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Sample records for linkage disequilibrium estimation

  1. Accounting for haplotype phase uncertainty in linkage disequilibrium estimation.

    PubMed

    Kulle, B; Frigessi, A; Edvardsen, H; Kristensen, V; Wojnowski, L

    2008-02-01

    The characterization of linkage disequilibrium (LD) is applied in a variety of studies including the identification of molecular determinants of the local recombination rate, the migration and population history of populations, and the role of positive selection in adaptation. LD suffers from the phase uncertainty of the haplotypes used in its calculation, which reflects limitations of the algorithms used for haplotype estimation. We introduce a LD calculation method, which deals with phase uncertainty by weighting all possible haplotype pairs according to their estimated probabilities as evaluated by PHASE. In contrast to the expectation-maximization (EM) algorithm as implemented in the HAPLOVIEW and GENETICS packages, our method considers haplotypes based on the entire genetic information available for the candidate region. We tested the method using simulated and real genotyping data. The results show that, for all practical purposes, the new method is advantageous in comparison with algorithms that calculate LD using only the most probable haplotype or bilocus haplotypes based on the EM algorithm. The new method deals especially well with low LD regions, which contribute strongly to phase uncertainty. Altogether, the method is an attractive alternative to standard LD calculation procedures, including those based on the EM algorithm. We implemented the method in the software suite R, together with an interface to the popular haplotype calculation package PHASE.

  2. Assortative Mating and Linkage Disequilibrium.

    PubMed

    Hedrick, Philip W

    2017-01-05

    Assortative mating has been suggested to result in an increase in heritability and additive genetic variance through an increase in linkage disequilibrium. The impact of assortative mating on linkage disequilibrium was explicitly examined for the two-locus model of Wright (1921) and two selective assortative mating models. For the Wright (1921) model, when the proportion of assortative mating was high, positive linkage disequilibrium was generated. However, when the proportion of assortative mating was similar to that found in some studies, the amount of linkage disequilibrium was quite low. In addition, the amount of linkage disequilibrium was independent of the level of recombination. For two selective assortative models, the amount of linkage disequilibrium was a function of the amount of recombination. For these models, the linkage disequilibrium generated was negative mainly because repulsion heterozygotes were favored over coupling heterozygotes. From these findings, the impact of assortative mating on linkage disequilibrium, and consequently heritability and additive genetic variance, appears to be small and model-specific.

  3. Assortative Mating and Linkage Disequilibrium

    PubMed Central

    Hedrick, Philip W.

    2016-01-01

    Assortative mating has been suggested to result in an increase in heritability and additive genetic variance through an increase in linkage disequilibrium. The impact of assortative mating on linkage disequilibrium was explicitly examined for the two-locus model of Wright (1921) and two selective assortative mating models. For the Wright (1921) model, when the proportion of assortative mating was high, positive linkage disequilibrium was generated. However, when the proportion of assortative mating was similar to that found in some studies, the amount of linkage disequilibrium was quite low. In addition, the amount of linkage disequilibrium was independent of the level of recombination. For two selective assortative models, the amount of linkage disequilibrium was a function of the amount of recombination. For these models, the linkage disequilibrium generated was negative mainly because repulsion heterozygotes were favored over coupling heterozygotes. From these findings, the impact of assortative mating on linkage disequilibrium, and consequently heritability and additive genetic variance, appears to be small and model-specific. PMID:27784755

  4. 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

  5. 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

    2013-04-09

    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.

  6. Positional cloning by linkage disequilibrium.

    PubMed

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

    2004-05-01

    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 efficient

  7. Estimating contemporary effective population size in non-model species using linkage disequilibrium across thousands of loci.

    PubMed

    Waples, R K; Larson, W A; Waples, R S

    2016-10-01

    Contemporary effective population size (Ne) can be estimated using linkage disequilibrium (LD) observed across pairs of loci presumed to be selectively neutral and unlinked. This method has been commonly applied to data sets containing 10-100 loci to inform conservation and study population demography. Performance of these Ne estimates could be improved by incorporating data from thousands of loci. However, these thousands of loci exist on a limited number of chromosomes, ensuring that some fraction will be physically linked. Linked loci have elevated LD due to limited recombination, which if not accounted for can cause Ne estimates to be downwardly biased. Here, we present results from coalescent and forward simulations designed to evaluate the bias of LD-based Ne estimates ([Ncirc ]e). Contrary to common perceptions, increasing the number of loci does not increase the magnitude of linkage. Although we show it is possible to identify some pairs of loci that produce unusually large r(2) values, simply removing large r(2) values is not a reliable way to eliminate bias. Fortunately, the magnitude of bias in [Ncirc ]e is strongly and negatively correlated with the process of recombination, including the number of chromosomes and their length, and this relationship provides a general way to adjust for bias. Additionally, we show that with thousands of loci, precision of [Ncirc ]e is much lower than expected based on the assumption that each pair of loci provides completely independent information.

  8. 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...

  9. Linkage disequilibrium at the SCA2 locus

    PubMed Central

    Didierjean, O.; Cancel, G.; Stevanin, G.; Durr, A.; Burk, K.; Benomar, A.; Lezin, A.; Belal, S.; Abada-Bendid, M.; Klockgether, T.; Brice, A.

    1999-01-01

    Spinocerebellar ataxia type 2 (SCA2) is caused by the expansion of an unstable CAG repeat encoding a polyglutamine tract. Repeats with 32 to 200 CAGs are associated with the disease, whereas normal chromosomes contain 13 to 33 repeats. We tested 220 families of different geographical origins for the SCA2 mutation. Thirty three were positive (15%). Twenty three families with at least two affected subjects were tested for linkage disequilibium (LD) between the SCA2 mutation and three microsatellite markers, two of which (D12S1332-D12S1333) closely flanked the mutation; the other (D12S1672) was intragenic. Many different haplotypes were observed, indicating the occurrence of several ancestral mutations. However, the same haplotype, not observed in controls, was detected in the German, the Serbian, and some of the French families, suggesting a founder effect or recurrent mutations on an at risk haplotype.


Keywords: linkage disequilibrium; SCA2; trinucleotide repeat expansion; founder effect PMID:10353790

  10. Estimation of linkage disequilibrium and interspecific gene flow in Ficedula flycatchers by a newly developed 50k single-nucleotide polymorphism array

    PubMed Central

    Kawakami, Takeshi; Backström, Niclas; Burri, Reto; Husby, Arild; Olason, Pall; Rice, Amber M; Ålund, Murielle; Qvarnström, Anna; Ellegren, Hans

    2014-01-01

    With the access to draft genome sequence assemblies and whole-genome resequencing data from population samples, molecular ecology studies will be able to take truly genome-wide approaches. This now applies to an avian model system in ecological and evolutionary research: Old World flycatchers of the genus Ficedula, for which we recently obtained a 1.1 Gb collared flycatcher genome assembly and identified 13 million single-nucleotide polymorphism (SNP)s in population resequencing of this species and its sister species, pied flycatcher. Here, we developed a custom 50K Illumina iSelect flycatcher SNP array with markers covering 30 autosomes and the Z chromosome. Using a number of selection criteria for inclusion in the array, both genotyping success rate and polymorphism information content (mean marker heterozygosity = 0.41) were high. We used the array to assess linkage disequilibrium (LD) and hybridization in flycatchers. Linkage disequilibrium declined quickly to the background level at an average distance of 17 kb, but the extent of LD varied markedly within the genome and was more than 10-fold higher in ‘genomic islands’ of differentiation than in the rest of the genome. Genetic ancestry analysis identified 33 F1 hybrids but no later-generation hybrids from sympatric populations of collared flycatchers and pied flycatchers, contradicting earlier reports of backcrosses identified from much fewer number of markers. With an estimated divergence time as recently as <1 Ma, this suggests strong selection against F1 hybrids and unusually rapid evolution of reproductive incompatibility in an avian system. PMID:24784959

  11. Mitonuclear linkage disequilibrium in human populations

    PubMed Central

    Sloan, Daniel B.; Fields, Peter D.; Havird, Justin C.

    2015-01-01

    There is extensive evidence from model systems that disrupting associations between co-adapted mitochondrial and nuclear genotypes can lead to deleterious and even lethal consequences. While it is tempting to extrapolate from these observations and make inferences about the human-health effects of altering mitonuclear associations, the importance of such associations may vary greatly among species, depending on population genetics, demographic history and other factors. Remarkably, despite the extensive study of human population genetics, the statistical associations between nuclear and mitochondrial alleles remain largely uninvestigated. We analysed published population genomic data to test for signatures of historical selection to maintain mitonuclear associations, particularly those involving nuclear genes that encode mitochondrial-localized proteins (N-mt genes). We found that significant mitonuclear linkage disequilibrium (LD) exists throughout the human genome, but these associations were generally weak, which is consistent with the paucity of population genetic structure in humans. Although mitonuclear LD varied among genomic regions (with especially high levels on the X chromosome), N-mt genes were statistically indistinguishable from background levels, suggesting that selection on mitonuclear epistasis has not preferentially maintained associations involving this set of loci at a species-wide level. We discuss these findings in the context of the ongoing debate over mitochondrial replacement therapy. PMID:26378221

  12. Nucleotide diversity and linkage disequilibrium in balsam poplar (Populus balsamifera).

    PubMed

    Olson, Matthew S; Robertson, Amanda L; Takebayashi, Naoki; Silim, Salim; Schroeder, William R; Tiffin, Peter

    2010-04-01

    *Current perceptions that poplars have high levels of nucleotide variation, large effective population sizes, and rapid decay of linkage disequilibrium are based primarily on studies from one poplar species, Populus tremula. *We analysed 590 gene fragments (average length 565 bp) from each of 15 individuals from different populations from throughout the range of Populus balsamifera. *Nucleotide diversity (theta(total) = 0.0028, pi = 0.0027) was low compared with other trees and model agricultural systems. Patterns of nucleotide diversity and site frequency spectra were consistent with purifying selection on replacement and intron sites. When averaged across all loci we found no evidence for decay of linkage disequilibrium across 750 bp, consistent with the low estimates of the scaled recombination parameter, rho = 0.0092. *Compared with P. tremula, a well studied congener with a similar distribution, P. balsamifera has low diversity and low effective recombination, both of which indicate a lower effective population size in P. balsamifera. Patterns of diversity and linkage indicate that there is considerable variation in population genomic patterns among poplar species and unlike P. tremula, association mapping techniques in balsam poplar should consider sampling single nucleotide polymorphisms (SNPs) at well-spaced intervals.

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

    PubMed Central

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

    1994-01-01

    To test the reliability of linkage-disequilibrium analysis for gene mapping, we 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 -.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. We 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. PMID:8178829

  14. Linkage disequilibrium in the neurofibromatosis I (NF1) region: Implications for gene mapping

    SciTech Connect

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

    1993-11-01

    To test the usefulness of linkage disequilibrium for gene mapping, the authors compared physical distances and linkage disequilibrium among eight RFLPs in the neutrofibromatosis 1 (NF1) region. Seven of the polymorphisms span most of the NF1 gene, while the remaining polymorphism lies approximately 70 kb 3[prime] 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[sup [minus]7]), even though they are separated by as much as 340 kb. The 3[prime] polymorphism is only 68 kb distal to the next polymorphism, but disequilibrium between the 3[prime] polymorphism and all others is comparatively low ([vert bar]r[vert bar] < .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[prime] to the stop codon could have implications for gene mapping studies. These are discussed, and guidelines for linkage disequilibrium studies are suggested. 80 refs., 2 figs., 5 tabs.

  15. 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

  16. Linkage disequilibrium and its expectation in human populations.

    PubMed

    Sved, John A

    2009-02-01

    Abstract Linkage disequilibrium (LD), the association in populations between genes at linked loci, has achieved a high degree of prominence in recent years, primarily because of its use in identifying and cloning genes of medical importance. The field has recently been reviewed by Slatkin (2008). The present article is largely devoted to a review of the theory of LD in populations, including historical aspects.

  17. Linkage Disequilibrium in a Finite Population That Is Partially Selfing

    PubMed Central

    Golding, G. B.; Strobeck, C.

    1980-01-01

    The linkage disequilibrium expected in a finite, partially selfing population is analyzed, assuming the infinite allele model. Formulas for the expected sum of squares of the linkage disequilibria and the squared standard linkage disequilibrium are derived from the equilibrium values of sixteen inbreeding coefficients required to describe the behavior of the system. These formulas are identical to those obtained with random mating if the effective population size Ne = (1-½S)N and the effective recombination value re = (1-S)r/(1-½S), where S is the proportion of selfing, are substituted for the population size and the recombination value. Therefore, the effect of partial selfing at equilibrium is to reduce the population size by a factor 1-½S and the recombination value by a factor (1-S)/(1-½S). PMID:17249017

  18. 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.

  19. 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

  20. Mendelian inheritance, linkage and genotypic disequilibrium in microsatellite loci isolated from Hymenaea courbaril (Leguminosae).

    PubMed

    Carneiro, F S; Lacerda, A E B; Lemes, M R; Gribel, R; Kanashiro, M; Sebbenn, A M

    2012-07-19

    The Neotropical tree Hymenaea courbaril, locally known as Jatobá, is a valuable source of lumber and also produces comestible and medicinal fruit. We characterized Mendelian inheritance, linkage and genotypic disequilibrium at nine microsatellite loci isolated from H. courbaril, in order to determine if they would provide accurate estimates of population genetic parameters of this important Amazon species. The study was made on 250 open-pollinated offspring originated from 14 seed trees. Only one of nine loci presented significant deviation from the expected Mendelian segregation (1:1). Genotypic disequilibrium between pairwise loci was investigated based on samples from 55 adult and 56 juvenile trees. No genetic linkage between any paired loci was observed. After Bonferroni's corrections for multiple tests, we found no evidence of genotypic disequilibrium between pairs of loci. We conclude that this set of loci can be used for genetic diversity/ structure, mating system, gene flow, and parentage analyses in H. courbaril populations.

  1. Linkage disequilibrium of polymorphic RAET1 genes in Thais.

    PubMed

    Rareongjai, S; Romphruk, A; Romphruk, A V; Sakuntabhai, A; Leelayuwat, C

    2010-09-01

    Retinoic acid early transcripts-1 (RAET1) or unique long 16 (UL-16) binding proteins (ULBPs) is a gene cluster encoding for molecules acting as ligands to natural killer group 2 D (NKG2D), a receptor expressed on immune cells. Binding of these ligands to the receptor activates immune cells leading to killing of tumor cells and also viral-infected cells. The information on polymorphism of RAET1 is limited. In this report, we analyze the linkages between four polymorphic RAET1 genes: RAET1E, RAET1G, RAET1H and RAET1L, in 318 unrelated Thais. The strongest linkage disequilibrium was found between RAET1E and RAET1G, with P-value, D' and r(2) of <5.0 x 10(-5), 0.707 and 0.840, respectively. RAET1E(*)001 was found to be in linkage disequilibrium with RAET1G(*)002, and RAET1E(*)002 with RAET1G(*)001. Evidently, there were possible RAET1 haplotypes with haplotype frequencies of more than 10% consisting of RAET1E(*)001; RAET1G(*)002; RAET1H(*)001; RAET1L(*)001 and RAET1E(*)002; RAET1G(*)001; RAET1H(*)002; RAET1L(*)003. This study provides basic information on polymorphisms of RAET1 and possible RAET1 haplotypes in Thais.

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

    PubMed

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

    2003-04-01

    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.

  3. Linkage disequilibrium, haplotype analysis and Werner`s syndrome

    SciTech Connect

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

    1994-09-01

    Werner`s syndrome (WS) is a rare, autosomal, recessive disorder of premature aging. Although the underlying defect is unknown, the gene for the disorder, WRN, has been mapped to the 8p11.1-21.1 region. We have assembled a sample of 30 Japanese and 24 non-Japanese (primary Caucasian) WS patients, as well as a control sample from each population. 25 of the Japanese patients and 10 of the Caucasian patients are from consanguineous marriages. We recently presented evidence from these families which places WRN in the 10.2 cM interval between D8S87 and D8S137. However, 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. The existence of linkage disequilibrium is now recognized as a key piece of evidence in defining a small region (typically under 1-2 cM) containing a gene of interest. Thus an alternative approach for refining the location of WRN may be to identify linked markers which are in linkage disequilibrium with the disease. We recently suggested that WRN may be close to D8S339 and GSR in the above interval because of the presence of statistically significant evidence of linkage disequilibrium in the Japanese sample. In addition, there was evidence in both populations that a limited number of haplotypes was associated with the disease. Here we report an extension of this study to include a number of additional markers. We present additional evidence that there is linkage disequilibrium between many of these markers and WRN in both the Japanese and Caucasian samples. In addition, the additional markers do not markedly subdivide the disease haplotypes defined by D8S339 and GSR, while at the same time they introduce substantial numbers of new haplotypes into the control populations. These results suggest that the haplotypes associated with WS may be used to further define the limits of WRN.

  4. Modeling Continuous Admixture Using Admixture-Induced Linkage Disequilibrium.

    PubMed

    Zhou, Ying; Qiu, Hongxiang; Xu, Shuhua

    2017-02-23

    Recent migrations and inter-ethnic mating of long isolated populations have resulted in genetically admixed populations. To understand the complex population admixture process, which is critical to both evolutionary and medical studies, here we used admixture induced linkage disequilibrium (LD) to infer continuous admixture events, which is common for most existing admixed populations. Unlike previous studies, we expanded the typical continuous admixture model to a more general scenario with isolation after a certain duration of continuous gene flow. Based on the new models, we developed a method, CAMer, to infer the admixture history considering continuous and complex demographic process of gene flow between populations. We evaluated the performance of CAMer by computer simulation and further applied our method to real data analysis of a few well-known admixed populations.

  5. Modeling Continuous Admixture Using Admixture-Induced Linkage Disequilibrium

    PubMed Central

    Zhou, Ying; Qiu, Hongxiang; Xu, Shuhua

    2017-01-01

    Recent migrations and inter-ethnic mating of long isolated populations have resulted in genetically admixed populations. To understand the complex population admixture process, which is critical to both evolutionary and medical studies, here we used admixture induced linkage disequilibrium (LD) to infer continuous admixture events, which is common for most existing admixed populations. Unlike previous studies, we expanded the typical continuous admixture model to a more general scenario with isolation after a certain duration of continuous gene flow. Based on the new models, we developed a method, CAMer, to infer the admixture history considering continuous and complex demographic process of gene flow between populations. We evaluated the performance of CAMer by computer simulation and further applied our method to real data analysis of a few well-known admixed populations. PMID:28230170

  6. Genetic variation and linkage disequilibrium in Bacillus anthracis.

    PubMed

    Zwick, Michael E; Thomason, Maureen Kiley; Chen, Peter E; Johnson, Henry R; Sozhamannan, Shanmuga; Mateczun, Alfred; Read, Timothy D

    2011-01-01

    We performed whole-genome amplification followed by hybridization of custom-designed resequencing arrays to resequence 303 kb of genomic sequence from a worldwide panel of 39 Bacillus anthracis strains. We used an efficient algorithm contained within a custom software program, UniqueMER, to identify and mask repetitive sequences on the resequencing array to reduce false-positive identification of genetic variation, which can arise from cross-hybridization. We discovered a total of 240 single nucleotide variants (SNVs) and showed that B. anthracis strains have an average of 2.25 differences per 10,000 bases in the region we resequenced. Common SNVs in this region are found to be in complete linkage disequilibrium. These patterns of variation suggest there has been little if any historical recombination among B. anthracis strains since the origin of the pathogen. This pattern of common genetic variation suggests a framework for recognizing new or genetically engineered strains.

  7. Linkage disequilibrium mapping in isolated populations: The example of Finland revisited

    PubMed Central

    de la Chapelle, Albert; Wright, Fred A.

    1998-01-01

    Linkage disequilibrium analysis can provide high resolution in the mapping of disease genes because it incorporates information on recombinations that have occurred during the entire period from the mutational event to the present. A circumstance particularly favorable for high-resolution mapping is when a single founding mutation segregates in an isolated population. We review here the population structure of Finland in which a small founder population some 100 generations ago has expanded into 5.1 million people today. Among the 30-odd autosomal recessive disorders that are more prevalent in Finland than elsewhere, several appear to have segregated for this entire period in the “panmictic” southern Finnish population. Linkage disequilibrium analysis has allowed precise mapping and determination of genetic distances at the 0.1-cM level in several of these disorders. Estimates of genetic distance have proven accurate, but previous calculations of the confidence intervals were too small because sampling variation was ignored. In the north and east of Finland the population can be viewed as having been “founded” only after 1500. Disease mutations that have undergone such a founding bottleneck only 20 or so generations ago exhibit linkage disequilibrium and haplotype sharing over long genetic distances (5–15 cM). These features have been successfully exploited in the mapping and cloning of many genes. We review the statistical issues of fine mapping by linkage disequilibrium and suggest that improved methodologies may be necessary to map diseases of complex etiology that may have arisen from multiple founding mutations. PMID:9770501

  8. 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

  9. 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.

  10. Linkage disequilibrium mapping of Arabidopsis CRY2 flowering time alleles.

    PubMed Central

    Olsen, Kenneth M; Halldorsdottir, Solveig S; Stinchcombe, John R; Weinig, Cynthia; Schmitt, Johanna; Purugganan, Michael D

    2004-01-01

    The selfing plant Arabidopsis thaliana has been proposed to be well suited for linkage disequilibrium (LD) mapping as a means of identifying genes underlying natural trait variation. Here we apply LD mapping to examine haplotype variation in the genomic region of the photoperiod receptor CRYPTOCHROME2 and associated flowering time variation. CRY2 DNA sequences reveal strong LD and the existence of two highly differentiated haplogroups (A and B) across the gene; in addition, a haplotype possessing a radical glutamine-to-serine replacement (AS) occurs within the more common haplogroup. Growth chamber and field experiments using an unstratified population of 95 ecotypes indicate that under short-day photoperiod, the AS and B haplogroups are both highly significantly associated with early flowering. Data from six genes flanking CRY2 indicate that these haplogroups are limited to an approximately 65-kb genomic region around CRY2. Whereas the B haplogroup cannot be delimited to <16 kb around CRY2, the AS haplogroup is characterized almost exclusively by the nucleotide polymorphisms directly associated with the serine replacement in CRY2; this finding strongly suggests that the serine substitution is directly responsible for the AS early flowering phenotype. This study demonstrates the utility of LD mapping for elucidating the genetic basis of natural, ecologically relevant variation in Arabidopsis. PMID:15280248

  11. Linkage disequilibrium mapping of Arabidopsis CRY2 flowering time alleles.

    PubMed

    Olsen, Kenneth M; Halldorsdottir, Solveig S; Stinchcombe, John R; Weinig, Cynthia; Schmitt, Johanna; Purugganan, Michael D

    2004-07-01

    The selfing plant Arabidopsis thaliana has been proposed to be well suited for linkage disequilibrium (LD) mapping as a means of identifying genes underlying natural trait variation. Here we apply LD mapping to examine haplotype variation in the genomic region of the photoperiod receptor CRYPTOCHROME2 and associated flowering time variation. CRY2 DNA sequences reveal strong LD and the existence of two highly differentiated haplogroups (A and B) across the gene; in addition, a haplotype possessing a radical glutamine-to-serine replacement (AS) occurs within the more common haplogroup. Growth chamber and field experiments using an unstratified population of 95 ecotypes indicate that under short-day photoperiod, the AS and B haplogroups are both highly significantly associated with early flowering. Data from six genes flanking CRY2 indicate that these haplogroups are limited to an approximately 65-kb genomic region around CRY2. Whereas the B haplogroup cannot be delimited to <16 kb around CRY2, the AS haplogroup is characterized almost exclusively by the nucleotide polymorphisms directly associated with the serine replacement in CRY2; this finding strongly suggests that the serine substitution is directly responsible for the AS early flowering phenotype. This study demonstrates the utility of LD mapping for elucidating the genetic basis of natural, ecologically relevant variation in Arabidopsis.

  12. Inferring Admixture Histories of Human Populations Using Linkage Disequilibrium

    PubMed Central

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

    2013-01-01

    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

  13. Linkage Disequilibrium and Demographic History of Wild and Domestic Canids

    PubMed Central

    Gray, Melissa M.; Granka, Julie M.; Bustamante, Carlos D.; Sutter, Nathan B.; Boyko, Adam R.; Zhu, Lan; Ostrander, Elaine A.; Wayne, Robert K.

    2009-01-01

    Assessing the extent of linkage disequilibrium (LD) in natural populations of a nonmodel species has been difficult due to the lack of available genomic markers. However, with advances in genotyping and genome sequencing, genomic characterization of natural populations has become feasible. Using sequence data and SNP genotypes, we measured LD and modeled the demographic history of wild canid populations and domestic dog breeds. In 11 gray wolf populations and one coyote population, we find that the extent of LD as measured by the distance at which r2 = 0.2 extends <10 kb in outbred populations to >1.7 Mb in populations that have experienced significant founder events and bottlenecks. This large range in the extent of LD parallels that observed in 18 dog breeds where the r2 value varies from ∼20 kb to >5 Mb. Furthermore, in modeling demographic history under a composite-likelihood framework, we find that two of five wild canid populations exhibit evidence of a historical population contraction. Five domestic dog breeds display evidence for a minor population contraction during domestication and a more severe contraction during breed formation. Only a 5% reduction in nucleotide diversity was observed as a result of domestication, whereas the loss of nucleotide diversity with breed formation averaged 35%. PMID:19189949

  14. Accounting for linkage disequilibrium in association analysis of diverse populations.

    PubMed

    Charles, Bashira A; Shriner, Daniel; Rotimi, Charles N

    2014-04-01

    The National Human Genome Research Institute's catalog of published genome-wide association studies (GWAS) lists over 10,000 genetic variants collectively associated with over 800 human diseases or traits. Most of these GWAS have been conducted in European-ancestry populations. Findings gleaned from these studies have led to identification of disease-associated loci and biologic pathways involved in disease etiology. In multiple instances, these genomic findings have led to the development of novel medical therapies or evidence for prescribing a given drug as the appropriate treatment for a given individual beyond phenotypic appearances or socially defined constructs of race or ethnicity. Such findings have implications for populations throughout the globe and GWAS are increasingly being conducted in more diverse populations. A major challenge for investigators seeking to follow up genomic findings between diverse populations is discordant patterns of linkage disequilibrium (LD). We provide an overview of common measures of LD and opportunities for their use in novel methods designed to address challenges associated with following up GWAS conducted in European-ancestry populations in African-ancestry populations or, more generally, between populations with discordant LD patterns. We detail the strengths and weaknesses associated with different approaches. We also describe application of these strategies in follow-up studies of populations with concordant LD patterns (replication) or discordant LD patterns (transferability) as well as fine-mapping studies. We review application of these methods to a variety of traits and diseases.

  15. Extensive linkage disequilibrium in small human populations in Eurasia.

    PubMed

    Kaessmann, Henrik; Zöllner, Sebastian; Gustafsson, Anna C; Wiebe, Victor; Laan, Maris; Lundeberg, Joakim; Uhlén, Mathias; Pääbo, Svante

    2002-03-01

    The extent of linkage disequilibrium (LD) was studied in two small food-gathering populations-Evenki and Saami-and two larger food-producing populations-Finns and Swedes-in northern Eurasia. In total, 50 single-nucleotide polymorphisms (SNPs) from five genes were genotyped using real-time pyrophosphate DNA sequencing, whereas 14 microsatellites were genotyped in two X-chromosomal regions. In addition, hypervariable region I of the mtDNA was sequenced to shed light on the demographic history of the populations. The SNP data, as well as the microsatellite data, reveal extensive levels of LD in Evenki and Saami when compared to Finns and Swedes. mtDNA-sequence variation is compatible with constant population size over time in Evenki and Saami but indicates population expansion in Finns and Swedes. Furthermore, the similarity between Finns and Swedes in SNP allele- and haplotype-frequency distributions indicate that these two populations may share a recent common origin. These findings suggest that populations such as the Evenki and the Saami, rather than the Finns, may be particularly suited for the initial coarse mapping of common complex diseases.

  16. 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.

  17. 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

  18. Single nucleotide polymorphisms and linkage disequilibrium in sunflower.

    PubMed

    Kolkman, Judith M; Berry, Simon T; Leon, Alberto J; Slabaugh, Mary B; Tang, Shunxue; Gao, Wenxiang; Shintani, David K; Burke, John M; Knapp, Steven J

    2007-09-01

    Genetic diversity in modern sunflower (Helianthus annuus L.) cultivars (elite oilseed inbred lines) has been shaped by domestication and breeding bottlenecks and wild and exotic allele introgression(-)the former narrowing and the latter broadening genetic diversity. To assess single nucleotide polymorphism (SNP) frequencies, nucleotide diversity, and linkage disequilibrium (LD) in modern cultivars, alleles were resequenced from 81 genic loci distributed throughout the sunflower genome. DNA polymorphisms were abundant; 1078 SNPs (1/45.7 bp) and 178 insertions-deletions (INDELs) (1/277.0 bp) were identified in 49.4 kbp of DNA/genotype. SNPs were twofold more frequent in noncoding (1/32.1 bp) than coding (1/62.8 bp) sequences. Nucleotide diversity was only slightly lower in inbred lines ( = 0.0094) than wild populations ( = 0.0128). Mean haplotype diversity was 0.74. When extraploted across the genome ( approximately 3500 Mbp), sunflower was predicted to harbor at least 76.4 million common SNPs among modern cultivar alleles. LD decayed more slowly in inbred lines than wild populations (mean LD declined to 0.32 by 5.5 kbp in the former, the maximum physical distance surveyed), a difference attributed to domestication and breeding bottlenecks. SNP frequencies and LD decay are sufficient in modern sunflower cultivars for very high-density genetic mapping and high-resolution association mapping.

  19. An analysis of linkage disequilibrium in the interleukin-1 gene cluster, using a novel grouping method for multiallelic markers.

    PubMed Central

    Cox, A; Camp, N J; Nicklin, M J; di Giovine, F S; Duff, G W

    1998-01-01

    In population- and family-based association studies, it is useful to have some knowledge of the patterns of linkage disequilibrium that exist between markers in candidate regions. When such studies are carried out with multiallelic markers, it is often convenient to group the alleles into a biallelic system, for analysis. In this study, we specifically examined the interleukin-1 (IL-1) gene cluster on chromosome 2, a region containing candidates for many inflammatory and autoimmune disorders. Data were collected on eight markers, four of which were multiallelic. Using these data, we investigated the effect of three allele-grouping strategies, including a novel method, on the detection of linkage disequilibrium. The novel approach, termed the "delta method," measures the deviation from the expected haplotype frequencies under linkage equilibrium, for each allelic combination. This information is then used to group the alleles, in an attempt to avoid the grouping together of alleles at one locus that are in opposite disequilibrium with the same allele at the second locus. The estimate haplotype frequencies (EH) program was used to estimate haplotype frequencies and the disequilibrium measure. In our data it was found that the delta method compared well with the other two strategies. Using this method, we found that there was a reasonable correlation between disequilibrium and physical distance in the region (r=-.540, P=.001, one-tailed). We also identified a common, eight-locus haplotype of the IL-1 gene cluster. PMID:9545388

  20. 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...

  1. Diversity and linkage disequilibrium in farmed Tasmanian Atlantic salmon.

    PubMed

    Kijas, J; Elliot, N; Kube, P; Evans, B; Botwright, N; King, H; Primmer, C R; Verbyla, K

    2017-04-01

    Farmed Atlantic salmon (Salmo salar) is a globally important production species, including in Australia where breeding and selection has been in progress since the 1960s. The recent development of SNP genotyping platforms means genome-wide association and genomic prediction can now be implemented to speed genetic gain. As a precursor, this study collected genotypes at 218 132 SNPs in 777 fish from a Tasmanian breeding population to assess levels of genetic diversity, the strength of linkage disequilibrium (LD) and imputation accuracy. Genetic diversity in Tasmanian Atlantic salmon was lower than observed within European populations when compared using four diversity metrics. The distribution of allele frequencies also showed a clear difference, with the Tasmanian animals carrying an excess of low minor allele frequency variants. The strength of observed LD was high at short distances (<25 kb) and remained above background for marker pairs separated by large chromosomal distances (hundreds of kb), in sharp contrast to the European Atlantic salmon tested. Genotypes were used to evaluate the accuracy of imputation from low density (0.5 to 5 K) up to increased density SNP sets (78 K). This revealed high imputation accuracies (0.89-0.97), suggesting that the use of low density SNP sets will be a successful approach for genomic prediction in this population. The long-range LD, comparatively low genetic diversity and high imputation accuracy in Tasmanian salmon is consistent with known aspects of their population history, which involved a small founding population and an absence of subsequent introgression. The findings of this study represent an important first step towards the design of methods to apply genomics in this economically important population.

  2. Demographic history and linkage disequilibrium in human populations.

    PubMed

    Laan, M; Pääbo, S

    1997-12-01

    In the human genome, linkage disequilibrium (LD)--the non-random association of alleles at chromosomal loci--has been studied mainly in regions surrounding disease genes on affected chromosomes. Consequently, little information is available on the distribution of LD across anonymous genomic regions in the general population. However, demographic history is expected to influence the extent of overall LD across the genome, so a population that has been of constant size will display higher levels of LD than a population that has expanded. In support of this, the extent of LD between anonymous loci on chromosome 4 in chimpanzees (as a model of a population of constant size) has been compared to that in Finns (as a model of an expanded population; refs 8,9) and found to exhibit more LD than in the latter population. In Europe, studies of mitochondrial (mt) DNA sequences have suggested that most populations have experienced expansion, whereas the Saami in northern Fenno-Scandinavia have been of constant size (Table 1). Thus, in northern Europe, populations with radically different demographic histories live in close geographic proximity to each other. We studied the allelic associations between anonymous microsatellite loci on the X chromosome in the Saami and neighbouring populations and found dramatically higher levels of LD in the Saami than in other populations in the region. This indicates that whereas recently expanded populations, such as the Finns, are well suited to map single disease genes affected by recent mutations, populations that have been of constant size, such as the Saami, may be much better suited to map genes for complex traits that are caused by older mutations.

  3. The Decay of Disease Association with Declining Linkage Disequilibrium: A Fine Mapping Theorem

    PubMed Central

    Maadooliat, Mehdi; Bansal, Naveen K.; Upadhya, Jiblal; Farazi, Manzur R.; Li, Xiang; He, Max M.; Hebbring, Scott J.; Ye, Zhan; Schrodi, Steven J.

    2016-01-01

    Several important and fundamental aspects of disease genetics models have yet to be described. One such property is the relationship of disease association statistics at a marker site closely linked to a disease causing site. A complete description of this two-locus system is of particular importance to experimental efforts to fine map association signals for complex diseases. Here, we present a simple relationship between disease association statistics and the decline of linkage disequilibrium from a causal site. Specifically, the ratio of Chi-square disease association statistics at a marker site and causal site is equivalent to the standard measure of pairwise linkage disequilibrium, r2. A complete derivation of this relationship from a general disease model is shown. Quite interestingly, this relationship holds across all modes of inheritance. Extensive Monte Carlo simulations using a disease genetics model applied to chromosomes subjected to a standard model of recombination are employed to better understand the variation around this fine mapping theorem due to sampling effects. We also use this relationship to provide a framework for estimating properties of a non-interrogated causal site using data at closely linked markers. Lastly, we apply this way of examining association data from high-density genotyping in a large, publicly-available data set investigating extreme BMI. We anticipate that understanding the patterns of disease association decay with declining linkage disequilibrium from a causal site will enable more powerful fine mapping methods and provide new avenues for identifying causal sites/genes from fine-mapping studies. PMID:28018425

  4. 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.

  5. 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

  6. A metric linkage disequilibrium map of a human chromosome.

    PubMed

    Tapper, W J; Maniatis, N; Morton, N E; Collins, A

    2003-11-01

    We used LDMAP (Maniatis et al. 2002) to analyse SNP data spanning chromosome 22 (Dawson et al. 2002), to obtain a whole-chromosome metric LD map. The LD map, with map distances analogous to the centiMorgan scale of linkage maps, identifies regions of high LD as plateaus ('blocks') and characterises steps which define the relationship between these regions. From this map we estimate that block regions comprise between 32% and 55% of the euchromatic portion of chromosome 22 and that increasing marker density within steps may increase block coverage. Steps are regions of low LD which correspond to areas of variable recombination intensity. The intensity of recombination is related to the height of the step and thus intense recombination hot-spots can be distinguished from more randomly distributed historical events. The LD maps are more closely related to the high-resolution linkage map (Kong et al. 2002) than average measures of rho with recombination accounting for between 34% and 52% of the variance in patterns of LD (r=0.58 - 0.71, p=0.0001). Step regions are closely correlated with a range of sequence motifs including GT/CA repeats. The LD map identifies holes in which greater marker density is required and defines the optimal SNP spacing for positional cloning, which suggests that some multiple of around 50,000 SNPs will be required to efficiently screen Caucasian genomes. Further analyses which investigate selection of informative SNPs and the effect of SNP allele frequency and marker density will refine this estimate.

  7. Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers.

    PubMed Central

    Cook, E H; Courchesne, R Y; Cox, N J; Lord, C; Gonen, D; Guter, S J; Lincoln, A; Nix, K; Haas, R; Leventhal, B L; Courchesne, E

    1998-01-01

    Autistic disorder is a complex genetic disease. Because of previous reports of individuals with autistic disorder with duplications of the Prader-Willi/Angelman syndrome critical region, we screened several markers across the 15q11-13 region, for linkage disequilibrium. One hundred forty families, consisting predominantly of a child with autistic disorder and both parents, were studied. Genotyping was performed by use of multiplex PCR and capillary electrophoresis. Two children were identified who had interstitial chromosome 15 duplications and were excluded from further linkage-disequilibrium analysis. Use of the multiallelic transmission-disequilibrium test (MTDT), for nine loci on 15q11-13, revealed linkage disequilibrium between autistic disorder and a marker in the gamma-aminobutyric acidA receptor subunit gene, GABRB3 155CA-2 (MTDT 28.63, 10 df, P=.0014). No evidence was found for parent-of-origin effects on allelic transmission. The convergence of GABRB3 as a positional and functional candidate along with the linkage-disequilibrium data suggests the need for further investigation of the role of GABRB3 or adjacent genes in autistic disorder. PMID:9545402

  8. The Effects of Migration and Assortative Mating on Admixture Linkage Disequilibrium.

    PubMed

    Zaitlen, Noah; Huntsman, Scott; Hu, Donglei; Spear, Melissa; Eng, Celeste; Oh, Sam S; White, Marquitta J; Mak, Angel; Davis, Adam; Meade, Kelly; Brigino-Buenaventura, Emerita; LeNoir, Michael A; Bibbins-Domingo, Kirsten; Burchard, Esteban G; Halperin, Eran

    2017-01-01

    Statistical models in medical and population genetics typically assume that individuals assort randomly in a population. While this simplifies model complexity, it contradicts an increasing body of evidence of nonrandom mating in human populations. Specifically, it has been shown that assortative mating is significantly affected by genomic ancestry. In this work, we examine the effects of ancestry-assortative mating on the linkage disequilibrium between local ancestry tracks of individuals in an admixed population. To accomplish this, we develop an extension to the Wright-Fisher model that allows for ancestry-based assortative mating. We show that ancestry-assortment perturbs the distribution of local ancestry linkage disequilibrium (LAD) and the variance of ancestry in a population as a function of the number of generations since admixture. This assortment effect can induce errors in demographic inference of admixed populations when methods assume random mating. We derive closed form formulae for LAD under an assortative-mating model with and without migration. We observe that LAD depends on the correlation of global ancestry of couples in each generation, the migration rate of each of the ancestral populations, the initial proportions of ancestral populations, and the number of generations since admixture. We also present the first direct evidence of ancestry-assortment in African Americans and examine LAD in simulated and real admixed population data of African Americans. We find that demographic inference under the assumption of random mating significantly underestimates the number of generations since admixture, and that accounting for assortative mating using the patterns of LAD results in estimates that more closely agrees with the historical narrative.

  9. Nucleotide Polymorphism and Linkage Disequilibrium Within and Among Natural Populations of European Aspen (Populus tremula L., Salicaceae)

    PubMed Central

    Ingvarsson, Pär K.

    2005-01-01

    Populus is an important model organism in forest biology, but levels of nucleotide polymorphisms and linkage disequilibrium have never been investigated in natural populations. Here I present a study on levels of nucleotide polymorphism, haplotype structure, and population subdivision in five nuclear genes in the European aspen Populus tremula. Results show substantial levels of genetic variation. Levels of silent site polymorphisms, πs, averaged 0.016 across the five genes. Linkage disequilibrium was generally low, extending only a few hundred base pairs, suggesting that rates of recombination are high in this obligate outcrossing species. Significant genetic differentiation was found at all five genes, with an average estimate of FST = 0.116. Levels of polymorphism in P. tremula are 2- to 10-fold higher than those in other woody, long-lived perennial plants, such as Pinus and Cryptomeria. The high levels of nucleotide polymorphism and low linkage disequilibrium suggest that it may be possible to map functional variation to very fine scales in P. tremula using association-mapping approaches. PMID:15489521

  10. 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 ...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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

  18. 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

  19. Polymorphic L1 retrotransposons are frequently in strong linkage disequilibrium with neighboring SNPs.

    PubMed

    Higashino, Saneyuki; Ohno, Tomoyuki; Ishiguro, Koichi; Aizawa, Yasunori

    2014-05-10

    L1 retrotransposons have been the major driver of structural variation of the human genome. L1 insertion polymorphism (LIP)-mediated genomic variation can alter the transcriptome and contribute to the divergence of human phenotypes. To assess this possibility, a genome-wide association study (GWAS) including LIPs is required. Toward this ultimate goal, the present study examined linkage disequilibrium between six LIPs and their neighboring single nucleotide polymorphisms (SNPs). Genomic PCR and sequencing of L1-plus and -minus alleles from different donors revealed that all six LIPs were in strong linkage disequilibrium with at least one SNP. In addition, comparison of syntenic regions containing the identified SNP nucleotides was performed among modern humans (L1-plus and -minus alleles), archaic humans and non-human primates, revealing two different evolutionary schemes that might have resulted in the observed strong SNP-LIP linkage disequilibria. This study provides an experimental framework and guidance for a future SNP-LIP integrative GWAS.

  20. Recovering Power in Association Mapping Panels with Variable Levels of Linkage Disequilibrium

    PubMed Central

    Rincent, Renaud; Moreau, Laurence; Monod, Hervé; Kuhn, Estelle; Melchinger, Albrecht E.; Malvar, Rosa A.; Moreno-Gonzalez, Jesus; Nicolas, Stéphane; Madur, Delphine; Combes, Valérie; Dumas, Fabrice; Altmann, Thomas; Brunel, Dominique; Ouzunova, Milena; Flament, Pascal; Dubreuil, Pierre; Charcosset, Alain; Mary-Huard, Tristan

    2014-01-01

    Association mapping has permitted the discovery of major QTL in many species. It can be applied to existing populations and, as a consequence, it is generally necessary to take into account structure and relatedness among individuals in the statistical model to control false positives. We analytically studied power in association studies by computing noncentrality parameter of the tests and its relationship with parameters characterizing diversity (genetic differentiation between groups and allele frequencies) and kinship between individuals. Investigation of three different maize diversity panels genotyped with the 50k SNPs array highlighted contrasted average power among panels and revealed gaps of power of classical mixed models in regions with high linkage disequilibrium (LD). These gaps could be related to the fact that markers are used for both testing association and estimating relatedness. We thus considered two alternative approaches to estimating the kinship matrix to recover power in regions of high LD. In the first one, we estimated the kinship with all the markers that are not located on the same chromosome than the tested SNP. In the second one, correlation between markers was taken into account to weight the contribution of each marker to the kinship. Simulations revealed that these two approaches were efficient to control false positives and were more powerful than classical models. PMID:24532779

  1. Nucleotide diversity and linkage disequilibrium in wild avocado (Persea americana Mill.).

    PubMed

    Chen, Haofeng; Morrell, Peter L; de la Cruz, Marlene; Clegg, Michael T

    2008-01-01

    Resequencing studies provide the ultimate resolution of genetic diversity because they identify all mutations in a gene that are present within the sampled individuals. We report a resequencing study of Persea americana, a subtropical tree species native to Meso- and Central America and the progenitor of cultivated avocado. The sample includes 21 wild accessions from Mexico, Costa Rica, Ecuador, and the Dominican Republic. Estimated levels of nucleotide polymorphism and linkage disequilibrium (LD) are obtained from fully resolved haplotype data from 4 nuclear loci that span 5960 nucleotide sites. Results show that, although avocado is a subtropical tree crop and a predominantly outcrossing plant, the overall level of genetic variation is not exceptionally high (nucleotide diversity at silent sites, pi(sil) = 0.0102) compared with available estimates from temperate plant species. Intralocus LD decays rapidly to half the initial value within about 1 kb. Estimates of recombination rate (based on the sequence data) show that the rate is not exceptionally high when compared with annual plants such as wild barley or maize. Interlocus LD is significant owing to substantial population structure induced by mixing of the 3 botanical races of avocado.

  2. 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.

  3. 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

  4. Extent of linkage disequilibrium and effective population size in Finnish Landrace and Finnish Yorkshire pig breeds.

    PubMed

    Uimari, P; Tapio, M

    2011-03-01

    The extent of linkage disequilibrium (LD) and effective population size in Finnish Landrace and Finnish Yorkshire pig populations were studied using a whole genome SNP panel (Illumina PorcineSNP60 BeadChip) and pedigree data. Genotypic data included 86 Finnish Landrace and 32 Finnish Yorkshire boars. Pedigree data included 608,138 Finnish Landrace 554,237 and Finnish Yorkshire pigs, and on average 15 ancestral generations were known for the reference animals, born in 2005 to 2009. The breeding animals of the 2 populations have been kept separate in the breeding programs. Based on the pedigree data, the current effective population size for Finnish Landrace is 91 and for Finnish Yorkshire 61. Linkage disequilibrium measures (D' and r(2)) were estimated for over 1.5 million pairs of SNP. Average r(2) for SNP 30 kb apart was 0.47 and 0.49 and for SNP 5 Mb apart 0.09 and 0.12 for Finnish Landrace and Finnish Yorkshire, respectively. Average LD (r(2)) between adjacent SNP in the Illumina PorcineSNP60 BeadChip was 0.43 (57% of the adjacent SNP pairs had r(2) > 0.2) for Finnish Landrace and 0.46 (60% of the adjacent SNP pairs had r(2) > 0.2) for Finnish Yorkshire, and average r(2) > 0.2 extended to 1.0 and 1.5 Mb for Finnish Landrace and Finnish Yorkshire, respectively. Effective population size estimates based on the decay of r(2) with distance were similar to those based on the pedigree data: 80 and 55 for Finnish Landrace and Finnish Yorkshire, respectively. Thus, the results indicate that the effective population size of Finnish Yorkshire is smaller than of Finnish Landrace and has a clear effect on the extent of LD. The current effective population size of both breeds is above the recommended minimum of 50 but may get smaller than that in the near future, if no action is taken to balance the inbreeding rate and selection response. Because a moderate level of LD extends over a long distance, selection based on whole genome SNP markers (genomic selection) is expected

  5. Modeling linkage disequilibrium and identifying recombination hotspots using single-nucleotide polymorphism data.

    PubMed Central

    Li, Na; Stephens, Matthew

    2003-01-01

    We introduce a new statistical model for patterns of linkage disequilibrium (LD) among multiple SNPs in a population sample. The model overcomes limitations of existing approaches to understanding, summarizing, and interpreting LD by (i) relating patterns of LD directly to the underlying recombination process; (ii) considering all loci simultaneously, rather than pairwise; (iii) avoiding the assumption that LD necessarily has a "block-like" structure; and (iv) being computationally tractable for huge genomic regions (up to complete chromosomes). We examine in detail one natural application of the model: estimation of underlying recombination rates from population data. Using simulation, we show that in the case where recombination is assumed constant across the region of interest, recombination rate estimates based on our model are competitive with the very best of current available methods. More importantly, we demonstrate, on real and simulated data, the potential of the model to help identify and quantify fine-scale variation in recombination rate from population data. We also outline how the model could be useful in other contexts, such as in the development of more efficient haplotype-based methods for LD mapping. PMID:14704198

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. A method for detecting recent changes in contemporary effective population size from linkage disequilibrium at linked and unlinked loci.

    PubMed

    Hollenbeck, C M; Portnoy, D S; Gold, J R

    2016-10-01

    Estimation of contemporary effective population size (Ne) from linkage disequilibrium (LD) between unlinked pairs of genetic markers has become an important tool in the field of population and conservation genetics. If data pertaining to physical linkage or genomic position are available for genetic markers, estimates of recombination rate between loci can be combined with LD data to estimate contemporary Ne at various times in the past. We extend the well-known, LD-based method of estimating contemporary Ne to include linkage information and show via simulation that even relatively small, recent changes in Ne can be detected reliably with a modest number of single-nucleotide polymorphism (SNP) loci. We explore several issues important to interpretation of the results and quantify the bias in estimates of contemporary Ne associated with the assumption that all loci in a large SNP data set are unlinked. The approach is applied to an empirical data set of SNP genotypes from a population of a marine fish where a recent, temporary decline in Ne is known to have occurred.

  13. Genome-wide analysis of zygotic linkage disequilibrium and its components in crossbred cattle

    PubMed Central

    2012-01-01

    Background Linkage disequilibrium (LD) between genes at linked or independent loci can occur at gametic and zygotic levels known asgametic LD and zygotic LD, respectively. Gametic LD is well known for its roles in fine-scale mapping of quantitative trait loci, genomic selection and evolutionary inference. The less-well studied is the zygotic LD and its components that can be also estimated directly from the unphased SNPs. Results This study was set up to investigate the genome-wide extent and patterns of zygotic LD and its components in a crossbred cattle population using the genomic data from the Illumina BovineSNP50 beadchip. The animal population arose from repeated crossbreeding of multiple breeds and selection for growth and cow reproduction. The study showed that similar genomic structures in gametic and zygotic LD were observed, with zygotic LD decaying faster than gametic LD over marker distance. The trigenic and quadrigenic disequilibria were generally two- to three-fold smaller than the usual digenic disequilibria (gametic or composite LD). There was less power of testing for these high-order genic disequilibria than for the digenic disequilibria. The power estimates decreased with the marker distance between markers though the decay trend is more obvious for the digenic disequilibria than for high-order disequilibria. Conclusions This study is the first major genome-wide survey of all non-allelic associations between pairs of SNPs in a cattle population. Such analysis allows us to assess the relative importance of gametic LD vs. all other non-allelic genic LDs regardless of whether or not the population is in HWE. The observed predominance of digenic LD (gametic or composite LD) coupled with insignificant high-order trigenic and quadrigenic disequilibria supports the current intensive focus on the use of high-density SNP markers for genome-wide association studies and genomic selection activities in the cattle population. PMID:22827586

  14. 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.

  15. 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.

  16. Mapping by admixture linkage disequilibrium in human populations: Limits and guidelines

    SciTech Connect

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

    1994-10-01

    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 {ge}.3 between admixed parent populations) to produce an efficient approach (>95% ascertainment) for locating genes not easily tracked in human pedigrees. 321 refs., 8 figs., 7 tabs.

  17. Genome-wide linkage disequilibrium and past effective population size in three Korean cattle breeds.

    PubMed

    Sudrajad, P; Seo, D W; Choi, T J; Park, B H; Roh, S H; Jung, W Y; Lee, S S; Lee, J H; Kim, S; Lee, S H

    2017-02-01

    The routine collection and use of genomic data are useful for effectively managing breeding programs for endangered populations. Linkage disequilibrium (LD) using high-density DNA markers has been widely used to determine population structures and predict the genomic regions that are associated with economic traits in beef cattle. The extent of LD also provides information about historical events, including past effective population size (Ne ), and it allows inferences on the genetic diversity of breeds. The objective of this study was to estimate the LD and Ne in three Korean cattle breeds that are genetically similar but have different coat colors (Brown, Brindle and Jeju Black Hanwoo). Brindle and Jeju Black are endangered breeds with small populations, whereas Brown Hanwoo is the main breeding population in Korea. DNA samples from these cattle breeds were genotyped using the Illumina BovineSNP50 Bead Chip. We examined 13 cattle breeds, including European taurines, African taurines and indicines, and hybrids to compare their LD values. Brown Hanwoo consistently had the lowest mean LD compared to Jeju Black, Brindle and the other 13 cattle breeds (0.13, 0.19, 0.21 and 0.15-0.22 respectively). The high LD values of Brindle and Jeju Black contributed to small Ne values (53 and 60 respectively), which were distinct from that of Brown Hanwoo (531) for 11 generations ago. The differences in LD and Ne for each breed reflect the breeding strategy applied. The Ne for these endangered cattle breeds remain low; thus, effort is needed to bring them back to a sustainable tract.

  18. Accounting for Linkage Disequilibrium in genome scans for selection without individual genotypes: the local score approach.

    PubMed

    Fariello, María Inés; Boitard, Simon; Mercier, Sabine; Robelin, David; Faraut, Thomas; Arnould, Cécile; Recoquillay, Julien; Bouchez, Olivier; Salin, Gérald; Dehais, Patrice; Gourichon, David; Leroux, Sophie; Pitel, Frédérique; Leterrier, Christine; SanCristobal, Magali

    2017-04-10

    Detecting genomic footprints of selection is an important step in the understanding of evolution. Accounting for linkage disequilibrium in genome scans increases detection power, but haplotype-based methods require individual genotypes and are not applicable on pool-sequenced samples. We propose to take advantage of the local score approach to account for linkage disequilibrium in genome scans for selection, cumulating (possibly small) signals from single markers over a genomic segment, to clearly pinpoint a selection signal. Using computer simulations, we demonstrate that this approach detects selection with higher power than several state-of-the-art single marker, windowing or haplotype-based approaches. We illustrate this on two benchmark data sets including individual genotypes, for which we obtain similar results with the local score and one haplotype-based approach. Finally, we apply the local score approach to Pool-Seq data obtained from a divergent selection experiment on behavior in quail, and obtain precise and biologically coherent selection signals: while competing methods fail to highlight any clear selection signature, our method detects several regions involving genes known to act on social responsiveness or autistic traits. Although we focus here on the detection of positive selection from multiple population data, the local score approach is general and can be applied to other genome scans for selection or other genome-wide analyses such as GWAS. This article is protected by copyright. All rights reserved.

  19. 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.

  20. 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.

  1. Linkage and linkage disequilibrium in chromosome band 1p36 in American Chaldeans with inflammatory bowel disease.

    PubMed

    Cho, J H; Nicolae, D L; Ramos, R; Fields, C T; Rabenau, K; Corradino, S; Brant, S R; Espinosa, R; LeBeau, M; Hanauer, S B; Bodzin, J; Bonen, D K

    2000-05-22

    The idiopathic inflammatory bowel diseases (IBDs), consisting of Crohn's disease and ulcerative colitis, are complex genetic disorders involving chronic inflammation of the intestines. Multiple genetic loci have been implicated through genome-wide searches, but refinement of localization sufficient to undertake positional cloning efforts has been problematic. This difficulty can be obviated through identification of ancestrally shared regions in genetic isolates, such as the Chaldean population, a Roman Catholic group from Iraq. We analyzed four multiply affected American Chaldean families with inflammatory bowel disease not known to be related. We observed evidence for linkage and linkage disequilibrium in precisely the same region of chromosome band 1p36 reported previously in an outbred population. Maximal evidence for linkage was observed near D1S1597 by multipoint analysis (MLOD = 3.01, P = 6.1 x 10(-5)). A shared haplotype (D1S507 to D1S1628) was observed over 27 cM between two families. There was homozygous sharing of a 5 cM portion of that haplotype in one family and over a <1 cM region in the second family. Homozygous sharing of this haplotype near D1S2697 and D1S3669 was observed in one individual in a third multiply affected family, with heterozygous sharing in a fourth family. Linkage in outbred families as well as in this genetic isolate indicates that a pathophysiologically crucial IBD susceptibility gene is located in 1p36. These findings provide a unique opportunity to refine the localization and identify a major susceptibility gene for a complex genetic disorder.

  2. 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

  3. 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

  4. Linkage Disequilibrium and Inversion-Typing of the Drosophila melanogaster Genome Reference Panel.

    PubMed

    Houle, David; Márquez, Eladio J

    2015-06-10

    We calculated the linkage disequilibrium between all pairs of variants in the Drosophila Genome Reference Panel with minor allele count ≥5. We used r(2) ≥ 0.5 as the cutoff for a highly correlated SNP. We make available the list of all highly correlated SNPs for use in association studies. Seventy-six percent of variant SNPs are highly correlated with at least one other SNP, and the mean number of highly correlated SNPs per variant over the whole genome is 83.9. Disequilibrium between distant SNPs is also common when minor allele frequency (MAF) is low: 37% of SNPs with MAF < 0.1 are highly correlated with SNPs more than 100 kb distant. Although SNPs within regions with polymorphic inversions are highly correlated with somewhat larger numbers of SNPs, and these correlated SNPs are on average farther away, the probability that a SNP in such regions is highly correlated with at least one other SNP is very similar to SNPs outside inversions. Previous karyotyping of the DGRP lines has been inconsistent, and we used LD and genotype to investigate these discrepancies. When previous studies agreed on inversion karyotype, our analysis was almost perfectly concordant with those assignments. In discordant cases, and for inversion heterozygotes, our results suggest errors in two previous analyses or discordance between genotype and karyotype. Heterozygosities of chromosome arms are, in many cases, surprisingly highly correlated, suggesting strong epsistatic selection during the inbreeding and maintenance of the DGRP lines.

  5. 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

  6. 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

  7. 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

  8. Linkage-disequilibrium mapping of disease genes by reconstruction of ancestral haplotypes in founder populations.

    PubMed Central

    Service, S K; Lang, D W; Freimer, N B; Sandkuijl, L A

    1999-01-01

    Linkage disequilibrium (LD) mapping may be a powerful means for genome screening to identify susceptibility loci for common diseases. A new statistical approach for detection of LD around a disease gene is presented here. This method compares the distribution of haplotypes in affected individuals versus that expected for individuals descended from a common ancestor who carried a mutation of the disease gene. Simulations demonstrate that this method, which we term "ancestral haplotype reconstruction" (AHR), should be powerful for genome screening of phenotypes characterized by a high degree of etiologic heterogeneity, even with currently available marker maps. AHR is best suited to application in isolated populations where affected individuals are relatively recently descended (< approximately 25 generations) from a common disease mutation-bearing founder. PMID:10330361

  9. Extreme Population-Dependent Linkage Disequilibrium Detected in an Inbreeding Plant Species, Hordeum vulgare

    PubMed Central

    Caldwell, Katherine S.; Russell, Joanne; Langridge, Peter; Powell, Wayne

    2006-01-01

    In human genetics a detailed knowledge of linkage disequilibrium (LD) is considered a prerequisite for effective population-based, high-resolution gene mapping and cloning. Similar opportunities exist for plants; however, differences in breeding system and population history need to be considered. Here we report a detailed study of localized LD in different populations of an inbreeding crop species. We measured LD between and within four gene loci within the region surrounding the hardness locus in three different gene pools of barley (Hordeum vulgare). We demonstrate that LD extends to at least 212 kb in elite barley cultivars but is rapidly eroded in related inbreeding ancestral populations. Our results indicate that haplotype-based sequence analysis in multiple populations will provide new opportunities to adjust the resolution of association studies in inbreeding crop species. PMID:16219791

  10. Detecting introgressive hybridization between free-ranging domestic dogs and wild wolves (Canis lupus) by admixture linkage disequilibrium analysis.

    PubMed

    Verardi, A; Lucchini, V; Randi, E

    2006-09-01

    Occasional crossbreeding between free-ranging domestic dogs and wild wolves (Canis lupus) has been detected in some European countries by mitochondrial DNA sequencing and genotyping unlinked microsatellite loci. Maternal and unlinked genomic markers, however, might underestimate the extent of introgressive hybridization, and their impacts on the preservation of wild wolf gene pools. In this study, we genotyped 220 presumed Italian wolves, 85 dogs and 7 known hybrids at 16 microsatellites belonging to four different linkage groups (plus four unlinked microsatellites). Population clustering and individual assignments were performed using a Bayesian procedure implemented in structure 2.1, which models the gametic disequilibrium arising between linked loci during admixtures, aiming to trace hybridization events further back in time and infer the population of origin of chromosomal blocks. Results indicate that (i) linkage disequilibrium was higher in wolves than in dogs; (ii) 11 out of 220 wolves (5.0%) were likely admixed, a proportion that is significantly higher than one admixed genotype in 107 wolves found previously in a study using unlinked markers; (iii) posterior maximum-likelihood estimates of the recombination parameter r revealed that introgression in Italian wolves is not recent, but could have continued for the last 70 (+/- 20) generations, corresponding to approximately 140-210 years. Bayesian clustering showed that, despite some admixture, wolf and dog gene pools remain sharply distinct (the average proportions of membership to wolf and dog clusters were Q(w) = 0.95 and Q(d) = 0.98, respectively), suggesting that hybridization was not frequent, and that introgression in nature is counteracted by behavioural or selective constraints.

  11. Genetic Structure, Linkage Disequilibrium and Signature of Selection in Sorghum: Lessons from Physically Anchored DArT Markers

    PubMed Central

    Bouchet, Sophie; Pot, David; Deu, Monique; Rami, Jean-François; Billot, Claire; Perrier, Xavier; Rivallan, Ronan; Gardes, Laëtitia; Xia, Ling; Wenzl, Peter; Kilian, Andrzej; Glaszmann, Jean-Christophe

    2012-01-01

    Population structure, extent of linkage disequilibrium (LD) as well as signatures of selection were investigated in sorghum using a core sample representative of worldwide diversity. A total of 177 accessions were genotyped with 1122 informative physically anchored DArT markers. The properties of DArTs to describe sorghum genetic structure were compared to those of SSRs and of previously published RFLP markers. Model-based (STRUCTURE software) and Neighbor-Joining diversity analyses led to the identification of 6 groups and confirmed previous evolutionary hypotheses. Results were globally consistent between the different marker systems. However, DArTs appeared more robust in terms of data resolution and bayesian group assignment. Whole genome linkage disequilibrium as measured by mean r2 decreased from 0.18 (between 0 to 10 kb) to 0.03 (between 100 kb to 1 Mb), stabilizing at 0.03 after 1 Mb. Effects on LD estimations of sample size and genetic structure were tested using i. random sampling, ii. the Maximum Length SubTree algorithm (MLST), and iii. structure groups. Optimizing population composition by the MLST reduced the biases in small samples and seemed to be an efficient way of selecting samples to make the best use of LD as a genome mapping approach in structured populations. These results also suggested that more than 100,000 markers may be required to perform genome-wide association studies in collections covering worldwide sorghum diversity. Analysis of DArT markers differentiation between the identified genetic groups pointed out outlier loci potentially linked to genes controlling traits of interest, including disease resistance genes for which evidence of selection had already been reported. In addition, evidence of selection near a homologous locus of FAR1 concurred with sorghum phenotypic diversity for sensitivity to photoperiod. PMID:22428056

  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. 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...

  14. 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...

  15. 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

  16. A first-generation metric linkage disequilibrium map of bovine chromosome 6.

    PubMed

    Khatkar, Mehar S; Collins, Andrew; Cavanagh, Julie A L; Hawken, Rachel J; Hobbs, Matthew; Zenger, Kyall R; Barris, Wes; McClintock, Alexander E; Thomson, Peter C; Nicholas, Frank W; Raadsma, Herman W

    2006-09-01

    We constructed a metric linkage disequilibrium (LD) map of bovine chromosome 6 (BTA6) on the basis of data from 220 SNPs genotyped on 433 Australian dairy bulls. This metric LD map has distances in LD units (LDUs) that are analogous to centimorgans in linkage maps. The LD map of BTA6 has a total length of 8.9 LDUs. Within the LD map, regions of high LD (represented as blocks) and regions of low LD (steps) are observed, when plotted against the integrated map in kilobases. At the most stringent block definition, namely a set of loci with zero LDU increase over the span of these markers, BTA6 comprises 40 blocks, accounting for 41% of the chromosome. At a slightly lower stringency of block definition (a set of loci covering a maximum of 0.2 LDUs on the LD map), up to 81% of BTA6 is spanned by 46 blocks and with 13 steps that are likely to reflect recombination hot spots. The mean swept radius (the distance over which LD is likely to be useful for mapping) is 13.3 Mb, confirming extensive LD in Holstein-Friesian dairy cattle, which makes such populations ideal for whole-genome association studies.

  17. Effects of identity disequilibrium and linkage on quantitative variation in finite populations.

    PubMed

    Tachida, H; Cockerham, C C

    1989-02-01

    Identity disequilibrium, ID, is the difference between joint identity by descent and the product of the separate probabilities of identity by descent for two loci. The effects of ID on the additive by additive (a*a) epistatic variance and joint dominance component between populations and in the additive, dominance and a*a variance within populations, including the effects on covariances of relatives within populations, were studied for finite monoecious populations. The effects are formulated in terms of three additive partitions, eta b, eta a and eta d, of the total ID, each of which increases from zero to a maximum at some generation dependent upon linkage and population size and decreases thereafter. eta d is about four times the magnitude of the other two but none is of any consequence except for tight linkage and very small populations. For single-generation bottleneck populations only eta d is not zero. With random mating of expanded populations eta b remains constant and eta a and eta d go to zero at a rate dependent upon linkage, very fast with free recombination. The contributions of joint dominance to the genetic components of variance within and between populations are entirely a function of the eta's while those of a*a variance to the components are functions mainly of the coancestry coefficient and only modified by the eta's. The contributions of both to the covariances of half-sibs, full-sibs and parent-offspring follow the pattern expected from their contributions to the genetic components of variance within populations except for minor terms which most likely are of little importance.

  18. Distribution of long-range linkage disequilibrium and Tajima's D values in Scandinavian populations of Norway Spruce (Picea abies).

    PubMed

    Larsson, Hanna; Källman, Thomas; Gyllenstrand, Niclas; Lascoux, Martin

    2013-05-20

    The site frequency spectrum of mutations (SFS) and linkage disequilibrium (LD) are the two major sources of information in population genetics studies. In this study we focus on the levels of LD and the SFS and on the effect of sample size on summary statistics in 10 Scandinavian populations of Norway spruce. We found that previous estimates of a low level of LD were highly influenced by both sampling strategy and the fact that data from multiple loci were analyzed jointly. Estimates of LD were in fact heterogeneous across loci and increased within individual populations compared with the estimate from the total data. The variation in levels of LD among populations most likely reflects different demographic histories, although we were unable to detect population structure by using standard approaches. As in previous studies, we also found that the SFS-based test Tajima's D was highly sensitive to sample size, revealing that care should be taken to draw strong conclusions from this test when sample size is small. In conclusion, the results from this study are in line with recent studies in other conifers that have revealed a more complex and variable pattern of LD than earlier studies suggested and with studies in trees and humans that suggest that Tajima's D is sensitive to sample size. This has large consequences for the design of future association and population genetic studies in Norway spruce.

  19. Theory of the effects of population structure and sampling on patterns of linkage disequilibrium applied to genomic data from humans.

    PubMed Central

    Wakeley, John; Lessard, Sabin

    2003-01-01

    We develop predictions for the correlation of heterozygosity and for linkage disequilibrium between two loci using a simple model of population structure that includes migration among local populations, or demes. We compare the results for a sample of size two from the same deme (a single-deme sample) to those for a sample of size two from two different demes (a scattered sample). The correlation in heterozygosity for a scattered sample is surprisingly insensitive to both the migration rate and the number of demes. In contrast, the correlation in heterozygosity for a single-deme sample is sensitive to both, and the effect of an increase in the number of demes is qualitatively similar to that of a decrease in the migration rate: both increase the correlation in heterozygosity. These same conclusions hold for a commonly used measure of linkage disequilibrium (r(2)). We compare the predictions of the theory to genomic data from humans and show that subdivision might account for a substantial portion of the genetic associations observed within the human genome, even though migration rates among local populations of humans are relatively large. Because correlations due to subdivision rather than to physical linkage can be large even in a single-deme sample, then if long-term migration has been important in shaping patterns of human polymorphism, the common practice of disease mapping using linkage disequilibrium in "isolated" local populations may be subject to error. PMID:12871914

  20. Accommodating Linkage Disequilibrium in Genetic-Association Analyses via Ridge Regression

    PubMed Central

    Malo, Nathalie; Libiger, Ondrej; Schork, Nicholas J.

    2008-01-01

    Large-scale genetic-association studies that take advantage of an extremely dense set of genetic markers have begun to produce very compelling statistical associations between multiple makers exhibiting strong linkage disequilibrium (LD) in a single genomic region and a phenotype of interest. However, the ultimate biological or “functional” significance of these multiple associations has been difficult to discern. In fact, the LD relationships between not only the markers found to be associated with the phenotype but also potential functionally or causally relevant genetic variations that reside near those markers have been exploited in such studies. Unfortunately, LD, especially strong LD, between variations at neighboring loci can make it difficult to distinguish the functionally relevant variations from nonfunctional variations. Although there are (rare) situations in which it is impossible to determine the independent phenotypic effects of variations in LD, there are strategies for accommodating LD between variations at different loci, and they can be used to tease out their independent effects on a phenotype. These strategies make it possible to differentiate potentially causative from noncausative variations. We describe one such approach involving ridge regression. We showcase the method by using both simulated and real data. Our results suggest that ridge regression and related techniques have the potential to distinguish causative from noncausative variations in association studies. PMID:18252218

  1. Linkage disequilibrium and genome-wide association mapping in tetraploid wheat (Triticum turgidum L.).

    PubMed

    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.

  2. Haplotype and linkage disequilibrium analysis of the CRMP1 and EVC genes.

    PubMed

    Sivakumaran, Theru A; Lesperance, Marci M

    2004-11-01

    In this report, we present the haplotype and linkage disequilibrium (LD) pattern in the Collapsin Response Mediator Protein 1 (CRMP1) and Ellis-van Creveld syndrome (EVC) gene region. We genotyped eight different single nucleotide polymorphisms (SNPs) in the CRMP1 and EVC genes in 90 control individuals of diverse ethnicity. The minor allele frequencies ranged from 3.3-49.4%, with most having a frequency >25%. A total of 37 haplotypes were derived from these eight polymorphisms, with only one haplotype having a frequency >10%. Pairwise LD analysis showed a weak but significant LD between markers located about 243 kb apart in this region. The LD was significant between markers spaced about 208 kb apart in EVC, whereas no LD was found between a pair of markers located about 5 kb apart in CRMP1. However, in general, LD correlated with the distance between loci. The CRMP1 and EVC genes are located near WFS1, the Wolfram syndrome type 1 gene, in which mutations also cause low frequency sensorineural hearing loss (LFSNHL). The haplotypes obtained from these polymorphisms will be useful to track the segregation of phenotypes in families with Ellis-van Creveld syndrome, Weyers acrodental dysostosis, LFSNHL and Wolfram syndrome type 1.

  3. Genome-wide linkage disequilibrium analysis in bread wheat and durum wheat.

    PubMed

    Somers, Daryl J; Banks, Travis; Depauw, Ron; Fox, Stephen; Clarke, John; Pozniak, Curtis; McCartney, Curt

    2007-06-01

    Bread wheat and durum wheat were examined for linkage disequilibrium (LD) using microsatellite markers distributed across the genome. The allele database consisted of 189 bread wheat accessions genotyped at 370 loci and 93 durum wheat accessions genotyped at 245 loci. A significance level of p < 0.001 was set for all comparisons. The bread and durum wheat collections showed that 47.9% and 14.0% of all locus pairs were in LD, respectively. LD was more prevalent between loci on the same chromosome compared with loci on independent chromosomes and was highest between adjacent loci. Only a small fraction (bread wheat, 0.9%; durum wheat, 3.2%) of the locus pairs in LD showed R2 values > 0.2. The LD between adjacent locus pairs extended (R2 > 0.2) approximately 2-3 cM, on average, but some regions of the bread and durum wheat genomes showed high levels of LD (R2 = 0.7 and 1.0, respectively) extending 41.2 and 25.5 cM, respectively. The wheat collections were clustered by similarity into subpopulations using unlinked microsatellite data and the software Structure. Analysis within subpopulations showed 14- to 16-fold fewer locus pairs in LD, higher R2 values for those pairs in LD, and LD extending further along the chromosome. The data suggest that LD mapping of wheat can be performed with simple sequence repeats to a resolution of <5 cM.

  4. The Impact of Genetic Relationship and Linkage Disequilibrium on Genomic Selection

    PubMed Central

    Li, Xiao; Zhao, Jing; Zuo, Tao; Zhang, Xuan; Zhang, Yongzhong; Liu, Sisi; Shen, Yaou; Lin, Haijian; Zhang, Zhiming; Huang, Kaijian; Lübberstedt, Thomas; Pan, Guangtang

    2015-01-01

    Genomic selection is a promising research area due to its practical application in breeding. In this study, impact of realized genetic relationship and linkage disequilibrium (LD) on marker density and training population size required was investigated and their impact on practical application was further discussed. This study is based on experimental data of two populations derived from the same two founder lines (B73, Mo17). Two populations were genotyped with different marker sets at different density: IBM Syn4 and IBM Syn10. A high-density marker set in Syn10 was imputed into the Syn4 population with low marker density. Seven different prediction scenarios were carried out with a random regression best linear unbiased prediction (RR-BLUP) model. The result showed that the closer the real genetic relationship between training and validation population, the fewer markers were required to reach a good prediction accuracy. Taken the short-term cost for consideration, relationship information is more valuable than LD information. Meanwhile, the result indicated that accuracies based on high LD between QTL and markers were more stable over generations, thus LD information would provide more robust prediction capacity in practical applications. PMID:26148055

  5. Recombination hotspots rather than population history dominate linkage disequilibrium in the MHC class II region.

    PubMed

    Kauppi, Liisa; Sajantila, Antti; Jeffreys, Alec J

    2003-01-01

    Recombination, demographic history, drift and selection influence the extent of linkage disequilibrium (LD) in the human genome, but their relative contributions remain unclear. To investigate the effect of meiotic recombination versus population history on LD, three populations with different demographic histories (UK north Europeans, Saami and Zimbabweans) were genotyped for high-frequency single-nucleotide polymorphisms (SNPs) across a 75 kb DNA segment of the MHC class II region. This region spans three well-characterized recombination hotspots and a 60 kb long LD block. Despite a high level of underlying haplotype diversity and considerable divergence in haplotype composition between populations, all three populations showed very similar patterns of LD. Surprisingly, the entire 60 kb LD block was present even in Africans, although it was relatively difficult to detect owing to a systematic deficiency of high frequency SNPs. In contrast, DNA within recombination hotspots did not show this low nucleotide diversity in Africans. Thus, while population history has some influence on LD, our findings suggest that recombination hotspots play a major global role in shaping LD patterns as well as helping to maintain localized SNP diversity in this region of the MHC.

  6. 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

  7. Structure of linkage disequilibrium and phenotypic associations in the maize genome

    PubMed Central

    Remington, David L.; Thornsberry, Jeffry M.; Matsuoka, Yoshihiro; Wilson, Larissa M.; Whitt, Sherry R.; Doebley, John; Kresovich, Stephen; Goodman, Major M.; Buckler, Edward S.

    2001-01-01

    Association studies based on linkage disequilibrium (LD) can provide high resolution for identifying genes that may contribute to phenotypic variation. We report patterns of local and genome-wide LD in 102 maize inbred lines representing much of the worldwide genetic diversity used in maize breeding, and address its implications for association studies in maize. In a survey of six genes, we found that intragenic LD generally declined rapidly with distance (r2 < 0.1 within 1500 bp), but rates of decline were highly variable among genes. This rapid decline probably reflects large effective population sizes in maize during its evolution and high levels of recombination within genes. A set of 47 simple sequence repeat (SSR) loci showed stronger evidence of genome-wide LD than did single-nucleotide polymorphisms (SNPs) in candidate genes. LD was greatly reduced but not eliminated by grouping lines into three empirically determined subpopulations. SSR data also supplied evidence that divergent artificial selection on flowering time may have played a role in generating population structure. Provided the effects of population structure are effectively controlled, this research suggests that association studies show great promise for identifying the genetic basis of important traits in maize with very high resolution. PMID:11562485

  8. 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.

  9. Distinguishing Functional Amino Acid Covariation from Background Linkage Disequilibrium in HIV Protease and Reverse Transcriptase

    PubMed Central

    Wang, Qi; Lee, Christopher

    2007-01-01

    Correlated amino acid mutation analysis has been widely used to infer functional interactions between different sites in a protein. However, this analysis can be confounded by important phylogenetic effects broadly classifiable as background linkage disequilibrium (BLD). We have systematically separated the covariation induced by selective interactions between amino acids from background LD, using synonymous (S) vs. amino acid (A) mutations. Covariation between two amino acid mutations, (A,A), can be affected by selective interactions between amino acids, whereas covariation within (A,S) pairs or (S,S) pairs cannot. Our analysis of the pol gene — including the protease and the reverse transcriptase genes — in HIV reveals that (A,A) covariation levels are enormously higher than for either (A,S) or (S,S), and thus cannot be attributed to phylogenetic effects. The magnitude of these effects suggests that a large portion of (A,A) covariation in the HIV pol gene results from selective interactions. Inspection of the most prominent (A,A) interactions in the HIV pol gene showed that they are known sites of independently identified drug resistance mutations, and physically cluster around the drug binding site. Moreover, the specific set of (A,A) interaction pairs was reproducible in different drug treatment studies, and vanished in untreated HIV samples. The (S,S) covariation curves measured a low but detectable level of background LD in HIV. PMID:17726544

  10. 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

  11. Linkage Disequilibrium Patterns and tagSNP Transferability among European Populations

    PubMed Central

    Mueller, Jakob C.; Lõhmussaar, Elin; Mägi, Reedik; Remm, Maido; Bettecken, Thomas; Lichtner, Peter; Biskup, Saskia; Illig, Thomas; Pfeufer, Arne; Luedemann, Jan; Schreiber, Stefan; Pramstaller, Peter; Pichler, Irene; Romeo, Giovanni; Gaddi, Anthony; Testa, Alessandra; Wichmann, Heinz-Erich; Metspalu, Andres; Meitinger, Thomas

    2005-01-01

    The pattern of linkage disequilibrium (LD) is critical for association studies, in which disease-causing variants are identified by allelic association with adjacent markers. The aim of this study is to compare the LD patterns in several distinct European populations. We analyzed four genomic regions (in total, 749 kb) containing candidate genes for complex traits. Individuals were genotyped for markers that are evenly distributed at an average spacing of ∼2–4 kb in eight population-based samples from ongoing epidemiological studies across Europe. The Centre d'Etude du Polymorphisme Humain (CEPH) trios of the HapMap project were included and were used as a reference population. In general, we observed a conservation of the LD patterns across European samples. Nevertheless, shifts in the positions of the boundaries of high-LD regions can be demonstrated between populations, when assessed by a novel procedure based on bootstrapping. Transferability of LD information among populations was also tested. In two of the analyzed gene regions, sets of tagging single-nucleotide polymorphisms (tagSNPs) selected from the HapMap CEPH trios performed surprisingly well in all local European samples. However, significant variation in the other two gene regions predicts a restricted applicability of CEPH-derived tagging markers. Simulations based on our data set show the extent to which further gain in tagSNP efficiency and transferability can be achieved by increased SNP density. PMID:15637659

  12. 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

  13. 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.

  14. 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

  15. [Frequency and linkage disequilibrium of specific HLA-DR and HLA-DQ genes in Chinese Han population].

    PubMed

    Yang, Su-Xia; Hu, Zhi-Fei; Zu, Qiang; Lu, Jin-Shan; Zhang, Xu; Dong, Jun

    2012-12-01

    This study was aimed to investigate the distribution feature of HLA-DR/DQ gene linkage disequilibrium in Chinese Han population and to improve the accuracy of HLA matching results. Genotyping of HLA-DR and HLA-DQ gene locus was performed using PCR-SSP typing in Chinese Han population receiving kidney transplantation. The results showed that there were 29 new linkage combinations in 1799 patients, in which DR13-DQ5, DR11-DQ8 and DR8-DQ8 were discovered for 11, 8 and 7 times respectively while DR9-DQ8, DR12-DQ6 and DR14-DQ4 were both discovered for 6 times. The linkage disequilibrium parameters of these haplotypes were negative, showing that these linkages were uncommon. It is concluded that this study not only enriches the classical HLA-DR/DQ linkage combinations, but also indicates the national relevance of combination distribution, and it has great importance in improving the accuracy of HLA matching experiments and reducing unnecessary repeated work.

  16. 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.

  17. Global similarity with local differences in linkage disequilibrium between the Dutch and HapMap–CEU populations

    PubMed Central

    Pardo, Luba; Bochdanovits, Zoltán; de Geus, Eco; Hottenga, Jouke J; Sullivan, Patrick; Posthuma, Danielle; Penninx, Brenda W J H; Boomsma, Dorret; Heutink, Peter

    2009-01-01

    The HapMap project has facilitated the selection of tagging single nucleotide polymorphisms (tagSNPs) for genome-wide association studies (GWAS) under the assumption that linkage disequilibrium (LD) in the HapMap populations is similar to the populations under investigation. Earlier reports support this assumption, although in most of these studies only a few loci were evaluated. We compared pair-wise LD and LD block structure across autosomes between the Dutch population and the CEU–HapMap reference panel. The impact of sampling distribution on the estimation of LD blocks was studied by bootstrapping. A high Pearson correlation (genome-wide; 0.93) between pair-wise r2 for the Dutch and the CEU populations was found, indicating that tagSNPs from the CEU–HapMap panel capture common variation in the Dutch population. However, some genomic regions exhibited, significantly lower correlation than the genome-wide estimate. This might decrease the validity of HapMap tagSNPs in these regions and the power of GWAS. The LD block structure differed considerably between the Dutch and CEU–HapMap populations. This was not explained by demographic differences between the CEU and Dutch samples, as testing for population stratification was not significant. We also found that sampling variation had a large effect on the estimation of LD blocks, as shown by the bootstrapping analysis. Thus, in small samples, most of the observed differences in LD blocks between populations are most likely the result of sampling variation. This poor concordance in LD block structure suggests that large samples are required for robust estimations of local LD block structure in populations. PMID:19127282

  18. A multilocus linkage disequilibrium measure based on mutual information theory and its applications.

    PubMed

    Zhang, Lei; Liu, Jianfeng; Deng, Hong-Wen

    2009-12-01

    Evaluating the patterns of linkage disequilibrium (LD) is important for association mapping study as well as for studying the genomic architecture of human genome (e.g., haplotype block structures). Commonly used bi-allelic pairwise measures for assessing LD between two loci, such as r(2) and D', may not make full and efficient use of modern multilocus data. Though extended to multilocus scenarios, their performance is still questionable. Meanwhile, most existing measures for an entire multilocus region, such as normalized entropy difference, do not consider existence of LD heterogeneity across the region under investigation. Additionally, these existing multilocus measures cannot handle distant regions where long-range LD patterns may exist. In this study, we proposed a novel multilocus LD measure developed based on mutual information theory. Our proposed measure described LD pattern between two chromosome regions each of which may consist of multiple loci (including multi-allele loci). As such, the proposed measure can better characterize LD patterns between two arbitrary regions. As potential applications, we developed algorithms on the proposed measure for partitioning haplotype blocks and for selecting haplotype tagging SNPs (htSNPs), which were helpful for follow-up association tests. The results on both simulated and empirical data showed that our LD measure had distinct advantages over pairwise and other multilocus measures. First, our measure was more robust, and can capture comprehensively the LD information between neighboring as well as disjointed regions. Second, haplotype blocks were better described via our proposed measure. Furthermore, association tests with htSNPs from the proposed algorithm had improved power over tests on single markers and on haplotypes.

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

    PubMed

    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 r (2)≥ 0.20 would require about 30,000-50,000 SNPs. However, r (2)≥ 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.

  20. 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

  1. Multiple linear combination (MLC) regression tests for common variants adapted to linkage disequilibrium structure

    PubMed Central

    Yoo, Yun Joo; Sun, Lei; Poirier, Julia G.; Paterson, Andrew D.

    2016-01-01

    ABSTRACT By jointly analyzing multiple variants within a gene, instead of one at a time, gene‐based multiple regression can improve power, robustness, and interpretation in genetic association analysis. We investigate multiple linear combination (MLC) test statistics for analysis of common variants under realistic trait models with linkage disequilibrium (LD) based on HapMap Asian haplotypes. MLC is a directional test that exploits LD structure in a gene to construct clusters of closely correlated variants recoded such that the majority of pairwise correlations are positive. It combines variant effects within the same cluster linearly, and aggregates cluster‐specific effects in a quadratic sum of squares and cross‐products, producing a test statistic with reduced degrees of freedom (df) equal to the number of clusters. By simulation studies of 1000 genes from across the genome, we demonstrate that MLC is a well‐powered and robust choice among existing methods across a broad range of gene structures. Compared to minimum P‐value, variance‐component, and principal‐component methods, the mean power of MLC is never much lower than that of other methods, and can be higher, particularly with multiple causal variants. Moreover, the variation in gene‐specific MLC test size and power across 1000 genes is less than that of other methods, suggesting it is a complementary approach for discovery in genome‐wide analysis. The cluster construction of the MLC test statistics helps reveal within‐gene LD structure, allowing interpretation of clustered variants as haplotypic effects, while multiple regression helps to distinguish direct and indirect associations. PMID:27885705

  2. Dissecting linkage disequilibrium in African-American genomes: roles of markers and individuals.

    PubMed

    Xu, Shuhua; Huang, Wei; Wang, Haifeng; He, Yungang; Wang, Ying; Wang, Yi; Qian, Ji; Xiong, Momiao; Jin, Li

    2007-09-01

    Substantial increases of linkage disequilibrium (LD) both in magnitude and in range have been observed in recently admixed populations such as African-American (AfA). On the other hand, it has also been shown that LD in AfAs was very similar to that of African. In this study, we attempted to resolve these contradicting observations by conducting a systematic examination of the LD structure in AfAs by genotyping a sample of AfA individuals at 24,341 single nucleotide polymorphisms (SNPs) spanning almost the entire chromosome 21, with an average density of 1.5 kb/SNP. The overall LD in AfAs is similar to that in African populations and much less than that in European populations. Even when the ancestry-informative markers (AIMs) were used, extended LD in AfA was found to be limited to certain magnitude range (0.2 < or = r(2) < or = 0.8) and certain distance range, that is, between-marker distance more than 200 kb. Furthermore, the inclusion of AfA individuals with predominant African ancestry was found to reduce the overall magnitude of LD. Elevation of LD in the AfA population, compared with its parental populations, can only be observed at the markers with large allele frequency differences between 2 parental populations at limited scenario. AfA individuals of wholly African ancestry contribute little to the extended LD in the AfA population, and further genotyping or association analysis conducted using only admixed individuals may lead to higher statistical power and possibly reduced cost.

  3. Using multilocus sequence data to assess population structure, natural selection, and linkage disequilibrium in wild tomatoes.

    PubMed

    Arunyawat, Uraiwan; Stephan, Wolfgang; Städler, Thomas

    2007-10-01

    We employed a multilocus approach to examine the effects of population subdivision and natural selection on DNA polymorphism in 2 closely related wild tomato species (Solanum peruvianum and Solanum chilense), using sequence data for 8 nuclear loci from populations across much of the species' range. Both species exhibit substantial levels of nucleotide variation. The species-wide level of silent nucleotide diversity is 18% higher in S. peruvianum (pi(sil) approximately 2.50%) than in S. chilense (pi(sil) approximately 2.12%). One of the loci deviates from neutral expectations, showing a clinal pattern of nucleotide diversity and haplotype structure in S. chilense. This geographic pattern of variation is suggestive of an incomplete (ongoing) selective sweep, but neutral explanations cannot be entirely dismissed. Both wild tomato species exhibit moderate levels of population differentiation (average F(ST) approximately 0.20). Interestingly, the pooled samples (across different demes) exhibit more negative Tajima's D and Fu and Li's D values; this marked excess of low-frequency polymorphism can only be explained by population (or range) expansion and is unlikely to be due to population structure per se. We thus propose that population structure and population/range expansion are among the most important evolutionary forces shaping patterns of nucleotide diversity within and among demes in these wild tomatoes. Patterns of population differentiation may also be impacted by soil seed banks and historical associations mediated by climatic cycles. Intragenic linkage disequilibrium (LD) decays very rapidly with physical distance, suggesting high recombination rates and effective population sizes in both species. The rapid decline of LD seems very promising for future association studies with the purpose of mapping functional variation in wild tomatoes.

  4. 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

  5. Genetic structure and linkage disequilibrium in landrace populations of barley in Sardinia.

    PubMed

    Rodriguez, Monica; Rau, Domenico; O'Sullivan, Donal; Brown, Anthony H D; Papa, Roberto; Attene, Giovanna

    2012-06-01

    Multilocus digenic linkage disequilibria (LD) and their population structure were investigated in eleven landrace populations of barley (Hordeum vulgare ssp. vulgare L.) in Sardinia, using 134 dominant simple-sequence amplified polymorphism markers. The analysis of molecular variance for these markers indicated that the populations were partially differentiated (F(ST) = 0.18), and clustered into three geographic areas. Consistent with this population pattern, STRUCTURE analysis allocated individuals from a bulk of all populations into four genetic groups, and these groups also showed geographic patterns. In agreement with other molecular studies in barley, the general level of LD was low (13% of locus pairs, with P < 0.01) in the bulk of 337 lines, and decayed steeply with map distance between markers. The partitioning of multilocus associations into various components indicated that genetic drift and founder effects played a major role in determining the overall genetic makeup of the diversity in these landrace populations, but that epistatic homogenising or diversifying selection was also present. Notably, the variance of the disequilibrium component was relatively high, which implies caution in the pooling of barley lines for association studies. Finally, we compared the analyses of multilocus structure in barley landrace populations with parallel analyses in both composite crosses of barley on the one hand and in natural populations of wild barley on the other. Neither of these serves as suitable mimics of landraces in barley, which require their own study. Overall, the results suggest that these populations can be exploited for LD mapping if population structure is controlled.

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

    DOE PAGES

    Ramstein, Guillaume P.; Evans, Joseph; Kaeppler, Shawn M.; ...

    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

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

    PubMed Central

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

    2012-01-01

    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 r2 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 r2=0.28), and a second group of 38 genes had weaker LD (mean r2=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. 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.

  9. 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

  10. 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.

  11. 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.

  12. Genome-Wide Divergence and Linkage Disequilibrium Analyses for Capsicum baccatum Revealed by Genome-Anchored Single Nucleotide Polymorphisms.

    PubMed

    Nimmakayala, Padma; Abburi, Venkata L; Saminathan, Thangasamy; Almeida, Aldo; Davenport, Brittany; Davidson, Joshua; Reddy, C V Chandra Mohan; Hankins, Gerald; Ebert, Andreas; Choi, Doil; Stommel, John; Reddy, Umesh K

    2016-01-01

    Principal component analysis (PCA) with 36,621 polymorphic genome-anchored single nucleotide polymorphisms (SNPs) identified collectively for Capsicum annuum and Capsicum baccatum was used to characterize population structure and species domestication of these two important incompatible cultivated pepper species. Estimated mean nucleotide diversity (π) and Tajima's D across various chromosomes revealed biased distribution toward negative values on all chromosomes (except for chromosome 4) in cultivated C. baccatum, indicating a population bottleneck during domestication of C. baccatum. In contrast, C. annuum chromosomes showed positive π and Tajima's D on all chromosomes except chromosome 8, which may be because of domestication at multiple sites contributing to wider genetic diversity. For C. baccatum, 13,129 SNPs were available, with minor allele frequency (MAF) ≥0.05; PCA of the SNPs revealed 283 C. baccatum accessions grouped into 3 distinct clusters, for strong population structure. The fixation index (FST ) between domesticated C. annuum and C. baccatum was 0.78, which indicates genome-wide divergence. We conducted extensive linkage disequilibrium (LD) analysis of C. baccatum var. pendulum cultivars on all adjacent SNP pairs within a chromosome to identify regions of high and low LD interspersed with a genome-wide average LD block size of 99.1 kb. We characterized 1742 haplotypes containing 4420 SNPs (range 9-2 SNPs per haplotype). Genome-wide association study (GWAS) of peduncle length, a trait that differentiates wild and domesticated C. baccatum types, revealed 36 significantly associated genome-wide SNPs. Population structure, identity by state (IBS) and LD patterns across the genome will be of potential use for future GWAS of economically important traits in C. baccatum peppers.

  13. Genome-Wide Divergence and Linkage Disequilibrium Analyses for Capsicum baccatum Revealed by Genome-Anchored Single Nucleotide Polymorphisms

    PubMed Central

    Nimmakayala, Padma; Abburi, Venkata L.; Saminathan, Thangasamy; Almeida, Aldo; Davenport, Brittany; Davidson, Joshua; Reddy, C. V. Chandra Mohan; Hankins, Gerald; Ebert, Andreas; Choi, Doil; Stommel, John; Reddy, Umesh K.

    2016-01-01

    Principal component analysis (PCA) with 36,621 polymorphic genome-anchored single nucleotide polymorphisms (SNPs) identified collectively for Capsicum annuum and Capsicum baccatum was used to characterize population structure and species domestication of these two important incompatible cultivated pepper species. Estimated mean nucleotide diversity (π) and Tajima's D across various chromosomes revealed biased distribution toward negative values on all chromosomes (except for chromosome 4) in cultivated C. baccatum, indicating a population bottleneck during domestication of C. baccatum. In contrast, C. annuum chromosomes showed positive π and Tajima's D on all chromosomes except chromosome 8, which may be because of domestication at multiple sites contributing to wider genetic diversity. For C. baccatum, 13,129 SNPs were available, with minor allele frequency (MAF) ≥0.05; PCA of the SNPs revealed 283 C. baccatum accessions grouped into 3 distinct clusters, for strong population structure. The fixation index (FST) between domesticated C. annuum and C. baccatum was 0.78, which indicates genome-wide divergence. We conducted extensive linkage disequilibrium (LD) analysis of C. baccatum var. pendulum cultivars on all adjacent SNP pairs within a chromosome to identify regions of high and low LD interspersed with a genome-wide average LD block size of 99.1 kb. We characterized 1742 haplotypes containing 4420 SNPs (range 9–2 SNPs per haplotype). Genome-wide association study (GWAS) of peduncle length, a trait that differentiates wild and domesticated C. baccatum types, revealed 36 significantly associated genome-wide SNPs. Population structure, identity by state (IBS) and LD patterns across the genome will be of potential use for future GWAS of economically important traits in C. baccatum peppers. PMID:27857720

  14. Genetic structure, linkage disequilibrium and association mapping of Verticillium wilt resistance in elite cotton (Gossypium hirsutum L.) germplasm population.

    PubMed

    Zhao, Yunlei; Wang, Hongmei; Chen, Wei; Li, Yunhai

    2014-01-01

    Understanding the population structure and linkage disequilibrium in an association panel can effectively avoid spurious associations and improve the accuracy in association mapping. In this study, one hundred and fifty eight elite cotton (Gossypium hirsutum L.) germplasm from all over the world, which were genotyped with 212 whole genome-wide marker loci and phenotyped with an disease nursery and greenhouse screening method, were assayed for population structure, linkage disequilibrium, and association mapping of Verticillium wilt resistance. A total of 480 alleles ranging from 2 to 4 per locus were identified from all collections. Model-based analysis identified two groups (G1 and G2) and seven subgroups (G1a-c, G2a-d), and differentiation analysis showed that subgroup having a single origin or pedigree was apt to differentiate with those having a mixed origin. Only 8.12% linked marker pairs showed significant LD (P<0.001) in this association panel. The LD level for linked markers is significantly higher than that for unlinked markers, suggesting that physical linkage strongly influences LD in this panel, and LD level was elevated when the panel was classified into groups and subgroups. The LD decay analysis for several chromosomes showed that different chromosomes showed a notable change in LD decay distances for the same gene pool. Based on the disease nursery and greenhouse environment, 42 marker loci associated with Verticillium wilt resistance were identified through association mapping, which widely were distributed among 15 chromosomes. Among which 10 marker loci were found to be consistent with previously identified QTLs and 32 were new unreported marker loci, and QTL clusters for Verticillium wilt resistanc on Chr.16 were also proved in our study, which was consistent with the strong linkage in this chromosome. Our results would contribute to association mapping and supply the marker candidates for marker-assisted selection of Verticillium wilt

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

    PubMed

    Jónás, Dávid; Ducrocq, Vincent; Croiseau, Pascal

    2017-04-01

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

  16. Extensive Linkage Disequilibrium in the Achaete-Scute Complex of Drosophila Melanogaster

    PubMed Central

    Macpherson, J. N.; Weir, B. S.; Leigh-Brown, A. J.

    1990-01-01

    We have analyzed the level of gametic association between restriction map variants in a sample of 44 X chromosomes from a natural population of Drosophila melanogaster. Of 21 pairwise tests involving 7 restriction map polymorphisms in the yellow-achaete-scute complex, 17 were found to be significant, including some between restriction sites over 80 kb apart. Three-way linkage disequilibria and their variances were also estimated for all 35 three-way comparisons between these loci. Twelve such tests were found to be significant, again spanning distances of up to 80 kb on the restriction map. Only 9 of a possible 128 haplotypes were represented in the sample and 8 of these could be linked together by changes at a single site. The strength of these associations at y-ac-sc is unusual by comparison with studies on other regions of the genome of D. melanogaster, and is consistent with the very low level of recombination which has been reported for the complex. However, our estimate of nucleotide diversity in the region is not significantly different from those made for some other loci in this species. PMID:2121592

  17. 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

  18. Population- and genome-specific patterns of linkage disequilibrium and SNP variation in spring and winter wheat (Triticum aestivum L.)

    PubMed Central

    2010-01-01

    Background 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 population structure in a panel of 478 spring and winter wheat cultivars (Triticum aestivum) from 17 populations across the United States and Mexico. Results Most of the wheat oligo pool assay (OPA) SNPs that were polymorphic within the complete set of 478 cultivars were also polymorphic in all subpopulations. Higher levels of genetic differentiation were observed among wheat lines within populations than among populations. A total of nine genetically distinct clusters were identified, suggesting that some of the pre-defined populations shared significant proportion of genetic ancestry. Estimates of population structure (FST) at individual loci showed a high level of heterogeneity across the genome. In addition, seven genomic regions with elevated FST were detected between the spring and winter wheat populations. Some of these regions overlapped with previously mapped flowering time QTL. Across all populations, the highest extent of significant LD was observed in the wheat D-genome, followed by lower LD in the A- and B-genomes. The differences in the extent of LD among populations and genomes were mostly driven by differences in long-range LD ( > 10 cM). Conclusions Genome- and population-specific patterns of genetic differentiation and LD were discovered in the populations of wheat cultivars from different geographic regions. Our study demonstrated that the estimates of population structure between spring and winter wheat lines can identify genomic regions harboring candidate genes involved in the regulation of growth habit. Variation in LD suggests that breeding and selection had a different impact on each wheat genome both within and among populations. The

  19. Linkage disequilibrium between polymorphisms at the 5{prime} untranslated region and intron 5 (Dde I) of the antithrombin III (ATIII) gene in the Chinese

    SciTech Connect

    Tay, J.S.H.; Liu, Y.; Low, P.S.

    1994-09-01

    A length polymorphism at the 5{prime} untranslated region of exon 1 and an RFLP (Dde I) in intron 5 (nt 160) of the ATIII gene were amplified by polymerase chain reaction with primers of published sequences. DNA fragments were size-fractionated by agarose gel electrophoresis (3% NuSieve and 1% Seakem GTG) and photographed over a UV transilluminator. A strong linkage disequilibrium was observed between these two polymorphisms of the ATIII gene in the Chinese ({chi}{sup 2} = 63.7; {triangle} 0.42, P < 0.001). The estimated frequencies of the three haplotypes were found to be 0.37 for SD+, 0.40 for LD+ and 0.23 for LD-.

  20. Beta s gene in Central Iran is in linkage disequilibrium with the Indian-Arab haplotype.

    PubMed

    Rahgozar, S; Poorfathollah, A A; Moafi, A R; Old, J M

    2000-11-01

    Sickle cell anemia is not considered to be a significant disease in Iran, although the sickle cell trait is estimated to have a high incidence in the Southern provinces. Since 1977, when the presence of a mild sickle cell anemia was reported in this country, there have been no further investigations published giving precise data on the incidence and origins of the sickle cell mutation in Iran. We report here the finding of patients with the sickle cell trait, sickle cell anemia, and sickle-beta thalassemia in Central Iran. A survey of 300 individuals from a village in Southeast Esfahan revealed an incidence of the sickle cell trait of 8.33%. "Cascade screening" enabled 96 relatives in four surrounding villages to be tested, and the at-risk couples were offered counseling as a "sickle cell control program." The hematological indices and HbF levels of the affected patients were determined. The HbF levels were unusually high, ranging from 18% to 41.4%, and SS patients with the highest levels were asymptomatic. Linkage analysis revealed the betaS gene haplotype in this population to be the Indian-Arab haplotype.

  1. Linkage analysis of human leukocyte antigen (HLA) markers in familial psoriasis: strong disequilibrium effects provide evidence for a major determinant in the HLA-B/-C region.

    PubMed Central

    Jenisch, S; Henseler, T; Nair, R P; Guo, S W; Westphal, E; Stuart, P; Krönke, M; Voorhees, J J; Christophers, E; Elder, J T

    1998-01-01

    Although psoriasis is strongly associated with certain human leukocyte antigens (HLAs), evidence for linkage to HLA markers has been limited. The objectives of this study were (1) to provide more definitive evidence for linkage of psoriasis to HLA markers in multiplex families; (2) to compare the major HLA risk alleles in these families with those determined by previous case-control studies; and (3) to localize the gene more precisely. By applying the transmission/disequilibrium test (TDT) and parametric linkage analysis, we found evidence for linkage of psoriasis to HLA-C, -B, -DR, and -DQ, with HLA-B and -C yielding the most-significant results. Linkage was detectable by parametric methods only when marker-trait disequilibrium was considered. Case-control association tests and the TDT identified alleles belonging to the EH57.1 ancestral haplotype as the major risk alleles in our sample. Among individuals carrying recombinant ancestral haplotypes involving EH57. 1, the class I markers were retained selectively among affecteds four times more often than among unaffecteds; among the few affected individuals carrying only the class II alleles from the ancestral haplotype, all but one also carried Cw6. These data show that familial and "sporadic" psoriasis share the same risk alleles. They also illustrate that substantial parametric linkage information can be extracted by accounting for linkage disequilibrium. Finally, they strongly suggest that a major susceptibility gene resides near HLA-C. PMID:9634500

  2. Chromosome 11-q24 region in Tourette syndrome: association and linkage disequilibrium study in the French Canadian population.

    PubMed

    Díaz-Anzaldúa, Adriana; Rivière, Jean-Baptiste; Dubé, Marie-Pierre; Joober, Ridha; Saint-Onge, Judith; Dion, Yves; Lespérance, Paul; Richer, Francois; Chouinard, Sylvain; Rouleau, Guy Armand

    2005-10-15

    Previous studies have found association and linkage between Tourette syndrome (TS) and markers at the 11q24 region, mainly with markers D11S1377 and D11S933. In order to determine if these positive findings could be replicated in our sample, we undertook a family-based association study in 199 French Canadian TS nuclear families. We genotyped 572 individuals from 174 complete and 25 incomplete TS trios. TDT analysis failed to detect an association between TS and six markers from 11q24. Furthermore, no haplotype combining alleles from D11S1377, D11S933, or any of the other four markers was associated with the disorder. Linkage disequilibrium analysis showed evidence of historical recombination between every contiguous pair of markers, indicating that these genetic variants are probably in equilibrium in the French Canadian population. Further analysis in additional families, with different methodologies (linkage and association) will be required in order to determine if the 11q24 region harbors a susceptibility locus for TS. If it does, this defect may not be frequent in the French Canadian population due to locus heterogeneity.

  3. 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

  4. Identification of Single Nucleotide Polymorphisms and analysis of Linkage Disequilibrium in sunflower elite inbred lines using the candidate gene approach

    PubMed Central

    Fusari, Corina M; Lia, Verónica V; Hopp, H Esteban; Heinz, Ruth A; Paniego, Norma B

    2008-01-01

    Background Association analysis is a powerful tool to identify gene loci that may contribute to phenotypic variation. This includes the estimation of nucleotide diversity, the assessment of linkage disequilibrium structure (LD) and the evaluation of selection processes. Trait mapping by allele association requires a high-density map, which could be obtained by the addition of Single Nucleotide Polymorphisms (SNPs) and short insertion and/or deletions (indels) to SSR and AFLP genetic maps. Nucleotide diversity analysis of randomly selected candidate regions is a promising approach for the success of association analysis and fine mapping in the sunflower genome. Moreover, knowledge of the distance over which LD persists, in agronomically meaningful sunflower accessions, is important to establish the density of markers and the experimental design for association analysis. Results A set of 28 candidate genes related to biotic and abiotic stresses were studied in 19 sunflower inbred lines. A total of 14,348 bp of sequence alignment was analyzed per individual. In average, 1 SNP was found per 69 nucleotides and 38 indels were identified in the complete data set. The mean nucleotide polymorphism was moderate (θ = 0.0056), as expected for inbred materials. The number of haplotypes per region ranged from 1 to 9 (mean = 3.54 ± 1.88). Model-based population structure analysis allowed detection of admixed individuals within the set of accessions examined. Two putative gene pools were identified (G1 and G2), with a large proportion of the inbred lines being assigned to one of them (G1). Consistent with the absence of population sub-structuring, LD for G1 decayed more rapidly (r2 = 0.48 at 643 bp; trend line, pooled data) than the LD trend line for the entire set of 19 individuals (r2 = 0.64 for the same distance). Conclusion Knowledge about the patterns of diversity and the genetic relationships between breeding materials could be an invaluable aid in crop improvement

  5. Systematic linkage disequilibrium analysis of SLC12A8 at PSORS5 confirms a role in susceptibility to psoriasis vulgaris.

    PubMed

    Hüffmeier, Ulrike; Lascorz, Jesús; Traupe, Heiko; Böhm, Beate; Schürmeier-Horst, Funda; Ständer, Markward; Kelsch, Reinhard; Baumann, Claudia; Küster, Wolfgang; Burkhardt, Harald; Reis, André

    2005-11-01

    The gene for solute carrier family 12 member A8 has recently been proposed as a candidate gene for psoriasis susceptibility (PSORS5) on chromosome 3q based on association of five single nucleotide polymorphisms (SNP) in Swedish patients. To investigate whether this locus is relevant for German psoriasis vulgaris (PsV) patients, we analyzed a group of 210 trios and a case-control group including 375 patients. Based on our investigation of the linkage disequilibrium (LD) structure of SLC12A8, we assayed 35 haplotype tag SNP and grouped them into nine LD-blocks. In the case-control study, we detected an association for six SNP and three LD-based haplotypes. Association was strongest for ss35527511 (chi2 = 11.224, p = 0.0008) and haplotype E-2 (chi2 = 11.788, p = 0.00059) and independent of the presence of an HLA-associated PSORS1 risk allele. Through extended haplotype analysis, we could show that two independent association signals exist in SLC12A8, suggesting allelic heterogeneity. None of the SNP showed association in trios, apart from a weak association of rs2228674 (transmission disequilibrium test statistics p = 0.048), probably due to insufficient power. We conclude that SLC12A8 is a susceptibility locus for PsV. In order to establish the exact nature of this association, efforts to identify the disease-causing variants are ongoing.

  6. 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.

  7. Modeling how reproductive ecology can drive protein diversification and result in linkage disequilibrium between sperm and egg proteins.

    PubMed

    Tomaiuolo, Maurizio; Levitan, Don R

    2010-07-01

    Gamete-recognition proteins determine whether sperm and eggs are compatible at fertilization, and they often evolve rapidly. The source of selection driving the evolution of these proteins is still debated. It has been suggested that sexual conflict can result in proliferation of genetic variation and possibly linkage disequilibrium between sperm and egg proteins. Empirical evidence suggests that both male and female reproductive success can be predicted by their sperm ligand genotype, but why female success can be predicted by a protein expressed only in males is unknown. Here we use mathematical modeling to investigate the interaction between reproductive behavior and sperm availability on the evolution of sperm ligands and egg receptors. We consider haploid and diploid expression in gametes in two possible ecological scenarios, monogamous spawning and competitive spawning. Reproductive behavior plays an important role in determining possible outcomes resulting from sexual conflict. Sperm limitation selects for common genotypes regardless of mating behavior. Under conditions of sperm abundance, competitive spawning provides conditions for the persistence of allelic variation and gametic disequilibrium. With monogamous spawning, such conditions are more restrictive.

  8. Linkage Disequilibrium and Haplotype Studies of Chromosome 8p 11.1-21.1 Markers and Werner Syndrome

    PubMed Central

    Yu, Chang-En; Oshima, Junko; Goddard, Katrina A. B.; Miki, Tetsuro; Nakura, Jun; Ogihara, Toshio; Poot, Martin; Hoehn, Holger; Fraccaro, Marco; Piussan, Charles; Martin, George M.; Schellenberg, Gerard D.; Wijsman, Ellen M.

    1994-01-01

    Werner syndrome (WS) is an autosomal recessive disorder, characterized as a progeroid syndrome, previously mapped to the 8p 11.1-21.1 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 we 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. We 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 ∼16.5 cM in total. We 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, we 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. PMID:8037212

  9. Major factors influencing linkage disequilibrium by analysis of different chromosome regions in distinct populations: demography, chromosome recombination frequency and selection.

    PubMed

    Zavattari, P; Deidda, E; Whalen, M; Lampis, R; Mulargia, A; Loddo, M; Eaves, I; Mastio, G; Todd, J A; Cucca, F

    2000-12-12

    Linkage disequilibrium (LD) mapping of disease genes is complicated by population- and chromosome-region-specific factors. We have analysed demographic factors by contrasting intermarker LD results obtained in a large cosmopolitan population (UK), a large genetic isolate (Sardinia) and a subisolate (village of Gavoi) for two regions of the X chromosome. A dramatic increase of LD was found in the subisolate. Demographic history of populations therefore influences LD. Chromosome-region-specific effects, namely the pattern and frequency of homologous recombination, were next delineated by the analysis of chromosome 6p21, including the HLA region. Patterns of global LD in this region were very similar in the UK and Sardinian populations despite their entirely distinct demographies, and correlate well with the pattern of recombinations. Nevertheless, haplotypes extend across recombination hot spots indicative of selection of certain haplotypes. Subisolate aside, chromosome-region-specific differences in LD patterns appear to be more important than the differences in intermarker LD between distinct populations.

  10. Patterns of Naturally Occurring Restriction Map Variation, Dopa Decarboxylase Activity Variation and Linkage Disequilibrium in the Ddc Gene Region of Drosophila Melanogaster

    PubMed Central

    Aquadro, C. F.; Jennings-Jr, R. M.; Bland, M. M.; Laurie, C. C.; Langley, C. H.

    1992-01-01

    Forty-six second-chromosome lines of Drosophila melanogaster isolated from five natural populations were surveyed for restriction map variation in a 65-kb region surrounding the gene (Ddc) encoding dopa decarboxylase (DDC). Sixty-nine restriction sites were scored, 13 of which were polymorphic. Average heterozygosity per nucleotide was estimated to be 0.005. Eight large (0.7-5.0 kb) inserts, two small inserts (100 and 200 bp) and three small deletions (100-300 bp) were also observed across the 65-kb region. We see no evidence for a reduction in either nucleotide heterozygosity or insertion/deletion variation in the central 26-kb segment containing Ddc and a dense cluster of lethal complementation groups and transcripts (>/=9 genes) compared to that seen in the adjacent regions (totaling 39 kb) in which only a single gene and transcript has been detected, or to that observed for other gene regions in D. melanogaster. The distribution of restriction site variation shows no significant departure from that expected under an equilibrium neutral model. However insertions and deletions show a significant departure from neutrality in that they are too rare in frequency, consistent with them being deleterious on average. Significant linkage disequilibrium among variants exists across much of the 65-kb region. Lower regional rates of recombination combined with the influence of polymorphic chromosomal inversions, rather than epistatic selection among genes in the dense cluster, probably are sufficient explanations for the creation and/or maintenance of the linkage disequilibrium observed in the Ddc region. We have also assayed adult DDC enzyme activity in these same lines. Twofold variation in activity among lines is observed within our sample. Significant associations are observed between level of DDC enzyme activity and restriction map variants. Surprisingly, one line with a 5.0-kb insert within an intron and one line with a 1.5-kb insert near the 5' end of Ddc each show

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

    PubMed Central

    Trachtenberg, E A; Erlich, H A; Rickards, O; DeStefano, G F; Klitz, W

    1995-01-01

    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 evenness 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. PMID:7668268

  12. 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...

  13. Linkage disequilibrium levels in Bos indicus and Bos taurus cattle using medium and high density SNP chip data and different minor allele frequency distributions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Linkage disequilibrium (LD), the observed correlation between alleles at different loci in the genome, is a determinant parameter in many applications of molecular genetics. With the wider use of genomic technologies in animal breeding and animal genetics, it is worthwhile revising and improving the...

  14. Assortative mating drives linkage disequilibrium between sperm and egg recognition protein loci in the sea urchin Strongylocentrotus purpuratus.

    PubMed

    Stapper, Andres Plata; Beerli, Peter; Levitan, Don R

    2015-04-01

    Sperm and eggs have interacting proteins on their surfaces that influence their compatibility during fertilization. These proteins are often polymorphic within species, producing variation in gamete affinities. We first demonstrate the fitness consequences of various sperm bindin protein (Bindin) variants in the sea urchin Strongylocentrotus purpuratus, and assortative mating between males and females based on their sperm Bindin genotype. This empirical finding of assortative mating based on sperm Bindin genotype could arise by linkage disequilibrium (LD) between interacting sperm and egg recognition loci. We then examine sequence variation in eight exons of the sea urchin egg receptor for sperm Bindin (EBR1). We find little evidence of LD among the eight exons of EBR1, yet strong evidence for LD between sperm Bindin and EBR1 overall, and varying degrees of LD between sperm Bindin among the eight exons. We reject the alternate hypotheses of LD driven by shared evolutionary histories, population structure, or close physical linkage between these interacting loci on the genome. The most parsimonious explanation for this pattern of LD is that it represents selection driven by assortative mating based on interactions among these sperm and egg loci. These findings indicate the importance of ongoing sexual selection in the maintenance of protein polymorphisms and LD, and more generally highlight how LD can be used as an indication of current mate choice, as opposed to historic selection.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. The impact of incomplete linkage disequilibrium and genetic model choice on the analysis and interpretation of genome-wide association studies.

    PubMed

    Iles, Mark M

    2010-07-01

    When conducting a genetic association study, it has previously been observed that a multiplicative risk model tends to fit better at a disease-associated marker locus than at the ungenotyped causative locus. This suggests that, while overall risk decreases as linkage disequilibrium breaks down, non-multiplicative components are more affected. This effect is investigated here, in particular the practical consequences it has on testing for trait/marker associations and the estimation of mode of inheritance and risk once an associated locus has been found. The extreme significance levels required for genome-wide association studies define a restricted range of detectable allele frequencies and effect sizes. For such parameters there is little to be gained by using a test that models the correct mode of inheritance rather than the multiplicative; thus the Cochran-Armitage trend test, which assumes a multiplicative model, is preferable to a more general model as it uses fewer degrees of freedom. Equally when estimating risk, it is likely that a multiplicative risk model will provide a good fit to the data, regardless of the underlying mode of inheritance at the true susceptibility locus. This may lead to problems in interpreting risk estimates.

  20. Linkage disequilibrium analysis by searching for shared segments: Mapping a locus for benign recurrent intrahepatic cholestasis (BRIC)

    SciTech Connect

    Freimer, N.; Baharloo, S.; Blankenship, K.

    1994-09-01

    The lod score method of linkage analysis has two important drawbacks: parameters must be specified for the transmission of the disease (e.g. penetrance), and large numbers of genetically informative individuals must be studied. Although several robust non-parametric methods are available, these also require large sample sizes. The availability of dense genetic maps permits genome screening to be conducted by linkage disequilibrium (LD) mapping methods, which are statistically powerful and non-parametric. Lander & Botstein proposed that LD mapping could be employed to screen the human genome for disease loci; we have now applied this strategy to map a gene for an autosomal recessive disorder, benign recurrent intrahepatic cholestatis (BRIC). Our approach to LD mapping was based on identifying chromosome segments shared between distantly related patients; we used 256 microsatellite markers to genotype three affected individuals, and their parents, from an isolated town in The Netherlands. Because endogamy occurred in this population for several generations, all of the BRIC patients are known to be distantly related to each other, but the pedigree structure and connections could not be certainly established more than three generations before the present, so lod score analysis was impossible. A 20 cM region on chromosome 18 is shared by 5/6 patient chromosomes; subsequently, we noted that 6/6 chromosomes shared an interval of about 3 cM in this region. Calculations indicate that it is extremely unlikely that such a region could be inherited by chance rather than by descent from a common ancestor. Thus, LD mapping by searching for shared chromosomal segments is an extremely powerful approach for genome screening to identify disease loci.

  1. 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

  2. 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.

  3. Chromosome-wide linkage disequilibrium caused by an inversion polymorphism in the white-throated sparrow (Zonotrichia albicollis).

    PubMed

    Huynh, L Y; Maney, D L; Thomas, J W

    2011-04-01

    Chromosomal inversions have been of long-standing interest to geneticists because they are capable of suppressing recombination and facilitating the formation of adaptive gene complexes. An exceptional inversion polymorphism (ZAL2(m)) in the white-throated sparrow (Zonotrichia albicollis) is linked to variation in plumage, social behavior and mate choice, and is maintained in the population by negative assortative mating. The ZAL2(m) polymorphism is a complex inversion spanning > 100 Mb and has been proposed to be a strong suppressor of recombination, as well as a potential model for studying neo-sex chromosome evolution. To quantify and evaluate these features of the ZAL2(m) polymorphism, we generated sequence from 8 ZAL2(m) and 16 ZAL2 chromosomes at 58 loci inside and 4 loci outside the inversion. Inside the inversion we found that recombination was completely suppressed between ZAL2 and ZAL2(m), resulting in uniformly high levels of genetic differentiation (F(ST)=0.94), the formation of two distinct haplotype groups representing the alternate chromosome arrangements and extensive linkage disequilibrium spanning ~104 Mb within the inversion, whereas gene flow was not suppressed outside the inversion. Finally, although ZAL2(m) homozygotes are exceedingly rare in the population, occurring at a frequency of < 1%, we detected evidence of historical recombination between ZAL2(m) chromosomes inside the inversion, refuting its potential status as a non-recombining autosome.

  4. Sequence diversity, natural selection and linkage disequilibrium in the human T cell receptor alpha/delta locus.

    PubMed

    Mackelprang, Rachel; Livingston, Robert J; Eberle, Michael A; Carlson, Christopher S; Yi, Qian; Akey, Joshua M; Nickerson, Deborah A

    2006-04-01

    T cell receptors (TR), through their interaction with the major histocompatibility complex, play a central role in immune responsiveness and potentially immune-related disorders. We resequenced all 57 variable (V) genes in the human T cell receptor alpha and delta (TRA/TRD) locus in 40 individuals of Northern European, Mexican, African-American and Chinese descent. Two hundred and eighty-four single nucleotide polymorphisms (SNPs) were identified. The distribution of SNPs between V genes was heterogeneous, with an average of five SNPs per gene and a range of zero to 15. We describe the patterns of linkage disequilibrium for these newly discovered SNPs and compare these patterns with other emerging large-scale datasets (e.g. Perlegen and HapMap projects) to place our findings into a framework for future analysis of genotype-phenotype associations across this locus. Furthermore, we explore signatures of natural selection across V genes. We find evidence of strong directional selection at this locus as evidenced by unusually high values of Fst.

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

    SciTech Connect

    Labuda, M.; Glorieux, F.H.; Labuda, D.; Korab-Laskowska, M.

    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-Delbruck 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. 48 refs., 5 figs., 2 tabs.

  6. A genome-wide set of SNPs detects population substructure and long range linkage disequilibrium in wild sheep.

    PubMed

    Miller, J M; Poissant, J; Kijas, J W; Coltman, D W

    2011-03-01

    The development of genomic resources for wild species is still in its infancy. However, cross-species utilization of technologies developed for their domestic counterparts has the potential to unlock the genomes of organisms that currently lack genomic resources. Here, we apply the OvineSNP50 BeadChip, developed for domestic sheep, to two related wild ungulate species: the bighorn sheep (Ovis canadensis) and the thinhorn sheep (Ovis dalli). Over 95% of the domestic sheep markers were successfully genotyped in a sample of fifty-two bighorn sheep while over 90% were genotyped in two thinhorn sheep. Pooling the results from both species identified 868 single-nucleotide polymorphisms (SNPs), 570 were detected in bighorn sheep, while 330 SNPs were identified in thinhorn sheep. The total panel of SNPs was able to discriminate between the two species, assign population of origin for bighorn sheep and detect known relationship classes within one population of bighorn sheep. Using an informative subset of these SNPs (n=308), we examined the extent of genome-wide linkage disequilibrium (LD) within one population of bighorn sheep and found that high levels of LD persist over 4 Mb.

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

    PubMed Central

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

    1996-01-01

    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. Images Figure 2 Figure 4 PMID:8751865

  8. Development of an Alfalfa SNP Array and Its Use to Evaluate Patterns of Population Structure and Linkage Disequilibrium

    PubMed Central

    Li, Xuehui; Han, Yuanhong; Wei, Yanling; Acharya, Ananta; Farmer, Andrew D.; Ho, Julie; Monteros, Maria J.; Brummer, E. Charles

    2014-01-01

    A large set of genome-wide markers and a high-throughput genotyping platform can facilitate the genetic dissection of complex traits and accelerate molecular breeding applications. Previously, we identified about 0.9 million SNP markers by sequencing transcriptomes of 27 diverse alfalfa genotypes. From this SNP set, we developed an Illumina Infinium array containing 9,277 SNPs. Using this array, we genotyped 280 diverse alfalfa genotypes and several genotypes from related species. About 81% (7,476) of the SNPs met the criteria for quality control and showed polymorphisms. The alfalfa SNP array also showed a high level of transferability for several closely related Medicago species. Principal component analysis and model-based clustering showed clear population structure corresponding to subspecies and ploidy levels. Within cultivated tetraploid alfalfa, genotypes from dormant and nondormant cultivars were largely assigned to different clusters; genotypes from semidormant cultivars were split between the groups. The extent of linkage disequilibrium (LD) across all genotypes rapidly decayed to 26 Kbp at r2 = 0.2, but the rate varied across ploidy levels and subspecies. A high level of consistency in LD was found between and within the two subpopulations of cultivated dormant and nondormant alfalfa suggesting that genome-wide association studies (GWAS) and genomic selection (GS) could be conducted using alfalfa genotypes from throughout the fall dormancy spectrum. However, the relatively low LD levels would require a large number of markers to fully saturate the genome. PMID:24416217

  9. 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.

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

    SciTech Connect

    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, 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.

  11. Nucleotide Variation, Linkage Disequilibrium and Founder-Facilitated Speciation in Wild Populations of the Zebra Finch (Taeniopygia guttata)

    PubMed Central

    Balakrishnan, Christopher N.; Edwards, Scott V.

    2009-01-01

    The zebra finch has long been an important model system for the study of vocal learning, vocal production, and behavior. With the imminent sequencing of its genome, the zebra finch is now poised to become a model system for population genetics. Using a panel of 30 noncoding loci, we characterized patterns of polymorphism and divergence among wild zebra finch populations. Continental Australian populations displayed little population structure, exceptionally high levels of nucleotide diversity (π = 0.010), a rapid decay of linkage disequilibrium (LD), and a high population recombination rate (ρ ≈ 0.05), all of which suggest an open and fluid genomic background that could facilitate adaptive variation. By contrast, substantial divergence between the Australian and Lesser Sunda Island populations (KST = 0.193), reduced genetic diversity (π = 0.002), and higher levels of LD in the island population suggest a strong but relatively recent founder event, which may have contributed to speciation between these populations as envisioned under founder-effect speciation models. Consistent with this hypothesis, we find that under a simple quantitative genetic model both drift and selection could have contributed to the observed divergence in six quantitative traits. In both Australian and Lesser Sundas populations, diversity in Z-linked loci was significantly lower than in autosomal loci. Our analysis provides a quantitative framework for studying the role of selection and drift in shaping patterns of molecular evolution in the zebra finch genome. PMID:19047416

  12. The Genetic Diversity and Structure of Linkage Disequilibrium of the MTHFR Gene in Populations of Northern Eurasia

    PubMed Central

    Trifonova, E.A.; Eremina, E.R.; Urnov, F.D.; Stepanov, V.A.

    2012-01-01

    The structure of the haplotypes and linkage disequilibrium (LD) of the methylenetetrahydrofolate reductase gene (MTHFR) in 9 population groups from Northern Eurasia and populations of the international HapMap project was investigated in the present study. The data suggest that the architecture of LD in the human genome is largely determined by the evolutionary history of populations; however, the results of phylogenetic and haplotype analyses seems to suggest that in fact there may be a common “old” mechanism for the formation of certain patterns of LD. Variability in the structure of LD and the level of diversity of MTHFRhaplotypes cause a certain set of tagSNPs with an established prognostic significance for each population. In our opinion, the results obtained in the present study are of considerable interest for understanding multiple genetic phenomena: namely, the association of interpopulation differences in the patterns of LD with structures possessing a genetic susceptibility to complex diseases, and the functional significance of the pleiotropicMTHFR gene effect. Summarizing the results of this study, a conclusion can be made that the genetic variability analysis with emphasis on the structure of LD in human populations is a powerful tool that can make a significant contribution to such areas of biomedical science as human evolutionary biology, functional genomics, genetics of complex diseases, and pharmacogenomics. PMID:22708063

  13. 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

  14. [Nucleotide diversity and linkage disequilibrium of adaptive significant genes in Larix (Pinaceae)].

    PubMed

    Semerikov, V L; Semerikova, S A; Polezhaeva, M A

    2013-09-01

    Nucleotide polymorphism in genes potentially responsible for the adaptation to the latitudinal gradient of climate was investigated in the Siberian larch (Larix sibirica). The genes were selected among those previously studied in Douglas fir (Pseudotsuga menziesii), the variability of which indicates the influence of selection or shows the association with phenotypic traits that are important for adaptation to low temperatures and to geographically heterogeneous environment. Nucleotide sequences of eight genes, including coding and noncoding regions, were amplified and sequenced using newly developed primers specific to Larix. The sample size was 123 megagametophytes per locus in L. sibirica and 16.2 in L. occidentalis, which was taken as the out-group. The length of the sequenced fragments was 246-1700 bp. Nucleotide polymorphism π averaged 0.00536 (0.002 - 0.008), and haplotype diversity was H(d): 0.822 (0.625-0.948). Tajima's D was negative in all fragments and significant in three, while statistics D* and F* was significant in three and four segments, respectively, and F(s) was significant in three. This may indicate the presence of purifying selection on these genes or population growth. The HKA test revealed no significant deviations from the neutral model of evolution in all genes. The recombination parameter ρ/θ = 0.28 was close to the value obtained from P. menziesii. To investigate the association of polymorphic sites (factor) in these eight genes to the latitude of investigated individuals (trait), the generalized linear model (GLM) was used taking into account the population structure. After the False Discovery Rate correction no significant associations were found. The age of the split of American and Eurasian Larix lineages based on the nucleotide differences in the eight genes between L. sibirica and L. occidentalis is estimated to be 12 million years, which is much younger than the age of the most ancient Larix discoveries.

  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

    2015-06-11

    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.

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

    PubMed

    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

  17. 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

  18. 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

  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. Mapping the Rust Resistant Loci MXC3 and MER in P. trichocarpa and Assessing the Intermarker Linkage Disequilibrium in MXC3 Region

    SciTech Connect

    Yin, Tongming; Difazio, Stephen P.; Gunter, Lee E; Tuskan, Gerald A

    2004-01-01

    In an attempt to elucidate the molecular mechanisms of Melampsora rust resistance in Populus trichocarpa, we have mapped two resistance loci, MXC3 and MER, and intensively characterized the flanking genomic sequence for the MXC3 locus and the level of linkage disequilibrium (LD) in natural populations. We used an interspecific backcross pedigree and a genetic map that was highly saturated with AFLP and SSR markers, and assembled shotgun-sequence data in the region containing markers linked to MXC3. The two loci were mapped to different linkage groups. Linkage disequilibrium for MXC3 was confined to two closely linked regions spanning 34 and 16 kb, respectively. The MXC3 region also contained six disease-resistance candidate genes. The MER and MXC3 loci are clearly distinct, and may have different mechanisms of resistance, as different classes of putative resistance genes were present near each locus. The suppressed recombination previously observed in the MXC3 region was possibly caused by extensive hemizygous rearrangements confined to the original parent tree. The relatively low observed LD may facilitate association studies using candidate genes for rust resistance, but will probably inhibit marker-aided selection.

  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. Linkage disequilibrium between two distinct loci in chromosomes 5 and 7 of Plasmodium falciparum and in vivo chloroquine resistance in Southwest Nigeria.

    PubMed

    Happi, C T; Gbotosho, G O; Folarin, O A; Sowunmi, A; Bolaji, O M; Fateye, B A; Kyle, D E; Milhous, W; Wirth, D F; Oduola, A M J

    2006-12-01

    Chloroquine (CQ) resistance in Plasmodium falciparum is associated with polymorphisms in loci on pfcrt and pfmdr1 genes. In this study, we determined the association and linkage disequilibrium between in vivo CQ resistance and P. falciparum polymorphisms in pfcrt gene at codon 76 and pfmdr1 gene at codon 86 in isolates obtained from 111 children with acute uncomplicated falciparum malaria in Nigeria. Patients were treated with standard dosage of CQ and followed up for 28 days. Filter paper samples were collected at enrollment and during follow-up for parasites genotypes and identification of pfcrt and pfmdr1 mutations. Association and linkage disequilibrium between mutant pfcrtT76 and pfmdr1Y86 alleles in pretreatment isolates of P. falciparum was determined. Fifty-five out of the 111 patients (49.5%) failed treatment. Single mutant pfcrtT76 or pfmdr1Y86 alleles were found in 55 out of 111 P. falciparum isolates screened at enrollment. Of these 55 isolates, the mutant pfcrtT76 and pfmdr1Y86 alleles were found in 84%. Both mutant pfcrtT76 (p=0.0196) and pfmdr1Y86 (p=0.000042) alleles were associated with in vivo CQ resistance. In addition, the mutant pfcrtT76 (p=0.047) and pfmdr1Y86 (p=0.006) alleles were significantly selected by CQ in patients who failed treatment. Association analysis between paired single alleles at pfcrt and pfmdr1 loci showed a significant association (p=0.0349 and chi(2)=4.45) between the pfcrt T76 allele on chromosome 7 and the pfmdr1Y86 allele on chromosome 5 and that these two mutant alleles were in linkage disequilibrium (p=0.000, D'=0.64, and r(2)=0.28). Considering the high level of CQ resistance and drug use in the study area, the observed linkage disequilibrium between the mutant pfcrtT76 and pfmdr1Y86 alleles is maintained epistatically through directional CQ selective pressure.

  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. Linkage disequilibrium between BLM, FES, D15S127, and IP15M9 in Ashkenazi Jews with Bloom`s syndrome (BS)

    SciTech Connect

    German, J.; Lennon, D.; Proytcheva, M.

    1994-09-01

    BS is more common in the Ashkenazi Jewish than in any other population. About 1 in 110 Ashkenazi Jews carries bbm, a BS mutation. The locus mutated in BS, BLM, maps to chromosome sub-band 15q26.1, tightly linked to the proto-oncogene FES. We have investigated the basis for the increased frequency of bbm in the Ashkenazim by genotyping polymorphic microsatellite loci tightly linked to BLM in affected and unaffected individuals from Ashkenazi Jewish and non-Ashkenazi populations. A striking linkage disequilibrium has been observed between BLM and FES, D15S127, and IP15M9 -- three loci unseparated by conventional pedigree analysis. The linkage disequilibrium constitutes strong support for a founder-effect hypothesis. We have also analyzed blm and BLM haplotypes when genotype information from the parents was available. The haplotype analysis indicates that the chromosome in the hypothetical founder carried the C3 allele at FES, either the 145 bp or the 147 bp allele at D15S127, and the 83 bp allele at IP15M9. Besides providing strong support for the founder-effect hypothesis, haplotype analysis in a fetus at risk for BS also provided evidence against either homozygosity or heterozygosity for mutation at BLM -- evidence shown valuable by the subsequent birth of a normal boy to a couple, the father being Ashkenazi Jewish and the mother being Sephardi-Egyptian Jewish.

  5. The use of family relationships and linkage disequilibrium to impute phase and missing genotypes in up to whole-genome sequence density genotypic data.

    PubMed

    Meuwissen, Theo; Goddard, Mike

    2010-08-01

    A novel method, called linkage disequilibrium multilocus iterative peeling (LDMIP), for the imputation of phase and missing genotypes is developed. LDMIP performs an iterative peeling step for every locus, which accounts for the family data, and uses a forward-backward algorithm to accumulate information across loci. Marker similarity between haplotype pairs is used to impute possible missing genotypes and phases, which relies on the linkage disequilibrium between closely linked markers. After this imputation step, the combined iterative peeling/forward-backward algorithm is applied again, until convergence. The calculations per iteration scale linearly with number of markers and number of individuals in the pedigree, which makes LDMIP well suited to large numbers of markers and/or large numbers of individuals. Per iteration calculations scale quadratically with the number of alleles, which implies biallelic markers are preferred. In a situation with up to 15% randomly missing genotypes, the error rate of the imputed genotypes was <1% and approximately 99% of the missing genotypes were imputed. In another example, LDMIP was used to impute whole-genome sequence data consisting of 17,321 SNPs on a chromosome. Imputation of the sequence was based on the information of 20 (re)sequenced founder individuals and genotyping their descendants for a panel of 3000 SNPs. The error rate of the imputed SNP genotypes was 10%. However, if the parents of these 20 founders are also sequenced, >99% of missing genotypes are imputed correctly.

  6. Combined linkage and linkage disequilibrium QTL mapping in multiple families of maize (Zea mays L.) line crosses highlights complementarities between models based on parental haplotype and single locus polymorphism.

    PubMed

    Bardol, N; Ventelon, M; Mangin, B; Jasson, S; Loywick, V; Couton, F; Derue, C; Blanchard, P; Charcosset, A; Moreau, Laurence

    2013-11-01

    Advancements in genotyping are rapidly decreasing marker costs and increasing marker density. This opens new possibilities for mapping quantitative trait loci (QTL), in particular by combining linkage disequilibrium information and linkage analysis (LDLA). In this study, we compared different approaches to detect QTL for four traits of agronomical importance in two large multi-parental datasets of maize (Zea mays L.) of 895 and 928 testcross progenies composed of 7 and 21 biparental families, respectively, and genotyped with 491 markers. We compared to traditional linkage-based methods two LDLA models relying on the dense genotyping of parental lines with 17,728 SNP: one based on a clustering approach of parental line segments into ancestral alleles and one based on single marker information. The two LDLA models generally identified more QTL (60 and 52 QTL in total) than classical linkage models (49 and 44 QTL in total). However, they performed inconsistently over datasets and traits suggesting that a compromise must be found between the reduction of allele number for increasing statistical power and the adequacy of the model to potentially complex allelic variation. For some QTL, the model exclusively based on linkage analysis, which assumed that each parental line carried a different QTL allele, was able to capture remaining variation not explained by LDLA models. These complementarities between models clearly suggest that the different QTL mapping approaches must be considered to capture the different levels of allelic variation at QTL involved in complex traits.

  7. Estimation of recombination frequency in genetic linkage studies.

    PubMed

    Nordheim, E V; O'Malley, D M; Guries, R P

    1983-09-01

    A binomial-like model is developed that may be used in genetic linkage studies when data are generated by a testcross with parental phase unknown. Four methods of estimation for the recombination frequency are compared for data from a single group and also from several groups; these methods are maximum likelihood, two Bayesian procedures, and an ad hoc technique. The Bayes estimator using a noninformative prior usually has a lower mean squared error than the other estimators and because of this it is the recommended estimator. This estimator appears particularly useful for estimation of recombination frequencies indicative of weak linkage from samples of moderate size. Interval estimates corresponding to this estimator can be obtained numerically by discretizing the posterior distribution, thereby providing researchers with a range of plausible recombination values. Data from a linkage study on pitch pine are used as an example.

  8. Linkage disequilibrium between alleles at highly polymorphic mini- and micro-satellite loci of Theileria parva isolated from cattle in three regions of Kenya.

    PubMed

    Odongo, D O; Oura, C A L; Spooner, P R; Kiara, H; Mburu, D; Hanotte, O H; Bishop, R P

    2006-07-01

    Theileria parva schizont-infected lymphocyte culture isolates from western, central and coastal Kenya were analysed for size polymorphism at 30 T. parva-specific variable number tandem repeat (VNTR) loci using a panel of mini- and micro-satellite markers. The mean number of alleles ranged from 3 to 11 at individual loci and 183 distinct alleles were observed in total, indicating high genetic diversity within the T. parva gene pool in Kenyan cattle. The frequency distribution of the length variation of specific alleles among isolates ranged from normal to markedly discontinuous. Genetic relationships between isolates were analysed using standard indices of genetic distance. Genetic distances and dendrograms derived from these using neighbour-joining algorithms did not indicate significant clustering on a geographical basis. Analysis of molecular variance demonstrated that the genetic variation between individual isolates was 72%, but only 2.3% when isolates from different regions were pooled. Both these observations suggest minimal genetic sub-structuring relative to geographical origin. Linkage disequilibrium was observed between pairs of loci within populations, as in certain Ugandan T. parva populations. A novel observation was that disequilibrium was also detected between alleles at three individual pairs of VNTR loci when isolates from the three regional meta-populations were pooled for analysis.

  9. The genetic differences with whole genome linkage disequilibrium mapping between responder and non-responder in interferon-alpha and ribavirin combined therapy for chronic hepatitis C patients.

    PubMed

    Chen, P-J; Hwang, Y; Lin, C G-J; Wu, Y-J; Wu, L S-H

    2008-04-01

    Interferon-alpha and ribavirin combined therapy has been a mainstream treatment for hepatitis C infection. The efficacy of this combined treatment is around 30% to 60%, and the factors affecting the responsiveness are still poorly defined. Our study is intended to investigate the genetic differences between responder and non-responder patients. The genome-wide linkage disequilibrium screening for loci associated with genetic difference between two patient groups was conducted by using 382 autosomal short tandem repeat (STR) markers involving 92 patients. We have identified 19 STR markers displaying different allele frequencies between the two patient groups. In addition, based on their genomic location and biological function, we selected the CD81 and IL15 genes to perform single nucleotide polymorphism genotyping. In conclusion, this study may provide a new approach for identifying the associated polymorphisms and the susceptible loci for interferon-alpha and ribavirin combined therapy in patients with chronic hepatitis C.

  10. High levels of linkage disequilibrium and associations with forage quality at a phenylalanine ammonia-lyase locus in European maize (Zea mays L.) inbreds.

    PubMed

    Andersen, Jeppe R; Zein, Imad; Wenzel, Gerhard; Krützfeldt, Birte; Eder, Joachim; Ouzunova, Milena; Lübberstedt, Thomas

    2007-01-01

    Forage quality of maize is influenced by both the content and structure of lignin in the cell wall. Phenylalanine Ammonia-Lyase (PAL) catalyzes the first step in lignin biosynthesis in plants; the deamination of L-phenylalanine to cinnamic acid. Successive enzymatic steps lead to the formation of three monolignols, constituting the complex structure of lignin. We have cloned and sequenced a PAL genomic sequence from 32 maize inbred lines currently employed in forage maize breeding programs in Europe. Low nucleotide diversity and excessive linkage disequilibrium (LD) was identified at this PAL locus, possibly reflecting selective constrains resulting from PAL being the first enzyme in the monolignol, and other, pathways. While the association analysis was affected by extended LD and population structure, several individual polymorphisms were associated with neutral detergent fiber (not considering population structure) and a single polymorphism was associated with in vitro digestibility of organic matter (considering population structure).

  11. 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.

  12. Quantitative linkage: a statistical procedure for its detection and estimation.

    PubMed

    Hill, A P

    1975-05-01

    A new approach for detecting and estimating quantitative linkage which uses sibship data is presented. Using a nested analysis of variance design (with marker genotype nested within sibship), it is shown that under the null hypothesis of no linkage, the expected between marker genotype within sibship mean square (EMSbeta) is equal to the expected within marker genotype within sibship mean square (EMSe), while under the alternative hypothesis of linkage, the first is greater than the second. Thus the regular F-ratio, MSbeta/MSe, can be used to test for quantitative linkage. This is true for both backcross and intercross matings and whether or not there is dominance at the marker locus. A second test involving the comparison of the within marker genotype within sibship variances is available for intercross matings. A maximum likelihood procedure for the estimation for the recombination frequency is also presented.

  13. 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.

  14. 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.

  15. Estimating the recombination frequency for the PTC-Kell linkage.

    PubMed

    Anne-Spence, M; Falk, C T; Neiswanger, K; Field, L L; Marazita, M L; Allen, F H; Siervogel, R M; Roche, A F; Crandall, B F; Sparkes, R S

    1984-01-01

    Two data sets are analyzed for linkage between the PTC and Kell blood group loci. The original report of close linkage for these loci was that of Conneally et al. (1976), where the maximum likelihood estimate of theta was 0.05. These two new data sets give a combined maximum likelihood estimate of theta m = f = 0.28. Estimating the recombination frequency for the sexes separately gave theta m = 0.29, theta f = 0.23. The combined maximum likelihood estimate over all published data sets including this report is theta m = f = 0.14, Zmax = 8.94. There is statistically significant evidence of heterogeneity among the published studies.

  16. Genome wide linkage disequilibrium in Chinese asparagus bean (Vigna. unguiculata ssp. sesquipedialis) germplasm: implications for domestication history and genome wide association studies.

    PubMed

    Xu, P; Wu, X; Wang, B; Luo, J; Liu, Y; Ehlers, J D; Close, T J; Roberts, P A; Lu, Z; Wang, S; Li, G

    2012-07-01

    Association mapping of important traits of crop plants relies on first understanding the extent and patterns of linkage disequilibrium (LD) in the particular germplasm being investigated. We characterize here the genetic diversity, population structure and genome wide LD patterns in a set of asparagus bean (Vigna. unguiculata ssp. sesquipedialis) germplasm from China. A diverse collection of 99 asparagus bean and normal cowpea accessions were genotyped with 1127 expressed sequence tag-derived single nucleotide polymorphism markers (SNPs). The proportion of polymorphic SNPs across the collection was relatively low (39%), with an average number of SNPs per locus of 1.33. Bayesian population structure analysis indicated two subdivisions within the collection sampled that generally represented the 'standard vegetable' type (subgroup SV) and the 'non-standard vegetable' type (subgroup NSV), respectively. Level of LD (r(2)) was higher and extent of LD persisted longer in subgroup SV than in subgroup NSV, whereas LD decayed rapidly (0-2 cM) in both subgroups. LD decay distance varied among chromosomes, with the longest (≈ 5 cM) five times longer than the shortest (≈ 1 cM). Partitioning of LD variance into within- and between-subgroup components coupled with comparative LD decay analysis suggested that linkage group 5, 7 and 10 may have undergone the most intensive epistatic selection toward traits favorable for vegetable use. This work provides a first population genetic insight into domestication history of asparagus bean and demonstrates the feasibility of mapping complex traits by genome wide association study in asparagus bean using a currently available cowpea SNPs marker platform.

  17. Linkage disequilibrium between the M470V variant and the IVS8 polyT alleles of the CFTR gene in CBAVD.

    PubMed Central

    de Meeus, A; Guittard, C; Desgeorges, M; Carles, S; Demaille, J; Claustres, M

    1998-01-01

    Congenital bilateral absence of the vas deferens (CBAVD) is a cause of male sterility mostly resulting from mutations in the cystic fibrosis transmembrane regulator (CFTR) gene. The most common defect is the 5T variant at the branch/acceptor site of intron 8, which induces high levels of exon 9 skipping leading to non-functional protein. However, this 5T variant has incomplete penetrance and variable expressivity, suggesting that some other regulatory factors may modulate the splicing of exon 9. To identify such factors, we report here the genetic analysis of a polymorphic locus, M470V, located in exon 10 of the CFTR gene in 60 patients with CBAVD, compared to a normal control population. The statistical analysis showed strong linkage disequilibrium between the 5T allele and the V allele of the M470V polymorphism in the CBAVD population, but not in the normal population. The V allele in a gene carrying 5T could, however, contribute to lowering the level of normal transcripts, as already suggested by in vitro transcriptional studies. These genetic findings, together with previous studies, suggest involvement of the M470V variant in the modulation of the splicing of exon 9 of the CFTR gene. PMID:9678705

  18. Deep Haplotype Divergence and Long-Range Linkage Disequilibrium at Xp21.1 Provide Evidence That Humans Descend From a Structured Ancestral Population

    PubMed Central

    Garrigan, Daniel; Mobasher, Zahra; Kingan, Sarah B.; Wilder, Jason A.; Hammer, Michael F.

    2005-01-01

    Fossil evidence links human ancestry with populations that evolved from modern gracile morphology in Africa 130,000–160,000 years ago. Yet fossils alone do not provide clear answers to the question of whether the ancestors of all modern Homo sapiens comprised a single African population or an amalgamation of distinct archaic populations. DNA sequence data have consistently supported a single-origin model in which anatomically modern Africans expanded and completely replaced all other archaic hominin populations. Aided by a novel experimental design, we present the first genetic evidence that statistically rejects the null hypothesis that our species descends from a single, historically panmictic population. In a global sample of 42 X chromosomes, two African individuals carry a lineage of noncoding 17.5-kb sequence that has survived for >1 million years without any clear traces of ongoing recombination with other lineages at this locus. These patterns of deep haplotype divergence and long-range linkage disequilibrium are best explained by a prolonged period of ancestral population subdivision followed by relatively recent interbreeding. This inference supports human evolution models that incorporate admixture between divergent African branches of the genus Homo. PMID:15937130

  19. 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

  20. Linkage disequilibrium mapping in domestic dog breeds narrows the progressive rod-cone degeneration interval and identifies ancestral disease-transmitting chromosome.

    PubMed

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

    2006-11-01

    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 approximately 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 the LD approach in the canine model.

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

    PubMed

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

    2010-04-01

    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 r(2) of 0.82, spanning a region that includes five 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.

  2. Linkage disequilibrium analysis reveals an albuminuria risk haplotype containing three missense mutations in the cubilin gene with striking differences among European and African ancestry populations

    PubMed Central

    2012-01-01

    Background A recent meta-analysis described a variant (p.Ile2984Val) in the cubilin gene (CUBN) that is associated with levels of albuminuria in the general population and in diabetics. Methods We implemented a Linkage Disequilibrium (LD) search with data from the 1000 Genomes Project, on African and European population genomic sequences. Results We found that the p.Ile2984Val variation is part of a larger haplotype in European populations and it is almost absent in west Africans. This haplotype contains 19 single nucleotide polymorphisms (SNPs) in very high LD, three of which are missense mutations (p.Leu2153Phe, p.Ile2984Val, p.Glu3002Gly), and two have not been previously reported. Notably, this European haplotype is absent in west African populations, and the frequency of each individual polymorphism differs significantly in Africans. Conclusions Genotyping of these variants in existing African origin sample sets coupled to measurements of urine albumin excretion levels should reveal which is the most likely functional candidate for albuminuria risk. The unique haplotypic structure of CUBN in different populations may leverage the effort to identify the functional variant and to shed light on evolution of the CUBN gene locus. PMID:23114252

  3. Coordinated Action of Biological Processes during Embryogenesis Can Cause Genome-Wide Linkage Disequilibrium in the Human Genome and Influence Age-Related Phenotypes

    PubMed Central

    Culminskaya, Irina; Kulminski, Alexander M.; Yashin, Anatoli I.

    2017-01-01

    A role of non-Mendelian inheritance in genetics of complex, age-related traits is becoming increasingly recognized. Recently, we reported on two inheritable clusters of SNPs in extensive genome-wide linkage disequilibrium (LD) in the Framingham Heart Study (FHS), which were associated with the phenotype of premature death. Here we address biologically-related properties of these two clusters. These clusters have been unlikely selected randomly because they are functionally and structurally different from matched sets of randomly selected SNPs. For example, SNPs in LD from each cluster are highly significantly enriched in genes (p=7.1×10−22 and p=5.8×10−18), in general, and in short genes (p=1.4×10−47 and p=4.6×10−7), in particular. Mapping of SNPs in LD to genes resulted in two, partly overlapping, networks of 1764 and 4806 genes. Both these networks were gene enriched in developmental processes and in biological processes tightly linked with development including biological adhesion, cellular component organization, locomotion, localization, signaling, (p<10−4, q<10−4 for each category). Thorough analysis suggests connections of these genetic networks with different stages of embryogenesis and highlights biological interlink of specific processes enriched for genes from these networks. The results suggest that coordinated action of biological processes during embryogenesis may generate genome-wide networks of genetic variants, which may influence complex age-related phenotypes characterizing health span and lifespan. PMID:28357417

  4. DQA1 and DQB1 promoter diversity and linkage disequilibrium with class II haplotypes in Mexican Mestizo population.

    PubMed

    Alaez, C; Vázquez-García, M N; Gorodezky, C

    2001-06-01

    The upstream sequences in the 5' flanking region of HLA class II genes, regulate their expression and contribute to the development of immunological diseases. We analyzed 105 healthy unrelated Mexican Mestizos for QAP and QBP polymorphism. DNA typing for DRB1, DQA1, DQB1, QAP1 and QBP1 was done using a standardized PCR-SSOP. Although all QAP alleles previously described were found in Mexicans, the distribution differed as compared to other populations. QAP-3.1, 4.1 and 4.2 were the most frequent alleles and were associated with DQA1*03, *0501 and *0402 respectively. The prevalent QBP alleles were 3.21, 3.1 and 4.1 found mainly associated with DQB1*0302, *0301 and *0501. Linkage disequilibria between the promoter and the corresponding DQA1 and DQB1 allele, are in general the same as described by others. A total of 61 different haplotypes were defined, only six of them with a frequency above 4%. The haplotypes DRB1*0407-QAP-3.1-DQA1*03-QBP-3.21-DQB1*0302 (HF = 14.37%) and DRB1*0802-QAP-4.2-DQA1*0401-QBP-4.1-DQB1*0402 (HF = 14.22%), which have an Amerindian ancestry, are the most frequent in Mexicans. Some rare combinations were detected such as DRB1*0405-QAP-1.3-DQA1*0101/4-QBP-5.11/5.12-DQB1*0501 and DRB1*0403-QAP-3.2-DQA1*03-QBP-3.21-DQB1*0302, probably due to ancient recombination events. This knowledge is relevant as a basis to evaluate functional implications and to explore the role of promoter diversity in disease expression.

  5. Trans-ethnic follow-up of breast cancer GWAS hits using the preferential linkage disequilibrium approach

    PubMed Central

    Zhu, Qianqian; Shepherd, Lori; Lunetta, Kathryn L.; Yao, Song; Liu, Qian; Hu, Qiang; Haddad, Stephen A.; Sucheston-Campbell, Lara; Bensen, Jeannette T.; Bandera, Elisa V.; Rosenberg, Lynn; Liu, Song; Haiman, Christopher A.; Olshan, Andrew F.; Palmer, Julie R.; Ambrosone, Christine B.

    2016-01-01

    Leveraging population-distinct linkage equilibrium (LD) patterns, trans-ethnic follow-up of variants discovered from genome-wide association studies (GWAS) has proved to be useful in facilitating the identification of bona fide causal variants. We previously developed the preferential LD approach, a novel method that successfully identified causal variants driving the GWAS signals within European-descent populations even when the causal variants were only weakly linked with the GWAS-discovered variants. To evaluate the performance of our approach in a trans-ethnic setting, we applied it to follow up breast cancer GWAS hits identified mostly from populations of European ancestry in African Americans (AA). We evaluated 74 breast cancer GWAS variants in 8,315 AA women from the African American Breast Cancer Epidemiology and Risk (AMBER) consortium. Only 27% of them were associated with breast cancer risk at significance level α=0.05, suggesting race-specificity of the identified breast cancer risk loci. We followed up on those replicated GWAS hits in the AMBER consortium utilizing the preferential LD approach, to search for causal variants or better breast cancer markers from the 1000 Genomes variant catalog. Our approach identified stronger breast cancer markers for 80% of the GWAS hits with at least nominal breast cancer association, and in 81% of these cases, the marker identified was among the top 10 of all 1000 Genomes variants in the corresponding locus. The results support trans-ethnic application of the preferential LD approach in search for candidate causal variants, and may have implications for future genetic research of breast cancer in AA women. PMID:27825120

  6. 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...

  7. Genome-wide divergence and linkage disequilibrium analyses for Capsicum baccatum revealed by genome-anchored single nucleotide polymorphisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Principal component analysis (PCA) with 36,621 polymorphic genome-anchored single nucleotide polymorphisms (SNPs) identified collectively for Capsicum annuum and Capsicum baccatum was used to show the distribution of these 2 important incompatible cultivated pepper species. Estimated mean nucleotide...

  8. Estimation of historical effective population size using linkage disequilibria with marker data.

    PubMed

    Corbin, L J; Liu, A Y H; Bishop, S C; Woolliams, J A

    2012-08-01

    Theory hypothesizes that the rate of decline in linkage disequilibrium (LD) as a function of distance between markers, measured by r(2), can be used to estimate effective population size (N(e)) and how it varies over time. The development of high-density genotyping makes feasible the application of this theory and has provided an impetus to improve predictions. This study considers the impact of several developments on the estimation of N(e) using both simulated and equine high-density single-nucleotide polymorphism data, when N(e) is assumed to be constant a priori and when it is not. In all models, estimates of N(e) were highly sensitive to thresholds imposed upon minor allele frequency (MAF) and to a priori assumptions on the expected r(2) for adjacent markers. Where constant N(e) was assumed a priori, then estimates with the lowest mean square error were obtained with MAF thresholds between 0.05 and 0.10, adjustment of r(2) for finite sample size, estimation of a [the limit for r(2) as recombination frequency (c) approaches 0] and relating N(e) to c (1 - c/2). The findings for predicting N(e) from models allowing variable N(e) were much less clear, apart from the desirability of correcting for finite sample size, and the lack of consistency in estimating recent N(e) (<7 generations) where estimates use data with large c. The theoretical conflicts over how estimation should proceed and uncertainty over where predictions might be expected to fit well suggest that the estimation of N(e) when it varies be carried out with extreme caution.

  9. Using SNP markers to dissect linkage disequilibrium at a major quantitative trait locus for resistance to the potato cyst nematode Globodera pallida on potato chromosome V.

    PubMed

    Achenbach, Ute; Paulo, Joao; Ilarionova, Evgenyia; Lübeck, Jens; Strahwald, Josef; Tacke, Eckhard; Hofferbert, Hans-Reinhard; Gebhardt, Christiane

    2009-02-01

    The damage caused by the parasitic root cyst nematode Globodera pallida is a major yield-limiting factor in potato cultivation . Breeding for resistance is facilitated by the PCR-based marker 'HC', which is diagnostic for an allele conferring high resistance against G. pallida pathotype Pa2/3 that has been introgressed from the wild potato species Solanum vernei into the Solanum tuberosum tetraploid breeding pool. The major quantitative trait locus (QTL) controlling this nematode resistance maps on potato chromosome V in a hot spot for resistance to various pathogens including nematodes and the oomycete Phytophthora infestans. An unstructured sample of 79 tetraploid, highly heterozygous varieties and breeding clones was selected based on presence (41 genotypes) or absence (38 genotypes) of the HC marker. Testing the clones for resistance to G. pallida confirmed the diagnostic power of the HC marker. The 79 individuals were genotyped for 100 single nucleotide polymorphisms (SNPs) at 10 loci distributed over 38 cM on chromosome V. Forty-five SNPs at six loci spanning 2 cM in the interval between markers GP21-GP179 were associated with resistance to G. pallida. Based on linkage disequilibrium (LD) between SNP markers, six LD groups comprising between 2 and 18 SNPs were identified. The LD groups indicated the existence of multiple alleles at a single resistance locus or at several, physically linked resistance loci. LD group C comprising 18 SNPs corresponded to the 'HC' marker. LD group E included 16 SNPs and showed an association peak, which positioned one nematode resistance locus physically close to the R1 gene family.

  10. An extensive candidate gene approach to speciation: diversity, divergence and linkage disequilibrium in candidate pigmentation genes across the European crow hybrid zone.

    PubMed

    Poelstra, J W; Ellegren, H; Wolf, J B W

    2013-12-01

    Colouration patterns have an important role in adaptation and speciation. The European crow system, in which all-black carrion crows and grey-coated hooded crows meet in a narrow hybrid zone, is a prominent example. The marked phenotypic difference is maintained by assortative mating in the absence of neutral genetic divergence, suggesting the presence of few pigmentation genes of major effect. We made use of the rich phenotypic and genetic resources in mammals and identified a comprehensive panel of 95 candidate pigmentation genes for birds. Based on functional annotation, we chose a subset of the most promising 37 candidates, for which we developed a marker system that demonstrably works across the avian phylogeny. In total, we sequenced 107 amplicons (∼3 loci per gene, totalling 60 kb) in population samples of crows (n=23 for each taxon). Tajima's D, Fu's FS, DHEW and HKA (Hudson-Kreitman-Aguade) statistics revealed several amplicons that deviated from neutrality; however, none of these showed significantly elevated differentiation between the two taxa. Hence, colour divergence in this system may be mediated by uncharacterized pigmentation genes or regulatory regions outside genes. Alternatively, the observed high population recombination rate (4Ner∼0.03), with overall linkage disequilibrium dropping rapidly within the order of few 100 bp, may compromise the power to detect causal loci with nearby markers. Our results add to the debate as to the utility of candidate gene approaches in relation to genomic features and the genetic architecture of the phenotypic trait in question.

  11. An extensive candidate gene approach to speciation: diversity, divergence and linkage disequilibrium in candidate pigmentation genes across the European crow hybrid zone

    PubMed Central

    Poelstra, J W; Ellegren, H; Wolf, J B W

    2013-01-01

    Colouration patterns have an important role in adaptation and speciation. The European crow system, in which all-black carrion crows and grey-coated hooded crows meet in a narrow hybrid zone, is a prominent example. The marked phenotypic difference is maintained by assortative mating in the absence of neutral genetic divergence, suggesting the presence of few pigmentation genes of major effect. We made use of the rich phenotypic and genetic resources in mammals and identified a comprehensive panel of 95 candidate pigmentation genes for birds. Based on functional annotation, we chose a subset of the most promising 37 candidates, for which we developed a marker system that demonstrably works across the avian phylogeny. In total, we sequenced 107 amplicons (∼3 loci per gene, totalling 60 kb) in population samples of crows (n=23 for each taxon). Tajima's D, Fu's FS, DHEW and HKA (Hudson–Kreitman–Aguade) statistics revealed several amplicons that deviated from neutrality; however, none of these showed significantly elevated differentiation between the two taxa. Hence, colour divergence in this system may be mediated by uncharacterized pigmentation genes or regulatory regions outside genes. Alternatively, the observed high population recombination rate (4Ner∼0.03), with overall linkage disequilibrium dropping rapidly within the order of few 100 bp, may compromise the power to detect causal loci with nearby markers. Our results add to the debate as to the utility of candidate gene approaches in relation to genomic features and the genetic architecture of the phenotypic trait in question. PMID:23881172

  12. 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.

  13. The role of the particle size spectrum in estimating POC fluxes from Th234/U238 disequilibrium

    NASA Astrophysics Data System (ADS)

    Burd, Adrian B.; Jackson, George A.; Moran, S. B.

    2007-06-01

    Thorium-234 is increasingly being used as a tracer for particulate organic carbon (POC) export in the oceans. In particular, POC fluxes are being estimated using disequilibrium between Th234 and its parent radionuclide, U238, and estimates of the POC/Th234 ratio of particles settling out of the water column. We have investigated the effect of variations in the particle size distribution on these estimates by using model particle size spectra and size distributions of organic carbon and Th234. Simulations indicate that the POC/Th234 ratio is sensitive to differences in the distributions of organic carbon and Th234 with particle size. If these size distributions differ, then the POC/Th234 ratio is a function of particle size and estimates of the POC/Th234 ratio using size-fractioned samples are inaccurate. Consequently, size fractioning techniques, such as filtration, yield biased estimates if the quantity being measured varies with particle size. We used a model with phytoplankton, fecal pellets and aggregates to examine the assumption that the particles responsible for the Th234 flux are also responsible for the POC flux. We found that variations in the size distributions of these three populations affected POC and Th234 fluxes differently, suggesting that changes in biological interactions can lead to a preferential increase in POC or Th234 flux. We suggest that further examination of the distributions of organic carbon and Th234 with particle size and type is required to refine our understanding of the factors affecting the POC/Th234 ratio.

  14. 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

  15. 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

  16. A rare form of persistent right aorta arch in linkage disequilibrium with the DiGeorge critical region on CFA26 in German Pinschers.

    PubMed

    Philipp, Ute; Menzel, Julia; Distl, Ottmar

    2011-01-01

    Persistent right aortic arch (PRAA) is a congenital vascular ring anomaly common in several dog breeds. In German Pinscher, the disorder is characterized by a left retroesophageal subclavian artery in combination with a ligamentum arteriosum originating at the aberrant left subclavian artery (PRAA-SA-LA). In this study, we genotyped 38 microsatellite markers on canine chromosome 26 (CFA26) in German Pinschers and tested them for linkage and association. We found a chromosome-wide significantly linked genomic region on CFA26, which corresponds to the human DiGeorge syndrome critical region (DGCR). Therefore, we analyzed sequences from 13 genes of DGCR and the canine t-box gene TBX1. We identified a total of 26 polymorphisms in German Pinschers. Three of these SNPs located within TBX1 and one in the mitochondrial ribosomal protein L40 gene (MRPL40) were associated with the PRAA-SA-LA phenotype in German Pinscher. Despite linkage and association between PRAA-SA-LA and the canine DGCR, none of these mutations appeared responsible for PRAA-SA-LA. As the orthologue human region on HSA22q11.2 is known for high susceptibility to genomic rearrangements, we suspect that in German Pinschers, chromosomal aberrations might cause PRAA-SA-LA.

  17. Linkage disequilibrium at the Machado-Joseph disease spinal cerebellar ataxia 3 locus: Evidence for a common founder effect in French and Portuguese-Brazilian families as well as a second ancestral Portuguese-Azorean mutation

    SciTech Connect

    Stevanin, G.; Cancel, G.; Didierjean, O.

    1995-11-01

    Spinal cerebellar ataxia 3 (SCA3) is a genetic subtype of the type I autosomal dominant cerebellar ataxias (ADCA type I), a clinically and genetically heterogeneous group of neurological disorders. SCA3 was mapped in French families to chromosome 14q24.3-qter in the same region as the gene for Machado-Joseph disease (MJD), which was classified as a form of ADCA type I on the basis of similarities in the clinical presentation of individual patients. The MJD gene was recently identified in Japanese kindreds, and the mutation was characterized as an unstable CAG repeat that is expanded in affected individuals. The same mutation is observed in families of Portuguese-Azorean ancestry, as well as in French SCA3 kindreds. In other disorders caused by unstable and expanded triplet repeats, such as fragile X syndrome (FRA-X), myotonic dystrophy (MD), Huntington disease (HD), and SCA1, linkage disequilibrium (LD) between the mutation and closely linked polymorphic markers was detected, suggesting that there were only one or a few founders or predisposing haplotypes. In the present study, 29 families of different geographical origins were tested for LD between the MJD/SCA3 mutation and four flanking microsatellite markers. 27 refs., 2 tabs.

  18. Sensibility of linkage information and effectiveness of estimated distributions.

    PubMed

    Chuang, Chung-Yao; Chen, Ying-ping

    2010-01-01

    The probabilistic model building performed by estimation of distribution algorithms (EDAs) enables these methods to use advanced techniques of statistics and machine learning for automatic discovery of problem structures. However, in some situations, it may not be possible to completely and accurately identify the whole problem structure by probabilistic modeling due to certain inherent properties of the given problem. In this work, we illustrate one possible cause of such situations with problems consisting of structures with unequal fitness contributions. Based on the illustrative example, we introduce a notion that the estimated probabilistic models should be inspected to reveal the effective search directions and further propose a general approach which utilizes a reserved set of solutions to examine the built model for likely inaccurate fragments. Furthermore, the proposed approach is implemented on the extended compact genetic algorithm (ECGA) and experiments are performed on several sets of additively separable problems with different scaling setups. The results indicate that the proposed method can significantly assist ECGA to handle problems comprising structures of disparate fitness contributions and therefore may potentially help EDAs in general to overcome those situations in which the entire problem structure cannot be recognized properly due to the temporal delay of emergence of some promising partial solutions.

  19. Transmission-disequilibrium tests for quantitative traits.

    PubMed Central

    Allison, D B

    1997-01-01

    The transmission-disequilibrium test (TDT) of Spielman et al. is a family-based linkage-disequilibrium test that offers a powerful way to test for linkage between alleles and phenotypes that is either causal (i.e., the marker locus is the disease/trait allele) or due to linkage disequilibrium. The TDT is equivalent to a randomized experiment and, therefore, is resistant to confounding. When the marker is extremely close to the disease locus or is the disease locus itself, tests such as the TDT can be far more powerful than conventional linkage tests. To date, the TDT and most other family-based association tests have been applied only to dichotomous traits. This paper develops five TDT-type tests for use with quantitative traits. These tests accommodate either unselected sampling or sampling based on selection of phenotypically extreme offspring. Power calculations are provided and show that, when a candidate gene is available (1) these TDT-type tests are at least an order of magnitude more efficient than two common sib-pair tests of linkage; (2) extreme sampling results in substantial increases in power; and (3) if the most extreme 20% of the phenotypic distribution is selectively sampled, across a wide variety of plausible genetic models, quantitative-trait loci explaining as little as 5% of the phenotypic variation can be detected at the .0001 alpha level with <300 observations. PMID:9042929

  20. Multipoint linkage mapping using sibpairs: non-parametric estimation of trait effects with quantitative covariates.

    PubMed

    Chiou, Jeng-Min; Liang, Kung-Yee; Chiu, Yen-Feng

    2005-01-01

    Multipoint linkage analysis using sibpair designs remains a common approach to help investigators to narrow chromosomal regions for traits (either qualitative or quantitative) of interest. Despite its popularity, the success of this approach depends heavily on how issues such as genetic heterogeneity, gene-gene, and gene-environment interactions are properly handled. If addressed properly, the likelihood of detecting genetic linkage and of efficiently estimating the location of the trait locus would be enhanced, sometimes drastically. Previously, we have proposed an approach to deal with these issues by modeling the genetic effect of the target trait locus as a function of covariates pertained to the sibpairs. Here the genetic effect is simply the probability that a sibpair shares the same allele at the trait locus from their parents. Such modeling helps to divide the sibpairs into more homogeneous subgroups, which in turn helps to enhance the chance to detect linkage. One limitation of this approach is the need to categorize the covariates so that a small and fixed number of genetic effect parameters are introduced. In this report, we take advantage of the fact that nowadays multiple markers are readily available for genotyping simultaneously. This suggests that one could estimate the dependence of the generic effect on the covariates nonparametrically. We present an iterative procedure to estimate (1) the genetic effect nonparametrically and (2) the location of the trait locus through estimating functions developed by Liang et al. ([2001a] Hum Hered 51:67-76). We apply this new method to the linkage study of schizophrenia to illustrate how the onset ages of each sibpair may help to address the issue of genetic heterogeneity. This analysis sheds new light on the dependence of the trait effect on onset ages from affected sibpairs, an observation not revealed previously. In addition, we have carried out some simulation work, which suggests that this method provides

  1. Linkage of viral sequences among HIV-infected village residents in Botswana: estimation of linkage rates in the presence of missing data.

    PubMed

    Carnegie, Nicole Bohme; Wang, Rui; Novitsky, Vladimir; De Gruttola, Victor

    2014-01-01

    Linkage analysis is useful in investigating disease transmission dynamics and the effect of interventions on them, but estimates of probabilities of linkage between infected people from observed data can be biased downward when missingness is informative. We investigate variation in the rates at which subjects' viral genotypes link across groups defined by viral load (low/high) and antiretroviral treatment (ART) status using blood samples from household surveys in the Northeast sector of Mochudi, Botswana. The probability of obtaining a sequence from a sample varies with viral load; samples with low viral load are harder to amplify. Pairwise genetic distances were estimated from aligned nucleotide sequences of HIV-1C env gp120. It is first shown that the probability that randomly selected sequences are linked can be estimated consistently from observed data. This is then used to develop estimates of the probability that a sequence from one group links to at least one sequence from another group under the assumption of independence across pairs. Furthermore, a resampling approach is developed that accounts for the presence of correlation across pairs, with diagnostics for assessing the reliability of the method. Sequences were obtained for 65% of subjects with high viral load (HVL, n = 117), 54% of subjects with low viral load but not on ART (LVL, n = 180), and 45% of subjects on ART (ART, n = 126). The probability of linkage between two individuals is highest if both have HVL, and lowest if one has LVL and the other has LVL or is on ART. Linkage across groups is high for HVL and lower for LVL and ART. Adjustment for missing data increases the group-wise linkage rates by 40-100%, and changes the relative rates between groups. Bias in inferences regarding HIV viral linkage that arise from differential ability to genotype samples can be reduced by appropriate methods for accommodating missing data.

  2. Development of an integrated genetic map of a sugarcane (Saccharum spp.) commercial cross, based on a maximum-likelihood approach for estimation of linkage and linkage phases.

    PubMed

    Garcia, A A F; Kido, E A; Meza, A N; Souza, H M B; Pinto, L R; Pastina, M M; Leite, C S; Silva, J A G da; Ulian, E C; Figueira, A; Souza, A P

    2006-01-01

    Sugarcane (Saccharum spp.) is a clonally propagated outcrossing polyploid crop of great importance in tropical agriculture. Up to now, all sugarcane genetic maps had been developed using either full-sib progenies derived from interspecific crosses or from selfing, both approaches not directly adopted in conventional breeding. We have developed a single integrated genetic map using a population derived from a cross between two pre-commercial cultivars ('SP80-180' x 'SP80-4966') using a novel approach based on the simultaneous maximum-likelihood estimation of linkage and linkage phases method specially designed for outcrossing species. From a total of 1,118 single-dose markers (RFLP, SSR and AFLP) identified, 39% derived from a testcross configuration between the parents segregating in a 1:1 fashion, while 61% segregated 3:1, representing heterozygous markers in both parents with the same genotypes. The markers segregating 3:1 were used to establish linkage between the testcross markers. The final map comprised of 357 linked markers, including 57 RFLPs, 64 SSRs and 236 AFLPs that were assigned to 131 co-segregation groups, considering a LOD score of 5, and a recombination fraction of 37.5 cM with map distances estimated by Kosambi function. The co-segregation groups represented a total map length of 2,602.4 cM, with a marker density of 7.3 cM. When the same data were analyzed using JoinMap software, only 217 linked markers were assigned to 98 co-segregation groups, spanning 1,340 cM, with a marker density of 6.2 cM. The maximum-likelihood approach reduced the number of unlinked markers to 761 (68.0%), compared to 901 (80.5%) using JoinMap. All the co-segregation groups obtained using JoinMap were present in the map constructed based on the maximum-likelihood method. Differences on the marker order within the co-segregation groups were observed between the two maps. Based on RFLP and SSR markers, 42 of the 131 co-segregation groups were assembled into 12 putative

  3. 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.

  4. 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

  5. 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.

  6. [Estimated parameters in linkage between mortality and hospitalization databases according to quality of records on underlying cause of death].

    PubMed

    Coeli, Cláudia Medina; Barbosa, Flávia dos Santos; Brito, Alexandre dos Santos; Pinheiro, Rejane Sobrino; Camargo, Kenneth Rochel de; Medronho, Roberto de Andrade; Bloch, Katia Vergetti

    2011-08-01

    The purpose of the study was to compare the linkage parameter estimates between hospitalization and mortality databases, calculated separately for the subsets of deaths from ill-defined causes and deaths from known causes. The databases for deaths from known causes and ill-defined causes were linked to a hospital admissions database. Parameters were estimated using two strategies: (1) first name, last name, and day, month, and year of birth, (2) full name and date of birth. In the first strategy, the estimates for the first and last name were at least 97% in both sets. However, the items day, month, and year of birth produced low values in both sets. In the second strategy there was an important difference between the two groups, with much lower values for full name and especially for date of birth in the group of deaths from ill-defined causes. Our results emphasize the need for pilot studies to evaluate possible internal heterogeneity of databases during the planning stage of linkage projects.

  7. Long lasting dynamic disequilibrium in river basins

    NASA Astrophysics Data System (ADS)

    Goren, Liran; Willett, Sean D.; McCoy, Scott W.; Perron, J. Taylor; Chen, Chia-Yu

    2014-05-01

    The river basins of ancient landscapes such as the southeastern United States exhibit disequilibrium in the form of migrating divides and stream capture. This observation is surprising in light of the relatively short theoretical fluvial response time, which is controlled by the celerity of the erosional wave that propagates upstream the fluvial channels. The response time is believed to determine the time required for fluvial landscapes to adjust to tectonic, climatic, and base-level perturbations, and its global estimations range between 0.1 Myr and 10s Myr. To address this discrepancy, we develop a framework for mapping continuous dynamic reorganization of natural river basins, and demonstrate the longevity of disequilibrium along the river basins in the southeastern United States that are reorganizing in response to escarpment retreat and coastal advance. The mapping of disequilibrium is based on a proxy for steady-state elevation, Ξ, that can be easily calculated from digital elevation models. Disequilibrium is inferred from differences in the value of Ξ across water divides. These differences indicate that with the present day drainage area distribution and river topology the steady-state channels elevation across the divides differs, and therefore divides are expected to migrate in the direction of the higher Ξ value. We further use the landscape evolution model DAC to explore the source of the longevity of disequilibrium in fluvial landscapes. DAC solves accurately for the location of water divides, using a combination of an analytical solution for hillslopes and low-order channels together with a numerical solution for higher order channels. DAC simulations demonstrate topological, geometrical, and topographical adjustments that persist much longer than the theoretical response time, and consequently, extend the time needed to diminish disequilibrium in the landscape and to reach topological and topographical steady-state. This behavior is interpreted

  8. Combined linkage and association mapping of flowering time in Sunflower (Helianthus annuus L.).

    PubMed

    Cadic, Elena; Coque, Marie; Vear, Felicity; Grezes-Besset, Bruno; Pauquet, Jerôme; Piquemal, Joël; Lippi, Yannick; Blanchard, Philippe; Romestant, Michel; Pouilly, Nicolas; Rengel, David; Gouzy, Jerôme; Langlade, Nicolas; Mangin, Brigitte; Vincourt, Patrick

    2013-05-01

    Association mapping and linkage mapping were used to identify quantitative trait loci (QTL) and/or causative mutations involved in the control of flowering time in cultivated sunflower Helianthus annuus. A panel of 384 inbred lines was phenotyped through testcrosses with two tester inbred lines across 15 location × year combinations. A recombinant inbred line (RIL) population comprising 273 lines was phenotyped both per se and through testcrosses with one or two testers in 16 location × year combinations. In the association mapping approach, kinship estimation using 5,923 single nucleotide polymorphisms was found to be the best covariate to correct for effects of panel structure. Linkage disequilibrium decay ranged from 0.08 to 0.26 cM for a threshold of 0.20, after correcting for structure effects, depending on the linkage group (LG) and the ancestry of inbred lines. A possible hitchhiking effect is hypothesized for LG10 and LG08. A total of 11 regions across 10 LGs were found to be associated with flowering time, and QTLs were mapped on 11 LGs in the RIL population. Whereas eight regions were demonstrated to be common between the two approaches, the linkage disequilibrium approach did not detect a documented QTL that was confirmed using the linkage mapping approach.

  9. Linkage mapping in tetraploid willows: segregation of molecular markers and estimation of linkage phases support an allotetraploid structure for Salix alba x Salix fragilis interspecific hybrids.

    PubMed

    Barcaccia, G; Meneghetti, S; Albertini, E; Triest, L; Lucchin, M

    2003-02-01

    Salix alba-Salix fragilis complex includes closely related dioecious polyploid species, which are obligate outcrossers. Natural populations of these willows and their hybrids are represented by a mixture of highly heterozygous genotypes sharing a common gene pool. Since nothing is known about their genomic constitution, tetraploidy (2n=4x=76) in willow species makes basic and applied genetic studies difficult. We have used a two-way pseudotestcross strategy and single-dose markers (SDMs) to construct the first linkage maps for both pistillate and staminate willows. A total of 242 amplified fragment length polymorphisms (AFLPs) and 50 selective amplifications of microsatellite polymorphic loci (SAMPL) markers, which showed 1:1 segregation in the F(1) mapping populations, were used in linkage analysis. In S. alba, 73 maternal and 48 paternal SDMs were mapped to 19 and 16 linkage groups covering 708 and 339 cM, respectively. In S. fragilis, 13 maternal and 33 paternal SDMs were mapped in six and 14 linkage groups covering 98 and 321 cM, respectively. For most cosegregation groups, a comparable number of markers linked in coupling and repulsion was identified. This finding suggests that most of chromosomes pair preferentially as occurs in allotetraploid species exhibiting disomic inheritance. The detection of 10 pairs of marker alleles from single parents showing codominant inheritance strengthens this hypothesis. The fact that, of the 1122 marker loci identified in the two male and female parents, the vast majority (77.5%) were polymorphic and as few as 22.5% were shared between parental species highlight that S. alba and S. fragilis genotypes are differentiated. The highly difference between S. alba- and S. fragilis-specific markers found in both parental combinations (on average, 65.3 vs 34.7%, respectively) supports the (phylogenetic) hypothesis that S. fragilis is derived from S. alba-like progenitors.

  10. Linkage disequilibrium extends across putative selected sites in FOXP2.

    PubMed

    Ptak, Susan E; Enard, Wolfgang; Wiebe, Victor; Hellmann, Ines; Krause, Johannes; Lachmann, Michael; Pääbo, Svante

    2009-10-01

    Polymorphism data in humans suggest that the gene encoding the transcription factor FOXP2, which influences speech and language development, has been subject to a selective sweep within the last 260,000 years. It has been proposed that one or both of two substitutions that occurred on the human evolutionary lineage and changed amino acids were the targets for selection. In apparent contradiction to this is the observation that these substitutions are present in Neandertals who diverged from humans maybe 300,000-400,000 years ago. We have collected polymorphism data upstream and downstream of the substitutions. Contrary to what is expected, following a selective sweep, we find that the haplotypes extend across the two sites. We discuss possible explanations for these observations. One of them is that the selective sweep reflected in FOXP2 polymorphism data was not associated with the two amino acid substitutions.

  11. 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...

  12. Estimating forest biomass using scale linkage from tree to Landsat TM reflectance data

    NASA Astrophysics Data System (ADS)

    Ung, Chhun-Huor; Lambert, Marie-Claude; Raulier, Frédéric

    2005-10-01

    Estimates of forest biomass are needed to account for carbon at the tree, stand and regional scales. Sample plots of national forest inventories provide the basic database for these estimates. At the tree scale, a common estimation method is the use of an allometric equation that relates a tree's predicted compartment biomass yi (i = foliage, branches, stem wood or stem bark) with easily obtained non-destructive measurements, i.e., diameter at breast height (D): yi=bi1Dbi2 or with both D and tree height (H): yi=bi1Dbi2Hbi3, bik being the parameters estimated. A common paradigm observed in biomass literature considers that parameter values vary between stands and regions. At the regional scale, however, when comparing national biomass equations to regional biomass equations, our results showed no significant differences between both types of equation. These results contribute to strengthening the allometric theory as an organizing principle for quantifying the relationship between tree size and biomass across spatial scales. In tandem with the allometry theory, we used a soil-canopy model based on Li-Strahler's approach for up-scaling biomass from the tree to stand scale in a mixed hardwood-coniferous forest. Our results indicated that the shadow fraction of Landsat TM reflectance was correlated with stand biomass. However, this model is indebted with heteroscedasticity, meaning that its error increases appreciably when stand biomass density is high.

  13. 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.

  14. Linkage relationships in the bovine MHC region. High recombination frequency between class II subregions.

    PubMed

    Andersson, L; Lundén, A; Sigurdardottir, S; Davies, C J; Rask, L

    1988-01-01

    Class II genes of the bovine major histocompatibility complex (MHC) have been investigated by Southern blot analysis using human DNA probes. Previous studies revealed the presence of bovine DO beta, DQ alpha, DQ beta, DR alpha, and DR beta genes, and restriction fragment length polymorphisms for each of these genes were documented. In the present study, the presence of three additional class II genes, designated DZ alpha, DY alpha, and DY beta, are reported. DZ alpha was assumed to correspond to the human DZ alpha gene while the other two were designated DY because their relationship to human class II genes could not be firmly established. The linkage relationships among bovine class II genes and two additional loci, TCP1B and C4, were investigated by family segregation analysis and analysis of linkage disequilibrium. The results clearly indicated that all these loci belong to the same linkage group. This linkage group is divided into two subregions separated by a fairly high recombination frequency. One region includes the C4, DQ alpha, DQ beta, DR alpha, and DR beta loci and the other one is composed of the DO beta, DY alpha, DY beta, and TCP1B loci. No recombinant was observed within any of these subregions and there was a strong or fairly strong linkage disequilibrium between loci within groups. In contrast, as many as five recombinants among three different families were detected in the interval between these subregions giving a recombination frequency estimate of 0.17 +/- 0.07. The fairly high recombination frequency observed between class II genes in cattle is strikingly different from the corresponding recombination estimates in man and mouse. The finding implies either a much larger molecular distance between some of the bovine class II genes or alternatively the presence of a recombinational "hot spot" in the bovine class II region.

  15. POC and particulate 234 Th export fluxes estimated using 234 Th/ 238 U disequilibrium in an enclosed Eastern Mediterranean region (Saronikos Gulf and Elefsis Bay, Greece) in seasonal scale

    NASA Astrophysics Data System (ADS)

    Evangeliou, Nikolaos; Florou, Heleny; Scoullos, Michael

    2011-10-01

    Activity concentrations of the naturally occurring, short-lived and highly particle-reactive radionuclide tracer 234Th in the dissolved and particulate phase were determined at 7 shallow-water stations (maximum depths: 30 (S.1 and S.2), 65 (S.3), 97 (S.5), 105 (S.6) and 220 m (S.4 and S.7) in Saronikos Gulf and Elefsis Bay (central Aegean Sea, Greece) during 3 seasonal cruises (summer 2008, autumn 2008 and winter 2009) to assess the time scales of the dynamics and the depositional fate of particulate matter (POC, particulate 234Th). For that reason, in situ filtrating systems were deployed in several depths of the water column consisting of GF/A disc prefilters to scavenge particulate fraction of 234Th and organic carbon and impregnated cartridges to adsorb dissolved 234Th. The obtained data showed average particulate 234Th activity concentrations of 3.7 ± 0.4 Bq m -3 in summer, 2.1 ± 0.2 Bq m -3 in autumn and 2.4 ± 0.2 Bq m -3 in winter. The respective average dissolved 234Th activity concentrations were 30.1 ± 2.8 Bq m -3 in summer, 30.2 ± 2.9 Bq m -3 in autumn and 27.4 ± 3.0 Bq m -3 in winter. The activity ratios of total 234Th and its long-lived conservative parent 238U were below unity in most of the stations indicating radioactive disequilibrium throughout the water column, thus very dynamic trace-metal scavenging and particle export from the water column. These profiles ( 234Th and 238U) were used to estimate the export fluxes and scavenging rates of 234Th, as well as their residence times in the water column. The average cumulative export fluxes of particulate 234Th were estimated to be 33 ± 4 Bq m -2 d -1 in summer, 35 ± 5 Bq m -2 d -1 in autumn and 45 ± 6 Bq m -2 d -1 in winter, whereas the respective average cumulative scavenging rates of dissolved 234Th were 39 ± 5, 33 ± 5 and 50 ± 7 Bq m -2 d -1. Moreover, the cumulative average residence times of 234Th were 25 ± 4 d in summer, 45 ± 6 d in autumn and 64 ± 7 d in winter 2009 for the

  16. Infrequent causes of disequilibrium in the adult.

    PubMed

    Cherchi, Marcello

    2011-04-01

    This content focuses on some of the less common causes of dizziness in the adult. The diseases have been divided into the 2 broad categories of those causing chronic symptoms and those causing episodic symptoms. Presented here are the unusual causes of chronic disequilibrium in the adult, including bilateral vestibular loss, progressive supranuclear palsy, spinocerebellar ataxias, and mal de debarquement. Also discussed are the unusual causes of episodic disequilibrium in the adult, including psychogenic disequilibrium, vestibular paroxysmia, episodic ataxia, vestibular seizures, and cervicogenic vertigo.

  17. An international collaborative family-based whole genome quantitative trait linkage scan for myopic refractive error

    PubMed Central

    Abbott, Diana; Li, Yi-Ju; Guggenheim, Jeremy A.; Metlapally, Ravikanth; Malecaze, Francois; Calvas, Patrick; Rosenberg, Thomas; Paget, Sandrine; Zayats, Tetyana; Mackey, David A.; Feng, Sheng

    2012-01-01

    Purpose To investigate quantitative trait loci linked to refractive error, we performed a genome-wide quantitative trait linkage analysis using single nucleotide polymorphism markers and family data from five international sites. Methods Genomic DNA samples from 254 families were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel IVb. Quantitative trait linkage analysis was performed on 225 Caucasian families and 4,656 markers after accounting for linkage disequilibrium and quality control exclusions. Two refractive quantitative phenotypes, sphere (SPH) and spherical equivalent (SE), were analyzed. The SOLAR program was used to estimate identity by descent probabilities and to conduct two-point and multipoint quantitative trait linkage analyses. Results We found 29 markers and 11 linkage regions reaching peak two-point and multipoint logarithms of the odds (LODs)>1.5. Four linkage regions revealed at least one LOD score greater than 2: chromosome 6q13–6q16.1 (LOD=1.96 for SPH, 2.18 for SE), chromosome 5q35.1–35.2 (LOD=2.05 for SPH, 1.80 for SE), chromosome 7q11.23–7q21.2 (LOD=1.19 for SPH, 2.03 for SE), and chromosome 3q29 (LOD=1.07 for SPH, 2.05 for SE). Among these, the chromosome 6 and chromosome 5 regions showed the most consistent results between SPH and SEM. Four linkage regions with multipoint scores above 1.5 are near or within the known myopia (MYP) loci of MYP3, MYP12, MYP14, and MYP16. Overall, we observed consistent linkage signals across the SPH and SEM phenotypes, although scores were generally higher for the SEM phenotype. Conclusions Our quantitative trait linkage analyses of a large myopia family cohort provided additional evidence for several known MYP loci, and identified two additional potential loci at chromosome 6q13–16.1 and chromosome 5q35.1–35.2 for myopia. These results will benefit the efforts toward determining genes for myopic refractive error. PMID:22509102

  18. Maternal transmission disequilibrium of the glutamate receptor GRIK2 in schizophrenia.

    PubMed

    Bah, J; Quach, H; Ebstein, R P; Segman, R H; Melke, J; Jamain, S; Rietschel, M; Modai, I; Kanas, K; Karni, O; Lerer, B; Gourion, D; Krebs, M O; Etain, B; Schürhoff, F; Szöke, A; Leboyer, M; Bourgeron, T

    2004-08-26

    Schizophrenia is characterized by thought disorders, hallucinations and delusions. Genetic studies have shown a high linkage at chromosome 6q16-21. Among the genes located in this region is the glutamate receptor ionotropic kainate 2 gene (GRIK2 or GLUR6), a functional candidate for susceptibility to schizophrenia. In this study, transmission of GRIK2 was evaluated in 356 schizophrenic patients from three different clinical centers. Whereas paternal transmission shows equilibrium, we observed maternal transmission disequilibrium of GRIK2 in the largest population (p=0.03), which was still significant when all populations were added (p=0.05). These results are similar to the maternal GRIK2 transmission disequilibrium previously reported for autism, and support the presence of a susceptibility gene for schizophrenia at 6q16.

  19. Genetic linkage in the horse. II. Distribution of male recombination estimates and the influence of age, breed and sex on recombination frequency.

    PubMed

    Andersson, L; Sandberg, K

    1984-01-01

    In the present study an extensive amount of data, comprising more than 30,000 offspring in total, was analyzed to evaluate the influence of age and sex on the recombination frequency in the K-PGD segment of the equine linkage group (LG) I and the influence of age, breed and sex on recombination in the Al-Es segment of LG II. A highly significant sex difference is reported for both segments. Male and female recombination values in the K-PGD segment were estimated at 25.8 +/- 0.8 and 33.3 +/- 2.5%, respectively. Similarly, recombination was less frequent in the male (36.6 +/- 0.7%) than in the female (46.6 +/- 1.2%) in the Al-Es segment. Comparison of data from two Swedish horse breeds revealed no significant breed differences in either sex for recombination in the Al-Es segment. No evidence of an age effect was found in any segment or sex. The distribution of individual male recombination estimates was also investigated, and a significant heterogeneity among stallions was revealed in the K-PGD segment. The results are discussed in relation to previous studies on factors affecting recombination in mammals.

  20. X-APL: An Improved Family-Based Test of Association in the Presence of Linkage for the X Chromosome

    PubMed Central

    Chung, Ren-Hua; Morris, Richard W.; Zhang, Li; Li, Yi-Ju; Martin, Eden R.

    2007-01-01

    Family-based association methods have been developed primarily for autosomal markers. The X-linked sibling transmission/disequilibrium test (XS-TDT) and the reconstruction-combined TDT for X-chromosome markers (XRC-TDT) are the first association-based methods for testing markers on the X chromosome in family data sets. These are valid tests of association in family triads or discordant sib pairs but are not theoretically valid in multiplex families when linkage is present. Recently, XPDT and XMCPDT, modified versions of the pedigree disequilibrium test (PDT), were proposed. Like the PDT, XPDT compares genotype transmissions from parents to affected offspring or genotypes of discordant siblings; however, the XPDT can have low power if there are many missing parental genotypes. XMCPDT uses a Monte Carlo sampling approach to infer missing parental genotypes on the basis of true or estimated population allele frequencies. Although the XMCPDT was shown to be more powerful than the XPDT, variability in the statistic due to the use of an estimate of allele frequency is not properly accounted for. Here, we present a novel family-based test of association, X-APL, a modification of the test for association in the presence of linkage (APL) test. Like the APL, X-APL can use singleton or multiplex families and properly infers missing parental genotypes in linkage regions by considering identity-by-descent parameters for affected siblings. Sampling variability of parameter estimates is accounted for through a bootstrap procedure. X-APL can test individual marker loci or X-chromosome haplotypes. To allow for different penetrances in males and females, separate sex-specific tests are provided. Using simulated data, we demonstrated validity and showed that the X-APL is more powerful than alternative tests. To show its utility and to discuss interpretation in real-data analysis, we also applied the X-APL to candidate-gene data in a sample of families with Parkinson disease. PMID

  1. Small Field: dosimetry in electron disequilibrium region

    NASA Astrophysics Data System (ADS)

    Zhu, Timothy C.

    2010-11-01

    Small fields are more commonly used for radiation therapy because of the development of IMRT, stereotactic radiosurgery, and other special equipments such as Cyberknife and Tomotherapy. The dosimetry in the sub-centimeter field can result in substantial uncertainties because of the presence of electron disequilibrium due to the large dose gradients in the field. It is further complicated by the introduction of various radiation detectors, which usually perturb the conditions of disequilibrium. Hence additional corrections are required to maintain the dosimetric accuracy previously achieved for standard radiation dosimetry. A review of small field dosimetry provides some insights into the methods to characterize the detector convolution kernel and other methods to characterize detector perturbation effect.

  2. Linkage analysis without defined pedigrees.

    PubMed

    Day-Williams, Aaron G; Blangero, John; Dyer, Thomas D; Lange, Kenneth; Sobel, Eric M

    2011-07-01

    The need to collect accurate and complete pedigree information has been a drawback of family-based linkage and association studies. Even in case-control studies, investigators should be aware of, and condition on, familial relationships. In single nucleotide polymorphism (SNP) genome scans, relatedness can be directly inferred from the genetic data rather than determined through interviews. Various methods of estimating relatedness have previously been implemented, most notably in PLINK. We present new fast and accurate algorithms for estimating global and local kinship coefficients from dense SNP genotypes. These algorithms require only a single pass through the SNP genotype data. We also show that these estimates can be used to cluster individuals into pedigrees. With these estimates in hand, quantitative trait locus linkage analysis proceeds via traditional variance components methods without any prior relationship information. We demonstrate the success of our algorithms on simulated and real data sets. Our procedures make linkage analysis as easy as a typical genomewide association study.

  3. Accounting for linkage in family-based tests of association with missing parental genotypes.

    PubMed

    Martin, Eden R; Bass, Meredyth P; Hauser, Elizabeth R; Kaplan, Norman L

    2003-11-01

    In studies of complex diseases, a common paradigm is to conduct association analysis at markers in regions identified by linkage analysis, to attempt to narrow the region of interest. Family-based tests for association based on parental transmissions to affected offspring are often used in fine-mapping studies. However, for diseases with late onset, parental genotypes are often missing. Without parental genotypes, family-based tests either compare allele frequencies in affected individuals with those in their unaffected siblings or use siblings to infer missing parental genotypes. An example of the latter approach is the score test implemented in the computer program TRANSMIT. The inference of missing parental genotypes in TRANSMIT assumes that transmissions from parents to affected siblings are independent, which is appropriate when there is no linkage. However, using computer simulations, we show that, when the marker and disease locus are linked and the data set consists of families with multiple affected siblings, this assumption leads to a bias in the score statistic under the null hypothesis of no association between the marker and disease alleles. This bias leads to an inflated type I error rate for the score test in regions of linkage. We present a novel test for association in the presence of linkage (APL) that correctly infers missing parental genotypes in regions of linkage by estimating identity-by-descent parameters, to adjust for correlation between parental transmissions to affected siblings. In simulated data, we demonstrate the validity of the APL test under the null hypothesis of no association and show that the test can be more powerful than the pedigree disequilibrium test and family-based association test. As an example, we compare the performance of the tests in a candidate-gene study in families with Parkinson disease.

  4. Reporting errors in siblings' survival histories and their impact on adult mortality estimates: results from a record linkage study in Senegal.

    PubMed

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

    2014-04-01

    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 45 q 15 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.

  5. Characterisation of SNP haplotype structure in chemokine and chemokine receptor genes using CEPH pedigrees and statistical estimation.

    PubMed

    Clark, Vanessa J; Dean, Michael

    2004-03-01

    Chemokine signals and their cell-surface receptors are important modulators of HIV-1 disease and cancer. To aid future case/control association studies, aim to further characterise the haplotype structure of variation in chemokine and chemokine receptor genes. To perform haplotype analysis in a population-based association study, haplotypes must be determined by estimation, in the absence of family information or laboratory methods to establish phase. Here, test the accuracy of estimates of haplotype frequency and linkage disequilibrium by comparing estimated haplotypes generated with the expectation maximisation (EM) algorithm to haplotypes determined from Centre d'Etude Polymorphisme Humain (CEPH) pedigree data. To do this, they have characterised haplotypes comprising alleles at 11 biallelic loci in four chemokine receptor genes (CCR3, CCR2, CCR5 and CCRL2), which span 150 kb on chromosome 3p21, and haplotyes of nine biallelic loci in six chemokine genes [MCP-1(CCL2), Eotaxin(CCL11), RANTES(CCL5), MPIF-1(CCL23), PARC(CCL18) and MIP-1alpha(CCL3)] on chromosome 17q11-12. Forty multi-generation CEPH families, totalling 489 individuals, were genotyped by the TaqMan 5'-nuclease assay. Phased haplotypes and haplotypes estimated from unphased genotypes were compared in 103 grandparents who were assumed to have mated at random. For the 3p21 single nucleotide polymorphism (SNP) data, haplotypes determined by pedigree analysis and haplotypes generated by the EM algorithm were nearly identical. Linkage disequilibrium, measured by the D' statistic, was nearly maximal across the 150 kb region, with complete disequilibrium maintained at the extremes between CCR3-Y17Y and CCRL2-I243V. D'-values calculated from estimated haplotypes on 3p21 had high concordance with pairwise comparisons between pedigree-phased chromosomes. Conversely, there was less agreement between analyses of haplotype frequencies and linkage disequilibrium using estimated haplotypes when compared with

  6. Faster sequential genetic linkage computations.

    PubMed Central

    Cottingham, R W; Idury, R M; Schäffer, A A

    1993-01-01

    Linkage analysis using maximum-likelihood estimation is a powerful tool for locating genes. As available data sets have grown, the computation required for analysis has grown exponentially and become a significant impediment. Others have previously shown that parallel computation is applicable to linkage analysis and can yield order-of-magnitude improvements in speed. In this paper, we demonstrate that algorithmic modifications can also yield order-of-magnitude improvements, and sometimes much more. Using the software package LINKAGE, we describe a variety of algorithmic improvements that we have implemented, demonstrating both how these techniques are applied and their power. Experiments show that these improvements speed up the programs by an order of magnitude, on problems of moderate and large size. All improvements were made only in the combinatorial part of the code, without restoring to parallel computers. These improvements synthesize biological principles with computer science techniques, to effectively restructure the time-consuming computations in genetic linkage analysis. PMID:8317490

  7. Efficient Estimation of Realized Kinship from Single Nucleotide Polymorphism Genotypes.

    PubMed

    Wang, Bowen; Sverdlov, Serge; Thompson, Elizabeth

    2017-03-01

    Realized kinship is a key statistic in analyses of genetic data involving relatedness of individuals or structure of populations. There are several estimators of kinship that make use of dense SNP genotypes. We introduce a class of estimators, of which some existing estimators are special cases. Within this class, we derive properties of the estimators and determine an optimal estimator. Additionally, we introduce an alternative marker weighting that takes allelic associations [linkage disequilibrium (LD)] into account, and apply this weighting to several estimators. In a simulation study, we show that improved estimators are obtained (1) by optimal weighting of markers, (2) by taking physical contiguity of genome into account, and (3) by weighting on the basis of LD.

  8. Disequilibrium melt distributions during static recrystallisation

    NASA Astrophysics Data System (ADS)

    Walte, N. P.; Bons, P. D.; Passchier, C. W.; Koehn, D.; Arnold, J.

    2003-04-01

    DISEQUILIBRIUM MELT DISTRIBUTIONS DURING STATIC RECRYSTALLISATION N.P. Walte (1), P.D. Bons (2), C.W. Passchier (1), D. Koehn (1), J. Arnold (1) (1) Institute for Earth Sciences, Johannes Gutenberg-University, Mainz, Germany, (2) Institute for Earth Sciences, Eberhard Karls University, Tübingen, Germany (walte@mail.uni-mainz.de) The geometry of melt-filled pores in a partially molten rock strongly controls the permeability, rheology and initial segregation of melt. Current theory for monomineralic aggregates, using only the wetting angle and melt fraction as parameters, predicts a perfectly regular melt framework or equally shaped melt inclusions on grain boundary junctions. However, published melt-present high-temperature experiments with rock forming minerals such as quartz or olivine show considerable deviations from this predicted regular equilibrium melt geometry. Disequilibrium features, such as fully wetted grain boundaries, melt lenses, and large melt patches have been described, and were attributed to surface energy anisotropy of the minerals. This study used static analogue experiments with norcamphor plus ethanol liquid, that allow continuous in-situ observation of the evolving distribution of melt during static recrystallisation. The liquid-crystal surface energy of norcamphor is effectively isotropic. For the experiments an approximately 0.1 mm thin sample of norcamphor plus ethanole was placed between two glass plates and observed with a miroscope. Ethanol was used as a melt analogue because it allows to run experiments at room temperature, avoiding any temperature gradients. The wetting angle is approximately 15°, which is well below 60° and within the range reported for quartz and olivine plus melt experiments. The experiments show that all described disequilibrium features can form during fluid-enhanced static recrystallisation, especially where surrounding grains consume small, few-sided grains. These features are unstable and transient: a

  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. 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.

  11. 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.

  12. 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.

  13. 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...

  14. SNP genotyping in melons: genetic variation, population structure, and linkage disequilibrium.

    PubMed

    Esteras, Cristina; Formisano, Gelsomina; Roig, Cristina; Díaz, Aurora; Blanca, José; Garcia-Mas, Jordi; Gómez-Guillamón, María Luisa; López-Sesé, Ana Isabel; Lázaro, Almudena; Monforte, Antonio J; Picó, Belén

    2013-05-01

    Novel sequencing technologies were recently used to generate sequences from multiple melon (Cucumis melo L.) genotypes, enabling the in silico identification of large single nucleotide polymorphism (SNP) collections. In order to optimize the use of these markers, SNP validation and large-scale genotyping are necessary. In this paper, we present the first validated design for a genotyping array with 768 SNPs that are evenly distributed throughout the melon genome. This customized Illumina GoldenGate assay was used to genotype a collection of 74 accessions, representing most of the botanical groups of the species. Of the assayed loci, 91 % were successfully genotyped. The array provided a large number of polymorphic SNPs within and across accessions. This set of SNPs detected high levels of variation in accessions from this crop's center of origin as well as from several other areas of melon diversification. Allele distribution throughout the genome revealed regions that distinguished between the two main groups of cultivated accessions (inodorus and cantalupensis). Population structure analysis showed a subdivision into five subpopulations, reflecting the history of the crop. A considerably low level of LD was detected, which decayed rapidly within a few kilobases. Our results show that the GoldenGate assay can be used successfully for high-throughput SNP genotyping in melon. Since many of the genotyped accessions are currently being used as the parents of breeding populations in various programs, this set of mapped markers could be used for future mapping and breeding efforts.

  15. 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 ...

  16. Extensive intragenic recombination and patterns of linkage disequilibrium at the CSN3 locus in European rabbit

    PubMed Central

    Carneiro, Miguel; Ferrand, Nuno

    2007-01-01

    Kappa-casein (CSN3) plays an important role in stabilising the Ca-sensitive caseins in the micelle. The European rabbit (Oryctolagus cuniculus) CSN3 has previously been shown to possess two alleles (A and B), which differ deeply in their intronic regions (indels of 100 and 1550 nucleotides in introns 1 and 4, respectively). Furthermore, a correlation between several reproductive performance traits and the different alleles was described. However, all these data were exclusively collected in rabbit domestic breeds, preventing a deeper understanding of the extensive polymorphism observed in the CSN3 gene. Additionally, the techniques available for the typing of both indel polymorphisms were until now not suitable for large-scale studies. In this report, we describe a simple, PCR-based typing method to distinguish rabbit CSN3 alleles. We analyse both ancient wild rabbit populations from the Iberian Peninsula and France, and the more recently derived English wild rabbits and domestic stocks. A new allele (C) showing another major indel (250 bp) in intron 1 was found, but exclusively detected in Iberian wild rabbits. In addition, our survey revealed the occurrence of new haplotypes in wild populations, suggesting that intragenic recombination is important in creating genetic diversity at this locus. This easy and low cost single-step PCR-based method results in an improvement over previous described techniques, can be easily set up in a routine molecular laboratory and would probably be a valuable tool in the management of rabbit domestic breeds. PMID:17433245

  17. 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...

  18. 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 ...

  19. 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...

  20. 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.

  1. Genome-wide association filtering using a highly locus-specific transmission/disequilibrium test.

    PubMed

    Abad-Grau, María M; Medina-Medina, Nuria; Montes-Soldado, Rosana; Moreno-Ortega, José; Matesanz, Fuencisla

    2010-09-01

    Multimarker transmission/disequilibrium tests (TDTs) are powerful association and linkage tests used to perform genome-wide filtering in the search for disease susceptibility loci. In contrast to case/control studies, they have a low rate of false positives for population stratification and admixture. However, the length of a region found in association with a disease is usually very large because of linkage disequilibrium (LD). Here, we define a multimarker proportional TDT (mTDT ( P )) designed to improve locus specificity in complex diseases that has good power compared to the most powerful multimarker TDTs. The test is a simple generalization of a multimarker TDT in which haplotype frequencies are used to weight the effect that each haplotype has on the whole measure. Two concepts underlie the features of the metric: the 'common disease, common variant' hypothesis and the decrease in LD with chromosomal distance. Because of this decrease, the frequency of haplotypes in strong LD with common disease variants decreases with increasing distance from the disease susceptibility locus. Thus, our haplotype proportional test has higher locus specificity than common multimarker TDTs that assume a uniform distribution of haplotype probabilities. Because of the common variant hypothesis, risk haplotypes at a given locus are relatively frequent and a metric that weights partial results for each haplotype by its frequency will be as powerful as the most powerful multimarker TDTs. Simulations and real data sets demonstrate that the test has good power compared with the best tests but has remarkably higher locus specificity, so that the association rate decreases at a higher rate with distance from a disease susceptibility or disease protective locus.

  2. Genome-wide association filtering using a highly locus-specific transmission/disequilibrium test

    PubMed Central

    Medina-Medina, Nuria; Montes-Soldado, Rosana; Moreno-Ortega, José; Matesanz, Fuencisla

    2010-01-01

    Multimarker transmission/disequilibrium tests (TDTs) are powerful association and linkage tests used to perform genome-wide filtering in the search for disease susceptibility loci. In contrast to case/control studies, they have a low rate of false positives for population stratification and admixture. However, the length of a region found in association with a disease is usually very large because of linkage disequilibrium (LD). Here, we define a multimarker proportional TDT (mTDTP) designed to improve locus specificity in complex diseases that has good power compared to the most powerful multimarker TDTs. The test is a simple generalization of a multimarker TDT in which haplotype frequencies are used to weight the effect that each haplotype has on the whole measure. Two concepts underlie the features of the metric: the ‘common disease, common variant’ hypothesis and the decrease in LD with chromosomal distance. Because of this decrease, the frequency of haplotypes in strong LD with common disease variants decreases with increasing distance from the disease susceptibility locus. Thus, our haplotype proportional test has higher locus specificity than common multimarker TDTs that assume a uniform distribution of haplotype probabilities. Because of the common variant hypothesis, risk haplotypes at a given locus are relatively frequent and a metric that weights partial results for each haplotype by its frequency will be as powerful as the most powerful multimarker TDTs. Simulations and real data sets demonstrate that the test has good power compared with the best tests but has remarkably higher locus specificity, so that the association rate decreases at a higher rate with distance from a disease susceptibility or disease protective locus. PMID:20603721

  3. 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 ...

  4. Linkage Maps in Pea

    PubMed Central

    Ellis, THN.; Turner, L.; Hellens, R. P.; Lee, D.; Harker, C. L.; Enard, C.; Domoney, C.; Davies, D. R.

    1992-01-01

    We have analyzed segregation patterns of markers among the late generation progeny of several crosses of pea. From the patterns of association of these markers we have deduced linkage orders. Salient features of these linkages are discussed, as is the relationship between the data presented here and previously published genetic and cytogenetic data. PMID:1551583

  5. Disequilibrium condensation environments in space - A frontier in thermodynamics

    NASA Technical Reports Server (NTRS)

    De, B. R.

    1979-01-01

    The thermal-disequilibrium aspect of the problem of dust-particle formation from a gas phase in an open space environment is discussed in an effort to draw attention to the space condensation environment as an interesting arena for application and extension of the ideas and formalisms of nonequilibrium thermodynamics. It is shown that quasi-steady states with a disequilibrium between the gas-phase kinetic temperature and the condensed-phase internal temperature appear to be the norm of condensation environments in space. Consideration of the case of condensation onto a bulk condensed phase indicates that these quasi-steady states may constitute Prigogine dissipative structures. It is suggested that a proper study of the process of condensation in a space environment should include any effects arising from thermal disequilibrium.

  6. Genetic basis of agronomically important traits in sugar beet (Beta vulgaris L.) investigated with joint linkage association mapping.

    PubMed

    Reif, Jochen C; Liu, Wenxin; Gowda, Manje; Maurer, Hans Peter; Möhring, Jens; Fischer, Sandra; Schechert, Axel; Würschum, Tobias

    2010-11-01

    Epistatic interactions may contribute substantially to the hybrid performance of sugar beet. The main goal of our study was to dissect the genetic basis of eight important physiological and agronomic traits using two different biometrical models for joint linkage association mapping. A total of 197 genotypes of an elite breeding population were evaluated in multi-location trials and fingerprinted with 194 SNP markers. Two different statistical models were used for the genome-wide scan for marker-trait associations: Model A, which corrects for the genetic background with markers as cofactors and Model B, which additionally models a population effect. Based on the extent of linkage disequilibrium in the parental population, we estimated that for a genome-wide scan at least 100 equally spaced markers are necessary. We mapped across the eight traits 39 QTL for Model A and 22 for Model B. Only 11% of the total number of QTL were identified based on Models A and B, which indicates that both models are complementary. Epistasis was detected only for two out of the eight traits, and contributed only to a minor extent to the genotypic variance. This low relevance of epistasis implies that in sugar beet breeding the prediction of performance of three-way hybrids is feasible with high accuracy based on the means of their single crosses.

  7. 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 ...

  8. Linked versus unlinked estimates of mortality and length of life by education and marital status: evidence from the first record linkage study in Lithuania.

    PubMed

    Shkolnikov, Vladimir M; Jasilionis, Domantas; Andreev, Evgeny M; Jdanov, Dmitri A; Stankuniene, Vladislava; Ambrozaitiene, Dalia

    2007-04-01

    Earlier studies have found large and increasing with time differences in mortality by education and marital status in post-Soviet countries. Their results are based on independent tabulations of population and deaths counts (unlinked data). The present study provides the first census-linked estimates of group-specific mortality and the first comparison between census-linked and unlinked mortality estimates for a post-Soviet country. The study is based on a data set linking 140,000 deaths occurring in 2001-2004 in Lithuania with the population census of 2001. The same socio-demographic information about the deceased is available from both the census and death records. Cross-tabulations and Poisson regressions are used to compare linked and unlinked data. Linked and unlinked estimates of life expectancies and mortality rate ratios are calculated with standard life table techniques and Poisson regressions. For the two socio-demographic variables under study, the values from the death records partly differ from those from the census records. The deviations are especially significant for education, with 72-73%, 66-67%, and 82-84% matching for higher education, secondary education, and lower education, respectively. For marital status, deviations are less frequent. For education and marital status, unlinked estimates tend to overstate mortality in disadvantaged groups and they understate mortality in advantaged groups. The differences in inter-group life expectancy and the mortality rate ratios thus are significantly overestimated in the unlinked data. Socio-demographic differences in mortality previously observed in Lithuania and possibly other post-Soviet countries are overestimated. The growth in inequalities over the 1990s is real but might be overstated. The results of this study confirm the existence of large and widening health inequalities but call for better data.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 210Po and 210Pb disequilibrium in the hydrothermal vent fluids and chimney deposits from Juan de Fuca Ridge

    NASA Astrophysics Data System (ADS)

    Hussain, N.; Church, T. M.; Luther, G. W., III; Moore, W. S.

    Significantly deficient 210Po/210Pb activity ratios (0.14±0.14) are measured in the hydrothermal vent fluids collected from Juan de Fuca Ridge. Chimney deposits generally showed <5 dpm of excess 210Po. However, one sample from the outermost layer of a sealed spire yielded >1200 dpm g-1 of excess 210Po.If the observed 210Po-210Pb disequilibrium in vent fluids is a result of 210Po removal by the precipitates, residence time of polonium with respect to its irreversible removal from hot fluids is estimated to be of the order of a few minutes. Alternatively, if the disequilibrium is a result of an insufficient growth of 210Po from in-situ 210Pb following heating, the residence time of hot fluids within the hydrothermal system can be shown to be less than 30 days, which is considerably lower than previously reported values.

  14. 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…

  15. 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

  16. 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.

  17. Can Genetic Estimators Provide Robust Estimates of the Effective Number of Breeders in Small Populations?

    PubMed Central

    Hoehn, Marion; Gruber, Bernd; Sarre, Stephen D.; Lange, Rebecca; Henle, Klaus

    2012-01-01

    The effective population size (Ne) is proportional to the loss of genetic diversity and the rate of inbreeding, and its accurate estimation is crucial for the monitoring of small populations. Here, we integrate temporal studies of the gecko Oedura reticulata, to compare genetic and demographic estimators of Ne. Because geckos have overlapping generations, our goal was to demographically estimate NbI, the inbreeding effective number of breeders and to calculate the NbI/Na ratio (Na = number of adults) for four populations. Demographically estimated NbI ranged from 1 to 65 individuals. The mean reduction in the effective number of breeders relative to census size (NbI/Na) was 0.1 to 1.1. We identified the variance in reproductive success as the most important variable contributing to reduction of this ratio. We used four methods to estimate the genetic based inbreeding effective number of breeders NbI(gen) and the variance effective populations size NeV(gen) estimates from the genotype data. Two of these methods - a temporal moment-based (MBT) and a likelihood-based approach (TM3) require at least two samples in time, while the other two were single-sample estimators - the linkage disequilibrium method with bias correction LDNe and the program ONeSAMP. The genetic based estimates were fairly similar across methods and also similar to the demographic estimates excluding those estimates, in which upper confidence interval boundaries were uninformative. For example, LDNe and ONeSAMP estimates ranged from 14–55 and 24–48 individuals, respectively. However, temporal methods suffered from a large variation in confidence intervals and concerns about the prior information. We conclude that the single-sample estimators are an acceptable short-cut to estimate NbI for species such as geckos and will be of great importance for the monitoring of species in fragmented landscapes. PMID:23139784

  18. Linkage disequilibria and haplotype structure of four SNPs of the interleukin 1 gene cluster in seven Asian Indian populations.

    PubMed

    Raj, Srilakshmi M; Chakraborty, Ranajit; Wang, Ning; Govindaraju, Diddahally R

    2006-02-01

    Variation at four single nucleotide polymorphism (SNP) sites of the interleukin 1 (IL1) gene cluster was investigated among 280 unrelated individuals, representing 7 caste groups from the state of Karnataka, India, and one European American community of Boston, Massachusetts. Allele and haplotype frequencies, strength of linkage disequilibrium, and signatures of recombination varied considerably among populations. Variable community sizes and traditions of consanguinity may account for the observed variation.

  19. The tetranucleotide repeat polymorphism C2_4_4: population data and linkage disequilibria with HLA class I.

    PubMed

    Stadlbacher, Simone; Dauber, Eva-Maria; Wenda, Sabine; Glock, Barbara; Hafner, Maria; Körmöczi, Günther F; Mayr, Wolfgang R

    2003-01-01

    The tetranucleotide repeat locus C2_4_4 situated in the HLA class I region (6p21.3) and the HLA-ABC specificities were investigated in an Austrian population sample of 240 unrelated Caucasoid individuals. The analysis of the linkage disequilibrium between C2_4_4 and HLA class I showed several significant values, especially when factors coded for by so-called "superhaplotypes" were considered; such linkage disequilibria are of importance for the practical use of HLA coded short tandem repeats.

  20. Significant Linkage Evidence for a Predisposition Gene for Pelvic Floor Disorders on Chromosome 9q21

    PubMed Central

    Allen-Brady, Kristina; Norton, Peggy A.; Farnham, James M.; Teerlink, Craig; Cannon-Albright, Lisa A.

    2009-01-01

    Predisposition factors for pelvic floor disorders (PFDs), including pelvic organ prolapse (POP), stress urinary incontinence (SUI), urge urinary incontinence (UUI), and hernias, are not well understood. We assessed linkage evidence for PFDs in mostly sister pairs who received treatment for moderate-to-severe POP. We genotyped 70 affected women of European descent from 32 eligible families with at least two affected cases by using the Illumina 1 million single-nucleotide polymorphism (SNP) marker set. Parametric linkage analysis with general dominant and recessive models was performed by the Markov chain Monte Carlo linkage analysis method, MCLINK, and a set of SNPs was formed, from which those in high linkage disequilibrium were eliminated. Significant genome-wide evidence for linkage was identified on chromosome 9q21 with a HLOD score of 3.41 under a recessive model. Seventeen pedigrees (53%) had at least nominal evidence for linkage on a by-pedigree basis at this region. These results provide evidence for a predisposition gene for PFDs on chromosome 9q. PMID:19393595

  1. 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.

  2. 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

  3. 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.

  4. Linkage on chromosome 14 in a genomewide linkage study of a broad anxiety phenotype

    PubMed Central

    Middeldorp, Christel M.; Hottenga, Jouke-Jan; Slagboom, P. Eline; Sullivan, Patrick F.; de Geus, Eco J.C.; Posthuma, Danielle; Willemsen, Gonneke; Boomsma, Dorret I.

    2014-01-01

    Several linkage studies on anxiety have been carried out in samples ascertained through probands with panic disorder. The results indicated that using a broad anxiety phenotype instead of a DSM-IV anxiety disorder diagnosis might enhance the chance of finding a linkage signal. In the current study, a genome-wide linkage analysis was performed on anxiety measured with a self-report questionnaire whose scores are highly correlated with DSM-IV anxiety disorders. The self-report questionnaire was included in five surveys of a longitudinal study of the Netherlands Twin Register. Genotype and phenotype data were available for 1,602 twins and siblings. To estimate Identity By Descent (IBD), additional genotype data for 564 parents and 22 siblings were used. Linkage analyses were carried out using MERLIN-Regress on the average anxiety scores across time. A linkage signal (LOD-score 3.4, empirical p-value 0.07) was obtained at chromosome 14 for marker D14S65 at 105 cM (90% confidence interval 99 cM - 115 cM bounded by markers D14S1434 and D14S985). This finding replicates a linkage finding for a broad anxiety phenotype in a clinically based sample, indicating that the region might harbor a QTL associated with the whole spectrum of general anxiety, i.e. from the normal to the clinical range. Moreover, genome-wide linkage and association studies on emotionality in mice obtained significant results in a syntenic region on mouse chromosome 12. Two homolog genes lie in this region –Dlk1 (delta-like 1 homolog, Drosophila) and Rtl1 (retrotransposon-like 1). Future association studies of these genes are warranted. PMID:17700576

  5. 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...

  6. Haplotype diversity and linkage disequilibrium at DRD2 locus--a study on four population groups of Andhra Pradesh, India.

    PubMed

    Saraswathy, Kallur Nava; Mukhopadhyay, Rupak; Shukla, Deepti; Kaur, Harpreet; Sachdeva, Mohinder Pal; Rao, A P; Saksena, Deepti; Kalla, Aloke Kumar

    2009-02-01

    Dopamine receptor D2 (DRD2) is expressed in the central nervous system and has a high affinity for many antipsychotic drugs. Besides several epidemiological investigations on association of DRD2 locus polymorphism(s) with neuropsychiatric problems and addictive behavior, a few polymorphisms in this locus have also been used to understand genomic diversity and population migratory histories globally. The present study attempts to understand the genomic diversity/affinity among four endogamous groups of Andhra Pradesh (India) against the backdrop of diversity studies from other parts of India and the rest of the world, with special reference to DRD2 locus. The four population groups from Adilabad District of Andhra Pradesh, namely, Brahmin (n=50), Nayakpod (n=49), Thoti (n=52), and Kolam (n=53), were included in the study. The DRD2 markers typed for the present study are three biallelic restriction fragments, that is, TaqI A (rs1800497), TaqI B (rs1079597), and TaqI D (rs1800498). Scoring of DRD2 haplotypes with respect to the three TaqI sites shows that five out of eight possible haplotypes are shared by the four populations. Ancestral haplotype B2D2A1 is most frequent among Thotis (0.359). The results of the present study indicate a differential gene flow into South India followed by certain important demographic events resulting in diversified peopling of India.

  7. Contrasting Effects of Selection on Sequence Diversity and Linkage Disequilibrium at Two Phytoene Synthase LociW⃞

    PubMed Central

    Palaisa, Kelly A.; Morgante, Michele; Williams, Mark; Rafalski, Antoni

    2003-01-01

    We investigated the effects of human selection for yellow endosperm color, representing increased carotenoid content, on two maize genes, the Y1 phytoene synthase and PSY2, a putative second phytoene synthase. Multiple polymorphic sites were identified at Y1 and PSY2 in 75 white and yellow maize inbred lines. Many polymorphic sites showed strong association with the endosperm color phenotype at Y1, but no detectable association was found at PSY2. Nucleotide diversity was equivalent for whites and yellows at PSY2 but was 19-fold less in yellows than in whites at Y1, consistent with the white ancestral state of the gene. The strong sequence haplotype conservation within yellows at Y1 and a significant, negative Tajima's D both verified positive selection for yellow endosperm. We propose that two independent gain-of-function events associated with insertions into the promoter of the Y1 gene and upregulation of expression in endosperm have been incorporated into yellow maize. PMID:12897253

  8. 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...

  9. 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

  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. Apprenticeship - School Linkage Implementation Manual.

    ERIC Educational Resources Information Center

    Martin, Sharon T.; And Others

    Developed to assist interested sponsors in implementing apprenticeship-school linkage projects, this guide is intended to organize the collective experiences of those who have implemented the demonstration projects to highlight the day-to-day mechanics involved. Section 1 overviews apprenticeship-school linkage. In section 2 factors are described…

  12. 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

  13. The accuracy of marker-assisted selection for quantitative traits within populations in linkage equilibrium.

    PubMed Central

    Ollivier, L

    1998-01-01

    Using the concept of conditional coancestry, given observed markers, an explicit expression of the accuracy of marker-based selection is derived in situations of linkage equilibrium between markers and quantitative trait loci (QTL), for the general case of full-sib families nested within half-sib families. Such a selection scheme is rather inaccurate for moderate values of family sizes and QTL variance, and the accuracies predicted for linkage disequilibrium can never be reached. The result is used to predict the accuracy of marker-assisted combined selection (MACS) and is shown to agree with previous MACS results obtained by simulation of a best linear unbiased prediction animal model. Low gains in accuracy are generally to be expected compared to standard combined selection. The maximum gain, assuming infinite family size and all QTLs marked, is about 50%. PMID:9539449

  14. The problem of ascertainment for linkage analysis

    SciTech Connect

    Vieland, V.; Hodge, S.E.

    1996-05-01

    It is generally believed that ascertainment corrections are unnecessary in linkage analysis, provided individuals are selected for study solely on the basis of trait phenotype and not on the basis of marker genotype. The theoretical rationale for this is that standard linkage analytic methods involve conditioning likelihoods on all the trait data, which may be viewed as an application of the ascertainment assumption-free (AAF) method of Ewens and Shute. In this paper, we show that when the observed pedigree structure depends on which relatives within a pedigree happen to have been the probands (proband-dependent, or PD, sampling) conditioning on all the trait data is not a valid application of the AAF method and will result in asymptotically biased estimates of genetic parameters (except under single ascertainment). Furthermore, this result holds even if the recombination fraction R is the only parameter of interest. Since the lod score is proportional to the likelihood of the marker data conditional on all the trait data, this means that when data are obtained under PD sampling the lod score will yield asymptotically biased estimates of R, and that so-called mod scores (i.e., lod scores maximized over both R and parameters {theta} of the trait distribution) will yield asymptotically biased estimates of R and {theta}. Furthermore, the problem appears to be intractable, in the sense that it is not possible to formulate the correct likelihood conditional on observed pedigree structure. In this paper we do not investigate the numerical magnitude of the bias, which may be small in many situations. On the other hand, virtually all linkage data sets are collected under PD sampling. Thus, the existence of this bias will be the rule rather than the exception in the usual applications. 25 refs., 2 figs., 3 tabs.

  15. Simultaneous estimation of the locations and effects of multiple disease loci in case-control studies.

    PubMed

    Chien, Li-Chu; Chiu, Yen-Feng; Liang, Kung-Yee; Chuang, Lee-Ming

    2015-04-01

    The genetic basis of complex diseases often involves multiple causative loci. Under such a disease etiology, assuming one disease locus in linkage disequilibrium mapping is likely to induce bias and lead to efficiency loss in disease locus estimation. An approach is needed for simultaneously localizing multiple functional loci within the same region. However, due to the increasing number of parameters accompanying disease loci, these estimates can be computationally infeasible. To circumvent this problem, we propose to estimate the main and two-adjacent-locus joint effects and a nuisance parameter at the disease loci separately through a linear approximation. Estimates of the genetic effects are entered into a generalized estimating equation to estimate disease loci, and the procedure is conducted iteratively until convergence. The proposed method provides estimates and confidence intervals (CIs) for the disease loci, the genetic main effects, and the joint effects of two adjacent disease loci, with the CIs for the disease loci providing useful regions for further fine-mapping. We apply the proposed approach to a data example of case-control studies. Results of the simulations and data example suggest that the developed method performs well in terms of bias, variance, and coverage probability under scenarios with up to three disease loci.

  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. On the comparison between equilibrium and disequilibrium condensation sequences of meteorites

    NASA Technical Reports Server (NTRS)

    De, B. R.

    1977-01-01

    A definition is presented of a simple formalism for calculating the condensation sequence of meteoritic minerals in a cooling vapor phase in temperature disequilibrium (between the vapor phase and the condensed phase) when such minerals condense congruently. Certain preliminary comments are made about the possibility of judging the relative plausibility of the equilibrium and the disequilibrium models from the observations in meteorites if a monotonic cooling were indeed the course of condensation in either case.

  18. A Disequilibrium Adjustment Mechanism for CPE Macroeconometric Models: Initial Testing on SOVMOD.

    DTIC Science & Technology

    1979-02-01

    062 1H0 SRI INTERNATIONAL ARLINGTON VA STRATEGIC STUDIES CENTER F/ T 5/3 DISEQUILIBRIUM ADJUSTMENT MECHANISM FOR CPE MACROECOAI0AIETRIC -E (U) FEB...wC) u Approved for Review Distribution: 0 Richard B. Foster, Director Strategic Studies Center Approved for public release; distribution unlimited...describes work on the model aimed at facilitating the integration of a disequilibrium adjustment mechanism into the macroeconometric model. The

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. A high-density SNP genome-wide linkage scan in a large autism extended pedigree.

    PubMed

    Allen-Brady, K; Miller, J; Matsunami, N; Stevens, J; Block, H; Farley, M; Krasny, L; Pingree, C; Lainhart, J; Leppert, M; McMahon, W M; Coon, H

    2009-06-01

    We performed a high-density, single nucleotide polymorphism (SNP), genome-wide scan on a six-generation pedigree from Utah with seven affected males, diagnosed with autism spectrum disorder. Using a two-stage linkage design, we first performed a nonparametric analysis on the entire genome using a 10K SNP chip to identify potential regions of interest. To confirm potentially interesting regions, we eliminated SNPs in high linkage disequilibrium (LD) using a principal components analysis (PCA) method and repeated the linkage results. Three regions met genome-wide significance criteria after controlling for LD: 3q13.2-q13.31 (nonparametric linkage (NPL), 5.58), 3q26.31-q27.3 (NPL, 4.85) and 20q11.21-q13.12 (NPL, 5.56). Two regions met suggestive criteria for significance 7p14.1-p11.22 (NPL, 3.18) and 9p24.3 (NPL, 3.44). All five chromosomal regions are consistent with other published findings. Haplotype sharing results showed that five of the affected subjects shared more than a single chromosomal region of interest with other affected subjects. Although no common autism susceptibility genes were found for all seven autism cases, these results suggest that multiple genetic loci within these regions may contribute to the autism phenotype in this family, and further follow-up of these chromosomal regions is warranted.

  4. Genetic variation in Arizona Mexican Americans: estimation and interpretation of admixture proportions.

    PubMed

    Long, J C; Williams, R C; McAuley, J E; Medis, R; Partel, R; Tregellas, W M; South, S F; Rea, A E; McCormick, S B; Iwaniec, U

    1991-02-01

    Mexican Americans are a numerous and fast growing ethnic population in the United States. Yet little is known about their genetic structure. Since they are a hybrid, it is of interest to identify their parental populations and to estimate the relative contributions of these groups. This information is relevant to historical, biomedical, and evolutionary concerns. New genetic typings on 730 Arizona Mexican Americans for the HLA-A, HLA-B, ABO, Rh, MNSs, Duffy, Kidd, and Kell loci are presented here and they are used to estimate ancestral contributions. We considered both a dihybrid model with Amerindians and Spaniards as proposed ancestors, and a trihybrid model with Amerindians, Spaniards, and Africans as proposed ancestors. A modified weighted least squares method that allows for linkage disequilibrium was used to estimate ancestral contributions for each model. The following admixture estimates were obtained: Amerindian, 0.29 +/- 0.04; Spaniard, 0.68 +/- 0.05; and African, 0.03 +/- 0.02. The interpretation of these results with respect to Amerindian and Spanish ancestry is straightforward. African ancestry is strongly supported by the presence of a marker of African descent, Fy, despite the fact that the standard error of the estimate is as large as the estimated admixture proportion. An evaluation of the sensitivity of these results to a number of variables is presented: 1) our choices of ancestral allele frequencies, 2) the possibility of selection at HLA and the blood groups, and 3) genetic drift in Mexican Americans.

  5. 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.

  6. Genetic Linkage Map of Fishes of the Genus Xiphophorus (Teleostei: Poeciliidae)

    PubMed Central

    Morizot, D. C.; Slaugenhaupt, S. A.; Kallman, K. D.; Chakravarti, A.

    1991-01-01

    Analysis of genotypes of 76 polymorphic loci in more than 2600 backcross hybrid individuals derived from intra- and interspecific genetic crosses of fishes of the genus Xiphophorus (Poeciliidae) resulted in the identification of 17 multipoint linkage groups containing 55 protein-coding loci and one sex chromosome-linked pigment pattern gene. Multipoint linkage analyses identified highly probable gene orders for 10 linkage groups. The total genome length was estimated to be ~18 Morgans. Comparisons of the Xiphophorus linkage map with those of other fishes, amphibians and mammals suggested that fish gene maps are remarkably similar and probably retain many syntenic groups present in the ancestor of all vertebrates. PMID:2004711

  7. 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

  8. Markov chain Monte Carlo linkage analysis: effect of bin width on the probability of linkage.

    PubMed

    Slager, S L; Juo, S H; Durner, M; Hodge, S E

    2001-01-01

    We analyzed part of the Genetic Analysis Workshop (GAW) 12 simulated data using Monte Carlo Markov chain (MCMC) methods that are implemented in the computer program Loki. The MCMC method reports the "probability of linkage" (PL) across the chromosomal regions of interest. The point of maximum PL can then be taken as a "location estimate" for the location of the quantitative trait locus (QTL). However, Loki does not provide a formal statistical test of linkage. In this paper, we explore how the bin width used in the calculations affects the max PL and the location estimate. We analyzed age at onset (AO) and quantitative trait number 5, Q5, from 26 replicates of the general simulated data in one region where we knew a major gene, MG5, is located. For each trait, we found the max PL and the corresponding location estimate, using four different bin widths. We found that bin width, as expected, does affect the max PL and the location estimate, and we recommend that users of Loki explore how their results vary with different bin widths.

  9. Nitrogen Isotopic Disequilibrium in the Cape York III A Iron

    NASA Astrophysics Data System (ADS)

    Zipfel, J.; Kim, Y.; Marti, K.

    1995-09-01

    disequilibrium as observed in Cape York include (a) survival of primary isotopic heterogeneities; (b) N loss during secondary processes, e.g., metamorphic heating and shock deformation: (a) Graphite grains within metal of the Acapulco meteorite were identified as carrier of isotopically distinct N and C components and were interpreted as surviving (possibly presolar) grains unaffected by the igneous alteration of the bulk meteorite (5). Obviously such grains exchanged N isotopically with metal and chromite, but not with sulfides and silicates, as these do not carry the light N of metal and chromite (6). The mechanism of this exchange is, however, unclear. No graphite has been observed so far in Cape York. Yet, isotopic heterogeneities in the precursor material of Cape York can not be excluded. During melting of the parent asteroid one would expect homogenization of the nitrogen isotopes. Since chromite and metal crystallize at high temperatures, a probable exchange of N between the S-rich melt and a distinct N reservoir at lower temperature might explain the disequilibrium. (b) Troilite nodules in Cape York indicate a small degree of shock deformation (2,3,5). One might argue that some N was lost and the residue fractionated during this event. However, 107Ag/109Ag ratios from metal and troilite correlate with Pd/Ag ratios, which is not the case in severely shocked magmatic irons (7). In addition, similar isotopic N fractionations are found in the "magmatic" Acapulco meteorite, which shows no indication of shock deformation. Therefore, secondary loss of N preferentially from troilite can be excluded. References: [1] Haak H. and Scott E. (1993) GCA, 57, 3457-3472. [2] Buchwald V. (1975) Handbook of Iron Meteorites, Vols. 1_3, Univ. of California and Arizona State Univ., Berkeley. [3] Kracher A et al. (1977) Geochem. J., 11, 207-217. [4] Murty S. and Marti K. (1994) GCA, 58, 1841-1848. [5] El Goresy A. et al. (1995) Nature, 373, 496-499. [6] Kim Y. et al. (1992) LPS XXIII, 691

  10. Education: Linkages with Economic Development.

    ERIC Educational Resources Information Center

    Clouser, Rodney L.

    A review of the literature of research in education and economics revealed very limited linkages between education (human capital) and economic development. Much of the economic development research has been carried out in developing nations and is case-study based. Many case studies concentrate on identifying factors that influence location or…

  11. 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

    2015-12-14

    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.

  12. Empirical Characteristics of Family-Based Linkage to a Complex Trait: the ADIPOQ Region and Adiponectin Levels

    PubMed Central

    Hellwege, Jacklyn N.; Palmer, Nicholette D.; Brown, W. Mark; Ziegler, Julie T.; An, S. Sandy; Guo, Xiuqing; Chen, Y.-D. Ida; Taylor, Kent; Hawkins, Gregory A.; Ng, Maggie C.Y.; Speliotes, Elizabeth K.; Lorenzo, Carlos; Norris, Jill M.; Rotter, Jerome I.; Wagenknecht, Lynne E.; Langefeld, Carl D.; Bowden, Donald W.

    2014-01-01

    We previously identified a low frequency (1.1%) coding variant (G45R; rs200573126) in the adiponectin gene (ADIPOQ) which was the basis for a multipoint microsatellite linkage signal (LOD=8.2) for plasma adiponectin levels in Hispanic families. We have empirically evaluated the ability of data from targeted common variants, exome chip genotyping, and genome-wide association study (GWAS) data to detect linkage and association to adiponectin protein levels at this locus. Simple two-point linkage and association analyses were performed in 88 Hispanic families (1150 individuals) using 10,958 SNPs on chromosome 3. Approaches were compared for their ability to map the functional variant, G45R, which was strongly linked (two-point LOD=20.98) and powerfully associated (p-value=8.1×10−50). Over 450 SNPs within a broad 61 Mb interval around rs200573126 showed nominal evidence of linkage (LOD>3) but only four other SNPs in this region were associated with p-values<1.0×10−4. When G45R was accounted for, the maximum LOD score across the interval dropped to 4.39 and the best p-value was 1.1×10−5. Linked and/or associated variants ranged in frequency (0.0018 to 0.50) and type (coding, non-coding) and had little detectable linkage disequilibrium with rs200573126 (r2<0.20). In addition, the two-point linkage approach empirically outperformed multipoint microsatellite and multipoint SNP analysis. In the absence of data for rs200573126, family-based linkage analysis using a moderately dense SNP dataset, including both common and low frequency variants, resulted in stronger evidence for an adiponectin locus than association data alone. Thus, linkage analysis can be a useful tool to facilitate identification of high impact genetic variants. PMID:25447270

  13. 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

  14. 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

  15. Accuracy of Haplotype Frequency Estimation for Biallelic Loci, via the Expectation-Maximization Algorithm for Unphased Diploid Genotype Data

    PubMed Central

    Fallin, Daniele; Schork, Nicholas J.

    2000-01-01

    Haplotype analyses have become increasingly common in genetic studies of human disease because of their ability to identify unique chromosomal segments likely to harbor disease-predisposing genes. The study of haplotypes is also used to investigate many population processes, such as migration and immigration rates, linkage-disequilibrium strength, and the relatedness of populations. Unfortunately, many haplotype-analysis methods require phase information that can be difficult to obtain from samples of nonhaploid species. There are, however, strategies for estimating haplotype frequencies from unphased diploid genotype data collected on a sample of individuals that make use of the expectation-maximization (EM) algorithm to overcome the missing phase information. The accuracy of such strategies, compared with other phase-determination methods, must be assessed before their use can be advocated. In this study, we consider and explore sources of error between EM-derived haplotype frequency estimates and their population parameters, noting that much of this error is due to sampling error, which is inherent in all studies, even when phase can be determined. In light of this, we focus on the additional error between haplotype frequencies within a sample data set and EM-derived haplotype frequency estimates incurred by the estimation procedure. We assess the accuracy of haplotype frequency estimation as a function of a number of factors, including sample size, number of loci studied, allele frequencies, and locus-specific allelic departures from Hardy-Weinberg and linkage equilibrium. We point out the relative impacts of sampling error and estimation error, calling attention to the pronounced accuracy of EM estimates once sampling error has been accounted for. We also suggest that many factors that may influence accuracy can be assessed empirically within a data set—a fact that can be used to create “diagnostics” that a user can turn to for assessing potential

  16. Preliminary genetic linkage map of the abalone Haliotis diversicolor Reeve

    NASA Astrophysics Data System (ADS)

    Shi, Yaohua; Guo, Ximing; Gu, Zhifeng; Wang, Aimin; Wang, Yan

    2010-05-01

    Haliotis diversicolor Reeve is one of the most important mollusks cultured in South China. Preliminary genetic linkage maps were constructed with amplified fragment length polymorphism (AFLP) markers. A total of 2 596 AFLP markers were obtained from 28 primer combinations in two parents and 78 offsprings. Among them, 412 markers (15.9%) were polymorphic and segregated in the mapping family. Chi-square tests showed that 151 (84.4%) markers segregated according to the expected 1:1 Mendelian ratio ( P<0.05) in the female parent, and 200 (85.8%) in the male parent. For the female map, 179 markers were used for linkage analysis and 90 markers were assigned to 17 linkage groups with an average interval length of 25.7 cm. For the male map, 233 markers were used and 94 were mapped into 18 linkage groups, with an average interval of 25.0 cm. The estimated genome length was 2 773.0 cm for the female and 2 817.1 cm for the male map. The observed length of the linkage map was 1 875.2 cm and 1 896.5 cm for the female and male maps, respectively. When doublets were considered, the map length increased to 2 152.8 cm for the female and 2 032.7 cm for the male map, corresponding to genome coverage of 77.6% and 72.2%, respectively.

  17. The first genetic linkage map of Eucommia ulmoides.

    PubMed

    Wang, Dawei; Li, Yu; Li, Long; Wei, Yongcheng; Li, Zhouqi

    2014-04-01

    In accordance with pseudo-testcross strategy, the first genetic linkage map of Eucommia ulmoides Oliv. was constructed by an F1 population of 122 plants using amplified fragment length polymorphism (AFLP) markers. A total of 22 AFLP primer combinations generated 363 polymorphic markers. We selected 289 markers segregating as 1:1 and used them for constructing the parent-specific linkage maps. Among the candidate markers, 127 markers were placed on the maternal map LF and 108 markers on the paternal map Q1. The maternal map LF spanned 1116.1 cM in 14 linkage groups with a mean map distance of 8.78 cM; the paternal map Q1 spanned 929.6 cM in 12 linkage groups with an average spacing of 8.61 cM. The estimated coverage of the genome through two methods was 78.5 and 73.9% for LF, and 76.8 and 71.2% for Q1, respectively. This map is the first linkage map of E. ulmoides and provides a basis for mapping quantitative-trait loci and breeding applications.

  18. 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.

  19. Influence of major element disequilibrium on mantle structure

    NASA Astrophysics Data System (ADS)

    Lithgow-Bertelloni, C.; Xu, W.; Stixrude, L.; Ritsema, J.

    2007-12-01

    At mid-ocean ridges, partial melting of a presumably homogeneous and equilibrated pyrolitic source generates a basaltic crust and leaves behind its depleted complement, harzburgite. The oceanic lithosphere that subducts into the mantle is thus physically and chemically layered. During subduction we expect basalt to separate from harzburgite and the rest of the oceanic lithosphere. Hence, over convective and diffusion time-scales, do basalt and harzburgite re-equilibrate chemically as pyrolite? Most mineralogical models, upon which comparisons to seismology are based, view the mantle as homogeneous and pyrolitic or chemically stratified with homogeneous and equilibrated compositions in each layer. Petrological experiments have shown that a homogeneous pyrolite source region explains MORB and the seismic velocity profile of upper mantle and transition zone to first order. However, this view appears to violate the dynamical constraints given the low chemical diffusivity for mantle materials (10-14-10-16 cm2s-1) in the solid-state, ignoring the effects of fluids and partial melting. Allègre and Turcotte (1986) suggested a mechanically mixed mantle, a marble cake structure in which subducted oceanic lithosphere is deformed into pervasive, narrow pyroxenite veins. Computer simulations suggest a heterogeneous mantle made of a mechanical mixture of basalt and harzburgite, in which pools of basalt may accumulate at the bottom. A stirring time of the mantle between 250 and 750 Myr limits the mixing, stretching and folding of heterogeneity in the mantle. Thus, it seems implausible to equilibrate basalt and harzburgite into pyrolite with a fine (0.1-10 m) stratification given typical chemical diffusivities. We demonstrate that, even with identical bulk compositions, an equilibrium assemblage (EA) along the basalt- harzburgite join and a mechanical mixture of basalt and harzburgite in perfect disequilibrium (MM) have different phase equilibria and therefore different seismic

  20. 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.

  1. Role of syn-eruptive plagioclase disequilibrium crystallization in basaltic magma ascent dynamics.

    PubMed

    La Spina, G; Burton, M; De' Michieli Vitturi, M; Arzilli, F

    2016-12-12

    Timescales of magma ascent in conduit models are typically assumed to be much longer than crystallization and gas exsolution for basaltic eruptions. However, it is now recognized that basaltic magmas may rise fast enough for disequilibrium processes to play a key role on the ascent dynamics. The quantification of the characteristic times for crystallization and exsolution processes are fundamental to our understanding of such disequilibria and ascent dynamics. Here we use observations from Mount Etna's 2001 eruption and a magma ascent model to constrain timescales for crystallization and exsolution processes. Our results show that plagioclase reaches equilibrium in 1-2 h, whereas ascent times were <1 h. Using these new constraints on disequilibrium plagioclase crystallization we also reproduce observed crystal abundances for different basaltic eruptions. The strong relation between magma ascent rate and disequilibrium crystallization and exsolution plays a key role in controlling eruption dynamics in basaltic volcanism.

  2. Role of syn-eruptive plagioclase disequilibrium crystallization in basaltic magma ascent dynamics

    NASA Astrophysics Data System (ADS)

    La Spina, G.; Burton, M.; de'Michieli Vitturi, M.; Arzilli, F.

    2016-12-01

    Timescales of magma ascent in conduit models are typically assumed to be much longer than crystallization and gas exsolution for basaltic eruptions. However, it is now recognized that basaltic magmas may rise fast enough for disequilibrium processes to play a key role on the ascent dynamics. The quantification of the characteristic times for crystallization and exsolution processes are fundamental to our understanding of such disequilibria and ascent dynamics. Here we use observations from Mount Etna's 2001 eruption and a magma ascent model to constrain timescales for crystallization and exsolution processes. Our results show that plagioclase reaches equilibrium in 1-2 h, whereas ascent times were <1 h. Using these new constraints on disequilibrium plagioclase crystallization we also reproduce observed crystal abundances for different basaltic eruptions. The strong relation between magma ascent rate and disequilibrium crystallization and exsolution plays a key role in controlling eruption dynamics in basaltic volcanism.

  3. Role of syn-eruptive plagioclase disequilibrium crystallization in basaltic magma ascent dynamics

    PubMed Central

    La Spina, G.; Burton, M.; de' Michieli Vitturi, M.; Arzilli, F.

    2016-01-01

    Timescales of magma ascent in conduit models are typically assumed to be much longer than crystallization and gas exsolution for basaltic eruptions. However, it is now recognized that basaltic magmas may rise fast enough for disequilibrium processes to play a key role on the ascent dynamics. The quantification of the characteristic times for crystallization and exsolution processes are fundamental to our understanding of such disequilibria and ascent dynamics. Here we use observations from Mount Etna's 2001 eruption and a magma ascent model to constrain timescales for crystallization and exsolution processes. Our results show that plagioclase reaches equilibrium in 1–2 h, whereas ascent times were <1 h. Using these new constraints on disequilibrium plagioclase crystallization we also reproduce observed crystal abundances for different basaltic eruptions. The strong relation between magma ascent rate and disequilibrium crystallization and exsolution plays a key role in controlling eruption dynamics in basaltic volcanism. PMID:27941750

  4. 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

  5. Efficient Record Linkage Algorithms Using Complete Linkage Clustering.

    PubMed

    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.

  6. [Haplotype and linkage analysis of HLA-I classical genes in Chinese Han population].

    PubMed

    Yuan, Fang; Sun, Yu-Ying; Luo, Yuan; Liang, Fei; Liu, Nan; Jin, Li; Liu, Jin-Feng; Liu, Shu-Guang; Xi, Yong-Zhi

    2007-10-01

    The aim of this study was to investigate the parameters of gene frequencies, haplotype frequencies and linkage disequilibrium of HLA-A, -B, -Cw in HLA classical I loci for Chinese Han population. HLA-A, HLA-B and HLA-Cw loci were genotyped in 1014 unrelated China people using low resolution PCR-SSP typing method, and their genetic parameters were analyzed by statistic methods. The results indicated that among all the detected HLA-I genes, A*02 (0.33), A*11 (0.24), B*15 (0.14), B*13 (0.13), Cw*03 (0.25) and Cw*07 (0.18) were the popular gene groups distributing in Chinese Han population, and A*02-B*46 (0.071), A*11-B*15 (0.051), A*02-Cw*01 (0.084), A*11-Cw*03 (0.079), B*46-Cw*01 (0.095) and B*13-Cw*03 (0.071) were the predominant haplotypes in Han population. Additionally, A*02-B*46, A*30-B*13, A*30-Cw*06, A*02-Cw*01, B*46-Cw*01 and B*58-Cw*03 were statistically significant with strong linkage disequilibrium. While A*02-B*15, A*02-B*40, A*24-Cw*03, A*02-Cw*03 and A*31-Cw*03 were in low linkage disequilibrium, among them A*24-Cw*03 appeared frequently in HLA recombination events. In addition, A*02-B*46-Cw*01 (0.075), A*30-B*13-Cw*06 (0.046), A*11-B*13-Cw*03 (0.045), A*33-B*58-Cw*03 (0.044), A*11-B*15-Cw*08 (0.027), A*02-B*38-Cw*07 (0.023) and A*11-B*40-Cw*07 (0.022) were the main extended haplotypes in Han population. In conclusions, this study investigated systematically the genetic polymorphism features of Chinese Han population, which may provide useful genetic parameters for researches in colonial evolution, clinical transplantation and disease susceptibility.

  7. An EST-derived SNP and SSR genetic linkage map of cassava (Manihot esculenta Crantz).

    PubMed

    Rabbi, Ismail Yusuf; Kulembeka, Heneriko Philbert; Masumba, Esther; Marri, Pradeep Reddy; Ferguson, Morag

    2012-07-01

    Cassava (Manihot esculenta Crantz) is one of the most important food security crops in the tropics and increasingly being adopted for agro-industrial processing. Genetic improvement of cassava can be enhanced through marker-assisted breeding. For this, appropriate genomic tools are required to dissect the genetic architecture of economically important traits. Here, a genome-wide SNP-based genetic map of cassava anchored in SSRs is presented. An outbreeder full-sib (F1) family was genotyped on two independent SNP assay platforms: an array of 1,536 SNPs on Illumina's GoldenGate platform was used to genotype a first batch of 60 F1. Of the 1,358 successfully converted SNPs, 600 which were polymorphic in at least one of the parents and was subsequently converted to KBiosciences' KASPar assay platform for genotyping 70 additional F1. High-precision genotyping of 163 informative SSRs using capillary electrophoresis was also carried out. Linkage analysis resulted in a final linkage map of 1,837 centi-Morgans (cM) containing 568 markers (434 SNPs and 134 SSRs) distributed across 19 linkage groups. The average distance between adjacent markers was 3.4 cM. About 94.2% of the mapped SNPs and SSRs have also been localized on scaffolds of version 4.1 assembly of the cassava draft genome sequence. This more saturated genetic linkage map of cassava that combines SSR and SNP markers should find several applications in the improvement of cassava including aligning scaffolds of the cassava genome sequence, genetic analyses of important agro-morphological traits, studying the linkage disequilibrium landscape and comparative genomics.

  8. Multipoint quantitative-trait linkage analysis in general pedigrees.

    PubMed Central

    Almasy, L; Blangero, J

    1998-01-01

    Multipoint linkage analysis of quantitative-trait loci (QTLs) has previously been restricted to sibships and small pedigrees. In this article, we show how variance-component linkage methods can be used in pedigrees of arbitrary size and complexity, and we develop a general framework for multipoint identity-by-descent (IBD) probability calculations. We extend the sib-pair multipoint mapping approach of Fulker et al. to general relative pairs. This multipoint IBD method uses the proportion of alleles shared identical by descent at genotyped loci to estimate IBD sharing at arbitrary points along a chromosome for each relative pair. We have derived correlations in IBD sharing as a function of chromosomal distance for relative pairs in general pedigrees and provide a simple framework whereby these correlations can be easily obtained for any relative pair related by a single line of descent or by multiple independent lines of descent. Once calculated, the multipoint relative-pair IBDs can be utilized in variance-component linkage analysis, which considers the likelihood of the entire pedigree jointly. Examples are given that use simulated data, demonstrating both the accuracy of QTL localization and the increase in power provided by multipoint analysis with 5-, 10-, and 20-cM marker maps. The general pedigree variance component and IBD estimation methods have been implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package. PMID:9545414

  9. 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.

  10. 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.

  11. 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

  12. 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…

  13. 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.

  14. Unconsciously Indigenous Leadership: The Role of Cognitive Disequilibrium in Preparing Democratic Educational Leaders

    ERIC Educational Resources Information Center

    Farmer, Tod Allen

    2008-01-01

    This paper focuses on the role of cognitive disequilibrium in preparing democratic educational leaders. Followers emerge into leaders with what are many times unconsciously socialized norms and values indigenous to their local culture. One of the roles of a democratic leadership preparation program is to challenge these unconsciously accepted…

  15. 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…

  16. 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

  17. Estimating heritability of complex traits from genome-wide association studies using IBS-based Haseman–Elston regression

    PubMed Central

    Chen, Guo-Bo

    2014-01-01

    Exploring heritability of complex traits is a central focus of statistical genetics. Among various previously proposed methods to estimate heritability, variance component methods are advantageous when estimating heritability using markers. Due to the high-dimensional nature of data obtained from genome-wide association studies (GWAS) in which genetic architecture is often unknown, the most appropriate heritability estimator model is often unclear. The Haseman–Elston (HE) regression is a variance component method that was initially only proposed for linkage studies. However, this study presents a theoretical basis for a modified HE that models linkage disequilibrium for a quantitative trait, and consequently can be used for GWAS. After replacing identical by descent (IBD) scores with identity by state (IBS) scores, we applied the IBS-based HE regression to single-marker association studies (scenario I) and estimated the variance component using multiple markers (scenario II). In scenario II, we discuss the circumstances in which the HE regression and the mixed linear model are equivalent; the disparity between these two methods is observed when a covariance component exists for the additive variance. When we extended the IBS-based HE regression to case-control studies in a subsequent simulation study, we found that it provided a nearly unbiased estimate of heritability, more precise than that estimated via the mixed linear model. Thus, for the case-control scenario, the HE regression is preferable. GEnetic Analysis Repository (GEAR; http://sourceforge.net/p/gbchen/wiki/GEAR/) software implemented the HE regression method and is freely available. PMID:24817879

  18. 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

  19. Linkage of Pep-2 and Apk on mouse chromosome 10.

    PubMed

    Womack, J E; Ashley, S; Barnett, L B; Lewis, S E

    1986-10-01

    An ethylnitrosourea (ENU)-induced electrophoretic variant of mouse PEP-2, a tripeptidase, has been used to determine the location of the structural gene on chromosome 10. Gene order and recombination frequencies were estimated as Apk-21.8 +/- 3.9%-Pep-2-3.7 +/- 2.1%-Sl. Methods for rapid determination of Apk and Pep-2 alleles by cellulose acetate electrophoresis and a valuable linkage testing stock carrying the unique Apkm and Pep-2b alleles are described.

  20. 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.

  1. A Genetic Linkage Map of Atlantic Halibut (Hippoglossus hippoglossus L.)

    PubMed Central

    Reid, Darrin P.; Smith, Cheryl-Anne; Rommens, Melissa; Blanchard, Brian; Martin-Robichaud, Debbie; Reith, Michael

    2007-01-01

    A genetic linkage map has been constructed for Atlantic halibut on the basis of 258 microsatellites and 346 AFLPs. Twenty-four linkage groups were identified, consistent with the 24 chromosomes seen in chromosome spreads. The total map distance is 1562.2 cM in the female and 1459.6 cM in the male with an average resolution of 4.3 and 3.5 cM, respectively. Using diploid gynogens, we estimated centromere locations in 19 of 24 linkage groups. Overall recombination in the female was approximately twice that of the male; however, this trend was not consistent along the linkage groups. In the centromeric regions, females had 11–17.5 times the recombination of the males, whereas this trend reversed toward the distal end with males having three times the recombination of the females. Correspondingly, in the male, markers clustered toward the centromeric region with 50% of markers within 20 cM of the putative centromere, whereas 35% of markers in the female were found between 60 and 80 cM from the putative centromere. Limited interspecies comparisons within Japanese flounder and Tetraodon nigroviridis revealed blocks of conservation in sequence and marker order, although regions of chromosomal rearrangement were also apparent. PMID:17720928

  2. 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

  3. Confirmatory linkage study of hypochondroplasia

    SciTech Connect

    Hecht, J.T.; Herrera, C.; Greenhaw, G.A.

    1994-09-01

    Hypochondroplasia is an autosomal dominant form of disproportionate short stature disorder that has clinical and radiographic findings similar to but milder than achondroplasia. Based on these findings it has been suggested that achondroplasia and hypochondroplasia are allelic conditions. We and others have mapped the achondroplasia locus to telomeric region of chromosome 4. Tested linkage to 4p markers in 6 hypochondroplasia families and a maximum LOD score of 1.7 at {theta} = 0 was found for IUDA. Here we report the results of a linkage study in 4 multigenerational families with hypochondroplasia using 7 short tandem repeat markers (D4S127, D4S412, D4S43, D4S115, IUDA, D4S227, D4S169) from the short arm of chromosome 4. These families have been well characterized and show the typical clinical and radiographic features of hypochondroplasia. One family was Afro-American, one Hispanic and two were Caucasian. We found a maximum multipoint LOD score of 2.9 at D4S115. The results of this study provide confirmatory evidence that achondroplasia and hypochondroplasia map to the same chromosomal location and suggests that they are indeed allelic conditions.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. Heritability and genome-wide linkage scan of subjective happiness.

    PubMed

    Bartels, Meike; Saviouk, Viatcheslav; de Moor, Marleen H M; Willemsen, Gonneke; van Beijsterveldt, Toos C E M; Hottenga, Jouke-Jan; de Geus, Eco J C; Boomsma, Dorret I

    2010-04-01

    Causes of individual differences in happiness, as assessed with the Subjective Happiness Scale, are investigated in a large of sample twins and siblings from the Netherlands Twin Register. Over 12,000 twins and siblings, average age 24.7 years (range 12 to 88), took part in the study. A genetic model with an age by sex design was fitted to the data with structural equation modeling in Mx. The heritability of happiness was estimated at 22% for males and 41% in females. No effect of age was observed. To identify the genomic regions contributing to this heritability, a genome-wide linkage study for happiness was conducted in sibling pairs. A subsample of 1157 offspring from 441 families was genotyped with an average of 371 micro-satellite markers per individual. Phenotype and genotype data were analyzed in MERLIN with multipoint variance component linkage analysis and age and sex as covariates. A linkage signal (logarithm of odds score 2.73, empirical p value 0.095) was obtained at the end of the long arm of chromosome 19 for marker D19S254 at 110 cM. A second suggestive linkage peak was found at the short arm of chromosome 1 (LOD of 2.37) at 153 cM, marker D1S534 (empirical p value of .209). These two regions of interest are not overlapping with the regions found for contrasting phenotypes (such as depression, which is negatively associated with happiness). Further linkage and future association studies are warranted.

  11. Genomic linkage map of the human blood fluke Schistosoma mansoni

    PubMed Central

    Criscione, Charles D; Valentim, Claudia LL; Hirai, Hirohisa; LoVerde, Philip T; Anderson, Timothy JC

    2009-01-01

    Background Schistosoma mansoni is a blood fluke that infects approximately 90 million people. The complete life cycle of this parasite can be maintained in the laboratory, making this one of the few experimentally tractable human helminth infections, and a rich literature reveals heritable variation in important biomedical traits such as virulence, host-specificity, transmission and drug resistance. However, there is a current lack of tools needed to study S. mansoni's molecular, quantitative, and population genetics. Our goal was to construct a genetic linkage map for S. mansoni, and thus provide a new resource that will help stimulate research on this neglected pathogen. Results We genotyped grandparents, parents and 88 progeny to construct a 5.6 cM linkage map containing 243 microsatellites positioned on 203 of the largest scaffolds in the genome sequence. The map allows 70% of the estimated 300 Mb genome to be ordered on chromosomes, and highlights where scaffolds have been incorrectly assembled. The markers fall into eight main linkage groups, consistent with seven pairs of autosomes and one pair of sex chromosomes, and we were able to anchor linkage groups to chromosomes using fluorescent in situ hybridization. The genome measures 1,228.6 cM. Marker segregation reveals higher female recombination, confirms ZW inheritance patterns, and identifies recombination hotspots and regions of segregation distortion. Conclusions The genetic linkage map presented here is the first for S. mansoni and the first for a species in the phylum Platyhelminthes. The map provides the critical tool necessary for quantitative genetic analysis, aids genome assembly, and furnishes a framework for comparative flatworm genomics and field-based molecular epidemiological studies. PMID:19566921

  12. An autosomal genetic linkage map of the domestic cat, Felis silvestris catus.

    PubMed

    Menotti-Raymond, Marilyn; David, Victor A; Schäffer, Alejandro A; Tomlin, James F; Eizirik, Eduardo; Phillip, Cornel; Wells, David; Pontius, Joan U; Hannah, Steven S; O'Brien, Stephen J

    2009-04-01

    We report on the completion of an autosomal genetic linkage (GL) map of the domestic cat (Felis silvestris catus). Unlike two previous linkage maps of the cat constructed with a hybrid pedigree between the domestic cat and the Asian leopard cat, this map was generated entirely with domestic cats, using a large multi-generational pedigree (n=256) maintained by the Nestlé Purina PetCare Company. Four hundred eighty-three simple tandem repeat (STR) loci have been assigned to linkage groups on the cat's 18 autosomes. A single linkage group spans each autosome. The length of the cat map, estimated at 4370 cM, is long relative to most reported mammalian maps. A high degree of concordance in marker order was observed between the third-generation map and the 1.5 Mb-resolution radiation hybrid (RH) map of the cat. Using the cat 1.9x whole-genome sequence, we identified map coordinates for 85% of the loci in the cat assembly, with high concordance observed in marker order between the linkage map and the cat sequence assembly. The present version represents a marked improvement over previous cat linkage maps as it (i) nearly doubles the number of markers that were present in the second-generation linkage map in the cat, (ii) provides a linkage map generated in a domestic cat pedigree which will more accurately reflect recombination distances than previous maps generated in a hybrid pedigree, and (iii) provides single linkage groups spanning each autosome. Marker order was largely consistent between this and the previous maps, though the use of a hybrid pedigree in the earlier versions appears to have contributed to some suppression of recombination. The improved linkage map will provide an added resource for the mapping of phenotypic variation in the domestic cat and the use of this species as a model system for biological research.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. CoVaMa: Co-Variation Mapper for disequilibrium analysis of mutant loci in viral populations using next-generation sequence data

    PubMed Central

    Routh, Andrew; Chang, Max W.; Okulicz, Jason F.; Johnson, John E.; Torbett, Bruce E.

    2015-01-01

    Next-generation sequencing (NGS) has transformed our understanding of the dynamics and diversity of virus populations for human pathogens and model systems alike. Due to the sensitivity and depth of coverage in NGS, it is possible to measure the frequency of mutations that may be present even at vanishingly low frequencies within the viral population. Here, we describe a simple bioinformatic pipeline called CoVaMa (Co-Variation Mapper) scripted in Python that detects correlated patterns of mutations in a viral sample. Our algorithm takes NGS alignment data and populates large matrices of contingency tables that correspond to every possible pairwise interaction of nucleotides in the viral genome or amino acids in the chosen open reading frame. These tables are then analysed using classical linkage disequilibrium to detect and report evidence of epistasis. We test our analysis with simulated data and then apply the approach to find epistatically linked loci in Flock House Virus genomic RNA grown under controlled cell culture conditions. We also reanalyze NGS data from a large cohort of HIV infected patients and find correlated amino acid substitution events in the protease gene that have arisen in response to anti-viral therapy. This both confirms previous findings and suggests new pairs of interactions within HIV protease. The script is publically available at http://sourceforge.net/projects/covama PMID:26408523

  18. Estimating African American admixture proportions by use of population-specific alleles.

    PubMed Central

    Parra, E J; Marcini, A; Akey, J; Martinson, J; Batzer, M A; Cooper, R; Forrester, T; Allison, D B; Deka, R; Ferrell, R E; Shriver, M D

    1998-01-01

    We analyzed the European genetic contribution to 10 populations of African descent in the United States (Maywood, Illinois; Detroit; New York; Philadelphia; Pittsburgh; Baltimore; Charleston, South Carolina; New Orleans; and Houston) and in Jamaica, using nine autosomal DNA markers. These markers either are population-specific or show frequency differences >45% between the parental populations and are thus especially informative for admixture. European genetic ancestry ranged from 6.8% (Jamaica) to 22.5% (New Orleans). The unique utility of these markers is reflected in the low variance associated with these admixture estimates (SEM 1.3%-2.7%). We also estimated the male and female European contribution to African Americans, on the basis of informative mtDNA (haplogroups H and L) and Y Alu polymorphic markers. Results indicate a sex-biased gene flow from Europeans, the male contribution being substantially greater than the female contribution. mtDNA haplogroups analysis shows no evidence of a significant maternal Amerindian contribution to any of the 10 populations. We detected significant nonrandom association between two markers located 22 cM apart (FY-null and AT3), most likely due to admixture linkage disequilibrium created in the interbreeding of the two parental populations. The strength of this association and the substantial genetic distance between FY and AT3 emphasize the importance of admixed populations as a useful resource for mapping traits with different prevalence in two parental populations. PMID:9837836

  19. Residual linkage: why do linkage peaks not disappear after an association study?

    PubMed

    Gordon, Scott; Visscher, Peter M

    2007-03-01

    Family-based candidate gene and genome-wide association studies are a logical progression from linkage studies for the identification of gene and polymorphisms underlying complex traits. An efficient way to analyse phenotypic and genotypic data is to model linkage and association simultaneously. An important result from such an analysis is whether any evidence for linkage remains after fitting polymorphisms at candidate genes (residual linkage), because this may indicate locus and allelic heterogeneity in the population and will influence subsequent molecular strategies. Here we report that substantial residual linkage is to be expected, even under genetic homogeneity and when the underlying causal polymorphisms are genotyped and fitted in the model. We simulated a powerful design to detect linkage to quantitative trait loci, with 5, 10 or 20 causal SNPs spread throughout the genome. These SNPs were responsible for all genetic variation, and hence for both linkage and association. Residual linkage at the largest linkage peak from a genome-wide scan was substantial, with mean LOD scores of 0.4, 0.7, and 1.4 for the case of 5, 10 and 20 underlying causal SNPs, respectively. For less powerful designs, the proportion of the original LOD scores that remains after association will be even larger. All cases of 'significant' residual linkage are false positives. The reason for the apparent paradox of detecting residual linkage after fitting causal polymorphisms is that the linkage signals at the largest peaks in a genome-scan are severely inflated, even if all peaks correspond to true linkage. Our findings are general and apply to linkage mapping of any phenotype and to any pedigree structure.

  20. Demographic and genetic estimates of effective population size (Ne) reveals genetic compensation in steelhead trout.

    PubMed

    Ardren, William R; Kapuscinski, Anne R

    2003-01-01

    Estimates of effective population size (Ne) are required to predict the impacts of genetic drift and inbreeding on the evolutionary dynamics of populations. How the ratio of Ne to the number of sexually mature adults (N) varies in natural vertebrate populations has not been addressed. We examined the sensitivity of Ne/N to fluctuations of N and determined the major variables responsible for changing the ratio over a period of 17 years in a population of steelhead trout (Oncorhynchus mykiss) from Washington State. Demographic and genetic methods were used to estimate Ne. Genetic estimates of Ne were gained via temporal and linkage disequilibrium methods using data from eight microsatellite loci. DNA for genetic analysis was amplified from archived smolt scales. The Ne/N from 1977 to 1994, estimated using the temporal method, was 0.73 and the comprehensive demographic estimate of Ne/N over the same time period was 0.53. Demographic estimates of Ne indicated that variance in reproductive success had the most substantial impact on reducing Ne in this population, followed by fluctuations in population size. We found increased Ne/N ratios at low N, which we identified as genetic compensation. Combining the information from the demographic and genetic methods of estimating Ne allowed us to determine that a reduction in variance in reproductive success must be responsible for this compensation effect. Understanding genetic compensation in natural populations will be valuable for predicting the effects of changes in N (i.e. periods of high population density and bottlenecks) on the fitness and genetic variation of natural populations.

  1. Evaluating the role of inbreeding depression in heterozygosity-fitness correlations: how useful are tests for identity disequilibrium?

    PubMed

    Kardos, Marty; Allendorf, Fred W; Luikart, Gordon

    2014-05-01

    Heterozygosity-fitness correlations (HFCs) have been observed for several decades, but their causes are often elusive. Tests for identity disequilibrium (ID, correlated heterozygosity between loci) are commonly used to determine if inbreeding depression is a possible cause of HFCs. We used computer simulations to determine how often ID is detected when HFCs are caused by inbreeding depression. We also used ID in conjunction with HFCs to estimate the proportion of variation (r(2)) in fitness explained by the individual inbreeding coefficient (F). ID was not detected in a large proportion of populations with statistically significant HFCs (sample size = 120 individuals) unless the variance of F was high (σ(2)(F) ≥ 0.005) or many loci were used (100 microsatellites or 1000 SNPs). For example, with 25 microsatellites, ID was not detected in 49% of populations when HFCs were caused by six lethal equivalents and σ(2)(F) was typical of vertebrate populations (σ(2)(F) ≈ 0.002). Estimates of r(2) between survival and F based on ID and HFCs were imprecise unless ID was strong and highly statistically significant (P ≈ 0.01). These results suggest that failing to detect ID in HFC studies should not be taken as evidence that inbreeding depression is absent. The number of markers necessary to simultaneously detect HFC and ID depends strongly on σ(2)(F). Thus the mating system and demography of populations, which influence σ(2) (F), should be considered when designing HFC studies. ID should be used in conjunction with HFCs to estimate the correlation between fitness and F, because HFCs alone reveal little about the strength of inbreeding depression.

  2. Nocturnal transpiration causing disequilibrium between soil and stem predawn water potential in mixed conifer forests of Idaho.

    PubMed

    Kavanagh, Kathleen L; Pangle, Robert; Schotzko, Alisa D

    2007-04-01

    Soil water potential (Psi(s)) is often estimated by measuring leaf water potential before dawn (Psi(pd)), based on the assumption that the plant water status has come into equilibrium with that of the soil. However, it has been documented for a number of plant species that stomata do not close completely at night, allowing for nocturnal transpiration and thus preventing nocturnal soil-plant water potential equilibration. The potential for nighttime transpiration necessitates testing the assumption of nocturnal equilibration before accepting Psi(pd) as a valid estimate of Psi(s). We determined the magnitude of disequilibrium between Psi(pd) and Psi(s) in four temperate conifer species across three height classes through a replicated study in northern Idaho. Based on both stomatal conductance and sap flux measurements, we confirmed that the combination of open stomata and high nocturnal atmospheric vapor pressure deficit (D) resulted in nocturnal transpiration in all four species. Nocturnal stomatal conductance (g(s-noc)) averaged about 33% of mid-morning conductance values. We used species-specific estimates of g(s-noc) and leaf specific conductance to correct Psi(pd) values for nocturnal transpiration at the time the samples were collected. Compared with the unadjusted values, corrected values reflected a significantly higher Psi(pd) (when D > 0.12 kPa). These results demonstrate that comparisons of Psi(pd) among species, canopy height classes and sites, and across growing seasons can be influenced by differential amounts of nocturnal transpiration, leading to flawed results. Consequently, it is important to account for the presence of nocturnal transpiration, either through a properly parameterized model or by making Psi(pd) measurements when D is sufficiently low that it cannot drive nocturnal transpiration. Violating these conditions will likely result in underestimation of Psi(s).

  3. The appropriate threshold for declaring linkage when allowing sex-specific recombination rates.

    PubMed Central

    Lander, E S; Lincoln, S E

    1988-01-01

    In human genetics, two loci are declared to be linked when the lod score at the maximum likelihood recombination fraction theta exceeds the threshold of 3.0. Since recombination rates differ between the sexes, one can alternatively detect linkage by estimating separate recombination rates, theta m and theta f, for male and female meiosis and examining the corresponding sex-specific lod scores. The question arises: In order to maintain the same chance of falsely declaring linkage, what is the correct threshold for declaring linkage when sex-specific lod scores are used? We show here that the appropriate threshold is about 3.5. If the restriction that theta f greater than theta m is added, the appropriate threshold falls to about 3.25. We also discuss the relative efficiency of detecting linkage by using sex-specific and sex-averaged lod scores. PMID:3177382

  4. 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.

  5. A second-generation genetic linkage map for bighead carp (Aristichthys nobilis) based on microsatellite markers.

    PubMed

    Zhu, C; Tong, J; Yu, X; Guo, W; Wang, X; Liu, H; Feng, X; Sun, Y; Liu, L; Fu, B

    2014-10-01

    Bighead carp (Aristichthys nobilis) is an important aquaculture fish worldwide. Genetic linkage maps for the species were previously reported, but map resolution remained to be improved. In this study, a second-generation genetic linkage map was constructed for bighead carp through a pseudo-testcross strategy using interspecific hybrids between bighead carp and silver carp. Of the 754 microsatellites genotyped in two interspecific mapping families (with 77 progenies for each family), 659 markers were assigned to 24 linkage groups, which were equal to the chromosome numbers of the haploid genome. The consensus map spanned 1917.3 cM covering 92.8% of the estimated bighead carp genome with an average marker interval of 2.9 cM. The length of linkage groups ranged from 52.2 to 133.5 cM with an average of 79.9 cM. The number of markers per linkage group varied from 11 to 55 with an average of 27.5 per linkage group. Normality tests on interval distances of the map showed a non-normal marker distribution; however, significant correlation was found between the length of linkage group and the number of markers below the 0.01 significance level (two-tailed). The length of the female map was 1.12 times that of the male map, and the average recombination ratio of female to male was 1.10:1. Visual inspection showed that distorted markers gathered in some linkage groups and in certain regions of the male and female maps. This well-defined genetic linkage map will provide a basic framework for further genome mapping of quantitative traits, comparative mapping and marker-assisted breeding in bighead carp.

  6. 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

  7. 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

    2014-07-25

    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.

  8. Ataxia with vitamin E deficiency: refinement of genetic localization and analysis of linkage disequilibrium by using new markers in 14 families

    SciTech Connect

    Doerflinger, N.; Linder, C.; Ouahchi, K.; Mandel, J.L.; Koenig, M.; Gyapay, G.; Weissenbach, J.; Le Paslier, D.; Rigault, P.; Landrieu, P.

    1995-05-01

    Ataxia with vitamin E deficiency (AVED) is an autosomal recessive disease characterized clinically by neurological symptoms with often striking resemblance to those of Friedreich ataxia. This disorder has been reported previously as familial isolated vitamin E deficiency. We have mapped recently the AVED locus to a 5-cM confidence interval on chromosome 8q by homozygosity mapping in six Mediterranean families. We have now analyzed six new and two previously described families and demonstrate genetic homgeneity despite important clinical variability and wide geographic origins. Analysis of nine new tightly linked microsatellite markers, including four characterized in this study, revealed a predominant but not unique mutation in northern African populations, where this condition is more frequent. Haplotype analysis but also classical recombinations allowed us to refine the AVED position to a 1-cM interval. A YAC contig over this interval was constructed from marker STSs and YAC fingerprint data, in order to facilitate the search of the AVED gene. 28 refs., 2 figs., 4 tabs.

  9. Linkage disequilibrium between the fragile X mutation and two closely linked CA repeats suggests that fragile X chromosomes are derived from a small number of founder chromosomes

    SciTech Connect

    Oudet, C.; Lentes-Zengerling, S.; Kretz, C.; Mandel, J.L. ); Mornet, E.; Thomas, F.; Deluchat, C.; Boue, J.; Boue, A. ); Serre, J.L. INSERM U155, Paris ); Tejada, I. )

    1993-02-01

    In order to investigate the origin of mutations responsible for the fragile X syndrome, two polymorphic CA repeats, one at 10 kb (FRAXAC2) and the other at 150 kb (DXS548) from the mutation target, were analyzed in normal and fragil X chromosomes. Contrary to observations made in myotonic dystrophy, fragil X mutations were not strongly associated with a single allele at the marker loci. However, significant differences in allelic and haplotypic distributions were observed between normal and fragile X chromosomes, indicating that a limited number of primary events may have been at the origin of most present-day fragile X chromosomes in Caucasian populations. The authors propose a putative scheme with six founder chromosomes from which most of the observed fragile X-linked haplotypes can be derived directly or by a single event at one of the marker loci, either a change of one repeat unit or a recombination between DXS548 and the mutation target. Such founder chromosomes may have carried a number of CGG repeats in an upper-normal range, from which recurrent multistep expansion mutations have arisen. 23 refs., 2 figs., 3 tabs.

  10. 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 ...

  11. Locating a Prostate Cancer Susceptibility Gene on the X Chromosome by Linkage Disequilibrium Mapping Using Three Founder Populations in Quebec and Switzerland

    DTIC Science & Technology

    2006-09-01

    Sun S, Stoffer SS, Goldgar DE, Romeo G, Houlston RS, Narod SA, Stratton MR and Foulkes WD: A familial non-toxic multinodular thyroid goiter locus...Dis 50: 184-186, 1991. 3*. Druker HA, Kasprzak L, Bégin LR, Jothy S, Narod SA and Foulkes WD: A family with Graves’ disease, multinodular goiter ...Goldgar DE, Romeo G, Houlston RS, Narod SA, Stratton MR and Foulkes WD: A familial non-toxic multinodular thyroid goiter locus maps to chromosome 14q

  12. 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

  13. Ataxia with Vitamin E Deficiency: Refinement of Genetic Localization and Analysis of Linkage Disequilibrium by Using New Markers in 14 Families

    PubMed Central

    Doerflinger, Nathalie; Linder, Catherine; Ouahchi, Karim; Gyapay, Gabor; Weissenbach, Jean; Le Paslier, Denis; Rigault, Philippe; Belal, Samir; Hamida, Christiane Ben; Hentati, Faycal; Hamida, Mongi Ben; Pandolfo, Massimo; DiDonato, Stephano; Sokol, Ronald; Kayden, Herbert; Landrieu, Pierre; Durr, Alexandra; Brice, Alexis; Goutières, Françoise; Kohlschütter, Alfried; Sabouraud, Pascal; Benomar, Ali; Yahyaoui, Mohamed; Mandel, Jean-Louis; Koenig, Michel

    1995-01-01

    Ataxia with vitamin E deficiency (AVED) is an autosomal recessive disease characterized clinically by neurological symptoms with often striking resemblance to those of Friedreich ataxia. This disorder has been reported previously as familial isolated vitamin E deficiency. We have mapped recently the AVED locus to a 5-cM confidence interval on chromosome 8q by homozygosity mapping in six Mediterranean families. We have now analyzed six new and two previously described families and demonstrate genetic homogeneity despite important clinical variability and wide geographic origins. Analysis of nine new tightly linked microsatellite markers, including four characterized in this study, revealed a predominant but not unique mutation in northern African populations, where this condition is more frequent. Haplotype analysis but also classical recombinations allowed us to refine the AVED position to a 1-cM interval. A YAC contig over this interval was constructed from marker STSs and YAC fingerprint data, in order to facilitate the search of the AVED gene. PMID:7726167

  14. 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...

  15. 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...

  16. 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...

  17. 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.

  18. Investigations of Three-Point Linkage

    ERIC Educational Resources Information Center

    Mertens, Thomas R.

    1972-01-01

    Describes sequence of activities for teaching three-point linkage concept and gene-mapping to high school biology students. Includes laboratory experiments and hypothetical examples for classroom discussion. (PS)

  19. 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.

  20. Genomewide High-Density SNP Linkage Analysis of 236 Japanese Families Supports the Existence of Schizophrenia Susceptibility Loci on Chromosomes 1p, 14q, and 20p

    PubMed Central

    Arinami, Tadao; Ohtsuki, Tsuyuka; Ishiguro, Hiroki; Ujike, Hiroshi; Tanaka, Yuji; Morita, Yukitaka; Mineta, Mari; Takeichi, Masashi; Yamada, Shigeto; Imamura, Akira; Ohara, Koichi; Shibuya, Haruo; Ohara, Kenshiro; Suzuki, Yasuo; Muratake, Tatsuyuki; Kaneko, Naoshi; Someya, Toshiyuki; Inada, Toshiya; Yoshikawa, Takeo; Toyota, Tomoko; Yamada, Kazuo; Kojima, Takuya; Takahashi, Sakae; Osamu, Ohmori; Shinkai, Takahiro; Nakamura, Michiko; Fukuzako, Hiroshi; Hashiguchi, Tomo; Niwa, Shin-ich; Ueno, Takuya; Tachikawa, Hirokazu; Hori, Takafumi; Asada, Takashi; Nanko, Shinichiro; Kunugi, Hiroshi; Hashimoto, Ryota; Ozaki, Norio; Iwata, Nakao; Harano, Mutsuo; Arai, Heii; Ohnuma, Tohru; Kusumi, Ichiro; Koyama, Tsukasa; Yoneda, Hiroshi; Fukumaki, Yasuyuki; Shibata, Hiroki; Kaneko, Sunao; Higuchi, Hisashi; Yasui-Furukori, Norio; Numachi, Yohtaro; Itokawa, Masanari; Okazaki, Yuji

    2005-01-01

    The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide–polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study—which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent—indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects. PMID:16380906

  1. Genomewide high-density SNP linkage analysis of 236 Japanese families supports the existence of schizophrenia susceptibility loci on chromosomes 1p, 14q, and 20p.

    PubMed

    Arinami, Tadao; Ohtsuki, Tsuyuka; Ishiguro, Hiroki; Ujike, Hiroshi; Tanaka, Yuji; Morita, Yukitaka; Mineta, Mari; Takeichi, Masashi; Yamada, Shigeto; Imamura, Akira; Ohara, Koichi; Shibuya, Haruo; Ohara, Kenshiro; Suzuki, Yasuo; Muratake, Tatsuyuki; Kaneko, Naoshi; Someya, Toshiyuki; Inada, Toshiya; Yoshikawa, Takeo; Toyota, Tomoko; Yamada, Kazuo; Kojima, Takuya; Takahashi, Sakae; Osamu, Ohmori; Shinkai, Takahiro; Nakamura, Michiko; Fukuzako, Hiroshi; Hashiguchi, Tomo; Niwa, Shin-ich; Ueno, Takuya; Tachikawa, Hirokazu; Hori, Takafumi; Asada, Takashi; Nanko, Shinichiro; Kunugi, Hiroshi; Hashimoto, Ryota; Ozaki, Norio; Iwata, Nakao; Harano, Mutsuo; Arai, Heii; Ohnuma, Tohru; Kusumi, Ichiro; Koyama, Tsukasa; Yoneda, Hiroshi; Fukumaki, Yasuyuki; Shibata, Hiroki; Kaneko, Sunao; Higuchi, Hisashi; Yasui-Furukori, Norio; Numachi, Yohtaro; Itokawa, Masanari; Okazaki, Yuji

    2005-12-01

    The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study--which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent--indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.

  2. Ecological processes dominate the 13C land disequilibrium in a Rocky Mountain subalpine forest

    NASA Astrophysics Data System (ADS)

    Bowling, D. R.; Ballantyne, A. P.; Miller, J. B.; Burns, S. P.; Conway, T. J.; Menzer, O.; Stephens, B. B.; Vaughn, B. H.

    2014-04-01

    Fossil fuel combustion has increased atmospheric CO2 by ≈ 115 µmol mol-1 since 1750 and decreased its carbon isotope composition (δ13C) by 1.7-2‰ (the 13C Suess effect). Because carbon is stored in the terrestrial biosphere for decades and longer, the δ13C of CO2 released by terrestrial ecosystems is expected to differ from the δ13C of CO2 assimilated by land plants during photosynthesis. This isotopic difference between land-atmosphere respiration (δR) and photosynthetic assimilation (δA) fluxes gives rise to the 13C land disequilibrium (D). Contemporary understanding suggests that over annual and longer time scales, D is determined primarily by the Suess effect, and thus, D is generally positive (δR > δA). A 7 year record of biosphere-atmosphere carbon exchange was used to evaluate the seasonality of δA and δR, and the 13C land disequilibrium, in a subalpine conifer forest. A novel isotopic mixing model was employed to determine the δ13C of net land-atmosphere exchange during day and night and combined with tower-based flux observations to assess δA and δR. The disequilibrium varied seasonally and when flux-weighted was opposite in sign than expected from the Suess effect (D = -0.75 ± 0.21‰ or -0.88 ± 0.10‰ depending on method). Seasonality in D appeared to be driven by photosynthetic discrimination (Δcanopy) responding to environmental factors. Possible explanations for negative D include (1) changes in Δcanopy over decades as CO2 and temperature have risen, and/or (2) post-photosynthetic fractionation processes leading to sequestration of isotopically enriched carbon in long-lived pools like wood and soil.

  3. 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

  4. Nonpaternity in linkage studies of extremely discordant sib pairs.

    PubMed

    Neale, Michael C; Neale, Benjamin M; Sullivan, Patrick F

    2002-02-01

    An approach commonly used to increase statistical power in linkage studies is the study of extremely discordant sibling pairs. This design is powerful under both additive and dominant-gene models and across a wide range of allele frequencies. A practical problem with the design is that extremely discordant pairs that are ostensibly full sibs may be half sibs. Although estimates vary, the population rates of such nonpaternity may be as high as 5%-10%. The proportion in discordant pairs may be much higher. The present article explores this potential inflation as a function of the resemblance of sib pairs and the criteria for discordance used for selection.

  5. A Monte Carlo method for combined segregation and linkage analysis

    SciTech Connect

    Guo, S.W. ); Thompson, E.A. )

    1992-11-01

    The authors 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. 40 refs, 5 figs., 5 tabs.

  6. Comparing Linkage Designs Based on Land Facets to Linkage Designs Based on Focal Species

    PubMed Central

    Brost, Brian M.; Beier, Paul

    2012-01-01

    Least-cost modeling for focal species is the most widely used method for designing conservation corridors and linkages. However, these designs depend on today's land covers, which will be altered by climate change. We recently proposed an alternative approach based on land facets (recurring landscape units of relatively uniform topography and soils). The rationale is that corridors with high continuity of individual land facets will facilitate movement of species associated with each facet today and in the future. Conservation practitioners might like to know whether a linkage design based on land facets is likely to provide continuity of modeled breeding habitat for species needing connectivity today, and whether a linkage for focal species provides continuity and interspersion of land facets. To address these questions, we compared linkages designed for focal species and land facets in three landscapes in Arizona, USA. We used two variables to measure linkage utility, namely distances between patches of modeled breeding habitat for 5–16 focal species in each linkage, and resistance profiles for focal species and land facets between patches connected by the linkage. Compared to focal species designs, linkage designs based on land facets provided as much or more modeled habitat connectivity for 25 of 28 species-landscape combinations, failing only for the three species with the most narrowly distributed habitat. Compared to land facets designs, focal species linkages provided lower connectivity for about half the land facets in two landscapes. In areas where a focal species approach to linkage design is not possible, our results suggest that conservation practitioners may be able to implement a land facets approach with some confidence that the linkage design would serve most potential focal species. In areas where focal species designs are possible, we recommend using the land facet approach to complement, rather than replace, focal species approaches. PMID

  7. Constructing linkage map based on a four-way cross population

    PubMed Central

    Beibei, Jiang; Shizhou, Yu; Bingguang, Xiao; Xiangyang, Lou; Haiming, Xu

    2014-01-01

    Summary Currently, developing genetic linkage map mostly use the derived-populations from crossing of two homogenous parents, which only covers limited genetic diversity and is inappropriate for some species, such as tobacco with lower diversity in genome. It is very general that there are no sufficient polymorphic markers to construct linkage map and ineffective to conduct marker-assisted selection (MAS) and quantitative trait locus (QTL) mapping based on lower density linkage map. This study proposed a method for developing genetic linkage map based on a four-way cross population. Computer simulation was conducted to investigate the feasibility and effectiveness of the method and a supporting program was designed. The main procedures and features of the proposed method were summarized as follows: 1) estimating genetic distance of any paired markers based on maximum likelihood method; 2) splitting all markers into different groups (linkage group) by cluster analysis based on genetic distance of markers; 3) for each linkage group, two end markers were first determined, then the marker order could be determined by inserting other markers in appropriate position by distance analysis of any three neighboring markers. Monte Carlo simulation showed that the proposed method is feasible, effective, and applicable in other derived populations from crossing of two homogenous parents. PMID:25541573

  8. Linkage mapping reveals sex-dimorphic map distances in a passerine bird

    PubMed Central

    Hansson, Bengt; Åkesson, Mikael; Slate, Jon; Pemberton, Josephine M

    2005-01-01

    Linkage maps are lacking for many highly influential model organisms in evolutionary research, including all passerine birds. Consequently, their full potential as research models is severely hampered. Here, we provide a partial linkage map and give novel estimates of sex-specific recombination rates in a passerine bird, the great reed warbler (Acrocephalus arundinaceus). Linkage analysis of genotypic data at 51 autosomal microsatellites and seven markers on the Z-chromosome (one of the sex chromosomes) from an extended pedigree resulted in 12 linkage groups with 2–8 loci. A striking feature of the map was the pronounced sex-dimorphism: males had a substantially lower recombination rate than females, which resulted in a suppressed autosomal map in males (sum of linkage groups: 110.2 cM) compared to females (237.2 cM; female/male map ratio: 2.15). The sex-specific recombination rates will facilitate the building of a denser linkage map and cast light on hypotheses about sex-specific recombination rates. PMID:16191642

  9. 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.

  10. RAPD linkage mapping in a longleaf pine x slash pine F1 family.

    PubMed

    Kubisiak, T L; Nelson, C D; Nance, W L; Stine, M

    1995-06-01

    Random amplified polymorphic DNAs (RAPDs) were used to construct linkage maps of the parent of a longleaf pine (Pinus palustris Mill.) slash pine (Pinus elliottii Englm.) F1 family. A total of 247 segregating loci [233 (1∶1), 14 (3∶1)] and 87 polymorphic (between parents), but non-segregating, loci were identified. The 233 loci segregating 1∶1 (testcross configuration) were used to construct parent-specific linkage maps, 132 for the longleaf-pine parent and 101 for the slash-pine parent. The resulting linkage maps consisted of 122 marker loci in 18 groups (three or more loci) and three pairs (1367.5 cM) for longleaf pine, and 91 marker loci in 13 groups and six pairs for slash pine (952.9 cM). Genome size estimates based on two-point linkage data ranged from 2348 to 2392 cM for longleaf pine, and from 2292 to 2372 cM for slash pine. Linkage of 3∶1 loci to testcross loci in each of the parental maps was used to infer further linkages within maps, as well as potentially homologous counterparts between maps. Three of the longleaf-pine linkage groups appear to be potentially homologous counterparts to four different slash-pine linkage groups. The number of heterozygous loci (previously testcross in parents) per F1 individual, ranged from 96 to 130. With the 87 polymorphic, but non-segregating, loci that should also be heterozygous in the F1 progeny, a maximum of 183-217 heterozygous loci could be available for mapping early height growth (EHG) loci and for applying genomic selection in backcross populations.

  11. Early detection of population declines: high power of genetic monitoring using effective population size estimators

    PubMed Central

    Antao, Tiago; Pérez-Figueroa, Andrés; Luikart, Gordon

    2011-01-01

    Early detection of population declines is essential to prevent extinctions and to ensure sustainable harvest. We evaluated the performance of two Ne estimators to detect population declines: the two-sample temporal method and a one-sample method based on linkage disequilibrium (LD). We used simulated data representing a wide range of population sizes, sample sizes and number of loci. Both methods usually detect a population decline only one generation after it occurs if Ne drops to less than approximately 100, and 40 microsatellite loci and 50 individuals are sampled. However, the LD method often out performed the temporal method by allowing earlier detection of less severe population declines (Ne approximately 200). Power for early detection increased more rapidly with the number of individuals sampled than with the number of loci genotyped, primarily for the LD method. The number of samples available is therefore an important criterion when choosing between the LD and temporal methods. We provide guidelines regarding design of studies targeted at monitoring for population declines. We also report that 40 single nucleotide polymorphism (SNP) markers give slightly lower precision than 10 microsatellite markers. Our results suggest that conservation management and monitoring strategies can reliably use genetic based methods for early detection of population declines. PMID:25567959

  12. 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

  13. Disulphide linkage in mouse ST6Gal-I: determination of linkage positions and mutant analysis.

    PubMed

    Hirano, Yuichi; Suzuki, Takehiro; Matsumoto, Takumi; Ishihara, Yoshimi; Takaki, Yoshie; Kono, Mari; Dohmae, Naoshi; Tsuji, Shuichi

    2012-02-01

    All cloned sialyltransferases from vertebrates are classified into four subfamilies and are characterized as having type II transmembrane topology. The catalytic domain has highly conserved motifs known as sialylmotifs. Besides sialylmotifs, each family has several unique conserved cysteine (Cys) residues mainly in the catalytic domain. The number and loci of conserved amino acids, however, differ with each subfamily, suggesting that the conserved Cys-residues and/or disulphide linkages they make may contribute to linkage specificity. Using Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF)-mass spectrometry, the present study performed disulphide linkage analysis on soluble mouse ST6Gal-I, which has six Cys-residues. Results confirmed that there were no free Cys-residues, and all six residues contributed to disulphide linkage formation, C(139)-C(403), C(181)-C(332) and C(350)-C(361). Study of single amino acid-substituted mutants revealed that the disulphide linkage C(181)-C(332) was necessary for molecular expression of the enzyme, and that the disulphide linkage C(350)-C(361) was necessary for enzyme activity. The remaining disulphide linkage C(139)-C(403) was not necessary for enzyme expression or for activity, including substrate specificity. Crystallographic study of pig ST3Gal I has recently been reported. Interestingly, the loci of disulphide linkages in ST6Gal-I differ from those in ST3Gal I, suggesting that the linkage specificity of sialyltransferase may results from significant structural differences, including the loci of disulphide linkages.

  14. Linkage analysis of quantitative trait loci in the presence of heterogeneity.

    PubMed

    Ekstrøm, Claus Thorn; Dalgaard, Peter

    2003-01-01

    Variance component modeling for linkage analysis of quantitative traits is a powerful tool for detecting and locating genes affecting a trait of interest, but the presence of genetic heterogeneity will decrease the power of a linkage study and may even give biased estimates of the location of the quantitative trait loci. Many complex diseases are believed to be influenced by multiple genes and therefore genetic heterogeneity is likely to be present for many real applications of linkage analysis. We consider a mixture of multivariate normals to model locus heterogeneity by allowing only a proportion of the sampled pedigrees to segregate trait-influencing allele(s) at a specific locus. However, for mixtures of normals the classical asymptotic distribution theory of the maximum likelihood estimates does not hold, so tests of linkage and/or heterogeneity are evaluated using resampling methods. It is shown that allowing for genetic heterogeneity leads to an increase in power to detect linkage. This increase is more prominent when the genetic effect of the locus is small or when the percentage of pedigrees not segregating trait-influencing allele(s) at the locus is high.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. A reference linkage map for Eucalyptus

    PubMed Central

    2012-01-01

    Background Genetic linkage maps are invaluable resources in plant research. They provide a key tool for many genetic applications including: mapping quantitative trait loci (QTL); comparative mapping; identifying unlinked (i.e. independent) DNA markers for fingerprinting, population genetics and phylogenetics; assisting genome sequence assembly; relating physical and recombination distances along the genome and map-based cloning of genes. Eucalypts are the dominant tree species in most Australian ecosystems and of economic importance globally as plantation trees. The genome sequence of E. grandis has recently been released providing unprecedented opportunities for genetic and genomic research in the genus. A robust reference linkage map containing sequence-based molecular markers is needed to capitalise on this resource. Several high density linkage maps have recently been constructed for the main commercial forestry species in the genus (E. grandis, E. urophylla and E. globulus) using sequenced Diversity Arrays Technology (DArT) and microsatellite markers. To provide a single reference linkage map for eucalypts a composite map was produced through the integration of data from seven independent mapping experiments (1950 individuals) using a marker-merging method. Results The composite map totalled 1107 cM and contained 4101 markers; comprising 3880 DArT, 213 microsatellite and eight candidate genes. Eighty-one DArT markers were mapped to two or more linkage groups, resulting in the 4101 markers being mapped to 4191 map positions. Approximately 13% of DArT markers mapped to identical map positions, thus the composite map contained 3634 unique loci at an average interval of 0.31 cM. Conclusion The composite map represents the most saturated linkage map yet produced in Eucalyptus. As the majority of DArT markers contained on the map have been sequenced, the map provides a direct link to the E. grandis genome sequence and will serve as an important reference for

  20. Postadoption and Guardianship: An Evaluation of the Adoption Preservation, Assessment, and Linkage Program

    ERIC Educational Resources Information Center

    Liao, Minli; Testa, Mark

    2016-01-01

    Objectives: This study evaluated the effects of the Adoption Preservation, Assessment, and Linkage (APAL) postpermanency program. Method: A quasi-experimental, posttest-only design was used to estimate the program's effects on youth discharged from foster care to adoption or legal guardianship. A random sample was surveyed (female = 44.7%; African…

  1. 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

  2. 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

  3. 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

  4. Posterior probability of linkage analysis of autism dataset identifies linkage to chromosome 16

    PubMed Central

    Wassink, Thomas H.; Vieland, Veronica J.; Sheffield, Val C.; Bartlett, Christopher W.; Goedken, Rhinda; Childress, Deborah; Piven, Joseph

    2015-01-01

    Objective To apply phenotypic and statistical methods designed to account for heterogeneity to linkage analyses of the autism Collaborative Linkage Study of Autism (CLSA) affected sibling pair families. Method The CLSA contains two sets of 57 families each; Set 1 has been analyzed previously, whereas this study presents the first analyses of Set 2. The two sets were analyzed independently, and were further split based on the degree of phrase speech delay in the siblings. Linkage analysis was carried out using the posterior probability of linkage (PPL), a Bayesian statistic that provides a mathematically rigorous mechanism for combining linkage evidence across multiple samples. Results Two-point PPLs from Set 1 led to the follow-up genotyping of 18 markers around linkage peaks on 1q, 13p, 13q, 16q, and 17q in both sets of families. Multipoint PPLs were then calculated for the entire CLSA sample. These analyses identified four regions with at least modest evidence in support of linkage: 1q at 173 cM, PPL = 0.12; 13p at 21 cM, PPL = 0.16; 16q at 63 cM, PPL= 0.36; Xq at 40 cM, PPL = 0.11. Conclusion We find strengthened evidence for linkage of autism to chromosomes 1q, 13p, 16q, and Xq, and diminished evidence for linkage to 7q and 13q. The verity of these findings will be tested by continuing to update our PPL analyses with data from additional autism datasets. PMID:18349700

  5. 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

  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. Genotype Correlation Analysis Reveals Pathway-Based Functional Disequilibrium and Potential Epistasis in the Human Interactome

    PubMed Central

    Bush, William S.; Haines, Jonathan L.

    2016-01-01

    Epistasis is thought to be a pervasive part of complex phenotypes due to the dynamics and complexity of biological systems, and a further understanding of epistasis in the context of biological pathways may provide insight into the etiology of complex disease. In this study, we use genotype data from the International HapMap Project to characterize the functional dependencies between alleles in the human interactome as defined by KEGG pathways. We performed chi-square tests to identify non-independence between functionally-related SNP pairs within parental Caucasian and Yoruba samples. We further refine this list by testing for skewed transmission of pseudo-haplotypes to offspring using a haplotype-based TDT test. From these analyses, we identify pathways enriched for functional disequilibrium, and a set of 863 SNP pairs (representing 453 gene pairs) showing consistent non-independence and transmission distortion. These results represent gene pairs with strong evidence of epistasis within the context of a biological function.

  8. 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.

  9. Evidence for disequilibrium of ortho and para hydrogen on Jupiter from Voyager IRIS measurements

    NASA Technical Reports Server (NTRS)

    Conrath, B. J.; Gierasch, P. J.

    1983-01-01

    Preliminary results of an analysis of the ortho state/para state ratio (parallel/antiparallel) for molecular H2 in the Jovian atmosphere using Voyager IR spectrometer (IRIS) data are reported. The study was undertaken to expand the understanding of the thermodynamics of a predominantly H2 atmosphere, which takes about 100 million sec to reach equilibrium. IRIS data provided 4.3/cm resolution in the 300-700/cm spectral range dominated by H2 lines. Approximately 600 spectra were examined to detect any disequilibrium between the hydrogen species. The results indicate that the ortho-para ratio is not in an equilibrium state in the upper Jovian troposphere. A thorough mapping of the para-state molecules in the upper atmosphere could therefore aid in mapping the atmospheric flowfield.

  10. Toward a Thermal Disequilibrium Multiphase Model for High Explosives Containing Metallic Particles

    NASA Astrophysics Data System (ADS)

    Baudin, Gerard; Lefrancois, Alexandre; Saurel, Richard; Petitpas, Fabien; Le Metayer, Olivier; Massoni, Jacques; Belski, Vladimir M.; Zotov, Eugène

    2010-10-01

    To investigate the effects of explosive composition on Al combustion, in particular regarding its oxygen balance, several liquid mixtures are experimentally studied with varying oxygen balance. They are then loaded with Al particles and the velocity of detonation (VOD) is recorded. Computational results with the help of conventional Chapman Jouguet (CJ) codes are compared but fail to reproduce experimental observations. A new multiphase flow model out of thermal equilibrium is then considered. Two options are considered as limiting cases: stiff thermal relaxation and vanishing heat exchange between Al and detonation products. With this last option, predictions are in excellent agreement with the experiments. This suggests that temperature disequilibrium plays a major role in heterogeneous explosives detonation dynamics.

  11. Testing for homogeneity of Hardy-Weinberg disequilibrium using data sampled from several populations.

    PubMed

    Olson, J M; Foley, M

    1996-09-01

    Olson (1993, Annals of Human Genetics 57, 291-295) proposed a large-sample test of Hardy-Weinberg equilibrium when genotype data are sampled from several populations with different allele frequencies. The test assumes that a ratio measure of disequilibrium is constant across the populations. In this paper, we consider the problem of testing the assumption of homogeneity of that ratio and propose both a large-sample test and an exact test. The large-sample test is appropriate if sample sizes in all strata are sufficiently large, but is strongly anticonservative if some strata are small. In the latter case, the exact test is preferred and we approximate the P-value of this test using a Markov chain Monte Carlo approach.

  12. A Novel Framework for Sib Pair Linkage Analysis

    PubMed Central

    Poznik, G. David; Adamska, Katarzyna; Xu, Xin; Krolewski, Andrzej S.; Rogus, John J.

    2006-01-01

    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

  13. 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…

  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. Composite Bloom Filters for Secure Record Linkage.

    PubMed

    Durham, Elizabeth Ashley; Kantarcioglu, Murat; Xue, Yuan; Toth, Csaba; Kuzu, Mehmet; Malin, Bradley

    2014-12-01

    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.

  16. 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...

  17. 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...

  18. The Iowa Record-Linkage Experience.

    ERIC Educational Resources Information Center

    Black, Donald W.

    1989-01-01

    Conducted Iowa Record-Linkage Study, reviewing records of psychiatric inpatients to 1 hospital in 10-year period and linking information with all Iowa death certificates for same period, resulting in identification of 331 deaths. Data analysis revealed that relative risk for premature death was greatest among women and the young. (NB)

  19. 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…

  20. Developing Industry Linkages: Learning from Practice.

    ERIC Educational Resources Information Center

    Misko, Josie

    Linkages between Australia's vocational education and training (VET) and technical and further education (TAFE) sectors and industry were examined through 13 case studies involving a variety of industrial sectors in South Australia, New South Wales, and Victoria. Special attention was paid to the processes established by school clusters to develop…

  1. 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...

  2. 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.

  3. Alocomotino Control Algorithm for Robotic Linkage Systems

    SciTech Connect

    Dohner, Jeffrey L.

    2016-10-01

    This dissertation describes the development of a control algorithm that transitions a robotic linkage system between stabilized states producing responsive locomotion. The developed algorithm is demonstrated using a simple robotic construction consisting of a few links with actuation and sensing at each joint. Numerical and experimental validation is presented.

  4. 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…

  5. 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.

  6. A microsatellite-based, physically anchored linkage map for the gray, short-tailed opossum (Monodelphis domestica).

    PubMed

    Samollow, Paul B; Gouin, Nicolas; Miethke, Pat; Mahaney, Susan M; Kenney, Margaret; VandeBerg, John L; Graves, Jennifer A Marshall; Kammerer, Candace M

    2007-01-01

    The genome of the gray, short-tailed opossum, Monodelphis domestica, will be the first of any marsupial to be fully sequenced. The utility of this sequence will be greatly enhanced by construction and integration of detailed genetic and physical maps. Therefore, it is important to verify the unusual recombinational characteristics that were suggested by the 'first-generation' M. domestica linkage map; specifically, very low levels of recombination and severely reduced female recombination, both of which are contrary to patterns in other vertebrates. We constructed a new linkage map based on a different genetic cross, using a new and much larger set of map markers, and physically anchored and oriented the linkage groups onto chromosomes via fluorescence in-situ hybridization mapping. This map includes 150 loci in eight autosomal linkage groups corresponding to the eight autosome pairs, and spans 86-89% of the autosomal genome. The sex-averaged autosomal map covers 715 cM, with a full-length estimate of 866 cM; the shortest full-length linkage map reported for any vertebrate. The sex-specific maps confirmed severely reduced female recombination in all linkage groups, and an overall F/M map ratio = 0.54. These results greatly extend earlier findings, and provide an improved microsatellite-based linkage map for this species.

  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.

  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.

  9. AFLP linkage map of hybridizing swallowtail butterflies, Papilio glaucus and Papilio canadensis.

    PubMed

    Winter, Clayton B; Porter, Adam H

    2010-01-01

    High-density linkage maps provide powerful tools for studying the genetic basis of ecologically relevant adaptations and the genomic scope of introgression. We backcrossed an F(1) hybrid male Papilio glaucus/Papilio canadensis tiger swallowtail butterfly to a pure P. glaucus female and constructed amplified fragment length polymorphism linkage maps from the progeny. The paternal map contains 309 markers distributed among 29 linkage groups, with a corrected map distance of 1167 cM (logarithm of the odds [LOD] = 4.0). The average linkage group contained 10.65 +/- 4.85 markers separated by 32.7 +/- 3.8 cM, with statistically significant clustering. The paternal hybrid map had 18.65% more markers than the maternal P. glaucus map, which provides a rough estimate of the extent of genetic differentiation between the species. The maternal map contains 253 markers among 28 linkage groups, without the X and Y chromosomes. Segregation distortion from expected Mendelian ratios was observed for 94/1096 scored loci (8.6%, P < 0.05). The X chromosome map includes 7 markers spanning 29.3 cM (LOD = 3.0). These naturally hybridizing, female heterogametic species are used to study important questions in the maintenance of species boundaries, sex chromosome introgression, sex-limited mimicry, and host plant use. The map will facilitate research into the physiological, ecological, and evolutionary genetics of these phenomena.

  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. Confirmation of Linkage to and Localization of Familial Colon Cancer Risk Haplotype on Chromosome 9q22

    PubMed Central

    Gray-McGuire, Courtney; Guda, Kishore; Adrianto, Indra; Lin, Chee Paul; Natale, Leanna; Potter, John D.; Newcomb, Polly; Poole, Elizabeth M.; Ulrich, Cornelia M.; Lindor, Noralane; Goode, Ellen L.; Fridley, Brooke L.; Jenkins, Robert; Marchand, Loic Le; Casey, Graham; Haile, Robert; Hopper, John; Jenkins, Mark; Young, Joanne; Buchanan, Daniel; Gallinger, Steve; Adams, Mark; Lewis, Susan; Willis, Joseph; Elston, Robert; Markowitz, Sanford D.; Wiesner, Georgia L.

    2010-01-01

    Colorectal cancer is the second leading cause of cancer mortality in adult Americans and is caused by both genetic and environmental risk factors. We have replicated our originally reported linkage signal at 9q22-31 by fine mapping an independent collection of colon cancer families. Then, using a custom array of single nucleotide polymorphisms (SNPs) densely spaced across the candidate region, we performed both single-SNP and moving-window association analyses to identify a colon neoplasia risk haplotype. We isolated the association effect to a five SNP haplotype centered around 98.15 megabases (Mb) on chromosome 9q. This haplotype is in strong linkage disequilibrium with the haplotype block containing HABP4 and may be a surrogate for the effect of this CD30 Ki-1 antigen. It is also in close proximity to the GALNT12, which has been recently shown to be altered in colon tumors. Finally, we used a predictive modeling algorithm to demonstrate the contribution of this risk haplotype and surrounding candidate genes in distinguishing between colon cancer cases and healthy controls. The ability to replicate this finding, the strength of the haplotype association (OR=3.68) and the accuracy of our prediction model (~60%) all strongly support the presence of a locus for familial colon cancer on chromosome 9q. PMID:20551049

  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. Effect of Hospital–SNF Referral Linkages on Rehospitalization

    PubMed Central

    Rahman, Momotazur; Foster, Andrew D; Grabowski, David C; Zinn, Jacqueline S; Mor, Vincent

    2013-01-01

    Objective. To determine whether the rate of rehospitalization is lower among patients discharged to skilled nursing facilities (SNFs) with which a hospital has a strong linkage. Data Sources/Collection. We used national Medicare enrollment, claims, and the Minimum Data Set to examine 2.8 million newly discharged patients to 15,063 SNFs from 2,477 general hospitals between 2004 and 2006. Study Design. We examined the relationship between the proportion of discharges from a hospital and alternative SNFs on the rehospitalization of patients treated by that hospital–SNF pair using an instrumental variable approach. We used distances to alternative SNFs from residence of the patients of the originating hospital as the instrument. Principal Findings. Our estimates suggest that if the proportion of a hospital's discharges to an SNF was to increase by 10 percentage points, the likelihood of patients treated by that hospital–SNF pair to be rehospitalized within 30 days would decline by 1.2 percentage points, largely driven by fewer rehospitalizations within a week of hospital discharge. Conclusions. Stronger hospital–SNF linkages, independent of hospital ownership, were found to reduce rehospitalization rates. As hospitals are held accountable for patients' outcomes postdischarge under the Affordable Care Act, hospitals may steer their patients preferentially to fewer SNFs. PMID:24134773

  14. A Genetic Linkage Map of Saccharum Spontaneum L. `ses 208'

    PubMed Central

    Al-Janabi, S. M.; Honeycutt, R. J.; McClelland, M.; Sobral, BWS.

    1993-01-01

    The arbitrarily primed polymerase chain reaction was used to detect single-dose polymorphisms that, in turn, were used to generate a linkage map of a polyploid relative of cultivated sugarcane, Saccharum spontaneum `SES 208' (2n = 64). The mapping population was composed of 88 progeny from a cross between SES 208 and a diploidized haploid derived from SES 208 by anther culture, ADP 85-0068. This cross allowed direct analysis of meiosis in SES 208 and gametic segregation ratios to be observed. One hundred twenty-seven 10-mer oligonucleotide primers of arbitrary sequence were selected from a pool of 420 primers used to screen the mapping parents. Three hundred thirty-six of the 420 primers amplified 4,540 loci or 13.5 loci per primer. The selected 127 primers revealed 2,160 loci of which 279 were present in SES 208 and absent in ADP 85-0068 and easily scored. Two hundred and eight (74.6%) of these 279 polymorphisms were single-dose polymorphisms (i.e., they displayed 1:1 segregation, χ(2) at 98% confidence level). Linkage analysis (θ = 0.25, LOD = 9.0 for two-point analysis, then θ = 0.25, LOD = 6.0 for multipoint analysis) of single-dose polymorphisms placed them into 42 linkage groups containing at least 2 markers. These single-dose markers span 1,500 contiguous centimorgans (cM) with 32 markers remaining unlinked (15.4%). From this 208-marker map we estimated the genome size of SES 208 to be 2,550 cM. The map has a predicted coverage of 85.1% at 30 cM, meaning that any new marker placed has an 85.1% chance of being within 30 cM of an existing marker. Furthermore, we show that SES 208 behaves like an autopolyploid because (i) the ratio of single-dose markers to higher dose markers fit the assumption of autooctaploidy and (ii) the absence of repulsion phase linkages. This is the first genetic map constructed directly on a polyploid species for which no diploid relatives are known. PMID:8375659

  15. EXPLoRA-web: linkage analysis of quantitative trait loci using bulk segregant analysis

    PubMed Central

    Pulido-Tamayo, Sergio; Duitama, Jorge; Marchal, Kathleen

    2016-01-01

    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

  16. Autosomal dominant familial spastic paraplegia; Linkage analysis and evidence for linkage to chromosome 2p

    SciTech Connect

    Figlewicz, D.A.; Dube, M.P.; Rouleau, G.A.

    1994-09-01

    Familial spastic paraplegia (FSP) is a degenerative disorder of the motor system characterized by progressive weakness and spasticity of the lower limbs. Little is known about the pathophysiology of this disorder. FSP can be inherited as an autosomal dominant (AD), autosomal recessive, or X-linked trait. We have undertaken linkage analysis for a group of 36 AD FSP families from which we have collected blood samples from 427 individuals, including 148 affected individuals. Typing of polymorphic markers has allowed us to exclude more than 50% of the genome. Recently, linkage for AD FSP to a locus on chromosome 14q was reported. Our AD FSP kindreds were tested for linkage to markers spanning the 20 cM region between D14S69 and D14S66; however, we were not able to establish linkage for any of our families to chromosome 14. Lod scores suggestive of linkage for some AD FSP kindreds have been obtained for markers on chromosome 2p. We have tested seven polymorphic markers spanning the region between D2S405 and D2S177. Our highest aggregate lod score, including all families tested, was obtained at the locus D2S352: 2.4 at 20 cM. Results from HOMOG analysis for linkage heterogeneity will be reported.

  17. Comprehensive linkage and association analyses identify haplotype, near to the TNFSF15 gene, significantly associated with spondyloarthritis.

    PubMed

    Zinovieva, Elena; Bourgain, Catherine; Kadi, Amir; Letourneur, Franck; Izac, Brigitte; Said-Nahal, Roula; Lebrun, Nicolas; Cagnard, Nicolas; Vigier, Agathe; Jacques, Sébastien; Miceli-Richard, Corinne; Garchon, Henri-Jean; Heath, Simon; Charon, Céline; Bacq, Delphine; Boland, Anne; Zelenika, Diana; Chiocchia, Gilles; Breban, Maxime

    2009-06-01

    Spondyloarthritis (SpA) is a chronic inflammatory disorder with a strong genetic predisposition dominated by the role of HLA-B27. However, the contribution of other genes to the disease susceptibility has been clearly demonstrated. We previously reported significant evidence of linkage of SpA to chromosome 9q31-34. The current study aimed to characterize this locus, named SPA2. First, we performed a fine linkage mapping of SPA2 (24 cM) with 28 microsatellite markers in 149 multiplex families, which allowed us to reduce the area of investigation to an 18 cM (13 Mb) locus delimited by the markers D9S279 and D9S112. Second, we constructed a linkage disequilibrium (LD) map of this region with 1,536 tag single-nucleotide polymorphisms (SNPs) in 136 families (263 patients). The association was assessed using a transmission disequilibrium test. One tag SNP, rs4979459, yielded a significant P-value (4.9 x 10(-5)). Third, we performed an extension association study with rs4979459 and 30 surrounding SNPs in LD with it, in 287 families (668 patients), and in a sample of 139 cases and 163 controls. Strong association was observed in both familial and case/control datasets for several SNPs. In the replication study, carried with 8 SNPs in an independent sample of 232 cases and 149 controls, one SNP, rs6478105, yielded a nominal P-value<3 x 10(-2). Pooled case/control study (371 cases and 312 controls) as well as combined analysis of extension and replication data showed very significant association (P<5 x 10(-4)) for 6 of the 8 latter markers (rs7849556, rs10817669, rs10759734, rs6478105, rs10982396, and rs10733612). Finally, haplotype association investigations identified a strongly associated haplotype (P<8.8 x 10(-5)) consisting of these 6 SNPs and located in the direct vicinity of the TNFSF15 gene. In conclusion, we have identified within the SPA2 locus a haplotype strongly associated with predisposition to SpA which is located near to TNFSF15, one of the major candidate

  18. Comprehensive Linkage and Association Analyses Identify Haplotype, Near to the TNFSF15 Gene, Significantly Associated with Spondyloarthritis

    PubMed Central

    Zinovieva, Elena; Bourgain, Catherine; Kadi, Amir; Letourneur, Franck; Izac, Brigitte; Said-Nahal, Roula; Lebrun, Nicolas; Cagnard, Nicolas; Vigier, Agathe; Jacques, Sébastien; Miceli-Richard, Corinne; Garchon, Henri-Jean; Heath, Simon; Charon, Céline; Bacq, Delphine; Boland, Anne; Zelenika, Diana

    2009-01-01

    Spondyloarthritis (SpA) is a chronic inflammatory disorder with a strong genetic predisposition dominated by the role of HLA-B27. However, the contribution of other genes to the disease susceptibility has been clearly demonstrated. We previously reported significant evidence of linkage of SpA to chromosome 9q31–34. The current study aimed to characterize this locus, named SPA2. First, we performed a fine linkage mapping of SPA2 (24 cM) with 28 microsatellite markers in 149 multiplex families, which allowed us to reduce the area of investigation to an 18 cM (13 Mb) locus delimited by the markers D9S279 and D9S112. Second, we constructed a linkage disequilibrium (LD) map of this region with 1,536 tag single-nucleotide polymorphisms (SNPs) in 136 families (263 patients). The association was assessed using a transmission disequilibrium test. One tag SNP, rs4979459, yielded a significant P-value (4.9×10−5). Third, we performed an extension association study with rs4979459 and 30 surrounding SNPs in LD with it, in 287 families (668 patients), and in a sample of 139 cases and 163 controls. Strong association was observed in both familial and case/control datasets for several SNPs. In the replication study, carried with 8 SNPs in an independent sample of 232 cases and 149 controls, one SNP, rs6478105, yielded a nominal P-value<3×10−2. Pooled case/control study (371 cases and 312 controls) as well as combined analysis of extension and replication data showed very significant association (P<5×10−4) for 6 of the 8 latter markers (rs7849556, rs10817669, rs10759734, rs6478105, rs10982396, and rs10733612). Finally, haplotype association investigations identified a strongly associated haplotype (P<8.8×10−5) consisting of these 6 SNPs and located in the direct vicinity of the TNFSF15 gene. In conclusion, we have identified within the SPA2 locus a haplotype strongly associated with predisposition to SpA which is located near to TNFSF15, one of the major candidate

  19. Sex-linked genes and linkage maps in amphibians.

    PubMed

    Sumida, M; Nishioka1, M

    2000-06-01

    This paper reviews sex-linked genes and linkage maps in amphibians. It appears that there is no common ancestral or conserved sex-linkage group in amphibians, whereas an important proportion of other linkage groups has been conserved in amphibians. Comparisons of amphibian linkage maps with those of fishes and mammals reveal several syntenic associations apparently conserved over a very long period of vertebrate divergence.

  20. 20 CFR 628.545 - Linkages and coordination.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Linkages and coordination. 628.545 Section... the Job Training Partnership Act § 628.545 Linkages and coordination. (a) General requirements. (1) To..., shall establish appropriate linkages and coordination procedures with other Federal programs...

  1. 20 CFR 628.545 - Linkages and coordination.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Linkages and coordination. 628.545 Section... the Job Training Partnership Act § 628.545 Linkages and coordination. (a) General requirements. (1) To..., shall establish appropriate linkages and coordination procedures with other Federal programs...

  2. Client and Birth Record Linkage: A Method, Biases, and Lessons.

    ERIC Educational Resources Information Center

    Holian, John

    1996-01-01

    Describes record linkage as a data-generating technique, and presents a method for linking client records to live and stillbirth records, using 32,974 births in the Cleveland (Ohio) area. Biases that can enter the linkage process and general research issues related to record linkage are discussed. (SLD)

  3. 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...

  4. 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

  5. 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.

  6. Anxiety and Depression: Linkages with Viral Diseases.

    PubMed

    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.

  7. Varieties of religion-family linkages.

    PubMed

    Snarey, J R; Dollahite, D C

    2001-12-01

    The 4 articles in this special issue make important contributions to both family and religious studies as well as to their interface. This commentary begins by considering 4 unifying themes present across all of the articles, including meaningful religion-family linkages, the importance of gender differences in the faith-family interface, the significance of intergenerational relationships, and the need for better theory. The authors then discuss the unique major strength and secondary limitations of each study. Finally, the commentary focuses on two challenges inhibiting the contemporary study of religion and the family--a relative lack of racial and religious diversity in samples and the lack of a unifying theory of religion-family linkages--and suggests how to adjust the trajectory of future theory and research to address these issues.

  8. 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.

  9. Complete genetic linkage can subvert natural selection

    PubMed Central

    Gerrish, Philip J.; Colato, Alexandre; Perelson, Alan S.; Sniegowski, Paul D.

    2007-01-01

    The intricate adjustment of organisms to their environment demonstrates the effectiveness of natural selection. But Darwin himself recognized that certain biological features could limit this effectiveness, features that generally reduce the efficiency of natural selection or yield suboptimal adaptation. Genetic linkage is known to be one such feature, and here we show theoretically that it can introduce a more sinister flaw: when there is complete linkage between loci affecting fitness and loci affecting mutation rate, positive natural selection and recurrent mutation can drive mutation rates in an adapting population to intolerable levels. We discuss potential implications of this finding for the early establishment of recombination, the evolutionary fate of asexual populations, and immunological clearance of clonal pathogens. PMID:17405865

  10. 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.

  11. Ascertainment correction for Markov chain Monte Carlo segregation and linkage analysis of a quantitative trait.

    PubMed

    Ma, Jianzhong; Amos, Christopher I; Warwick Daw, E

    2007-09-01

    Although extended pedigrees are often sampled through probands with extreme levels of a quantitative trait, Markov chain Monte Carlo (MCMC) methods for segregation and linkage analysis have not been able to perform ascertainment corrections. Further, the extent to which ascertainment of pedigrees leads to biases in the estimation of segregation and linkage parameters has not been previously studied for MCMC procedures. In this paper, we studied these issues with a Bayesian MCMC approach for joint segregation and linkage analysis, as implemented in the package Loki. We first simulated pedigrees ascertained through individuals with extreme values of a quantitative trait in spirit of the sequential sampling theory of Cannings and Thompson [Cannings and Thompson [1977] Clin. Genet. 12:208-212]. Using our simulated data, we detected no bias in estimates of the trait locus location. However, in addition to allele frequencies, when the ascertainment threshold was higher than or close to the true value of the highest genotypic mean, bias was also found in the estimation of this parameter. When there were multiple trait loci, this bias destroyed the additivity of the effects of the trait loci, and caused biases in the estimation all genotypic means when a purely additive model was used for analyzing the data. To account for pedigree ascertainment with sequential sampling, we developed a Bayesian ascertainment approach and implemented Metropolis-Hastings updates in the MCMC samplers used in Loki. Ascertainment correction greatly reduced biases in parameter estimates. Our method is designed for multiple, but a fixed number of trait loci.

  12. Molecular linkage maps of the Populus genome.

    PubMed

    Yin, Tongming; Zhang, Xinye; Huang, Minren; Wang, Minxiu; Zhuge, Qiang; Tu, Shengming; Zhu, Li-Huang; Wu, Rongling

    2002-06-01

    We report molecular genetic linkage maps for an interspecific hybrid population of Populus, a model system in forest-tree biology. The hybrids were produced by crosses between P. deltoides (mother) and P. euramericana (father), which is a natural hybrid of P. deltoides (grandmother) and P. nigra (grandfather). Linkage analysis from 93 of the 450 backcross progeny grown in the field for 15 years was performed using random amplified polymorphic DNAs (RAPDs), amplified fragment length polymorphisms (AFLPs), and inter-simple sequence repeats (ISSRs). Of a total of 839 polymorphic markers identified, 560 (67%) were testcross markers heterozygous in one parent but null in the other (segregating 1:1), 206 (25%) were intercross dominant markers heterozygous in both parents (segregating 3:1), and the remaining 73 (9%) were 19 non-parental RAPD markers (segregating 1:1) and 54 codominant AFLP markers (segregating 1:1:1:1). A mixed set of the testcross markers, non-parental RAPD markers, and codominant AFLP markers was used to construct two linkage maps, one based on the P. deltoides (D) genome and the other based on P. euramericana (E). The two maps showed nearly complete coverage of the genome, spanning 3801 and 3452 cM, respectively. The availability of non-parental RAPD and codominant AFLP markers as orthologous genes allowed for a direct comparison of the rate of meiotic recombination between the two different parental species. Generally, the rate of meiotic recombination was greater for males than females in our interspecific poplar hybrids. The confounded effect of sexes and species causes the mean recombination distance of orthologous markers to be 11% longer for the father (P. euramericana; interspecific hybrid) than for the mother (P. deltoides; pure species). The linkage maps constructed and the interspecific poplar hybrid population in which clonal replicates for individual genotypes are available present a comprehensive foundation for future genomic studies and

  13. 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 years. Such

  14. 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

  15. A Molecular Marker-Based Linkage Map of Phaseolus Vulgaris L

    PubMed Central

    Vallejos, C. E.; Sakiyama, N. S.; Chase, C. D.

    1992-01-01

    A seed and flower color marker (P), nine seed protein, nine isozyme and 224 restriction fragment length polymorphism marker loci were used to construct a linkage map of the common bean, Phaseolus vulgaris L. (n = 11). The mapping population consisted of a backcross progeny between the Mesoamerican breeding line `XR-235-1-1' and the Andean cultivar `Calima'; the former was used as the recurrent parent. A bean PstI genomic library enriched for single copy sequences (95%) was the source of DNA probes. Sixty percent of the probes tested detected polymorphisms betwen the parental genotypes with at least one of the four restriction enzymes used here (DraI, EcoRI, EcoRV and HindIII). The computer software Mapmaker was used to determine the linkage relationships and linear order of segregating markers. These markers assorted into 11 linkage groups covering 960 cM of the bean genome. Partial linkage data were used to estimate the total length of the genome at 1200 cM. This estimate and that for the physical size of the genome yield an average ratio of 530 kb/cM. The relatively small size of the genome makes this crop species a good candidate for the isolation of genes via chromosome walking techniques. PMID:1352759

  16. A molecular marker-based linkage map of Phaseolus vulgaris L.

    PubMed

    Vallejos, C E; Sakiyama, N S; Chase, C D

    1992-07-01

    A seed and flower color marker (P), nine seed protein, nine isozyme and 224 restriction fragment length polymorphism marker loci were used to construct a linkage map of the common bean, Phaseolus vulgaris L. (n = 11). The mapping population consisted of a backcross progeny between the Mesoamerican breeding line 'XR-235-1-1' and the Andean cultivar 'Calima'; the former was used as the recurrent parent. A bean PstI genomic library enriched for single copy sequences (95%) was the source of DNA probes. Sixty percent of the probes tested detected polymorphisms between the parental genotypes with at least one of the four restriction enzymes used here (DraI, EcoRI, EcoRV and HindIII). The computer software Mapmaker was used to determine the linkage relationships and linear order of segregating markers. These markers assorted into 11 linkage groups covering 960 cM of the bean genome. Partial linkage data were used to estimate the total length of the genome at 1200 cM. This estimate and that for the physical size of the genome yield an average ratio of 530 kb/cM. The relatively small size of the genome makes this crop species a good candidate for the isolation of genes via chromosome walking techniques.

  17. Confirmation and Fine Mapping of a Major QTL for Aflatoxin Resistance in Maize Using a Combination of Linkage and Association Mapping

    PubMed Central

    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

  18. Structural synthesis of linkages for quadruped bio-robot legs

    NASA Astrophysics Data System (ADS)

    Antonescu, O.; Robu, C.; Antonescu, P.

    2016-08-01

    The paper presents a few kinematic schemes of planar mechanisms with bars (linkages) used as part of the quadruped robot legs. The Dunshee linkage having only four elements as crank-rocker mechanism is analyzed. Further, the Klann linkage, which is accomplished by amplifying the crank-rocker mechanism with a dyadic kinematic chain, is also presented. More than that, the Jansen linkage, which is obtained by extending and amplifying the crank-rocker mechanism with two dyadic kinematic chains, is also analyzed. At the end of the paper, the authors present a novel linkage application consisting of a quadric kinematic chain.

  19. Construction of multilocus genetic linkage maps in humans.

    PubMed Central

    Lander, E S; Green, P

    1987-01-01

    Human genetic linkage maps are most accurately constructed by using information from many loci simultaneously. Traditional methods for such multilocus linkage analysis are computationally prohibitive in general, even with supercomputers. The problem has acquired practical importance because of the current international collaboration aimed at constructing a complete human linkage map of DNA markers through the study of three-generation pedigrees. We describe here several alternative algorithms for constructing human linkage maps given a specified gene order. One method allows maximum-likelihood multilocus linkage maps for dozens of DNA markers in such three-generation pedigrees to be constructed in minutes. PMID:3470801

  20. 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

  1. 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

  2. Gravel threshold of motion: a state function of sediment transport disequilibrium?

    NASA Astrophysics Data System (ADS)

    Johnson, Joel P. L.

    2016-08-01

    In most sediment transport models, a threshold variable dictates the shear stress at which non-negligible bedload transport begins. Previous work has demonstrated that nondimensional transport thresholds (τc*) vary with many factors related not only to grain size and shape, but also with characteristics of the local bed surface and sediment transport rate (qs). I propose a new model in which qs-dependent τc*, notated as τc(qs)*, evolves as a power-law function of net erosion or deposition. In the model, net entrainment is assumed to progressively remove more mobile particles while leaving behind more stable grains, gradually increasing τc(qs)* and reducing transport rates. Net deposition tends to fill in topographic lows, progressively leading to less stable distributions of surface grains, decreasing τc(qs)* and increasing transport rates. Model parameters are calibrated based on laboratory flume experiments that explore transport disequilibrium. The τc(qs)* equation is then incorporated into a simple morphodynamic model. The evolution of τc(qs)* is a negative feedback on morphologic change, while also allowing reaches to equilibrate to sediment supply at different slopes. Finally, τc(qs)* is interpreted to be an important but nonunique state variable for morphodynamics, in a manner consistent with state variables such as temperature in thermodynamics.

  3. Mineral disequilibrium in lavas explained by convective self-mixing in open magma chambers.

    PubMed

    Couch, S; Sparks, R S; Carroll, M R

    2001-06-28

    Characteristic features of many porphyritic andesite and dacite lavas are that they are rich in crystals and display a range of disequilibrium features, including reversely zoned crystals, resorption surfaces, wide ranges of mineral compositions and minerals which are not in equilibrium with the surrounding rock matrix. These features are often interpreted as evidence of the mixing of magmas of contrasting composition, temperature and origin. Here, however, we propose that such features can also be caused by convection within a magma body with a single composition, that is heated from below and cooled from above. We describe petrological observations of andesite lava erupted at the Soufrière Hills volcano, Montserrat, which indicate a heating event and the intermingling of crystals that have very different thermal histories. We present experimental data on a representative groundmass composition of this lava, which indicate that it is difficult to explain the calcic compositions of plagioclase overgrowth rims and microphenocrysts unless parts of the magma were at temperatures much higher than the inferred average temperature. The concept of convective self-mixing allows us to explain the occurrence of compositions of minerals that apparently cannot coexist under equilibrium conditions.

  4. Contemporaneous Disequilibrium, a New Hypothesis to Explain the „Paradox of the Plankton”*

    PubMed Central

    Richerson, Peter; Armstrong, Richard; Goldman, Charles R.

    1970-01-01

    The diversity of lake phytoplankton is unexpectedly high, since the epilimnion of a lake is continuously mixing and might be expected to have only one or at most a few niches for primary producers. However, a carefully replicated series of samples from Castle Lake, Calif., showed a high degree of patchiness for many phytoplankton species, indicating that the rate of mixing is slow enough relative to the reproductive rate of the algae for many different niches to exist simultaneously. Productivity per unit biomass ratios, measured at Lake Tahoe, California-Nevada, shows that the turnover times for carbon in even this ultraoligotrophic lake are often less than 1 day. High diversity is associated with high productivity per unit biomass and high zooplankton populations in this lake. A contemporaneous disequilibrium model to explain the diversity of the lake phytoplankton is therefore highly plausible. At any one time, many patches of water exist in which one species is at a competitive advantage relative to the others. These water masses are stable enough to permit a considerable degree of patchiness to occur in phytoplankton, but are obliterated frequently enough to prevent the exclusive occupation of each niche by a single species. PMID:5275371

  5. Disequilibrium in the uranium and actinium series in oil scale samples.

    PubMed

    Landsberger, S; Tamalis, D; Leblanc, C; Yoho, M D

    2017-01-01

    We have investigated the disequilibrium of the uranium and actinium series and have found both (226)Ra (90,200 ± 4300 Bq/kg) and (228)Ra have activity concentrations orders of magnitude higher that (238)U (1.83 ± 0.36 Bq/kg) and (232)Th (7.0 ± 0.4) which are at the head of the decay series. As well the activity concentration of (210)Pb (24,400 ± 1200 Bg/kg) was about 3.6 times less than (226)Ra. Once an efficiency curve was constructed summing corrections for specific isotopes in the decay change also needed to be taken in consideration. Furthermore, self-attenuation of the photons especially the 46.5 keV belonging to (210)Pb was calculated to be 78% since the scale had elevated elemental concentrations of high-Z elements such as barium and strontium.

  6. Possible thermochemical disequilibrium in the atmosphere of the exoplanet GJ 436b.

    PubMed

    Stevenson, Kevin B; Harrington, Joseph; Nymeyer, Sarah; Madhusudhan, Nikku; Seager, Sara; Bowman, William C; Hardy, Ryan A; Deming, Drake; Rauscher, Emily; Lust, Nate B

    2010-04-22

    The nearby extrasolar planet GJ 436b-which has been labelled as a 'hot Neptune'-reveals itself by the dimming of light as it crosses in front of and behind its parent star as seen from Earth. Respectively known as the primary transit and secondary eclipse, the former constrains the planet's radius and mass, and the latter constrains the planet's temperature and, with measurements at multiple wavelengths, its atmospheric composition. Previous work using transmission spectroscopy failed to detect the 1.4-mum water vapour band, leaving the planet's atmospheric composition poorly constrained. Here we report the detection of planetary thermal emission from the dayside of GJ 436b at multiple infrared wavelengths during the secondary eclipse. The best-fit compositional models contain a high CO abundance and a substantial methane (CH(4)) deficiency relative to thermochemical equilibrium models for the predicted hydrogen-dominated atmosphere. Moreover, we report the presence of some H(2)O and traces of CO(2). Because CH(4) is expected to be the dominant carbon-bearing species, disequilibrium processes such as vertical mixing and polymerization of methane into substances such as ethylene may be required to explain the hot Neptune's small CH(4)-to-CO ratio, which is at least 10(5) times smaller than predicted.

  7. sup 13 C and sup 18 O isotopic disequilibrium in biological carbonates: I. Patterns

    SciTech Connect

    McConnaughey, T. )

    1989-01-01

    Biological carbonates frequently precipitate out of {sup 18}O and {sup 13}C equilibrium with ambient waters. Two patterns of isotopic disequilibrium are particularly common. Kinetic disequilibria, so designated because they apparently result from kinetic isotope effects during CO{sub 2} hydration and hydroxylation, involve simultaneous depletions of {sup 18}O and {sup 13}C as large as 4{per thousand} and 10 to 15{per thousand}, respectively. Rapid skeletogenesis favors strong kinetic effects, and approximately linear correlations between skeletal {delta}{sup 18}O and {delta}{sup 13}C are common in carbonates showing mainly the kinetic pattern. Metabolic effects involve additional positive or negative modulation of skeletal {delta}{sup 13}C, reflecting changes in the {delta}{sup 13}C of dissolved inorganic carbon, caused mainly by photosynthesis and respiration. Kinetic isotope disequilibria tend to be fairly consistent in rapidly growing parts of photosynthetic corals, and time dependent isotopic variations therefore reflect changes in environmental conditions. {delta}{sup 18}O variations from Galapagos corals yields meaningful clues regarding seawater temperature, while {delta}{sup 13}C variations reflect changes in photosynthesis, modulated by cloudiness.

  8. Uranium series disequilibrium and high thorium and radium enrichments in Karst formations

    SciTech Connect

    Gunten, H.R. von; Roessler, E.; Surbeck, H.

    1996-04-01

    We found, in limestone Karst soils of the Jura Mountains and of the mountains in the central part of Switzerland, an enrichment up to a factor 20 of {sup 230}Th and {sup 226}Ra with respect to the activities of their progenitors, {sup 234}U and {sup 238}U. Thus, a significant radioactive disequilibrium exists between {sup 238/234}U and {sup 230}Th and {sup 226}Ra. The enrichment of {sup 226}Ra leads to locally high concentrations of its decay product, the noble gas {sup 222}Rn. We propose continuous chemical weathering of limestone (calcite) fragments within the soil column as a plausible cause for the high {sup 230}Th, {sup 226}Ra, and {sup 222}Rn activities. Uranium, contained within calcite, is released during weathering and migrates as stable uranyl carbonate complexes through the soil column. In contrast, its decay products ({sup 230}Th and {sup 226}Ra) hydrolyze, are strongly sorbed to soil particles, and/or form insoluble compounds that become more and more enriched in the soil as this process continues in time. 39 refs., 3 figs., 5 tabs.

  9. Handling missing data in transmission disequilibrium test in nuclear families with one affected offspring.

    PubMed

    Bourget, Gulhan

    2012-01-01

    The Transmission