequilibrium energy comparable to the thermal energy per mole of atmosphere (excluding comparison to Titan with lakes, where quantification is precluded because the mean lake composition is unknown). Earth's disequilibrium is biogenic, mainly caused by the coexistence of N2, O2, and liquid water instead of more stable nitrate. In comparison, the O2-CH4 disequilibrium is minor, although kinetics requires a large CH4 flux into the atmosphere. We identify abiotic processes that cause disequilibrium in the other atmospheres. Our metric requires minimal assumptions and could potentially be calculated from observations of exoplanet atmospheres. However, further work is needed to establish whether thermodynamic disequilibrium is a practical exoplanet biosignature, requiring an assessment of false positives, noisy

  10. The current disequilibrium of North Cascade glaciers

    NASA Astrophysics Data System (ADS)

    Pelto, Mauri S.

    2006-03-01

    Three lines of evidence indicate that North Cascade (Washington, USA) glaciers are currently in a state of disequilibrium. First, annual balance measured on nine glaciers yields a mean cumulative balance for the 1984-2004 period of -8.58 m water equivalent (w.e.), a net loss of ice thickness exceeding 9.5 m. This is a significant loss for glaciers that average 30-50 m in thickness, representing 18-32% of their entire volume.Second, longitudinal profiles completed in 1984 and 2002 on 12 North Cascade glaciers confirm this volume change indicating a loss of -5.7 to -6.3 m in thickness (5.0-5.6 m w.e.) between 1984 and 2002, agreeing well with the measured cumulative balance of -5.52 m w.e. for the same period. The change in thickness on several glaciers has been equally substantial in the accumulation zone and the ablation zone, indicating that there is no point to which the glacier can retreat to achieve equilibrium. Substantial thinning along the entire length of a glacier is the key indicator that a glacier is in disequilibrium.Third, North Cascade glacier retreat is rapid and ubiquitous. All 47 glaciers monitored are currently undergoing significant retreat or, in the case of four, have disappeared. Two of the glaciers where mass balance observations were begun, Spider Glacier and Lewis Glacier, have disappeared. The retreat since 1984 of eight Mount Baker glaciers that were all advancing in 1975 has averaged 297 m. These observations indicate broad regional continuity in glacial response to climate.

  11. A model for linkage analysis with apomixis.

    PubMed

    Hou, Wei; Lin, Shen; Li, Yao; Pang, Xiaoming; Zeng, Yanru; Wu, Rongling

    2011-09-01

    Apomixis, or asexual reproduction through seeds, occurs in over 400 species of angiosperms. Although apomixis can favorably perpetuate desired genotypes through successive seed generation, it may also bring about some difficulty for linkage analysis and quantitative trait locus mapping. In this article, we explore the issue of how apomixis affects the precision and power of linkage analysis with molecular markers. We derive a statistical model for estimating the linkage between different markers when some progeny are derived from apomixis. The model was constructed within the maximum likelihood framework and implemented with the EM algorithm. A series of procedures are formulated to test the linkage of markers, the rate of apomixis, and the degree of genetic interference during meiosis. The model was examined and validated through simulation studies. The model will provide a tool for linkage mapping and evolutionary studies for plant species that undergo apomixis. PMID:21625991

  12. Disequilibrium in planetary atmospheres and the search for habitability

    NASA Astrophysics Data System (ADS)

    Simoncini, E.

    It has long been observed that Earth's atmosphere is uniquely far from its thermochemical equilibrium state in terms of its chemical composition. Studying this state of disequilibrium is important for its potential role in the detection of life on other suitable planets \\citep{Lovelock_1965,Kleidon_2010,Simoncini_2015}. We developed a methodology to calculate the extent of atmospheric chemical disequilibrium\\citep{Simoncini_2015,Kondepudi_1996}. This tool allows us to understand, on a thermodynamic basis, how life affected - and still affects - geochemical processes on Earth, and if other planetary atmospheres are habitable or have a disequilibrium similar to the Earth's one. A new computational framework called KROME has been applied to atmospheric models in order to give a correct computation of reactions´ kinetics \\citep{Grassi_2015}. In this work we present a first computation of the extent of disequilibrium for the present Earth atmosphere, considering the specific contribution of the different atmospheric processes, such as thermochemical reactions, eddy diffusion, photochemistry, deposition, and the effect of the biosphere. We then assess the effect of life on atmospheric disequilibrium of the Earth and provide a useful discussion about how the study of atmospheric disequilibrium can help in finding habitable (exo)planets. We finally compare the chemical disequilibrium of Earth and Mars atmospheres, for present and early conditions.

  13. Genome-wide linkage disequilibruim revealed by microsatellite markers and association study of fiber quality traits in cotton

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The application of association mapping based on existing genome-wide linkage disequilibrium (LD) between DNA polymorphisms and genes underlying traits is becoming powerful tool that overcome many limitations (high cost, poor resolution, requirement for bi-parentally crossed lines assessing only two ...

  14. Regeneration of Russian wildrye foundation seed and its effect on genetic diversity and linkage disequilibrium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintaining the genetic integrity and performance of released cultivars over multiple generations of seed increase continues to be of concern in cross-pollinating grasses. It is not an uncommon practice when seed supplies are low or foundation seed is not available to designate registered seed as f...

  15. Linkage Disequilibrium And Genome-Wide Association Studies In O. sativa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is increasing evidence that genome-wide association studies provide a powerful approach to find the genetic basis of complex phenotypic variation in all kinds of species. For this purpose, we developed the first generation 44K Affymetrix SNP array in rice (see Tung et al. poster). We genotyped...

  16. Population structure and linkage disequilibrium in US barley germplasm: implications for association mapping

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous studies have shown that there is considerable population structure in cultivated barley, with the strongest structure corresponding to differences in row number and growth habit. US barley breeding programs include 6-row and 2-row types and winter and spring types in all combinations. To fa...

  17. Population structure and linkage disequilibrium in Lupinus albus L. germplasm and its implication for association mapping

    Technology Transfer Automated Retrieval System (TEKTRAN)

    White lupin (Lupinus albus L.) has been around since 300 B.C. and is recognized for its ability to grow on poor soils and applications as green manure in addition to seed harvest. The seed has very high levels of protein (33-47%) and oil (6-13%). It also has many secondary metabolites that are pote...

  18. Linkage disequilibrium in the region of the autosomal dominant polycystic kidney disease gene (PKD1)

    SciTech Connect

    Snarey, A. ); Thomas, S.; Harris, P.C. ); Schneider, M.C. ); Pound, S.E.; Wright, A.F. ); Barton, N.; Somlo, S.; Germino, G.G.; Reeders, S.T.

    1994-08-01

    The gene for autosomal dominant polycystic kidney disease (PKD1) is located on chromosome 16p, between the flanking markers D16S84 and D16S125 (26.6 prox). This region is 750 kb long and has been cloned. The authors have looked at the association of 10 polymorphic markers from the region, with the disease and with each other. This was done in a set of Scottish families that had previously shown association with D16S94, a marker proximal to the PKD1 region. They report significant association between two CA repeat markers and the disease but have not found evidence for a single founder haplotype in these families, indicating the presence of several mutations in this population. Their results favor a location of the PKD1 gene in the proximal part of the candidate region. 25 refs., 1 fig., 4 tabs.

  19. Genetic diversity, linkage disequilibrium, and genome evolution in a soft winter wheat population

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Understanding genetic diversity within a crop is fundamental to its efficient exploitation. The advent of new high-throughput marker systems offers the opportunity to expand the scope and depth of our investigation of diversity. Our objectives were to analyze the genetic diversity of two populatio...

  20. Linkage Disequilibrium Among Two Lolium Perenne CBF Genes and Association With Freezing Susceptibility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Perennial ryegrass(Lolium perenne) is one of the most abundantly utilized forage and turfgrass species; however, its lack of tolerance to freezing temperatures relative to other forage/turf grasses limits its use. A pseudo-testcross genetic mapping population was previously developed for perennial ...

  1. Accuracy of genomic prediction in switchgrass (Panicum virgatum L.) improved by accounting for linkage disequilibrium

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Switchgrass is a relatively high-yielding and environmentally sustainable biomass crop, but further genetic gains in biomass yield must be achieved to make it an economically viable bioenergy feedstock. Genomic selection is an attractive technology to generate rapid genetic gains in switchgrass and ...

  2. An integrated approach to exploit linkage disequilibrium for ultra high dimensional genome-wide data

    Technology Transfer Automated Retrieval System (TEKTRAN)

    With the advent of recent DNA sequencing methods (determining molecule order) that quickly produce millions of DNA sequences, variation among sequences in a genome (all the DNA contained in chromosomes of an organism) can be tested for association with traits of economic interest on a relatively lar...

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

    PubMed Central

    Thompson, E A; Neel, J V

    1997-01-01

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

  4. Genomewide linkage scan of schizophrenia in a large multicenter pedigree sample using single nucleotide polymorphisms

    PubMed Central

    Holmans, PA; Riley, B; Pulver, AE; Owen, MJ; Wildenauer, DB; Gejman, PV; Mowry, BJ; Laurent, C; Kendler, KS; Nestadt, G; Williams, NM; Schwab, SG; Sanders, AR; Nertney, D; Mallet, J; Wormley, B; Lasseter, VK; O’Donovan, MC; Duan, J; Albus, M; Alexander, M; Godard, S; Ribble, R; Liang, KY; Norton, N; Maier, W; Papadimitriou, G; Walsh, D; Jay, M; O’Neill, A; Lerer, FB; Dikeos, D; Crowe, RR; Silverman, JM; Levinson, DF

    2008-01-01

    A genomewide linkage scan was carried out in eight clinical samples of informative schizophrenia families. After all quality control checks, the analysis of 707 European-ancestry families included 1,615 affected and 1,602 unaffected genotyped individuals, and the analysis of all 807 families included 1900 affected and 1839 unaffected individuals. Multipoint linkage analysis with correction for marker-marker linkage disequilibrium was carried out with 5,861 single nucleotide polymorphisms (SNPs; Illumina 4.0 linkage map). Suggestive evidence for linkage (European families) was observed on chromosomes 8p21, 8q24.1, 9q34 and 12q24.1 in non-parametric and/or parametric analyses. In a logistic regression allele-sharing analysis of linkage allowing for intersite heterogeneity, genomewide significant evidence for linkage was observed on chromosome 10p12. Significant heterogeneity was also observed on chromosome 22q11.1. Evidence for linkage across family sets and analyses was most consistent on chromosome 8p21, with a one-lod support interval that does not include the candidate gene NRG1, suggesting that one or more other susceptibility loci might exist in the region. In this era of genomewide association and deep resequencing studies, consensus linkage regions deserve continued attention, given that linkage signals can be produced by many types of genomic variation, including any combination of multiple common or rare SNPs or copy number variants in a region. PMID:19223858

  5. Probabilistic record linkage

    PubMed Central

    Sayers, Adrian; Ben-Shlomo, Yoav; Blom, Ashley W; Steele, Fiona

    2016-01-01

    Studies involving the use of probabilistic record linkage are becoming increasingly common. However, the methods underpinning probabilistic record linkage are not widely taught or understood, and therefore these studies can appear to be a ‘black box’ research tool. In this article, we aim to describe the process of probabilistic record linkage through a simple exemplar. We first introduce the concept of deterministic linkage and contrast this with probabilistic linkage. We illustrate each step of the process using a simple exemplar and describe the data structure required to perform a probabilistic linkage. We describe the process of calculating and interpreting matched weights and how to convert matched weights into posterior probabilities of a match using Bayes theorem. We conclude this article with a brief discussion of some of the computational demands of record linkage, how you might assess the quality of your linkage algorithm, and how epidemiologists can maximize the value of their record-linked research using robust record linkage methods. PMID:26686842

  6. Estimation of Particle Flux and Remineralization Rate from Radioactive Disequilibrium

    SciTech Connect

    Michael P. Bacon; Roger Francois

    2004-05-24

    Reactive radionuclides, such as the thorium isotopes, show measurable deficiencies in the oceanic water column because of their removal by chemical scavenging due to the particle flux. Measurement of the deficiency, coupled with measurement of the radionuclide concentration in particles, allows a determination of the effective particle sinking velocity. Results to date suggest that the effective particle sinking velocity is remarkably invariant with depth. This leads to the tentative suggestion that POC concentration profiles may, to a good approximation, be used directly to determine length scales for the remineralization of sinking organic matter. Further measurements are in progress to test this idea and to evaluate its limitations. Knowledge of the remineralization length scale is essential to an evaluation of the efficiency of the biological pump as a means for deep sequestering of carbon in the ocean.

  7. Thorium-uranium disequilibrium in a geothermal discharge zone at yellowstone

    NASA Astrophysics Data System (ADS)

    Sturchio, Neil C.; Binz, Carl M.; Lewis, Carter H., III

    1987-07-01

    Whole rock samples of hydrothermally-altered Biscuit Basin rhyolite from Yellowstone drill cores Y-7 and Y-8 were analyzed for 230Th, 234U, 238U, and 232Th. Extreme disequilibrium was found, with ( 230Th/ 234U) ranging from 0.30 to 1.27. Values of ( 230Th/ 232Th) and ( 234U/ 232Th) define a linear correlation with a slope of 0.16 ± 0.01, which corresponds to a ( 230Th/ 234U) age of approximately 19 ka. The ( 230Th/ 234U) disequilibrium was apparently caused by U redistribution which occurred mostly at about 19 ka, and is not related simply to the relative degree of hydrothermal alteration and self-sealing of the rhyolite. Mass balance of U requires a large flux of U-bearing groundwater through the rhyolite at the time of U redistribution; rough estimates of minimum water/rock ratio range from 10 2 to 10 4, for a range of possible groundwater U concentrations. Conservative hydraulic calculations indicate that the required groundwater flux could have occurred within a period of hundreds of years prior to self-sealing. The disequilibrium data are consistent with a model involving U redistribution during the initial stages of development of a geothermal discharge zone that formed in response to the hydrogeologic effects of glacial melting and unloading during the decline of the Pinedale Glaciation.

  8. Radium-thorium disequilibrium and zeolite-water ion exchange in a Yellowstone hydrothermal environment

    NASA Astrophysics Data System (ADS)

    Sturchio, N. C.; Bohlke, J. K.; Binz, C. M.

    1989-05-01

    Whole rock samples of hydrothermally altered Biscuit Basin rhyolite from Yellowstone drill cores Y-7 and Y-8 were analyzed for 226Ra and 230Th to determine the extent of radioactive disequilibrium and its relation to the rates and mechanisms of element transport in the shallow portion of an active hydrothermal system. The ( 226Ra/230Th) activity ratios range from 0.73 to 1.46 and are generally correlated with Th-normalized Ba concentrations (Ba N). Values of ( 226Ra/230Th) and Ba N > 1 were found in samples containing large modal fractions of clinoptilolite; whereas values of ( 226Ra/230Th) and Ba N < 1 were found in samples containing large modal fractions of mordenite. Composition clinoptilolite and mordenite in these samples are consistent with ion exchange equilibrium between zeolites and coexisting thermal waters. Average K d mineral-waterBa values are 1.0·10 5 mL/g for clinoptilolite and 1.4·10 4 mL/g for mordenite. Apparent diffustvities through matrix porosity estimated for Ra and Ba range from ˜10 -12 to ˜10 -10 cm 2s -1 in thoroughly zeolitic rhyolite; these rates of diffusion are too low to account for the observed distance scale of ( 226Ra/230Th) disequilibrium. The correlated values of ( 226Ra /230Th) disequilibrium and Ba N represent zeolite-water ion exchange equilibrium that is caused by porous flow of water through the rock matrix and by the relatively rapid diffusion of cations within the zeolite lattices. A water flux of at least ˜2.5 ( cm water3/cm rock3) yr -1 is required to produce measurable ( 226Ra/230Th) disequilibrium, whereas at least ˜23 ( cm water3/cm rock3) yr -1 is r for the sample exhibiting the most extreme ( 226Ra/230Th) disequilibrium; these fluxes are much higher than those that can be inferred from net mass transfers of stable species. The zeolite-water ion exchange process appears to have been operating for at least 8000 yr in the environment of the Y-7 and Y-8 drill holes.

  9. Radium-thorium disequilibrium and zeolite-water ion exchange in a Yellowstone hydrothermal environment

    SciTech Connect

    Sturchio, N.C.; Bohlke, J.K. ); Binz, C.M. )

    1989-05-01

    Whole rock samples of hydrothermally altered Biscuit Basin rhyolite from Yellowstone drill cores Y-7 and Y-8 were analyzed for {sup 226}Ra and {sup 230}Th to determine the extent of radioactive disequilibrium and its relation to the rates and mechanisms of element transport in the shallow portion of an active hydrothermal system. The ({sup 226}Ra/{sup 230}Th) activity ratios range from 0.73 to 1.46 and are generally correlated with Th-normalized Ba concentrations (Ba{sub N}). Compositions of clinoptilolite and mordenite in these samples are consistent with ion exchange equilibrium between zeolites and coexisting thermal waters. Average K{sup Ba}{sub d mineral-water} values are 1.0 {center dot} 10{sup 5} mL/g for clinoptilolite and 1.4 {center dot} 10{sup 4} mL/g for mordenite. Apparent diffusivities through matrix porosity estimated for R and Ba range from {approximately}10{sup {minus}12} to {approximately}10{sup {minus}10} cm{sup 2} s{sup {minus}1} in thoroughly zeolitic rhyolite; these rates of diffusion are too low to account for the observed distance scale of ({sup 226}Ra/{sup 230}Th) disequilibrium. The correlated values of ({sup 226}Ra/{sup 230}Th) disequilibrium and Ba{sub N} represent zeolite-water ion exchange equilibrium that is caused by porous flow of water through the rock matrix and by the relatively rapid diffusion of cations within the zeolite lattices. A water flux of at least {approximately}2.5 (cm{sup 3}{sub water}/cm{sup 3}{sub rock}) yr{sup {minus}1} is required to produce measurable ({sup 226}Ra/{sup 230}Th) disequilibrium, whereas at least {approximately}23 (cm{sup 3}{sub water}/cm{sup 3}{sub rock}) yr{sup {minus}1} is required for the sample exhibiting the most extreme ({sup 226}Ra/{sup 230}Th) disequilibrium; these fluxes are much higher than those that can be inferred from net mass transfers of stable species.

  10. Linkage of Inflammatory Bowel Disease to Human Chromosome 6p

    PubMed Central

    Hampe, Jochen; Shaw, Sarah H.; Saiz, Robert; Leysens, Nancy; Lantermann, Annette; Mascheretti, Silvia; Lynch, Nicholas J.; MacPherson, Andrew J. S.; Bridger, Stephen; van Deventer, Sander; Stokkers, Pieter; Morin, Phil; Mirza, Mudassar M.; Forbes, Alastair; Lennard-Jones, John E.; Mathew, Christopher G.; Curran, Mark E.; Schreiber, Stefan

    1999-01-01

    Summary Inflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation. IBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Given the immunologic dysregulation in IBD, the human-leukocyte-antigen region on chromosome 6p is of significant interest. Previous association and linkage analysis has provided conflicting evidence as to the existence of an IBD-susceptibility locus in this region. Here we report on a two-stage linkage and association analysis of both a basic population of 353 affected sibling pairs (ASPs) and an extension of this population to 428 white ASPs of northern European extraction. Twenty-eight microsatellite markers on chromosome 6 were genotyped. A peak multipoint LOD score of 4.2 was observed, at D6S461, for the IBD phenotype. A transmission/disequilibrium test (TDT) result of P=.006 was detected for D6S426 in the basic population and was confirmed in the extended cohort (P=.004; 97 vs. 56 transmissions). The subphenotypes of Crohn disease, ulcerative colitis, and mixed IBD contributed equally to this linkage, suggesting a general role for the chromosome 6 locus in IBD. Analysis of five single-nucleotide polymorphisms in the TNFA and LTA genes did not reveal evidence for association of these important candidate genes with IBD. In summary, we provide firm linkage evidence for an IBD-susceptibility locus on chromosome 6p and demonstrate that TNFA and LTA are unlikely to be susceptibility loci for IBD. PMID:10577918

  11. THE ROLE OF TEMPERATURE DISEQUILIBRIUM IN MONITORING LOW VOLATILITY CONTAMINANT MIGRATION

    EPA Science Inventory

    Temperature disequilibrium is a common phenomenon within and among envirornnental media at local regional continental and global scales. The significance of temperature disequilibrium on low vapor pressure environmental contaminant migration has only rarely been addressed in the ...

  12. Linkage results in Schizophrenia

    SciTech Connect

    Baron, M.

    1996-04-09

    In setting a model for replication studies, the collective effort by the various investigators is praiseworthy. The linkage reported is intriguing, but given the aforementioned caveats it would be premature to dub it {open_quotes}significant -- and, probably, confirmed.{close_quotes} The extent to which a real genetic effect exists on chromosome 6p24-22 remains to be seen. Compelling confirmation, which further study might proffer, would be a welcome boost to a fledgling enterprise, where other findings of promise have faltered or failed to gain unequivocal support. The caution advised in this commentary may guide the design and interpretation of other linkage studies in psychiatric disorders.

  13. The Market Linkage.

    ERIC Educational Resources Information Center

    Fuchs, Victor E.

    The Market Linkage Project (ML) for Special Education and the Basic Skills Validation and Marketing Program are two federally sponsored marketing projects developed under contract by LINC Resources, Inc., a professional marketing organization, for the U.S. Department of Education. LINC developed the marketing programs to provide the option for the…

  14. Transitions and Linkages.

    ERIC Educational Resources Information Center

    Ilfeld, Ellen M., Ed.; Hanssen, Elizabeth, Ed.

    1997-01-01

    If children are to benefit from a healthy, supportive early childhood experience, it is important to strengthen transitions between early childhood experiences in educational and care settings and the more formal educational system. This issue of Coordinator's Notebook focuses on strengthening linkages and transitions between home, preschool, and…

  15. Thirty-seven candidate genes for polycystic ovary syndrome: Strongest evidence for linkage is with follistatin

    PubMed Central

    Urbanek, Margrit; Legro, Richard S.; Driscoll, Deborah A.; Azziz, Ricardo; Ehrmann, David A.; Norman, Robert J.; Strauss, Jerome F.; Spielman, Richard S.; Dunaif, Andrea

    1999-01-01

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women, characterized by hyperandrogenism and chronic anovulation. It is a leading cause of female infertility and is associated with polycystic ovaries, hirsutism, obesity, and insulin resistance. We tested a carefully chosen collection of 37 candidate genes for linkage and association with PCOS or hyperandrogenemia in data from 150 families. The strongest evidence for linkage was with the follistatin gene, for which affected sisters showed increased identity by descent (72%; χ2 = 12.97; nominal P = 3.2 × 10−4). After correction for multiple testing (33 tests), the follistatin findings were still highly significant (Pc = 0.01). Although the linkage results for CYP11A were also nominally significant (P = 0.02), they were no longer significant after correction. In 11 candidate gene regions, at least one allele showed nominally significant evidence for population association with PCOS in the transmission/disequilibrium test (χ2 ≥ 3.84; nominal P < 0.05). The strongest effect in the transmission/disequilibrium test was observed in the INSR region (D19S884; allele 5; χ2 = 8.53) but was not significant after correction. Our study shows how a systematic screen of candidate genes can provide strong evidence for genetic linkage in complex diseases and can identify those genes that should have high (or low) priority for further study. PMID:10411917

  16. Thorium-uranium disequilibrium in a geothermal discharge zone at Yellowstone

    SciTech Connect

    Sturchio, N.C.; Binz, C.M.; Lewis C.H. III

    1987-07-01

    Whole rock samples of hydrothermally-altered Biscuit Basin rhyolite from Yellowstone drill cores Y-7 and Y-8 were analyzed for /sup 230/Th, /sup 234/U, /sup 238/U, and /sup 232/Th. Extreme disequilibrium was found, with (/sup 230/Th//sup 234/U) ranging from 0.30 to 1.27. Values of (/sup 230/Th//sup 232/Th) and (/sup 234/U//sup 232/Th) define a linear correlation with a slope of 0.16 +/- 0.01, which corresponds to a (/sup 230/Th//sup 234/) age of approximately 19 ka. The (/sup 230/Th//sup 234/U) disequilibrium was apparently caused by U redistribution which occurred mostly at about 19 ka, and is not related simply to the relative degree of hydrothermal alteration and self-sealing of the rhyolite. Mass balance of U requires a large flux of U-bearing ground water through the rhyolite at the time of U redistribution; rough estimates of minimum water/rock ratio range from 10/sup 2/ to 10/sup 4/, for a range of possible ground water U concentrations. Conservative hydraulic calculations indicate that the required ground water flux could have occurred within a period of hundreds of years prior to self-sealing. The disequilibrium data are consistent with a model involving U redistribution during the initial stages of development of a geothermal discharge zone that formed in response to the hydrogeologic effects of glacial melting and unloading during the decline of the Pinedale Glaciation.

  17. Chemical evolution of the Earth: Equilibrium or disequilibrium process?

    NASA Technical Reports Server (NTRS)

    Sato, M.

    1985-01-01

    To explain the apparent chemical incompatibility of the Earth's core and mantle or the disequilibrium process, various core forming mechanisms have been proposed, i.e., rapid disequilibrium sinking of molten iron, an oxidized core or protocore materials, and meteorite contamination of the upper mantle after separation from the core. Adopting concepts used in steady state thermodynamics, a method is devised for evaluating how elements should distribute stable in the Earth's interior for the present gradients of temperature, pressure, and gravitational acceleration. Thermochemical modeling gives useful insights into the nature of chemical evolution of the Earth without overly speculative assumptions. Further work must be done to reconcile siderophile elements, rare gases, and possible light elements in the outer core.

  18. A microsatellite-based linkage map for song sparrows (Melospiza melodia).

    PubMed

    Nietlisbach, Pirmin; Camenisch, Glauco; Bucher, Thomas; Slate, Jon; Keller, Lukas F; Postma, Erik

    2015-11-01

    Although linkage maps are important tools in evolutionary biology, their availability for wild populations is limited. The population of song sparrows (Melospiza melodia) on Mandarte Island, Canada, is among the more intensively studied wild animal populations. Its long-term pedigree data, together with extensive genetic sampling, have allowed the study of a range of questions in evolutionary biology and ecology. However, the availability of genetic markers has been limited. We here describe 191 new microsatellite loci, including 160 high-quality polymorphic autosomal, 7 Z-linked and 1 W-linked markers. We used these markers to construct a linkage map for song sparrows with a total sex-averaged map length of 1731 cM and covering 35 linkage groups, and hence, these markers cover most of the 38-40 chromosomes. Female and male map lengths did not differ significantly. We then bioinformatically mapped these loci to the zebra finch (Taeniopygia guttata) genome and found that linkage groups were conserved between song sparrows and zebra finches. Compared to the zebra finch, marker order within small linkage groups was well conserved, whereas the larger linkage groups showed some intrachromosomal rearrangements. Finally, we show that as expected, recombination frequency between linked loci explained the majority of variation in gametic phase disequilibrium. Yet, there was substantial overlap in gametic phase disequilibrium between pairs of linked and unlinked loci. Given that the microsatellites described here lie on 35 of the 38-40 chromosomes, these markers will be useful for studies in this species, as well as for comparative genomics studies with other species. PMID:25865627

  19. Model-free linkage analysis using likelihoods

    SciTech Connect

    Curtis, D.; Sham, P.C.

    1995-09-01

    Misspecification of transmission model parameters can produce artifactually lod scores at small recombination fractions and in multipoint analysis. To avoid this problem, we have tried to devise a test that aims to detect a genetic effect at a particular locus, rather than attempting to estimate the map position of a locus with specified effect. Maximizing likelihoods over transmission model parameters, as well as linkage parameters, can produce seriously biased parameter estimates and so yield tests that lack power for the detection of linkage. However, constraining the transmission model parameters to produce the correct population prevalence largely avoids this problem. For computational convenience, we recommend that the likelihoods under linkage and nonlinkage are independently maximized over a limited set of transmission models, ranging from Mendelian dominant to null effect and from null effect to Mendelian recessive. In order to test for a genetic effect at a given map position, the likelihood under linkage is maximized over admixture, the proportion of families linked. Application to simulated data for a wide range of transmission models in both affected sib pairs and pedigrees demonstrates that the new method is well behaved under the null hypothesis and provides a powerful test for linkage when it is present. This test requires no specification of transmission model parameters, apart from an approximate estimate of the population prevalence. It can be applied equally to sib pairs and pedigrees, and, since it does not diminish the lod score at test positions very close to a marker, it is suitable for application to multipoint data. 24 refs., 1 fig., 4 tabs.

  20. Demographic Disequilibrium in Early Twentieth Century Thailand: Falling Mortality, Rising Fertility, or Both?

    PubMed Central

    Carmichael, Gordon A.

    2011-01-01

    Estimates of Thai crude birth and death rates date from 1920 when the former was around 20 per thousand higher than the latter, implying natural increase of 2 percent per annum. Such disequilibrium cannot have been the norm over the long term historical past, when population growth must have been comparatively slow. This paper explores the bases for likely past relative equilibrium between Siamese birth and death rates, then seeks to explain the disequilibrium apparent by 1920. Classic demographic transition theory postulates initially high birth and death rates, this equilibrium eventually being broken by falling mortality. In Thailand, however, there is likely to have been both significant mortality decline and appreciable fertility increase after 1850, as the virtual elimination of indigenous warfare, rapid growth of the export rice economy and the demise of slavery and corvée labour created a new domestic environment. Characterized by more dispersed, often frontier, settlement, this environment was unprecedentedly sedate and settled, afforded ordinary households a previously unknown level of control over their resources of labour, and generated optimism about prospects for the next generation. PMID:21966299

  1. Infinite dimensional variational inequalities and dynamic network disequilibrium modeling

    SciTech Connect

    Friesz, T.; Bernstein, D.

    1994-12-31

    In this paper we explain the importance of modeling disequilibrium flow patterns occurring on networks, with special emphasis on automobile networks and the role of information technology. We show how elementary notions of disequilibrium, whether abstract, physical or economic in nature, give rise to an adjustment process expressible as a dynamical system. We comment that when such a system is autonomous its steady states can be given the traditional finite dimensional variational inequality/fixed point representations common to static network equilibria. Beyond this, and unique to our work, we show that if the disequilibrium dynamical system is nonautonomous it may tend toward moving or dynamic (instead of static) network equilibria expressible as infinite dimensional variational inequalities. Using concepts of fast and slow dynamic systems, we show how day-to-day and within-day aspects of automobile travel decision making can be combined to yield a nonautonomous dynamical system with the mathematical properties reviewed previously. We introduce axioms for a proper predictive model of urban network flows which integrates both day-to-day and within-day considerations and postulate one such model for further study.

  2. Disequilibrium dihedral angles in dolerite sills

    USGS Publications Warehouse

    Holness, Marian B.; Richardson, Chris; Helz, Rosalind T.

    2012-01-01

    The geometry of clinopyroxene-plagioclase-plagioclase junctions in mafic rocks, measured by the median dihedral angle Θcpp, is created during solidification. In the solidifying Kilauea Iki (Hawaii) lava lake, the wider junctions between plagioclase grains are the first to be filled by pyroxene, followed by the narrower junctions. The final Θcpp, attained when all clinopyroxene-plagioclase-plagioclase junctions are formed, is 78° in the upper crust of the lake, and 85° in the lower solidification front. Θcpp in the 3.5-m-thick Traigh Bhàn na Sgùrra sill (Inner Hebrides) is everywhere 78°. In the Whin Sill (northern England, 38 m thick) and the Portal Peak sill (Antarctica, 129 m thick), Θcpp varies symmetrically, with the lowest values at the margins. The 266-m-thick Basement Sill (Antarctica) has asymmetric variation of Θcpp, attributed to a complex filling history. The chilled margins of the Basement Sill are partially texturally equilibrated, with high Θcpp. The plagioclase grain size in the two widest sills varies asymmetrically, with the coarsest rocks found in the upper third. Both Θcpp and average grain size are functions of model crystallization times. Θcpp increases from 78° to a maximum of ∼100° as the crystallization time increases from 1 to 500 yr. Because the use of grain size as a measure of crystallization time is dependent on an estimate of crystal growth rates, dihedral angles provide a more direct proxy for cooling rates in dolerites.

  3. Preliminary U-series disequilibrium and thermoluminescence ages of surficial deposits and paleosols associated with Quaternary faults, eastern Yucca Mountain

    SciTech Connect

    Paces, J.B.; Menges, C.M.; Bush, C.A.; Futa, K.; Millard, H.T.; Maat, P.B.; Whitney, J.W.; Widmann, B.; Wesling, J.R.

    1994-12-31

    Geochronological control is an essential component of paleoseismic evaluation of faults in the Yucca Mountain region. New U-series disequilibrium and thermoluminescence age estimates for pedogenic deposits that bracket surface-rupture events are presented from four sites exposing the Paintbrush Canyon, Bow Ridge and Stagecoach Road faults. Ages show an internal consistency with stratigraphic relationships as well as an overall concordancy between the two independent geochronometers. Age estimates are therefore interpreted to date depositional events or episodes of pedogenic carbonate mobility that can be used to establish a paleoseismic fault chronology. Ultimately, this type of chronological information will be used to evaluate seismic hazards at Yucca Mountain.

  4. Preliminary U-series disequilibrium and thermoluminescence ages of surficial deposits and paleosols associated with Quaternary fault, Eastern Yucca Mountain

    SciTech Connect

    Paces, J.B.; Menges, C.M.; Bush, C.A.; Futa, K.; Millard, H.T.; Maat, P.B.; Whitney, J.W.; Widmann, B.; Wesling, J.R.

    1994-12-31

    Geochronological control is an essential component of paleoseismic evaluation of faults in the Yucca Mountain region. New U-series disequilibrium and thermoluminescence age estimates for pedogenic deposits that bracket surface-rupture events are presented from four sites exposing the Paintbrush Canyon, Bow Ridge and Stagecoach Road faults. Ages show an internal consistency with stratigraphic relationships as well as an overall concordancy between the two independent geochronometers. Age estimates are therefore interpreted to date depositional events or episodes of pedogenic carbonate mobility that can be used to establish a paleoseismic fault chronology. Ultimately, this type of chronological information will be used to evaluate seismic hazards at Yucca Mountain.

  5. [sup 226]Ra-[sup 230]Th disequilibrium in axial and off-axis mid-ocean ridge basalts

    SciTech Connect

    Volpe, A.M.; Goldstein, S.J. Los Alamos National Lab., NM )

    1993-03-01

    The authors describe [sup 226]Ra-[sup 230]Th disequilibrium in mid-ocean ridge basalt (MORB) glasses from the Juan de Fuca, Gorda, and East Pacific ridges. These first mass spectrometric measurements of [sup 226]Ra in MORB glasses at sub-picogram abundance levels confirm the large excesses over [sup 230]Th determined by radon-emanation techniques and alpha spectrometry. All off-axis MORB glasses have [sup 226]Ra-[sup 230]Th and [sup 234]U-[sup 238]U in secular equilibrium. This suggests that magmatic processes, not secondary post-eruption alteration, generate [sup 238]U-series disequilibrium in these MORB. Least evolved, N-MORB from axial valleys have ([sup 226]Ra/[sup 230]Th) between 2.2-2.3. Differentiated and enriched E-type MORB have consistently low ([sup 226]Ra/[sup 230]Th) ratios compared with N-MORB from the same ridge sections. Ra-Th fractionation may be less pronounced, or magma residence-transit periods may be long for differentiated MORB. Also, E-MORB may be generated by different melt extraction volumes and rates. Estimated [sup 226]Ra-[sup 230]Th ages for N-MORB agree with location on and off ridge segments, and with Th-U model ages. These preliminary results show that [sup 226]Ra-[sup 230]Th disequilibrium could be used to quantify volcanic episodicity at ocean ridges. 39 refs., 6 figs., 4 tabs.

  6. Some methods for blindfolded record linkage

    PubMed Central

    Churches, Tim; Christen, Peter

    2004-01-01

    Background The linkage of records which refer to the same entity in separate data collections is a common requirement in public health and biomedical research. Traditionally, record linkage techniques have required that all the identifying data in which links are sought be revealed to at least one party, often a third party. This necessarily invades personal privacy and requires complete trust in the intentions of that party and their ability to maintain security and confidentiality. Dusserre, Quantin, Bouzelat and colleagues have demonstrated that it is possible to use secure one-way hash transformations to carry out follow-up epidemiological studies without any party having to reveal identifying information about any of the subjects – a technique which we refer to as "blindfolded record linkage". A limitation of their method is that only exact comparisons of values are possible, although phonetic encoding of names and other strings can be used to allow for some types of typographical variation and data errors. Methods A method is described which permits the calculation of a general similarity measure, the n-gram score, without having to reveal the data being compared, albeit at some cost in computation and data communication. This method can be combined with public key cryptography and automatic estimation of linkage model parameters to create an overall system for blindfolded record linkage. Results The system described offers good protection against misdeeds or security failures by any one party, but remains vulnerable to collusion between or simultaneous compromise of two or more parties involved in the linkage operation. In order to reduce the likelihood of this, the use of last-minute allocation of tasks to substitutable servers is proposed. Proof-of-concept computer programmes written in the Python programming language are provided to illustrate the similarity comparison protocol. Conclusion Although the protocols described in this paper are not

  7. Dialysis disequilibrium syndrome occurring during continuous renal replacement therapy

    PubMed Central

    Tuchman, Shamir; Khademian, Zarir P.; Mistry, Kirtida

    2013-01-01

    The dialysis disequilibrium syndrome (DDS) is characterized by progressive neurological symptoms and signs attributable to cerebral edema that occurs due to fluid shifts into the brain following a relatively rapid decrease in serum osmolality during hemodialysis (HD). Since continuous renal replacement therapy (CRRT) is less efficient at solute clearance than intermittent HD, it seems logical that this mode of therapy is less likely to cause DDS. This entity has not been previously reported to occur with this modality. Here, we report two cases of DDS associated with CRRT that provide insights into its pathophysiological mechanisms and suggest strategies for its prevention. PMID:26120445

  8. LINKAGE programs: linkage analysis for monogenic cardiovascular diseases.

    PubMed

    Li, Lin; Wang, Qing K; Rao, Shaoqi

    2006-01-01

    Identification of the genes for a human disease provides significant insights into the molecular mechanism underlying the pathogenesis of the disease. A human disease gene can be identified by its chromosomal location (positional cloning). Linkage analysis is a key step in positional cloning. For monogenic disorders with a known inheritance pattern, model-based linkage analysis is effective in mapping the disease location. Therefore, model-based linkage analysis can provide a powerful tool to positional cloning of some specific molecular determinants that co-segregate with disease phenotypes in the isolated samples (e.g., large and multiplex impaired pedigrees). This chapter describes model-based human genetic linkage analysis as implemented in the LINKAGE computer package. First, we introduce the basic concepts and principles for genetic analysis of monogenic disorders. Then, we demonstrate the usages of the programs by analyzing several examples of hypothetical pedigrees with the inheritance modes of autosomal-dominant, autosomal-recessive, and genetic heterogeneity. PMID:17071989

  9. Estimate of effective recombination rate and average selection coefficient for HIV in chronic infection

    PubMed Central

    Batorsky, Rebecca; Kearney, Mary F.; Palmer, Sarah E.; Maldarelli, Frank; Rouzine, Igor M.; Coffin, John M.

    2011-01-01

    HIV adaptation to a host in chronic infection is simulated by means of a Monte-Carlo algorithm that includes the evolutionary factors of mutation, positive selection with varying strength among sites, random genetic drift, linkage, and recombination. By comparing two sensitive measures of linkage disequilibrium (LD) and the number of diverse sites measured in simulation to patient data from one-time samples of pol gene obtained by single-genome sequencing from representative untreated patients, we estimate the effective recombination rate and the average selection coefficient to be on the order of 1% per genome per generation (10−5 per base per generation) and 0.5%, respectively. The adaptation rate is twofold higher and fourfold lower than predicted in the absence of recombination and in the limit of very frequent recombination, respectively. The level of LD and the number of diverse sites observed in data also range between the values predicted in simulation for these two limiting cases. These results demonstrate the critical importance of finite population size, linkage, and recombination in HIV evolution. PMID:21436045

  10. Estimating the proportion of variation in susceptibility to multiple sclerosis captured by common SNPs

    NASA Astrophysics Data System (ADS)

    Watson, Corey T.; Disanto, Giulio; Breden, Felix; Giovannoni, Gavin; Ramagopalan, Sreeram V.

    2012-10-01

    Multiple sclerosis (MS) is a complex disease with underlying genetic and environmental factors. Although the contribution of alleles within the major histocompatibility complex (MHC) are known to exert strong effects on MS risk, much remains to be learned about the contributions of loci with more modest effects identified by genome-wide association studies (GWASs), as well as loci that remain undiscovered. We use a recently developed method to estimate the proportion of variance in disease liability explained by 475,806 single nucleotide polymorphisms (SNPs) genotyped in 1,854 MS cases and 5,164 controls. We reveal that ~30% of MS genetic liability is explained by SNPs in this dataset, the majority of which is accounted for by common variants. These results suggest that the unaccounted for proportion could be explained by variants that are in imperfect linkage disequilibrium with common GWAS SNPs, highlighting the potential importance of rare variants in the susceptibility to MS.

  11. Plagioclase-melt (dis)equilibrium due to cooling dynamics: Implications for thermometry, barometry and hygrometry

    NASA Astrophysics Data System (ADS)

    Mollo, Silvio; Putirka, Keith; Iezzi, Gianluca; Del Gaudio, Pierdomenico; Scarlato, Piergiorgio

    2011-07-01

    The compositional variation of plagioclase and the partitioning of major elements between plagioclase and melt have been experimentally measured as a function of the cooling rate. Crystals were grown from a basaltic melt at a pressure of 500 MPa under (i) variable cooling rates of 0.5, 2.1, 3, 9.4, and 15 °C/min from 1250 °C down to 1000 °C, (ii) quenching temperatures of 1025, 1050, 1075, 1090, and 1100 °C at the fixed cooling rate of 0.5 °C/min, and (iii) isothermal temperatures of 1000, 1025, 1050, 1075, 1090, and 1100 °C. Our results show that euhedral, faceted plagioclases form during isothermal and slower cooling experiments exhibiting idiomorphic tabular shapes. In contrast, dendritic shapes are observed from faster cooled charges. As the cooling rate is increased, concentrations of Al + Ca + Fe + Mg increase and Si + Na + K decrease in plagioclase favoring higher An and lower Ab + Or contents. Significant variations of pl-liqKd are also observed by the comparison between isothermal and cooled charges; notably, pl-liqKdAb-An, pl-liqKdCa-Na and pl-liqKdFe-Mg progressively change with increasing cooling rate. Therefore, crystal-melt exchange reactions have the potential to reveal the departure from equilibrium for plagioclase-bearing cooling magmas. Finally, thermometers, barometers, and hygrometers derived through the plagioclase-liquid equilibria have been tested at these non-equilibrium experimental conditions. Since such models are based on assumption of equilibrium, any form of disequilibrium will yield errors. Results show that errors on estimates of temperature, pressure, and melt-water content increase systematically with increasing cooling rate (i.e. disequilibrium condition) depicting monotonic trends towards drastic overestimates. These trends are perfectly correlated with those of pl-liqKdCa-Na, pl-liqKdAb-An, and pl-liqKdFe-Mg, thus demonstrating their ability to test (dis)equilibrium conditions.

  12. Local thermodynamic equilibrium for globally disequilibrium open systems under stress

    NASA Astrophysics Data System (ADS)

    Podladchikov, Yury

    2016-04-01

    Predictive modeling of far and near equilibrium processes is essential for understanding of patterns formation and for quantifying of natural processes that are never in global equilibrium. Methods of both equilibrium and non-equilibrium thermodynamics are needed and have to be combined. For example, predicting temperature evolution due to heat conduction requires simultaneous use of equilibrium relationship between internal energy and temperature via heat capacity (the caloric equation of state) and disequilibrium relationship between heat flux and temperature gradient. Similarly, modeling of rocks deforming under stress, reactions in system open for the porous fluid flow, or kinetic overstepping of the equilibrium reaction boundary necessarily needs both equilibrium and disequilibrium material properties measured under fundamentally different laboratory conditions. Classical irreversible thermodynamics (CIT) is the well-developed discipline providing the working recipes for the combined application of mutually exclusive experimental data such as density and chemical potential at rest under constant pressure and temperature and viscosity of the flow under stress. Several examples will be presented.

  13. Genomic Scans of Zygotic Disequilibrium and Epistatic SNPs in HapMap Phase III Populations

    PubMed Central

    Hu, Xin-Sheng; Hu, Yang

    2015-01-01

    Previous theory indicates that zygotic linkage disequilibrium (LD) is more informative than gametic or composite digenic LD in revealing natural population history. Further, the difference between the composite digenic and maximum zygotic LDs can be used to detect epistatic selection for fitness. Here we corroborate the theory by investigating genome-wide zygotic LDs in HapMap phase III human populations. Results show that non-Africa populations have much more significant zygotic LDs than do Africa populations. Africa populations (ASW, LWK, MKK, and YRI) possess more significant zygotic LDs for the double-homozygotes (DAABB) than any other significant zygotic LDs (DAABb, DAaBB, and DAaBb), while non-Africa populations generally have more significant DAaBb’s than any other significant zygotic LDs (DAABB, DAABb, and DAaBB). Average r-squares for any significant zygotic LDs increase generally in an order of populations YRI, MKK, CEU, CHB, LWK, JPT, CHD, TSI, GIH, ASW, and MEX. Average r-squares are greater for DAABB and DAaBb than for DAaBB and DAABb in each population. YRI and MKK can be separated from LWK and ASW in terms of the pattern of average r-squares. All population divergences in zygotic LDs can be interpreted with the model of Out of Africa for modern human origins. We have also detected 19735-95921 SNP pairs exhibiting strong signals of epistatic selection in different populations. Gene-gene interactions for some epistatic SNP pairs are evident from empirical findings, but many more epistatic SNP pairs await evidence. Common epistatic SNP pairs rarely exist among all populations, but exist in distinct regions (Africa, Europe, and East Asia), which helps to understand geographical genomic medicine. PMID:26126177

  14. Characterization of genetic diversity and linkage disequilibrium of ZmLOX4 and ZmLOX5 loci in maize.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maize lipoxygenases (ZmLOXs) are well recognized as important players in plant defense against pathogens, especially in cross kingdom lipid communication with pathogenic fungi. This study is among the first to investigate genetic diversity at important gene paralogs ZmLOX4 and ZmLOX5 believed to be...

  15. Pair-wise linkage disequilibrium decay among linked loci suggests meiotic recombination in natural populations of Sclerotinia sclerotiorum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Both clonal and recombining population structures have been reported in Sclerotinia sclerotiorum populations around the world. Association of independent and putatively unlinked markers indicates clonal population structure, whereas random association of the markers suggests recombination and outcro...

  16. Molecular diversity and genome-wide linkage disequilibrium patterns in a worldwide collection of Oryza sativa and its wild relatives

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marker-trait association mapping techniques were first developed by computational biologists to analyze the genotypes of individual people in human populations and subsequently identify DNA markers associated with important traits, especially diseases. If populations of agronomically important crop...

  17. Genetic Diversity, Population Structure and Linkage Disequilibrium in U.S. Elite Winter Wheat (Triticum Aestivum L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Information on genetic diversity and population structure of elite wheat breeding lines promotes effective use of genetic resources. We analyzed 205 elite wheat breeding lines from major winter wheat breeding programs in the U.S.A. using 245 markers across the wheat genomes. This collection showed a...

  18. Population Structure, Linkage Disequilibrium, and Genetic Diversity in Soft Winter Wheat Enriched for Fusarium Head Blight Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The occurrence of epidemics of Fusarium head blight (FHB), caused by Fusarium graminearum Schwabe, in U.S. winter wheat (Triticum aestivum L.) during the past two decades has resulted in increased emphasis on development of resistant cultivars. Understanding the effect of focused breeding efforts fo...

  19. Linkage Disequilibrium Based Association Mapping of Fiber Quality Traits in Cotton Using Diverse Cotton Germplasm from Uzbekistan

    Technology Transfer Automated Retrieval System (TEKTRAN)

    QTL-mapping, a now-classical approach to identify molecular markers linked to complex traits in specific experimental populations, is extremely time-consuming, high-risk, and expensive work - prohibitively expensive if dozens, let alone hundreds or thousands, of germplasm accessions are to be examin...

  20. Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans.

    PubMed

    Ban, Maria; Booth, David; Heard, Robert; Stewart, Graeme; Goris, An; Vandenbroeck, Koen; Dubois, Bénédicte; Laaksonen, Mikko; Ilonen, Jorma; Alizadeh, Mehdi; Edan, Gilles; Babron, Marie Claude; Brassat, David; Clanet, Michael; Cournu-Rebeix, Isabelle; Fontaine, Bertrand; Semana, Gilbert; Goedde, Rene; Epplen, Jorg; Weber, Alexandra; Infante-Duarte, Carmen; Zipp, Frauke; Rajda, Cecilia; Bencsik, Krisztina; Vécsei, László; Heggarty, Shirley; Graham, Colin; Hawkins, Stanley; Liguori, Maria; Momigliano-Richiardi, Patricia; Caputo, Domenico; Grimaldi, Luigi M E; Leone, Maurizio; Massacesi, Luca; Milanese, Clara; Salvetti, Marco; Savettieri, Giovani; Trojano, Maria; Bielecki, Bartosz; Mycko, Marcin P; Selmaj, Krzysztof; Santos, Monica; Maciel, Patricia; Pereira, Clara; Silva, Ana; Silva, Berta Martins; Coraddu, Francesca; Marrosu, Maria Giovanna; Akesson, Eva; Hillert, Jan; Datta, Pameli; Oturai, Annette; Harbo, Hanne F; Spurkland, Anne; Goertsches, Robert; Villoslada, Pablo; Eraksoy, Mefkure; Hensiek, Anke; Compston, Alastair; Setakis, Efrosini; Gray, Julia; Yeo, Tai Wai; Sawcer, Stephen

    2006-10-01

    By combining all the data available from the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) project, we have been able to identify 17 microsatellite markers showing consistent evidence for apparent association. As might be expected five of these markers map within the Major Histocompatibility Complex (MHC) and are in LD with HLA-DRB1. Individual genotyping of the 12 non-MHC markers confirmed association for three of them--D11S1986, D19S552 and D20S894. Association mapping across the candidate genes implicated by these markers in 937 UK trio families revealed modestly associated haplotypes in JAG1 (p=0.019) on chromosome 20p12.2 and POU2AF1 (p=0.003) on chromosome 11q23.1. PMID:16934875

  1. Distribution and linkage disequilibrium analysis of polymorphisms of GH1 gene in different populations of pigs associated with body size.

    PubMed

    Cheng, Yunyun; Liu, Songcai; Su, Dan; Lu, Chao; Zhang, Xin; Wu, Qingyan; Li, Siming; Fu, Haoyu; Yu, Hao; Hao, Linlin

    2016-03-01

    Growth hormone (GH) has been considered as a candidate gene for growth and body size in pigs. In this study, polymorphisms of the GH1 gene were evaluated for associations with body size traits in 190 pig individuals. Seventeen single-nucleotide polymorphisms (SNPs) were identified in GH1 gene of the large pig breeds and miniature pig breeds using direct sequencing and genotyped by allele-specific PCR approach. Notably, six (g.237A>G, g.283T>C, g.309A>G, g.318A>G, g.540A>G and g.544A>G) of them were significantly associated with body size, of which three loci (g.283T>C, g.309A>G, g.318A>G) located in the signal-peptide coding region of GH1 gene compose a CGG haplotype for large pigs and TAA haplotype for miniature pigs (P <0.001), two loci (g.540A>G and g.544A>G) located in the second intron of GH1 gene compose a GG haplotype for large pigs and AA haplotype for miniature pigs (P < 0.001). Our results demonstrate that these SNPs in GH1 gene are associated with the body size of pigs providing genetic basis for pig breeding with the improved economic benefits. PMID:27019435

  2. Linkage disequilibria at the D[sub 2] dopamine receptor locus (DRD2) in alcoholics and controls

    SciTech Connect

    Suarez, B.K.; Parsian, A.; Hampe, C.L.; Todd, R.D.; Reich, T.; Cloninger, C.R. )

    1994-01-01

    Because of its central role in the neuromodulation of appetitive behaviors, the D[sub 2] dopamine receptor gene (DRD2) has received considerable scrutiny as a possible candidate that may affect susceptibility to addictive behaviors--especially alcoholism. Association studies that compare the frequencies of anonymous restriction fragment length polymorphisms (RFLPs) in alcoholics and controls have yielded equivocal results, suggesting that any role played by this receptor will account for only part of the variation. Since these RFLPs are not located in coding regions, the hypothesis has been advanced that the association seen in some studies results from linkage disequilibrium between these markers and one or more functional DRD2 alleles that affect susceptibility. To test this hypothesis, the authors have assayed four DRD2 RFLPs that span coding regions as well as a 3[prime] flanking RFLP in an expanded sample of 88 unrelated Caucasian alcoholics and 89 unrelated race-matched controls. No significant difference for any RFLP frequency between these samples was observed, although for one marker (phD2-244), the alcoholic sample showed a significant departure from the Hardy-Weinberg equilibrium. The pattern of pairwise composite disequilibrium coefficients is broadly similar in the two samples, although when the five-marker haplotype frequencies are compared, a significant difference is revealed. This difference appears to be due to greater linkage disequilibrium of the control sample. These results do not support the involvement of the DRD2 region in the etiology of alcoholism. 64 refs., 2 figs., 6 tabs.

  3. Resource linkages and sustainable development

    NASA Astrophysics Data System (ADS)

    Anouti, Yahya

    prices we estimate that the demand for gasoline could be reduced by 7.8 percent and that of diesel by 5.9 percent. This would lead to not only reduction in the associated negative externalities, but also to the generation of more than USD400 billion in revenues for governments. However, the partial equilibrium analysis in essay one ignores the general equilibrium effects that will be mainly driven by how the government spends the subsidy. In essay 2, we build the case for phasing out these subsidies and accompanying that by a welfare compensating cash transfer. In order to evaluate the impact of that on consumer's welfare, we develop a numerical model for Saudi Arabia in a general equilibrium setting to discuss a phase out of transport fuel subsidies that is. Results show that the Saudi government can increase its consumers' welfare up to five percentage points. In case the cash transfer is adjusted to keep consumers' utility at the pre-reform level, the required compensating transfer would leave the government with three percentage points of additional revenues. Finally, we highlight policy implications of phasing out the transport fuel subsidies. Finally, in essay 3 we turn our focus to the application of local content policies in the oil and gas sector. There is limited literature that investigates economic linkages from the extractive industries, assesses intertemporal tradeoffs, and guides the design of efficient and sustainable policies. Our contribution in this essay is three-fold. First, we present the first comprehensive analysis of economic linkages from the oil and gas sector across 48 countries. Then, we analyze the economic distortions from applying local content policies using a Hotelling type optimal control model with an international oil company maximizing its profits subject to a local content requirement. Finally, we investigate the presence of a socially optimal local content level when the social planner maximizing the net benefits from the

  4. Disequilibrium of uranium isotopes in some Syrian groundwater.

    PubMed

    Abdul-Hadi, A; Alhassanieh, O; Ghafar, M

    2001-07-01

    Uranium concentration in groundwater samples from three areas of Syria was determined using alpha-spectrometry and INAA. It was in the range of 0-6.13 microg/l in the phosphate areas, and lower than 1 ppb in the volcanic areas. The activity ratio of 234U/238U was investigated, and disequilibrium of uranium isotopes was found to occur (234U/238U = 0.52-2.02). The excess of 234U was calculated. This excess can be interpreted by higher mobility of 234U, which more readily forms the soluble (UO2)2+ ion in comparison with 238U, most of which remains in the insoluble 4+ state. This excess increases with increase in uranium concentration. Thorium concentration was measured using INAA, it was found to be in the rang 0-1.15 microg/l. PMID:11339524

  5. Equilibrium and Disequilibrium Chemistry in Evolved Exoplanet Atmospheres

    NASA Astrophysics Data System (ADS)

    Hu, Renyu

    2015-11-01

    It has been found that sub-Neptune-sized planets, although not existing in our Solar System, are ubiquitous in our interstellar neighborhood. This revelation is profound because, due to their special sizes and proximity to their host stars, Neptune- and sub-Neptune-sized exoplanets may have highly evolved atmospheres. I will discuss helium-dominated atmospheres as one of the outcomes of extensive atmospheric evolution on warm Neptune- and sub-Neptune-sized exoplanets. Due to depleted hydrogen abundance, the dominant carbon and oxygen species may not be methane or water on these evolved planets. Equilibrium and disequilibrium chemistry models are used to compute the molecular compositions of the atmospheres and their spectral features. Applications to GJ 436 b and other Neptune- and sub-Neptune-sized exoplanets will be discussed. As the observations to obtain the spectra of these planets continue to flourish, we will have the opportunity to study unconventional atmospheric chemical processes and test atmosphere evolution theories

  6. Equilibrium and Disequilibrium Chemistry in Evolved Exoplanet Atmospheres

    NASA Astrophysics Data System (ADS)

    Hu, Renyu

    2015-12-01

    It has been found that sub-Neptune-sized planets, although not existing in our Solar System, are ubiquitous in our interstellar neighborhood. This revelation is profound because, due to their special sizes and proximity to their host stars, Neptune- and sub-Neptune-sized exoplanets may have highly evolved atmospheres. I will discuss helium-dominated atmospheres as one of the outcomes of extensive atmospheric evolution on warm Neptune- and sub-Neptune-sized exoplanets. Due to depleted hydrogen abundance, the dominant carbon and oxygen species may not be methane or water on these evolved planets. Equilibrium and disequilibrium chemistry models are used to compute the molecular compositions of the atmospheres and their spectral features. Applications to GJ 436 b and other Neptune- and sub-Neptune-sized exoplanets will be discussed. As the observations to obtain the spectra of these planets continue to flourish, we will have the opportunity to study unconventional atmospheric chemical processes and test atmosphere evolution theories

  7. Neuroendocrine–immune disequilibrium and endometriosis: an interdisciplinary approach

    PubMed Central

    Tariverdian, Nadja; Theoharides, Theoharis C.; Siedentopf, Friederike; Gutiérrez, Gabriela; Jeschke, Udo; Rabinovich, Gabriel A.; Blois, Sandra M.

    2007-01-01

    Endometriosis, a chronic disease characterized by endometrial tissue located outside the uterine cavity, affects one fourth of young women and is associated with chronic pelvic pain and infertility. However, an in-depth understanding of the pathophysiology and effective treatment strategies of endometriosis is still largely elusive. Inadequate immune and neuroendocrine responses are significantly involved in the pathophysiology of endometriosis, and key findings are summarized in the present review. We discuss here the role of different immune mechanisms particularly adhesion molecules, protein–glycan interactions, and pro-angiogenic mediators in the development and progression of the disease. Finally, we introduce the concept of endometrial dissemination as result of a neuroendocrine-immune disequilibrium in response to high levels of perceived stress caused by cardinal clinical symptoms of endometriosis. PMID:17621704

  8. Methods for genetic linkage analysis using trisomies

    SciTech Connect

    Feingold, E.; Lamb, N.E.; Sherman, S.L.

    1995-02-01

    Certain genetic disorders are rare in the general population, but more common in individuals with specific trisomies. Examples of this include leukemia and duodenal atresia in trisomy 21. This paper presents a linkage analysis method for using trisomic individuals to map genes for such traits. It is based on a very general gene-specific dosage model that posits that the trait is caused by specific effects of different alleles at one or a few loci and that duplicate copies of {open_quotes}susceptibility{close_quotes} alleles inherited from the nondisjoining parent give increased likelihood of having the trait. Our mapping method is similar to identity-by-descent-based mapping methods using affected relative pairs and also to methods for mapping recessive traits using inbred individuals by looking for markers with greater than expected homozygosity by descent. In the trisomy case, one would take trisomic individuals and look for markers with greater than expected homozygosity in the chromosomes inherited from the nondisjoining parent. We present statistical methods for performing such a linkage analysis, including a test for linkage to a marker, a method for estimating the distance from the marker to the trait gene, a confidence interval for that distance, and methods for computing power and sample sizes. We also resolve some practical issues involved in implementing the methods, including how to use partially informative markers and how to test candidate genes. 20 refs., 5 figs., 1 tab.

  9. Higher Education: Labor Market Linkage.

    ERIC Educational Resources Information Center

    Asayeghn, Desta

    1982-01-01

    Examines the methodology of three case studies investigating the linkage between higher education and the world of work in the Sudan, Zambia, and Tanzania. Summarizes 12 main findings. Suggests the studies remain traditional human resources planning efforts. (NEC)

  10. Nonsyndromic cleft lip with or without cleft palate: Evidence of linkage to BCL3 in 17 multigenerational families

    SciTech Connect

    Stein, J.; Hecht, T.; Stal, S.

    1995-08-01

    Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common craniofacial developmental defect. Recent segregation analyses have suggested that major genes play a role in the etiology of CL/P. Linkage to 22 candidate genes was tested in 11 multigenerational families with CL/P, and 21 of these candidates were excluded. APOC2, 19q13.1, which is linked to the proto-oncogene BCL3, gave suggestive evidence for linkage to CL/P. The study was expanded to include a total of 39 multigenerational CL/P families. Linkage was tested in all families, using anonymous marker, D19S178, and intragenic markers in BCL3 and APOC2. Linkage was tested under two models, autosomal dominant with reduced penetrance and affecteds-only model. Both models showed evidence of heterogeneity, with 43% of families linked at zero recombination to BCL3 when marker data from BCL3 and APOC2 were included. A maximum multipoint LOD score of 7.00 at BCL3 was found among the 17 families that had posterior probabilities {ge}50% in favor of linkage. The transmission disequilibrium test provided additional evidence for linkage with the 3 allele of BCL3 more often transmitted to affected children. These results suggest that BCL3, or a nearby gene, plays a role in the etiology of CL/P in some families. 39 refs., 8 figs., 4 tabs.

  11. Linkages in thermal copolymers of lysine

    NASA Technical Reports Server (NTRS)

    Fox, S. W.; Suzuki, F.

    1975-01-01

    The thermal copolymerization of lysine with other alpha-amino acids was studied. The identity of the second amino acid influences various properties of the polymer obtained, including the proportion of alpha and epsilon linkages of lysine. A review of linkages in proteinoids indicates alpha and beta linkages for aspartic acid, alpha and gamma linkages for glutamic acid, alpha and epsilon linkages for lysine, and alpha linkages for other amino acids. Thermal proteinoids are thus more complex in types of linkage than are proteins.

  12. Linkages in thermal copolymers of lysine

    NASA Technical Reports Server (NTRS)

    Fox, S. W.; Suzuki, F.

    1976-01-01

    The thermal copolymerization of lysine with other alpha-amino acids has been studied further. The identity of the second amino acid influences various properties of the polymer obtained, including the proportion of alpha and epsilon linkages of lysine. A review of linkages in proteinoids indicates alpha and beta linkages for aspartic acid, alpha and gamma linkages for glutamic acid, alpha and epsilon linkages for lysine, and alpha linkages for other amino acids. Thermal proteinoids are thus more complex in types of linkage than are proteins

  13. Disequilibrium Textures vs Equilibrium Modelling: Geochronology at the Crossroads

    NASA Astrophysics Data System (ADS)

    Villa, I. M.

    2007-12-01

    Observations made by electron microscopy show the processes affecting minerals at the atomic scale. The majority of reported analyses demonstrate chemical disequilibrium. A classic example are overgrowths of one mineral generation by a secondary one, which may be recognized on textural grounds. Disequilibrium recrystallization is promoted by water, which is everywhere on this planet (granites, contact aureoles, regional metamorphism, faults). It is mostly easier and energetically less costly to recrystallize a mineral at any temperature than to induce genuine volume diffusion in it. However, these observations are only relevant to geochronologists if chemical disequilibria are also accompanied by isotopic disequilibria. If a mineral mixture gives a mixed isotope record, then the interpretation of ages does not come cheap. If, on the contrary, diffusive reequilibration of the isotopic record is faster than that of chemical heterogeneities, then the petrology and microchemistry of a mineral could be ignored and its apparent age termed a "cooling age". First principle arguments and experimental data of the last decade concordantly show that the diffusivity of radiogenic isotopes is never higher than that of major elements forming the mineral structure. And indeed, end- member ages of mineral mixtures can be unravelled if the petrogenesis is understood. This was first shown by CL images of zircon grains (Gebauer et al, Schweiz Min Pet Mitt 68 (1988) 485-490). Similar progress was reported on monazite (Williams et al, Ann Rev Earth Planet Sci 35 (2007) 137-175), amphibole (Belluso et al, Eur J Mineral 12 (2000) 45-62), K-feldspar (Nyfeler et al, Schweiz Min Pet Mitt 78 (1998) 11-21), biotite (Villa et al, Water Rock Interaction 10 (2001) 1589-92). The mechanism for resetting the isotope record in nature thus seems more dependent on the availability of water to enhance disequilibrium recrystallization than on reaching a preset temperature. Intercomparison of laboratory

  14. [Accounting for Expected Linkage in Biometric Analysis of Quantitative Traits].

    PubMed

    Mikhailov, M E

    2015-08-01

    The problem of accounting for a genetic estimation of expected linkage in the disposition of random loci was solved for the additive-dominant model. The Comstock-Robinson estimations for the sum of squares of dominant effects, the sum of squares of additive effects, and the average degree of dominance were modified. Also, the Wright's estimation for the number of loci controlling the variation of a quantitative trait was modified and its application sphere was extended. Formulas that should eliminate linkage, on average, were derived for these estimations. Nonbiased estimations were applied to the analysis of maize data. Our result showed that the most likely cause of heterosis is dominance rather than overdominance and that the main part of the heterotic effect is provided by dozens of genes. PMID:26601496

  15. Meta-analysis of genome-wide linkage scans for renal function traits

    PubMed Central

    Rao, Madhumathi; Mottl, Amy K.; Cole, Shelley A.; Umans, Jason G.; Freedman, Barry I.; Bowden, Donald W.; Langefeld, Carl D.; Fox, Caroline S.; Yang, Qiong; Cupples, Adrienne; Iyengar, Sudha K.; Hunt, Steven C.

    2012-01-01

    Background. Several genome scans have explored the linkage of chronic kidney disease phenotypes to chromosomic regions with disparate results. Genome scan meta-analysis (GSMA) is a quantitative method to synthesize linkage results from independent studies and assess their concordance. Methods. We searched PubMed to identify genome linkage analyses of renal function traits in humans, such as estimated glomerular filtration rate (GFR), albuminuria, serum creatinine concentration and creatinine clearance. We contacted authors for numerical data and extracted information from individual studies. We applied the GSMA nonparametric approach to combine results across 14 linkage studies for GFR, 11 linkage studies for albumin creatinine ratio, 11 linkage studies for serum creatinine and 4 linkage studies for creatinine clearance. Results. No chromosomal region reached genome-wide statistical significance in the main analysis which included all scans under each phenotype; however, regions on Chromosomes 7, 10 and 16 reached suggestive significance for linkage to two or more phenotypes. Subgroup analyses by disease status or ethnicity did not yield additional information. Conclusions. While heterogeneity across populations, methodologies and study designs likely explain this lack of agreement, it is possible that linkage scan methodologies lack the resolution for investigating complex traits. Combining family-based linkage studies with genome-wide association studies may be a powerful approach to detect private mutations contributing to complex renal phenotypes. PMID:21622988

  16. Disequilibrium between [sup 226]Ra and supported [sup 210]Pb in a sediment core from a shallow Florida lake

    SciTech Connect

    Brenner, M.; Peplov, A.J.; Schelske, C.L. )

    1994-07-01

    [sup 210]Pb dating can be used to assign ages in lake sediment cores, calculate rates of sediment accumulation, and determine the timing of recent changes in lake-watershed ecosystems. We used low-background gamma counting to measure [sup 226]Ra and total [sup 210]Pb activity in a core from Lake Rowell, Florida. [sup 226]Ra activity was high and strongly variable throughout the core, even exceeding total [sup 210]Pb activity in recently deposited sediments. We traced one source of Ra-rich sediments to the only inflow, Alligator Creek, where stream-bottom deposits display disequilibrium between [sup 226]Ra and supported [sup 210]Pb. High and variable [sup 226]Ra activity in the Lake Rowell profile argues for direct estimates of in situ Ra in lake sediment cores from disturbed watersheds that have Ra-bearing bedrock. Isotopic disequilibrium between [sup 226]Ra and supported [sup 210]Pb makes it difficult to distinguish between supported and unsupported [sup 210]Pb activity throughout the Lake Rowell core and would require special assumptions and nonconventional dating models to establish age-depth relationships. 78 refs., 3 figs., 1 tab.

  17. Disequilibrium in naturally occurring radioactive series in some phosphate ores.

    PubMed

    Hamidalddin, Safia H Q; Fakeha, Afaf A; Yeslam, Mai S; Ibraheim, Nagdya M

    2012-01-01

    Eight phosphate ore samples from Egypt and Saudi Arabia were studied by atomic absorption spectrometry for the Bi, Pb, Th and Al concentrations in ppm or ppb or per cent. Also X-ray diffraction spectrometry was applied for determining the mineral and chemical composition of the phosphate ore samples. A gamma spectrometry system, based on HPGe crystal, was applied for determining the concentrations of the radioactive elements in (238)U, (226)Ra and (232)Th series as well as (40)K, in Bq/kg dry weight. Concentrations in ppm were found to be from <10.0 to 20.48, from <7.50 to 27.30 and from <1.0 to 50.0 for Bi, Pb and Th, respectively. Al ranged from <0.05 to 3.13%. Major, minor and trace chemical and mineral compositions were assigned for each sample by XRD spectrometry. Concentrations of the different elements in both radioactive series, (238)U, (226)Ra and (232)Th were compared. Disequilibrium was found in both series. PMID:21982734

  18. Equilibrium and Disequilibrium Chemistry in Evolved Exoplanet Atmospheres

    NASA Astrophysics Data System (ADS)

    Hu, Renyu

    2015-08-01

    It has been found that sub-Neptune-sized planets, although not existing in our Solar System, are ubiquitous in our interstellar neighborhood. This revelation is profound because, due to their special sizes and proximity to their host stars, Neptune- and sub-Neptune-sized exoplanets may have highly evolved atmospheres. I will discuss helium-dominated atmospheres as one of the outcomes of extensive atmospheric evolution on warm Neptune- and sub-Neptune-sized exoplanets. Due to depleted hydrogen abundance, the dominant carbon and oxygen species may not be methane or water on these evolved planets. Equilibrium and disequilibrium chemistry models are used to compute the molecular compositions of the atmospheres and their spectral features. Applications to GJ 436 b, HD 97658 b, and other Neptune- and sub-Neptune-sized exoplanets will be discussed. As the observations to obtain the spectra of these planets continue to flourish, we will have the opportunity to study unconventional atmospheric chemical processes and test atmosphere evolution theories.

  19. Dialysis disequilibrium syndrome: A preventable fatal acute complication.

    PubMed

    Mah, D Y; Yia, H J; Cheong, W S

    2016-04-01

    Dialysis disequilibrium syndrome (DDS) is a neurological disorder with varying severity that is postulated to be associated with cerebral oedema. We described a case of DDS resulting in irreversible brain injury and death following acute haemodialysis. A 13-year-old male with no past medical history and weighing 30kg, presented to hospital with severe urosepsis complicated by acute kidney injury (Creatinine 1422mmol/L; Urea 74.2mmol/L, Potassium 6.3mmol/L, Sodium 137mmol/L) and severe metabolic acidosis (pH 6.99, HC03 1.7mmol/L). Chest radiograph was normal. Elective intubation was done for respiratory distress. Acute haemodialysis performed due to refractory metabolic acidosis. Following haemodialysis, he became hypotensive which required inotropes. His Riker's score was low with absence of brainstem reflexes after withholding sedation. CT Brain showed generalised cerebral oedema consistent with global hypoxic changes involving the brainstem. The symptoms of DDS are caused by water movement into the brain causing cerebral oedema. Two theories have been proposed: reverse osmotic shift induced by urea removal and a fall in cerebral intracellular pH. Prevention is the key to the management of DDS. It is important to identify high risk patients and haemodialysis with reduced dialysis efficacy and gradual urea reduction is recommended. Patients who are vulnerable to DDS should be monitored closely. Low efficiency haemodialysis is recommended. Acute peritoneal dialysis might be an alternative option, but further studies are needed. PMID:27326954

  20. NeEstimator v2: re-implementation of software for the estimation of contemporary effective population size (Ne ) from genetic data.

    PubMed

    Do, C; Waples, R S; Peel, D; Macbeth, G M; Tillett, B J; Ovenden, J R

    2014-01-01

    NeEstimator v2 is a completely revised and updated implementation of software that produces estimates of contemporary effective population size, using several different methods and a single input file. NeEstimator v2 includes three single-sample estimators (updated versions of the linkage disequilibrium and heterozygote-excess methods, and a new method based on molecular coancestry), as well as the two-sample (moment-based temporal) method. New features include the following: (i) an improved method for accounting for missing data; (ii) options for screening out rare alleles; (iii) confidence intervals for all methods; (iv) the ability to analyse data sets with large numbers of genetic markers (10 000 or more); (v) options for batch processing large numbers of different data sets, which will facilitate cross-method comparisons using simulated data; and (vi) correction for temporal estimates when individuals sampled are not removed from the population (Plan I sampling). The user is given considerable control over input data and composition, and format of output files. The freely available software has a new JAVA interface and runs under MacOS, Linux and Windows. PMID:23992227

  1. Resource linkages and sustainable development

    NASA Astrophysics Data System (ADS)

    Anouti, Yahya

    prices we estimate that the demand for gasoline could be reduced by 7.8 percent and that of diesel by 5.9 percent. This would lead to not only reduction in the associated negative externalities, but also to the generation of more than USD400 billion in revenues for governments. However, the partial equilibrium analysis in essay one ignores the general equilibrium effects that will be mainly driven by how the government spends the subsidy. In essay 2, we build the case for phasing out these subsidies and accompanying that by a welfare compensating cash transfer. In order to evaluate the impact of that on consumer's welfare, we develop a numerical model for Saudi Arabia in a general equilibrium setting to discuss a phase out of transport fuel subsidies that is. Results show that the Saudi government can increase its consumers' welfare up to five percentage points. In case the cash transfer is adjusted to keep consumers' utility at the pre-reform level, the required compensating transfer would leave the government with three percentage points of additional revenues. Finally, we highlight policy implications of phasing out the transport fuel subsidies. Finally, in essay 3 we turn our focus to the application of local content policies in the oil and gas sector. There is limited literature that investigates economic linkages from the extractive industries, assesses intertemporal tradeoffs, and guides the design of efficient and sustainable policies. Our contribution in this essay is three-fold. First, we present the first comprehensive analysis of economic linkages from the oil and gas sector across 48 countries. Then, we analyze the economic distortions from applying local content policies using a Hotelling type optimal control model with an international oil company maximizing its profits subject to a local content requirement. Finally, we investigate the presence of a socially optimal local content level when the social planner maximizing the net benefits from the

  2. Construction of Ultradense Linkage Maps with Lep-MAP2: Stickleback F2 Recombinant Crosses as an Example.

    PubMed

    Rastas, Pasi; Calboli, Federico C F; Guo, Baocheng; Shikano, Takahito; Merilä, Juha

    2016-01-01

    High-density linkage maps are important tools for genome biology and evolutionary genetics by quantifying the extent of recombination, linkage disequilibrium, and chromosomal rearrangements across chromosomes, sexes, and populations. They provide one of the best ways to validate and refine de novo genome assemblies, with the power to identify errors in assemblies increasing with marker density. However, assembly of high-density linkage maps is still challenging due to software limitations. We describe Lep-MAP2, a software for ultradense genome-wide linkage map construction. Lep-MAP2 can handle various family structures and can account for achiasmatic meiosis to gain linkage map accuracy. Simulations show that Lep-MAP2 outperforms other available mapping software both in computational efficiency and accuracy. When applied to two large F2-generation recombinant crosses between two nine-spined stickleback (Pungitius pungitius) populations, it produced two high-density (∼6 markers/cM) linkage maps containing 18,691 and 20,054 single nucleotide polymorphisms. The two maps showed a high degree of synteny, but female maps were 1.5-2 times longer than male maps in all linkage groups, suggesting genome-wide recombination suppression in males. Comparison with the genome sequence of the three-spined stickleback (Gasterosteus aculeatus) revealed a high degree of interspecific synteny with a low frequency (<5%) of interchromosomal rearrangements. However, a fairly large (ca. 10 Mb) translocation from autosome to sex chromosome was detected in both maps. These results illustrate the utility and novel features of Lep-MAP2 in assembling high-density linkage maps, and their usefulness in revealing evolutionarily interesting properties of genomes, such as strong genome-wide sex bias in recombination rates. PMID:26668116

  3. Construction of Ultradense Linkage Maps with Lep-MAP2: Stickleback F2 Recombinant Crosses as an Example

    PubMed Central

    Rastas, Pasi; Calboli, Federico C. F.; Guo, Baocheng; Shikano, Takahito; Merilä, Juha

    2016-01-01

    High-density linkage maps are important tools for genome biology and evolutionary genetics by quantifying the extent of recombination, linkage disequilibrium, and chromosomal rearrangements across chromosomes, sexes, and populations. They provide one of the best ways to validate and refine de novo genome assemblies, with the power to identify errors in assemblies increasing with marker density. However, assembly of high-density linkage maps is still challenging due to software limitations. We describe Lep-MAP2, a software for ultradense genome-wide linkage map construction. Lep-MAP2 can handle various family structures and can account for achiasmatic meiosis to gain linkage map accuracy. Simulations show that Lep-MAP2 outperforms other available mapping software both in computational efficiency and accuracy. When applied to two large F2-generation recombinant crosses between two nine-spined stickleback (Pungitius pungitius) populations, it produced two high-density (∼6 markers/cM) linkage maps containing 18,691 and 20,054 single nucleotide polymorphisms. The two maps showed a high degree of synteny, but female maps were 1.5–2 times longer than male maps in all linkage groups, suggesting genome-wide recombination suppression in males. Comparison with the genome sequence of the three-spined stickleback (Gasterosteus aculeatus) revealed a high degree of interspecific synteny with a low frequency (<5%) of interchromosomal rearrangements. However, a fairly large (ca. 10 Mb) translocation from autosome to sex chromosome was detected in both maps. These results illustrate the utility and novel features of Lep-MAP2 in assembling high-density linkage maps, and their usefulness in revealing evolutionarily interesting properties of genomes, such as strong genome-wide sex bias in recombination rates. PMID:26668116

  4. A systematic retrieval analysis of secondary eclipse spectra. III. Diagnosing chemical disequilibrium in planetary atmospheres

    SciTech Connect

    Line, Michael R.; Yung, Yuk L.

    2013-12-10

    Chemical disequilibrium has recently become a relevant topic in the study of the atmospheres of transiting extrasolar planets, brown dwarfs, and directly imaged exoplanets. We present a new way of assessing whether or not a Jovian-like atmosphere is in chemical disequilibrium from observations of detectable or inferred gases such as H{sub 2}O, CH{sub 4}, CO, and H{sub 2}. Our hypothesis, based on previous kinetic modeling studies, is that cooler atmospheres will show stronger signs of disequilibrium than hotter atmospheres. We verify this with chemistry-transport models and show that planets with temperatures less than ∼1200 K are likely to show the strongest signs of disequilibrium due to the vertical quenching of CO, and that our new approach is able to capture this process. We also find that in certain instances a planetary composition may appear in equilibrium when it actually is not due to the degeneracy in the shape of the vertical mixing ratio profiles. We determine the state of disequilibrium in eight exoplanets using the results from secondary eclipse temperature and abundance retrievals. We find that all of the planets in our sample are consistent with thermochemical equilibrium to within 3σ. Future observations are needed to further constrain the abundances in order to definitively identify disequilibrium in exoplanet atmospheres.

  5. Th-230 - U-238 series disequilibrium of the Olkaria basalts Gregory Rift Valley, Kenya

    NASA Technical Reports Server (NTRS)

    Black, S.; Macdonald, R.; Kelly, M.

    1993-01-01

    U-Th disequilibrium analyses of the Naivasha basalts show a very small (U-238/Th-230) ratios which are lower than any previously analyzed basalts. The broadly positive internal isochron trend from one sample indicates that the basalts may have source heterogeneities, this is supported by earlier work. The Naivasha complex comprises a bimodal suite of basalts and rhyolites. The basalts are divided into two stratigraphic groups each of a transitional nature. The early basalt series (EBS) which were erupted prior to the Group 1 comendites and, the late basalt series (LBS) which erupted temporally between the Broad Acres and the Ololbutot centers. The basalts represent a very small percentage of the overall eruptive volume of material at Naivasha (less than 2 percent). The analyzed samples come from four stratigraphic units in close proximity around Ndabibi, Hell's Gate and Akira areas. The earliest units occur as vesicular flows from the Ndabibi plain. These basalts are olivine-plagioclase phyric with the associated hawaiites being sparsely plagioclase phyric. An absolute age of 0.5Ma was estimated for these basalts. The next youngest basalts flows occur as younger tuft cones in the Ndabibi area and are mainly olivine-plagioclase-clinopyroxcene phyric with one purely plagioclase phyric sample. The final phase of activity at Ndabibi resulted in much younger tuft cones consisting of air fall ashes and lapilli tufts. Many of these contain resorbed plagioclase phenocrysts with sample number 120c also being clinopyroxene phyric. The isotopic evidence for the basalt formation is summarized.

  6. Task Structure Design: Beyond Linkage.

    ERIC Educational Resources Information Center

    Baker, Eva L.; Herman, Joan L.

    1983-01-01

    This analysis of the role of testing in educational programs and services maintains that the connection between tests and instruction is best made integrally through an understanding of the design of learning tasks rather than through linkage. The context for, use of, and limitations of task structures are described. (Author/CM)

  7. Segregation and linkage analysis of serum angiotensin I-converting enzyme levels: Evidence for two quantitative-trait loci

    SciTech Connect

    McKenzie, C.A.; Keavney, B.; Farrall, M.

    1995-12-01

    Human serum angiotensin I-converting enzyme (ACE) levels vary substantially between individuals and are highly heritable. Segregation analysis in European families has shown that more than half of the total variability in ACE levels is influenced by quantitative-trait loci (QTL). One of these QTLs is located within or close to the ACE locus itself. Combined segregation/linkage analysis in a series of African Caribbean families from Jamaica shows that the ACE insertion-deletion polymorphism is in moderate linkage disequilibrium with an ACE-linked QTL. Linkage analysis with a highly informative polymorphism at the neighboring growth hormone gene (GH) shows surprisingly little support for linkage (LOD score [Z] = 0.12). An extended analysis with a two-QTL model, where an ACE-linked QTL interacts additively with an unlinked QTL, significantly improves both the fit of the model (P = .002) and the support for linkage between the ACE-linked QTL and GH polymorphism (Z = 5.0). We conclude that two QTLs jointly influence serum ACE levels in this population. One QTL is located within or close to the ACE locus and explains 27% of the total variability; the second QTL is unlinked to the ACE locus and explains 52% of the variability. The identification of the molecular mechanisms underlying both QTLs is necessary in order to interpret the role of ACE in cardiovascular disease. 44 refs., 7 tabs.

  8. Applying Association Rule Discovery Algorithm to Multipoint Linkage Analysis.

    PubMed

    Mitsuhashi; Hishigaki; Takagi

    1997-01-01

    Knowledge discovery in large databases (KDD) is being performed in several application domains, for example, the analysis of sales data, and is expected to be applied to other domains. We propose a KDD approach to multipoint linkage analysis, which is a way of ordering loci on a chromosome. Strict multipoint linkage analysis based on maximum likelihood estimation is a computationally tough problem. So far various kinds of approximate methods have been implemented. Our method based on the discovery of association between genetic recombinations is so different from others that it is useful to recheck the result of them. In this paper, we describe how to apply the framework of association rule discovery to linkage analysis, and also discuss that filtering input data and interpretation of discovered rules after data mining are practically important as well as data mining process itself. PMID:11072310

  9. Extreme isotopologue disequilibrium in molecular SIMS species during SHRIMP geochronology

    NASA Astrophysics Data System (ADS)

    Magee, Charles W., Jr.; Danišík, Martin; Mernagh, Terry

    2016-04-01

    Isotopologue deficits of up to 200 ‰ below ideal mixing are observed in UO2+ species during SIMS gechronological analyses using the SHRIMP IIe instrument. These are identified by bombarding natural U-bearing minerals with an 18O2-primary beam. The large anomalies are associated with repeat analyses down a single SIMS sputtering crater (Compston et al., 1984), analysis of high-uranium, radiation damaged zircon, and analysis of baddeleyite. Analysis of zircon under routine conditions yield UO2+ isotopologue anomalies generally within a few percent of equilibrium. The conditions under which the isotopologue anomalies are observed are also conditions in which the UOx-based corrections, or calibration, for relative U vs. Pb ionization efficiencies fail. The existence of these isotopologue anomalies suggest that failure of the various UOx species to equilibrate with each other is the reason that none of them will successfully correct the U / Pb ratio. No simple isotopologue-based correction is apparent. However, isotopologue disequilibrium appears to be a more sensitive tool for detecting hi U calibration breakdowns than Raman spectroscopy, which showed sharper peaks for ~ 37 Ma high uranium 20 zircons than for reference zircons OG1 and Temora. U-Th-Sm/He ages were determined for aliquots of reference zircons OG1 (755 ± 71 Ma) and Temora (323 ± 43 Ma), suggesting that the broader Raman lines for the Temora reference zircons may be due to something other than accumulated radiation damage. Isotopologue abundances for UO+ and ThO+ and their energy spectra are consistent with most or all molecular species being 25 the product of atomic recombination when the primary beam impact energy is greater than 5.7 kV. This, in addition with the large UO2+ instrumentally generated isotopologue disequilibria, suggest any attempts to use SIMS to detect naturally occurring isotopologue deviations could be tricky.

  10. Uranium-thorium disequilibrium in north-east Atlantic waters.

    PubMed

    Smith, K J; León Vintró, L; Mitchell, P I; Bally de Bois, P; Boust, D

    2004-01-01

    In this paper we report and compare the concentrations of 234Th and 238U measured in surface and subsurface waters collected in the course of a sampling campaign in the north east Atlantic in June-July 1998. Dissolved 234Th concentrations in surface waters ranged from 5 to 20 Bq m(-3), showing a large deficiency relative to 238U concentrations (typically 42 Bq m-3). This disequilibrium is indicative of active 234Th scavenging from surface waters. Observed 234Th/238U activity ratios, together with corresponding 234Th particulate concentrations, were used to calculate mean residence times for 234Th with respect to scavenging onto particles (tau(diss)) and subsequent removal from surface waters (tau(part)). Residence times in the range 5-30 days were determined for tau(diss) and 4-18 days for tau(part) (n=14). In addition, ultrafiltration experiments at six stations in the course of the same expedition revealed that in north-east Atlantic surface waters a significant fraction (46+/-17%; n=6) of the thorium in the (operationally-defined) dissolved phase (<0.45 microm) is in colloidal form. These observations are consistent with the 'colloidal pumping' model in which it is assumed that 234Th is rapidly absorbed by colloidal particles, which then aggregate, albeit at a slower rate, into larger filterable particles. In essence, colloids act as intermediaries in the transition from the fully dissolved to the filter-retained (>0.45 microm) phase. Thus, the time (tau(c)) for fully dissolved 234Th to appear in the filter-retained fraction is dependent on the rate of colloidal aggregation. Here, we determined tau(c) values in the range 3-17 days. PMID:15063548

  11. Using identity by descent estimation with dense genotype data to detect positive selection.

    PubMed

    Han, Lide; Abney, Mark

    2013-02-01

    Identification of genomic loci and segments that are identical by descent (IBD) allows inference on problems such as relatedness detection, IBD disease mapping, heritability estimation and detection of recent or ongoing positive selection. Here, employing a novel statistical method, we use IBD to find signals of selection in the Maasai from Kinyawa, Kenya (MKK). In doing so, we demonstrate the advantage of statistical tools that can probabilistically estimate IBD sharing without having to thin genotype data because of linkage disequilibrium (LD), and that allow for both inbreeding and more than one allele to be shared IBD. We use our novel method, GIBDLD, to estimate IBD sharing between all pairs of individuals at all genotyped SNPs in the MKK, and, by looking for genomic regions showing excess IBD sharing in unrelated pairs, find loci that are known to have undergone recent selection (eg, the LCT gene and the HLA region) as well as many novel loci. Intriguingly, those loci that show the highest amount of excess IBD, with the exception of HLA, also show a substantial number of unrelated pairs sharing all four of their alleles IBD. In contrast to other IBD detection methods, GIBDLD provides accurate probabilistic estimates at each locus for all nine possible IBD sharing states between a pair of individuals, thus allowing for consanguinity, while also modeling LD, thus removing the need to thin SNPs. These characteristics will prove valuable for those doing genetic studies, and estimating IBD, in the wide variety of human populations. PMID:22781100

  12. A method to estimate the contribution of regional genetic associations to complex traits from summary association statistics

    PubMed Central

    Pare, Guillaume; Mao, Shihong; Deng, Wei Q.

    2016-01-01

    Despite considerable efforts, known genetic associations only explain a small fraction of predicted heritability. Regional associations combine information from multiple contiguous genetic variants and can improve variance explained at established association loci. However, regional associations are not easily amenable to estimation using summary association statistics because of sensitivity to linkage disequilibrium (LD). We now propose a novel method, LD Adjusted Regional Genetic Variance (LARGV), to estimate phenotypic variance explained by regional associations using summary statistics while accounting for LD. Our method is asymptotically equivalent to a multiple linear regression model when no interaction or haplotype effects are present. It has several applications, such as ranking of genetic regions according to variance explained or comparison of variance explained by two or more regions. Using height and BMI data from the Health Retirement Study (N = 7,776), we show that most genetic variance lies in a small proportion of the genome and that previously identified linkage peaks have higher than expected regional variance. PMID:27273519

  13. Methods for genetic linkage analysis using trisomies

    SciTech Connect

    Feingold, E.; Lamb, N.E.; Sherman, S.L.

    1994-09-01

    Certain genetic disorders (e.g. congenital cataracts, duodenal atresia) are rare in the general population, but more common in people with Down`s syndrome. We present a method for using individuals with trisomy 21 to map genes for such traits. Our methods are analogous to methods for mapping autosomal dominant traits using affected relative pairs by looking for markers with greater than expected identity-by-descent. In the trisomy case, one would take trisomic individuals and look for markers with greater than expected reduction to homozygosity in the chromosomes inherited form the non-disjoining parent. We present statistical methods for performing such a linkage analysis, including a test for linkage to a marker, a method for estimating the distance from the marker to the gene, a confidence interval for that distance, and methods for computing power and sample sizes. The methods are described in the context of gene-dosage model for the etiology of the disorder, but can be extended to other models. We also resolve some practical issues involved in implementing the methods, including how to use partially informative markers, how to test candidate genes, and how to handle the effect of reduced recombination associated with maternal meiosis I non-disjunction.

  14. Efficient Record Linkage Algorithms Using Complete Linkage Clustering

    PubMed Central

    Mamun, Abdullah-Al; Aseltine, Robert; Rajasekaran, Sanguthevar

    2016-01-01

    Data from different agencies share data of the same individuals. Linking these datasets to identify all the records belonging to the same individuals is a crucial and challenging problem, especially given the large volumes of data. A large number of available algorithms for record linkage are prone to either time inefficiency or low-accuracy in finding matches and non-matches among the records. In this paper we propose efficient as well as reliable sequential and parallel algorithms for the record linkage problem employing hierarchical clustering methods. We employ complete linkage hierarchical clustering algorithms to address this problem. In addition to hierarchical clustering, we also use two other techniques: elimination of duplicate records and blocking. Our algorithms use sorting as a sub-routine to identify identical copies of records. We have tested our algorithms on datasets with millions of synthetic records. Experimental results show that our algorithms achieve nearly 100% accuracy. Parallel implementations achieve almost linear speedups. Time complexities of these algorithms do not exceed those of previous best-known algorithms. Our proposed algorithms outperform previous best-known algorithms in terms of accuracy consuming reasonable run times. PMID:27124604

  15. A computer model allowing maintenance of large amounts of genetic variability in Mendelian populations. II. The balance of forces between linkage and random assortment.

    PubMed

    Wills, C; Miller, C

    1976-02-01

    It is shown, through theory and computer simulations of outbreeding Mendelian populations, that there may be conditions under which a balance is struck between two facotrs. The first is the advantage of random assortment, which will, when multilocus selection is for intermediate equilibrium values, lead to higher average heterozygosity than when linkage is introduced. There is some indication that random assortment is also advantageous when selection is toward a uniform distribution of equilibrium values. The second factor is the advantage of linkage between loci having positive epistatic interactions. When multilocus selection is for a bimodal distribution of equilibrium values an early advantage of random assortment is replaced by a later disadvantage. Linkage disequilibrium, which in finite populations is increased only by random or selective sampling, may hinder the movement of alleles to their selective equilibria, thus leading to the advantage of random assortment.-Some consequences of this approach to the structure of natural populations are discussed. PMID:1261798

  16. Sample selection and spatial models of housing price indexes, and, A disequilibrium analysis of the U.S. gasoline market using panel data

    NASA Astrophysics Data System (ADS)

    Hu, Haixin

    This dissertation consists of two parts. The first part studies the sample selection and spatial models of housing price index using transaction data on detached single-family houses of two California metropolitan areas from 1990 through 2008. House prices are often spatially correlated due to shared amenities, or when the properties are viewed as close substitutes in a housing submarket. There have been many studies that address spatial correlation in the context of housing markets. However, none has used spatial models to construct housing price indexes at zip code level for the entire time period analyzed in this dissertation to the best of my knowledge. In this paper, I study a first-order autoregressive spatial model with four different weighing matrix schemes. Four sets of housing price indexes are constructed accordingly. Gatzlaff and Haurin (1997, 1998) study the sample selection problem in housing index by using Heckman's two-step method. This method, however, is generally inefficient and can cause multicollinearity problem. Also, it requires data on unsold houses in order to carry out the first-step probit regression. Maximum likelihood (ML) method can be used to estimate a truncated incidental model which allows one to correct for sample selection based on transaction data only. However, convergence problem is very prevalent in practice. In this paper I adopt Lewbel's (2007) sample selection correction method which does not require one to model or estimate the selection model, except for some very general assumptions. I then extend this method to correct for spatial correlation. In the second part, I analyze the U.S. gasoline market with a disequilibrium model that allows lagged-latent variables, endogenous prices, and panel data with fixed effects. Most existing studies (see the survey of Espey, 1998, Energy Economics) of the gasoline market assume equilibrium. In practice, however, prices do not always adjust fast enough to clear the market

  17. Genetic mapping of the gene for Usher syndrome: Linkage analysis in a large Samaritan kindred

    SciTech Connect

    Bonne-Tamir, B.; Korostishevsky, M.; Kalinsky, H.; Seroussi, E.; Beker, R.; Weiss, S. ); Godel, V. )

    1994-03-01

    Usher syndrome is a group of autosomal recessive disorders associated with congenital sensorineural deafness and progressive visual loss due to retinitis pigmentosa. Sixteen members of the small inbred Samaritan isolate with autosomal recessive deafness from 59 individuals including parents and affected and nonaffected sibs were typed for markers on chromosomes 1q and 11q for which linkage has recently been established for Usher syndrome types II and I. Statistically significant linkage was observed with four markers on 11q (D11S533, D11S527, OMP, and INT2) with a maximum six-point location score of 11.61 at the D11S533 locus. Analysis of haplotypes supports the notion that the mutation arose only once in an ancestral chromosome carrying a specific haplotype. The availability of markers closely linked to the disease locus allows indirect genotype analysis and identifies all carriers of the gene within the community. Furthermore, the detection of complete linkage disequilibrium between the D11S533 marker and the Usher gene suggests that these loci are either identical or adjacent and narrows the critical region to which physical mapping efforts are currently directed. 35 refs., 2 figs., 6 tabs.

  18. Exploring causality via identification of SNPs or haplotypes responsible for a linkage signal

    PubMed Central

    Biernacka, Joanna M; Cordell, Heather J

    2007-01-01

    In a small chromosomal region, a number of polymorphisms may be both linked to and associated with a disease. Distinguishing the potential causal sites from those indirectly associated due to linkage disequilibrium (LD) with a causal site is an important problem. This problem may be approached by determining which of the associations can explain the observed linkage signal. Recently, several methods have been proposed to aid in the identification of disease associated polymorphisms that may explain an observed linkage signal, using genotype data from affected sib pairs (ASPs) [Li et al. [2005] Am. J. Hum. Genet. 76:934–949; Sun et al. [2002] Am. J. Hum. Genet. 70:399–411]. These methods can be used to test the null hypothesis that a candidate single nucleotide polymorphism (SNP) is the sole causal variant in the region, or is in complete LD with the sole causal variant in the region. We extend variations of these methods to test for complete LD between a disease locus and haplotypes composed of two or more tightly linked candidate SNPs. We study properties of the proposed methods by simulation and apply them to type 1 diabetes data for ASPs and their parents at candidate SNP and microsatellite marker loci in the Insulin (INS) gene region. Genet. Epidemiol. 31:2727–740, 2007. © 2007 Wiley-Liss, Inc. PMID:17508343

  19. Validation of the STR DXS7424 and the linkage situation on the X-chromosome.

    PubMed

    Edelmann, Jeanett; Hering, Sandra; Kuhlisch, Eberhard; Szibor, Reinhard

    2002-02-18

    X-linked microsatellite markers have proven to be powerful tools for parentage testing, mainly in deficiency paternity cases when the disputed child is female. However, only a small number of X-linked short tandem repeats (STRs) have been comprehensively described for forensic applications to date. We present sequence and population genetic data of the DXS7424 STR (GDB-G00-577-633) which is a trinucleotide repeat polymorphism representing 12 alleles of 147-180 bp in length. DXS7424 is located at Xq22 and closely linked to DXS101, corresponding to a genetic localisation of 104.9-121 cM from Xp-tel.PCR fragment length measurements and sequencing were carried out using the automatic gene analyser ABI 310 (Applied Biosystems). The population of 764 unrelated Germans checked for this STR exhibited the following features: polymorphism information content (PIC) = 0.780; heterozygosity (Het) = 0.843; mean exclusion chance (MEC = 0.766. Kinship tests revealed a typical X-linked inheritance. In 300 meioses under investigation, mutations were not found. Significant deviations from the Hardy-Weinberg equilibrium (HWE) were not established. Linkage studies confirmed closely linkage to DXS101. Additional we found linkage disequilibrium between DXS7424 and DXS101. This requires to use the established haplotype frequencies in kinship testing. PMID:11909667

  20. Record linkage for drug monitoring.

    PubMed Central

    Skegg, D C; Doll, R

    1981-01-01

    A study was carried out to assess the feasibility of using record linkage for drug monitoring. For two years, three types of records were collected for a total of 43 117 people: (1) details of basic attributes, such as sex and age; (2) details of prescriptions dispensed; and (3) records of hospital admissions, obstetric deliveries, and deaths. The records about each person were linked together, and analyses were performed to reveal associations between drugs and diagnoses. The study suggested that record linkage would be useful both for generating and for testing hypotheses about the adverse effects of drugs. The method would be especially valuable for detection of delayed effects (such as the induction of cancer), sudden deaths outside hospital, and effects of the fetus-all of which are difficult to study by other means. A full-scale project would need to cover a large population, and some of the practical issues that would arise are discussed. PMID:7264530

  1. Observations of 231Pa/ 235U disequilibrium in volcanic rocks

    NASA Astrophysics Data System (ADS)

    Pickett, David A.; Murrell, Michael T.

    1997-04-01

    We present here the first survey of ( 231Pa/ 235U) ratios in volcanic rocks; such measurements are made possible by new mass spectrometric techniques. The data place new constraints on the timing and extent of magma source and evolutionary processes, particularly due to the sensitivity of the 231Pa- 235U pair and its intermediate time scale ( 231Pat 1/2 = 33 ky). ( 231Pa/ 235U) is found to vary widely, from 0.2 in carbonatites to 1.1-2.9 in basalts and 0.9-2.2 in arcs. Substantial Pa enrichment is nearly ubiquitous, suggestive of the relative incompatibility of Pa, qualitatively consistent with available partitioning data. The level of 231Pa- 235U disequilibrium typically far exceeds that of 230Th- 238U and is comparable to 226Ra- 230Th. The high ( 231Pa/ 235U) ratios in MORB and other basalts reflect a large degree of discrimination between two incompatible elements, posing challenges for modelling of melt generation and migration. Fundamental differences in ( 231Pa/ 235U) among different basaltic environments are likely related to contrasts in melting zone conditions (e.g., melting rate). Strong ( 231Pa/ 235U) disequilibria in continental basalts, for which ( 230Th/ 238U) disequilibria are small or absent, demonstrate that Pa-U fractionation is possible in both garnet and spinel mantle stability fields. In arcs, correlation of ( 231Pa/ 235U) and ( 230Th/ 238U) is consistent with U enrichment via slab-derived fluids, a process which is additional to the still dominant Pa enrichment. An important new constraint is provided by the observation that the near-equilibrium ( 230Th/ 238U) common to arcs and continental basalts is not typically accompanied by near-equilibrium ( 231Pa/ 235U), arguing against the influence of long magma history, crustal material, or equilibrium mantle sources in affecting decay-series ratios. Small sample sets from two silicic centers illustrate: (1) recent, rapid U enrichment in the magma chamber (El Chichón); and (2) the failure of

  2. Linkage isomerism in coordination polymers.

    PubMed

    Benmansour, Samia; Setifi, Fatima; Triki, Smail; Gómez-García, Carlos J

    2012-02-20

    The use of the recently prepared polynitrile ligand tcnopr3OH(-) ([(NC)(2)CC(OCH(2)CH(2)CH(2)OH)C(CN)(2)](-)) with different salts of Fe(II), Co(II), and Ni(II) has led to a very rare example of linkage isomerism in a coordination chain. These pairs of linkage isomers can be formulated as [M(tcnopr3OH-κN,κO)(2)(H(2)O)(2)]; M = Fe (1), Co (3), and Ni(5) and [M(tcnopr3OH-κN,κN')(2)(H(2)O)(2)]; M = Fe (2), Co (4), and Ni (6). Compounds 1-2, 3-4, and 5-6 are three pairs of linkage isomers since they present the same formula and chain structure and they only differ in the connectivity of the polynitrile ligand bridging the metal ions in the chain: through a N and an O atom (1κN:2κO-isomer) or through two N atoms (1κN:2κN'-isomer). The magnetic properties show, as expected, very similar behaviors for both isomers. PMID:22296602

  3. Linkage and haplotype analysis for chemokine receptors clustered on chromosome 3p21.3 and transmitted in family pedigrees with asthma and atopy

    PubMed Central

    Al-Abdulhadi, Saleh A.; Al-Rabia, Mohammed W. O.

    2010-01-01

    BACKGROUND AND OBJECTIVES: Genomic scan analyses have suggested that the chemokine receptor cluster (CCR2, CCR3, CCR5 <300 kb span) on the short arm of chromosome 3 may contribute to susceptibility to HIV-1 infection and to the expression of a number of inflammatory diseases. Two single nucleotide polymorphisms (SNP) and a deletion in these chemokine receptors have also been found in case-control studies to be associated with susceptibility for asthma and related phenotypes. We extended these case-control studies by establishing whether these polymorphisms were in linkage and linkage disequilibrium with asthma and related phenotypes using linkage and haplotype analyses. METHODS: We genotyped 154 nuclear families identified through two child probands with physician-diagnosed asthma (453 unrelated individuals) including 303 unrelated parents and 150 unrelated children. Atopy was defined as a positive skin prick test (SPT 3 mm) to a panel of common inhaled allergens. RESULTS: From a panel of ten known SNPs, only three polymorphisms: –G190A in CCR2, –T51C in CCR3, and a 32 bp deletion in CCR5 were found to occur at clinically relevant frequencies. All 154 families were used for haplotype analysis but only 12 nuclear families were eligible for linkage analysis. Both analyses confirmed that the mutations were in linkage with asthma, but not with atopy. CONCLUSION: The chemokine receptor genes on 3p21.3 are significantly plausible candidate genes that can influence the expression of asthma. The previous association of the CCR5Δ32 deletion with protection from childhood asthma appears to be explained by linkage disequilibrium with the –G190A mutation in the CCR2 receptor gene. PMID:20220260

  4. Dialysis disequilibrium syndrome induced by neoplastic meningitis in a patient receiving maintenance hemodialysis

    PubMed Central

    2013-01-01

    Background Dialysis disequilibrium syndrome is characterized by neurological symptoms resulting from cerebral edema, which occurs as a consequence of hemodialysis. Dialysis disequilibrium syndrome most often occurs in patients who have just started hemodialysis, during hemodialysis, or soon after hemodialysis; although it may also occur in patients who are under maintenance hemodialysis with pre-existing neurological disease. Case presentation A 70-year-old woman, who had been receiving maintenance hemodialysis for one year, was diagnosed with ovarian cancer by ascites cytological examination. Two years later, she reported severe headache and nausea during hemodialysis and was diagnosed with dialysis disequilibrium syndrome. Although brain images revealed mild hydrocephalus without any mass lesions, poorly differentiated adenocarcinoma cells were detected in her cerebrospinal fluid. These findings indicated that DDS was induced by neoplastic meningitis due to ovarian cancer metastasis. Conclusion Neoplastic meningitis should be considered and excluded in hemodialysis patients with dialysis disequilibrium syndrome and malignancy by cytological examination of the cerebrospinal fluid even if cerebral imaging shows no obvious lesions. This is the first reported case of dialysis disequilibrium syndrome induced by neoplastic meningitis in a patient receiving maintenance hemodialysis. PMID:24238645

  5. Uranium series disequilibrium studies in Chenchu colony area, Guntur district, Andhra Pradesh, India.

    PubMed

    Shrivastava, H B; Koteswara Rao, V; Singh, R V; Rahman, M; Rout, G B; Banerjee, Rahul; Pandey, B K; Verma, M B

    2015-11-01

    An attempt is made to understand uranium series disequilibrium in unconformity proximal related uranium mineralisation in Chenchu colony area, Guntur district, Andhra Pradesh, India. The uranium mineralization in Chenchu colony is the western continuity of the Koppunuru uranium deposit and predominantly hosted by gritty quartzite/conglomerate, which occasionally transgresses to underlying basement granite/basic rock. Disequilibrium studies are based on borehole core samples (35 boreholes, No. of samples=634) broadly divided in two groups of cover rocks of Banganapalle formation (above unconformity) and basement granites (below unconformity). Linear regression coefficient between uranium and radium is 0.95, which reflects excellent correlation and significant enrichment of parent uranium. Disequilibrium studies have indicated predominant disequilibrium in favour of parent uranium (35%), which is probably due to the weathering process causing migration of some of the radionuclides while dissolution of minerals due to groundwater action might have also played a significant role. Further, escape of radon might have accentuated the disequilibrium factor resulting in an increase in the grade of the mineralization. This is well corroborated by the presence of fractures and faults in the study area providing channels for radon migration/escape. PMID:26313623

  6. Ethnic-affiliation estimation by use of population-specific DNA markers.

    PubMed Central

    Shriver, M D; Smith, M W; Jin, L; Marcini, A; Akey, J M; Deka, R; Ferrell, R E

    1997-01-01

    During the past 10 years, DNA analysis has revolutionized the determination of identity in a forensic context. Statements about the biological identity of two human DNA samples now can be made with complete confidence. Although DNA markers are very powerful for distinguishing among individuals, most offer little power to distinguish ethnicity or to support any statement about the physical characteristics of an individual. Through a search of the literature and of unpublished data on allele frequencies we have identified a panel of population-specific genetic markers that enable robust ethnic-affiliation estimation for major U.S. resident populations. In this report, we identify these loci and present their levels of allele-frequency differential between ethnically defined samples, and we demonstrate, using log-likelihood analysis, that this panel of markers provides significant statistical power for ethnic-affiliation estimation. In addition to their use in forensic ethnic-affiliation estimation, population-specific genetic markers are very useful in both population- and individual-level admixture estimation and in mapping genes by use of the linkage disequilibrium created when populations hybridize. PMID:9106543

  7. The 87Sr/86Sr and 143Nd/144Nd disequilibrium between Polynesian hot spot lavas and the clinopyroxenes they host: Evidence complementing isotopic disequilibrium in melt inclusions

    NASA Astrophysics Data System (ADS)

    Jackson, Matthew G.; Hart, Stanley R.; Shimizu, Nobumichi; Blusztajn, Jerzy S.

    2009-03-01

    We report 87Sr/86Sr and 143Nd/144Nd data on clinopyroxenes recovered from 10 ocean island lavas from three different hot spots (Samoa, Society, and Cook-Austral island chains). The clinopyroxenes recovered from eight of the 10 lavas analyzed in this study exhibit 87Sr/86Sr disequilibrium with respect to the host lava. The 87Sr/86Sr ratios in clinopyroxene separates are 95-3146 ppm (0.0095-0.31%) different from their respective host whole rocks. Clinopyroxenes in three lavas have 143Nd/144Nd ratios that are 70-160 ppm (0.007-0.016%) different from the host lavas. The 87Sr/86Sr and 143Nd/144Nd disequilibrium in one lava (the oldest lava considered in this study, Mangaia sample MGA-B-47) can be attributed to posteruptive radiogenic ingrowth, but the isotope disequilibrium in the other, younger lavas cannot be explained by this mechanism. In five of the lava samples, two populations of clinopyroxene were isolated (black and green, separated by color). In four out of five of these samples, the 87Sr/86Sr ratios of the two clinopyroxene populations are isotopically different from each other. In addition to 87Sr/86Sr disequilibrium, the two clinopyroxene populations in one of the lavas (Tahaa sample TAA-B-26) have 143Nd/144Nd ratios that are ˜100 ppm different from each other. Given the resilience of clinopyroxene to seawater alteration and the likelihood that the Sr and Nd isotope composition of fresh clinopyroxene separates provides a faithful record of primary magmatic compositions, the clinopyroxene-clinopyroxene isotope disequilibrium in these four lavas provides strong evidence that a mechanism other than seawater alteration has generated the observed isotopic disequilibrium. This study confirms the isotopic diversity in ocean island lavas previously observed in olivine-hosted melt inclusions. For example, the Sr isotopic variability previously observed in olivine-hosted melt inclusions is mirrored by the isotopic diversity in clinopyroxenes isolated from many of

  8. Privacy preserving interactive record linkage (PPIRL)

    PubMed Central

    Kum, Hye-Chung; Krishnamurthy, Ashok; Machanavajjhala, Ashwin; Reiter, Michael K; Ahalt, Stanley

    2014-01-01

    Objective Record linkage to integrate uncoordinated databases is critical in biomedical research using Big Data. Balancing privacy protection against the need for high quality record linkage requires a human–machine hybrid system to safely manage uncertainty in the ever changing streams of chaotic Big Data. Methods In the computer science literature, private record linkage is the most published area. It investigates how to apply a known linkage function safely when linking two tables. However, in practice, the linkage function is rarely known. Thus, there are many data linkage centers whose main role is to be the trusted third party to determine the linkage function manually and link data for research via a master population list for a designated region. Recently, a more flexible computerized third-party linkage platform, Secure Decoupled Linkage (SDLink), has been proposed based on: (1) decoupling data via encryption, (2) obfuscation via chaffing (adding fake data) and universe manipulation; and (3) minimum information disclosure via recoding. Results We synthesize this literature to formalize a new framework for privacy preserving interactive record linkage (PPIRL) with tractable privacy and utility properties and then analyze the literature using this framework. Conclusions Human-based third-party linkage centers for privacy preserving record linkage are the accepted norm internationally. We find that a computer-based third-party platform that can precisely control the information disclosed at the micro level and allow frequent human interaction during the linkage process, is an effective human–machine hybrid system that significantly improves on the linkage center model both in terms of privacy and utility. PMID:24201028

  9. Empirical aspects of record linkage across multiple data sets using statistical linkage keys: the experience of the PIAC cohort study

    PubMed Central

    2010-01-01

    Background In Australia, many community service program data collections developed over the last decade, including several for aged care programs, contain a statistical linkage key (SLK) to enable derivation of client-level data. In addition, a common SLK is now used in many collections to facilitate the statistical examination of cross-program use. In 2005, the Pathways in Aged Care (PIAC) cohort study was funded to create a linked aged care database using the common SLK to enable analysis of pathways through aged care services. Linkage using an SLK is commonly deterministic. The purpose of this paper is to describe an extended deterministic record linkage strategy for situations where there is a general person identifier (e.g. an SLK) and several additional variables suitable for data linkage. This approach can allow for variation in client information recorded on different databases. Methods A stepwise deterministic record linkage algorithm was developed to link datasets using an SLK and several other variables. Three measures of likely match accuracy were used: the discriminating power of match key values, an estimated false match rate, and an estimated step-specific trade-off between true and false matches. The method was validated through examining link properties and clerical review of three samples of links. Results The deterministic algorithm resulted in up to an 11% increase in links compared with simple deterministic matching using an SLK. The links identified are of high quality: validation samples showed that less than 0.5% of links were false positives, and very few matches were made using non-unique match information (0.01%). There was a high degree of consistency in the characteristics of linked events. Conclusions The linkage strategy described in this paper has allowed the linking of multiple large aged care service datasets using a statistical linkage key while allowing for variation in its reporting. More widely, our deterministic algorithm

  10. Uranium series disequilibrium in the Bargmann property area of Karnes County, Texas

    SciTech Connect

    Davidson, J.R.

    1998-02-01

    Historical evidence is presented for natural uranium series radioactive disequilibrium in uranium bearing soils in the Bargmann property area of karnes County on the Gulf Coastal Plain of south Texas. The early history of uranium exploration in the area is recounted and records of disequilibrium before milling and mining operations began are given. The property contains an open pit uranium mine associated with a larger ore body. In 1995, the US Department of Energy (DOE) directed Oak Ridge National Laboratory (ORNL) to evaluate the Bargmann tract for the presence of uranium mill tailings (ORNL 1996). There was a possibility that mill tailings had washed onto or blown onto the property from the former tailings piles in quantities that would warrant remediation under the Uranium Mill Tailings Remediation Action Project. Activity ratios illustrating disequilibrium between {sup 226}Ra and {sup 238}U in background soils during 1986 are listed and discussed. Derivations of uranium mass-to-activity conversion factors are covered in detail.

  11. A high-density SNP genome-wide linkage search of 206 families identifies susceptibility loci for chronic lymphocytic leukemia.

    PubMed

    Sellick, Gabrielle S; Goldin, Lynn R; Wild, Ruth W; Slager, Susan L; Ressenti, Laura; Strom, Sara S; Dyer, Martin J S; Mauro, Francesca R; Marti, Gerald E; Fuller, Stephen; Lyttelton, Matthew; Kipps, Thomas J; Keating, Michael J; Call, Timothy G; Catovsky, Daniel; Caporaso, Neil; Houlston, Richard S

    2007-11-01

    Chronic lymphocytic leukemia (CLL) and other B-cell lymphoproliferative disorders display familial aggregation. To identify a susceptibility gene for CLL, we assembled families from the major European (ICLLC) and American (GEC) consortia to conduct a genome-wide linkage analysis of 101 new CLL pedigrees using a high-density single nucleotide polymorphism (SNP) array and combined the results with data from our previously reported analysis of 105 families. Here, we report on the combined analysis of the 206 families. Multipoint linkage analyses were undertaken using both nonparametric (model-free) and parametric (model-based) methods. After the removal of high linkage disequilibrium SNPs, we obtained a maximum nonparametric linkage (NPL) score of 3.02 (P = .001) on chromosome 2q21.2. The same genomic position also yielded the highest multipoint heterogeneity LOD (HLOD) score under a common recessive model of disease susceptibility (HLOD = 3.11; P = 7.7 x 10(-5)), which was significant at the genome-wide level. In addition, 2 other chromosomal positions, 6p22.1 (corresponding to the major histocompatibility locus) and 18q21.1, displayed HLOD scores higher than 2.1 (P < .002). None of the regions coincided with areas of common chromosomal abnormalities frequently observed in CLL. These findings provide direct evidence for Mendelian predisposition to CLL and evidence for the location of disease loci. PMID:17687107

  12. Combined segregation and linkage analysis of Graves disease with a thyroid autoantibody diathesis

    SciTech Connect

    Shields, D.C.; Ratanachaiyavong, S.; McGregor, A.M.; Collins, A.; Morton, N.E.

    1994-09-01

    Combined segregation and linkage analysis is a powerful technique for modeling linkage to diseases whose etiology is more complex than the effect of a well-described single genetic locus and for investigating the influence of single genes on various aspects of the disease phenotype. Graves disease is familial and is associated with human leukocyte antigen (HLA) allele DR3. Probands with Graves disease, as well as close relatives, have raised levels of thyroid autoantibodies. This phenotypic information additional to affection status may be considered by the computer program COMDS for combined segregation and linkage analysis, when normals are classified into diathesis classes of increasing thyroid autoantibody titer. The ordinal model considers the cumulative odds of lying in successive classes, and a single additional parameter is introduced for each gene modeled. Distributional assumptions are avoided by providing estimates of the population frequencies of each class. Evidence for linkage was increased by considering the thyroid autoantibody diathesis and by testing two-locus models. The analysis revealed evidence for linkage to HLA-DR when the strong coupling of the linked locus to allele DR3 was considered (lod score of 6.6). Linkage analysis of the residual variation revealed no evidence of linkage to Gm, but a suggestion of linkage to Km. 32 refs., 10 tabs.

  13. A Genetic Linkage Map of the Mimetic Butterfly Heliconius melpomene

    PubMed Central

    Jiggins, Chris D.; Mavarez, Jesus; Beltrán, Margarita; McMillan, W. Owen; Johnston, J. Spencer; Bermingham, Eldredge

    2005-01-01

    Heliconius melpomene is a mimetic butterfly that exhibits great geographic variation in color pattern. We present here a genetic linkage map based on analysis of genetic markers in 73 individuals from a single F2 family, offspring of a cross between H. m. cythera from western Ecuador and H. m. melpomene from French Guiana. A novel “three-step method” is described for the analysis of dominant markers in an F2 cross, using outbred parental strains and taking advantage of the lack of crossing over in female Lepidoptera. This method is likely to prove useful for future mapping studies in outbred species with crossing over restricted to one sex, such as the Lepidoptera and Drosophila. The resulting linkage map has 21 linkage groups corresponding to the 21 chromosomes of H. melpomene and includes 219 AFLP markers, 23 microsatellites, 19 single-copy nuclear genes, and the color pattern switch genes Yb and Sb. The marker density is high, averaging >1/7 cM. The total map length is 1616 cM and the average chromosome length is 77 cM. The genome size of H. melpomene was estimated to be 292 Mb, giving a relationship of physical-to-map distance of 180 kb/cM. This map forms the basis for future comparative linkage analysis of color pattern evolution in Heliconius. PMID:15489522

  14. Linkage map construction involving a reciprocal translocation.

    PubMed

    Farré, A; Benito, I Lacasa; Cistué, L; de Jong, J H; Romagosa, I; Jansen, J

    2011-03-01

    This paper is concerned with a novel statistical-genetic approach for the construction of linkage maps in populations obtained from reciprocal translocation heterozygotes of barley (Hordeum vulgare L.). Using standard linkage analysis, translocations usually lead to 'pseudo-linkage': the mixing up of markers from the chromosomes involved in the translocation into a single linkage group. Close to the translocation breakpoints recombination is severely suppressed and, as a consequence, ordering markers in those regions is not feasible. The novel strategy presented in this paper is based on (1) disentangling the "pseudo-linkage" using principal coordinate analysis, (2) separating individuals into translocated types and normal types and (3) separating markers into those close to and those more distant from the translocation breakpoints. The methods make use of a consensus map of the species involved. The final product consists of integrated linkage maps of the distal parts of the chromosomes involved in the translocation. PMID:21153624

  15. Gripper deploying and inverting linkage

    DOEpatents

    Minichan, Richard L.; Killian, Mark A.

    1993-01-01

    An end effector deploying and inverting linkage. The linkage comprises an air cylinder mounted in a frame or tube, a sliding bracket next to the air cylinder, a stopping bracket depending from the frame and three, pivotally-attached links that are attached to the end effector and to each other in such a way as to be capable of inverting the end effector and translating it laterally. The first of the three links is a straight element that is moved up and down by the shaft of the air cylinder. The second link is attached at one end to the stopping bracket and to the side of the end effector at the other end. The first link is attached near the middle of the second, sharply angled link so that, as the shaft of the air cylinder moves up and down, the second link rotates about an axis perpendicular to the frame and inverts and translates the end effector. The rotation of the second link is stopped at both ends when the link engages stops on the stopping bracket. The third link, slightly angled, is attached to the sliding bracket at one end and to the end of the end effector at the other. The third helps to control the end effector in its motion.

  16. Gripper deploying and inverting linkage

    DOEpatents

    Minichan, R.L.; Killian, M.A.

    1993-03-02

    An end effector deploying and inverting linkage. The linkage comprises an air cylinder mounted in a frame or tube, a sliding bracket next to the air cylinder, a stopping bracket depending from the frame and three, pivotally-attached links that are attached to the end effector and to each other in such a way as to be capable of inverting the end effector and translating it laterally. The first of the three links is a straight element that is moved up and down by the shaft of the air cylinder. The second link is attached at one end to the stopping bracket and to the side of the end effector at the other end. The first link is attached near the middle of the second, sharply angled link so that, as the shaft of the air cylinder moves up and down, the second link rotates about an axis perpendicular to the frame and inverts and translates the end effector. The rotation of the second link is stopped at both ends when the link engages stops on the stopping bracket. The third link, slightly angled, is attached to the sliding bracket at one end and to the end of the end effector at the other. The third helps to control the end effector in its motion.

  17. URANIUM-SERIES DISEQUILIBRIUM IN TUFF AND GRANITE:HYDROGEOLOGICAL IMPLICATIONS

    SciTech Connect

    M. Gasscoyne; N.H. Miller

    2000-10-27

    radionuclide involved. Depending on the analytical precision obtained, the observation of a {sup 234}U/{sup 238}U activity ratio that is less than or greater than 1.000 clearly shows that an isotope of uranium has migrated within the rock in the last 1-2 million years. Other daughter/parent activity ratios can be used to detect radionuclide migration over shorter time-scales, such as {sup 230}Th/{sup 234}U (300,000 years) and {sup 226}Ra/{sup 230}Th (8,000 years). Uranium-series disequilibrium is, therefore, a useful technique for application to site evaluation for nuclear fuel waste disposal because it can be used to: (1) show that so-called ''intact rock'' is indeed intact (i.e. radionuclides are in secular equilibrium and are immobile), (2) determine the principal flow regimes in a rock mass by analysis of rock matrix, fracture material, etc., (3) estimate the time period of recent radionuclide migration in the rock, and (4) proxy as a natural analogue for the potential mobility of uranium at the site. Several examples of these applications have been reported. This paper describes the use of uranium-series disequilibrium in the comparison of two North American sites: the water-saturated Lac du Bonnet granite batholith on the Canadian Shield and the unsaturated tuffs from the Exploratory Studies Facility (ESF) and Cross-Drift Tunnels at Yucca Mountain, Nevada. In particular, the fact that unfractured rock should be at secular equilibrium is applied to both sites to determine if the rock matrix is a significant flow path for groundwater.

  18. Uranium-series disequilibrium in volcanic rocks from the Northeast Japan Arc

    NASA Astrophysics Data System (ADS)

    Yokoyama, T.; Iwamori, H.; Ueki, K.

    2011-12-01

    Subducting slabs are considered to release fluid components as a result of mineralogical reactions during progressive metamorphic dehydration. The fluid released from the slab subsequently induces melting in the mantle wedge as it ascends, resulting in island arc volcanism [1]. To understand the characteristics of slab-derived materials, geochemical tracers such as trace elements, radiogenic isotopes (e.g., Sr, Nd, Pb), and stable isotopes (e.g., B, Li) have been commonly used [2-3]. U-series disequilibria of island arc volcanic rocks have been used to understand melt generation in the source mantle and the timescales of fluid/melt migration in subduction zones. This is possible because of the short half-lives of daughter nuclides of 238U, 235U and 232Th (e.g., 75 kyr for 230Th, and 1.6 kyr for 226Ra). We report our preliminary measurements on 238U-230Th disequilibrium in volcanic rocks from the Northeast Japan Arc. Lava samples of basalts and basaltic andesites were collected from four volcanoes (Iwate, Akita-Komagatake, Yakeyama and Kampu). The eruption ages of these rocks are estimated to be range from 0 to 30 ka. The frontal-arc lavas (Iwate and Akita-Komagatake) are characterized by 238U-230Th disequilibrium with moderate 238U enrichments (5-10%). This is due to the addition to the mantle wedge of slab-derived fluids enriched in fluid-mobile elements (U) relative to less fluid-mobile elements (Th). The extent of 238U enrichment decreases as the slab depth increases, and the rear-arc lavas (Kampu) show 230Th enrichments relative to 238U (~5%). This generally reflects gradual decrease of the amount of slab derived fluid mixed into the wedge mantle. Thus, the 230Th excesses in rear-arc lavas may be predominantly produced by the melting of garnet-bearing upwelling mantle as observed in MORB (dynamic melting). However, our data show 230Th excess with an extremely low (230Th/232Th) ratio (~0.8) that plots outside the MORB data. This strongly argues against a model

  19. Segregation and linkage analysis of serum angiotensin I-converting enzyme levels: evidence for two quantitative-trait loci.

    PubMed Central

    McKenzie, C A; Julier, C; Forrester, T; McFarlane-Anderson, N; Keavney, B; Lathrop, G M; Ratcliffe, P J; Farrall, M

    1995-01-01

    Human serum angiotensin I-converting enzyme (ACE) levels vary substantially between individuals and are highly heritable. Segregation analysis in European families has shown that more than half of the total variability in ACE levels is influenced by quantitative-trait loci (QTL). One of these QTLs is located within or close to the ACE locus itself. Combined segregation/linkage analysis in a series of African Caribbean families from Jamaica shows that the ACE insertion-deletion polymorphism is in moderate linkage disequilibrium with an ACE-linked QTL. Linkage analysis with a highly informative polymorphism at the neighboring growth-hormone gene (GH) shows surprisingly little support for linkage (LOD score [Z] = 0.12). An extended analysis with a two-QTL model, where an ACE-linked QTL interacts additively with an unlinked QTL, significantly improves both the fit of the model (P = .002) and the support for linkage between the ACe-linked QTL interacts additively with an unlinked QTL, significantly improves both the fit of the model (P = .002) and the support for linkage between the ACe-linked QTL and GH polymorphism (Z = 5.0). We conclude that two QTLs jointly influence serum ACE levels in this population. One QTL is located within or close to the ACE locus and explains 27% of the total variability; the second QTL is unlinked to the ACE locus and explains 52% of the variability. The identification of the molecular mechanisms underlying both QTLs is necessary in order to interpret the role of ACE in cardiovascular disease. PMID:8533773

  20. An introduction to recombination and linkage analysis

    SciTech Connect

    Mcpeek, M.S.

    1996-12-31

    With a garden as his laboratory, Mendel was able to discern basic probabilistic laws of heredity. Although it first appeared as a baffling exception to one of Mendel`s principles, the phenomenon of variable linkage between characters was soon recognized to be a powerful tool in the process of chromosome mapping and location of genes of interest. In this introduction, we first describe Mendel`s work and the subsequent discovery of linkage. Next we describe the apparent cause of variable linkage, namely recombination, and we introduce linkage analysis. 33 refs., 1 fig., 2 tabs.

  1. Linkage Analysis with an Alternative Formulation for the Mixed Model of Inheritance: The Finite Polygenic Mixed Model

    PubMed Central

    Stricker, C.; Fernando, R. L.; Elston, R. C.

    1995-01-01

    This paper presents an extension of the finite polygenic mixed model of FERNANDO et al. (1994) to linkage analysis. The finite polygenic mixed model, extended for linkage analysis, leads to a likelihood that can be calculated using efficient algorithms developed for oligogenic models. For comparison, linkage analysis of 5 simulated 4021-member pedigrees was performed using the usual mixed model of inheritance, approximated by HASSTEDT (1982), and the finite polygenic mixed model extended for linkage analysis presented here. Maximum likelihood estimates of the finite polygenic mixed model could be inferred to be closer to the simulated values in these pedigrees. PMID:8601502

  2. Germany's Persistent Balance-of-Payments Disequilibrium Revisited. German Studies Notes.

    ERIC Educational Resources Information Center

    Kindleberger, Charles P.

    This essay compares Germany's persistent financial disequilibrium with the balance of payments situation in the United States. Delivered at a Symposium on German Economic Growth and Stability, the author concentrates on Germany's balance of payments surplus and presents U.S. figures mainly as a point of comparison. The material on Germany has been…

  3. Observations of Jupiter at 5 micron from IRTF/TEXES : latitudinal variability of disequilibrium species

    NASA Astrophysics Data System (ADS)

    Drossart, P.; Encrenaz, T.; Greathouse, T. K.; DeWitt, C.; Fouchet, T.; Janssen, M.; Gulkis, S.; Orton, G. S.; Fletcher, L.; Giles, R.; Atreya, S. K.; Boudon, V.

    2015-10-01

    Observations of Jupiter in the 5 μm spectral window,obtained in March/April 2015 at IRTF are presented, in preparation of the arrival of the NASA/JUNO mission in 2016. Sounding of the troposphere of Jupiter below 2 bars is obtained from the observations, to search for the variability of disequilibrium species, related to deep atmospheric circulation.

  4. Disequilibrium and Questioning in the Primary Classroom: Establishing Routines that Help Students Learn

    ERIC Educational Resources Information Center

    Carter, Susan

    2008-01-01

    Jean Piaget (1970) defined "disequilibrium" as a conflict between new ideas and current conceptions. In this article, the author describes how introducing this concept to her first graders improved formative assessment results and the overall classroom climate during mathematics class. Students feel success in mathematics even without mastering a…

  5. Nucleon-Alpha Particle Disequilibrium and Short-Lived r-Process Radioactivities

    NASA Technical Reports Server (NTRS)

    Meyer, B. S.; Clayton, D. D.; Chellapilla, S.; The, L.-S.

    2002-01-01

    r-Process yields can be extremely sensitive to expansion parameters when a persistent disequilibrium between free nucleons and alpha particles is present. This may provide a natural scenario for understanding the variation of heavy and light r-process isotopes in different r-process events. Additional information is contained in the original extended abstract.

  6. Comparing atmospheric chemical disequilibrium of Earth and Mars to detect the traces of Life

    NASA Astrophysics Data System (ADS)

    Simoncini, Eugenio; Brucato, John Robert; Grassi, Tommaso

    Thanks to rover explorations, satellite mapping and in loco measurements, there are many evidence nowadays that early Mars could have hold extended oceans of liquid water. This makes early Mars similar to early Earth, and a deeper understanding of the conditions which led to the emergence of Life on Earth is needed. It has long been observed that Earth's atmosphere is uniquely far from its thermochemical equilibrium state in terms of its chemical composition. Studying this state of disequilibrium is important for its potential role in the detection of life on other suitable planets [1][2][3]. We developed a methodology to calculate the extent of atmospheric chemical disequilibrium [3][4]. This tool allows us to understand, on a thermodynamic basis, how life affected - and still affects - geochemical processes on Earth, and if other planetary atmospheres are habitable or have a disequilibrium similar to the Earth's one. A new computational framework called KROME has been applied to atmospheric models in order to give a correct computation of reactionś kinetics [5]. In this work we present a first computation of the extent of disequilibrium for the present and early Earth and Mars atmospheres, considering the specific contribution of the different atmospheric processes, such as thermochemical reactions, eddy diffusion, photochemistry, deposition, and the effect of the biosphere. We then assess the effect of life on atmospheric disequilibrium of the Earth and provide a comparison between “alive” and “dead” Earth, present and (plausible) early Mars. Our results provide a comprehensive analysis of atmospheric disequilibrium for rocky and habitable planets, which can be also used for the detection of habitable conditions on farther planetary bodies. [1] Lovelock, J. E.: A physical basis for life detection experiments, Nature, 207, 568 (1965) [2] Kleidon, A., Physics of Life Reviews, 7, 424 (2010) [3] Simoncini E., Grassi T., Disequilibrium in planetary

  7. A genetic linkage map and comparative mapping of the prairie vole (Microtus ochrogaster) genome

    PubMed Central

    2011-01-01

    Background The prairie vole (Microtus ochrogaster) is an emerging rodent model for investigating the genetics, evolution and molecular mechanisms of social behavior. Though a karyotype for the prairie vole has been reported and low-resolution comparative cytogenetic analyses have been done in this species, other basic genetic resources for this species, such as a genetic linkage map, are lacking. Results Here we report the construction of a genome-wide linkage map of the prairie vole. The linkage map consists of 406 markers that are spaced on average every 7 Mb and span an estimated ~90% of the genome. The sex average length of the linkage map is 1707 cM, which, like other Muroid rodent linkage maps, is on the lower end of the length distribution of linkage maps reported to date for placental mammals. Linkage groups were assigned to 19 out of the 26 prairie vole autosomes as well as the X chromosome. Comparative analyses of the prairie vole linkage map based on the location of 387 Type I markers identified 61 large blocks of synteny with the mouse genome. In addition, the results of the comparative analyses revealed a potential elevated rate of inversions in the prairie vole lineage compared to the laboratory mouse and rat. Conclusions A genetic linkage map of the prairie vole has been constructed and represents the fourth genome-wide high-resolution linkage map reported for Muroid rodents and the first for a member of the Arvicolinae sub-family. This resource will advance studies designed to dissect the genetic basis of a variety of social behaviors and other traits in the prairie vole as well as our understanding of genome evolution in the genus Microtus. PMID:21736755

  8. Disequilibrium in the malate dehydrogenase reaction in rat liver mitochondria in vivo

    PubMed Central

    Heath, D. F.; Phillips, J. C.

    1972-01-01

    1. When [2-14C]pyruvate is injected into rats the C3-position of liver glutamate becomes more heavily labelled than the C2-position, thus establishing that oxaloacetate and fumarate are not in equilibrium in rat liver mitochondria in vivo. The amount of disequilibrium was shown to be simply related to the value that the C3-label/C2-label ratio would have were no label recycled. This ratio, z, was calculated for post-absorptive rats in environmental temperatures of 20° and 30°C from determinations of the distribution of label within glutamate 1, 3 and 10min after intravenous injection of [2-14C]pyruvate. The values of z (best estimate and range) were 1.65 (1.60–1.69) in rats at 20°C and 2.43 (2.23–2.63) in rats at 30°C. These values of z imply the following rates of interconversion in mitochondria of fumarate and oxaloacetate (in terms of the oxaloacetate→citrate flux, R) in rats at 20°C: [Formula: see text] and in rats at 30°C: [Formula: see text] 2. The kinetic parameters of malate dehydrogenase and fumarate hydratase and the intramitochondrial concentrations of NAD+ and NADH under (as far as could be judged) conditions in vivo were collated. From them and the best estimates of R now available were calculated the rates of interconversion of fumarate, malate and oxaloacetate required to give the found values of z. These rates showed that the fumarate hydratase reaction was nearly in equilibrium, but that the malate dehydrogenase reaction was considerably out of equilibrium. The calculations also led to the following conclusions. 3. In livers of rats at 20° and 30°C mitochondrial malate concentrations were respectively about 5 and 1.5 times mean cellular concentrations. 4. Mitochondrial oxaloacetate concentrations were less than 0.2 of the mean cellular concentrations. They were also only 0.65 and 0.55 of the equilibrium concentrations for the malate dehydrogenase reaction in rats at 20° and 30°C respectively. 5. Malate dehydrogenase activity was low

  9. Magma storage depths in the Eastern Volcanic Zone of Iceland: disentangling disequilibrium and tuning thermobarometers

    NASA Astrophysics Data System (ADS)

    Neave, D.; Maclennan, J.; Thordarson, T.; Hartley, M. E.; Buisman, I.; Namur, O.; Halldorsson, S. A.

    2015-12-01

    The Eastern Volcanic Zone (EVZ) is the most volcanically productive of Iceland's neovolcanic zones. In addition to being the source of numerous small but disruptive eruptions, such Eyjafjallajökull in 2010 and Grímsvötn in 2011, the EVZ is notable for generating very large eruptions such as the environmentally impacting Laki eruption in 1783-84 and the widely dispersed Saksunarvatn Ash. Thus, investigating the plumbing systems of volcanoes in the EVZ not only reveals information about magma reservoir behaviour and crustal structure, but also has important implications for hazard management. However, in order to obtain reliable estimates of pre-eruptive magma storage conditions and depths from minerals a number of conditions need to be met first. Firstly, all estimates of pre-eruptive conditions need to be placed into petrogenetic frameworks that consider the extensive disequilibrium that results not only from fractionation, but also from magma mixing and crystal mush entrainment. Secondly, it is important to verify that the mineral-melt equilibrium, i.e. thermobarometeric, models used are well calibrated at the expected conditions of magma storage. Using a range of techniques including QEMSCAN imaging, textural analysis and geochemical microanalysis of crystals, glasses and melt inclusions, we present internally consistent models of magma evolution and storage for a number of eruptions in the EVZ, including Laki and the 10ka Grímsvötn tephra series (i.e. Saksunarvatn Ash). All eruptions studied preserve evidence of mixing and crystallisation of primitive melts in the mid-crust (8-20 km) followed by crystallisation of evolved and, in general, more incompatible element-enriched melts in the shallow crust (0-8 km) shortly before eruption. Substantial uncertainties in storage depths nevertheless remain because of incomplete calibration of clinopyroxene-melt equilibria at mid-crustal pressures. As part of an ongoing experimental campaign on Icelandic magma

  10. Examining the Linkage Between FRAMES and GMS

    SciTech Connect

    Whelan, Gene; Castleton, Karl J.

    2006-02-13

    Because GMS provides so many features, of which some are also addressed by FRAMES, it could represent a platform to link to FRAMES, or FRAMES could represent a platform to link to GMS. The focus of this summary is to examine the strengths and weaknesses of the potential linkage direction and provide recommendations for the linkage between FRAMES and GMS.

  11. Compensating linkage for main rotor control

    NASA Technical Reports Server (NTRS)

    Jeffery, P. A. E.; Huber, R. F. (Inventor)

    1981-01-01

    A compensating linkage for the rotor control system on rotary wing aircraft is described. The main rotor and transmission are isolated from the airframe structure by clastic suspension. The compensating linkage prevents unwanted signal inputs to the rotor control system caused by relative motion of the airframe structure and the main rotor and transmission.

  12. Developing a correlation index and U disequilibrium factor for the exploratory boreholes in Wahkut block of West Khasi Hills district, Meghalaya (India).

    PubMed

    Kukreti, B M; Kumar, Pramod

    2013-02-01

    With the objective to affirm the apparent uranium ore zone grade/thickness with good confidence for the non-cored as well as those boreholes with poor core recovery in the sedimentary environment of Wahkut block, West Khasi Hills district of Meghalaya, a systematic study between the in situ measured γ-ray logs under field conditions and laboratory analyzed core assay under controlled conditions has been carried out. The study area spans 2 sqkm having 33 cored and 39 non-cored boreholes with a cumulative drilled depth of about 11,000 m. On this available cored borehole database, simultaneous uranium ore zone continuity, both for in situ γ-ray logs and radiometric core assay, was evaluated with the experimental parameters of 1.0m ore zone thickness at 0.010% eU(3)O(8) cut off grade. A population of 18 such simultaneous qualifying zone (borehole log and core assay) across the 15 cored boreholes gave a grade thickness continuity index of 0.92 with a moderately strong relationship between the radiometric core assay and the in situ γ-ray logs. After validation of an in situ uranium ore zone, study boreholes were examined for their uranium disequilibrium status by fitting regression equations for the radiometric U(3)O(8)(β/γ) and spectrometric radium measurements, done on the borehole core samples. A parent favoring uranium disequilibrium was observed in the sedimentary environment of Wahkut block, with a log normal distribution. An average uranium disequilibrium factor 1.46 ± 0.245 was estimated for the 19 study boreholes, across the block. PMID:23202436

  13. Integration of the Aedes aegypti mosquito genetic linkage and physical maps.

    PubMed

    Brown, S E; Severson, D W; Smith, L A; Knudson, D L

    2001-03-01

    Two approaches were used to correlate the Aedes aegypti genetic linkage map to the physical map. STS markers were developed for previously mapped RFLP-based genetic markers so that large genomic clones from cosmid libraries could be found and placed to the metaphase chromosome physical maps using standard FISH methods. Eight cosmids were identified that contained eight RFLP marker sequences, and these cosmids were located on the metaphase chromosomes. Twenty-one cDNAs were mapped directly to metaphase chromosomes using a FISH amplification procedure. The chromosome numbering schemes of the genetic linkage and physical maps corresponded directly and the orientations of the genetic linkage maps for chromosomes 2 and 3 were inverted relative to the physical maps. While the chromosome 2 linkage map represented essentially 100% of chromosome 2, approximately 65% of the chromosome 1 linkage map mapped to only 36% of the short p-arm and 83% of the chromosome 3 physical map contained the complete genetic linkage map. Since the genetic linkage map is a RFLP cDNA-based map, these data also provide a minimal estimate for the size of the euchromatic regions. The implications of these findings on positional cloning in A. aegypti are discussed. PMID:11238414

  14. Estimation of the dispersal of a major pest of maize by cline analysis of a temporary contact zone between two invasive outbreaks.

    PubMed

    Bermond, Gérald; Blin, Aurélie; Vercken, Elodie; Ravigné, Virginie; Rieux, Adrien; Mallez, Sophie; Morel-Journel, Thibaut; Guillemaud, Thomas

    2013-11-01

    Dispersal is a key factor in invasion and in the persistence and evolution of species. Despite the importance of estimates of dispersal distance, dispersal measurement remains a real methodological challenge. In this study, we characterized dispersal by exploiting a specific case of biological invasion, in which multiple introductions in disconnected areas lead to secondary contact between two differentiated expanding outbreaks. By applying cline theory to this ecological setting, we estimated σ, the standard deviation of the parent-offspring distance distribution, of the western corn rootworm, Diabrotica virgifera virgifera, one of the most destructive pests of maize. This species is currently invading Europe, and the two largest invasive outbreaks, in northern Italy and Central Europe, have recently formed a secondary contact zone in northern Italy. We identified vanishing clines at 12 microsatellite loci throughout the contact zone. By analysing both the rate of change of cline slope and the spatial variation of linkage disequilibrium at these markers, we obtained two σ estimates of about 20 km/generation(1/2). Simulations indicated that these estimates were robust to changes in dispersal kernels and differences in population density between the two outbreaks, despite a systematic weak bias. These estimates are consistent with the results of direct methods for measuring dispersal applied to the same species. We conclude that secondary contact resulting from multiple introductions is very useful for the inference of dispersal parameters and should be more widely used in other species. PMID:24118290

  15. Particulate organic carbon export fluxes on Chukchi Shelf, western Arctic Ocean, derived from 210Po/210Pb disequilibrium

    NASA Astrophysics Data System (ADS)

    He, Jianhua; Yu, Wen; Lin, Wuhui; Men, Wu; Chen, Liqi

    2015-05-01

    Fluxes of particulate organic carbon (POC) were derived from 210Po/210Pb disequilibrium during the 4th Chinese National Arctic Research Expedition (CHINARE-4) from July 1 to September 28, 2010. Average residence times of particulate 210Po in the euphotic zone were -16.00 a to 1.54 a, which are higher than those of dissolved 210Po (-6.89 a to -0.70 a). Great excesses of dissolved 210Po were observed at all stations, with an average 210Po/210Pb ratio of 1.91±0.20, resulting from 210Pb atmospheric deposition after sea ice melt. POC fluxes from the euphotic zone were estimated by two methods (E and B) in the irreversible scavenging model. Estimated POC fluxes were 945-126 mmol C/(m2·a) and 1 848-109 mmol C/(m2·a) by methods E and B, respectively, both decreasing from low to high latitude. The results are comparable to previous works for the same region, indicating efficient biological pumping in the Chukchi Sea. The results can improve understanding of the carbon cycle in the western Arctic Ocean.

  16. Uranium-series disequilibrium, sedimentation, diatom frustules, and paleoclimate change in Lake Baikal.

    SciTech Connect

    Edgington, D. N.; Robbins, J. A.; Colman, S. M.; Orlandini, K. A.; Gustin, M.-P.; Environmental Research; Univ. of Wisconsin; NOAA; US Geological Survey

    1996-09-01

    The large volume of water, approximately one-fifth of the total surface fresh water on the planet, contained in Lake Baikal in southeastern Siberia is distinguished by having a relatively high concentration of uranium (ca. 2 nM), and, together with the surface sediments, an unusually high {sup 234}U{sup 238}U alpha activity ratio of 1.95. About 80% of the input of uranium to the lake, with a {sup 234}U{sup 238}U ratio of 2.0, comes from the Selenga River. Profiles of uranium, as well as the extent of isotopic disequilibrium in a 9 m sediment core collected on Academic Ridge, generally show high values during interglacial periods corresponding to high diatom frustule numbers (DiFr) and biogenic silica (BSi) data that have been reported elsewhere. During glacial periods (low DiFr and BSi), uranium progeny ({sup 234}U and {sup 230}Th) were in secular equilibrium with low concentrations of their parent {sup 238}U. Radionuclide distributions were interpreted in terms of a quantitative model allowing for adsorption of riverine inputs of uranium onto two classes of sedimenting particles with differing {sup 238}U{sup 232}Th ratios and uranium progeny in secular equilibrium. If the {sup 234}U{sup 238}U activity ratio of adsorbed uranium has remained constant, mean sedimentation rates can be independently estimated as 3.6 {+-} 0.6 and 3.7 {+-} 0.9 cm x kyr{sup -1} for the decay of {sup 234}U and in-growth of {sup 230}Th, respectively. These rates are consistent with a mean rate of 3.76 cm x kyr{sup -1}, calculated by optimization of the correspondence between adsorbed {sup 238}U and {delta}{sup 18}O in dated oceanic sediments. The adsorbed uranium apparently tracks variable river flow during interglacials and is drastically reduced during periods of glaciation. Evidently, uranium has not been significantly redistributed within Baikal sediments over at least the past 250 kyr and is a unique, biologically non-essential, tracer for climate-sensitive processes, which provide

  17. Uranium-series disequilibrium, sedimentation, diatom frustules, and paleoclimate change in Lake Baikal

    USGS Publications Warehouse

    Edgington, D.N.; Robbins, J.A.; Colman, Steven M.; Orlandini, K.A.; Gustin, M.-P.

    1996-01-01

    The large volume of water, approximately one-fifth of the total surface fresh water on the planet, contained in Lake Baikal in southeastern Siberia is distinguished by having a relatively high concentration of uranium (ca. 2 nM), and, together with the surface sediments, an unusually high 234U/238U alpha activity ratio of 1.95. About 80% of the input of uranium to the lake, with a 234U/238U ratio of 2.0, comes from the Selenga River. Profiles of uranium, as well as the extent of isotopic disequilibrium in a 9 m sediment core collected on Academic Ridge, generally show high values during interglacial periods corresponding to high diatom frustule numbers (DiFr) and biogenic silica (BSi) data that have been reported elsewhere. During glacial periods (low DiFr and BSi), uranium progeny (234U and 230Th) were in secular equilibrium with low concentrations of their parent 238U. Radionuclide distributions were interpreted in terms of a quantitative model allowing for adsorption of riverine inputs of uranium onto two classes of sedimenting particles with differing 238U/232Th ratios and uranium progeny in secular equilibrium. If the 234U/238U activity ratio of adsorbed uranium has remained constant, mean sedimentation rates can be independently estimated as 3.6 ?? 0.6 and 3.7 ?? 0.9 cm ?? kyr-1 for the decay of 234U and in-growth of 230Th, respectively. These rates are consistent with a mean rate of 3.76 cm ?? kyr-1, calculated by optimization of the correspondence between adsorbed 238U and ??18O in dated oceanic sediments. The adsorbed uranium apparently tracks variable river flow during interglacials and is drastically reduced during periods of glaciation. Evidently, uranium has not been significantly redistributed within Baikal sediments over at least the past 250 kyr and is a unique, biologically non-essential, tracer for climate-sensitive processes, which provide their own internal geochronometers, potentially useful for ages up to 1 Myr BP.

  18. Water disequilibrium in olivines from Hawaiian peridotites: Recent metasomatism, H diffusion and magma ascent rates

    NASA Astrophysics Data System (ADS)

    Peslier, Anne H.; Bizimis, Michael; Matney, Mark

    2015-04-01

    Constraining the distribution and mobility of H in olivine, the main mineral of the upper mantle, is crucial to our understanding of Earth's geodynamics because this trace element influences melting, rheology, and electrical and thermal conductivities of peridotite. For this purpose, the olivines from fresh and well-characterized peridotite xenoliths from Salt Lake Crater and Pali (Oahu, Hawaii), representing samples of the oceanic mantle lithosphere, were analyzed by FTIR. Water concentrations decrease from core to edge and near fractures of olivine grains, and are best interpreted as H loss during xenolith ascent to the surface in its host magma. Diffusion modeling of these profiles allowed the calculation of diffusion times, which were in turn used to estimate the average ascent rates of the xenolith host nephelinite at 0.2-25.3 m s-1. These rates are similar to those of continental basaltic magmas. Diffusion modeling further shows that the water contents at the core of olivines are preserved mantle values and are heterogeneous within each xenolith. In addition, the discrepant behavior of the 3225 cm-1 OH band (due to H in a Mg vacancy) relative to the other OH bands (in particular the Ti-H defect) along profiles evidences that H is heterogeneously distributed amongst olivine defects. These defect profiles are modeled to calculate that the diffusion rate of the Mg-H defect is about 1.3-6.8 times faster than that of the Ti-H defect. The heterogeneous distribution of H in the mantle between olivine cores in single xenoliths and within olivine grains testifies of a state of disequilibrium for water in these samples. The Salt Lake Crater peridotite olivines record two processes; recent metasomatism by a melt bringing water followed by water loss during ascent in the host magma, neither having lasted long enough for water to reach equilibrium. The observed decoupling between the heterogeneous distribution of H and the homogeneous distribution of lithophile elements

  19. An AFLP genetic linkage map of pacific abalone ( Haliotis discus hannai)

    NASA Astrophysics Data System (ADS)

    Qi, Li; Yanhong, Xu; Ruihai, Yu; Akihiro, Kijima

    2007-07-01

    A genetic linkage map of Pacific abalone ( Haliotis discus hannai) was constructed using AFLP markers based on a two-way pseudo-testeross strategy in a full-sib family. With 33 primer combinations, a total of 455 markers (225 from the female parent and 230 from the male parent) segregated in a 1:1 ratio, corresponding to DNA polymorphism: heterozygous in one parent and null in the other. The female framework map consisted of 174 markers distributed in 18 linkage groups, equivalent to the H. discus hannai haploid chromosome number, and spanning a total length of 2031.4 cM, with an average interval of 13.0 cM between adjacent markers. The male framework map consisted of 195 markers mapped on 19 linkage groups, spanning a total length of 2273.4 cM, with an average spacing of 12.9 cM between adjacent markers. The estimated coverage for the framework linkage maps was 81.2% for the female and 82.1% for the male, on the basis of two estimates of genome length. Fifty-two markers (11.4%) remained unlinked. The level of segregation distortion observed in this cross was 20.4%. These linkage maps will serve as a starting point for linkage studies in the Pacific abalone with potential application for marker-assisted selection in breeding programs.

  20. Replication of genetic linkage by follow-up of previously studied pedigrees

    SciTech Connect

    Gershon, E.S.; Goldin, L.R. )

    1994-04-01

    Independent replication of linkage in previously studied pedigrees is desirable when genetic heterogeneity is suspected or when the illness is very rare. When the likelihood of the new data in this type of replication study is computed as conditional on the previously reported linkage results, it can be considered independent. The authors describe a simulation method using the SLINK program in which the initial data are fixed and newly genotyped individuals are simulated under [theta] = .01 and [theta] = .50. These give appropriate lod score criteria for rejection and acceptance of linkage in the follow-up study, which take into account the original marker genotypes in the data. An estimate of the power to detect linkage in the follow-up data is also generated. 13 refs., 1 fig., 1 tab.

  1. The REBUS-MCNP linkage.

    SciTech Connect

    Stevens, J. G.; Nuclear Engineering Division

    2009-04-24

    The Reduced Enrichment Research and Test Reactor (RERTR) Program uses the REBUS-PC computer code to provide reactor physics and core design information such as neutron flux distributions in space, energy, and time, and to track isotopic changes in fuel and neutron absorbers with burnup. REBUS-PC models the complete fuel cycle including shuffling capability. REBUS-PC evolved using the neutronic capabilities of multi-group diffusion theory code DIF3D 9.0, but was extended to apply the continuous energy Monte Carlo code MCNP for one-group fluxes and cross-sections. The linkage between REBUS-PC and MCNP has recently been modernized and extended, as described in this manual. REBUS-PC now calls MCNP via a system call so that the user can apply any valid MCNP executable. The interface between REBUS-PC and MCNP requires minimal changes to an existing MCNP model, and little additional input. The REBUS-MCNP interface can also be used in conjunction with DIF3D neutronics to update an MCNP model with fuel compositions predicted using a DIF3D based depletion.

  2. Alpha-recoil damage: Relation to isotopic disequilibrium and leaching of radionuclides

    SciTech Connect

    Fleischer, R.L. )

    1988-06-01

    The observation by Raabe et al. (1973) of large differences between the solubilities of isotopically different plutonium dioxides, has led to the recognition of preferential etching of recoil damage as a widespread phenomenon for alpha-active radionuclides. The associated preferential solubility of the products of alpha decay, along with direct recoil ejection, are the two specific microscopic mechanisms that are documented as causes of isotopic disequilibrium in the U and Th decay series. Similarly, leaching plays a significant role in releasing {sup 222}Rn from natural substances, {sup 222}Rn being the alpha-decay product of {sup 226}Ra. The average annealing time in nature of the damage sites can be inferred from the extent of isotopic disequilibrium for different isotopic pairs in the Th and U decay chains.

  3. Influence of random daughter exposure rate, unattachment fraction, and disequilibrium on occurrence of lung tumors

    SciTech Connect

    Cross, F.T.; Palmer, R.F.; Dagle, G.E.; Busch, R.H.; Buschbom, R.L.

    1983-10-01

    Groups of male, specific-pathogen-free (SPF), Wistar rats were exposed to several concentrations of radon daughters and uranium ore dust to clarify the roles of exposure rate, unattached RaA daughters, and the degree of radon daughter disequilibrium, in the development of respiratory system disease. Modeled, human-dosimetric data indicate that the dose to sensitive tissues of the respiratory tract increases with increasing radon-daughter unattachment fraction and degree of disequilibrium. Experimental verification of these dose-effect relationships is needed to protect the health of workers and of the public exposed to radon-daughter environments. Data bearing on these relationships as well as updated results of experiments designed to test the role of radon-daughter exposure rate on lung-tumor incidence are reported. 13 references, 3 tables.

  4. Th-230 - U-238 series disequilibrium of the Olkaria rhyolites Gregory Rift Valley, Kenya: Residence times

    NASA Technical Reports Server (NTRS)

    Black, S.; Macdonald, R.; Kelly, M.

    1993-01-01

    U-series disequilibrium analyses have been conducted on samples from Olkaria rhyolite centers with ages being available for all but one center using both internal and whole rock isochrons. 67 percent of the rhyolites analyzed show U-Th disequilibrium, ranging from 27 percent excess thorium to 36 percent excess uranium. Internal and whole rock isochrons give crystallization/formation ages between 65 ka and 9 ka, in every case these are substantially older than the eruptive dates. The residence times of the rhyolites (U-Th age minus the eruption date) have decreased almost linearly with time, from 45 ka to 7 Ka suggesting a possible increase of activity within the system related to increased basaltic input. The long residence times are mirrored by large Rn-222 fluxes from the centers which cannot be explained by larger U contents.

  5. Study of natural radioactivity and the state of radioactive disequilibrium in U-series for rock samples, North Eastern Desert, Egypt.

    PubMed

    El-Dine, Nadia Walley

    2008-01-01

    Twenty rock samples collected from North Eastern Desert in Egypt have been investigated. Natural radionuclide contents have been measured by gamma-ray spectrometry employing a shielded HPGe detector. The activities of (238)U, (232)Th and (40)K have been determined in Bq/kg dry weight. The absorbed dose rate of gamma radiation ranged from 100.48 to 22,140.53 nGy/h. The representative external hazard index values (H(ex)) for the corresponding samples were estimated. In the present work, the state of radioactive disequilibrium in the U-series at Wadi Baligh area was studied. The activity ratios between (226)Ra/(214)Pb and (214)Pb/(214)Bi were measured. The thorium-to-uranium concentration ratios (Clark value) were also estimated. PMID:17869529

  6. Linkage of a locus for carbohydrate-deficient glycoprotein syndrome type I (CDG1) to chromosome 16p-markers

    SciTech Connect

    Martinsson, T.; Bjursell, C.; Wahlstroem, J.

    1994-09-01

    Carbohydrate-deficient glycoprotein syndrome type I is a multisystem disease with early severe nervous system involvement. The disease, which is inherited as a recessive autosomal trait, is biochemically characterized by complex defects in the terminal carbohydrate residues of a number of serum glycoproteins. This can be most readily detected in transferrin. A whole genome scan was initiated in order to try localizing the gene (CDG1) with linkage technique. We therefore analyzed 25 CDG1-pedigrees with several highly polymorphic microsatellite markers and after exclusion of about 30% of the genome, linkage was detected with markers located in chromosome region 16p. The lod score (Zmax) was above 8 (theta=0.00) for several markers in the region. In order to further sublocalize the CDG1 gene, recombination and linkage disequilibrium analyses were performed. Recombination events in some pedigrees indicated that the CDG1 gene is located in a 13 cM interval between microsatellite markers D16S406 and D16S500. Furthermore, allelic association was shown for marker D16S406, indicating that the CDG1 gene is located close to this. No heterogeneity could be detected in the European family material tested by us.

  7. A genetic linkage map for the saltwater crocodile (Crocodylus porosus)

    PubMed Central

    2009-01-01

    Background Genome elucidation is now in high gear for many organisms, and whilst genetic maps have been developed for a broad array of species, surprisingly, no such maps exist for a crocodilian, or indeed any other non-avian member of the Class Reptilia. Genetic linkage maps are essential tools for the mapping and dissection of complex quantitative trait loci (QTL), and in order to permit systematic genome scans for the identification of genes affecting economically important traits in farmed crocodilians, a comprehensive genetic linage map will be necessary. Results A first-generation genetic linkage map for the saltwater crocodile (Crocodylus porosus) was constructed using 203 microsatellite markers amplified across a two-generation pedigree comprising ten full-sib families from a commercial population at Darwin Crocodile Farm, Northern Territory, Australia. Linkage analyses identified fourteen linkage groups comprising a total of 180 loci, with 23 loci remaining unlinked. Markers were ordered within linkage groups employing a heuristic approach using CRIMAP v3.0 software. The estimated female and male recombination map lengths were 1824.1 and 319.0 centimorgans (cM) respectively, revealing an uncommonly large disparity in recombination map lengths between sexes (ratio of 5.7:1). Conclusion We have generated the first genetic linkage map for a crocodilian, or indeed any other non-avian reptile. The uncommonly large disparity in recombination map lengths confirms previous preliminary evidence of major differences in sex-specific recombination rates in a species that exhibits temperature-dependent sex determination (TSD). However, at this point the reason for this disparity in saltwater crocodiles remains unclear. This map will be a valuable resource for crocodilian researchers, facilitating the systematic genome scans necessary for identifying genes affecting complex traits of economic importance in the crocodile industry. In addition, since many of the markers

  8. Uranium disequilibrium in groundwater: An isotope dilution approach in hydrologic investigations

    USGS Publications Warehouse

    Osmond, J.K.; Rydell, H.S.; Kaufman, M.I.

    1968-01-01

    The distribution and environmental disequilibrium patterns of naturally occurring uranium isotopes (U234 and U238) in waters of the Floridan aquifer suggest that variations in the ratios of isotopic activity and concentrations can be used quantitatively to evaluate mixing proportions of waters from differing sources. Uranium is probably unique in its potential for this approach, which seems to have general usefulness in hydrologic investigations.

  9. Uranium disequilibrium in groundwater: an isotope dilution approach in hydrologic investigations.

    PubMed

    Osmond, J K; Rydell, H S; Kaufman, M I

    1968-11-29

    The distribution and environmental disequilibrium patterns of naturally occurring uranium isotopes (U(234) and U(238)) in waters of the Floridan aquifer suggest that variations in the ratios of isotopic activity and concentrations can be used quantitatively to evaluate mixing proportions of waters from differing sources. Uranium is probably unique in its potential for this approach, which seems to have general usefulness in hydrologic investigations. PMID:4880720

  10. Selection, Hitchhiking and Disequilibrium Analysis at Three Linked Loci with Application to Hla Data

    PubMed Central

    Robinson, W. P.; Cambon-Thomsen, A.; Borot, N.; Klitz, W.; Thomson, G.

    1991-01-01

    The HLA system has been extensively studied from an evolutionary perspective. Although it is clear that selection has acted on the genes in the HLA complex, the nature of this selection has yet to be fully clarified. A study of constrained disequilibrium values is presented that is applicable to HLA and other less polymorphic systems with three or more linked loci, with the purpose of identifying selection events. The method uses the fact that three locus systems impose additional constraints on the range of possible disequilibrium values for any pair of loci. We have thus examined the behavior of the normalized pairwise disequilibrium measures using two locus (D'), and also three locus (D''), constraints on pairwise disequilibria in a three locus system when one of the three loci is under positive selection. The difference between these measures, δ = |D'| - |D''|, has a distribution for the two unselected loci differing from that for the selected locus with either of the unselected loci (the hallmark is a high positive value of δ for the two unselected loci). An examination of genetic drift indicates that positive δ values are unlikely to be found in human populations in the absence of selection when recombination is greater than about 0.1%. This measure can thus provide insight into which allele of several linked loci might have been subject to selection. Application of this method to HLA haplotypes from a large French population study (Provinces Francaise) identifies selected alleles on particular haplotypes. Application of a complementary method, disequilibrium pattern analysis also confirms the action of selection on these haplotypes. PMID:1752429

  11. Modeling the disequilibrium species for Jupiter and Saturn: Implications for Juno and Saturn entry probe

    NASA Astrophysics Data System (ADS)

    Wang, Dong; Lunine, Jonathan I.; Mousis, Olivier

    2016-09-01

    Disequilibrium species have been used previously to probe the deep water abundances and the eddy diffusion coefficient for giant planets. In this paper, we present a diffusion-kinetics code that predicts the abundances of disequilibrium species in the tropospheres of Jupiter and Saturn with updated thermodynamic and kinetic data. The dependence on the deep water abundance and the eddy diffusion coefficient is investigated. We quantified the disagreements in CO kinetics that comes from using different reaction networks and identified C2H6 as a useful tracer for the eddy diffusion coefficient. We first apply an H/P/O reaction network to Jupiter and Saturn's atmospheres and suggest a new PH3 destruction pathway. New chemical pathways for SiH4 and GeH4 destruction are also suggested, and another AsH3 destruction pathway is investigated thanks to new thermodynamic and kinetic data. These new models should enhance the interpretation of the measurement of disequilibrium species by JIRAM on board Juno and allow disentangling between methods for constraining the Saturn's deep water abundance with the Saturn entry probes envisaged by NASA or ESA.

  12. Disequilibrium macro model and catastrophe theory: the case of an oil shock

    SciTech Connect

    German, I.

    1983-01-01

    This study builds a simple disequilibrium macromodel of a small open economy that imports oil from an exogenous unit. The model is motivated by very slow adjustment of prices and wages to disequilibrium. Output on the other hand adjusts to its final level instantaneously. A rationing scheme is specified that explicitly takes into account the spillover effects and differentiates between notional, effective, and actual quantities. In a Solow-Stiglitz (1968) setting, a dynamic model is developed in which the dynamic forces depend on the economic environment specified by the Malinvandian regimes: Classical Unemployment, Keynesian Unemployment, Repressed Inflation, and the Walrasian Equilibrium. Given that dynamic system, the author seeks to identify the stationary points of the system (quasi-equilibria) and to find their stability properties. To the disequilibrium model an oil shock is introduced and its effects on employment, real output, real wage, and the stationary points of the system are investigated. A one-time increase (decrease) in the real price of oil and a continuous increase (decrease) in the real price of oil are considered. The path the economy takes and, in particular, the continuous and discontinuous behavior of the quasi-equilibria are investigated. Finally, the model government policy is incorporated and different policy alternatives are studied.

  13. New Insights on Jupiter's Deep Water Abundance from Disequilibrium Species

    NASA Astrophysics Data System (ADS)

    Wang, Dong; Gierasch, Peter; Lunine, Jonathan; Mousis, Olivier

    2014-11-01

    The bulk water abundance on Jupiter potentially constrains the planet's formation conditions. We aim to improve the chemical constraints on Jupiter's deep water abundance in this paper. The eddy diffusion coefficient is used to model vertical mixing in planetary atmosphere, and based on laboratory studies dedicated to turbulent rotating convection, we propose a new formulation of eddy diffusion coefficient. The new formulation predicts a smooth transition from slow rotation regime (near the equator) to the rapid rotation regime (near the pole). We estimate an uncertainty for newly derived coefficient of less than 25%, which is much better than the one order of magnitude uncertainty used in the literature. We then reevaluate the water constraintprovided by CO, using the newer eddy diffusion coefficient. We considered two updated CO kinetic models, one model constrains the water enrichment (relative to solar) between 0.1 and 0.75, while the other one constrains the water enrichment between 7 and 23. This difference calls for a better assessment of CO kinetic models.

  14. New insights on Jupiter's deep water abundance from disequilibrium species

    NASA Astrophysics Data System (ADS)

    Wang, Dong; Gierasch, Peter J.; Lunine, Jonathan I.; Mousis, Olivier

    2015-04-01

    The bulk water abundance on Jupiter potentially constrains the planet's formation conditions. We improve the chemical constraints on Jupiter's deep water abundance in this paper. The eddy diffusion coefficient is used to model vertical mixing in planetary atmosphere, and based on laboratory studies dedicated to turbulent rotating convection, we propose a new formulation of the eddy diffusion coefficient for the troposphere of giant planets. The new formulation predicts a smooth transition from the slow rotation regime (near the equator) to the rapid rotation regime (near the pole). We estimate an uncertainty for the newly derived coefficient of less than 25%, which is much better than the one order of magnitude uncertainty used in the literature. We then reevaluate the water constraint provided by CO, using the newer eddy diffusion coefficient. We considered two updated CO kinetic models, one model constrains the water enrichment (relative to solar) between 0.1 and 0.75, while the other constrains the water enrichment between 3 and 11.

  15. Linkage studies in primary open angle glaucoma

    SciTech Connect

    Avramopoulos, D.; Grigoriadu, M.; Kitsos, G.

    1994-09-01

    Glaucoma is a leading cause of blindness worldwide. The majority of glaucoma is associated with an open, normal appearing anterior chamber angle and is termed primary open angle glaucoma (POAG, MIM 137760). It is characterized by elevated intraocular pressure and onset in middle age or later. A subset of POAG with juvenile onset has recently been linked to chromosome 1q in two families with autosomal dominant inheritance. Eleven pedigrees with autosomal dominant POG (non-juvenile-onset) have been identified in Epirus, Greece. In the present study DNA samples have been collected from 50 individuals from one large pedigree, including 12 affected individuals. Preliminary results of linkage analysis with chromosome 1 microsatellites using the computer program package LINKAGE Version 5.1 showed no linkage with the markers previously linked to juvenile-onset POAG. Further linkage analysis is being pursued, and the results will be presented.

  16. Linkage: from particulate to interactive genetics.

    PubMed

    Falk, Raphael

    2003-01-01

    Genetics was established on a strict particulate conception of heredity. Genetic linkage, the deviation from independent segregation of Mendelian factors, was conceived as a function of the material allocation of the factors to the chromosomes, rather than to the multiple effects (pleiotropy) of discrete factors. Although linkage maps were abstractions they provided strong support for the chromosomal theory of inheritance. Direct Cytogenetic evidence was scarce until X-ray induced major chromosomal rearrangements allowed direct correlation of genetic and cytological rearrangements. Only with the discovery of the polytenic giant chromosomes in Drosophila larvae in the 1930s were the virtual maps backed up by physical maps of the genetic loci. Genetic linkage became a pivotal experimental tool for the examination of the integration of genetic functions in development and in evolution. Genetic mapping has remained a hallmark of genetic analysis. The location of genes in DNA is a modern extension of the notion of genetic linkage. PMID:12778899

  17. Impact of reduced marker set estimation of genomic relationship matrices on genomic selection for feed efficiency in Angus cattle

    PubMed Central

    2010-01-01

    Background Molecular estimates of breeding value are expected to increase selection response due to improvements in the accuracy of selection and a reduction in generation interval, particularly for traits that are difficult or expensive to record or are measured late in life. Several statistical methods for incorporating molecular data into breeding value estimation have been proposed, however, most studies have utilized simulated data in which the generated linkage disequilibrium may not represent the targeted livestock population. A genomic relationship matrix was developed for 698 Angus steers and 1,707 Angus sires using 41,028 single nucleotide polymorphisms and breeding values were estimated using feed efficiency phenotypes (average daily feed intake, residual feed intake, and average daily gain) recorded on the steers. The number of SNPs needed to accurately estimate a genomic relationship matrix was evaluated in this population. Results Results were compared to estimates produced from pedigree-based mixed model analysis of 862 Angus steers with 34,864 identified paternal relatives but no female ancestors. Estimates of additive genetic variance and breeding value accuracies were similar for AFI and RFI using the numerator and genomic relationship matrices despite fewer animals in the genomic analysis. Bootstrap analyses indicated that 2,500-10,000 markers are required for robust estimation of genomic relationship matrices in cattle. Conclusions This research shows that breeding values and their accuracies may be estimated for commercially important sires for traits recorded in experimental populations without the need for pedigree data to establish identity by descent between members of the commercial and experimental populations when at least 2,500 SNPs are available for the generation of a genomic relationship matrix. PMID:20403185

  18. A Monte Carlo method for combined segregation and linkage analysis.

    PubMed Central

    Guo, S W; Thompson, E A

    1992-01-01

    We introduce a Monte Carlo approach to combined segregation and linkage analysis of a quantitative trait observed in an extended pedigree. In conjunction with the Monte Carlo method of likelihood-ratio evaluation proposed by Thompson and Guo, the method provides for estimation and hypothesis testing. The greatest attraction of this approach is its ability to handle complex genetic models and large pedigrees. Two examples illustrate the practicality of the method. One is of simulated data on a large pedigree; the other is a reanalysis of published data previously analyzed by other methods. PMID:1415253

  19. Simple models for disequilibrium fractional melting and batch melting with application to REE fractionation in abyssal peridotites

    NASA Astrophysics Data System (ADS)

    Liang, Yan; Liu, Boda

    2016-01-01

    Disequilibrium melting arises when the kinetics of chemical exchange between a residual mineral and partial melt is sluggish compare to the rate of melting. To better understand the role of a finite crystal-melt exchange rate on trace element fractionation during mantle melting, we have developed a disequilibrium melting model for partial melting in an upwelling steady-state column. We use linear kinetics to approximate crystal-melt mass exchange rate and obtain simple analytical solutions for cases of perfect fractional melting and batch melting. A key parameter determining the extent of chemical disequilibrium during partial melting is an element specific dimensionless ratio (ε) defined as the melting rate relative to the solid-melt chemical exchange rate for the trace element of interest. In the case of diffusion in mineral limited chemical exchange, ε is inversely proportional to diffusivity of the element of interest. Disequilibrium melting is important for the trace element when ε is comparable to or greater than the bulk solid-melt partition coefficient for the trace element (k). The disequilibrium fractional melting model is reduced to the equilibrium perfect fractional melting model when ε is much smaller than k. Hence highly incompatible trace elements with smaller mobilities in minerals are more susceptible to disequilibrium melting than moderately incompatible and compatible trace elements. Effect of chemical disequilibrium is to hinder the extent of fractionation between residual solid and partial melt, making the residual solid less depleted and the accumulated melt more depleted in incompatible trace element abundances relative the case of equilibrium melting. Application of the disequilibrium fractional melting model to REE and Y abundances in clinopyroxene in abyssal peridotites from the Central Indian Ridge and the Vema Lithospheric Section, Mid-Atlantic Ridge revealed a positive correlation between the disequilibrium parameter ε and the

  20. Linkage mapping of a polymorphic plumage locus associated with intermorph incompatibility in the Gouldian finch (Erythrura gouldiae).

    PubMed

    Kim, K-W; Griffith, S C; Burke, T

    2016-04-01

    Colour polymorphism is known to facilitate speciation but the genetic basis of animal pigmentation and how colour polymorphisms contribute to speciation is poorly understood. Restricted recombination may promote linkage disequilibrium between the colour locus and incompatibility genes. Genomic rearrangement and the position of relevant loci within a chromosome are important factors that influence the frequency of recombination. Therefore, it is important to know the position of the colour locus, gene order and recombination landscape of the chromosome to understand the mechanism that generates incompatibilities between morphs. Recent studies showed remarkable pre- and postzygotic incompatibilities between sympatric colour morphs of the Gouldian finch (Erythrura gouldiae), in which head feather colour is genetically determined by a single sex-linked locus, Red. We constructed a genetic map for the Z chromosome of the Gouldian finch (male-specific map distance=131 cM), using 618 captive-bred birds and 34 microsatellite markers, to investigate the extent of inter- and intraspecific genomic rearrangements and variation in recombination rate within the Z chromosome. We refined the location of the Red locus to a ~7.2-cM interval in a region with a moderate recombination rate but outside the least-recombining, putative centromeric region. There was no evidence of chromosome-wide genomic rearrangements between the chromosomes carrying the red or black alleles with the current marker resolution. This work will contribute to identifying the causal gene, which will in turn enable alternative explanations for the association between incompatibility and colouration, such as fine-scale linkage disequilibrium, genomic rearrangements and pleiotropy, to be tested. PMID:26786066

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

    PubMed Central

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

    2008-01-01

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

  2. Identification of complete linkage disequilibrium in the DSG4 gene and its association with wool length and crimp in Chinese indigenous sheep.

    PubMed

    Ling, Y H; Xiang, H; Zhang, G; Ding, J P; Zhang, Z J; Zhang, Y H; Han, J L; Ma, Y H; Zhang, X R

    2014-01-01

    The desmoglein 4 (DSG4) gene is a potential candidate in the search for genes that may affect wool traits, because of its function. This study aimed to screen for polymorphisms in partial exon 16 and 3ꞌUTR of the sheep desmoglein 4 DSG4 gene, and to test its possible association with wool length and crimp associated with fur. Overall, 326 sheep were scanned via single-strand conformational polymorphism assay, through three pairs of primers. The breeds included Tan, Han, and TanxHan from China, Polled Dorset from Australia, and Suffolk from Britain genotypes AA, BB, and AB for primer2 and genotypes DD, EE, and DE for primer3 were detected in native breeds. Six SNPs and 3-bp insertion/deletions were found in exon 16, of which 4 lead to amino acid substitutions. In addition, 1 SNP was found in 3ꞌUTR. The DSG4 genotype was found to be strongly associated with all wool traits that were considered in this study (P < 0.01). Sheep with the genotype MM had a higher least square mean compared to sheep with the genotype WW or WM with respect to birth scapular wool length (P < 0.01), crimp number of birth scapular wool crimp (P < 0.01), crimp number of weaning scapular wool crimp (P < 0.01), and crimp number of weaning rump wool crimp (P < 0.01, P < 0.05). In conclusion, our study is the first to demonstrate that the DSG4 gene may be a candidate, or major gene, which influences important wool traits. PMID:25117319

  3. MHC Class I Chain-Related Gene A Polymorphisms and Linkage Disequilibrium with HLA-B and HLA-C Alleles in Ocular Toxoplasmosis

    PubMed Central

    Ayo, Christiane Maria; Camargo, Ana Vitória da Silveira; Frederico, Fábio Batista; Siqueira, Rubens Camargo; Previato, Mariana; Murata, Fernando Henrique Antunes; Silveira-Carvalho, Aparecida Perpétuo; Barbosa, Amanda Pires; Brandão de Mattos, Cinara de Cássia; de Mattos, Luiz Carlos

    2015-01-01

    This study investigated whether polymorphisms of the MICA (major histocompatibility complex class I chain-related gene A) gene are associated with eye lesions due to Toxoplasma gondii infection in a group of immunocompetent patients from southeastern Brazil. The study enrolled 297 patients with serological diagnosis of toxoplasmosis. Participants were classified into two distinct groups after conducting fundoscopic exams according to the presence (n = 148) or absence (n = 149) of ocular scars/lesions due to toxoplasmosis. The group of patients with scars/lesions was further subdivided into two groups according to the type of the ocular manifestation observed: primary (n = 120) or recurrent (n = 28). Genotyping of the MICA and HLA alleles was performed by the polymerase chain reaction-sequence specific oligonucleotide technique (PCR-SSO; One Lambda®) and the MICA-129 polymorphism (rs1051792) was identified by nested polymerase chain reaction (PCR-RFLP). Significant associations involving MICA polymorphisms were not found. Although the MICA*002~HLA-B*35 haplotype was associated with increased risk of developing ocular toxoplasmosis (P-value = 0.04; OR = 2.20; 95% CI = 1.05–4.60), and the MICA*008~HLA-C*07 haplotype was associated with protection against the development of manifestations of ocular toxoplasmosis (P-value = 0.009; OR: 0.44; 95% CI: 0.22–0.76), these associations were not statistically significant after adjusting for multiple comparisons. MICA polymorphisms do not appear to influence the development of ocular lesions in patients diagnosed with toxoplasmosis in this study population. PMID:26672749

  4. "Extended" A1, B8, DR3 haplotype shows remarkable linkage disequilibrium but is similar to nonextended haplotypes in terms of diabetes risk.

    PubMed

    Ide, Akane; Babu, Sunanda R; Robles, David T; Wang, Tianbao; Erlich, Henry A; Bugawan, Teodorica L; Rewers, Marian; Fain, Pamela R; Eisenbarth, George S

    2005-06-01

    To evaluate potential differential diabetes risk of DR3 haplotypes we have evaluated class I alleles as well as two microsatellites previously associated with differential risk associated with DR3 haplotypes. We found that over one-third of patient DR3 chromosomes consisted of an extended DR3 haplotype, from DQ2 to D6S2223 (DQ2, DR3, D6S273-143, MIC-A5.1, HLA-B8, HLA-Cw7, HLA-A1, and D6S2223-177) with an identical extended haplotype in controls. The extended haplotype was present more frequently (35.1% of autoimmune-associated DR3 haplotypes, 39.4% of control DR3 haplotypes) than other haplotypes (no other haplotype >5% of DR3 haplotypes) and remarkably conserved, but it was not transmitted from parents to affected children more frequently than nonconserved DR3-bearing haplotypes. This suggests that if all alleles are truly identical for the major A1, B8, DR3 haplotype (between A1 and DR3), with different alleles on nonconserved haplotypes without differential diabetes risk, then in this region of the genome DR3-DQ2 may be the primary polymorphisms of common haplotypes contributing to diabetes risk. PMID:15919812

  5. A consensus framework map of durum wheat (Triticum durum Desf.) suitable for linkage disequilibrium analysis and genome-wide association mapping

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomics applications in durum (Triticum durum Desf.) wheat have the potential to boost exploitation of genetic resources and to advance understanding of the genetics of important complex traits (e.g. resilience to environmental and biotic stresses). A dense and accurate consensus map specific for ...

  6. Single nucleotide polymorphisms in linkage disequilibrium with the male-fertility restoration (Ms) locus in open-pollinated and inbred populations of onion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintainer lines are used to seed propagate male-sterile lines for the development of hybrid-onion cultivars. The identification of maintainer lines would be more efficient with molecular markers distinguishing genotypes at the nuclear male-fertility restoration (Ms) locus. Ms has been mapped to chr...

  7. A microsatellite-based genome-wide analysis of genetic diversity and linkage disequilibrium in Upland cotton (Gossypium hirsutum L.) cultivars from major cotton-growing countries

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To better understand the genetic diversity of the cultivated Upland cotton (Gossypium hirsutum L.) and its structure at the molecular level, 193 Upland cotton cultivars collected from 26 countries were genotyped using 448 microsatellite markers. These markers were selected based on their mapping po...

  8. The use of marker-data transformations to account for linkage disequilibrium in genomic selection: a case study in switchgrass (Panicum virgatum L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic selection (GS) is an attractive technology to generate rapid genetic gains, particularly in perennial grass species like switchgrass, where phenotyping generally requires at least two years of field trial. In this study, we empirically assessed prediction procedures for GS in two different p...

  9. High-resolution genetic map for understanding the effect of genome-wide recombination rate, selection sweep and linkage disequilibrium on nucleotide diversity in watermelon

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genotyping by sequencing (GBS) technology was used to identify a set of 9,933 single nucleotide polymorphism (SNP) markers for constructing a high-resolution genetic map of 1,087 cM for watermelon. The genome-wide variation of recombination rate (GWRR) across the map was evaluated and a positive co...

  10. Microsatellite marker based genetic linkage maps of Oreochromis aureus and O. niloticus (Cichlidae): extensive linkage group segment homologies revealed.

    PubMed

    McConnell, S K; Beynon, C; Leamon, J; Skibinski, D O

    2000-06-01

    Partial genetic linkage maps, based on microsatellite markers, were constructed for two tilapia species, Oreochromis aureus and Oreochromis niloticus using an interspecific backcross population. The linkage map for O. aureus comprised 28 markers on 10 linkage groups and covered 212.8 CM. Nine markers were mapped to four linkage groups on an O. niloticus female linkage map covering 40.6 CM. Results revealed a high degree of conservation of synteny between the linkage groups defined in O. aureus and the previously published genetic linkage map of O. niloticus. PMID:10895314

  11. Measuring demand for flat water recreation using a two-stage/disequilibrium travel cost model with adjustment for overdispersion and self-selection

    NASA Astrophysics Data System (ADS)

    McKean, John R.; Johnson, Donn; Taylor, R. Garth

    2003-04-01

    An alternate travel cost model is applied to an on-site sample to estimate the value of flat water recreation on the impounded lower Snake River. Four contiguous reservoirs would be eliminated if the dams are breached to protect endangered Pacific salmon and steelhead trout. The empirical method applies truncated negative binomial regression with adjustment for endogenous stratification. The two-stage decision model assumes that recreationists allocate their time among work and leisure prior to deciding among consumer goods. The allocation of time and money among goods in the second stage is conditional on the predetermined work time and income. The second stage is a disequilibrium labor market which also applies if employers set work hours or if recreationists are not in the labor force. When work time is either predetermined, fixed by contract, or nonexistent, recreationists must consider separate prices and budgets for time and money.

  12. Linkage and association of haplotypes at the APOA1/C3/A4/A5 genecluster to familial combined hyperlipidemia

    SciTech Connect

    Eichenbaum-Voline, Sophie; Olivier, Michael; Jones, Emma L.; Naoumova, Rossitza P.; Jones, Bethan; Gau, Brian; Seed, Mary; Betteridge,D. John; Galton, David J.; Rubin, Edward M.; Scott, James; Shoulders,Carol C.; Pennacchio, Len A.

    2002-09-15

    Combined hyperlipidemia (CHL) is a common disorder of lipidmetabolism that leads to an increased risk of cardiovascular disease. Thelipid profile of CHL is characterised by high levels of atherogeniclipoproteins and low levels of high-density-lipoprotein-cholesterol.Apolipoprotein (APO) A5 is a newly discovered gene involved in lipidmetabolism located within 30kbp of the APOA1/C3/A4 gene cluster. Previousstudies have indicated that sequence variants in this cluster areassociated with increased plasma lipid levels. To establish whethervariation at the APOA5 gene contributes to the transmission of CHL, weperformed linkage and linkage disequilibrium (LD) tests on a large cohortof families (n=128) with familial CHL (FCHL). The linkage data producedevidence for linkage of the APOA1/C3/A4/A5 genomic interval to FCHL (NPL= 1.7, P = 0.042). The LD studies substantiated these data. Twoindependent rare alleles, APOA5c.56G and APOC3c.386G of this gene clusterwere over-transmitted in FCHL (P = 0.004 and 0.007, respectively), andthis was associated with a reduced transmission of the most commonAPOA1/C3/A4/A5 haplotype (frequency 0.4425) to affected subjects (P =0.013). The APOA5c.56G allele was associated with increased plasmatriglyceride levels in FCHL probands, whereas the second, andindependent, APOC3c.386G allele was associated with increased plasmatriglyceride levels in FCHL pedigree founders. Thus, this allele (or anallele in LD) may mark a quantitative trait associated with FCHL, as wellas representing a disease susceptibility locus for the condition. Thisstudy establishes that sequence variation in the APOA1/C3/A4/A5 genecluster contributes to the transmission of FCHL in a substantialproportion of affected families, and that these sequence variants mayalso contribute to the lipid abnormalities of the metabolic syndrome,which is present in up to 40 percent of persons with cardiovasculardisease.

  13. Private Medical Record Linkage with Approximate Matching

    PubMed Central

    Durham, Elizabeth; Xue, Yuan; Kantarcioglu, Murat; Malin, Bradley

    2010-01-01

    Federal regulations require patient data to be shared for reuse in a de-identified manner. However, disparate providers often share data on overlapping populations, such that a patient’s record may be duplicated or fragmented in the de-identified repository. To perform unbiased statistical analysis in a de-identified setting, it is crucial to integrate records that correspond to the same patient. Private record linkage techniques have been developed, but most methods are based on encryption and preclude the ability to determine similarity, decreasing the accuracy of record linkage. The goal of this research is to integrate a private string comparison method that uses Bloom filters to provide an approximate match, with a medical record linkage algorithm. We evaluate the approach with 100,000 patients’ identifiers and demographics from the Vanderbilt University Medical Center. We demonstrate that the private approximation method achieves sensitivity that is, on average, 3% higher than previous methods. PMID:21346965

  14. A Genetic Linkage Map for Cattle

    PubMed Central

    Bishop, M. D.; Kappes, S. M.; Keele, J. W.; Stone, R. T.; Sunden, SLF.; Hawkins, G. A.; Toldo, S. S.; Fries, R.; Grosz, M. D.; Yoo, J.; Beattie, C. W.

    1994-01-01

    We report the most extensive physically anchored linkage map for cattle produced to date. Three-hundred thirteen genetic markers ordered in 30 linkage groups, anchored to 24 autosomal chromosomes (n = 29), the X and Y chromosomes, four unanchored syntenic groups and two unassigned linkage groups spanning 2464 cM of the bovine genome are summarized. The map also assigns 19 type I loci to specific chromosomes and/or syntenic groups and four cosmid clones containing informative microsatellites to chromosomes 13, 25 and 29 anchoring syntenic groups U11, U7 and U8, respectively. This map provides the skeletal framework prerequisite to development of a comprehensive genetic map for cattle and analysis of economic trait loci (ETL). PMID:7908653

  15. Intragroup Emotions: Physiological Linkage and Social Presence.

    PubMed

    Järvelä, Simo; Kätsyri, Jari; Ravaja, Niklas; Chanel, Guillaume; Henttonen, Pentti

    2016-01-01

    We investigated how technologically mediating two different components of emotion-communicative expression and physiological state-to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression) and visualization of group level physiological heart rates and their dyadic linkage (physiology) was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member's physiological components of emotion by technological means to enhance mediated communication and strengthen social presence. PMID:26903913

  16. Intragroup Emotions: Physiological Linkage and Social Presence

    PubMed Central

    Järvelä, Simo; Kätsyri, Jari; Ravaja, Niklas; Chanel, Guillaume; Henttonen, Pentti

    2016-01-01

    We investigated how technologically mediating two different components of emotion—communicative expression and physiological state—to group members affects physiological linkage and self-reported feelings in a small group during video viewing. In different conditions the availability of second screen text chat (communicative expression) and visualization of group level physiological heart rates and their dyadic linkage (physiology) was varied. Within this four person group two participants formed a physically co-located dyad and the other two were individually situated in two separate rooms. We found that text chat always increased heart rate synchrony but HR visualization only with non-co-located dyads. We also found that physiological linkage was strongly connected to self-reported social presence. The results encourage further exploration of the possibilities of sharing group member's physiological components of emotion by technological means to enhance mediated communication and strengthen social presence. PMID:26903913

  17. Creative Activities in Music--A Genome-Wide Linkage Analysis.

    PubMed

    Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

    2016-01-01

    Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose

  18. Creative Activities in Music – A Genome-Wide Linkage Analysis

    PubMed Central

    Oikkonen, Jaana; Kuusi, Tuire; Peltonen, Petri; Raijas, Pirre; Ukkola-Vuoti, Liisa; Karma, Kai; Onkamo, Päivi; Järvelä, Irma

    2016-01-01

    Creative activities in music represent a complex cognitive function of the human brain, whose biological basis is largely unknown. In order to elucidate the biological background of creative activities in music we performed genome-wide linkage and linkage disequilibrium (LD) scans in musically experienced individuals characterised for self-reported composing, arranging and non-music related creativity. The participants consisted of 474 individuals from 79 families, and 103 sporadic individuals. We found promising evidence for linkage at 16p12.1-q12.1 for arranging (LOD 2.75, 120 cases), 4q22.1 for composing (LOD 2.15, 103 cases) and Xp11.23 for non-music related creativity (LOD 2.50, 259 cases). Surprisingly, statistically significant evidence for linkage was found for the opposite phenotype of creative activity in music (neither composing nor arranging; NCNA) at 18q21 (LOD 3.09, 149 cases), which contains cadherin genes like CDH7 and CDH19. The locus at 4q22.1 overlaps the previously identified region of musical aptitude, music perception and performance giving further support for this region as a candidate region for broad range of music-related traits. The other regions at 18q21 and 16p12.1-q12.1 are also adjacent to the previously identified loci with musical aptitude. Pathway analysis of the genes suggestively associated with composing suggested an overrepresentation of the cerebellar long-term depression pathway (LTD), which is a cellular model for synaptic plasticity. The LTD also includes cadherins and AMPA receptors, whose component GSG1L was linked to arranging. These results suggest that molecular pathways linked to memory and learning via LTD affect music-related creative behaviour. Musical creativity is a complex phenotype where a common background with musicality and intelligence has been proposed. Here, we implicate genetic regions affecting music-related creative behaviour, which also include genes with neuropsychiatric associations. We also propose

  19. Anosov Geodesic Flows, Billiards and Linkages

    NASA Astrophysics Data System (ADS)

    Kourganoff, Mickaël

    2016-06-01

    Any smooth surface in {{mathbb R}3} may be flattened along the z-axis, and the flattened surface becomes close to a billiard table in {{mathbb R}2}. We show that, under some hypotheses, the geodesic flow of this surface converges locally uniformly to the billiard flow. Moreover, if the billiard is dispersive and has finite horizon, then the geodesic flow of the corresponding surface is Anosov. We apply this result to the theory of mechanical linkages and their dynamics: we provide a new example of a simple linkage whose physical behavior is Anosov. For the first time, the edge lengths of the mechanism are given explicitly.

  20. Annotated genetic linkage maps of Pinus pinaster Ait. from a Central Spain population using microsatellite and gene based markers

    PubMed Central

    2012-01-01

    Background Pinus pinaster Ait. is a major resin producing species in Spain. Genetic linkage mapping can facilitate marker-assisted selection (MAS) through the identification of Quantitative Trait Loci and selection of allelic variants of interest in breeding populations. In this study, we report annotated genetic linkage maps for two individuals (C14 and C15) belonging to a breeding program aiming to increase resin production. We use different types of DNA markers, including last-generation molecular markers. Results We obtained 13 and 14 linkage groups for C14 and C15 maps, respectively. A total of 211 and 215 markers were positioned on each map and estimated genome length was between 1,870 and 2,166 cM respectively, which represents near 65% of genome coverage. Comparative mapping with previously developed genetic linkage maps for P. pinaster based on about 60 common markers enabled aligning linkage groups to this reference map. The comparison of our annotated linkage maps and linkage maps reporting QTL information revealed 11 annotated SNPs in candidate genes that co-localized with previously reported QTLs for wood properties and water use efficiency. Conclusions This study provides genetic linkage maps from a Spanish population that shows high levels of genetic divergence with French populations from which segregating progenies have been previously mapped. These genetic maps will be of interest to construct a reliable consensus linkage map for the species. The importance of developing functional genetic linkage maps is highlighted, especially when working with breeding populations for its future application in MAS for traits of interest. PMID:23036012

  1. Importance sampling. I. Computing multimodel p values in linkage analysis

    SciTech Connect

    Kong, A.; Frigge, M.; Irwin, M.; Cox, N. )

    1992-12-01

    In linkage analysis, when the lod score is maximized over multiple genetic models, standard asymptotic approximation of the significance level does not apply. Monte Carlo methods can be used to estimate the p value, but procedures currently used are extremely inefficient. The authors propose a Monte Carlo procedure based on the concept of importance sampling, which can be thousands of times more efficient than current procedures. With a reasonable amount of computing time, extremely accurate estimates of the p values can be obtained. Both theoretical results and an example of maturity-onset diabetes of the young (MODY) are presented to illustrate the efficiency performance of their method. Relations between single-model and multimodel p values are explored. The new procedure is also used to investigate the performance of asymptotic approximations in a single model situation. 22 refs., 6 figs., 1 tab.

  2. Analysis of spontaneous MEG activity in mild cognitive impairment using spectral entropies and disequilibrium measures.

    PubMed

    Bruña, Ricardo; Poza, Jesús; Gómez, Carlos; Fernández, Alberto; Hornero, Roberto

    2010-01-01

    The aim of this study was to explore the ability of several spectral entropies and disequilibrium measures to discriminate between spontaneous magnetoencephalographic (MEG) oscillations from 18 mild cognitive impairment (MCI) patients and 24 controls. The Shannon spectral entropy (SSE), Tsallis spectral entropy (TSE), and Rényi spectral entropy (RSE) were calculated from the normalized power spectral density to evaluate the irregularity patterns. In addition, the Euclidean (ED) and Wootters (WD) distances were computed as disequilibrium measures. Results revealed statistically significant lower SSE and TSE(2) values for MCI patients than for controls (p < 0.05) in the right lateral region of the brain. ED also obtained statistically significant lower values for MCI patients than for controls using the (p < 0.05) in the right lateral region of the brain. These findings suggest that MCI is associated with a significant decrease in irregularity of MEG activity. In addition, the highest accuracy of 64.3% was achieved by the SSE. We conclude that measures from information theory can be useful to both characterize abnormal brain dynamics and help in MCI detection. PMID:21097360

  3. The importance of temporal stress variation and dynamic disequilibrium for the initiation of plate tectonics

    NASA Astrophysics Data System (ADS)

    Stamenković, V.; Höink, T.; Lenardic, A.

    2016-06-01

    We use 1-D thermal history models and 3-D numerical experiments to study the impact of dynamic thermal disequilibrium and large temporal variations of normal and shear stresses on the initiation of plate tectonics. Previous models that explored plate tectonics initiation from a steady state, single plate mode of convection concluded that normal stresses govern the initiation of plate tectonics, which based on our 1-D model leads to plate yielding being more likely with increasing interior heat and planet mass for a depth-dependent Byerlee yield stress. Using 3-D spherical shell mantle convection models in an episodic regime allows us to explore larger temporal stress variations than can be addressed by considering plate failure from a steady state stagnant lid configuration. The episodic models show that an increase in convective mantle shear stress at the lithospheric base initiates plate failure, which leads with our 1-D model to plate yielding being less likely with increasing interior heat and planet mass. In this out-of-equilibrium and strongly time-dependent stress scenario, the onset of lithospheric overturn events cannot be explained by boundary layer thickening and normal stresses alone. Our results indicate that in order to understand the initiation of plate tectonics, one should consider the temporal variation of stresses and dynamic disequilibrium.

  4. Anti-Citrullinated Protein Antibodies Induce Macrophage Subset Disequilibrium in RA Patients.

    PubMed

    Zhu, Wei; Li, Xiu; Fang, Shaohong; Zhang, Xiaoli; Wang, Ying; Zhang, Tongshuai; Li, Zhaoying; Xu, Yanwen; Qu, Siying; Liu, Chuanliang; Gao, Fei; Pan, Haile; Wang, Guangyou; Li, Hulun; Sun, Bo

    2015-12-01

    We used samples from rheumatoid arthritis (RA) patients to examine whether Anti-citrullinated protein antibodies (ACPAs) alter macrophage subset distribution and promote RA development. Macrophage subset distributions and interferon regulatory factor 4 (IRF4) and IRF5 expressions were analyzed. ACPAs were purified by affinity column. After RA and osteoarthritis (OA) patients' macrophages were cocultured with ACPAs, macrophage subsets and IRF4 and IRF5 expressions were measured. Small interfering RNAs (siRNAs) were transfected into ACPA-activated cells to suppress IRF4 or IRF5. Fluorescence-activated cell sorting (FACS), Western blot, and immunohistochemistry were performed. Macrophage subset disequilibrium occurred in RA patient synovial fluids. IRF4 and IRF5 were all expressed in the synovial fluid and synovium. ACPAs (40 IU/ml) could induce macrophages to polarize to M1 subsets, and the percentage of increased M1/M2 ratio of RA patients was higher than that of the OA patients. ACPAs also induce IRF4 and IRF5 protein expressions. IRF5 siRNA transfection impaired ACPA activity significantly. We demonstrated that macrophage subset disequilibrium occurred in RA patients. ACPAs induced IRF5 activity and led to M1 macrophage polarization. PMID:26063186

  5. Determination of scatter factor parameters and electron disequilibrium for monoenergetic photon beams.

    PubMed

    McDonough, J; Bloch, P; Bjärngard, B E

    1999-02-01

    The tissue-phantom-ratio (TPR) is expressed as the product of the phantom scatter factor (SF), an electron disequilibrium factor, and an attenuation factor, equal to the zero-area TPR. The scatter factor, as a function of depth d and field size s, has been described by two parameters a and w, SF(d,s) = 1 + asd/(ws + d). We have determined the parameters a and w for 20 monoenergetic photon beams between 1 and 20 MeV. Pencil-beam energy-deposition kernels were obtained using Monte Carlo simulations. The kernels were used to calculate broad-beam depth-dose data, which were converted to TPR and fitted to the equation above using an iterative search over a-w space. The parameter a is nearly equal to the attenuation coefficient for all energies while the parameter w increases with energy. The resulting a and w compare favorably to values determined for clinical photon beams, as a function of the measured attenuation coefficient. With the scatter factor determined, we isolated the electron disequilibrium factor for each monoenergetic beam. It can be characterized as a quadratic function of the depth. The coefficients of the quadratic function can be related to the range of the most energetic secondary electron produced. PMID:10076974

  6. The utility of ancient human DNA for improving allele age estimates, with implications for demographic models and tests of natural selection

    PubMed Central

    Sams, Aaron J.; Hawks, John; Keinan, Alon

    2015-01-01

    The age of polymorphic alleles in humans is often estimated from population genetic patterns in extant human populations, such as allele frequencies, linkage disequilibrium, and rate of mutations. Ancient DNA can improve the accuracy of such estimates, as well as facilitate testing the validity of demographic models underlying many population genetic methods. Specifically, the presence of an allele in a genome derived from an ancient sample testifies that the allele is at least as old as that sample. In this study, we consider a common method for estimating allele age based on allele frequency as applied to variants from the US National Institutes of Health (NIH) Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project. We view these estimates in the context of the presence or absence of each allele in the genomes of the 5300 year old Tyrolean Iceman, Ötzi, and of the 50,000 year old Altai Neandertal. Our results illuminate the accuracy of these estimates and their sensitivity to demographic events that were not included in the model underlying age estimation. Specifically, allele presence in the Iceman genome provides a good fit of allele age estimates to the expectation based on the age of that specimen. The equivalent based on the Neandertal genome leads to a poorer fit. This is likely due in part to the older age of the Neandertal and the older time of the split between modern humans and Neandertals, but also due to gene flow from Neandertals to modern humans not being considered in the underlying demographic model. Thus, the incorporation of ancient DNA can improve allele age estimation, demographic modeling, and tests of natural selection. Our results also point to the importance of considering a more diverse set of ancient samples for understanding the geographic and temporal range of individual alleles. PMID:25467111

  7. The utility of ancient human DNA for improving allele age estimates, with implications for demographic models and tests of natural selection.

    PubMed

    Sams, Aaron J; Hawks, John; Keinan, Alon

    2015-02-01

    The age of polymorphic alleles in humans is often estimated from population genetic patterns in extant human populations, such as allele frequencies, linkage disequilibrium, and rate of mutations. Ancient DNA can improve the accuracy of such estimates, as well as facilitate testing the validity of demographic models underlying many population genetic methods. Specifically, the presence of an allele in a genome derived from an ancient sample testifies that the allele is at least as old as that sample. In this study, we consider a common method for estimating allele age based on allele frequency as applied to variants from the US National Institutes of Health (NIH) Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project. We view these estimates in the context of the presence or absence of each allele in the genomes of the 5300 year old Tyrolean Iceman, Ötzi, and of the 50,000 year old Altai Neandertal. Our results illuminate the accuracy of these estimates and their sensitivity to demographic events that were not included in the model underlying age estimation. Specifically, allele presence in the Iceman genome provides a good fit of allele age estimates to the expectation based on the age of that specimen. The equivalent based on the Neandertal genome leads to a poorer fit. This is likely due in part to the older age of the Neandertal and the older time of the split between modern humans and Neandertals, but also due to gene flow from Neandertals to modern humans not being considered in the underlying demographic model. Thus, the incorporation of ancient DNA can improve allele age estimation, demographic modeling, and tests of natural selection. Our results also point to the importance of considering a more diverse set of ancient samples for understanding the geographic and temporal range of individual alleles. PMID:25467111

  8. A novel framework for sib pair linkage analysis.

    PubMed

    Poznik, G David; Adamska, Katarzyna; Xu, Xin; Krolewski, Andrzej S; Rogus, John J

    2006-02-01

    Sib pair linkage analysis of a dichotomous trait is a popular method for narrowing the search for genes that influence complex diseases. Although the pedigree structures are uncomplicated and the underlying genetic principles straightforward, a surprising degree of complexity is involved in implementing a sib pair study and interpreting the results. Ascertainment may be based on affected, discordant, or unaffected sib pairs, as well as on pairs defined by threshold values for quantitative traits, such as extreme discordant sib pairs. To optimize power, various domain restrictions and null hypotheses have been proposed for each of these designs, yielding a wide array of choices for the analyst. To begin, we systematically classify the major sources of discretion in sib pair linkage analysis. Then, we extend the work of Kruglyak and Lander (1995), to bring the various forms into a unified framework and to facilitate a more general approach to the analysis. Finally, we describe a new, freely available computer program, Splat (Sib Pair Linkage Analysis Testing), that can perform any sib pair statistical test currently in use, as well as any user-defined test yet to be proposed. Splat uses the expectation maximization algorithm to calculate maximum-likelihood estimates of sharing (subject to user-specified conditions) and then plots LOD scores versus chromosomal position. It includes a novel grid-scanning capability that enables simultaneous visualization of multiple test statistics. This can lead to further insight into the genetic basis of the disease process under consideration. In addition, phenotype definitions can be modified without the recalculation of inheritance vectors, thereby providing considerable flexibility for exploratory analysis. The application of Splat will be illustrated with data from studies on the genetics of diabetic nephropathy. PMID:16358216

  9. Isotopic disequilibrium and lower crustal contamination in slowly ascending magmas: Insights from Proterozoic anorthosites

    NASA Astrophysics Data System (ADS)

    Bybee, G. M.; Ashwal, L. D.

    2015-10-01

    Many Proterozoic anorthosite massifs show crustal isotopic signatures that have, for decades, fuelled debate regarding the source of these temporally-restricted magmas. Are these signatures indicative of lower crustal melting or of significant assimilation of crustal material into mantle-derived magmas? Traditional whole rock isotopic tracers (Sr, Nd, Pb and Os), like other geochemical, petrological and experimental tools, have failed to identify unambiguously the origins of the crust-like signature and resolve the source controversies for these feldspathic, cumulate intrusives. We make use of high precision Sr, Nd and Pb isotopic compositions of mineral phases (plag, opx, mag) and comagmatic, high-pressure orthopyroxene megacrysts as well as whole rock anorthosites/leuconorites from the Mealy Mountains Intrusive Suite (MMIS) and the Nain Plutonic Suite (NPS) to probe the origin of the crustal isotopic signatures and assess the importance of differentiation at lower crustal depths. This selection of samples represents fragments from various stages of the polybaric ascent of the magmas, while the study of the Mealy Mountains Intrusive Suite and the Nain Plutonic Suite is instructive as each is intruded into crust of significantly different age and isotopic composition. We observe marked differences in the whole-rock isotopic composition of Proterozoic anorthosites and high-pressure megacrysts (e.g. εNd;T = +2 to -10) intruded into crustal terranes of different ages and isotopic compositions. Evidence for varying degrees of internal isotopic disequilibrium (ΔNd, ΔSr, ΔPb) in anorthosites from these different terranes reinforces the notion that crustal contamination, and more importantly, the nature of the crustal assimilant, has a profound influence on the chemical signature of Proterozoic anorthosites. While most samples from the MMIS and NPS show significant and measurable ΔNd and ΔPb disequilibrium, ΔSr compositions cluster around zero. This decoupling in

  10. Automated linkage analysis in psychiatric disorders

    SciTech Connect

    He, L.; Mansfield, D.C.; Brown, A.F.; Green, D.K.

    1995-06-19

    A genome-wide search for linkage of microsatellite markers to chromosomal loci containing genes responsible for the major psychoses is a laborious task which can be carried out with greater speed and economy by introducing automation to several steps in the procedure. We describe the use of the Automated Linkage Preprocessor (ALP) program for the computer analysis of the waveform generated by fluorescein-labelled markers after electrophoretic separation. (To obtain a copy send a request to A.F. Brown at the below MRC address or use Anonymous FTP to ftp.hgu.mrc.ac.uk. Software is in directory pub/ALP.) The program runs on a PC in the Microsoft Windows environment, and is used in conjunction with an automated laser fluorescence (ALF) sequencer (Pharmacia) and its Fragment Manager{trademark} software to detect and size the PCR products, filter out peaks of fluorescence due to nonallele fragments, and generate genotypes in a format suitable for direct input to standard linkage analysis programs. The method should offer the advantages of speed, accuracy, and reduced cost. Its use in linkage studies in a large family with manic-depressive illness is discussed. 14 refs., 3 figs., 1 tab.

  11. Linkage Drag: Implication for Plant Breeding

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Linkage drag is commonly observed in plant breeding, yet the molecular mechanisms controlling this is unclear. The Pi-ta gene, a single copy gene near the centromere region of chromosome 12, confers resistance to races of Magnaporthe oryzae that contain AVR-Pita. The Pi-ta gene in Tetep has been su...

  12. Dialogic Linkage and Resonance in Autism

    ERIC Educational Resources Information Center

    Hobson, R. Peter; Hobson, Jessica A.; Garcia-Perez, Rosa; Du Bois, John

    2012-01-01

    We evaluated how children with autism make linguistic adjustments when talking with someone else. We devised two novel measures to assess (a) overall conversational linkage and (b) utterance-by-utterance resonance within dialogue between an adult and matched participants with and without autism (n = 12 per group). Participants with autism were…

  13. Permethylation Linkage Analysis Techniques for Residual Carbohydrates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Permethylation analysis is the classic approach to establishing the position of glycosidic linkages between sugar residues. Typically, the carbohydrate is derivatized to form acid-stable methyl ethers, hydrolyzed, peracetylated, and analyzed by gas chromatography-mass spectrometry (GC-MS). The pos...

  14. Past CETA Linkages: Models for the Future.

    ERIC Educational Resources Information Center

    Lapin, Joel D.

    1982-01-01

    Examines lessons learned from successful linkages between community colleges and Comprehensive Employment and Training Act (CETA) sponsors as the basis for future occupational training and employment programs. Reviews research examining CETA funding patterns in California and exemplary arrangements between community colleges and CETA nationwide.…

  15. Regional Workshops on CETA/Educational Linkages.

    ERIC Educational Resources Information Center

    McGough, Robert; And Others

    This document presents a summary of the proceedings of five regional workshops in Virginia which focused on planning for future involvement and linkages, as well as giving an orientation to the capabilities and operational philosophies of both Comprehensive Employment and Training Act (CETA) programs and educational organizations. Following…

  16. Rotating sample holder without mechanical linkages.

    PubMed

    Azevedo, L J

    1979-02-01

    A sample rotator which operates in applied magnetic fields is described. The design eliminates mechanical linkages by magnetically orienting a gimbal ring. Three mutually orthogonal coils mounted on the gimbal provide a magnetic moment which is aligned along the field direction. The rotator is useful from room temperature down to the liquid helium range. Rotations about any desired axis are possible. PMID:18699475

  17. Job Linkages Review: Promise and Challenge.

    ERIC Educational Resources Information Center

    Welch, Nancy

    In 1996, the City of Phoenix Enterprise Community Job Linkages Initiative sought to increase employment by matching local people with local jobs. Evaluation of the second project at Friendly House found that Friendly House, during the 18 months of the grant, increased residents' employability skills and linked them with Enterprise Community…

  18. ARE COASTAL WETLAND-LAKE LINKAGES IMPORTANT?

    EPA Science Inventory

    Because coastal werlands typically comprise only a small percentage of the overall surface area in large lakes, an assumption has often been made that functional links between wetlands and the lake proper are of little significance. Recent investigations of functional linkages be...

  19. Composite Bloom Filters for Secure Record Linkage

    PubMed Central

    Durham, Elizabeth Ashley; Kantarcioglu, Murat; Xue, Yuan; Toth, Csaba; Kuzu, Mehmet; Malin, Bradley

    2014-01-01

    The process of record linkage seeks to integrate instances that correspond to the same entity. Record linkage has traditionally been performed through the comparison of identifying field values (e.g., Surname), however, when databases are maintained by disparate organizations, the disclosure of such information can breach the privacy of the corresponding individuals. Various private record linkage (PRL) methods have been developed to obscure such identifiers, but they vary widely in their ability to balance competing goals of accuracy, efficiency and security. The tokenization and hashing of field values into Bloom filters (BF) enables greater linkage accuracy and efficiency than other PRL methods, but the encodings may be compromised through frequency-based cryptanalysis. Our objective is to adapt a BF encoding technique to mitigate such attacks with minimal sacrifices in accuracy and efficiency. To accomplish these goals, we introduce a statistically-informed method to generate BF encodings that integrate bits from multiple fields, the frequencies of which are provably associated with a minimum number of fields. Our method enables a user-specified tradeoff between security and accuracy. We compare our encoding method with other techniques using a public dataset of voter registration records and demonstrate that the increases in security come with only minor losses to accuracy. PMID:25530689

  20. Three Degree of Freedom Parallel Mechanical Linkage

    NASA Technical Reports Server (NTRS)

    Adelstein, Bernard D. (Inventor)

    1998-01-01

    A three degree of freedom parallel mechanism or linkage that couples three degree of freedom translational displacements at an endpoint, such as a handle, a hand grip, or a robot tool, to link rotations about three axes that are fixed with respect to a common base or ground link. The mechanism includes a three degree of freedom spherical linkage formed of two closed loops, and a planar linkage connected to the endpoint. The closed loops are rotatably interconnected, and made of eight rigid links connected by a plurality of single degree of freedom revolute joints. Three of these revolute joints are base joints and are connected to a common ground. such that the axis lines passing through the revolute joints intersect at a common fixed center point K forming the center of a spherical work volume in which the endpoint is capable of moving. 'Me three degrees of freedom correspond to the spatial displacement of the endpoint, for instance. The mechanism provides a new overall spatial kinematic linkage composed of a minimal number of rigid links and rotary joints. The mechanism has improved mechanical stiffness, and conveys mechanical power bidirectionally between the human operator and the electromechanical actuators. It does not require gears, belts. cable, screw or other types of transmission elements, and is useful in applications requiring full backdrivability. Thus, this invention can serve as the mechanical linkage for actively powered devices such as compliant robotic manipulators and force-reflecting hand controllers, and passive devices such as manual input devices for computers and other systems.

  1. Linkage of hiccup with heartbeat.

    PubMed

    Chen, B Y; Vasilakos, K; Boisteanu, D; Garma, L; Derenne, J P; Whitelaw, W A

    2000-06-01

    We explored a possible link between the cardiac cycle and the timing of recurrent hiccups in 10 patients with chronic, intractable hiccups. Recordings made during daytime naps in a sleep laboratory included sleep state; electrocardiogram; and respiration by means of a thermistor to detect airflow, bands around the rib cage and abdomen to assess expansion, and a bipolar surface electrode electromyogram over parasternal intercostal muscles. Hiccups could be detected on the abdominal bands and the parasternal electromyogram. The time of occurrence of each hiccup and each R wave in a continuous tracing of 100 or more hiccups were recorded and analyzed together with semiquantitive estimates of the phase of hiccup respiration. Whereas the hiccup rate ranged from approximately one-third to one-eighth of heart rate and was more variable than heart rate, hiccups showed a tendency, stronger in some subjects than others, to occur in midsystole. Variation in R-wave-R-wave (R-R) interval in association with hiccups was found in five patients. In three of these patients, hiccups were synchronized with respiration so that the cyclic change in R-R interval posthiccup could be explained as sinus arrhythmia, but, in two patients, the hiccups were not synchronized with respiration, so that hiccups are most likely responsible for the variation in heart rate. Also, the variation of R-R interval with hiccups suggests that there is some phasic autonomic efferent activity associated with hiccups. PMID:10846031

  2. A genetic linkage map of a cichlid fish, the tilapia (Oreochromis niloticus).

    PubMed Central

    Kocher, T D; Lee, W J; Sobolewska, H; Penman, D; McAndrew, B

    1998-01-01

    We have constructed a genetic map for a tilapia, Oreochromis niloticus, using DNA markers. The segregation of 62 microsatellite and 112 anonymous fragment length polymorphisms (AFLPs) was studied in 41 haploid embryos derived from a single female. We have identified linkages among 162 (93.1%) of these markers. 95% of the microsatellites and 92% of the AFLPs were linked in the final map. The map spans 704 Kosambi cM in 30 linkage groups covering the 22 chromosomes of this species. Twenty-four of these linkage groups contain at least one microsatellite polymorphism. From the number of markers 15 or fewer cM apart, we estimate a total map length of approximately 1000-1200 cM. High levels of interference are observed, consistent with measurements in other fish species. This map is a starting point for the mapping of single loci and quantitative traits in cichlid fishes. PMID:9539437

  3. A genetic linkage map of a cichlid fish, the tilapia (Oreochromis niloticus).

    PubMed

    Kocher, T D; Lee, W J; Sobolewska, H; Penman, D; McAndrew, B

    1998-03-01

    We have constructed a genetic map for a tilapia, Oreochromis niloticus, using DNA markers. The segregation of 62 microsatellite and 112 anonymous fragment length polymorphisms (AFLPs) was studied in 41 haploid embryos derived from a single female. We have identified linkages among 162 (93.1%) of these markers. 95% of the microsatellites and 92% of the AFLPs were linked in the final map. The map spans 704 Kosambi cM in 30 linkage groups covering the 22 chromosomes of this species. Twenty-four of these linkage groups contain at least one microsatellite polymorphism. From the number of markers 15 or fewer cM apart, we estimate a total map length of approximately 1000-1200 cM. High levels of interference are observed, consistent with measurements in other fish species. This map is a starting point for the mapping of single loci and quantitative traits in cichlid fishes. PMID:9539437

  4. Record linkage to correct under-ascertainment of cancers in HIV cohorts: The Sinikithemba HIV clinic linkage project.

    PubMed

    Sengayi, Mazvita; Spoerri, Adrian; Egger, Matthias; Kielkowski, Danuta; Crankshaw, Tamaryn; Cloete, Christie; Giddy, Janet; Bohlius, Julia

    2016-09-15

    The surveillance of HIV-related cancers in South Africa is hampered by the lack of systematic collection of cancer diagnoses in HIV cohorts and the absence of HIV status in cancer registries. To improve cancer ascertainment and estimate cancer incidence, we linked records of adults (aged ≥ 16 years) on antiretroviral treatment (ART) enrolled at Sinikithemba HIV clinic, McCord Hospital in KwaZulu-Natal (KZN) with the cancer records of public laboratories in KZN province using probabilistic record linkage (PRL) methods. We calculated incidence rates for all cancers, Kaposi sarcoma (KS), cervix, non-Hodgkin's lymphoma and non-AIDS defining cancers (NADCs) before and after inclusion of linkage-identified cancers with 95% confidence intervals (CIs). A total of 8,721 records of HIV-positive patients were linked with 35,536 cancer records. Between 2004 and 2010, we identified 448 cancers, 82% (n = 367) were recorded in the cancer registry only, 10% (n = 43) in the HIV cohort only and 8% (n = 38) both in the HIV cohort and the cancer registry. The overall cancer incidence rate in patients starting ART increased from 134 (95% CI 91-212) to 877 (95% CI 744-1,041) per 100,000 person-years after inclusion of linkage-identified cancers. Incidence rates were highest for KS (432, 95% CI 341-555), followed by cervix (259, 95% CI 179-390) and NADCs (294, 95% CI 223-395) per 100,000 person-years. Ascertainment of cancer in HIV cohorts is incomplete, PRL is both feasible and essential for cancer ascertainment. PMID:27098265

  5. Measuring U-series Disequilibrium in Weathering Rinds to Study the Influence of Environmental Factors to Weathering Rates in Tropical Basse-Terre Island (French Guadeloupe)

    NASA Astrophysics Data System (ADS)

    Guo, J.; Ma, L.; Sak, P. B.; Gaillardet, J.; Chabaux, F. J.; Brantley, S. L.

    2015-12-01

    Chemical weathering is a critical process to global CO2 consumption, river/ocean chemistry, and nutrient import to biosphere. Weathering rinds experience minimal physical erosion and provide a well-constrained system to study the chemical weathering process. Here, we applied U-series disequilibrium dating method to study weathering advance rates on the wet side of Basse-Terre Island, French Guadeloupe, aiming to understand the role of the precipitation in controlling weathering rates and elucidate the behavior and immobilization mechanisms of U-series isotopes during rind formation. Six weathering clasts from 5 watersheds with mean annual precipitation varying from 2000 to 3000 mm/yr were measured for U-series isotope ratios and major element compositions on linear core-to-rind transects. One sample experienced complete core-to-rind transformation, while the rest clasts contain both rinds and unweathered cores. Our results show that the unweathered cores are under U-series secular equilibrium, while all the rind materials show significant U-series disequilibrium. For most rinds, linear core-to-rind increases of (230Th/232Th) activity ratios suggest a simple continuous U addition history. However, (234U/238U) and (238U/232Th) trends in several clasts show evidences of remobilization of Uranium besides the U addition, complicating the use of U-series dating method. The similarity between U/Th ratios and major elements trends like Fe, Al, P in some transects and the ongoing leaching experiments suggest that redox and organic colloids could control the mobilization of U-series isotopes in the rinds. Rind formation ages and weathering advance rate (0.07-0.29mm/kyr) were calculated for those rinds with a simple U-addition history. Our preliminary results show that local precipitation gradient significantly influenced the weathering advance rate, revealing the potential of estimating weathering advance rates at a large spatial scale using the U-series dating method.

  6. GADS software for parametric linkage analysis of quantitative traits distributed as a point-mass mixture.

    PubMed

    Axenovich, Tatiana I; Zorkoltseva, Irina V

    2012-02-01

    Often the quantitative data coming from proteomics and metabolomics studies have irregular distribution with a spike. None of the wide used methods for human QTL mapping are applicable to such traits. Researchers have to reduce the sample, excluding the spike, and analyze only continuous measurements. In this study, we propose a method for the parametric linkage analysis of traits with a spike in the distribution, and a software GADS, which implements this method. Our software includes not only the programs for parametric linkage analysis, but also the program for complex segregation analysis, which allows the estimation of the model parameters used in linkage. We tested our method on the real data about vertical cup-to-disc ratio, the important characteristic of the optic disc associated with glaucoma, in a large pedigree from a Dutch isolated population. Significant linkage signal was identified on chromosome 6 with the help of GADS, whereas the analysis of the normal distributed part of the sample demonstrated only a suggestive linkage peak on this chromosome. The software GADS is freely available at http://mga.bionet.nsc.ru/soft/index.html. PMID:22340440

  7. Barriers and facilitators of linkage to HIV primary care in New York City.

    PubMed

    Bauman, Laurie J; Braunstein, Sarah; Calderon, Yvette; Chhabra, Rosy; Cutler, Blayne; Leider, Jason; Rivera, Angelic; Sclafane, Jamie; Tsoi, Benjamin; Watnick, Dana

    2013-11-01

    One in 5 people living with HIV are unaware of their status; they account for an estimated 51% of new infections. HIV transmission can be reduced through a "Test and Treat" strategy, which can decrease both viral load and risk behaviors. However, linkage of newly diagnosed HIV-positive persons to care has proved challenging. We report quantitative and qualitative data on linkage to care from HIV testing sites that partnered with the New York City Department of Health and Mental Hygiene to implement "The Bronx Knows" (TBK), an initiative that tested 607,570 residents over 3 years. During TBK, partner agencies reported the aggregate number of HIV tests conducted, the number of confirmed positives (overall and new), and the number of confirmed positives linked to medical care. We conducted qualitative interviews with directors of 24 of 30 TBK HIV testing agencies to identify linkage barriers and selected 9 for case studies. Barriers to linkage fell into 3 domains: (1) health care system factors (long wait for provider appointments, requirement of a positive confirmatory test before scheduling an appointment, system navigation, and disrespect to patients); (2) social factors (HIV stigma); and (3) characteristics of risk populations (eg, mental illness, homelessness, substance use, and immigrant). Best practices for linkage included networking among community organizations, individualized care plans, team approach, comprehensive and coordinated care services, and patient peer navigation. Research and public health implications are discussed. PMID:24126445

  8. A ddRAD Based Linkage Map of the Cultivated Strawberry, Fragaria xananassa.

    PubMed

    Davik, Jahn; Sargent, Daniel James; Brurberg, May Bente; Lien, Sigbjørn; Kent, Matthew; Alsheikh, Muath

    2015-01-01

    The cultivated strawberry (Fragaria ×ananassa Duch.) is an allo-octoploid considered difficult to disentangle genetically due to its four relatively similar sub-genomic chromosome sets. This has been alleviated by the recent release of the strawberry IStraw90 whole genome genotyping array. However, array resolution relies on the genotypes used in the array construction and may be of limited general use. SNP detection based on reduced genomic sequencing approaches has the potential of providing better coverage in cases where the studied genotypes are only distantly related from the SNP array's construction foundation. Here we have used double digest restriction-associated DNA sequencing (ddRAD) to identify SNPs in a 145 seedling F1 hybrid population raised from the cross between the cultivars Sonata (♀) and Babette (♂). A linkage map containing 907 markers which spanned 1,581.5 cM across 31 linkage groups representing the 28 chromosomes of the species. Comparing the physical span of the SNP markers with the F. vesca genome sequence, the linkage groups resolved covered 79% of the estimated 830 Mb of the F. × ananassa genome. Here, we have developed the first linkage map for F. × ananassa using ddRAD and show that this technique and other related techniques are useful tools for linkage map development and downstream genetic studies in the octoploid strawberry. PMID:26398886

  9. A ddRAD Based Linkage Map of the Cultivated Strawberry, Fragaria xananassa

    PubMed Central

    Davik, Jahn; Sargent, Daniel James; Brurberg, May Bente; Lien, Sigbjørn; Kent, Matthew; Alsheikh, Muath

    2015-01-01

    The cultivated strawberry (Fragaria ×ananassa Duch.) is an allo-octoploid considered difficult to disentangle genetically due to its four relatively similar sub-genomic chromosome sets. This has been alleviated by the recent release of the strawberry IStraw90 whole genome genotyping array. However, array resolution relies on the genotypes used in the array construction and may be of limited general use. SNP detection based on reduced genomic sequencing approaches has the potential of providing better coverage in cases where the studied genotypes are only distantly related from the SNP array’s construction foundation. Here we have used double digest restriction-associated DNA sequencing (ddRAD) to identify SNPs in a 145 seedling F1 hybrid population raised from the cross between the cultivars Sonata (♀) and Babette (♂). A linkage map containing 907 markers which spanned 1,581.5 cM across 31 linkage groups representing the 28 chromosomes of the species. Comparing the physical span of the SNP markers with the F. vesca genome sequence, the linkage groups resolved covered 79% of the estimated 830 Mb of the F. ×ananassa genome. Here, we have developed the first linkage map for F. ×ananassa using ddRAD and show that this technique and other related techniques are useful tools for linkage map development and downstream genetic studies in the octoploid strawberry. PMID:26398886

  10. A detailed linkage map of rainbow trout produced using doubled haploids.

    PubMed Central

    Young, W P; Wheeler, P A; Coryell, V H; Keim, P; Thorgaard, G H

    1998-01-01

    We report the first detailed genetic linkage map of rainbow trout (Oncorhynchus mykiss). The segregation analysis was performed using 76 doubled haploid rainbow trout produced by androgenesis from a hybrid between the "OSU" and "Arlee" androgenetically derived homozygous lines. Four hundred and seventy-six markers segregated into 31 major linkage groups and 11 small groups (< 5 markers/group). The minimum genome size is estimated to be 2627.5 cM in length. The sex-determining locus segregated to a distal position on one of the linkage groups. We analyzed the chromosomal distribution of three classes of markers: (1) amplified fragment length polymorphisms, (2) variable number of tandem repeats, and (3) markers obtained using probes homologous to the 5' or 3' end of salmonid-specific small interspersed nuclear elements. Many of the first class of markers were clustered in regions that appear to correspond to centromeres. The second class of markers were more telomeric in distribution, and the third class were intermediate. Tetrasomic inheritance, apparently related to the tetraploid ancestry of salmonid fishes, was detected at one simple sequence repeat locus and suggested by the presence of one extremely large linkage group that appeared to consist of two smaller groups linked at their tips. The double haploid rainbow trout lines and linkage map present a foundation for further genomic studies. PMID:9504929

  11. EXPLoRA-web: linkage analysis of quantitative trait loci using bulk segregant analysis.

    PubMed

    Pulido-Tamayo, Sergio; Duitama, Jorge; Marchal, Kathleen

    2016-07-01

    Identification of genomic regions associated with a phenotype of interest is a fundamental step toward solving questions in biology and improving industrial research. Bulk segregant analysis (BSA) combined with high-throughput sequencing is a technique to efficiently identify these genomic regions associated with a trait of interest. However, distinguishing true from spuriously linked genomic regions and accurately delineating the genomic positions of these truly linked regions requires the use of complex statistical models currently implemented in software tools that are generally difficult to operate for non-expert users. To facilitate the exploration and analysis of data generated by bulked segregant analysis, we present EXPLoRA-web, a web service wrapped around our previously published algorithm EXPLoRA, which exploits linkage disequilibrium to increase the power and accuracy of quantitative trait loci identification in BSA analysis. EXPLoRA-web provides a user friendly interface that enables easy data upload and parallel processing of different parameter configurations. Results are provided graphically and as BED file and/or text file and the input is expected in widely used formats, enabling straightforward BSA data analysis. The web server is available at http://bioinformatics.intec.ugent.be/explora-web/. PMID:27105844

  12. External linkage tie permits reduction in ducting system flange thickness

    NASA Technical Reports Server (NTRS)

    Pfleger, R. O.

    1966-01-01

    External linkage tie reduces flange thickness and increases seal efficiency in high pressure ducting and piping systems. The linkage transmits the pressure separating load to the tube wall behind the flange allowing the flange to support only the seal.

  13. Desertification: a question of linkages.

    PubMed

    Stiles, D

    1985-01-01

    Desertification threatens 35% of the earth's land surface and 19% of the world's population. Each year, 60,000 sq km of land are reduced to desert-like conditions. Of the world's drylands, 60% has already been affected by the desertification process. The direct cost of desertification in the form of loss in agricultural production has been estimated at US$26 billion/year. To halt and perhaps reverse the desertification process, the United Nations Conference on Desertification (UNCOD) formulated a comprehensive Plan of Action to Combat Desertification (PACD) in 1977. However, there has been little progress in implementing the 28 recommendations contained within the PACD. Less than US$50,000, none of it from developed countries, has been raised toward the US$90 billion needed over a 20-year period. Developed nations prefer to give assistance through bilateral aid agreements that allow them to secure secondary benefits such as contracts, employment, and political influence. Another problem involves policies within the affected countries. Environmental programs tend not to be awarded high priority because of their lack of quick visual evidence of results. Government leaders must be convinced that desertification is a steady process that is robbing their lands of productive capabilities and increasing economic dependence on outside sources of support. A national machinery and institutional support to coordinate national action must be established. This requires development of a national plan of action to combat desertification, in which a detailed assessment is made of a country's desertification problems, priority projects are identified, and the institutional support to organize and coordinate the national plan is outlined. The United Nations Environment Program is prepared to assist any developing country in the preparation of such plans. PMID:12266990

  14. Linkage Maps of Microsatellite DNA Markers for the Pacific Oyster Crassostrea gigas

    PubMed Central

    Hubert, Sophie; Hedgecock, Dennis

    2004-01-01

    We constructed male and female consensus linkage maps for the Pacific oyster Crassostrea gigas, using a total of 102 microsatellite DNA markers typed in 11-day-old larvae from three families. We identified 11 and 12 linkage groups in the male and female consensus maps, respectively. Alignment of these separate maps, however, suggests 10 linkage groups, which agrees with the haploid chromosome number. The male linkage map comprises 88 loci and spans 616.1 cM, while the female map comprises 86 loci and spans 770.5 cM. The male and the female maps share 74 loci; 2 markers remain unlinked. The estimated coverages for the consensus linkage maps are 79% for the male and 70–75% for the female, on the basis of two estimates of genome length. Ninety-five percent of the genome is expected to lie within 16 and 21 cM of markers on the male and female maps, respectively, while 95% of simulated minimum distances to the male and female maps are within 10.1 and 13.6 cM, respectively. Females have significantly more recombination than males, across 118 pairs of linked markers in common to the parents of the three families. Significant differences in recombination and orders of markers are also evident among same-sex parents of different families as well as sibling parents of opposite sex. These observations suggest that polymorphism for chromosomal rearrangements may exist in natural populations, which could have profound implications for interpreting the evolutionary genetics of the oyster. These are the first linkage maps for a bivalve mollusc that use microsatellite DNA markers, which should enable them to be transferred to other families and to be useful for further genetic analyses such as QTL mapping. PMID:15454548

  15. A Disequilibrium Melting Spectrum: Partially Melted Crustal Xenoliths from the Wudalianchi Volcanic Field, NE China.

    NASA Astrophysics Data System (ADS)

    McLeod, C. L.; McGee, L. E.

    2015-12-01

    Disequilibrium melting has been established as a common process occurring during crustal anatexis and thus demonstrates that crustal assimilation by ascending mantle-derived magmas is likley not a closed system. Observations of extreme compositional heterogeneity within partial melts derived from crustal xenoliths have been documented in several recent examples, however, the retention or transfer of elements to and from residues and glasses, and their relative contributions to potential crustal contaminants warrants further investigation. Sampled lavas from the Huoshaoshan volcano in the Holocene Wudalianchi volcanic field of Northeast China contain crustal xenoliths which preserve a spectrum of partial melting both petrographically and geochemically, thus providing an excellent, natural example of crustal anatexis. Correlations exist between the volume of silicic glass preserved within the xenoliths and bulk rock SiO2 (70-83 wt%), Al2O3 (16-8 wt%), glass 87Sr/86Sr (0.715-0.908), abundances of elements common in feldspars and micas (Sr, Ba, Rb) and elements common in accessory minerals (Y, Zr, Nb). These correlations are likely associated with the consumption of feldspars and micas and the varying retention of accessory phases during partial melting. The xenoliths which contain the greater volumes of silicic glass and residual quartz (interpreted as being the most melted) were found within pahoehoe lava, whilst the least melted xenoliths were found within scoria of the summit cone of Huoshaoshan; thus it is interpreted that the extent of melting is linked to the immersion time in the lava. Small-scale (mm) mingling and transfer of material from the enclosing lava to the xenolith is observed, however, modelling of potential contaminant compositions is inconsistent with crustal contamination during lava petrogenesis. It is inferred that crustal contamination in sampled lavas is localized within the open magmatic system and most likely occurs at the contact zone

  16. Standard nomenclature for common bean chromosomes and linkage groups

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several DNA-based linkage maps have been developed for common bean including the core common bean linkage map using the BAT93 x Jalo EEP558 recombinant inbred line (RIL) population. Correlation of common bean chromosomes to the genetic linkage groups was completed using RFLP markers to assign each l...

  17. Soiled-based uranium disequilibrium and mixed uranium-thorium series radionuclide reference materials

    SciTech Connect

    Donivan, S.; Chessmore, R.

    1988-12-01

    The US Department of Energy (DOE) Office of Remedial Action and Waste Technology has assigned the Technical Measurements Center (TMC), located at the DOE Grand Junction Colorado, Projects Office and operated by UNC Geotech (UNC), the task of supporting ongoing remedial action programs by providing both technical guidance and assistance in making the various measurements required in all phases of remedial action work. Pursuant to this task, the Technical Measurements Center prepared two sets of radionuclide reference materials for use by remedial action contractors and cognizant federal and state agencies. A total of six reference materials, two sets comprising three reference materials each, were prepared with varying concentrations of radionuclides using mill tailings materials, ores, and a river-bottom soil diluent. One set (disequilibrium set) contains varying amounts of uranium with nominal amounts of radium-226. The other set (mixed-nuclide set) contains varying amounts of uranium-238 and thorium-232 decay series nuclides. 14 refs., 10 tabs.

  18. Disequilibrium in the 238uranium series in samples from yeelirrie, Western Australia

    USGS Publications Warehouse

    Lively, R.S.; Harmon, R.S.; Levinson, A.A.; Bland, C.J.

    1979-01-01

    Uranium-series disequilibrium studies carried out on samples from the Yeelirrie uranium deposit, Western Australia, indicate that uranium and radium have been migrating within the deposit during recent times, and are actually being removed from the deposit. Samples collected for 230Th/234U age dating were found to be substantially out of equilibrium, with 230Th/234U activity ratios ranging from 0.750 to 1.345. This can be explained by a dynamic hydrologic system in which there has been, and continues to be, uranium migration caused by leaching in this arid, oxidizing environment, and a fluctuating water table. Recent, extensive 226Ra migration (226Ra/230Th activity ratios range from 0.53 to 1.30), and a very low emanation factor (E) of 222Rn limit the quantitative application of radon exploration techniques in this environment. ?? 1979.

  19. Small-scale disequilibrium in a magmatic inclusion and its more silicic host

    NASA Technical Reports Server (NTRS)

    Davidson, Jon P.; Holden, Peter; Halliday, Alex N.; De Silva, Shanaka L.

    1990-01-01

    An investigation of small-scale isotopic, compositional, and mineralogical variation across the interface of a basaltic-andesite inclusion and its dacitic host from Cerro-Chascon, a Holocene dome in northern Chile, is discussed. Serial sectioning across the interface of the inclusion and its host dacite, complemented by microdrill sampling and detailed microprobe work, has enabled an examination of the scale of mixing and chemical disequilibrium. The composition of the inclusion is found to be relatively homogeneous; the dacite host is heterogeneous on a small scale; the isotopic composition in the marginal zone shows the highest Sr-87/Sr-86 and lowest Nd-143/Nd-144; the large plagioclase crystals in the inclusions and host are xenocrystic. These differences are reconciled with a model of magma evolution in a crustal magma chamber.

  20. Technical challenges of providing record linkage services for research

    PubMed Central

    2014-01-01

    Background Record linkage techniques are widely used to enable health researchers to gain event based longitudinal information for entire populations. The task of record linkage is increasingly being undertaken by specialised linkage units (SLUs). In addition to the complexity of undertaking probabilistic record linkage, these units face additional technical challenges in providing record linkage ‘as a service’ for research. The extent of this functionality, and approaches to solving these issues, has had little focus in the record linkage literature. Few, if any, of the record linkage packages or systems currently used by SLUs include the full range of functions required. Methods This paper identifies and discusses some of the functions that are required or undertaken by SLUs in the provision of record linkage services. These include managing routine, on-going linkage; storing and handling changing data; handling different linkage scenarios; accommodating ever increasing datasets. Automated linkage processes are one way of ensuring consistency of results and scalability of service. Results Alternative solutions to some of these challenges are presented. By maintaining a full history of links, and storing pairwise information, many of the challenges around handling ‘open’ records, and providing automated managed extractions are solved. A number of these solutions were implemented as part of the development of the National Linkage System (NLS) by the Centre for Data Linkage (part of the Population Health Research Network) in Australia. Conclusions The demand for, and complexity of, linkage services is growing. This presents as a challenge to SLUs as they seek to service the varying needs of dozens of research projects annually. Linkage units need to be both flexible and scalable to meet this demand. It is hoped the solutions presented here can help mitigate these difficulties. PMID:24678656

  1. Follow-up to genome-wide linkage and admixture mapping studies implicates components of the extracellular matrix in susceptibility to and size of uterine fibroids

    PubMed Central

    Aissani, Brahim; Zhang, Kui; Wiener, Howard

    2014-01-01

    Objective To conduct a follow-up association mapping to independent genome-wide linkage and admixture mapping studies of uterine leiomyoma. Design Case-control study. Setting Cross sectional study. Patients A total of 1,045 premenopausal North American women participants to the NIEHS uterine fibroid study. Intervention(s) None. Main Outcome Measure(s) We genotyped 2,772 single nucleotide polymorphisms from candidate genes located in peaks from linkage mapping (2q37, 3p21, 5p13, 10p11, 11p15, 12q14, 17q25) or admixture linkage disequilibrium mapping (2q37, 4p16.1, 10q26) and reported to have regulated expression in uterine fibroids. Results We report significant associations of variant members of the collagen gene family with the risk and tumor size, including missense variants in COL6A3 and COL13A, with replications in the African and European American study groups. Furthermore, the cell-matrix Rho GTPase-encoding ARHGAP26 gene and MAN1C1, a gene encoding a Golgi mannosidase involved in the maturation of procollagens emerged as new candidate UL genes affecting both the risk and tumor size. Conclusion Our data converge onto a model of UL pathogenesis possibly resulting from altered regulation, maintenance and/or renewal of the extracellular matrix. PMID:25455875

  2. Confirmation and Fine Mapping of a Major QTL for Aflatoxin Resistance in Maize Using a Combination of Linkage and Association Mapping.

    PubMed

    Zhang, Yu; Cui, Min; Zhang, Jimin; Zhang, Lei; Li, Chenliu; Kan, Xin; Sun, Qian; Deng, Dexiang; Yin, Zhitong

    2016-01-01

    Maize grain contamination with aflatoxin from Aspergillus flavus (A. flavus) is a serious health hazard to animals and humans. To map the quantitative trait loci (QTLs) associated with resistance to A. flavus, we employed a powerful approach that differs from previous methods in one important way: it combines the advantages of the genome-wide association analysis (GWAS) and traditional linkage mapping analysis. Linkage mapping was performed using 228 recombinant inbred lines (RILs), and a highly significant QTL that affected aflatoxin accumulation, qAA8, was mapped. This QTL spanned approximately 7 centi-Morgan (cM) on chromosome 8. The confidence interval was too large for positional cloning of the causal gene. To refine this QTL, GWAS was performed with 558,629 single nucleotide polymorphisms (SNPs) in an association population comprising 437 maize inbred lines. Twenty-five significantly associated SNPs were identified, most of which co-localised with qAA8 and explained 6.7% to 26.8% of the phenotypic variation observed. Based on the rapid linkage disequilibrium (LD) and the high density of SNPs in the association population, qAA8 was further localised to a smaller genomic region of approximately 1500 bp. A high-resolution map of the qAA8 region will be useful towards a marker-assisted selection (MAS) of A. flavus resistance and a characterisation of the causal gene. PMID:27598199

  3. The Effect of Educational Disequilibrium in Field Work on Graduate Social Work Students' Self-Concept and Mental Health

    ERIC Educational Resources Information Center

    Ying, Yu-Wen

    2011-01-01

    The author used a mixed methods design to assess field work-related educational disequilibrium and its effect on the self-concept and mental health of MSW students. Twenty-eight advanced, fourth-semester MSW students were compared with 37 entering, first-semester MSW students in practice-related sense of accomplishment. Compared with first-year…

  4. DECAY-SERIES DISEQUILIBRIUM STUDY OF IN-SITU, LONG-TERM RADIONUCLIDE TRANSPORT IN WATER-ROCK SYSTEMS

    EPA Science Inventory

    Uranium and thorium-series disequilibrium in nature permits the determination of many in-situphysico-chemical, geologic and hydrologic variables that control the long-term migration ofradionuclides in geologic systems. It also provides site-specific, natural analog information...

  5. Linkages among global and regional air issues

    SciTech Connect

    Maarouf, A.R.

    1997-11-01

    Six air issues are currently on science and policy agendas in Canada and elsewhere. These are climate change, stratospheric ozone depletion, acidic deposition, SMOG, suspended particulate matter, and hazardous air pollutants. It is now recognized that these issues are interrelated, and they may interact to cause negative as well as some beneficial effects. The linkages among these issues must therefore be better understood in order to develop effective policies to deal with this ensemble of related issues. This paper illustrates through several examples the linkages among the air issues. It also points to potentially conflicting policies arising from the single-issue approach, and it emphasizes the need for better integration of air issues. 14 refs., 1 tab.

  6. Adjustable throttle linkage for outboard motors

    SciTech Connect

    Dunham, W.D.; Miller, G.L.

    1986-02-17

    An adjustable throttle linkage is described for use in controlling operation of an internal combustion engine having a carburetor including a pivotable throttle valve, a throttle valve position control member operably connected to the throttle valve and movable so as to control the position of the throttle valve, and a throttle lever for controlling the position of the throttle valve. The adjustable throttle linkage comprises a connecting link having one end connected to one of the throttle lever and the control member, and having a threaded portion, means for adjustably connecting the threaded portion to the other of the throttle lever and the control member. The adjustable connecting means includes a slot in the other of the throttle lever and the control member, and a rotatable member threaded onto the threaded portion and receive in the slot such that rotation of the rotatable member causes relative movement between the link and the other of the throttle lever and the control member.

  7. Anxiety and Depression: Linkages with Viral Diseases

    PubMed Central

    Coughlin, Steven S.

    2012-01-01

    Anxiety and mood disorders are common in the general population in countries around the world. This article provides a review of the recent literature on anxiety and depressive disorders with a focus on linkages with several important viral diseases. Although the majority of studies have been conducted in developed countries such as the United States and Great Britain, some studies have been carried out in less developed nations where only a small percentage of persons with mental illness receive treatment for their condition. The studies summarized in this review indicate that there are important linkages between anxiety and depression and viral diseases such as influenza A (H1N1) and other influenza viruses, varicella-zoster virus, herpes simplex virus, human immunodeficiency virus/acquired immune deficiency syndrome, and hepatitis C. Additional studies are needed to further clarify the mechanisms for interactions between mental health and communicable diseases, in order to assist patients and further prevention and control efforts. PMID:25264396

  8. Linkage of typical pseudoachondroplasia to chromosome 19

    SciTech Connect

    Hecht, J.T.; Deere, M.; Conner, B.; Horton, W.A. ); Francomano, C.A. ); Briggs, M.D.; Cohn, D.H. ); Warman, M. ); Blanton, S.H. )

    1993-12-01

    Pseudoachondroplasia (PSACH) is an autosomal dominant dwarfing condition associated with disproportionate short stature, marked joint deformities, and early onset osteoarthritis. Previous linkage studies have excluded linkage to cartilage and noncartilagenous extracellular matrix candidate genes. Here, the authors report mapping the pseudoachondroplasia gene to chromosome 19. Maximum lod scores of 4.70, 4.15, and 4.86 at [theta] = 0.00 were found for D19S212, D19S215, and D19S49, respectively. Multipoint analysis suggests the following order: D19S253-D19S199-(D19S212/PSACH/D19S215)-D19S222-D19S49. 24 refs., 4 figs., 1 tab.

  9. Genome-Wide Linkage and Admixture Mapping of Type 2 Diabetes in African American Families From the American Diabetes Association GENNID (Genetics of NIDDM) Study Cohort

    PubMed Central

    Elbein, Steven C.; Das, Swapan K.; Hallman, D. Michael; Hanis, Craig L.; Hasstedt, Sandra J.

    2009-01-01

    OBJECTIVE—We used a single nucleotide polymorphism (SNP) map in a large cohort of 580 African American families to identify regions linked to type 2 diabetes, age of type 2 diabetes diagnosis, and BMI. RESEARCH DESIGN AND METHODS—After removing outliers and problematic samples, we conducted linkage analysis using 5,914 SNPs in 1,344 individuals from 530 families. Linkage analysis was conducted using variance components for type 2 diabetes, age of type 2 diabetes diagnosis, and BMI and nonparametric linkage analyses. Ordered subset analyses were conducted ranking on age of type 2 diabetes diagnosis, BMI, waist circumference, waist-to-hip ratio, and amount of European admixture. Admixture mapping was conducted using 4,486 markers not in linkage disequilibrium. RESULTS—The strongest signal for type 2 diabetes (logarithm of odds [LOD] 4.53) was a broad peak on chromosome 2, with weaker linkage to age of type 2 diabetes diagnosis (LOD 1.82). Type 2 diabetes and age of type 2 diabetes diagnosis were linked to chromosome 13p (3–22 cM; LOD 2.42 and 2.46, respectively). Age of type 2 diabetes diagnosis was linked to 18p (66 cM; LOD 2.96). We replicated previous reports on chromosome 7p (79 cM; LOD 2.93). Ordered subset analysis did not overlap with linkage of unselected families. The best admixture score was on chromosome 12 (90 cM; P = 0.0003). CONCLUSIONS—The linkage regions on chromosomes 7 (27–78 cM) and 18p overlap prior reports, whereas regions on 2p and 13p linkage are novel. Among potential candidate genes implicated are TCF7L1, VAMP5, VAMP8, CDK8, INSIG2, IPF1, PAX8, IL18R1, members of the IL1 and IL1 receptor families, and MAP4K4. These studies provide a complementary approach to genome-wide association scans to identify causative genes for African American diabetes. PMID:18840782

  10. A variable age of onset segregation model for linkage analysis, with correction for ascertainment, applied to glioma

    PubMed Central

    Sun, Xiangqing; Vengoechea, Jaime; Elston, Robert; Chen, Yanwen; Amos, Christopher I.; Armstrong, Georgina; Bernstein, Jonine L; Claus, Elizabeth; Davis, Faith; Houlston, Richard S; Il'yasova, Dora; Jenkins, Robert B; Johansen, Christoffer; Lai, Rose; Lau, Ching C; Liu, Yanhong; McCarthy, Bridget J; Olson, Sara H; Sadetzki, Siegal; Schildkraut, Joellen; Shete, Sanjay; Yu, Robert; Vick, Nicholas A; Merrell, Ryan; Wrensch, Margaret; Yang, Ping; Melin, Beatrice; Bondy, Melissa L.; Barnholtz-Sloan, Jill S.

    2012-01-01

    Background We propose a two-step model-based approach, with correction for ascertainment, to linkage analysis of a binary trait with variable age of onset and apply it to a set of multiplex pedigrees segregating for adult glioma. Methods First, we fit segregation models by formulating the likelihood for a person to have a bivariate phenotype, affection status and age of onset, along with other covariates, and from these we estimate population trait allele frequencies and penetrance parameters as a function of age (N=281 multiplex glioma pedigrees). Second, the best fitting models are used as trait models in multipoint linkage analysis (N=74 informative multiplex glioma pedigrees). To correct for ascertainment, a prevalence constraint is used in the likelihood of the segregation models for all 281 pedigrees. Then the trait allele frequencies are re-estimated for the pedigree founders of the subset of 74 pedigrees chosen for linkage analysis. Results Using the best fitting segregation models in model-based multipoint linkage analysis, we identified two separate peaks on chromosome 17; the first agreed with a region identified by Shete et al. who used model-free affected-only linkage analysis, but with a narrowed peak: and the second agreed with a second region they found but had a larger maximum log of the odds (LOD). Conclusions/Impact Our approach has the advantage of not requiring markers to be in linkage equilibrium unless the minor allele frequency is small (markers which tend to be uninformative for linkage), and of using more of the available information for LOD-based linkage analysis. PMID:22962404

  11. Investigating disequilibrium effects in magma ascent dynamics with a new multiphase flow model

    NASA Astrophysics Data System (ADS)

    de'Michieli Vitturi, Mattia; Clarke, Amanda B.; Neri, Augusto; Voight, Barry; La Spina, Giuseppe

    2013-04-01

    Numerical and physical models have greatly enhanced our understanding of eruption dynamics. The multiphase non-equilibrium nature of magma inside a conduit, the development of gas overpressure, and the possibilities for open-system degassing are all recognized as controlling factors affecting changes in eruptive rate and style, yet models of magma ascent considering both distinct velocities and pressures for the different phases have not been deeply studied. The numerical model we present here considers a set of multiphase compressible equations governing magma movement through a subsurface pathway (e.g., from chamber to surface). This model represents a significant advance in its quantitative description of the magma system in that it: 1) is capable of treating both dilute and dense flow regimes; 2) describes flow above and below the fragmentation level in a coupled and consistent way; 3) quantifies the interaction between two phases forming the magmatic mixture with two distinct pressures and two velocities; 4) accounts for disequilibrium crystallization and degassing; and 5) allows for open-system degassing. Here we investigate, through a sensitivity analysis, the role of different disequilibrium processes, in particular those controlling overpressure increase and the retention of gas, in controlling vent conditions and transitions in eruptive style. We develop a reference case using conditions appropriate for the ongoing eruption of Soufrière Hills volcano. As an example, if an andesitic magma with a 5 wt% total water content (about 1.5 vol% of exsolved gas) decompresses to atmospheric pressure from 5km depth as a homogeneous mixture (single pressure and single velocity), the gas volume fraction at the vent should exceed 95 vol% if no further gas exsolution is considered, and 99 vol% with equilibrium exsolution. These values changes significantly when development of gas overpressure and open-system degassing are allowed and considered in the model, and thus

  12. The changing distribution of a major surgical procedure across hospitals: were supply shifts and disequilibrium important?

    PubMed

    Friedman, B; Elixhauser, A

    1995-01-01

    This paper describes and analyzes the changing distribution across hospitals in the U.S. of total hip replacement surgery (THR) for the period 1980-1987. THR is one of the most costly single procedures contributing to health care expenses. Also, the use of THR exhibits a particularly high degree of geographic variation. Recent research pointed to shifts in demand as one plausible economic explanation for increasing use of THR. This paper questions whether shifts in supply may have been large enough to explain changes in patient mix and the relationship of patient mix to the number of procedures performed at a particular hospital. In addition, the relationship between total use of THR and the local availability of orthopaedic surgeons as well as the average allowable Medicare fee for standardized physician services is analyzed. These relationships might yield evidence to support a scenario of induced demand beyond the optimum for patients' welfare, or evidence of supply increase within a disequilibrium scenario. This study, using data for all THR patients in a large sample of hospitals, tends to reject the formulation of a market with independent supply and demand shifts where the supply shifts were the dominant forces. Hospitals with a larger number of THRs performed did not see a higher percentage of older, sicker, and lower income patients. It was more likely that demand shifts generated increases in capacity for surgical services. Moreover, there was little evidence for a persistent disequilibrium and only weak evidence for inducement. Also, we found little evidence that hospitals responded to financial incentives inherent in the Medicare payment system after 1983 to select among THR candidates in favour of those with below average expected cost. We did observe increased concentration over time of THR procedures in facilities with high volume--suggesting plausible demand shifts towards hospitals with a priori quality and cost advantages or who obtained those

  13. U-series disequilibrium constraints on magma generation at the Jan Mayen hotspot

    NASA Astrophysics Data System (ADS)

    Rivers, E. R.; Chernow, R.; Elkins, L. J.; Sims, K. W.; Blichert-Toft, J.; Devey, C. W.

    2013-12-01

    The incompatible element-enriched magma source beneath the Jan Mayen Island hotspot influences melt generation on the adjacent northern Mid-Atlantic Ridge system and likely derives from either a small, local mantle plume, ancient Icelandic plume material emplaced in the mantle source, and/or sub-continental lithospheric mantle remnants emplaced locally by rifting of Greenland. The slow spreading Northern Kolbeinsey and Southern Mohns Ridges are immediately adjacent to Jan Mayen Island. Both have relatively shallow ridge axes, particularly the extremely shallow Eggvin Bank region of the Northern Kolbeinsey Ridge, which host anomalously large central volcanic edifices. We are currently collecting U-series disequilibrium and long-lived radiogenic isotope data for fresh, glassy mid-ocean ridge basalts from the Northern Kolbeinsey and Southern Mohns Ridge segments to better constrain source composition, depth of melting in the garnet peridotite stability field, solid mantle upwelling rates, and the nature of melt extraction beneath those segments. In particular, we are measuring isotopic data for geographically well-located samples collected from hummocky pillow basalt flows within the axial valley of the Northern Kolbeinsey Ridge segment as well as from the large volcanoes on both ridge segments, to further determine the role of the Jan Mayen hotspot in crustal construction on the Mid-Atlantic Ridge. Recently collected data show particularly high strontium isotope ratios consistent with trace element patterns that suggest a distinct local plume located beneath the Jan Mayen hotspot. A plume model for Jan Mayen is supported by new bathymetric imaging of adjacent ridge segments that reveals excess volcanism beneath the large axial volcanoes and a radial distribution of enrichment surrounding Jan Mayen Island. We predict that age-constrained U-series disequilibrium measurements will support active mantle upwelling focused beneath both Jan Mayen Island and the large axial

  14. Genome-wide high-density SNP linkage search for glioma susceptibility loci: results from the Gliogene Consortium

    PubMed Central

    Shete, Sanjay; Lau, Ching C; Houlston, Richard S; Claus, Elizabeth B; Barnholtz-Sloan, Jill; Lai, Rose; Il’yasova, Dora; Schildkraut, Joellen; Sadetzki, Siegal; Johansen, Christoffer; Bernstein, Jonine L; Olson, Sara H; Jenkins, Robert B; Yang, Ping; Vick, Nicholas A; Wrensch, Margaret; Davis, Faith G; McCarthy, Bridget J; Leung, Eastwood Hon-chiu; Davis, Caleb; Cheng, Rita; Hosking, Fay J; Armstrong, Georgina N; Liu, Yanhong; Yu, Robert K; Henriksson, Roger; Consortium, The Gliogene; Melin, Beatrice S; Bondy, Melissa L

    2011-01-01

    Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have demonstrated that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium SNPs, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P=0.0005) at 17q12–21.32 and the Z-score of 4.20 (P=0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P=0.008) and the Z-score of 1.47 (P=0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P=0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma. PMID:22037877

  15. Hidden linkages between urbanization and food systems.

    PubMed

    Seto, Karen C; Ramankutty, Navin

    2016-05-20

    Global societies are becoming increasingly urban. This shift toward urban living is changing our relationship with food, including how we shop and what we buy, as well as ideas about sanitation and freshness. Achieving food security in an era of rapid urbanization will require considerably more understanding about how urban and food systems are intertwined. Here we discuss some potential understudied linkages that are ripe for further examination. PMID:27199419

  16. The CEPH consortium linkage map of human chromosome 13

    SciTech Connect

    Bowcock, A.M.; Barnes, R.I.; Gerken, S.C.; Leppert, M.; Shiang, R.; Jabs, E.W.; Warren, A.C.; Antonarakis, S.; Retief, A.E.; Vergnaud, G.

    1993-05-01

    The CEPH consortium map of chromosome 13 is presented. This map contains 59 loci defined by genotypes generated from CEPH family DNAs with 94 different probe and restriction enzyme combinations contributed by 9 laboratories. A total of 25 loci have been placed on the map with likelihood support of at least 1000:1. The map extends from loci in the centromeric region of chromosome 13 to the terminal band of the long arm. Multipoint linkage analyses provided estimates that the male, female, and sex-averaged maps extend for 158, 203, and 178cM respectively. The largest interval is 24 cM and is between D13Z1 (alphaRI) and ATP1AL1. The mean genetic distance between the 25 uniquely placed loci is 7 cM. 76 refs., 3 figs., 5 tabs.

  17. Linkage and association analysis in pedigrees from different populations.

    PubMed

    Beyene, Joseph; Yan, Jun; Greenwood, Celia M T

    2005-01-01

    Using the Genetic Analysis Workshop 14 simulated datasets we carried out nonparametric linkage analyses and applied a log-linear method for analysis of case-parent-triad data with stratification on parental mating type. We proposed and applied a random effect modelling approach to explore the impact of population heterogeneity on tests of association between genetic markers and disease status. The estimated genetic effect may appear to be strongly significant in one population but nonsignificant in another population, leading to confusion about interpretation. However, when results are interpreted in the light of a random effects model, both studies may be making similar statements about a genetic effect that varies depending on environment and background. PMID:16451671

  18. Linkage Analysis of Glomerular Filtration Rate in American Indians: The Strong Heart Family Study

    PubMed Central

    Mottl, Amy K.; Vupputuri, Suma; Cole, Shelley A.; Almasy, Laura; Göring, Harald HH; Diego, Vincent P.; Laston, Sandra; Franceschini, Nora; Shara, Nawar; Lee, Elisa T.; Best, Lyle G.; Fabsitz, Richard R.; MacCluer, Jean W.; Umans, Jason G.; North, Kari E.

    2009-01-01

    American Indians have a disproportionately high rate of kidney disease likely due to a combination of increased environmental and genetic risk factors. In an attempt to localize genes influencing kidney disease risk factors, we performed a genome wide scan of estimated glomerular filtration rate on participants of the Strong Heart Family Study. Over 3 600 men and women from 13 American Indian tribes were recruited from 3 centers (Arizona, North and South Dakota, Oklahoma). Using SOLAR 2.1.2, multipoint variance component linkage analysis was performed in each center as well as the entire cohort after controlling for center effects. Two modeling strategies were utilized: model 1 incorporated age, sex and interaction terms and model 2 additionally controlled for diabetic status, systolic and diastolic blood pressure, body mass index, low density lipoproteins, high density lipoproteins, triglycerides and smoking status. Significant evidence for linkage in Arizona lay on 12p12.2 at 39cM nearest marker D12S310 (LOD=3.5). Additional loci with suggestive evidence for linkage were detected at 1p36.31 (LOD=2.0–2.3), 2q33.3 (LOD=1.8) and 9q34.2 (LOD=2.4). No significant evidence for additive interaction with diabetes, hypertension or obesity was noted. In conclusion, we found evidence for linkage of a quantitative trait locus influencing estimated glomerular filtration rate to a region of chromosome 12p in a large cohort of American Indians. PMID:18854848

  19. Genetic linkage for Darier disease (keratosis follicularis)

    SciTech Connect

    Kennedy, J.L.; King, N.; Perkins, M.

    1995-01-30

    Darier disease is an autosomal dominant skin disorder characterized by abnormal keratinocyte adhesion. Recent data have provided evidence for linkage of the Darier disease locus to 12q23-24.1 in British families. We have carried out linkage analysis using the 12q markers D12S58, D12S84, D12S79, D12S86, PLA2, and D12S63 in 6 Canadian families. Pairwise linkage analysis generated positive lod scores at all 6 markers at various recombination fractions, and each family showed positive lod scores with more than one marker. The peak lod score in the multipoint analysis (Z{sub max}) was 5.5 in the interval between markers D12S58 and D12S84. These positive lod scores in North American families of varied European ancestry confirm the location of the Darier disease gene, and suggest genetic homogeneity. The future identification and sequencing of the gene responsible for Darier disease should lead to improved understanding of the disease and of keratinocyte adhesion in general. 22 refs., 2 figs., 2 tabs.

  20. 'Linkage' pharmaceutical evergreening in Canada and Australia.

    PubMed

    Faunce, Thomas A; Lexchin, Joel

    2007-01-01

    'Evergreening' is not a formal concept of patent law. It is best understood as a social idea used to refer to the myriad ways in which pharmaceutical patent owners utilise the law and related regulatory processes to extend their high rent-earning intellectual monopoly privileges, particularly over highly profitable (either in total sales volume or price per unit) 'blockbuster' drugs. Thus, while the courts are an instrument frequently used by pharmaceutical brand name manufacturers to prolong their patent royalties, 'evergreening' is rarely mentioned explicitly by judges in patent protection cases. The term usually refers to threats made to competitors about a brand-name manufacturer's tactical use of pharmaceutical patents (including over uses, delivery systems and even packaging), not to extension of any particular patent over an active product ingredient. This article focuses in particular on the 'evergreening' potential of so-called 'linkage' provisions, imposed on the regulatory (safety, quality and efficacy) approval systems for generic pharmaceuticals of Canada and Australia, by specific articles in trade agreements with the US. These 'linkage' provisions have also recently appeared in the Korea-US Free Trade Agreement (KORUSFTA). They require such drug regulators to facilitate notification of, or even prevent, any potential patent infringement by a generic pharmaceutical manufacturer. This article explores the regulatory lessons to be learnt from Canada's and Australia's shared experience in terms of minimizing potential adverse impacts of such 'linkage evergreening' provisions on drug costs and thereby potentially on citizen's access to affordable, essential medicines. PMID:17543113

  1. Interannual variation in effective number of breeders and estimation of effective population size in long-lived iteroparous lake sturgeon (Acipenser fulvescens).

    PubMed

    Duong, Thuy Yen; Scribner, Kim T; Forsythe, Patrick S; Crossman, James A; Baker, Edward A

    2013-03-01

    Quantifying interannual variation in effective adult breeding number (N(b)) and relationships between N(b), effective population size (N(e)), adult census size (N) and population demographic characteristics are important to predict genetic changes in populations of conservation concern. Such relationships are rarely available for long-lived iteroparous species like lake sturgeon (Acipenser fulvescens). We estimated annual N(b) and generational N(e) using genotypes from 12 microsatellite loci for lake sturgeon adults (n = 796) captured during ten spawning seasons and offspring (n = 3925) collected during larval dispersal in a closed population over 8 years. Inbreeding and variance N(b) estimated using mean and variance in individual reproductive success derived from genetically identified parentage and using linkage disequilibrium (LD) were similar within and among years (interannual range of N(b) across estimators: 41-205). Variance in reproductive success and unequal sex ratios reduced N(b) relative to N on average 36.8% and 16.3%, respectively. Interannual variation in N(b)/N ratios (0.27-0.86) resulted from stable N and low standardized variance in reproductive success due to high proportions of adults breeding and the species' polygamous mating system, despite a 40-fold difference in annual larval production across years (437-16 417). Results indicated environmental conditions and features of the species' reproductive ecology interact to affect demographic parameters and N(b)/N. Estimates of N(e) based on three single-sample estimators, including LD, approximate Bayesian computation and sibship assignment, were similar to annual estimates of N(b). Findings have important implications concerning applications of genetic monitoring in conservation planning for lake sturgeon and other species with similar life histories and mating systems. PMID:23293919

  2. Monitoring Dolphins in an Urban Marine System: Total and Effective Population Size Estimates of Indo-Pacific Bottlenose Dolphins in Moreton Bay, Australia

    PubMed Central

    Ansmann, Ina C.; Lanyon, Janet M.; Seddon, Jennifer M.; Parra, Guido J.

    2013-01-01

    Moreton Bay, Queensland, Australia is an area of high biodiversity and conservation value and home to two sympatric sub-populations of Indo-Pacific bottlenose dolphins (Tursiops aduncus). These dolphins live in close proximity to major urban developments. Successful management requires information regarding their abundance. Here, we estimate total and effective population sizes of bottlenose dolphins in Moreton Bay using photo-identification and genetic data collected during boat-based surveys in 2008–2010. Abundance (N) was estimated using open population mark-recapture models based on sighting histories of distinctive individuals. Effective population size (Ne) was estimated using the linkage disequilibrium method based on nuclear genetic data at 20 microsatellite markers in skin samples, and corrected for bias caused by overlapping generations (Nec). A total of 174 sightings of dolphin groups were recorded and 365 different individuals identified. Over the whole of Moreton Bay, a population size N of 554±22.2 (SE) (95% CI: 510–598) was estimated. The southern bay sub-population was small at an estimated N = 193±6.4 (SE) (95% CI: 181–207), while the North sub-population was more numerous, with 446±56 (SE) (95% CI: 336–556) individuals. The small estimated effective population size of the southern sub-population (Nec = 56, 95% CI: 33–128) raises conservation concerns. A power analysis suggested that to reliably detect small (5%) declines in size of this population would require substantial survey effort (>4 years of annual mark-recapture surveys) at the precision levels achieved here. To ensure that ecological as well as genetic diversity within this population of bottlenose dolphins is preserved, we consider that North and South sub-populations should be treated as separate management units. Systematic surveys over smaller areas holding locally-adapted sub-populations are suggested as an alternative method for increasing ability to detect

  3. A Microsatellite Genetic Linkage Map for Xiphophorus

    PubMed Central

    Walter, R. B.; Rains, J. D.; Russell, J. E.; Guerra, T. M.; Daniels, C.; Johnston, Dennis A.; Kumar, Jay; Wheeler, A.; Kelnar, K.; Khanolkar, V. A.; Williams, E. L.; Hornecker, J. L.; Hollek, L.; Mamerow, M. M.; Pedroza, A.; Kazianis, S.

    2004-01-01

    Interspecies hybrids between distinct species of the genus Xiphophorus are often used in varied research investigations to identify genomic regions associated with the inheritance of complex traits. There are 24 described Xiphophorus species and a greater number of pedigreed strains; thus, the number of potential interspecies hybrid cross combinations is quite large. Previously, select Xiphophorus experimental crosses have been shown to exhibit differing characteristics between parental species and among the hybrid fishes derived from crossing them, such as widely differing susceptibilities to chemical or physical agents. For instance, genomic regions harboring tumor suppressor and oncogenes have been identified via linkage association of these loci with a small set of established genetic markers. The power of this experimental strategy is related to the number of genetic markers available in the Xiphophorus interspecies cross of interest. Thus, we have undertaken the task of expanding the suite of easily scored markers by characterization of Xiphophorus microsatellite sequences. Using a cross between Xiphophorus maculatus and X. andersi, we report a linkage map predominantly composed of microsatellite markers. All 24 acrocentric chromosome sets of Xiphophorus are represented in the assembled linkage map with an average intergenomic distance of 7.5 cM. Since both male and female F1 hybrids were used to produce backcross progeny, these recombination rates were compared between “male” and “female” maps. Although several genomic regions exhibit differences in map length, male- and female-derived maps are similar. Thus Xiphophorus, in contrast to zebrafish, Danio rerio, and several other vertebrate species, does not show sex-specific differences in recombination. The microsatellite markers we report can be easily adapted to any Xiphophorus interspecies and some intraspecies crosses, and thus provide a means to directly compare results derived from independent

  4. Temperature and precipitation records from stalagmites grown under disequilibrium conditions: A model approach.

    NASA Astrophysics Data System (ADS)

    Mühlinghaus, C.; Scholz, D.; Mangini, A.

    2009-04-01

    To reconstruct past variations in Earth's climate, a variety of climate archives are studied. During the last decades stalagmites came into focus due to their long, continuous growth and absolute dating techniques. In this study a numerical model was developed, which calculates variations in temperature and precipitation during the growth period of stalagmites grown under isotopic disequilibrium conditions using the isotope profiles both along the growth axis and individual growth layers as well as the growth depth relation. The model is based on the inversion and combination of existing models (Dreybrodt 1999, Kaufmann et al. 2004, Mühlinghaus et al. 2007, Scholz et al. 2008, Mühlinghaus et al. 2008b) and incorporates important parameters describing the cave and the overlying soil. Beside the dependence on temperature and water supply it depends on the isotopic composition of the drip water, the pCO2 pressure of the soil and the cave atmosphere as well as on the mixing coefficient, which describes mixing between the impinging drop and the existing solution layer. To determine the characteristics of temperature and precipitation, in a first step all other parameters are assumed to remain constant over the whole growth period to simplify calculations. This allows to run the model with only two input variables: the isotopic composition ^13C of the drip water and a temperature information at any point of time during the growth period of the stalagmite (e.g. the recent cave temperature). All other parameters are determined by the model. The CSM (Combined Stalagmite Model, Mühlinghaus et al. 2008a) was applied to three stalagmites from the Marcelo Arévalo cave in Southern Patagonia, Chile (Schimpf 2005, Kilian et al. 2006, Schimpf et al. in prep). These stalagmites grew in a small cave next to each other during the last 4500 years. However, their isotopic profiles along the growth axis show different kinetic influences. Despite these conditions, the temperature

  5. Delayed, disequilibrium degassing in rhyolite magma: Decompression experiments and implications for explosive volcanism

    USGS Publications Warehouse

    Mangan, M.; Sisson, T.

    2000-01-01

    Recent numerical models and analog shock tube experiments show that disequilibrium degassing during magma ascent may lead to violent vesiculation very near the surface. In this study a series of decompression experiments using crystal-free, rhyolite melt were conducted to examine the development of large supersaturations due to delayed, homogenous (spontaneous) bubble nucleation. Melts were saturated at 900??C and 200 MPa with either 5.2 wt% dissolved H2O, or with 4.2 wt% H2O and 640 ppm CO2, and isothermally decompressed at linear rates of either 0.003, 0.025, or 8.5 MPa/s to final pressures between 25 and 175 MPa. Additional isobaric saturation experiments (900??C, 200-25 MPa) using pure H2O or mixed H2O-CO2 fluids establish reference equilibrium solubility curves/values. Homogenous nucleation is triggered in both H2O-only and H2O-CO2 experiments once the supersaturation pressure (??Pss) reaches ?? 120-150 MPa and the melt contains ?? two times its equilibrium water contents. Bubble number density and nucleation rate depend on the supersaturation pressure, with values on the order of 102/cm3 and < 1/cm3/s for ??Pss~120 MPa; 106/cm3 and 103-105/cm3/s for ??Pss??~130-150 MPa; and 107/cm3 and 106/cm3/s for ??Pss??160-175 MPa. Nucleation rates are consistent with classical nucleation theory, and infer an activation energy for nucleation of 1.5 x 10-18 J/nucleus, a critical bubble radius of 2 x 10-9 m, and an effective surface tension for rhyolite at 5.2 wt% H2O and 900??C of 0.10-0.11 N/m. The long nucleation delay limits the time available for subsequent diffusion such that disequilibrium dissolved H2O and CO2 contents persist to the end of our runs. The disequilibrium degassing paths inferred from our experiments contrast markedly with the equilibrium or quasi-equilibrium paths found in other studies where bubble nucleation occurs heterogenously on crystals or other discontinuities in the melt at low ??Pss. Homogenous and heterogenous nucleation rates are

  6. Linkage analysis in a Dutch population isolate shows no major gene for left-handedness or atypical language lateralization.

    PubMed

    Somers, Metten; Ophoff, Roel A; Aukes, Maartje F; Cantor, Rita M; Boks, Marco P; Dauwan, Meenakshi; de Visser, Kees L; Kahn, René S; Sommer, Iris E

    2015-06-10

    Cerebral dominance of language function and hand preference are suggested to be heritable traits with possible shared genetic background. However, joined genetic studies of these traits have never been conducted. We performed a genetic linkage study in 37 multigenerational human pedigrees of both sexes (consisting of 355 subjects) enriched with left-handedness in which we also measured language lateralization. Hand preference was measured with the Edinburgh Handedness Inventory, and language lateralization was measured with functional transcranial Doppler during language production. The estimated heritability of left-handedness and language lateralization in these pedigrees is 0.24 and 0.31, respectively. A parametric major gene model was tested for left-handedness. Nonparametric analyses were performed for left-handedness, atypical lateralization, and degree of language lateralization. We did not observe genome-wide evidence for linkage in the parametric or nonparametric analyses for any of the phenotypes tested. However, multiple regions showed suggestive evidence of linkage. The parametric model showed suggestive linkage for left-handedness in the 22q13 region [heterogeneity logarithm of odds (HLOD) = 2.18]. Nonparametric multipoint analysis of left-handedness showed suggestive linkage in the same region [logarithm of odds (LOD) = 2.80]. Atypical language lateralization showed suggestive linkage in the 7q34 region (LODMax = 2.35). For strength of language lateralization, we observed suggestive linkage in the 6p22 (LODMax = 2.54), 7q32 (LODMax = 1.93), and 9q33 (LODMax = 2.10) regions. We did not observe any overlap of suggestive genetic signal between handedness and the extent of language lateralization. The absence of significant linkage argues against the presence of a major gene coding for both traits; rather, our results are suggestive of these traits being two independent polygenic complex traits. PMID:26063907

  7. Linkage Analysis in a Dutch Population Isolate Shows No Major Gene for Left-Handedness or Atypical Language Lateralization

    PubMed Central

    Ophoff, Roel A.; Aukes, Maartje F.; Cantor, Rita M.; Boks, Marco P.; Dauwan, Meenakshi; de Visser, Kees L.; Kahn, René S.; Sommer, Iris E.

    2015-01-01

    Cerebral dominance of language function and hand preference are suggested to be heritable traits with possible shared genetic background. However, joined genetic studies of these traits have never been conducted. We performed a genetic linkage study in 37 multigenerational human pedigrees of both sexes (consisting of 355 subjects) enriched with left-handedness in which we also measured language lateralization. Hand preference was measured with the Edinburgh Handedness Inventory, and language lateralization was measured with functional transcranial Doppler during language production. The estimated heritability of left-handedness and language lateralization in these pedigrees is 0.24 and 0.31, respectively. A parametric major gene model was tested for left-handedness. Nonparametric analyses were performed for left-handedness, atypical lateralization, and degree of language lateralization. We did not observe genome-wide evidence for linkage in the parametric or nonparametric analyses for any of the phenotypes tested. However, multiple regions showed suggestive evidence of linkage. The parametric model showed suggestive linkage for left-handedness in the 22q13 region [heterogeneity logarithm of odds (HLOD) = 2.18]. Nonparametric multipoint analysis of left-handedness showed suggestive linkage in the same region [logarithm of odds (LOD) = 2.80]. Atypical language lateralization showed suggestive linkage in the 7q34 region (LODMax = 2.35). For strength of language lateralization, we observed suggestive linkage in the 6p22 (LODMax = 2.54), 7q32 (LODMax = 1.93), and 9q33 (LODMax = 2.10) regions. We did not observe any overlap of suggestive genetic signal between handedness and the extent of language lateralization. The absence of significant linkage argues against the presence of a major gene coding for both traits; rather, our results are suggestive of these traits being two independent polygenic complex traits. PMID:26063907

  8. Carburetion system including an adjustable throttle linkage

    SciTech Connect

    Du Bois, C.G.; Falig, J.D.

    1986-03-25

    A throttle linkage assembly is described comprising a throttle shaft rotatable about a throttle shaft axis between an idle position and a wide open throttle position, a throttle plate fixed on the throttle shaft, a driven lever pivotable about the throttle shaft axis between various angles relative to the throttle plate, and means for fixing the driven lever at a selected angle relative to the throttle plate an adjustment lever fixedly connected to the throttle adjacent the driven lever, and means for releasably securing the driven lever to the adjustment lever.

  9. Linkage mapping bovine EST-based SNP

    PubMed Central

    Snelling, Warren M; Casas, Eduardo; Stone, Roger T; Keele, John W; Harhay, Gregory P; Bennett, Gary L; Smith, Timothy PL

    2005-01-01

    Background Existing linkage maps of the bovine genome primarily contain anonymous microsatellite markers. These maps have proved valuable for mapping quantitative trait loci (QTL) to broad regions of the genome, but more closely spaced markers are needed to fine-map QTL, and markers associated with genes and annotated sequence are needed to identify genes and sequence variation that may explain QTL. Results Bovine expressed sequence tag (EST) and bacterial artificial chromosome (BAC)sequence data were used to develop 918 single nucleotide polymorphism (SNP) markers to map genes on the bovine linkage map. DNA of sires from the MARC reference population was used to detect SNPs, and progeny and mates of heterozygous sires were genotyped. Chromosome assignments for 861 SNPs were determined by twopoint analysis, and positions for 735 SNPs were established by multipoint analyses. Linkage maps of bovine autosomes with these SNPs represent 4585 markers in 2475 positions spanning 3058 cM . Markers include 3612 microsatellites, 913 SNPs and 60 other markers. Mean separation between marker positions is 1.2 cM. New SNP markers appear in 511 positions, with mean separation of 4.7 cM. Multi-allelic markers, mostly microsatellites, had a mean (maximum) of 216 (366) informative meioses, and a mean 3-lod confidence interval of 3.6 cM Bi-allelic markers, including SNP and other marker types, had a mean (maximum) of 55 (191) informative meioses, and were placed within a mean 8.5 cM 3-lod confidence interval. Homologous human sequences were identified for 1159 markers, including 582 newly developed and mapped SNP. Conclusion Addition of these EST- and BAC-based SNPs to the bovine linkage map not only increases marker density, but provides connections to gene-rich physical maps, including annotated human sequence. The map provides a resource for fine-mapping quantitative trait loci and identification of positional candidate genes, and can be integrated with other data to guide and

  10. A new genome scan for primary nonsyndromic vesicoureteric reflux emphasizes high genetic heterogeneity and shows linkage and association with various genes already implicated in urinary tract development

    PubMed Central

    Darlow, J M; Dobson, M G; Darlay, R; Molony, C M; Hunziker, M; Green, A J; Cordell, H J; Puri, P; Barton, D E

    2014-01-01

    Primary vesicoureteric reflux (VUR), the retrograde flow of urine from the bladder toward the kidneys, results from a developmental anomaly of the vesicoureteric valve mechanism, and is often associated with other urinary tract anomalies. It is the most common urological problem in children, with an estimated prevalence of 1–2%, and is a major cause of hypertension in childhood and of renal failure in childhood or adult life. We present the results of a genetic linkage and association scan using 900,000 markers. Our linkage results show a large number of suggestive linkage peaks, with different results in two groups of families, suggesting that VUR is even more genetically heterogeneous than previously imagined. The only marker achieving P < 0.02 for linkage in both groups of families is 270 kb from EMX2. In three sibships, we found recessive linkage to KHDRBS3, previously reported in a Somali family. In another family we discovered sex-reversal associated with VUR, implicating PRKX, for which there was weak support for dominant linkage in the overall data set. Several other candidate genes are suggested by our linkage or association results, and four of our linkage peaks are within copy-number variants recently found to be associated with renal hypodysplasia. Undoubtedly there are many genes related to VUR. Our study gives support to some loci suggested by earlier studies as well as suggesting new ones, and provides numerous indications for further investigations. PMID:24498626

  11. Isotopic Disequilibrium and High-Crystallinity Magma Ascent: Clues to the Temporal Restriction of Proterozoic Anorthosites

    NASA Astrophysics Data System (ADS)

    Bybee, G. M.

    2014-12-01

    Many Proterozoic anorthosite massifs show crustal isotopic signatures that have fuelled debate regarding the source (mantle vs. lower crust) of these temporally restricted magmas. The models advocating a mantle derivation for these rocks suggest that lower crustal assimilation plays an important role in developing the isotopic signature of the massifs, but no evidence exists to support this. We make use of Sr, Nd and Pb isotopic compositions of anorthosites from the Mealy Mountains Intrusive Suite (MMIS), the Nain Plutonic Suite (NPS) and the Rogaland Anorthosite Province (RAP), their internal mineral phases and comagmatic, high-pressure pyroxene megacrysts, which represent samples from various stages of the polybaric ascent of the magmas, to probe the origin of the crustal isotopic signatures and assess the importance of differentiation at lower crustal depths. Study of the MMIS and NPS is instructive as each is intruded into crust of significantly different age and isotopic composition. We observe varying degrees of internal isotopic disequilibrium, enforcing the notion that the nature of the crustal assimilant has a profound influence on the chemical signature of the magmas (Fig. 1). We also find unexpected patterns of internal isotopic disequilibrium, such as isotopically depleted orthopyroxene relative to plagioclase (Fig. 1), which suggests that anorthosite petrogenesis is not a "simple" case of progressive crustal contamination during polybaric magma ascent, but is more likely to involve significant differentiation and solidification at lower crust depths. The 100 m.y. magmatic timescales observed in these anorthosite systems may be caused by significant magmatic differentiation at Moho/lower crustal levels, as well as formation in long-lived arc environments. These long-lived magmatic timescales contrast with recent observations suggesting that the duration of magma ascent from the Moho to surface in arc environments is on the order of months to