Refining the Use of Linkage Disequilibrium as a Robust Signature of Selective Sweeps

PubMed Central

Jacobs, Guy S.; Sluckin, Timothy J.; Kivisild, Toomas

2016-01-01

During a selective sweep, characteristic patterns of linkage disequilibrium can arise in the genomic region surrounding a selected locus. These have been used to infer past selective sweeps. However, the recombination rate is known to vary substantially along the genome for many species. We here investigate the effectiveness of current (Kelly’s ZnS and ωmax) and novel statistics at inferring hard selective sweeps based on linkage disequilibrium distortions under different conditions, including a human-realistic demographic model and recombination rate variation. When the recombination rate is constant, Kelly’s ZnS offers high power, but is outperformed by a novel statistic that we test, which we call Zα. We also find this statistic to be effective at detecting sweeps from standing variation. When recombination rate fluctuations are included, there is a considerable reduction in power for all linkage disequilibrium-based statistics. However, this can largely be reversed by appropriately controlling for expected linkage disequilibrium using a genetic map. To further test these different methods, we perform selection scans on well-characterized HapMap data, finding that all three statistics—ωmax, Kelly’s ZnS, and Zα—are able to replicate signals at regions previously identified as selection candidates based on population differentiation or the site frequency spectrum. While ωmax replicates most candidates when recombination map data are not available, the ZnS and Zα statistics are more successful when recombination rate variation is controlled for. Given both this and their higher power in simulations of selective sweeps, these statistics are preferred when information on local recombination rate variation is available. PMID:27516617

Genetic diversity, linkage disequilibrium, population structure and construction of a core collection of Prunus avium L. landraces and bred cultivars.

PubMed

Campoy, José Antonio; Lerigoleur-Balsemin, Emilie; Christmann, Hélène; Beauvieux, Rémi; Girollet, Nabil; Quero-García, José; Dirlewanger, Elisabeth; Barreneche, Teresa

2016-02-24

Depiction of the genetic diversity, linkage disequilibrium (LD) and population structure is essential for the efficient organization and exploitation of genetic resources. The objectives of this study were to (i) to evaluate the genetic diversity and to detect the patterns of LD, (ii) to estimate the levels of population structure and (iii) to identify a 'core collection' suitable for association genetic studies in sweet cherry. A total of 210 genotypes including modern cultivars and landraces from 16 countries were genotyped using the RosBREED cherry 6 K SNP array v1. Two groups, mainly bred cultivars and landraces, respectively, were first detected using STRUCTURE software and confirmed by Principal Coordinate Analysis (PCoA). Further analyses identified nine subgroups using STRUCTURE and Discriminant Analysis of Principal Components (DAPC). Several sub-groups correspond to different eco-geographic regions of landraces distribution. Linkage disequilibrium was evaluated showing lower values than in peach, the reference Prunus species. A 'core collection' containing 156 accessions was selected using the maximum length sub tree method. The present study constitutes the first population genetics analysis in cultivated sweet cherry using a medium-density SNP (single nucleotide polymorphism) marker array. We provided estimations of linkage disequilibrium, genetic structure and the definition of a first INRA's Sweet Cherry core collection useful for breeding programs, germplasm management and association genetics studies.

Refining the Use of Linkage Disequilibrium as a Robust Signature of Selective Sweeps.

PubMed

Jacobs, Guy S; Sluckin, Tim J; Kivisild, Toomas

2016-08-01

During a selective sweep, characteristic patterns of linkage disequilibrium can arise in the genomic region surrounding a selected locus. These have been used to infer past selective sweeps. However, the recombination rate is known to vary substantially along the genome for many species. We here investigate the effectiveness of current (Kelly's [Formula: see text] and [Formula: see text]) and novel statistics at inferring hard selective sweeps based on linkage disequilibrium distortions under different conditions, including a human-realistic demographic model and recombination rate variation. When the recombination rate is constant, Kelly's [Formula: see text] offers high power, but is outperformed by a novel statistic that we test, which we call [Formula: see text] We also find this statistic to be effective at detecting sweeps from standing variation. When recombination rate fluctuations are included, there is a considerable reduction in power for all linkage disequilibrium-based statistics. However, this can largely be reversed by appropriately controlling for expected linkage disequilibrium using a genetic map. To further test these different methods, we perform selection scans on well-characterized HapMap data, finding that all three statistics-[Formula: see text] Kelly's [Formula: see text] and [Formula: see text]-are able to replicate signals at regions previously identified as selection candidates based on population differentiation or the site frequency spectrum. While [Formula: see text] replicates most candidates when recombination map data are not available, the [Formula: see text] and [Formula: see text] statistics are more successful when recombination rate variation is controlled for. Given both this and their higher power in simulations of selective sweeps, these statistics are preferred when information on local recombination rate variation is available. Copyright © 2016 by the Genetics Society of America.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 racialmore » 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.« less

Detecting Recombination Hotspots from Patterns of Linkage Disequilibrium.

PubMed

Wall, Jeffrey D; Stevison, Laurie S

2016-08-09

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. Copyright © 2016 Wall and Stevison.

Using Object Oriented Bayesian Networks to Model Linkage, Linkage Disequilibrium and Mutations between STR Markers

PubMed Central

Kling, Daniel; Egeland, Thore; Mostad, Petter

2012-01-01

In a number of applications there is a need to determine the most likely pedigree for a group of persons based on genetic markers. Adequate models are needed to reach this goal. The markers used to perform the statistical calculations can be linked and there may also be linkage disequilibrium (LD) in the population. The purpose of this paper is to present a graphical Bayesian Network framework to deal with such data. Potential LD is normally ignored and it is important to verify that the resulting calculations are not biased. Even if linkage does not influence results for regular paternity cases, it may have substantial impact on likelihood ratios involving other, more extended pedigrees. Models for LD influence likelihoods for all pedigrees to some degree and an initial estimate of the impact of ignoring LD and/or linkage is desirable, going beyond mere rules of thumb based on marker distance. Furthermore, we show how one can readily include a mutation model in the Bayesian Network; extending other programs or formulas to include such models may require considerable amounts of work and will in many case not be practical. As an example, we consider the two STR markers vWa and D12S391. We estimate probabilities for population haplotypes to account for LD using a method based on data from trios, while an estimate for the degree of linkage is taken from the literature. The results show that accounting for haplotype frequencies is unnecessary in most cases for this specific pair of markers. When doing calculations on regular paternity cases, the markers can be considered statistically independent. In more complex cases of disputed relatedness, for instance cases involving siblings or so-called deficient cases, or when small differences in the LR matter, independence should not be assumed. (The networks are freely available at http://arken.umb.no/~dakl/BayesianNetworks.) PMID:22984448

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

USDA-ARS?s Scientific Manuscript database

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...

Significant linkage disequilibrium between the Huntington disease gene and the loci D4S10 and D4S95 in the Dutch population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skraastad, M.I.; Van de Vosse, E.; Belfroid, R.

1992-10-01

Significant linkage disequilibrium has been found between the Huntington disease (HD) gene and DNA markers located around D4S95 and D4S98. The linkage-disequilibrium studies favor the proximal location of the HD gene, in contrast to the conflicting results of recombination analyses. The authors have analyzed 45 Dutch HD families with 19 DNA markers and have calculated the strength of linkage disequilibrium. Highly significant linkage disequilibrium has been detected with D4S95, consistent with the studies in other populations. In contrast with most other studies, however, the area of linkage disequilibrium extends from D4S10 proximally to D4S95, covering 1,100 kb. These results confirmmore » that the HD gene most likely maps near D4S95. 28 refs., 1 fig., 2 tabs.« less

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

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

Effects of Demographic History on the Detection of Recombination Hotspots from Linkage Disequilibrium

PubMed Central

Dapper, Amy L; Payseur, Bret A

2018-01-01

Abstract In some species, meiotic recombination is concentrated in small genomic regions. These “recombination hotspots” leave signatures in fine-scale patterns of linkage disequilibrium, raising the prospect that the genomic landscape of hotspots can be characterized from sequence variation. This approach has led to the inference that hotspots evolve rapidly in some species, but are conserved in others. Historic demographic events, such as population bottlenecks, are known to affect patterns of linkage disequilibrium across the genome, violating population genetic assumptions of this approach. Although such events are prevalent, demographic history is generally ignored when making inferences about the evolution of recombination hotspots. To determine the effect of demography on the detection of recombination hotspots, we use the coalescent to simulate haplotypes with a known recombination landscape. We measure the ability of popular linkage disequilibrium-based programs to detect hotspots across a range of demographic histories, including population bottlenecks, hidden population structure, population expansions, and population contractions. We find that demographic events have the potential to greatly reduce the power and increase the false positive rate of hotspot discovery. Neither the power nor the false positive rate of hotspot detection can be predicted without also knowing the demographic history of the sample. Our results suggest that ignoring demographic history likely overestimates the power to detect hotspots and therefore underestimates the degree of hotspot sharing between species. We suggest strategies for incorporating demographic history into population genetic inferences about recombination hotspots. PMID:29045724

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

PubMed Central

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

2006-01-01

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

MICA diversity and linkage disequilibrium with HLA-B alleles in renal-transplant candidates in southern Brazil.

PubMed

Yamakawa, Roger Haruki; Saito, Patrícia Keiko; Gelmini, Geórgia Fernanda; da Silva, José Samuel; Bicalho, Maria da Graça; Borelli, Sueli Donizete

2017-01-01

The major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located centromerically to the human leukocyte antigen (HLA)-B. The short distance between these loci in the MHC indicates the presence of linkage disequilibrium (LD). Similarly to the HLA, the MICA is highly polymorphic, and this polymorphism has not been well documented in different populations. In this study, we estimated the allelic frequencies of MICA and the linkage disequilibrium with HLA-B alleles in 346 renal-transplant candidates in southern Brazil. MICA and HLA were typed using the polymerase chain reaction-sequence-specific primer method (PCR-SSO), combined with the Luminex technology. A total of 19 MICA allele groups were identified. The most frequent allele groups were MICA*008 (21.6%), MICA*002 (17.0%) and MICA*004 (14.8%). The most common haplotypes were MICA*009-B*51 (7.8%), MICA*004-B*44 (6.06%) and MICA*002-B*35 (5.63%). As expected from the proximity of the MICA and HLA-B loci, most haplotypes showed strong LD. Renal patients and healthy subjects in the same region of Brazil showed statistically significant differences in their MICA polymorphisms. The MICA*027 allele group was more frequent in renal patients (Pc = 0.018, OR: 3.421, 95% CI: 1.516-7.722), while the MICA*019 allele group was more frequent in healthy subjects (Pc = 0.001, OR: 0.027, 95% CI: 0.002-0.469). This study provided information on the distribution of MICA polymorphisms and linkage disequilibrium with HLA-B alleles in Brazilian renal-transplant candidates. This information should help to determine the mechanisms of susceptibility to different diseases in patients with chronic kidney disease, and to elucidate the mechanisms involved in allograft rejection associated with MICA polymorphisms in a Brazilian population.

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

PubMed

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

2016-07-29

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

Effects of Demographic History on the Detection of Recombination Hotspots from Linkage Disequilibrium.

PubMed

Dapper, Amy L; Payseur, Bret A

2018-02-01

In some species, meiotic recombination is concentrated in small genomic regions. These "recombination hotspots" leave signatures in fine-scale patterns of linkage disequilibrium, raising the prospect that the genomic landscape of hotspots can be characterized from sequence variation. This approach has led to the inference that hotspots evolve rapidly in some species, but are conserved in others. Historic demographic events, such as population bottlenecks, are known to affect patterns of linkage disequilibrium across the genome, violating population genetic assumptions of this approach. Although such events are prevalent, demographic history is generally ignored when making inferences about the evolution of recombination hotspots. To determine the effect of demography on the detection of recombination hotspots, we use the coalescent to simulate haplotypes with a known recombination landscape. We measure the ability of popular linkage disequilibrium-based programs to detect hotspots across a range of demographic histories, including population bottlenecks, hidden population structure, population expansions, and population contractions. We find that demographic events have the potential to greatly reduce the power and increase the false positive rate of hotspot discovery. Neither the power nor the false positive rate of hotspot detection can be predicted without also knowing the demographic history of the sample. Our results suggest that ignoring demographic history likely overestimates the power to detect hotspots and therefore underestimates the degree of hotspot sharing between species. We suggest strategies for incorporating demographic history into population genetic inferences about recombination hotspots. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Extended Intermarker Linkage Disequilibrium in the Afrikaners

PubMed Central

Hall, Diana; Wijsman, Ellen M.; Roos, J. Louw; Gogos, Joseph A.; Karayiorgou, Maria

2002-01-01

In this study we conducted an investigation of the background level of linkage disequilibrium (LD) in the Afrikaner population to evaluate the appropriateness of this genetic isolate for mapping complex traits. We analyzed intermarker LD in 62 nuclear families using microsatellite markers covering extended chromosomal regions. The markers were selected to allow the first direct comparison of long-range LD in the Afrikaners to LD in other demographic groups. Using several statistical measures, we find significant evidence for LD in the Afrikaners extending remarkably over a 6-cM range. In contrast, LD decays significantly beyond 3-cM distances in the other founder and outbred populations examined. This study strongly supports the appropriateness of the Afrikaner population for genome-wide scans that exploit LD to map common, multigenic disorders. PMID:12045148

Extended intermarker linkage disequilibrium in the Afrikaners.

PubMed

Hall, Diana; Wijsman, Ellen M; Roos, J Louw; Gogos, Joseph A; Karayiorgou, Maria

2002-06-01

In this study we conducted an investigation of the background level of linkage disequilibrium (LD) in the Afrikaner population to evaluate the appropriateness of this genetic isolate for mapping complex traits. We analyzed intermarker LD in 62 nuclear families using microsatellite markers covering extended chromosomal regions. The markers were selected to allow the first direct comparison of long-range LD in the Afrikaners to LD in other demographic groups. Using several statistical measures, we find significant evidence for LD in the Afrikaners extending remarkably over a 6-cM range. In contrast, LD decays significantly beyond 3-cM distances in the other founder and outbred populations examined. This study strongly supports the appropriateness of the Afrikaner population for genome-wide scans that exploit LD to map common, multigenic disorders.

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.

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

USDA-ARS?s Scientific Manuscript database

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 ...

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

USDA-ARS?s Scientific Manuscript database

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...

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

USDA-ARS?s Scientific Manuscript database

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...

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

USDA-ARS?s Scientific Manuscript database

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...

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

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 amore » schizophrenia susceptibility gene. 12 refs., 1 tab.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yaouanq, J.; Perichon, M.; Treut, A.L.

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 normalmore » 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

Genomewide Linkage Disequilibrium Mapping of Severe Bipolar Disorder in a Population Isolate

PubMed Central

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

2002-01-01

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

Temporal dynamics of linkage disequilibrium in two populations of bighorn sheep

PubMed Central

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

2015-01-01

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

Genomic polymorphism, recombination, and linkage disequilibrium in human major histocompatibility complex-encoded antigen-processing genes.

PubMed Central

van Endert, P M; Lopez, M T; Patel, S D; Monaco, J J; McDevitt, H O

1992-01-01

Recently, two subunits of a large cytosolic protease and two putative peptide transporter proteins were found to be encoded by genes within the class II region of the major histocompatibility complex (MHC). These genes have been suggested to be involved in the processing of antigenic proteins for presentation by MHC class I molecules. Because of the high degree of polymorphism in MHC genes, and previous evidence for both functional and polypeptide sequence polymorphism in the proteins encoded by the antigen-processing genes, we tested DNA from 27 consanguineous human cell lines for genomic polymorphism by restriction fragment length polymorphism (RFLP) analysis. These studies demonstrate a strong linkage disequilibrium between TAP1 and LMP2 RFLPs. Moreover, RFLPs, as well as a polymorphic stop codon in the telomeric TAP2 gene, appear to be in linkage disequilibrium with HLA-DR alleles and RFLPs in the HLA-DO gene. A high rate of recombination, however, seems to occur in the center of the complex, between the TAP1 and TAP2 genes. Images PMID:1360671

Uneven recombination and linkage disequilibrium across a reference SNP map for common bean (Phaseolus vulgaris L.)

USDA-ARS?s Scientific Manuscript database

Linkage disequilibrium (LD) and recombination (R) analyses are the basis for plant breeding. LD and R vary by breeding system, by generation of inbreeding or outcrossing and by region of the chromosome. Common bean (Phaseolus vulgaris L.) is a favored food legume with a small sequenced genome and n=...

Estimation of linkage disequilibrium and analysis of genetic diversity in Korean chicken lines.

PubMed

Seo, Dongwon; Lee, Doo Ho; Choi, Nuri; Sudrajad, Pita; Lee, Seung-Hwan; Lee, Jun-Heon

2018-01-01

The development of genetic markers for animal breeding is an effective strategy to reduce the time and cost required to improve economically important traits. To implement genomic selection in the multibreed chicken population of Korea, an understanding of the linkage disequilibrium (LD) status of the target population is essential. In this study, we performed population genetic analyses to investigate LD decay, the effective population size, and breed diversity using 600K high-density single nucleotide polymorphism genotypes of 189 native chickens in 14 lines (including Korean native chicken, imported and adapted purebred and commercial chickens). The results indicated that commercial native chickens have less calculated LD (average, r2 = 0.13-0.26) and purebred native chickens have more calculated LD (average, r2 = 0.24-0.37) across the entire genome. The effective population sizes of the examined lines showed patterns opposite to those of population LD. The phylogeny and admixture analyses showed that commercial and purebred chickens were well distinguished, except for Rhode Island Red (RIR) purebred lines of NC (NIAS_RIR_C) and ND (NIAS_RIR_D). These lines are difficult to distinguish clearly because they originated from the same respective breeds. The results of this study may provide important information for the development of genetic markers that can be used in breeding to improve the economic traits of native chickens.

Estimation of linkage disequilibrium and analysis of genetic diversity in Korean chicken lines

PubMed Central

Seo, Dongwon; Lee, Doo Ho; Choi, Nuri; Sudrajad, Pita; Lee, Seung-Hwan

2018-01-01

The development of genetic markers for animal breeding is an effective strategy to reduce the time and cost required to improve economically important traits. To implement genomic selection in the multibreed chicken population of Korea, an understanding of the linkage disequilibrium (LD) status of the target population is essential. In this study, we performed population genetic analyses to investigate LD decay, the effective population size, and breed diversity using 600K high-density single nucleotide polymorphism genotypes of 189 native chickens in 14 lines (including Korean native chicken, imported and adapted purebred and commercial chickens). The results indicated that commercial native chickens have less calculated LD (average, r2 = 0.13–0.26) and purebred native chickens have more calculated LD (average, r2 = 0.24–0.37) across the entire genome. The effective population sizes of the examined lines showed patterns opposite to those of population LD. The phylogeny and admixture analyses showed that commercial and purebred chickens were well distinguished, except for Rhode Island Red (RIR) purebred lines of NC (NIAS_RIR_C) and ND (NIAS_RIR_D). These lines are difficult to distinguish clearly because they originated from the same respective breeds. The results of this study may provide important information for the development of genetic markers that can be used in breeding to improve the economic traits of native chickens. PMID:29425208

The effect of missing data on linkage disequilibrium mapping and haplotype association analysis in the GAW14 simulated datasets

PubMed Central

McCaskie, Pamela A; Carter, Kim W; McCaskie, Simon R; Palmer, Lyle J

2005-01-01

We used our newly developed linkage disequilibrium (LD) plotting software, JLIN, to plot linkage disequilibrium between pairs of single-nucleotide polymorphisms (SNPs) for three chromosomes of the Genetic Analysis Workshop 14 Aipotu simulated population to assess the effect of missing data on LD calculations. Our haplotype analysis program, SIMHAP, was used to assess the effect of missing data on haplotype-phenotype association. Genotype data was removed at random, at levels of 1%, 5%, and 10%, and the LD calculations and haplotype association results for these levels of missingness were compared to those for the complete dataset. It was concluded that ignoring individuals with missing data substantially affects the number of regions of LD detected which, in turn, could affect tagging SNPs chosen to generate haplotypes. PMID:16451612

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

PubMed Central

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

2013-01-01

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

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.

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

PubMed

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

2016-05-31

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). 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. 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. 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.

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

PubMed Central

2014-01-01

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

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.

speed-ne: Software to simulate and estimate genetic effective population size (Ne ) from linkage disequilibrium observed in single samples.

PubMed

Hamilton, Matthew B; Tartakovsky, Maria; Battocletti, Amy

2018-05-01

The genetic effective population size, N e , can be estimated from the average gametic disequilibrium (r2^) between pairs of loci, but such estimates require evaluation of assumptions and currently have few methods to estimate confidence intervals. speed-ne is a suite of matlab computer code functions to estimate Ne^ from r2^ with a graphical user interface and a rich set of outputs that aid in understanding data patterns and comparing multiple estimators. speed-ne includes functions to either generate or input simulated genotype data to facilitate comparative studies of Ne^ estimators under various population genetic scenarios. speed-ne was validated with data simulated under both time-forward and time-backward coalescent models of genetic drift. Three classes of estimators were compared with simulated data to examine several general questions: what are the impacts of microsatellite null alleles on Ne^, how should missing data be treated, and does disequilibrium contributed by reduced recombination among some loci in a sample impact Ne^. Estimators differed greatly in precision in the scenarios examined, and a widely employed Ne^ estimator exhibited the largest variances among replicate data sets. speed-ne implements several jackknife approaches to estimate confidence intervals, and simulated data showed that jackknifing over loci and jackknifing over individuals provided ~95% confidence interval coverage for some estimators and should be useful for empirical studies. speed-ne provides an open-source extensible tool for estimation of Ne^ from empirical genotype data and to conduct simulations of both microsatellite and single nucleotide polymorphism (SNP) data types to develop expectations and to compare Ne^ estimators. © 2018 John Wiley & Sons Ltd.

Ignoring Intermarker Linkage Disequilibrium Induces False-Positive Evidence of Linkage for Consanguineous Pedigrees when Genotype Data Is Missing for Any Pedigree Member

PubMed Central

Li, Bingshan; Leal, Suzanne M.

2008-01-01

Missing genotype data can increase false-positive evidence for linkage when either parametric or nonparametric analysis is carried out ignoring intermarker linkage disequilibrium (LD). Previously it was demonstrated by Huang et al. [1] that no bias occurs in this situation for affected sib-pairs with unrelated parents when either both parents are genotyped or genotype data is available for two additional unaffected siblings when parental genotypes are missing. However, this is not the case for autosomal recessive consanguineous pedigrees, where missing genotype data for any pedigree member within a consanguinity loop can increase false-positive evidence of linkage. False-positive evidence for linkage is further increased when cryptic consanguinity is present. The amount of false-positive evidence for linkage, and which family members aid in its reduction, is highly dependent on which family members are genotyped. When parental genotype data is available, the false-positive evidence for linkage is usually not as strong as when parental genotype data is unavailable. For a pedigree with an affected proband whose first-cousin parents have been genotyped, further reduction in the false-positive evidence of linkage can be obtained by including genotype data from additional affected siblings of the proband or genotype data from the proband's sibling-grandparents. For the situation, when parental genotypes are unavailable, false-positive evidence for linkage can be reduced by including genotype data from either unaffected siblings of the proband or the proband's married-in-grandparents in the analysis. PMID:18073490

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

Genetic structure, linkage disequilibrium and signature of selection in Sorghum: lessons from physically anchored DArT markers.

PubMed

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 r(2) 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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Escamilla, M.A.; Reus, V.I.; Smith, L.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, andmore » 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.« less

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

USDA-ARS?s Scientific Manuscript database

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...

Linkage disequilibrium in HLA cannot be explained by selective recombination.

PubMed

Termijtelen, A; D'Amaro, J; van Rood, J J; Schreuder, G M

1995-11-01

Some combinations of HLA-A, -B and -DR antigens occur more frequently than would be expected from their gene frequencies in the population. This phenomenon, referred to as Linkage Disequilibrium (LD) has been the origin of many speculations. One hypothesis to explain LD is that some haplotypes are protected from recombination. A second hypothesis is that these HLA antigens preferentially recombine after cross-over to create an LD haplotype. We tested these 2 hypotheses: from a pool of over 10,000 families typed in our department, we analyzed 126 families in which HLA-A:B or B:DR recombinant offspring was documented. To overcome a possible bias in our material, we used the non-recombined haplotypes from the same 126 families as a control group. Our results show that the number of cross-overs through LD haplotypes is not significantly lower then would be expected if recombination occurred randomly. Also the number of LD haplotypes created upon recombination was not significantly increased.

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

USDA-ARS?s Scientific Manuscript database

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...

Genome-wide patterns of recombination, linkage disequilibrium and nucleotide diversity from pooled resequencing and single nucleotide polymorphism genotyping unlock the evolutionary history of Eucalyptus grandis.

PubMed

Silva-Junior, Orzenil B; Grattapaglia, Dario

2015-11-01

We used high-density single nucleotide polymorphism (SNP) data and whole-genome pooled resequencing to examine the landscape of population recombination (ρ) and nucleotide diversity (ϴw ), assess the extent of linkage disequilibrium (r(2) ) and build the highest density linkage maps for Eucalyptus. At the genome-wide level, linkage disequilibrium (LD) decayed within c. 4-6 kb, slower than previously reported from candidate gene studies, but showing considerable variation from absence to complete LD up to 50 kb. A sharp decrease in the estimate of ρ was seen when going from short to genome-wide inter-SNP distances, highlighting the dependence of this parameter on the scale of observation adopted. Recombination was correlated with nucleotide diversity, gene density and distance from the centromere, with hotspots of recombination enriched for genes involved in chemical reactions and pathways of the normal metabolic processes. The high nucleotide diversity (ϴw = 0.022) of E. grandis revealed that mutation is more important than recombination in shaping its genomic diversity (ρ/ϴw = 0.645). Chromosome-wide ancestral recombination graphs allowed us to date the split of E. grandis (1.7-4.8 million yr ago) and identify a scenario for the recent demographic history of the species. Our results have considerable practical importance to Genome Wide Association Studies (GWAS), while indicating bright prospects for genomic prediction of complex phenotypes in eucalypt breeding. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

Novel linkage disequilibrium clustering algorithm identifies new lupus genes on meta-analysis of GWAS datasets.

PubMed

Saeed, Mohammad

2017-05-01

Systemic lupus erythematosus (SLE) is a complex disorder. Genetic association studies of complex disorders suffer from the following three major issues: phenotypic heterogeneity, false positive (type I error), and false negative (type II error) results. Hence, genes with low to moderate effects are missed in standard analyses, especially after statistical corrections. OASIS is a novel linkage disequilibrium clustering algorithm that can potentially address false positives and negatives in genome-wide association studies (GWAS) of complex disorders such as SLE. OASIS was applied to two SLE dbGAP GWAS datasets (6077 subjects; ∼0.75 million single-nucleotide polymorphisms). OASIS identified three known SLE genes viz. IFIH1, TNIP1, and CD44, not previously reported using these GWAS datasets. In addition, 22 novel loci for SLE were identified and the 5 SLE genes previously reported using these datasets were verified. OASIS methodology was validated using single-variant replication and gene-based analysis with GATES. This led to the verification of 60% of OASIS loci. New SLE genes that OASIS identified and were further verified include TNFAIP6, DNAJB3, TTF1, GRIN2B, MON2, LATS2, SNX6, RBFOX1, NCOA3, and CHAF1B. This study presents the OASIS algorithm, software, and the meta-analyses of two publicly available SLE GWAS datasets along with the novel SLE genes. Hence, OASIS is a novel linkage disequilibrium clustering method that can be universally applied to existing GWAS datasets for the identification of new genes.

The Power to Detect Linkage Disequilibrium with Quantitative Traits in Selected Samples

PubMed Central

Abecasis, Gonçalo R.; Cookson, William O. C.; Cardon, Lon R.

2001-01-01

Results from power studies for linkage detection have led to many ongoing and planned collections of phenotypically extreme nuclear families. Given the great expense of collecting these families and the imminent availability of a dense diallelic marker map, the families are likely to be used in allelic-association as well as linkage studies. However, optimal selection strategies for linkage may not be equally powerful for association. We examine the power to detect linkage disequilibrium for quantitative traits after phenotypic selection. The results encompass six selection strategies that are in widespread use, including single selection (two designs), affected sib pairs, concordant and discordant pairs, and the extreme-concordant and -discordant design. Selection of sibships on the basis of one extreme proband with high or low trait scores provides as much power as discordant sib pairs but requires the screening and phenotyping of substantially fewer initial families from which to select. Analysis of the role of allele frequencies within each selection design indicates that common trait alleles generally offer the most power, but similarities between the marker- and trait-allele frequencies are much more important than the trait-locus frequency alone. Some of the most widespread selection designs, such as single selection, yield power gains only when both the marker and quantitative trait loci (QTL) are relatively rare in the population. In contrast, discordant pairs and the extreme-proband design provide power for the broadest range of QTL–marker-allele frequency differences. Overall, proband selection from either tail provides the best balance of power, robustness, and simplicity of ascertainment for family-based association analysis. PMID:11349228

Genetic variation, population structure and linkage disequilibrium in Switchgrass with ISSR, SCoT and EST-SSR markers.

PubMed

Zhang, Yu; Yan, Haidong; Jiang, Xiaomei; Wang, Xiaoli; Huang, Linkai; Xu, Bin; Zhang, Xinquan; Zhang, Lexin

2016-01-01

To evaluate genetic variation, population structure, and the extent of linkage disequilibrium (LD), 134 switchgrass ( Panicum virgatum L.) samples were analyzed with 51 markers, including 16 ISSRs, 20 SCoTs, and 15 EST-SSRs. In this study, a high level of genetic variation was observed in the switchgrass samples and they had an average Nei's gene diversity index (H) of 0.311. A total of 793 bands were obtained, of which 708 (89.28 %) were polymorphic. Using a parameter marker index (MI), the efficiency of the three types of markers (ISSR, SCoT, and EST-SSR) in the study were compared and we found that SCoT had a higher marker efficiency than the other two markers. The 134 switchgrass samples could be divided into two sub-populations based on STRUCTURE, UPGMA clustering, and principal coordinate analyses (PCA), and upland and lowland ecotypes could be separated by UPGMA clustering and PCA analyses. Linkage disequilibrium analysis revealed an average r 2 of 0.035 across all 51 markers, indicating a trend of higher LD in sub-population 2 than that in sub-population 1 ( P  < 0.01). The population structure revealed in this study will guide the design of future association studies using these switchgrass samples.

Linkage disequilibrium matches forensic genetic records to disjoint genomic marker sets.

PubMed

Edge, Michael D; Algee-Hewitt, Bridget F B; Pemberton, Trevor J; Li, Jun Z; Rosenberg, Noah A

2017-05-30

Combining genotypes across datasets is central in facilitating advances in genetics. Data aggregation efforts often face the challenge of record matching-the identification of dataset entries that represent the same individual. We show that records can be matched across genotype datasets that have no shared markers based on linkage disequilibrium between loci appearing in different datasets. Using two datasets for the same 872 people-one with 642,563 genome-wide SNPs and the other with 13 short tandem repeats (STRs) used in forensic applications-we find that 90-98% of forensic STR records can be connected to corresponding SNP records and vice versa. Accuracy increases to 99-100% when ∼30 STRs are used. Our method expands the potential of data aggregation, but it also suggests privacy risks intrinsic in maintenance of databases containing even small numbers of markers-including databases of forensic significance.

Linkage disequilibrium compared between five populations of domestic sheep.

PubMed

Meadows, Jennifer R S; Chan, Eva K F; Kijas, James W

2008-09-30

The success of genome-wide scans depends on the strength and magnitude of linkage disequilibrium (LD) present within the populations under investigation. High density SNP arrays are currently in development for the sheep genome, however little is known about the behaviour of LD in this livestock species. This study examined the behaviour of LD within five sheep populations using two LD metrics, D' and x2'. Four economically important Australian sheep flocks, three pure breeds (White Faced Suffolk, Poll Dorset, Merino) and a crossbred population (Merino x Border Leicester), along with an inbred Australian Merino museum flock were analysed. Short range LD (0 - 5 cM) was observed in all five populations, however the persistence with increasing distance and magnitude of LD varied considerably between populations. Average LD (x2') for markers spaced up to 20 cM exceeded the non-syntenic average within the White Faced Suffolk, Poll Dorset and Macarthur Merino. LD decayed faster within the Merino and Merino x Border Leicester, with LD below or consistent with observed background levels. Using marker-marker LD as a guide to the behaviour of marker-QTL LD, estimates of minimum marker spacing were made. For a 95% probability of detecting QTL, a microsatellite marker would be required every 0.1 - 2.5 centimorgans, depending on the population used. Sheep populations were selected which were inbred (Macarthur Merino), highly heterogeneous (Merino) or intermediate between these two extremes. This facilitated analysis and comparison of LD (x2') between populations. The strength and magnitude of LD was found to differ markedly between breeds and aligned closely with both observed levels of genetic diversity and expectations based on breed history. This confirmed that breed specific information is likely to be important for genome wide selection and during the design of successful genome scans where tens of thousands of markers will be required.

Measuring and partitioning the high-order linkage disequilibrium by multiple order Markov chains.

PubMed

Kim, Yunjung; Feng, Sheng; Zeng, Zhao-Bang

2008-05-01

A map of the background levels of disequilibrium between nearby markers can be useful for association mapping studies. In order to assess the background levels of linkage disequilibrium (LD), multilocus LD measures are more advantageous than pairwise LD measures because the combined analysis of pairwise LD measures is not adequate to detect simultaneous allele associations among multiple markers. Various multilocus LD measures based on haplotypes have been proposed. However, most of these measures provide a single index of association among multiple markers and does not reveal the complex patterns and different levels of LD structure. In this paper, we employ non-homogeneous, multiple order Markov Chain models as a statistical framework to measure and partition the LD among multiple markers into components due to different orders of marker associations. Using a sliding window of multiple markers on phased haplotype data, we compute corresponding likelihoods for different Markov Chain (MC) orders in each window. The log-likelihood difference between the lowest MC order model (MC0) and the highest MC order model in each window is used as a measure of the total LD or the overall deviation from the gametic equilibrium for the window. Then, we partition the total LD into lower order disequilibria and estimate the effects from two-, three-, and higher order disequilibria. The relationship between different orders of LD and the log-likelihood difference involving two different orders of MC models are explored. By applying our method to the phased haplotype data in the ENCODE regions of the HapMap project, we are able to identify high/low multilocus LD regions. Our results reveal that the most LD in the HapMap data is attributed to the LD between adjacent pairs of markers across the whole region. LD between adjacent pairs of markers appears to be more significant in high multilocus LD regions than in low multilocus LD regions. We also find that as the multilocus total LD

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yin, Tongming; Difazio, Stephen P.; Gunter, Lee E

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 16more » 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.« less

Identification of positive selection signatures in pigs by comparing linkage disequilibrium variances.

PubMed

Li, X; Yang, S; Dong, K; Tang, Z; Li, K; Fan, B; Wang, Z; Liu, B

2017-10-01

Selection affects the patterns of linkage disequilibrium (LD) around the site of a beneficial allele with an increase in LD among the hitchhiking alleles. Comparing the differences in regional LD between pig populations could help to identify putative genomic regions with potential adaptations for economic traits. In this study, using Illumina Porcine SNP60K BeadChip genotyping data from 207 Chinese indigenous, 117 South American village and 408 Large White pigs, we estimated the variation of genome-wide LD between populations using the varld program. The top 0.1% standardized VarLD scores were used as a criterion for all comparisons, and compared with LD blocks, a total of four selection signatures on Sus scrofa chromosome (SSC) 7, 9, 13 and 14 were identified in all populations. These signatures overlapped with quantitative trait loci for linoleic acid content, age at puberty, number of muscle fibers per unit area, hip structure and body weight traits in pigs. Among them, one of the signatures (56.5-56.6 Mb on SSC7) in Large White pigs harbored the ADAMTSL3 gene, which is known to affect body length. The findings of this study seem to point toward recent selection in different pig populations. Further investigations are encouraged to confirm the selection signatures detected by varld in the present study. © 2017 Stichting International Foundation for Animal Genetics.

Natural Allelic Diversity, Genetic Structure and Linkage Disequilibrium Pattern in Wild Chickpea

PubMed Central

Kujur, Alice; Das, Shouvik; Badoni, Saurabh; Kumar, Vinod; Singh, Mohar; Bansal, Kailash C.; Tyagi, Akhilesh K.; Parida, Swarup K.

2014-01-01

Characterization of natural allelic diversity and understanding the genetic structure and linkage disequilibrium (LD) pattern in wild germplasm accessions by large-scale genotyping of informative microsatellite and single nucleotide polymorphism (SNP) markers is requisite to facilitate chickpea genetic improvement. Large-scale validation and high-throughput genotyping of genome-wide physically mapped 478 genic and genomic microsatellite markers and 380 transcription factor gene-derived SNP markers using gel-based assay, fluorescent dye-labelled automated fragment analyser and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass array have been performed. Outcome revealed their high genotyping success rate (97.5%) and existence of a high level of natural allelic diversity among 94 wild and cultivated Cicer accessions. High intra- and inter-specific polymorphic potential and wider molecular diversity (11–94%) along with a broader genetic base (13–78%) specifically in the functional genic regions of wild accessions was assayed by mapped markers. It suggested their utility in monitoring introgression and transferring target trait-specific genomic (gene) regions from wild to cultivated gene pool for the genetic enhancement. Distinct species/gene pool-wise differentiation, admixed domestication pattern, and differential genome-wide recombination and LD estimates/decay observed in a six structured population of wild and cultivated accessions using mapped markers further signifies their usefulness in chickpea genetics, genomics and breeding. PMID:25222488

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

PubMed

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

2015-09-01

Recent advances in sequencing allow population-genomic data to be generated for virtually any species. However, approaches to analyse such data lag behind the ability to generate it, particularly in nonmodel species. Linkage disequilibrium (LD, the nonrandom association of alleles from different loci) is a highly sensitive indicator of many evolutionary phenomena including chromosomal inversions, local adaptation and geographical structure. Here, we present linkage disequilibrium network analysis (LDna), which accesses information on LD shared between multiple loci genomewide. In LD networks, vertices represent loci, and connections between vertices represent the LD between them. We analysed such networks in two test cases: a new restriction-site-associated DNA sequence (RAD-seq) data set for Anopheles baimaii, a Southeast Asian malaria vector; and a well-characterized single nucleotide polymorphism (SNP) data set from 21 three-spined stickleback individuals. In each case, we readily identified five distinct LD network clusters (single-outlier clusters, SOCs), each comprising many loci connected by high LD. In A. baimaii, further population-genetic analyses supported the inference that each SOC corresponds to a large inversion, consistent with previous cytological studies. For sticklebacks, we inferred that each SOC was associated with a distinct evolutionary phenomenon: two chromosomal inversions, local adaptation, population-demographic history and geographic structure. LDna is thus a useful exploratory tool, able to give a global overview of LD associated with diverse evolutionary phenomena and identify loci potentially involved. LDna does not require a linkage map or reference genome, so it is applicable to any population-genomic data set, making it especially valuable for nonmodel species. © 2015 The Authors. Molecular Ecology Resources Published by John Wiley & Sons Ltd.

Intrahaplotypic Variants Differentiate Complex Linkage Disequilibrium within Human MHC Haplotypes

PubMed Central

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

2015-01-01

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

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

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

PubMed Central

Houle, David; Márquez, Eladio J.

2015-01-01

We calculated the linkage disequilibrium between all pairs of variants in the Drosophila Genome Reference Panel with minor allele count ≥5. We used r2 ≥ 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. PMID:26068573

Estimating glacier response times and disequilibrium in a changing climate

NASA Astrophysics Data System (ADS)

Christian, J. E.; Koutnik, M.; Roe, G.

2017-12-01

Glaciers respond to climate variations according to a characteristic timescale that, for most mountain glaciers, is on the order of 10—100 years. An important consequence of this multi-decadal memory is that a glacier's transient response to a climate trend exhibits a persistent lag behind the equilibrium response. In the context of anthropogenic warming, this means that most glaciers are currently well out of equilibrium, and that a substantial amount of retreat is committed even without further warming. The degree of disequilibrium depends fundamentally on the glacier response timescale, making it an important parameter to constrain. A common and robust metric for the response timescale is τ=H/bt, where H and bt are characteristic values for ice thickness and the terminus mass-balance rate, respectively. However, sparse observations, climate variability, and glacier disequilibrium make it difficult to define these characteristic values. We compare several sources of uncertainty that will affect estimates of the response timescale and thus the degree of disequilibrium. Ice thickness is poorly constrained for many glaciers, which bears directly on estimates of the response timescale. However, errors may also arise from estimating thickness and mass-balance rates in a variable climate. We assess how noisy mass balance and observed terminus fluctuations introduce sampling errors into estimates of the glacier's response timescale and the expected equilibrium response to a climate change. Additionally, the instantaneous value of τ evolves during sustained warming as the glacier thins and retreats. Perhaps counterintuitively, τ can increase if retreat into higher elevations exceeds thinning. This has implications for estimating the timescale based on currently observed geometry and mass balance. We use shallow-ice and 3-stage linear models to explore these effects with synthetic glacier geometries and climate forcings. In this way, we can diagnose the geometric and

Impact of population structure, effective bottleneck time, and allele frequency on linkage disequilibrium maps

PubMed Central

Zhang, Weihua; Collins, Andrew; Gibson, Jane; Tapper, William J.; Hunt, Sarah; Deloukas, Panos; Bentley, David R.; Morton, Newton E.

2004-01-01

Genetic maps in linkage disequilibrium (LD) units play the same role for association mapping as maps in centimorgans provide at much lower resolution for linkage mapping. Association mapping of genes determining disease susceptibility and other phenotypes is based on the theory of LD, here applied to relations with three phenomena. To test the theory, markers at high density along a 10-Mb continuous segment of chromosome 20q were studied in African-American, Asian, and Caucasian samples. Population structure, whether created by pooling samples from divergent populations or by the mating pattern in a mixed population, is accurately bioassayed from genotype frequencies. The effective bottleneck time for Eurasians is substantially less than for migration out of Africa, reflecting later bottlenecks. The classical dependence of allele frequency on mutation age does not hold for the generally shorter time span of inbreeding and LD. Limitation of the classical theory to mutation age justifies the assumption of constant time in a LD map, except for alleles that were rare at the effective bottleneck time or have arisen since. This assumption is derived from the Malecot model and verified in all samples. Tested measures of relative efficiency, support intervals, and localization error determine the operating characteristics of LD maps that are applicable to every sexually reproducing species, with implications for association mapping, high-resolution linkage maps, evolutionary inference, and identification of recombinogenic sequences. PMID:15604137

Impact of population structure, effective bottleneck time, and allele frequency on linkage disequilibrium maps.

PubMed

Zhang, Weihua; Collins, Andrew; Gibson, Jane; Tapper, William J; Hunt, Sarah; Deloukas, Panos; Bentley, David R; Morton, Newton E

2004-12-28

Genetic maps in linkage disequilibrium (LD) units play the same role for association mapping as maps in centimorgans provide at much lower resolution for linkage mapping. Association mapping of genes determining disease susceptibility and other phenotypes is based on the theory of LD, here applied to relations with three phenomena. To test the theory, markers at high density along a 10-Mb continuous segment of chromosome 20q were studied in African-American, Asian, and Caucasian samples. Population structure, whether created by pooling samples from divergent populations or by the mating pattern in a mixed population, is accurately bioassayed from genotype frequencies. The effective bottleneck time for Eurasians is substantially less than for migration out of Africa, reflecting later bottlenecks. The classical dependence of allele frequency on mutation age does not hold for the generally shorter time span of inbreeding and LD. Limitation of the classical theory to mutation age justifies the assumption of constant time in a LD map, except for alleles that were rare at the effective bottleneck time or have arisen since. This assumption is derived from the Malecot model and verified in all samples. Tested measures of relative efficiency, support intervals, and localization error determine the operating characteristics of LD maps that are applicable to every sexually reproducing species, with implications for association mapping, high-resolution linkage maps, evolutionary inference, and identification of recombinogenic sequences.

Linkage disequilibrium between STRPs and SNPs across the human genome.

PubMed

Payseur, Bret A; Place, Michael; Weber, James L

2008-05-01

Patterns of linkage disequilibrium (LD) reveal the action of evolutionary processes and provide crucial information for association mapping of disease genes. Although recent studies have described the landscape of LD among single nucleotide polymorphisms (SNPs) from across the human genome, associations involving other classes of molecular variation remain poorly understood. In addition to recombination and population history, mutation rate and process are expected to shape LD. To test this idea, we measured associations between short-tandem-repeat polymorphisms (STRPs), which can mutate rapidly and recurrently, and SNPs in 721 regions across the human genome. We directly compared STRP-SNP LD with SNP-SNP LD from the same genomic regions in the human HapMap populations. The intensity of STRP-SNP LD, measured by the average of D', was reduced, consistent with the action of recurrent mutation. Nevertheless, a higher fraction of STRP-SNP pairs than SNP-SNP pairs showed significant LD, on both short (up to 50 kb) and long (cM) scales. These results reveal the substantial effects of mutational processes on LD at STRPs and provide important measures of the potential of STRPs for association mapping of disease genes.

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. Copyright © 2015 Houle and Márquez.

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

USDA-ARS?s Scientific Manuscript database

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...

Patterns of Genetic Structure and Linkage Disequilibrium in a Large Collection of Pea Germplasm

PubMed Central

Siol, Mathieu; Jacquin, Françoise; Chabert-Martinello, Marianne; Smýkal, Petr; Le Paslier, Marie-Christine; Aubert, Grégoire; Burstin, Judith

2017-01-01

Pea (Pisum sativum, L.) is a major pulse crop used both for animal and human alimentation. Owing to its association with nitrogen-fixing bacteria, it is also a valuable component for low-input cropping systems. To evaluate the genetic diversity and the scale of linkage disequilibrium (LD) decay in pea, we genotyped a collection of 917 accessions, gathering elite cultivars, landraces, and wild relatives using an array of ∼13,000 single nucleotide polymorphisms (SNP). Genetic diversity is broadly distributed across three groups corresponding to wild/landraces peas, winter types, and spring types. At a finer subdivision level, genetic groups relate to local breeding programs and type usage. LD decreases steeply as genetic distance increases. When considering subsets of the data, LD values can be higher, even if the steep decay remains. We looked for genomic regions exhibiting high level of differentiation between wild/landraces, winter, and spring pea, respectively. Two regions on linkage groups 5 and 6 containing 33 SNPs exhibit stronger differentiation between winter and spring peas than would be expected under neutrality. Interestingly, QTL for resistance to cold acclimation and frost resistance have been identified previously in the same regions. PMID:28611254

Significant evidence for linkage disequilibrium over a 5-cM region among Afrikaners.

PubMed

Gordon, D; Simonic, I; Ott, J

2000-05-15

We explore the extent of deviations from Hardy-Weinberg equilibrium (HWE) at a marker locus and linkage disequilibrium (LD) between pairs of marker loci in the Afrikaner population of South Africa. DNA samples were used for genotyping of 23 loci on six chromosomes. The samples were collected from 91 healthy unrelated Afrikaner adults. Exact tests were used to determine evidence for deviations from HWE at a single marker locus or LD between pairs of marker loci. At the 0.05 level of significance, evidence was found for deviation from HWE at only one of the 23 loci. At the same level of significance, LD was found among 8 of the 34 intrachromosomal pairs of loci. On chromosome 21, there was evidence for LD (P = 0.02) between a pair of loci with a genetic distance of 5.51 cM. On chromosome 2, there was evidence for LD between a pair of loci with a genetic distance of 5.28 cM (P = 0.002) and a pair of loci with a genetic distance of 3.68 cM (P = 0.0004). Detailed analysis of LD for one locus pair indicated that only a few of all alleles participated in the LD and that strong LD was most often positive. Our findings indicate that Afrikaans-speaking Afrikaners represent one of those special populations deemed particularly suitable for disequilibrium mapping. Copyright 2000 Academic Press.

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

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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+ andmore » 0.23 for LD-.« less

The linkage disequilibrium pattern of the angiotensin converting enzyme gene in Arabic and Asian population groups.

PubMed

Kharrat, Najla; Abdelmouleh, Wafa; Abdelhedi, Rania; Alfadhli, Suad; Rebai, Ahmed

2012-01-01

DNA variations within the Angiotensin-Converting Enzyme (ACE) gene have been shown to be involved in the aetiology of several common diseases and the therapeutic response. This study reports a comparison of haplotype analysis of five SNPs in the ACE gene region using a sample of 100 healthy subjects derived from five different populations (Tunisian, Iranian, Kuwaiti, Bahraini and Indian). Strong linkage disequilibrium was found among all SNPs studied for all populations. Two SNPs (rs1800764 and rs4340) were identified as key SNPs for all populations. These SNPs will be valuable for future effective association studies of the ACE gene polymorphisms in Arab and Asian populations.

Genetic Structure, Linkage Disequilibrium and Association Mapping of Verticillium Wilt Resistance in Elite Cotton (Gossypium hirsutum L.) Germplasm Population

PubMed Central

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

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

PubMed Central

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

2015-01-01

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

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

PubMed Central

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

2013-01-01

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

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Hongshu; Lee, A.; Gasser, D.L.

1994-11-01

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

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

Extended Linkage Disequilibrium Surrounding the Hemoglobin E Variant Due to Malarial Selection

PubMed Central

Ohashi, Jun ; Naka, Izumi ; Patarapotikul, Jintana ; Hananantachai, Hathairad ; Brittenham, Gary ; Looareesuwan, Sornchai ; Clark, Andrew G. ; Tokunaga, Katsushi 

2004-01-01

The hemoglobin E variant (HbE; β26Glu→Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240–4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection. PMID:15114532

Extended linkage disequilibrium surrounding the hemoglobin E variant due to malarial selection.

PubMed

Ohashi, Jun; Naka, Izumi; Patarapotikul, Jintana; Hananantachai, Hathairad; Brittenham, Gary; Looareesuwan, Sornchai; Clark, Andrew G; Tokunaga, Katsushi

2004-06-01

The hemoglobin E variant (HbE; ( beta )26Glu-->Lys) is concentrated in parts of Southeast Asia where malaria is endemic, and HbE carrier status has been shown to confer some protection against Plasmodium falciparum malaria. To examine the effect of natural selection on the pattern of linkage disequilibrium (LD) and to infer the evolutionary history of the HbE variant, we analyzed biallelic markers surrounding the HbE variant in a Thai population. Pairwise LD analysis of HbE and 43 surrounding biallelic markers revealed LD of HbE extending beyond 100 kb, whereas no LD was observed between non-HbE variants and the same markers. The inferred haplotype network suggests a single origin of the HbE variant in the Thai population. Forward-in-time computer simulations under a variety of selection models indicate that the HbE variant arose 1,240-4,440 years ago. These results support the conjecture that the HbE mutation occurred recently, and the allele frequency has increased rapidly. Our study provides another clear demonstration that a high-resolution LD map across the human genome can detect recent variants that have been subjected to positive selection.

Identification of a psoriasis susceptibility candidate gene by linkage disequilibrium mapping with a localized single nucleotide polymorphism map.

PubMed

Hewett, Duncan; Samuelsson, Lena; Polding, Joanne; Enlund, Fredrik; Smart, Devi; Cantone, Kathryn; See, Chee Gee; Chadha, Sapna; Inerot, Annica; Enerback, Charlotta; Montgomery, Doug; Christodolou, Chris; Robinson, Phil; Matthews, Paul; Plumpton, Mary; Wahlstrom, Jan; Swanbeck, Gunnar; Martinsson, Tommy; Roses, Allen; Riley, John; Purvis, Ian

2002-03-01

Psoriasis is a chronic inflammatory disease of the skin with both genetic and environmental risk factors. Here we describe the creation of a single-nucleotide polymorphism (SNP) map spanning 900-1200 kb of chromosome 3q21, which had been previously recognized as containing a psoriasis susceptibility locus, PSORS5. We genotyped 644 individuals, from 195 Swedish psoriatic families, for 19 polymorphisms. Linkage disequilibrium (LD) between marker and disease was assessed using the transmission/disequilibrium test (TDT). In the TDT analysis, alleles of three of these SNPs showed significant association with disease (P<0.05). A 160-kb interval encompassing these three SNPs was sequenced, and a coding sequence consisting of 13 exons was identified. The predicted protein shares 30-40% homology with the family of cation/chloride cotransporters. A five-marker haplotype spanning the 3' half of this gene is associated with psoriasis to a P value of 3.8<10(-5). We have called this gene SLC12A8, coding for a member of the solute carrier family 12 proteins. It belongs to a class of genes that were previously unrecognized as playing a role in psoriasis pathogenesis.

Chromosome-wide linkage disequilibrium as a consequence of meiotic drive

PubMed Central

Dyer, Kelly A.; Charlesworth, Brian; Jaenike, John

2007-01-01

Adaptation by natural selection proceeds most efficiently when alleles compete solely on the basis of their effects on the survival and reproduction of their carriers. A major condition for this is equal Mendelian segregation, but meiotic drive can short-circuit this process. The evolution of drive often involves multiple, interacting genetic components, together with enhancers and suppressors of drive. Chromosomal inversions that suppress crossing over are also frequently associated with drive systems. This study investigates the effects of these processes on patterns of molecular evolution in the fly Drosophila recens, which is polymorphic for a driving X chromosome (XD). Whereas standard wild-type chromosomes exhibit high levels of polymorphism at multiple loci, all of the XD chromosomes effectively carry a single multilocus haplotype that spans at least 130 cM. The XD is associated with a complex set of inversions that completely suppresses recombination between the standard wild-type chromosome and XD in heterozygous females, which maintain nonrandom associations among loci that presumably interact epistatically for the expression of drive. The long-term costs of foregoing recombination may be substantial; in combination with its low equilibrium frequency, this makes the XD chromosome susceptible to the accumulation of deleterious mutations. Consistent with this, XD chromosomes are apparently fixed for a recessive mutation that causes female sterility. Thus, the XD in D. recens appears to be in chromosome-wide linkage disequilibrium and in the early stages of mutational degradation. PMID:17242362

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. © 2014 WILEY PERIODICALS, INC.

Construction of the model for the Genetic Analysis Workshop 14 simulated data: genotype-phenotype relationships, gene interaction, linkage, association, disequilibrium, and ascertainment effects for a complex phenotype.

PubMed

Greenberg, David A; Zhang, Junying; Shmulewitz, Dvora; Strug, Lisa J; Zimmerman, Regina; Singh, Veena; Marathe, Sudhir

2005-12-30

The Genetic Analysis Workshop 14 simulated dataset was designed 1) To test the ability to find genes related to a complex disease (such as alcoholism). Such a disease may be given a variety of definitions by different investigators, have associated endophenotypes that are common in the general population, and is likely to be not one disease but a heterogeneous collection of clinically similar, but genetically distinct, entities. 2) To observe the effect on genetic analysis and gene discovery of a complex set of gene x gene interactions. 3) To allow comparison of microsatellite vs. large-scale single-nucleotide polymorphism (SNP) data. 4) To allow testing of association to identify the disease gene and the effect of moderate marker x marker linkage disequilibrium. 5) To observe the effect of different ascertainment/disease definition schemes on the analysis. Data was distributed in two forms. Data distributed to participants contained about 1,000 SNPs and 400 microsatellite markers. Internet-obtainable data consisted of a finer 10,000 SNP map, which also contained data on controls. While disease characteristics and parameters were constant, four "studies" used varying ascertainment schemes based on differing beliefs about disease characteristics. One of the studies contained multiplex two- and three-generation pedigrees with at least four affected members. The simulated disease was a psychiatric condition with many associated behaviors (endophenotypes), almost all of which were genetic in origin. The underlying disease model contained four major genes and two modifier genes. The four major genes interacted with each other to produce three different phenotypes, which were themselves heterogeneous. The population parameters were calibrated so that the major genes could be discovered by linkage analysis in most datasets. The association evidence was more difficult to calibrate but was designed to find statistically significant association in 50% of datasets. We also

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

PubMed

He, Shui-Lian; Yang, Yang; Morrell, Peter L; Yi, Ting-Shuang

2015-01-01

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

Genome wide linkage disequilibrium and genetic structure in Sicilian dairy sheep breeds.

PubMed

Mastrangelo, Salvatore; Di Gerlando, Rosalia; Tolone, Marco; Tortorici, Lina; Sardina, Maria Teresa; Portolano, Baldassare

2014-10-10

The recent availability of sheep genome-wide SNP panels allows providing background information concerning genome structure in domestic animals. The aim of this work was to investigate the patterns of linkage disequilibrium (LD), the genetic diversity and population structure in Valle del Belice, Comisana, and Pinzirita dairy sheep breeds using the Illumina Ovine SNP50K Genotyping array. Average r (2) between adjacent SNPs across all chromosomes was 0.155 ± 0.204 for Valle del Belice, 0.156 ± 0.208 for Comisana, and 0.128 ± 0.188 for Pinzirita breeds, and some variations in LD value across chromosomes were observed, in particular for Valle del Belice and Comisana breeds. Average values of r (2) estimated for all pairwise combinations of SNPs pooled over all autosomes were 0.058 ± 0.023 for Valle del Belice, 0.056 ± 0.021 for Comisana, and 0.037 ± 0.017 for Pinzirita breeds. The LD declined as a function of distance and average r (2) was lower than the values observed in other sheep breeds. Consistency of results among the several used approaches (Principal component analysis, Bayesian clustering, F ST, Neighbor networks) showed that while Valle del Belice and Pinzirita breeds formed a unique cluster, Comisana breed showed the presence of substructure. In Valle del Belice breed, the high level of genetic differentiation within breed, the heterogeneous cluster in Admixture analysis, but at the same time the highest inbreeding coefficient, suggested that the breed had a wide genetic base with inbred individuals belonging to the same flock. The Sicilian breeds were characterized by low genetic differentiation and high level of admixture. Pinzirita breed displayed the highest genetic diversity (He, Ne) whereas the lowest value was found in Valle del Belice breed. This study has reported for the first time estimates of LD and genetic diversity from a genome-wide perspective in Sicilian dairy sheep breeds. Our results indicate that breeds formed non

Mapping genes underlying ethnic differences in disease risk by linkage disequilibrium in recently admixed populations.

PubMed Central

McKeigue, P M

1997-01-01

Where recent admixture has occurred between two populations that have different disease rates for genetic reasons, family-based association studies can be used to map the genes underlying these differences, if the ancestry of the alleles at each locus examined can be assigned to one of the two founding populations. This article explores the statistical power and design requirements of this approach. Markers suitable for assigning the ancestry of genomic regions could be defined by grouping alleles at closely spaced microsatellite loci into haplotypes, or generated by representational difference analysis. For a given relative risk between populations, the sample size required to detect a disease locus that accounts for this relative risk by linkage-disequilibrium mapping in an admixed population is not critically dependent on assumptions about genotype penetrances or allele frequencies. Using the transmission-disequilibrium test to search the genome for a locus that accounts for a relative risk of between 2 and 3 in a high-risk population, compared with a low-risk population, generally requires between 150 and 800 case-parent pairs of mixed descent. The optimal strategy is to conduct an initial study using markers spaced at < or = 10 cM with cases from the second and third generations of mixed descent, and then to map the disease loci more accurately in a subsequent study of a population with a longer history of admixture. This approach has greater statistical power than allele-sharing designs and has obvious applications to the genetics of hypertension, non-insulin-dependent diabetes, and obesity. PMID:8981962

Estimating parameters for probabilistic linkage of privacy-preserved datasets.

PubMed

Brown, Adrian P; Randall, Sean M; Ferrante, Anna M; Semmens, James B; Boyd, James H

2017-07-10

Probabilistic record linkage is a process used to bring together person-based records from within the same dataset (de-duplication) or from disparate datasets using pairwise comparisons and matching probabilities. The linkage strategy and associated match probabilities are often estimated through investigations into data quality and manual inspection. However, as privacy-preserved datasets comprise encrypted data, such methods are not possible. In this paper, we present a method for estimating the probabilities and threshold values for probabilistic privacy-preserved record linkage using Bloom filters. Our method was tested through a simulation study using synthetic data, followed by an application using real-world administrative data. Synthetic datasets were generated with error rates from zero to 20% error. Our method was used to estimate parameters (probabilities and thresholds) for de-duplication linkages. Linkage quality was determined by F-measure. Each dataset was privacy-preserved using separate Bloom filters for each field. Match probabilities were estimated using the expectation-maximisation (EM) algorithm on the privacy-preserved data. Threshold cut-off values were determined by an extension to the EM algorithm allowing linkage quality to be estimated for each possible threshold. De-duplication linkages of each privacy-preserved dataset were performed using both estimated and calculated probabilities. Linkage quality using the F-measure at the estimated threshold values was also compared to the highest F-measure. Three large administrative datasets were used to demonstrate the applicability of the probability and threshold estimation technique on real-world data. Linkage of the synthetic datasets using the estimated probabilities produced an F-measure that was comparable to the F-measure using calculated probabilities, even with up to 20% error. Linkage of the administrative datasets using estimated probabilities produced an F-measure that was higher

Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes.

PubMed

Long, Ji-Rong; Zhao, Lan-Juan; Liu, Peng-Yuan; Lu, Yan; Dvornyk, Volodymyr; Shen, Hui; Liu, Yong-Jun; Zhang, Yuan-Yuan; Xiong, Dong-Hai; Xiao, Peng; Deng, Hong-Wen

2004-05-24

The adequacy of association studies for complex diseases depends critically on the existence of linkage disequilibrium (LD) between functional alleles and surrounding SNP markers. We examined the patterns of LD and haplotype distribution in eight candidate genes for osteoporosis and/or obesity using 31 SNPs in 1,873 subjects. These eight genes are apolipoprotein E (APOE), type I collagen alpha1 (COL1A1), estrogen receptor-alpha (ER-alpha), leptin receptor (LEPR), parathyroid hormone (PTH)/PTH-related peptide receptor type 1 (PTHR1), transforming growth factor-beta1 (TGF-beta1), uncoupling protein 3 (UCP3), and vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR). Yin yang haplotypes, two high-frequency haplotypes composed of completely mismatching SNP alleles, were examined. To quantify LD patterns, two common measures of LD, D' and r2, were calculated for the SNPs within the genes. The haplotype distribution varied in the different genes. Yin yang haplotypes were observed only in PTHR1 and UCP3. D' ranged from 0.020 to 1.000 with the average of 0.475, whereas the average r2 was 0.158 (ranging from 0.000 to 0.883). A decay of LD was observed as the intermarker distance increased, however, there was a great difference in LD characteristics of different genes or even in different regions within gene. The differences in haplotype distributions and LD patterns among the genes underscore the importance of characterizing genomic regions of interest prior to association studies.

Patterns of linkage disequilibrium in mitochondrial DNA of 16 ruminant populations.

PubMed

Slate, J; Phua, S H

2003-03-01

Mitochondrial DNA (mtDNA) is a widely employed molecular tool in phylogeography, in the inference of human evolutionary history, in dating the domestication of livestock and in forensic science. In humans and other vertebrates the popularity of mtDNA can be partially attributed to an assumption of strict maternal inheritance, such that there is no recombination between mitochondrial lineages. The recent demonstration that linkage disequilibrium (LD) declines as a function of distance between polymorphic sites in hominid mitochondrial genomes has been interpreted as evidence of recombination between mtDNA haplotypes, and hence nonclonal inheritance. However, critics of mtDNA recombination have suggested that this association is an artefact of an inappropriate measure of LD or of sequencing error, and subsequent studies of other populations have failed to replicate the initial finding. Here we report the analysis of 16 ruminant populations and present evidence that LD significantly declines with distance in five of them. A meta-analysis of the data indicates a nonsignificant trend of LD declining with distance. Most of the earlier criticisms of patterns between LD and distance in hominid mtDNA are not applicable to this data set. Our results suggest that either ruminant mtDNA is not strictly clonal or that compensatory selection has influenced patterns of variation at closely linked sites within the mitochondrial control region. The potential impact of these processes should be considered when using mtDNA as a tool in vertebrate population genetic, phylogenetic and forensic studies.

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 (N e ), and it allows inferences on the genetic diversity of breeds. The objective of this study was to estimate the LD and N e 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 N e values (53 and 60 respectively), which were distinct from that of Brown Hanwoo (531) for 11 generations ago. The differences in LD and N e for each breed reflect the breeding strategy applied. The N e for these endangered cattle breeds remain low; thus, effort is needed to bring them back to a sustainable tract. © 2016 Stichting International Foundation for Animal Genetics.

Exploiting excess sharing: a more powerful test of linkage for affected sib pairs than the transmission/disequilibrium test.

PubMed Central

Wicks, J

2000-01-01

The transmission/disequilibrium test (TDT) is a popular, simple, and powerful test of linkage, which can be used to analyze data consisting of transmissions to the affected members of families with any kind pedigree structure, including affected sib pairs (ASPs). Although it is based on the preferential transmission of a particular marker allele across families, it is not a valid test of association for ASPs. Martin et al. devised a similar statistic for ASPs, Tsp, which is also based on preferential transmission of a marker allele but which is a valid test of both linkage and association for ASPs. It is, however, less powerful than the TDT as a test of linkage for ASPs. What I show is that the differences between the TDT and Tsp are due to the fact that, although both statistics are based on preferential transmission of a marker allele, the TDT also exploits excess sharing in identity-by-descent transmissions to ASPs. Furthermore, I show that both of these statistics are members of a family of "TDT-like" statistics for ASPs. The statistics in this family are based on preferential transmission but also, to varying extents, exploit excess sharing. From this family of statistics, we see that, although the TDT exploits excess sharing to some extent, it is possible to do so to a greater extent-and thus produce a more powerful test of linkage, for ASPs, than is provided by the TDT. Power simulations conducted under a number of disease models are used to verify that the most powerful member of this family of TDT-like statistics is more powerful than the TDT for ASPs. PMID:10788332

Exploiting excess sharing: a more powerful test of linkage for affected sib pairs than the transmission/disequilibrium test.

PubMed

Wicks, J

2000-06-01

The transmission/disequilibrium test (TDT) is a popular, simple, and powerful test of linkage, which can be used to analyze data consisting of transmissions to the affected members of families with any kind pedigree structure, including affected sib pairs (ASPs). Although it is based on the preferential transmission of a particular marker allele across families, it is not a valid test of association for ASPs. Martin et al. devised a similar statistic for ASPs, Tsp, which is also based on preferential transmission of a marker allele but which is a valid test of both linkage and association for ASPs. It is, however, less powerful than the TDT as a test of linkage for ASPs. What I show is that the differences between the TDT and Tsp are due to the fact that, although both statistics are based on preferential transmission of a marker allele, the TDT also exploits excess sharing in identity-by-descent transmissions to ASPs. Furthermore, I show that both of these statistics are members of a family of "TDT-like" statistics for ASPs. The statistics in this family are based on preferential transmission but also, to varying extents, exploit excess sharing. From this family of statistics, we see that, although the TDT exploits excess sharing to some extent, it is possible to do so to a greater extent-and thus produce a more powerful test of linkage, for ASPs, than is provided by the TDT. Power simulations conducted under a number of disease models are used to verify that the most powerful member of this family of TDT-like statistics is more powerful than the TDT for ASPs.

LD2SNPing: linkage disequilibrium plotter and RFLP enzyme mining for tag SNPs

PubMed Central

Chang, Hsueh-Wei; Chuang, Li-Yeh; Chang, Yan-Jhu; Cheng, Yu-Huei; Hung, Yu-Chen; Chen, Hsiang-Chi; Yang, Cheng-Hong

2009-01-01

Background Linkage disequilibrium (LD) mapping is commonly used to evaluate markers for genome-wide association studies. Most types of LD software focus strictly on LD analysis and visualization, but lack supporting services for genotyping. Results We developed a freeware called LD2SNPing, which provides a complete package of mining tools for genotyping and LD analysis environments. The software provides SNP ID- and gene-centric online retrievals for SNP information and tag SNP selection from dbSNP/NCBI and HapMap, respectively. Restriction fragment length polymorphism (RFLP) enzyme information for SNP genotype is available to all SNP IDs and tag SNPs. Single and multiple SNP inputs are possible in order to perform LD analysis by online retrieval from HapMap and NCBI. An LD statistics section provides D, D', r2, δQ, ρ, and the P values of the Hardy-Weinberg Equilibrium for each SNP marker, and Chi-square and likelihood-ratio tests for the pair-wise association of two SNPs in LD calculation. Finally, 2D and 3D plots, as well as plain-text output of the results, can be selected. Conclusion LD2SNPing thus provides a novel visualization environment for multiple SNP input, which facilitates SNP association studies. The software, user manual, and tutorial are freely available at . PMID:19500380

Linkage disequilibrium and signatures of positive selection around LINE-1 retrotransposons in the human genome.

PubMed

Kuhn, Alexandre; Ong, Yao Min; Cheng, Ching-Yu; Wong, Tien Yin; Quake, Stephen R; Burkholder, William F

2014-06-03

Insertions of the human-specific subfamily of LINE-1 (L1) retrotransposon are highly polymorphic across individuals and can critically influence the human transcriptome. We hypothesized that L1 insertions could represent genetic variants determining important human phenotypic traits, and performed an integrated analysis of L1 elements and single nucleotide polymorphisms (SNPs) in several human populations. We found that a large fraction of L1s were in high linkage disequilibrium with their surrounding genomic regions and that they were well tagged by SNPs. However, L1 variants were only partially captured by SNPs on standard SNP arrays, so that their potential phenotypic impact would be frequently missed by SNP array-based genome-wide association studies. We next identified potential phenotypic effects of L1s by looking for signatures of natural selection linked to L1 insertions; significant extended haplotype homozygosity was detected around several L1 insertions. This finding suggests that some of these L1 insertions may have been the target of recent positive selection.

A Comprehensive Linkage Map of the Dog Genome

PubMed Central

Wong, Aaron K.; Ruhe, Alison L.; Dumont, Beth L.; Robertson, Kathryn R.; Guerrero, Giovanna; Shull, Sheila M.; Ziegle, Janet S.; Millon, Lee V.; Broman, Karl W.; Payseur, Bret A.; Neff, Mark W.

2010-01-01

We have leveraged the reference sequence of a boxer to construct the first complete linkage map for the domestic dog. The new map improves access to the dog's unique biology, from human disease counterparts to fascinating evolutionary adaptations. The map was constructed with ∼3000 microsatellite markers developed from the reference sequence. Familial resources afforded 450 mostly phase-known meioses for map assembly. The genotype data supported a framework map with ∼1500 loci. An additional ∼1500 markers served as map validators, contributing modestly to estimates of recombination rate but supporting the framework content. Data from ∼22,000 SNPs informing on a subset of meioses supported map integrity. The sex-averaged map extended 21 M and revealed marked region- and sex-specific differences in recombination rate. The map will enable empiric coverage estimates and multipoint linkage analysis. Knowledge of the variation in recombination rate will also inform on genomewide patterns of linkage disequilibrium (LD), and thus benefit association, selective sweep, and phylogenetic mapping approaches. The computational and wet-bench strategies can be applied to the reference genome of any nonmodel organism to assemble a de novo linkage map. PMID:19966068

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.

Genome-wide linkage disequilibrium and genetic diversity in five populations of Australian domestic sheep.

PubMed

Al-Mamun, Hawlader Abdullah; Clark, Samuel A; Kwan, Paul; Gondro, Cedric

2015-11-24

Knowledge of the genetic structure and overall diversity of livestock species is important to maximise the potential of genome-wide association studies and genomic prediction. Commonly used measures such as linkage disequilibrium (LD), effective population size (N e ), heterozygosity, fixation index (F ST) and runs of homozygosity (ROH) are widely used and help to improve our knowledge about genetic diversity in animal populations. The development of high-density single nucleotide polymorphism (SNP) arrays and the subsequent genotyping of large numbers of animals have greatly increased the accuracy of these population-based estimates. In this study, we used the Illumina OvineSNP50 BeadChip array to estimate and compare LD (measured by r (2) and D'), N e , heterozygosity, F ST and ROH in five Australian sheep populations: three pure breeds, i.e., Merino (MER), Border Leicester (BL), Poll Dorset (PD) and two crossbred populations i.e. F1 crosses of Merino and Border Leicester (MxB) and MxB crossed to Poll Dorset (MxBxP). Compared to other livestock species, the sheep populations that were analysed in this study had low levels of LD and high levels of genetic diversity. The rate of LD decay was greater in Merino than in the other pure breeds. Over short distances (<10 kb), the levels of LD were higher in BL and PD than in MER. Similarly, BL and PD had comparatively smaller N e than MER. Observed heterozygosity in the pure breeds ranged from 0.3 in BL to 0.38 in MER. Genetic distances between breeds were modest compared to other livestock species (highest F ST = 0.063) but the genetic diversity within breeds was high. Based on ROH, two chromosomal regions showed evidence of strong recent selection. This study shows that there is a large range of genome diversity in Australian sheep breeds, especially in Merino sheep. The observed range of diversity will influence the design of genome-wide association studies and the results that can be obtained from them. This

Localization of an ataxia-telangiectasia gene by linkage disequilibrium in the Costa Rican population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Uhrhammer, N.A.; Lange, E.; Gatti, R.A.

1994-09-01

Linkage disequilibrium (LD) was studied in 27 Costa Rican families with ataxia-telangiectasia. Previous studies indicate that the ATA and ATC gene(s) are on chromosome 11q22.3, between D11S1819 and D11S927. We studied the ordered loci D11-S1816, S1817, S1343, S1819, S384, S535, S1295, S1818, S927, S1300 and S1004 by PCR and Southern blotting. We noted moderate LD at the more distant markers S1816, S1300, and S1004. LD was higher at markers closer to A-T, and also where A-T was associated with rarer alleles. This broad region of disequilibrium did not by itself contribute to further localization of the A-T gene(s). We analyzedmore » 54 affected chromosomal haplotypes. The most common haplotype occurred 34 times, including some that had recombined outside the known A-T region. Other haplotypes occurred seven times, five times, two occurred twice, and the four remaining were unique. The most common haplotype had `broken` at S927 in five different patients, placing A-T proximal to this marker. We looked for recombination events in 15 of the families to further localize A-T. We observed one family with a recombination event placing A-T distal to S1819. A second family appears to either not link to 11q22.3 or to have a double-crossover between the markers S384 and S927; two affected sibs share haplotypes for the entire region studied, and a normal sib shared the same two haplotypes. Since all or part of this A-T haplotype occurs in 32 other, unrelated, Costa Rican patients, we anticipate a double-crossover in the 1600 kb between the informative flanking markers. All other families show segregation patterns consistent with placing A-T at 11q22.3. These results demonstrate that the major A-T gene in the Costa Rican population is located between S1819 and S927 at 11q22.3.« less

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

PubMed Central

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

2009-01-01

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

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

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 ( F ST ) 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.

Linkage disequilibrium between polymorphisms of ABCB1 and ABCC2 to predict the treatment outcome of Malaysians with complex partial seizures on treatment with carbamazepine mono-therapy at the Kuala Lumpur Hospital.

PubMed

Subenthiran, Soobitha; Abdullah, Noor Rain; Joseph, Joyce Pauline; Muniandy, Prem Kumar; Mok, Boon Teck; Kee, Chee Cheong; Ismail, Zakiah; Mohamed, Zahurin

2013-01-01

Carbamazepine (CBZ) is used as the first line of treatment of Complex Partial Seizures (CPS) in the Epilepsy Clinic, Neurology Department of Kuala Lumpur Hospital (KLH). More than 30% of the patients remain drug resistant to CBZ mono-therapy. CBZ is transported by the P-glycoprotein (P-gp). The P-gp encoded by the ABCB1 and ABCC2 genes are expressed in drug resistant patients with epilepsy. A few studies have shown significant association between CBZ resistant epilepsy and Linkage Disequilibrium (LD) with adjacent polymorphisms of these genes. Our study is aimed at determining the correlation between patients' response to CBZ mono-therapy to Single Nucleotide Polymorphisms G2677T and C3435T of the ABCB1 gene as well as G1249A and -24C>T of the ABCC2 gene. 314 patients with CPS were recruited from the Neurology Department of the KLH based on stringent inclusion and exclusion criteria, of whom 152 were responders and the other 162 were non-responders. DNA was extracted from their blood samples and Taqman technology for allelic discrimination was performed. Results were described as genotype frequencies. The SHEsis analysis platform was used to calculate linkage disequilibrium index and infer haplotype frequencies. Haploview was used to do permutation test to obtain a corrected p-value. Resistance to treatment with CBZ mono-therapy was significantly associated with the 2677TT and the 3435TT genotypes while it was not significantly associated with the G1249A and -24C>T polymorphisms. The GCGC haplotype combination of the 2677G>T, 3435C>T, 1249G>A and -24C>T respectively was found to be extremely significant (p = 1.10e-20) with good drug response to CBZ mono-therapy. Linkage disequilibrium between the 2677G>T, 3435C>T, 1249G>A and -24C>T SNPs may be used as a reliable screening marker to determine the treatment outcome of CBZ mono-therapy with CPS irrespective of race or gender.

Testing association and linkage using affected-sib-parent study designs.

PubMed

Millstein, Joshua; Siegmund, Kimberly D; Conti, David V; Gauderman, W James

2005-11-01

We have developed a method for jointly testing linkage and association using data from affected sib pairs and their parents. We specify a conditional logistic regression model with two covariates, one that quantifies association (either direct association or indirect association via linkage disequilibrium), and a second that quantifies linkage. The latter covariate is computed based on expected identity-by-descend (ibd) sharing of marker alleles between siblings. In addition to a joint test of linkage and association, our general framework can be used to obtain a linkage test comparable to the mean test (Blackwelder and Elston [1985] Genet. Epidemiol. 2:85-97), and an association test comparable to the Family-Based Association Test (FBAT; Rabinowitz and Laird [2000] Hum. Hered. 50:211-223). We present simulation results demonstrating that our joint test can be more powerful than some standard tests of linkage or association. For example, with a relative risk of 2.7 per variant allele at a disease locus, the estimated power to detect a nearby marker with a modest level of LD was 58.1% by the mean test (linkage only), 69.8% by FBAT, and 82.5% by our joint test of linkage and association. Our model can also be used to obtain tests of linkage conditional on association and association conditional on linkage, which can be helpful in fine mapping. Copyright 2005 Wiley-Liss, Inc.

Identification of a Linkage Disequilibrium Block in Chromosome 1q Associated With BMD in Premenopausal White Women

PubMed Central

Ichikawa, Shoji; Koller, Daniel L; Curry, Leah R; Lai, Dongbing; Xuei, Xiaoling; Pugh, Elizabeth W; Tsai, Ya-Yu; Doheny, Kimberly F; Edenberg, Howard J; Hui, Siu L; Foroud, Tatiana; Peacock, Munro; Econs, Michael J

2008-01-01

Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporotic fractures is peak BMD obtained during young adulthood. We previously reported linkage of chromosome 1q (LOD = 4.3) with variation in spinal areal BMD in healthy premenopausal white women. In this study, we used a two-stage genotyping approach to identify genes in the linked region that contributed to the variation of femoral neck and lumbar spine areal BMD. In the first stage, 654 SNPs across the linked region were genotyped in a sample of 1309 premenopausal white women. The most significant evidence of association for lumbar spine (p = 1.3 × 10−6) was found with rs1127091 in the GATAD2B gene. In the second stage, 52 SNPs around this candidate gene were genotyped in an expanded sample of 1692 white women. Significant evidence of association with spinal BMD (p < 10−5), and to a lesser extent with femoral neck BMD, was observed with eight SNPs within a single 230-kb linkage disequilibrium (LD) block. The most significant SNP (p = 3.4 × 10−7) accounted for >2.5% of the variation in spinal BMD in these women. The 230-kb LD block contains 11 genes, but because of the extensive LD, the specific gene(s) contributing to the variation in BMD could not be determined. In conclusion, the significant association between spinal BMD and SNPs in the 230-kb LD block in chromosome 1q indicates that genetic factor(s) in this block plays an important role in peak spinal BMD in healthy premenopausal white women. PMID:18505370

Uneven recombination rate and linkage disequilibrium across a reference SNP map for common bean (Phaseolus vulgaris L.)

PubMed Central

Farmer, Andrew D.; Huang, Wei; Ambachew, Daniel; Penmetsa, R. Varma; Carrasquilla-Garcia, Noelia; Assefa, Teshale; Cannon, Steven B.

2018-01-01

Recombination (R) rate and linkage disequilibrium (LD) analyses are the basis for plant breeding. These vary by breeding system, by generation of inbreeding or outcrossing and by region in the chromosome. Common bean (Phaseolus vulgaris L.) is a favored food legume with a small sequenced genome (514 Mb) and n = 11 chromosomes. The goal of this study was to describe R and LD in the common bean genome using a 768-marker array of single nucleotide polymorphisms (SNP) based on Trans-legume Orthologous Group (TOG) genes along with an advanced-generation Recombinant Inbred Line reference mapping population (BAT93 x Jalo EEP558) and an internationally available diversity panel. A whole genome genetic map was created that covered all eleven linkage groups (LG). The LGs were linked to the physical map by sequence data of the TOGs compared to each chromosome sequence of common bean. The genetic map length in total was smaller than for previous maps reflecting the precision of allele calling and mapping with SNP technology as well as the use of gene-based markers. A total of 91.4% of TOG markers had singleton hits with annotated Pv genes and all mapped outside of regions of resistance gene clusters. LD levels were found to be stronger within the Mesoamerican genepool and decay more rapidly within the Andean genepool. The recombination rate across the genome was 2.13 cM / Mb but R was found to be highly repressed around centromeres and frequent outside peri-centromeric regions. These results have important implications for association and genetic mapping or crop improvement in common bean. PMID:29522524

Linkage Disequilibrium and Haplotype Diversity in the Genes of the Renin–Angiotensin System: Findings From the Family Blood Pressure Program

PubMed Central

Zhu, Xiaofeng; Yan, Denise; Cooper, Richard S.; Luke, Amy; Ikeda, Morna A.; Chang, Yen-Pei C.; Weder, Alan; Chakravarti, Aravinda

2003-01-01

Association studies of candidate genes with complex traits have generally used one or a few single nucleotide polymorphisms (SNPs), although variation in the extent of linkage disequilibrium (LD) within genes markedly influences the sensitivity and precision of association studies. The extent of LD and the underlying haplotype structure for most candidate genes are still unavailable. We sampled 193 blacks (African-Americans) and 160 whites (European-Americans) and estimated the intragenic LD and the haplotype structure in four genes of the renin–angiotensin system. We genotyped 25 SNPs, with all but one of the pairs spaced between 1 and 20 kb, thus providing resolution at small scale. The pattern of LD within a gene was very heterogeneous. Using a robust method to define haplotype blocks, blocks of limited haplotype diversity were identified at each locus; between these blocks, LD was lost owing to the history of recombination events. As anticipated, there was less LD among blacks, the number of haplotypes was substantially larger, and shorter haplotype segments were found, compared with whites. These findings have implications for candidate-gene association studies and indicate that variation between populations of European and African origin in haplotype diversity is characteristic of most genes. [The sequence data described in this paper are available in GenBank under the following accession nos: AGT, MIM 106150; Renin, MIM 179820; ACE, MIM 106180; Angiotensin receptor I, MIM 106165. Supplementary material is available online at http://www.genome.org.] PMID:12566395

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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toda, Tatsushi; Ikegawa, Shiro; Okui, Keiko

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.more » 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.« less

A tool for selecting SNPs for association studies based on observed linkage disequilibrium patterns.

PubMed

De La Vega, Francisco M; Isaac, Hadar I; Scafe, Charles R

2006-01-01

The design of genetic association studies using single-nucleotide polymorphisms (SNPs) requires the selection of subsets of the variants providing high statistical power at a reasonable cost. SNPs must be selected to maximize the probability that a causative mutation is in linkage disequilibrium (LD) with at least one marker genotyped in the study. The HapMap project performed a genome-wide survey of genetic variation with about a million SNPs typed in four populations, providing a rich resource to inform the design of association studies. A number of strategies have been proposed for the selection of SNPs based on observed LD, including construction of metric LD maps and the selection of haplotype tagging SNPs. Power calculations are important at the study design stage to ensure successful results. Integrating these methods and annotations can be challenging: the algorithms required to implement these methods are complex to deploy, and all the necessary data and annotations are deposited in disparate databases. Here, we present the SNPbrowser Software, a freely available tool to assist in the LD-based selection of markers for association studies. This stand-alone application provides fast query capabilities and swift visualization of SNPs, gene annotations, power, haplotype blocks, and LD map coordinates. Wizards implement several common SNP selection workflows including the selection of optimal subsets of SNPs (e.g. tagging SNPs). Selected SNPs are screened for their conversion potential to either TaqMan SNP Genotyping Assays or the SNPlex Genotyping System, two commercially available genotyping platforms, expediting the set-up of genetic studies with an increased probability of success.

Increased level of linkage disequilibrium in rural compared with urban communities: a factor to consider in association-study design.

PubMed

Vitart, Veronique; Carothers, Andrew D; Hayward, Caroline; Teague, Peter; Hastie, Nicholas D; Campbell, Harry; Wright, Alan F

2005-05-01

Few studies have investigated genetic differentiation within nonisolate European populations, despite the initiation of large national sample collections such as U.K. Biobank. Here, we used short tandem repeat markers to explore fine-scale genetic structure and to examine the extent of linkage disequilibrium (LD) within national subpopulations. We studied 955 unrelated individuals of local ancestry from nine Scottish rural regions and the urban center of Edinburgh, as well as 96 unrelated individuals from the general U.K. population. Despite little overall differentiation on the basis of allele frequencies, there were clear differences among subpopulations in the extent of pairwise LD, measured between a subset of X-linked markers, that reflected presumed differences in the depths of the underlying genealogies within these subpopulations. Therefore, there are strategic advantages in studying rural subpopulations, in terms of increased power and reduced cost, that are lost by sampling across regions or within urban populations. Similar rural-urban contrasts are likely to exist in many other populations with stable rural subpopulations, which could influence the design of genetic association studies and national biobank data collections.

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

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.

Multilocus Patterns of Nucleotide Diversity, Linkage Disequilibrium and Demographic History of Norway Spruce [Picea abies (L.) Karst

PubMed Central

Heuertz, Myriam; De Paoli, Emanuele; Källman, Thomas; Larsson, Hanna; Jurman, Irena; Morgante, Michele; Lascoux, Martin; Gyllenstrand, Niclas

2006-01-01

DNA polymorphism at 22 loci was studied in an average of 47 Norway spruce [Picea abies (L.) Karst.] haplotypes sampled in seven populations representative of the natural range. The overall nucleotide variation was limited, being lower than that observed in most plant species so far studied. Linkage disequilibrium was also restricted and did not extend beyond a few hundred base pairs. All populations, with the exception of the Romanian population, could be divided into two main domains, a Baltico–Nordic and an Alpine one. Mean Tajima's D and Fay and Wu's H across loci were both negative, indicating the presence of an excess of both rare and high-frequency-derived variants compared to the expected frequency spectrum in a standard neutral model. Multilocus neutrality tests based on D and H led to the rejection of the standard neutral model and exponential growth in the whole population as well as in the two main domains. On the other hand, in all three cases the data are compatible with a severe bottleneck occurring some hundreds of thousands of years ago. Hence, demographic departures from equilibrium expectations and population structure will have to be accounted for when detecting selection at candidate genes and in association mapping studies, respectively. PMID:17057229

Linkage disequilibrium with HLA-DRB1-DQB1 haplotypes explains the association of TNF-308G>A variant with type 1 diabetes in a Brazilian cohort.

PubMed

Patente, Thiago A; Monteiro, Maria B; Vieira, Suzana M; Rossi da Silva, Maria E; Nery, Márcia; Queiroz, Márcia; Azevedo, Mirela J; Canani, Luis H; Parisi, Maria C; Pavin, Elizabeth J; Mainardi, Débora; Javor, Juraj; Velho, Gilberto; Coimbra, Cássio N; Corrêa-Giannella, Maria Lúcia

2015-08-15

A functional variant in the promoter region of the gene encoding tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility to T1D. However, TNF rs1800629 was found, in several populations, to be in linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and assessed the impact of HLA susceptibility haplotypes in this association. 659 subjects with T1D and 539 control subjects were genotyped for TNF-308G>A variant. HLA-DRB1 and HLA-DQB1 genes were genotyped in a subset of 313 subjects with T1D and 139 control subjects. Associations with T1D were observed for the A-allele of rs1800629 (OR 1.69, 95% CI 1.33-2.15, p<0.0001, in a codominant model) and for 3 HLA haplotypes: DRB1*03:01-DQB1*02:01 (OR 5.37, 95% CI 3.23-8.59, p<0.0001), DRB1*04:01-DQB1*03:02 (OR 2.95, 95% CI 1.21-7.21, p=0.01) and DRB1*04:02-DQB1*03:02 (OR 2.14, 95% CI 1.02-4.50, p=0.04). Linkage disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1 alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629, remained independently associated with T1D. Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

Blair, Matthew W; Prieto, Sergio; Díaz, Lucy M; Buendía, Héctor F; Cardona, César

2010-04-29

An interesting seed protein family with a role in preventing insect herbivory is the multi-gene, APA family encoding the alpha-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. 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. 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 and association studies for

When are genetic methods useful for estimating contemporary abundance and detecting population trends?

Treesearch

David A. Tallmon; Dave Gregovich; Robin S. Waples; C. Scott Baker; Jennifer Jackson; Barbara L. Taylor; Eric Archer; Karen K. Martien; Fred W. Allendorf; Michael K. Schwartz

2010-01-01

The utility of microsatellite markers for inferring population size and trend has not been rigorously examined, even though these markers are commonly used to monitor the demography of natural populations. We assessed the ability of a linkage disequilibrium estimator of effective population size (Ne) and a simple capture-recapture estimator of abundance (N) to quantify...

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

Extent of genome-wide linkage disequilibrium in Australian Holstein-Friesian cattle based on a high-density SNP panel.

PubMed

Khatkar, Mehar S; Nicholas, Frank W; Collins, Andrew R; Zenger, Kyall R; Cavanagh, Julie A L; Barris, Wes; Schnabel, Robert D; Taylor, Jeremy F; Raadsma, Herman W

2008-04-24

The extent of linkage disequilibrium (LD) within a population determines the number of markers that will be required for successful association mapping and marker-assisted selection. Most studies on LD in cattle reported to date are based on microsatellite markers or small numbers of single nucleotide polymorphisms (SNPs) covering one or only a few chromosomes. This is the first comprehensive study on the extent of LD in cattle by analyzing data on 1,546 Holstein-Friesian bulls genotyped for 15,036 SNP markers covering all regions of all autosomes. Furthermore, most studies in cattle have used relatively small sample sizes and, consequently, may have had biased estimates of measures commonly used to describe LD. We examine minimum sample sizes required to estimate LD without bias and loss in accuracy. Finally, relatively little information is available on comparative LD structures including other mammalian species such as human and mouse, and we compare LD structure in cattle with public-domain data from both human and mouse. We computed three LD estimates, D', Dvol and r2, for 1,566,890 syntenic SNP pairs and a sample of 365,400 non-syntenic pairs. Mean D' is 0.189 among syntenic SNPs, and 0.105 among non-syntenic SNPs; mean r2 is 0.024 among syntenic SNPs and 0.0032 among non-syntenic SNPs. All three measures of LD for syntenic pairs decline with distance; the decline is much steeper for r2 than for D' and Dvol. The value of D' and Dvol are quite similar. Significant LD in cattle extends to 40 kb (when estimated as r2) and 8.2 Mb (when estimated as D'). The mean values for LD at large physical distances are close to those for non-syntenic SNPs. Minor allelic frequency threshold affects the distribution and extent of LD. For unbiased and accurate estimates of LD across marker intervals spanning < 1 kb to > 50 Mb, minimum sample sizes of 400 (for D') and 75 (for r2) are required. The bias due to small samples sizes increases with inter-marker interval. LD in cattle

CYP21A2 polymorphisms in patients with autoimmune Addison's disease, and linkage disequilibrium to HLA risk alleles.

PubMed

Brønstad, Ingeborg; Skinningsrud, Beate; Bratland, Eirik; Løvås, Kristian; Undlien, Dag; Sverre Husebye, Eystein; Wolff, Anette Susanne Bøe

2014-12-01

Steroid 21-hydroxylase, encoded by CYP21A2, is the major autoantigen in autoimmune Addison's disease (AAD). CYP21A2 is located in the region of the HLA complex on chromosome 6p21.3, which harbours several risk alleles for AAD. The objective was to investigate whether CYP21A2 gene variants confer risk of AAD independently of other risk alleles in the HLA loci. DNA samples from 381 Norwegian patients with AAD and 340 healthy controls (HC) previously genotyped for the HLA-A, -B, -DRB1, and -DQB1 and MICA loci were used for genotyping of CYP21A2. Genotyping of CYP21A2 was carried out by direct sequencing. Linkage of CYP21A2 to the HLA loci was assessed using UNPHASED version 3.0.10 and PHASE version 2.1. Heterozygotes of the single-nucleotide polymorphisms (SNPs) rs397515394, rs6467, rs6474, rs76565726 and rs6473 were detected significantly more frequently in AAD patients compared with HC (P<0.005), but all SNPs were in a linkage disequilibrium (LD) with high-risk HLA-DRB1 haplotypes. rs6472C protected against AAD (odds ratio=0.15, 95% CI (0.08-0.30), P=3.8×10(-10)). This SNP was not in an LD with HLA loci (P=0.02), but did not increase protection when considering the effect of HLA-DRB1 alleles. Mutations causing congenital adrenal hyperplasia were found in heterozygosity in <1.5% of the cases in both groups. Genetic variants of CYP21A2 associated to AAD are in LD with the main AAD risk locus HLA-DRB1, and CYP21A2 does not constitute an independent susceptibility locus. © 2014 European Society of Endocrinology.

Whole genome sequences are required to fully resolve the linkage disequilibrium structure of human populations.

PubMed

Pengelly, Reuben J; Tapper, William; Gibson, Jane; Knut, Marcin; Tearle, Rick; Collins, Andrew; Ennis, Sarah

2015-09-03

An understanding of linkage disequilibrium (LD) structures in the human genome underpins much of medical genetics and provides a basis for disease gene mapping and investigating biological mechanisms such as recombination and selection. Whole genome sequencing (WGS) provides the opportunity to determine LD structures at maximal resolution. We compare LD maps constructed from WGS data with LD maps produced from the array-based HapMap dataset, for representative European and African populations. WGS provides up to 5.7-fold greater SNP density than array-based data and achieves much greater resolution of LD structure, allowing for identification of up to 2.8-fold more regions of intense recombination. The absence of ascertainment bias in variant genotyping improves the population representativeness of the WGS maps, and highlights the extent of uncaptured variation using array genotyping methodologies. The complete capture of LD patterns using WGS allows for higher genome-wide association study (GWAS) power compared to array-based GWAS, with WGS also allowing for the analysis of rare variation. The impact of marker ascertainment issues in arrays has been greatest for Sub-Saharan African populations where larger sample sizes and substantially higher marker densities are required to fully resolve the LD structure. WGS provides the best possible resource for LD mapping due to the maximal marker density and lack of ascertainment bias. WGS LD maps provide a rich resource for medical and population genetics studies. The increasing availability of WGS data for large populations will allow for improved research utilising LD, such as GWAS and recombination biology studies.

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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

A New Method for Assessing How Sensitivity and Specificity of Linkage Studies Affects Estimation

PubMed Central

Moore, Cecilia L.; Amin, Janaki; Gidding, Heather F.; Law, Matthew G.

2014-01-01

Background While the importance of record linkage is widely recognised, few studies have attempted to quantify how linkage errors may have impacted on their own findings and outcomes. Even where authors of linkage studies have attempted to estimate sensitivity and specificity based on subjects with known status, the effects of false negatives and positives on event rates and estimates of effect are not often described. Methods We present quantification of the effect of sensitivity and specificity of the linkage process on event rates and incidence, as well as the resultant effect on relative risks. Formulae to estimate the true number of events and estimated relative risk adjusted for given linkage sensitivity and specificity are then derived and applied to data from a prisoner mortality study. The implications of false positive and false negative matches are also discussed. Discussion Comparisons of the effect of sensitivity and specificity on incidence and relative risks indicate that it is more important for linkages to be highly specific than sensitive, particularly if true incidence rates are low. We would recommend that, where possible, some quantitative estimates of the sensitivity and specificity of the linkage process be performed, allowing the effect of these quantities on observed results to be assessed. PMID:25068293

Linkage disequilibrium and association analysis of stripe rust resistance in wild emmer wheat (Triticum turgidum ssp. dicoccoides) population in Israel.

PubMed

Sela, Hanan; Ezrati, Smadar; Ben-Yehuda, Pnina; Manisterski, Jacob; Akhunov, Eduard; Dvorak, Jan; Breiman, Adina; Korol, Abraham

2014-11-01

Rapid LD decay in wild emmer population from Israel allows high-resolution association mapping. Known and putative new stripe rust resistance genes were found. Genome-wide association mapping (GWAM) is becoming an important tool for the discovery and mapping of loci underlying trait variation in crops, but in the wild relatives of crops the use of GWAM has been limited. Critical factors for the use of GWAM are the levels of linkage disequilibrium (LD) and genetic diversity in mapped populations, particularly in those of self-pollinating species. Here, we report LD estimation in a population of 128 accessions of self-pollinating wild emmer, Triticum turgidum ssp. dicoccoides, the progenitor of cultivated wheat, collected in Israel. LD decayed fast along wild emmer chromosomes and reached the background level within 1 cM. We employed GWAM for the discovery and mapping of genes for resistance to three isolates of Puccinia striiformis, the causative agent of wheat stripe rust. The wild emmer population was genotyped with the wheat iSelect assay including 8643 gene-associated SNP markers (wheat 9K Infinium) of which 2,278 were polymorphic. The significance of association between stripe rust resistance and each of the polymorphic SNP was tested using mixed linear model implemented in EMMA software. The model produced satisfactory results and uncovered four significant associations on chromosome arms 1BS, 1BL and 3AL. The locus on 1BS was located in a region known to contain stripe rust resistance genes. These results show that GWAM is an effective strategy for gene discovery and mapping in wild emmer that will accelerate the utilization of this genetic resource in wheat breeding.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Labuda, M.; Glorieux, F.H.; Labuda, D.

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,more » 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.« less

Multilocus Patterns of Nucleotide Diversity, Population Structure and Linkage Disequilibrium in Boechera stricta, a Wild Relative of Arabidopsis

PubMed Central

Song, Bao-Hua; Windsor, Aaron J.; Schmid, Karl J.; Ramos-Onsins, Sebastian; Schranz, M. Eric; Heidel, Andrew J.; Mitchell-Olds, Thomas

2009-01-01

Information about polymorphism, population structure, and linkage disequilibrium (LD) is crucial for association studies of complex trait variation. However, most genomewide studies have focused on model systems, with very few analyses of undisturbed natural populations. Here, we sequenced 86 mapped nuclear loci for a sample of 46 genotypes of Boechera stricta and two individuals of B. holboellii, both wild relatives of Arabidopsis. Isolation by distance was significant across the species range of B. stricta, and three geographic groups were identified by structure analysis, principal coordinates analysis, and distance-based phylogeny analyses. The allele frequency spectrum indicated a genomewide deviation from an equilibrium neutral model, with silent nucleotide diversity averaging 0.004. LD decayed rapidly, declining to background levels in ∼10 kb or less. For tightly linked SNPs separated by <1 kb, LD was dependent on the reference population. LD was lower in the specieswide sample than within populations, suggesting that low levels of LD found in inbreeding species such as B. stricta, Arabidopsis thaliana, and barley may result from broad geographic sampling that spans heterogeneous genetic groups. Finally, analyses also showed that inbreeding B. stricta and A. thaliana have ∼45% higher recombination per kilobase than outcrossing A. lyrata. PMID:19104077

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

PubMed

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.

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

PubMed

Porto-Neto, Laercio R; Kijas, James W; Reverter, Antonio

2014-03-24

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. 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. 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.

A Simple Sampling Method for Estimating the Accuracy of Large Scale Record Linkage Projects.

PubMed

Boyd, James H; Guiver, Tenniel; Randall, Sean M; Ferrante, Anna M; Semmens, James B; Anderson, Phil; Dickinson, Teresa

2016-05-17

Record linkage techniques allow different data collections to be brought together to provide a wider picture of the health status of individuals. Ensuring high linkage quality is important to guarantee the quality and integrity of research. Current methods for measuring linkage quality typically focus on precision (the proportion of incorrect links), given the difficulty of measuring the proportion of false negatives. The aim of this work is to introduce and evaluate a sampling based method to estimate both precision and recall following record linkage. In the sampling based method, record-pairs from each threshold (including those below the identified cut-off for acceptance) are sampled and clerically reviewed. These results are then applied to the entire set of record-pairs, providing estimates of false positives and false negatives. This method was evaluated on a synthetically generated dataset, where the true match status (which records belonged to the same person) was known. The sampled estimates of linkage quality were relatively close to actual linkage quality metrics calculated for the whole synthetic dataset. The precision and recall measures for seven reviewers were very consistent with little variation in the clerical assessment results (overall agreement using the Fleiss Kappa statistics was 0.601). This method presents as a possible means of accurately estimating matching quality and refining linkages in population level linkage studies. The sampling approach is especially important for large project linkages where the number of record pairs produced may be very large often running into millions.

Nucleotide variability and linkage disequilibrium patterns in the porcine MUC4 gene

PubMed Central

2012-01-01

Background MUC4 is a type of membrane anchored glycoprotein and serves as the major constituent of mucus that covers epithelial surfaces of many tissues such as trachea, colon and cervix. MUC4 plays important roles in the lubrication and protection of the surface epithelium, cell proliferation and differentiation, immune response, cell adhesion and cancer development. To gain insights into the evolution of the porcine MUC4 gene, we surveyed the nucleotide variability and linkage disequilibrium (LD) within this gene in Chinese indigenous breeds and Western commercial breeds. Results A total of 53 SNPs covering the MUC4 gene were genotyped on 5 wild boars and 307 domestic pigs representing 11 Chinese breeds and 3 Western breeds. The nucleotide variability, haplotype phylogeny and LD extent of MUC4 were analyzed in these breeds. Both Chinese and Western breeds had considerable nucleotide diversity at the MUC4 locus. Western pig breeds like Duroc and Large White have comparable nucleotide diversity as many of Chinese breeds, thus artificial selection for lean pork production have not reduced the genetic variability of MUC4 in Western commercial breeds. Haplotype phylogeny analyses indicated that MUC4 had evolved divergently in Chinese and Western pigs. The dendrogram of genetic differentiation between breeds generally reflected demographic history and geographical distribution of these breeds. LD patterns were unexpectedly similar between Chinese and Western breeds, in which LD usually extended less than 20 kb. This is different from the presumed high LD extent (more than 100 kb) in Western commercial breeds. The significant positive Tajima’D, and Fu and Li’s D statistics in a few Chinese and Western breeds implied that MUC4 might undergo balancing selection in domestic breeds. Nevertheless, we cautioned that the significant statistics could be upward biased by SNP ascertainment process. Conclusions Chinese and Western breeds have similar nucleotide diversity

Nucleotide variability and linkage disequilibrium patterns in the porcine MUC4 gene.

PubMed

Yang, Ming; Yang, Bin; Yan, Xueming; Ouyang, Jing; Zeng, Weihong; Ai, Huashui; Ren, Jun; Huang, Lusheng

2012-07-13

MUC4 is a type of membrane anchored glycoprotein and serves as the major constituent of mucus that covers epithelial surfaces of many tissues such as trachea, colon and cervix. MUC4 plays important roles in the lubrication and protection of the surface epithelium, cell proliferation and differentiation, immune response, cell adhesion and cancer development. To gain insights into the evolution of the porcine MUC4 gene, we surveyed the nucleotide variability and linkage disequilibrium (LD) within this gene in Chinese indigenous breeds and Western commercial breeds. A total of 53 SNPs covering the MUC4 gene were genotyped on 5 wild boars and 307 domestic pigs representing 11 Chinese breeds and 3 Western breeds. The nucleotide variability, haplotype phylogeny and LD extent of MUC4 were analyzed in these breeds. Both Chinese and Western breeds had considerable nucleotide diversity at the MUC4 locus. Western pig breeds like Duroc and Large White have comparable nucleotide diversity as many of Chinese breeds, thus artificial selection for lean pork production have not reduced the genetic variability of MUC4 in Western commercial breeds. Haplotype phylogeny analyses indicated that MUC4 had evolved divergently in Chinese and Western pigs. The dendrogram of genetic differentiation between breeds generally reflected demographic history and geographical distribution of these breeds. LD patterns were unexpectedly similar between Chinese and Western breeds, in which LD usually extended less than 20 kb. This is different from the presumed high LD extent (more than 100 kb) in Western commercial breeds. The significant positive Tajima'D, and Fu and Li's D statistics in a few Chinese and Western breeds implied that MUC4 might undergo balancing selection in domestic breeds. Nevertheless, we cautioned that the significant statistics could be upward biased by SNP ascertainment process. Chinese and Western breeds have similar nucleotide diversity but evolve divergently in the MUC4

The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern

PubMed Central

De La Vega, Francisco M.; Isaac, Hadar; Collins, Andrew; Scafe, Charles R.; Halldórsson, Bjarni V.; Su, Xiaoping; Lippert, Ross A.; Wang, Yu; Laig-Webster, Marion; Koehler, Ryan T.; Ziegle, Janet S.; Wogan, Lewis T.; Stevens, Junko F.; Leinen, Kyle M.; Olson, Sheri J.; Guegler, Karl J.; You, Xiaoqing; Xu, Lily H.; Hemken, Heinz G.; Kalush, Francis; Itakura, Mitsuo; Zheng, Yi; de Thé, Guy; O'Brien, Stephen J.; Clark, Andrew G.; Istrail, Sorin; Hunkapiller, Michael W.; Spier, Eugene G.; Gilbert, Dennis A.

2005-01-01

The extent and patterns of linkage disequilibrium (LD) determine the feasibility of association studies to map genes that underlie complex traits. Here we present a comparison of the patterns of LD across four major human populations (African-American, Caucasian, Chinese, and Japanese) with a high-resolution single-nucleotide polymorphism (SNP) map covering almost the entire length of chromosomes 6, 21, and 22. We constructed metric LD maps formulated such that the units measure the extent of useful LD for association mapping. LD reaches almost twice as far in chromosome 6 as in chromosomes 21 or 22, in agreement with their differences in recombination rates. By all measures used, out-of-Africa populations showed over a third more LD than African-Americans, highlighting the role of the population's demography in shaping the patterns of LD. Despite those differences, the long-range contour of the LD maps is remarkably similar across the four populations, presumably reflecting common localization of recombination hot spots. Our results have practical implications for the rational design and selection of SNPs for disease association studies. PMID:15781572

Whole-genome patterns of linkage disequilibrium across flycatcher populations clarify the causes and consequences of fine-scale recombination rate variation in birds.

PubMed

Kawakami, Takeshi; Mugal, Carina F; Suh, Alexander; Nater, Alexander; Burri, Reto; Smeds, Linnéa; Ellegren, Hans

2017-08-01

Recombination rate is heterogeneous across the genome of various species and so are genetic diversity and differentiation as a consequence of linked selection. However, we still lack a clear picture of the underlying mechanisms for regulating recombination. Here we estimated fine-scale population recombination rate based on the patterns of linkage disequilibrium across the genomes of multiple populations of two closely related flycatcher species (Ficedula albicollis and F. hypoleuca). This revealed an overall conservation of the recombination landscape between these species at the scale of 200 kb, but we also identified differences in the local rate of recombination despite their recent divergence (<1 million years). Genetic diversity and differentiation were associated with recombination rate in a lineage-specific manner, indicating differences in the extent of linked selection between species. We detected 400-3,085 recombination hotspots per population. Location of hotspots was conserved between species, but the intensity of hotspot activity varied between species. Recombination hotspots were primarily associated with CpG islands (CGIs), regardless of whether CGIs were at promoter regions or away from genes. Recombination hotspots were also associated with specific transposable elements (TEs), but this association appears indirect due to shared preferences of the transposition machinery and the recombination machinery for accessible open chromatin regions. Our results suggest that CGIs are a major determinant of the localization of recombination hotspots, and we propose that both the distribution of TEs and fine-scale variation in recombination rate may be associated with the evolution of the epigenetic landscape. © 2017 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

Genetics of recurrent early-onset major depression (GenRED): significant linkage on chromosome 15q25-q26 after fine mapping with single nucleotide polymorphism markers.

PubMed

Levinson, Douglas F; Evgrafov, Oleg V; Knowles, James A; Potash, James B; Weissman, Myrna M; Scheftner, William A; Depaulo, J Raymond; Crowe, Raymond R; Murphy-Eberenz, Kathleen; Marta, Diana H; McInnis, Melvin G; Adams, Philip; Gladis, Madeline; Miller, Erin B; Thomas, Jo; Holmans, Peter

2007-02-01

The authors studied a dense map of single nucleotide polymorphism (SNP) DNA markers on chromosome 15q25-q26 to maximize the informativeness of genetic linkage analyses in a region where they previously reported suggestive evidence for linkage of recurrent early-onset major depressive disorder. In 631 European-ancestry families with multiple cases of recurrent early-onset major depressive disorder, 88 SNPs were genotyped, and multipoint allele-sharing linkage analyses were carried out. Marker-marker linkage disequilibrium was minimized, and a simulation study with founder haplotypes from these families suggested that linkage scores were not inflated by linkage disequilibrium. The dense SNP map increased the information content of the analysis from around 0.7 to over 0.9. The maximum evidence for linkage was the Z likelihood ratio score statistic of Kong and Cox (Z(LR))=4.69 at 109.8 cM. The exact p value was below the genomewide significance threshold. By contrast, in the genome scan with microsatellite markers at 9 cM spacing, the maximum Z(LR) for European-ancestry families was 3.43 (106.53 cM). It was estimated that the linked locus or loci in this region might account for a 20% or less populationwide increase in risk to siblings of cases. This region has produced modestly positive evidence for linkage to depression and related traits in other studies. These results suggest that DNA sequence variations in one or more genes in the 15q25-q26 region can increase susceptibility to major depression and that efforts are warranted to identify these genes.

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

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

1998-07-01

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.

Linkage disequilibrium, persistence of phase, and effective population size in Spanish local beef cattle breeds assessed through a high-density single nucleotide polymorphism chip.

PubMed

Cañas-Álvarez, J J; Mouresan, E F; Varona, L; Díaz, C; Molina, A; Baro, J A; Altarriba, J; Carabaño, M J; Casellas, J; Piedrafita, J

2016-07-01

Linkage disequilibrium (LD) and persistence of phase are fundamental approaches for exploring the genetic basis of economically important traits in cattle, including the identification of QTL for genomic selection and the estimation of effective population size () to determine the size of the training populations. In this study, we have used the Illumina BovineHD chip in 168 trios of 7 Spanish beef cattle breeds to obtain an overview of the magnitude of LD and the persistence of LD phase through the physical distance between markers. Also, we estimated the time of divergence based on the persistence of the LD phase and calculated past from LD estimates using different alternatives to define the recombination rate. Estimates of average (as a measure of LD) for adjacent markers were close to 0.52 in the 7 breeds and decreased with the distance between markers, although in long distances, some LD still remained (0.07 and 0.05 for markers 200 kb and 1 Mb apart, respectively). A panel with a lower boundary of 38,000 SNP would be necessary to launch a successful within-breed genomic selection program. Persistence of phase, measured as the pairwise correlations between estimates of in 2 breeds at short distances (10 kb), was in the 0.89 to 0.94 range and decreased from 0.33 to 0.52 to a range of 0.01 to 0.08 when marker distance increased from 200 kb to 1 Mb, respectively. The magnitude of the persistence of phase between the Spanish beef breeds was similar to those found in dairy breeds. For across-breed genomic selection, the size of the SNP panels must be in the range of 50,000 to 83,000 SNP. Estimates of past showed values ranging from 26 to 31 for 1 generation ago in all breeds. The divergence among breeds occurred between 129 and 207 generations ago. The results of this study are relevant for the future implementation of within- and across-breed genomic selection programs in the Spanish beef cattle populations. Our results suggest that a reduced subset of the SNP

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.

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

PubMed Central

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

2015-01-01

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

X-chromosome as a marker for population history: linkage disequilibrium and haplotype study in Eurasian populations

PubMed Central

Laan, Maris; Wiebe, Victor; Khusnutdinova, Elza; Remm, Maido; Pääbo, Svante

2005-01-01

Linkage disequilibrium structure is still unpredictable because the interplay of regional recombination rate and demographic history is poorly understood. We have compared the distribution of LD across two genomic regions differing in crossing-over activity – Xq13 (0.166 cM/Mb) and Xp22 (1.3 cM/Mb) – in 15 Eurasian populations. Demographic events predicted to increase the LD level – genetic drift, bottleneck and admixture – had a very strong impact on extent and patterns of regional LD across Xq13 compared to Xp22. The haplotype distribution of the DXS1225-DXS8082 microsatellites from Xq13 exhibiting strong association in all populations was remarkably influenced by population history. European populations shared one common haplotype with a frequency of 25-40%. The Volga-Ural populations studied, living at the geographic borderline of Europe, showed elevated LD as well as harboring a significant fraction of haplotypes originating from East Asia, thus reflecting their past migrations and admixture. In the young Kuusamo isolate from Finland, a bottleneck has led to allelic associations between loci and shifted the haplotype distribution, but has much less affected single microsatellite allele frequencies compared to the main Finnish population. The data show that the footprint of a demographic event is longer preserved in haplotype distribution within a region of low crossing-over rate, than in the information content of a single marker, or between actively recombining markers. As the knowledge of LD patterns is often chosen to assist association mapping of common disease, our conclusions emphasise the importance of understanding the history, structure and variation of a study population. PMID:15657606

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.

High Prevalence of Posterior Polymorphous Corneal Dystrophy in the Czech Republic; Linkage Disequilibrium Mapping and Dating an Ancestral Mutation

PubMed Central

Filipec, Martin; Jirsova, Katerina; Reinstein Merjava, Stanislava; Deloukas, Panos; Webb, Tom R.; Bhattacharya, Shomi S.; Ebenezer, Neil D.; Morris, Alex G.; Hardcastle, Alison J.

2012-01-01

Posterior polymorphous corneal dystrophy (PPCD) is a rare autosomal dominant genetically heterogeneous disorder. Nineteen Czech PPCD pedigrees with 113 affected family members were identified, and 17 of these kindreds were genotyped for markers on chromosome 20p12.1- 20q12. Comparison of haplotypes in 81 affected members, 20 unaffected first degree relatives and 13 spouses, as well as 55 unrelated controls, supported the hypothesis of a shared ancestor in 12 families originating from one geographic location. In 38 affected individuals from nine of these pedigrees, a common haplotype was observed between D20S48 and D20S107 spanning approximately 23 Mb, demonstrating segregation of disease with the PPCD1 locus. This haplotype was not detected in 110 ethnically matched control chromosomes. Within the common founder haplotype, a core mini-haplotype was detected for D20S605, D20S182 and M189K2 in all 67 affected members from families 1–12, however alleles representing the core mini-haplotype were also detected in population matched controls. The most likely location of the responsible gene within the disease interval, and estimated mutational age, were inferred by linkage disequilibrium mapping (DMLE+2.3). The appearance of a disease-causing mutation was dated between 64–133 generations. The inferred ancestral locus carrying a PPCD1 disease-causing variant within the disease interval spans 60 Kb on 20p11.23, which contains a single known protein coding gene, ZNF133. However, direct sequence analysis of coding and untranslated exons did not reveal a potential pathogenic mutation. Microdeletion or duplication was also excluded by comparative genomic hybridization using a dense chromosome 20 specific array. Geographical origin, haplotype and statistical analysis suggest that in 14 unrelated families an as yet undiscovered mutation on 20p11.23 was inherited from a common ancestor. Prevalence of PPCD in the Czech Republic appears to be the highest worldwide and our data

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

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.

Improving the detection of pathways in genome-wide association studies by combined effects of SNPs from Linkage Disequilibrium blocks.

PubMed

Zhao, Huiying; Nyholt, Dale R; Yang, Yuanhao; Wang, Jihua; Yang, Yuedong

2017-06-14

Genome-wide association studies (GWAS) have successfully identified single variants associated with diseases. To increase the power of GWAS, gene-based and pathway-based tests are commonly employed to detect more risk factors. However, the gene- and pathway-based association tests may be biased towards genes or pathways containing a large number of single-nucleotide polymorphisms (SNPs) with small P-values caused by high linkage disequilibrium (LD) correlations. To address such bias, numerous pathway-based methods have been developed. Here we propose a novel method, DGAT-path, to divide all SNPs assigned to genes in each pathway into LD blocks, and to sum the chi-square statistics of LD blocks for assessing the significance of the pathway by permutation tests. The method was proven robust with the type I error rate >1.6 times lower than other methods. Meanwhile, the method displays a higher power and is not biased by the pathway size. The applications to the GWAS summary statistics for schizophrenia and breast cancer indicate that the detected top pathways contain more genes close to associated SNPs than other methods. As a result, the method identified 17 and 12 significant pathways containing 20 and 21 novel associated genes, respectively for two diseases. The method is available online by http://sparks-lab.org/server/DGAT-path .

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

Linkage of Viral Sequences among HIV-Infected Village Residents in Botswana: Estimation of Linkage Rates in the Presence of Missing Data

PubMed Central

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. PMID:24415932

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.

Genetic Diversity and Linkage Disequilibrium in Chinese Bread Wheat (Triticum aestivum L.) Revealed by SSR Markers

PubMed Central

Hao, Chenyang; Wang, Lanfen; Ge, Hongmei; Dong, Yuchen; Zhang, Xueyong

2011-01-01

Two hundred and fifty bread wheat lines, mainly Chinese mini core accessions, were assayed for polymorphism and linkage disequilibrium (LD) based on 512 whole-genome microsatellite loci representing a mean marker density of 5.1 cM. A total of 6,724 alleles ranging from 1 to 49 per locus were identified in all collections. The mean PIC value was 0.650, ranging from 0 to 0.965. Population structure and principal coordinate analysis revealed that landraces and modern varieties were two relatively independent genetic sub-groups. Landraces had a higher allelic diversity than modern varieties with respect to both genomes and chromosomes in terms of total number of alleles and allelic richness. 3,833 (57.0%) and 2,788 (41.5%) rare alleles with frequencies of <5% were found in the landrace and modern variety gene pools, respectively, indicating greater numbers of rare variants, or likely new alleles, in landraces. Analysis of molecular variance (AMOVA) showed that A genome had the largest genetic differentiation and D genome the lowest. In contrast to genetic diversity, modern varieties displayed a wider average LD decay across the whole genome for locus pairs with r2>0.05 (P<0.001) than the landraces. Mean LD decay distance for the landraces at the whole genome level was <5 cM, while a higher LD decay distance of 5–10 cM in modern varieties. LD decay distances were also somewhat different for each of the 21 chromosomes, being higher for most of the chromosomes in modern varieties (<5∼25 cM) compared to landraces (<5∼15 cM), presumably indicating the influences of domestication and breeding. This study facilitates predicting the marker density required to effectively associate genotypes with traits in Chinese wheat genetic resources. PMID:21365016

Exploiting genotyping by sequencing to characterize the genomic structure of the American cranberry through high-density linkage mapping.

PubMed

Covarrubias-Pazaran, Giovanny; Diaz-Garcia, Luis; Schlautman, Brandon; Deutsch, Joseph; Salazar, Walter; Hernandez-Ochoa, Miguel; Grygleski, Edward; Steffan, Shawn; Iorizzo, Massimo; Polashock, James; Vorsa, Nicholi; Zalapa, Juan

2016-06-13

The application of genotyping by sequencing (GBS) approaches, combined with data imputation methodologies, is narrowing the genetic knowledge gap between major and understudied, minor crops. GBS is an excellent tool to characterize the genomic structure of recently domesticated (~200 years) and understudied species, such as cranberry (Vaccinium macrocarpon Ait.), by generating large numbers of markers for genomic studies such as genetic mapping. We identified 10842 potentially mappable single nucleotide polymorphisms (SNPs) in a cranberry pseudo-testcross population wherein 5477 SNPs and 211 short sequence repeats (SSRs) were used to construct a high density linkage map in cranberry of which a total of 4849 markers were mapped. Recombination frequency, linkage disequilibrium (LD), and segregation distortion at the genomic level in the parental and integrated linkage maps were characterized for first time in cranberry. SSR markers, used as the backbone in the map, revealed high collinearity with previously published linkage maps. The 4849 point map consisted of twelve linkage groups spanning 1112 cM, which anchored 2381 nuclear scaffolds accounting for ~13 Mb of the estimated 470 Mb cranberry genome. Bin mapping identified 592 and 672 unique bins in the parentals and a total of 1676 unique marker positions in the integrated map. Synteny analyses comparing the order of anchored cranberry scaffolds to their homologous positions in kiwifruit, grape, and coffee genomes provided initial evidence of homology between cranberry and closely related species. GBS data was used to rapidly saturate the cranberry genome with markers in a pseudo-testcross population. Collinearity between the present saturated genetic map and previous cranberry SSR maps suggests that the SNP locations represent accurate marker order and chromosome structure of the cranberry genome. SNPs greatly improved current marker genome coverage, which allowed for genome-wide structure investigations such

Extent of linkage disequilibrium, consistency of gametic phase, and imputation accuracy within and across Canadian dairy breeds.

PubMed

Larmer, S G; Sargolzaei, M; Schenkel, F S

2014-05-01

Genomic selection requires a large reference population to accurately estimate single nucleotide polymorphism (SNP) effects. In some Canadian dairy breeds, the available reference populations are not large enough for accurate estimation of SNP effects for traits of interest. If marker phase is highly consistent across multiple breeds, it is theoretically possible to increase the accuracy of genomic prediction for one or all breeds by pooling several breeds into a common reference population. This study investigated the extent of linkage disequilibrium (LD) in 5 major dairy breeds using a 50,000 (50K) SNP panel and 3 of the same breeds using the 777,000 (777K) SNP panel. Correlation of pair-wise SNP phase was also investigated on both panels. The level of LD was measured using the squared correlation of alleles at 2 loci (r(2)), and the consistency of SNP gametic phases was correlated using the signed square root of these values. Because of the high cost of the 777K panel, the accuracy of imputation from lower density marker panels [6,000 (6K) or 50K] was examined both within breed and using a multi-breed reference population in Holstein, Ayrshire, and Guernsey. Imputation was carried out using FImpute V2.2 and Beagle 3.3.2 software. Imputation accuracies were then calculated as both the proportion of correct SNP filled in (concordance rate) and allelic R(2). Computation time was also explored to determine the efficiency of the different algorithms for imputation. Analysis showed that LD values >0.2 were found in all breeds at distances at or shorter than the average adjacent pair-wise distance between SNP on the 50K panel. Correlations of r-values, however, did not reach high levels (<0.9) at these distances. High correlation values of SNP phase between breeds were observed (>0.94) when the average pair-wise distances using the 777K SNP panel were examined. High concordance rate (0.968-0.995) and allelic R(2) (0.946-0.991) were found for all breeds when imputation

Genetic diversity and linkage disequilibrium in the chemokine receptor CCR2-CCR5 region among individuals and populations

PubMed Central

Lawhorn, Collene; Yuferov, Vadim; Randesi, Matthew; Ho, Ann; Morgello, Susan; Kreek, Mary Jeanne; Levran, Orna

2013-01-01

Background Chemokine receptors CCR2 and CCR5 play a key role in immune and inflammatory responses and have been associated with several diseases, including AIDS. In order to comprehend health disparities it is important to understand the nature of genetic variation in specific genes of interest in different populations. Current studies of the CCR2 and CCR5 receptor genes are primarily focused on the CCR5-Δ32, and CCR2-V64I SNPs. Methods Sanger sequencing was used to sequence the regions containing 16 SNPs in the adjacent CCR2 and CCR5 genes (including CCR5-Δ32, and CCR2-V64I) in 249 subjects of African, European and Hispanic ancestry. Linkage disequilibrium (LD) and haplotypes were determined using Haploview. Results The data revealed large differences in allele frequencies of several SNPs and LD patterns among the ethnic groups, including SNPs that were restricted to Africans or Europeans. Seven known CCR5 haplotypes and six novel CCR2 haplotypes were identified. A rare case of an HIV+ subject with the CCR5-Δ32/Δ32 was identified. Conclusions These data demonstrate a LD between CCR2 and CCR5 at several loci and provide new information about CCR2 that contributes to our understanding of its population-specific genetic variability. The data indicate that in addition to CCR5-Δ32 and CCR2-V64I, other SNPs and haplotypes may be important genetic determinants of disease and should be investigated. PMID:24011637

Marker selection for the transmission/disequilibrium test, in recently admixed populations.

PubMed Central

Kaplan, N L; Martin, E R; Morris, R W; Weir, B S

1998-01-01

Recent admixture between genetically differentiated populations can result in high levels of association between alleles at loci that are <=10 cM apart. The transmission/disequilibrium test (TDT) proposed by Spielman et al. (1993) can be a powerful test of linkage between disease and marker loci in the presence of association and therefore could be a useful test of linkage in admixed populations. The degree of association between alleles at two loci depends on the differences in allele frequencies, at the two loci, in the founding populations; therefore, the choice of marker is important. For a multiallelic marker, one strategy that may improve the power of the TDT is to group marker alleles within a locus, on the basis of information about the founding populations and the admixed population, thereby collapsing the marker into one with fewer alleles. We have examined the consequences of collapsing a microsatellite into a two-allele marker, when two founding populations are assumed for the admixed population, and have found that if there is random mating in the admixed population, then typically there is a collapsing for which the power of the TDT is greater than that for the original microsatellite marker. A method is presented for finding the optimal collapsing that has minimal dependence on the disease and that uses estimates either of marker allele frequencies in the two founding populations or of marker allele frequencies in the current, admixed population and in one of the founding populations. Furthermore, this optimal collapsing is not always the collapsing with the largest difference in allele frequencies in the founding populations. To demonstrate this strategy, we considered a recent data set, published previously, that provides frequency estimates for 30 microsatellites in 13 populations. PMID:9497257

Can statistical linkage of missing variables reduce bias in treatment effect estimates in comparative effectiveness research studies?

PubMed

Crown, William; Chang, Jessica; Olson, Melvin; Kahler, Kristijan; Swindle, Jason; Buzinec, Paul; Shah, Nilay; Borah, Bijan

2015-09-01

Missing data, particularly missing variables, can create serious analytic challenges in observational comparative effectiveness research studies. Statistical linkage of datasets is a potential method for incorporating missing variables. Prior studies have focused upon the bias introduced by imperfect linkage. This analysis uses a case study of hepatitis C patients to estimate the net effect of statistical linkage on bias, also accounting for the potential reduction in missing variable bias. The results show that statistical linkage can reduce bias while also enabling parameter estimates to be obtained for the formerly missing variables. The usefulness of statistical linkage will vary depending upon the strength of the correlations of the missing variables with the treatment variable, as well as the outcome variable of interest.

Disequilibrium biosignatures over Earth history and implications for detecting exoplanet life.

PubMed

Krissansen-Totton, Joshua; Olson, Stephanie; Catling, David C

2018-01-01

Chemical disequilibrium in planetary atmospheres has been proposed as a generalized method for detecting life on exoplanets through remote spectroscopy. Among solar system planets with substantial atmospheres, the modern Earth has the largest thermodynamic chemical disequilibrium due to the presence of life. However, how this disequilibrium changed over time and, in particular, the biogenic disequilibria maintained in the anoxic Archean or less oxic Proterozoic eons are unknown. We calculate the atmosphere-ocean disequilibrium in the Precambrian using conservative proxy- and model-based estimates of early atmospheric and oceanic compositions. We omit crustal solids because subsurface composition is not detectable on exoplanets, unlike above-surface volatiles. We find that (i) disequilibrium increased through time in step with the rise of oxygen; (ii) both the Proterozoic and Phanerozoic may have had remotely detectable biogenic disequilibria due to the coexistence of O 2 , N 2 , and liquid water; and (iii) the Archean had a biogenic disequilibrium caused by the coexistence of N 2 , CH 4 , CO 2 , and liquid water, which, for an exoplanet twin, may be remotely detectable. On the basis of this disequilibrium, we argue that the simultaneous detection of abundant CH 4 and CO 2 in a habitable exoplanet's atmosphere is a potential biosignature. Specifically, we show that methane mixing ratios greater than 10 -3 are potentially biogenic, whereas those exceeding 10 -2 are likely biogenic due to the difficulty in maintaining large abiotic methane fluxes to support high methane levels in anoxic atmospheres. Biogenicity would be strengthened by the absence of abundant CO, which should not coexist in a biological scenario.

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

PubMed

Iqbal, Muhammad Javed; Mamidi, Sujan; Ahsan, Rubina; Kianian, Shahryar F; Coyne, Clarice J; Hamama, Anwar A; Narina, Satya S; Bhardwaj, Harbans L

2012-08-01

White lupin (Lupinus albus L.) has been around since 300 B.C. and is recognized for its ability to grow on poor soils and application as green manure in addition to seed harvest. The seed has very high levels of protein (33-47 %) and oil (6-13 %). It also has many secondary metabolites that are potentially of nutraceutical value to animals and humans. Despite such a great potential, lupins role in modern agriculture began only in the twentieth century. Although a large collection of Lupinus germplasm accessions is available worldwide, rarely have they been genetically characterized. Additionally, scarce genomic resources in terms of recombinant populations and genome information have been generated for L. albus. With the advancement in association mapping methods, the natural populations have the potential to replace the recombinant populations in gene mapping and marker-trait associations. Therefore, we studied the genetic similarity, population structure and marker-trait association in a USDA germplasm collection for their current and future application in this crop improvement. A total of 122 PI (Plant Inventory) lines were screened with 18 AFLP primer pairs that generated 2,277 fragments. A subset of 892 polymorphic markers with MAF >0.05 (minor allele frequency) were used for association mapping. The cluster analysis failed to group accessions on the basis of their passport information, and a weak structure and low linkage disequilibrium (LD) were observed indicating the usefulness of the collection for association mapping. Moreover, we were also able to identify two markers (a p value of 1.53 × 10(-4) and 2.3 × 10(-4)) that explained 22.69 and 20.5 % of seed weight variation determined using R (LR) (2) . The implications of lack of geographic clustering, population structure, low LD and the ability of AFLP to map seed weight trait using association mapping and the usefulness of the PI collections in breeding programs are discussed.

Disequilibrium biosignatures over Earth history and implications for detecting exoplanet life

PubMed Central

Krissansen-Totton, Joshua; Olson, Stephanie; Catling, David C.

2018-01-01

Chemical disequilibrium in planetary atmospheres has been proposed as a generalized method for detecting life on exoplanets through remote spectroscopy. Among solar system planets with substantial atmospheres, the modern Earth has the largest thermodynamic chemical disequilibrium due to the presence of life. However, how this disequilibrium changed over time and, in particular, the biogenic disequilibria maintained in the anoxic Archean or less oxic Proterozoic eons are unknown. We calculate the atmosphere-ocean disequilibrium in the Precambrian using conservative proxy- and model-based estimates of early atmospheric and oceanic compositions. We omit crustal solids because subsurface composition is not detectable on exoplanets, unlike above-surface volatiles. We find that (i) disequilibrium increased through time in step with the rise of oxygen; (ii) both the Proterozoic and Phanerozoic may have had remotely detectable biogenic disequilibria due to the coexistence of O2, N2, and liquid water; and (iii) the Archean had a biogenic disequilibrium caused by the coexistence of N2, CH4, CO2, and liquid water, which, for an exoplanet twin, may be remotely detectable. On the basis of this disequilibrium, we argue that the simultaneous detection of abundant CH4 and CO2 in a habitable exoplanet’s atmosphere is a potential biosignature. Specifically, we show that methane mixing ratios greater than 10−3 are potentially biogenic, whereas those exceeding 10−2 are likely biogenic due to the difficulty in maintaining large abiotic methane fluxes to support high methane levels in anoxic atmospheres. Biogenicity would be strengthened by the absence of abundant CO, which should not coexist in a biological scenario. PMID:29387792

Tests for linkage and association in nuclear families.

PubMed Central

Martin, E R; Kaplan, N L; Weir, B S

1997-01-01

The transmission/disequilibrium test (TDT) originally was introduced to test for linkage between a genetic marker and a disease-susceptibility locus, in the presence of association. Recently, the TDT has been used to test for association in the presence of linkage. The motivation for this is that linkage analysis typically identifies large candidate regions, and further refinement is necessary before a search for the disease gene is begun, on the molecular level. Evidence of association and linkage may indicate which markers in the region are closest to a disease locus. As a test of linkage, transmissions from heterozygous parents to all of their affected children can be included in the TDT; however, the TDT is a valid chi2 test of association only if transmissions to unrelated affected children are used in the analysis. If the sample contains independent nuclear families with multiple affected children, then one procedure that has been used to test for association is to select randomly a single affected child from each sibship and to apply the TDT to those data. As an alternative, we propose two statistics that use data from all of the affected children. The statistics give valid chi2 tests of the null hypothesis of no association or no linkage and generally are more powerful than the TDT with a single, randomly chosen, affected child from each family. PMID:9311750

Estimation and test for linkage between markers: a comparison of lod score and χ (2) test in a linkage study of maritime pine (Pinus pinaster Ait.).

PubMed

Gerber, S; Rodolphe, F

1994-06-01

The first step in the construction of a linkage map involves the estimation and test for linkage between all possible pairs of markers. The lod score method is used in many linkage studies for the latter purpose. In contrast with classical statistical tests, this method does not rely on the choice of a first-type error level. We thus provide a comparison between the lod score and a χ (2) test on linkage data from a gymnosperm, the maritime pine. The lod score appears to be a very conservative test with the usual thresholds. Its severity depends on the type of data used.

Estimating time-varying RSA to examine psychophysiological linkage of marital dyads.

PubMed

Gates, Kathleen M; Gatzke-Kopp, Lisa M; Sandsten, Maria; Blandon, Alysia Y

2015-08-01

One of the primary tenets of polyvagal theory dictates that parasympathetic influence on heart rate, often estimated by respiratory sinus arrhythmia (RSA), shifts rapidly in response to changing environmental demands. The current standard analytic approach of aggregating RSA estimates across time to arrive at one value fails to capture this dynamic property within individuals. By utilizing recent methodological developments that enable precise RSA estimates at smaller time intervals, we demonstrate the utility of computing time-varying RSA for assessing psychophysiological linkage (or synchrony) in husband-wife dyads using time-locked data collected in a naturalistic setting. © 2015 Society for Psychophysiological Research.

Detection of gene-environment interactions in the presence of linkage disequilibrium and noise by using genetic risk scores with internal weights from elastic net regression.

PubMed

Hüls, Anke; Ickstadt, Katja; Schikowski, Tamara; Krämer, Ursula

2017-06-12

SNPs estimated by a multivariate elastic net regression were shown to be a powerful tool to detect gene-environment interactions in scenarios of high Linkage disequilibrium and noise.

Significant Linkage for Tourette Syndrome in a Large French Canadian Family

PubMed Central

Mérette, Chantal; Brassard, Andrée; Potvin, Anne; Bouvier, Hélène; Rousseau, François; Émond, Claudia; Bissonnette, Luc; Roy, Marc-André; Maziade, Michel; Ott, Jurg; Caron, Chantal

2000-01-01

Family and twin studies provide strong evidence that genetic factors are involved in the transmission of Gilles de la Tourette syndrome (TS) and related psychiatric disorders. To detect the underlying susceptibility gene(s) for TS, we performed linkage analysis in one large French Canadian family (127 members) from the Charlevoix region, in which 20 family members were definitely affected by TS and 20 others showed related tic disorders. Using model-based linkage analysis, we observed a LOD score of 3.24 on chromosome 11 (11q23). This result was obtained in a multipoint approach involving marker D11S1377, the marker for which significant linkage disequilibrium with TS recently has been detected in an Afrikaner population. Altogether, 25 markers were studied, and, for level of significance, we derived a criterion that took into account the multiple testing arising from the use of three phenotype definitions and three modes of inheritance, a procedure that yielded a LOD score of 3.18. Hence, even after adjustment for multiple testing, the present study shows statistically significant evidence for genetic linkage with TS. PMID:10986045

[Transmission disequilibrium test for nonsyndromic cleft lip and palate and segment homeobox gene-1 gene].

PubMed

Wu, Ping-An; Li, Yun-Liang; Wu, Han-Jiang; Wang, Kai; Fan, Guo-Zheng

2007-09-01

To investigate the relationship between muscle segment homeobox gene-1 (MSX1) and the genetic susceptibility of nonsyndromic cleft lip and palate (NSCLP) in Hunan Hans. One microsatellite DNA marker CA repeat in MSX1 intron region was used as genetic marker. The genotypes of 387 members in 129 NSCLP nuclear family trios were analyzed by polymerase chain reaction (PCR) and denaturing polyacrylamide gel electrophoresis. Then transmission disequilibrium test (TDT) and Logistic regression analysis were used to conduct association analysis. TDT analysis confirmed that CA4 allele in CL/P and CPO groups preferentially transmitted to the affected offspring (P = 0.018, P = 0.041). Logistic regression analysis indicated that the recessive model of inheritance was supported, and CA4 itself or CA4 acting as a marker for a disease allele or haplotype was inherited in a recessive fashion (P = 0.009). MSX1 gene is associated with NSCLP, and MSX1 gene may be directly involved either in the etiology of NSCLP or in linkage disequilibrium with disease-predisposing sites.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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.

Normalization Ridge Regression in Practice II: The Estimation of Multiple Feedback Linkages.

ERIC Educational Resources Information Center

Bulcock, J. W.

The use of the two-stage least squares (2 SLS) procedure for estimating nonrecursive social science models is often impractical when multiple feedback linkages are required. This is because 2 SLS is extremely sensitive to multicollinearity. The standard statistical solution to the multicollinearity problem is a biased, variance reduced procedure…

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suarez, B.K.; Parsian, A.; Hampe, C.L.

1994-01-01

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

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.

Linkage disequilibrium between the CYP2C19*2,*17 and CYP2C9*1 alleles and impact of VKORC1, CYP2C9, CYP2C19 gene polymorphisms and gene-gene interactions on warfarin therapy.

PubMed

Khalighi, Koroush; Cheng, Gang; Mirabbasi, Seyedabbas; Khalighi, Bahar; Wu, Yin; Fan, Wuqiang

2017-01-01

Warfarin therapy is complicated by its large inter-individual and intra-individual variability. Both genetic and non-genetic factors can affect warfarin therapy. This study aims to investigate the allele distribution of VKORC1, CYP2C9 and CYP2C19, contribution of different allele variants and possible gene-gene interaction on warfarin therapy. Four hundreds and ninety-two patients were enrolled and single nucleotide polymorphisms for vitamin K epoxide reductase complex subunit 1 (VKORC1), cytochrome P450 CYP2C9 and cytochrome P450 CYP2C19 were genotyped. CYP2C9*1 allele is in complete linkage disequilibrium with CYP2C19*2 and CYP2C19*17 (D' = 1) in our study population. Patient with VKORC1-1639 G > A, CYP2C9*2 and CYP2C9*3 genetic variants need significant lower warfarin dose than patient with wild type allele of VKORC1 1639 G or CYP2C9*1. There is no significant differences between CYP2C19 allele variants for warfarin stable dose and INR > 5 event. Because of the complete linkage disequilibrium between CYP2C19*2,*17 and CYP2C9*1, patient with CYP2C19 *2/*2, *2/*17 and *17/*17 genotypes tend to have higher warfarin dose than patient with CYP2C19*1/*1 genotype. Stepwise regression analysis showed that VKORC1, CYP2C9, body mass index (BMI), age and gender were included as a factor significantly contributing to warfarin dose, whereas CYP2C19 did not contribute to warfarin dose. No statistically significant interaction between CYP2C9 and VKORC1 on warfarin dose and INR > 5 event was detected in univariate general linear model analysis. Our study suggests that polymorphic variants of VKORC1 and CYP2C9 affect warfarin dose independently, whereas CYP2C19 did not contribute to warfarin therapy.

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

Linkage of A-to-I RNA Editing in Metazoans and the Impact on Genome Evolution

PubMed Central

Duan, Yuange; Dou, Shengqian; Zhang, Hong; Wu, Changcheng; Wu, Mingming

2018-01-01

Abstract The adenosine-to-inosine (A-to-I) RNA editomes have been systematically characterized in various metazoan species, and many editing sites were found in clusters. However, it remains unclear whether the clustered editing sites tend to be linked in the same RNA molecules or not. By adopting a method originally designed to detect linkage disequilibrium of DNA mutations, we examined the editomes of ten metazoan species and detected extensive linkage of editing in Drosophila and cephalopods. The prevalent linkages of editing in these two clades, many of which are conserved between closely related species and might be associated with the adaptive proteomic recoding, are maintained by natural selection at the cost of genome evolution. Nevertheless, in worms and humans, we only detected modest proportions of linked editing events, the majority of which were not conserved. Furthermore, the linkage of editing in coding regions of worms and humans might be overall deleterious, which drives the evolution of DNA sites to escape promiscuous editing. Altogether, our results suggest that the linkage landscape of A-to-I editing has evolved during metazoan evolution. This present study also suggests that linkage of editing should be considered in elucidating the functional consequences of RNA editing. PMID:29048557

A method to estimate the contribution of regional genetic associations to complex traits from summary association statistics.

PubMed

Pare, Guillaume; Mao, Shihong; Deng, Wei Q

2016-06-08

Despite considerable efforts, known genetic associations only explain a small fraction of predicted heritability. Regional associations combine information from multiple contiguous genetic variants and can improve variance explained at established association loci. However, regional associations are not easily amenable to estimation using summary association statistics because of sensitivity to linkage disequilibrium (LD). We now propose a novel method, LD Adjusted Regional Genetic Variance (LARGV), to estimate phenotypic variance explained by regional associations using summary statistics while accounting for LD. Our method is asymptotically equivalent to a multiple linear regression model when no interaction or haplotype effects are present. It has several applications, such as ranking of genetic regions according to variance explained or comparison of variance explained by two or more regions. Using height and BMI data from the Health Retirement Study (N = 7,776), we show that most genetic variance lies in a small proportion of the genome and that previously identified linkage peaks have higher than expected regional variance.

A method to estimate the contribution of regional genetic associations to complex traits from summary association statistics

PubMed Central

Pare, Guillaume; Mao, Shihong; Deng, Wei Q.

2016-01-01

Despite considerable efforts, known genetic associations only explain a small fraction of predicted heritability. Regional associations combine information from multiple contiguous genetic variants and can improve variance explained at established association loci. However, regional associations are not easily amenable to estimation using summary association statistics because of sensitivity to linkage disequilibrium (LD). We now propose a novel method, LD Adjusted Regional Genetic Variance (LARGV), to estimate phenotypic variance explained by regional associations using summary statistics while accounting for LD. Our method is asymptotically equivalent to a multiple linear regression model when no interaction or haplotype effects are present. It has several applications, such as ranking of genetic regions according to variance explained or comparison of variance explained by two or more regions. Using height and BMI data from the Health Retirement Study (N = 7,776), we show that most genetic variance lies in a small proportion of the genome and that previously identified linkage peaks have higher than expected regional variance. PMID:27273519

Accommodating Chromosome Inversions in Linkage Analysis

PubMed Central

Chen, Gary K.; Slaten, Erin; Ophoff, Roel A.; Lange, Kenneth

2006-01-01

This work develops a population-genetics model for polymorphic chromosome inversions. The model precisely describes how an inversion changes the nature of and approach to linkage equilibrium. The work also describes algorithms and software for allele-frequency estimation and linkage analysis in the presence of an inversion. The linkage algorithms implemented in the software package Mendel estimate recombination parameters and calculate the posterior probability that each pedigree member carries the inversion. Application of Mendel to eight Centre d'Étude du Polymorphisme Humain pedigrees in a region containing a common inversion on 8p23 illustrates its potential for providing more-precise estimates of the location of an unmapped marker or trait gene. Our expanded cytogenetic analysis of these families further identifies inversion carriers and increases the evidence of linkage. PMID:16826515

New generation pharmacogenomic tools: a SNP linkage disequilibrium Map, validated SNP assay resource, and high-throughput instrumentation system for large-scale genetic studies.

PubMed

De La Vega, Francisco M; Dailey, David; Ziegle, Janet; Williams, Julie; Madden, Dawn; Gilbert, Dennis A

2002-06-01

Since public and private efforts announced the first draft of the human genome last year, researchers have reported great numbers of single nucleotide polymorphisms (SNPs). We believe that the availability of well-mapped, quality SNP markers constitutes the gateway to a revolution in genetics and personalized medicine that will lead to better diagnosis and treatment of common complex disorders. A new generation of tools and public SNP resources for pharmacogenomic and genetic studies--specifically for candidate-gene, candidate-region, and whole-genome association studies--will form part of the new scientific landscape. This will only be possible through the greater accessibility of SNP resources and superior high-throughput instrumentation-assay systems that enable affordable, highly productive large-scale genetic studies. We are contributing to this effort by developing a high-quality linkage disequilibrium SNP marker map and an accompanying set of ready-to-use, validated SNP assays across every gene in the human genome. This effort incorporates both the public sequence and SNP data sources, and Celera Genomics' human genome assembly and enormous resource ofphysically mapped SNPs (approximately 4,000,000 unique records). This article discusses our approach and methodology for designing the map, choosing quality SNPs, designing and validating these assays, and obtaining population frequency ofthe polymorphisms. We also discuss an advanced, high-performance SNP assay chemisty--a new generation of the TaqMan probe-based, 5' nuclease assay-and high-throughput instrumentation-software system for large-scale genotyping. We provide the new SNP map and validation information, validated SNP assays and reagents, and instrumentation systems as a novel resource for genetic discoveries.

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

PubMed Central

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

2010-01-01

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

Linkage of A-to-I RNA Editing in Metazoans and the Impact on Genome Evolution.

PubMed

Duan, Yuange; Dou, Shengqian; Zhang, Hong; Wu, Changcheng; Wu, Mingming; Lu, Jian

2018-01-01

The adenosine-to-inosine (A-to-I) RNA editomes have been systematically characterized in various metazoan species, and many editing sites were found in clusters. However, it remains unclear whether the clustered editing sites tend to be linked in the same RNA molecules or not. By adopting a method originally designed to detect linkage disequilibrium of DNA mutations, we examined the editomes of ten metazoan species and detected extensive linkage of editing in Drosophila and cephalopods. The prevalent linkages of editing in these two clades, many of which are conserved between closely related species and might be associated with the adaptive proteomic recoding, are maintained by natural selection at the cost of genome evolution. Nevertheless, in worms and humans, we only detected modest proportions of linked editing events, the majority of which were not conserved. Furthermore, the linkage of editing in coding regions of worms and humans might be overall deleterious, which drives the evolution of DNA sites to escape promiscuous editing. Altogether, our results suggest that the linkage landscape of A-to-I editing has evolved during metazoan evolution. This present study also suggests that linkage of editing should be considered in elucidating the functional consequences of RNA editing. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

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.

A Targeted Capture Linkage Map Anchors the Genome of the Schistosomiasis Vector Snail, Biomphalaria glabrata.

PubMed

Tennessen, Jacob A; Bollmann, Stephanie R; Blouin, Michael S

2017-07-05

The aquatic planorbid snail Biomphalaria glabrata is one of the most intensively-studied mollusks due to its role in the transmission of schistosomiasis. Its 916 Mb genome has recently been sequenced and annotated, but it remains poorly assembled. Here, we used targeted capture markers to map over 10,000 B. glabrata scaffolds in a linkage cross of 94 F1 offspring, generating 24 linkage groups (LGs). We added additional scaffolds to these LGs based on linkage disequilibrium (LD) analysis of targeted capture and whole-genome sequences of 96 unrelated snails. Our final linkage map consists of 18,613 scaffolds comprising 515 Mb, representing 56% of the genome and 75% of genic and nonrepetitive regions. There are 18 large (> 10 Mb) LGs, likely representing the expected 18 haploid chromosomes, and > 50% of the genome has been assigned to LGs of at least 17 Mb. Comparisons with other gastropod genomes reveal patterns of synteny and chromosomal rearrangements. Linkage relationships of key immune-relevant genes may help clarify snail-schistosome interactions. By focusing on linkage among genic and nonrepetitive regions, we have generated a useful resource for associating snail phenotypes with causal genes, even in the absence of a complete genome assembly. A similar approach could potentially improve numerous poorly-assembled genomes in other taxa. This map will facilitate future work on this host of a serious human parasite. Copyright © 2017 Tennessen et al.

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.

Disequilibrium, complexity, the Schottky effect, and q-entropies, in paramagnetism

NASA Astrophysics Data System (ADS)

Pennini, F.; Plastino, A.

2017-12-01

We investigate connections between statistical quantifiers and paramagnetism. More concretely, we apply the notions of (i) disequilibrium and (ii) statistical complexity, to a paramagnetic system of non-coupled dipoles. Interesting insights are thereby obtained. In particular, we encounter a kind of criticality, not associated to the temperature but to the disequilibrium.

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 ...

Strong linkage disequilibrium of a HbE variant with the (AT)9(T)5 repeat in the BP1 binding site upstream of the beta-globin gene in the Thai population.

PubMed

Ohashi, Jun; Naka, Izumi; Patarapotikul, Jintana; Hananantachai, Hathairad; Brittenham, Gary; Looareesuwan, Sornchai; Clark, Andrew G; Tokunaga, Katsushi

2005-01-01

A binding site for the repressor protein BP1, which contains a tandem (AT)x(T)y repeat, is located approximately 530 bp 5' to the human beta-globin gene (HBB). There is accumulating evidence that BP1 binds to the (AT)9(T)5 allele more strongly than to other alleles, thereby reducing the expression of HBB. In this study, we investigated polymorphisms in the (AT)x(T)y repeat in 57 individuals living in Thailand, including three homozygotes for the hemoglobin E variant (HbE; beta26Glu-->Lys), 22 heterozygotes, and 32 normal homozygotes. We found that (AT)9(T)5 and (AT)7(T)7 alleles were predominant in the studied population and that the HbE variant is in strong linkage disequilibrium with the (AT)9(T)5 allele, which can explain why the betaE chain is inefficiently synthesized compared to the normal betaA chain. Moreover, the mildness of the HbE disease compared to other hemoglobinopathies in Thai may be due, in part, to the presence of the (AT)9(T)5 repeat on the HbE chromosome. In addition, a novel (AC)n polymorphism adjacent to the (AT)x(T)y repeat (i.e., (AC)3(AT)7(T)5) was found through the variation screening in this study.

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

A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND).

PubMed

Thameem, Farook; Igo, Robert P; Freedman, Barry I; Langefeld, Carl; Hanson, Robert L; Schelling, Jeffrey R; Elston, Robert C; Duggirala, Ravindranath; Nicholas, Susanne B; Goddard, Katrina A B; Divers, Jasmin; Guo, Xiuqing; Ipp, Eli; Kimmel, Paul L; Meoni, Lucy A; Shah, Vallabh O; Smith, Michael W; Winkler, Cheryl A; Zager, Philip G; Knowler, William C; Nelson, Robert G; Pahl, Madeline V; Parekh, Rulan S; Kao, W H Linda; Rasooly, Rebekah S; Adler, Sharon G; Abboud, Hanna E; Iyengar, Sudha K; Sedor, John R

2013-01-01

Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR. Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula. The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4 × 10(-5)) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5 × 10(-4)) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5 × 10(-4)) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome. The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers

Empirical characteristics of family-based linkage to a complex trait: the ADIPOQ region and adiponectin levels.

PubMed

Hellwege, Jacklyn N; Palmer, Nicholette D; Mark Brown, W; Brown, Mark W; Ziegler, Julie T; Sandy An, S; An, Sandy S; Guo, Xiuqing; Ida Chen, Y-D; Chen, Ida Y-D; 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

2015-02-01

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 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 (1,150 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 (0.0018-0.50) and type (coding, non-coding) and had little detectable linkage disequilibrium with rs200573126 (r (2) < 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.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

1995-08-01

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

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

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

PubMed

Carmichael, Gordon A

2008-07-17

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.

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

A Genome-Wide Search for Linkage of Estimated Glomerular Filtration Rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND)

PubMed Central

Thameem, Farook; Igo, Robert P.; Freedman, Barry I.; Langefeld, Carl; Hanson, Robert L.; Schelling, Jeffrey R.; Elston, Robert C.; Duggirala, Ravindranath; Nicholas, Susanne B.; Goddard, Katrina A. B.; Divers, Jasmin; Guo, Xiuqing; Ipp, Eli; Kimmel, Paul L.; Meoni, Lucy A.; Shah, Vallabh O.; Smith, Michael W.; Winkler, Cheryl A.; Zager, Philip G.; Knowler, William C.; Nelson, Robert G.; Pahl, Madeline V.; Parekh, Rulan S.; Kao, W. H. Linda; Rasooly, Rebekah S.; Adler, Sharon G.; Abboud, Hanna E.; Iyengar, Sudha K.; Sedor, John R.

2013-01-01

Objective Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR. Methods Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula. Results The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4×10−5) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5×10−4) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5×10−4) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome. Conclusion The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional

Genetic mapping of the gene for Usher syndrome: linkage analysis in a large Samaritan kindred.

PubMed

Bonné-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 were studied in 10 related sibships. DNA samples 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.

Convective dynamics and chemical disequilibrium in the atmospheres of substellar objects

NASA Astrophysics Data System (ADS)

Bordwell, Baylee; Brown, Benjamin P.; Oishi, Jeffrey S.

2017-11-01

The thousands of substellar objects now known provide a unique opportunity to test our understanding of atmospheric dynamics across a range of environments. The chemical timescales of certain species transition from being much shorter than the dynamical timescales to being much longer than them at a point in the atmosphere known as the quench point. This transition leads to a state of dynamical disequilibrium, the effects of which can be used to probe the atmospheric dynamics of these objects. Unfortunately, due to computational constraints, models that inform the interpretation of these observations are run at dynamical parameters which are far from realistic values. In this study, we explore the behavior of a disequilibrium chemical process with increasingly realistic planetary conditions, to quantify the effects of the approximations used in current models. We simulate convection in 2-D, plane-parallel, polytropically-stratified atmospheres, into which we add reactive passive tracers that explore disequilibrium behavior. We find that as we increase the Rayleigh number, and thus achieve more realistic planetary conditions, the behavior of these tracers does not conform to the classical predictions of disequilibrium chemistry.

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

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.

Linkage of the National Health Interview Survey to air quality data.

PubMed

Parker, Jennifer D; Kravets, Nataliya; Woodruff, Tracey J

2008-02-01

This report describes the linkage between the National Health Interview Survey (NHIS) and air monitoring data from the U.S. Environmental Protection Agency (EPA). There have been few linkages of these data sources, partly because of restrictions on releasing geographic detail from NHIS on public-use files in order to protect participant confidentiality. Pollution exposures for NHIS respondents were calculated by averaging the annual average exposure estimates from EPA air monitors both within 5, 10, 15, and 20 miles of the respondent's block-group location (which is available on restricted NHIS data files) and by county of residence. The 1987-2005 linked data files--referred to as NHIS-EPAAnnualAir--were used to describe the percentage of NHIS respondents linked and the median exposures by linkage method, survey year, and pollutant. Using the 2005 NHIS-EPAAnnualAir data file, the percentage linked and median exposure were described by respondent characteristics, linkage method, and pollutant. Many decisions were made to define pollution exposures for NHIS respondents, including monitor selection, location assignment for NHIS respondents, and geographic linkage criteria. Geographic linkage criteria for assigning area-level exposure estimates affected the percentage and composition of respondents included in the resulting linked sample. Median exposure estimates, however, were similar among geographic linkage methods. NHIS-EPAAnnualAir data files for 1985 through 2005 are currently available to users in the NCHS Research Data Center.

A linkage and family-based association analysis of a potential neurocognitive endophenotype of bipolar disorder.

PubMed

Savitz, Jonathan; van der Merwe, Lize; Solms, Mark; Ramesar, Rajkumar

2007-01-01

The identification of the genetic variants underpinning bipolar disorder (BPD) has been impeded by a complex pattern of inheritance characterized by genetic and phenotypic heterogeneity, genetic epistasis, and gene-environment interactions. In this paper two strategies were used to ameliorate these confounding factors. A unique South African sample including 190 individuals of the relatively, reproductively isolated Afrikaner population was assessed with a battery of neuropsychological tests in an attempt to identify a BPD-associated quantitative trait or endophenotype. BPD individuals performed significantly worse than their unaffected relatives on visual and verbal memory tasks, a finding congruent with the literature. Afocused linkage and family-based association study was carried out using this memory-related endophenotype. In the largest 77-strong Afrikaner pedigree significant evidence for linkage was detected on chromosome 22q11, a region previously implicated in BPD. The quantitative transmission disequilibrium tests-based association analysis suggested that functional variants of the DRD4 and MAO-A genes modulate memory-related cognition. We speculate that polymorphisms at these loci may predispose to a subtype of BPD characterized by memory-related deficits.

A study of disequilibrium between 220Rn and 216Po for 220Rn measurements using a flow-through Lucas scintillation cell.

PubMed

Sathyabama, N; Datta, D; Gaware, J J; Mayya, Y S; Tripathi, R M

2014-01-01

Lucas-type scintillation cells (LSCs) are commonly used for rapid measurements of (220)Rn concentrations in flow-through mode in field and for calibration experiments in laboratories. However, in those measurements, equilibrium between (220)Rn and (216)Po is generally assumed and two alpha particles are considered to be emitted per (220)Rn decay due to very short half-life of (216)Po. In this paper, a small, yet significant disequilibrium existing between (220)Rn and (216)Po has been examined and shown that less than two alpha particles are actually emitted per (220)Rn decay in the cell when flow is maintained. A theoretical formula has been derived for the first time for a correction factor (CF) to be applied to this measured concentration to account for the disequilibrium. The existence of this disequilibrium has been verified experimentally and is found to increase with the increase in the ratio of flow rate to cell volume. The reason for the disequilibrium is attributed to the flushing out of (216)Po formed in the cell before its decay due to the flow. Uncertainties in measured concentrations have been estimated and the estimated CF values have been found to be significant for the flow rates considered above 5 dm(3) min(-1) for a cell of volume 0.125 dm(3). The calculated values of the CF are about 1.055 to 1.178 in the flow rate range of 4 to 15 dm(3) min(-1) for the cell of volume 0.125 dm(3), while the corresponding experimental values are 1.023 to 1.264. This is a systematic error introduced in (220)Rn measurements using a flow-through LSC, which can be removed either by correct formulation or by proper design of a measurement set-up.

Distribution of lod scores in oligogenic linkage analysis.

PubMed

Williams, J T; North, K E; Martin, L J; Comuzzie, A G; Göring, H H; Blangero, J

2001-01-01

In variance component oligogenic linkage analysis it can happen that the residual additive genetic variance bounds to zero when estimating the effect of the ith quantitative trait locus. Using quantitative trait Q1 from the Genetic Analysis Workshop 12 simulated general population data, we compare the observed lod scores from oligogenic linkage analysis with the empirical lod score distribution under a null model of no linkage. We find that zero residual additive genetic variance in the null model alters the usual distribution of the likelihood-ratio statistic.

[Linkage to care among new human immunodeficiency virus diagnoses in Spain].

PubMed

Oliva, Jesús; Malo, Carmen; Fernández, Ana; Izquierdo, Ana; Marcos, Henar; Cevallos, Carlos; Castilla, Jesús; García, Rocio; Díez, Mercedes

2014-03-01

To describe linkage to care among new HIV diagnoses in Spain; and to estimate factors associated to linkage to care within three months after diagnosis. The distribution of the time elapsing between the date of HIV diagnosis and the date of first determination of CD4 (considered to be the date of linkage to care) was calculated among new HIV diagnoses in 2010 in the seven Autonomous Regions participating, where data on date of CD4 count was available. Linkage to care was considered «correct» if done within three months after diagnosis. Factors associated to correct linkage to care were estimated using logistic regression. A total of 1769 new HIV diagnoses were included. Of them, 83.1% had evidence of linkage to care within a year, and 75.7% were linked within three months after diagnosis. Being an injectable drug user (IDU) was the only factor inversely associated with linkage to care within 3 months (OR = 0.3; 95% CI: 0.2-0.6). In Spain linkage to care after HIV diagnosis is good, but there is still room for improvement, especially among IDUs. Copyright © 2013 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

The evolutionary history of Drosophila buzzatii. XXXII. Linkage disequilibrium between allozymes and chromosome inversions in two colonizing populations.

PubMed

Betrán, E; Quezada-Díaz, J E; Ruiz, A; Santos, M; Fontdevila, A

1995-02-01

Chromosome polymorphism in Drosophila buzzatii is under selection but the genes responsible for the effect of the inversions of fitness are unknown. On the other hand, there is evidence for selection on several allozyme loci but the presence of paracentric inversions on the second chromosome, where most of the polymorphic loci are located, complicates the interpretation. Studies of the associations between allozymes and inversions are thus necessary to help understand the effect of selection at both the chromosomal and allozymic level. Until now this kind of information has only been available in D. buzzatii for two loci, Est-1 and Est-2, in Australian populations. Here we describe the genetic constitution of two Old World populations, Carboneras and Colera. Emphasis has been placed on the analysis of the linkage disequilibria between the second chromosome arrangements and three allozyme loci, Est-2, Pept-2 and Aldox, located on this chromosome. In addition, the recombination frequencies between the loci, and between the loci and the inversion breakpoints, have been estimated and a genetic map of the three loci has been produced. The two populations differ in allele and arrangement frequencies, as well as in the pattern of one-locus disequilibria. Est-2 and Aldox are associated with the second chromosome arrangements in both populations. On the other hand, Pept-2 is associated with the inversions in Colera but not in Carboneras. The gametic associations among the three loci are discussed taking into account the position of these loci on the chromosome map and the lack of recombination in the heterokaryotypes.

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

The Impact of Accelerating Faster than Exponential Population Growth on Genetic Variation

PubMed Central

Reppell, Mark; Boehnke, Michael; Zöllner, Sebastian

2014-01-01

Current human sequencing projects observe an abundance of extremely rare genetic variation, suggesting recent acceleration of population growth. To better understand the impact of such accelerating growth on the quantity and nature of genetic variation, we present a new class of models capable of incorporating faster than exponential growth in a coalescent framework. Our work shows that such accelerated growth affects only the population size in the recent past and thus large samples are required to detect the models’ effects on patterns of variation. When we compare models with fixed initial growth rate, models with accelerating growth achieve very large current population sizes and large samples from these populations contain more variation than samples from populations with constant growth. This increase is driven almost entirely by an increase in singleton variation. Moreover, linkage disequilibrium decays faster in populations with accelerating growth. When we instead condition on current population size, models with accelerating growth result in less overall variation and slower linkage disequilibrium decay compared to models with exponential growth. We also find that pairwise linkage disequilibrium of very rare variants contains information about growth rates in the recent past. Finally, we demonstrate that models of accelerating growth may substantially change estimates of present-day effective population sizes and growth times. PMID:24381333

The impact of accelerating faster than exponential population growth on genetic variation.

PubMed

Reppell, Mark; Boehnke, Michael; Zöllner, Sebastian

2014-03-01

Current human sequencing projects observe an abundance of extremely rare genetic variation, suggesting recent acceleration of population growth. To better understand the impact of such accelerating growth on the quantity and nature of genetic variation, we present a new class of models capable of incorporating faster than exponential growth in a coalescent framework. Our work shows that such accelerated growth affects only the population size in the recent past and thus large samples are required to detect the models' effects on patterns of variation. When we compare models with fixed initial growth rate, models with accelerating growth achieve very large current population sizes and large samples from these populations contain more variation than samples from populations with constant growth. This increase is driven almost entirely by an increase in singleton variation. Moreover, linkage disequilibrium decays faster in populations with accelerating growth. When we instead condition on current population size, models with accelerating growth result in less overall variation and slower linkage disequilibrium decay compared to models with exponential growth. We also find that pairwise linkage disequilibrium of very rare variants contains information about growth rates in the recent past. Finally, we demonstrate that models of accelerating growth may substantially change estimates of present-day effective population sizes and growth times.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 wasmore » 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.« less

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.

A systematic retrieval analysis of secondary eclipse spectra. III. Diagnosing chemical disequilibrium in planetary atmospheres

DOE Office of Scientific and Technical Information (OSTI.GOV)

Line, Michael R.; Yung, Yuk L., E-mail: mrl@gps.caltech.edu

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 themore » 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.« less

Precise Estimation of Allele Frequencies of Single-Nucleotide Polymorphisms by a Quantitative SSCP Analysis of Pooled DNA

PubMed Central

Sasaki, Tomonari; Tahira, Tomoko; Suzuki, Akari; Higasa, Koichiro; Kukita, Yoji; Baba, Shingo; Hayashi, Kenshi

2001-01-01

We show that single-nucleotide polymorphisms (SNPs) of moderate to high heterozygosity (minor allele frequencies >10%) can be efficiently detected, and their allele frequencies accurately estimated, by pooling the DNA samples and applying a capillary-based SSCP analysis. In this method, alleles are separated into peaks, and their frequencies can be reliably and accurately quantified from their peak heights (SD <1.8%). We found that as many as 40% of publicly available SNPs that were analyzed by this method have widely differing allele frequency distributions among groups of different ethnicity (parents of Centre d'Etude Polymorphisme Humaine families vs. Japanese individuals). These results demonstrate the effectiveness of the present pooling method in the reevaluation of candidate SNPs that have been collected by examination of limited numbers of individuals. The method should also serve as a robust quantitative technique for studies in which a precise estimate of SNP allele frequencies is essential—for example, in linkage disequilibrium analysis. PMID:11083945

Identification of Genetic Loci Associated with Quality Traits in Almond via Association Mapping

PubMed Central

Font i Forcada, Carolina; Oraguzie, Nnadozie; Reyes-Chin-Wo, Sebastian; Espiau, Maria Teresa; Socias i Company, Rafael; Fernández i Martí, Angel

2015-01-01

To design an appropriate association study, we need to understand population structure and the structure of linkage disequilibrium within and among populations as well as in different regions of the genome in an organism. In this study, we have used a total of 98 almond accessions, from five continents located and maintained at the Centro de Investigación y Tecnología Agroalimentaria de Aragón (CITA; Spain), and 40 microsatellite markers. Population structure analysis performed in ‘Structure’ grouped the accessions into two principal groups; the Mediterranean (Western-Europe) and the non-Mediterranean, with K = 3, being the best fit for our data. There was a strong subpopulation structure with linkage disequilibrium decaying with increasing genetic distance resulting in lower levels of linkage disequilibrium between more distant markers. A significant impact of population structure on linkage disequilibrium in the almond cultivar groups was observed. The mean r2 value for all intra-chromosomal loci pairs was 0.040, whereas, the r2 for the inter-chromosomal loci pairs was 0.036. For analysis of association between the markers and phenotypic traits, five models comprising both general linear models and mixed linear models were selected to test the marker trait associations. The mixed linear model (MLM) approach using co-ancestry values from population structure and kinship estimates (K model) as covariates identified a maximum of 16 significant associations for chemical traits and 12 for physical traits. This study reports for the first time the use of association mapping for determining marker-locus trait associations in a world-wide almond germplasm collection. It is likely that association mapping will have the most immediate and largest impact on the tier of crops such as almond with the greatest economic value. PMID:26111146

Identification of Genetic Loci Associated with Quality Traits in Almond via Association Mapping.

PubMed

Font i Forcada, Carolina; Oraguzie, Nnadozie; Reyes-Chin-Wo, Sebastian; Espiau, Maria Teresa; Socias i Company, Rafael; Fernández i Martí, Angel

2015-01-01

To design an appropriate association study, we need to understand population structure and the structure of linkage disequilibrium within and among populations as well as in different regions of the genome in an organism. In this study, we have used a total of 98 almond accessions, from five continents located and maintained at the Centro de Investigación y Tecnología Agroalimentaria de Aragón (CITA; Spain), and 40 microsatellite markers. Population structure analysis performed in 'Structure' grouped the accessions into two principal groups; the Mediterranean (Western-Europe) and the non-Mediterranean, with K = 3, being the best fit for our data. There was a strong subpopulation structure with linkage disequilibrium decaying with increasing genetic distance resulting in lower levels of linkage disequilibrium between more distant markers. A significant impact of population structure on linkage disequilibrium in the almond cultivar groups was observed. The mean r2 value for all intra-chromosomal loci pairs was 0.040, whereas, the r2 for the inter-chromosomal loci pairs was 0.036. For analysis of association between the markers and phenotypic traits, five models comprising both general linear models and mixed linear models were selected to test the marker trait associations. The mixed linear model (MLM) approach using co-ancestry values from population structure and kinship estimates (K model) as covariates identified a maximum of 16 significant associations for chemical traits and 12 for physical traits. This study reports for the first time the use of association mapping for determining marker-locus trait associations in a world-wide almond germplasm collection. It is likely that association mapping will have the most immediate and largest impact on the tier of crops such as almond with the greatest economic value.

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.

DNA Commission of the International Society for Forensic Genetics (ISFG): Guidelines on the use of X-STRs in kinship analysis.

PubMed

Tillmar, Andreas O; Kling, Daniel; Butler, John M; Parson, Walther; Prinz, Mechthild; Schneider, Peter M; Egeland, Thore; Gusmão, Leonor

2017-07-01

Forensic genetic laboratories perform an increasing amount of genetic analyses of the X chromosome, in particular to solve complex cases of kinship analysis. For some biological relationships X-chromosomal markers can be more informative than autosomal markers, and there are a large number of markers, methods and databases that have been described for forensic use. Due to their particular mode of inheritance, and their physical location on a single chromosome, some specific considerations are required when estimating the weight of evidence for X-chromosomal marker DNA data. The DNA Commission of the International Society for Forensic Genetics (ISFG) hereby presents guidelines and recommendations for the use of X-chromosomal markers in kinship analysis with a special focus on the biostatistical evaluation. Linkage and linkage disequilibrium (association of alleles) are of special importance for such evaluations and these concepts and the implications for likelihood calculations are described in more detail. Furthermore it is important to use appropriate computer software that accounts for linkage and linkage disequilibrium among loci, as well as for mutations. Even though some software exist, there is still a need for further improvement of dedicated software. Copyright © 2017 Elsevier B.V. All rights reserved.

Analysis of the linkage between rain and flood regime and its application to regional flood frequency estimation

NASA Astrophysics Data System (ADS)

Cunderlik, Juraj M.; Burn, Donald H.

2002-04-01

Improving techniques of flood frequency estimation at ungauged sites is one of the foremost goals of contemporary hydrology. River flood regime is a resultant reflection of a composite catchment hydrologic response to flood producing processes. In this sense the process of identifying homogeneous pooling groups can be plausibly based on catchment similarity in flood regime. Unfortunately the application of any pooling approach that is based on flood regime is restricted to gauged sites. Because flood regime can be markedly determined by rainfall regime, catchment similarity in rainfall regime can be an alternative option for identifying flood frequency pooling groups. An advantage of such a pooling approach is that rainfall data are usually spatially and temporary more abundant than flood data and the approach can also be applied at ungauged sites. Therefore in this study we have quantified the linkage between rainfall and flood regime and explored the appropriateness of substituting rainfall regime for flood regime in regional pooling schemes. Two different approaches to describing rainfall regime similarity using tools of directional statistics have been tested and used for evaluation of the potential of rainfall regime for identification of hydrologically homogeneous pooling groups. The outputs were compared to an existing pooling framework adopted in the Flood Estimation Handbook. The results demonstrate that regional pooling based on rainfall regime information leads to a high number of initially homogeneous groups and seems to be a sound pooling alternative for catchments with a close linkage between rain and flood regimes.

Y-chromosome specific alleles and haplotypes in European and Asian populations: linkage disequilibrium and geographic diversity.

PubMed

Mitchell, R J; Earl, L; Fricke, B

1997-10-01

Variation on the Y chromosome may permit our understanding the evolution of the human paternal lineage and male gene flow. This study reports upon the distribution and non random association of alleles at four Y-chromosome specific loci in four populations, three Caucasoid (Italian, Greek and Slav) and one Asian. The markers include insertion/deletion (p12f), point mutation (92R7 and pY alpha I), and repeat sequence (p21A1) polymorphisms. Our data confirm that the p12f/TaqI 8 kb allele is a Caucasoid marker and that Asians are monomorphic at three of the loci (p12f, 92R7, and pY alpha I). The alleles at 92R7 and pY alpha I were found to be in complete disequilibrium in Europeans. Y-haplotype diversity was highly significant between Asians and all three European groups (P < 0.001), but the Greeks and Italians were also significantly different with respect to some alleles and haplotypes (P < 0.02). We find strong evidence that the p12f/TaqI 8 kb allele may have arisen only once, as a deletion event, and, additionally, that the present-day frequency distribution of Y chromosomes carrying the p12f/8 kb allele suggests that it may have been spread by colonising sea-faring peoples from the Near East, possibly the Phoenicians, rather than by expansion of Neolithic farmers into continental Europe. The p12f deletion is the key marker of a unique Y chromosome, found only in Caucasians to date, labelled 'Mediterranean' and this further increases the level of Y-chromosome diversity seen among Caucasoids when compared to the other major population groups.

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

No association detected between a D{sub 3} receptor gene-expressed variant and schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rothschild, L.G.; Badner, J.; Cravchik, A.

1996-04-09

A missense polymorphism (glycine to serine) in the first exon of the dopamine D{sub 3} (DRD3) gene was examined in a sib-pairs schizophrenia collection by the transmission test for linkage disequilibrium (TDT). No association due to linkage disequilibrium was detected using TDT. Additionally, no evidence for excess homozygosity was found. 26 refs., 3 tabs.

Probabilistic record linkage

PubMed Central

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

2016-01-01

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

Improving record linkage performance in the presence of missing linkage data.

PubMed

Ong, Toan C; Mannino, Michael V; Schilling, Lisa M; Kahn, Michael G

2014-12-01

Existing record linkage methods do not handle missing linking field values in an efficient and effective manner. The objective of this study is to investigate three novel methods for improving the accuracy and efficiency of record linkage when record linkage fields have missing values. By extending the Fellegi-Sunter scoring implementations available in the open-source Fine-grained Record Linkage (FRIL) software system we developed three novel methods to solve the missing data problem in record linkage, which we refer to as: Weight Redistribution, Distance Imputation, and Linkage Expansion. Weight Redistribution removes fields with missing data from the set of quasi-identifiers and redistributes the weight from the missing attribute based on relative proportions across the remaining available linkage fields. Distance Imputation imputes the distance between the missing data fields rather than imputing the missing data value. Linkage Expansion adds previously considered non-linkage fields to the linkage field set to compensate for the missing information in a linkage field. We tested the linkage methods using simulated data sets with varying field value corruption rates. The methods developed had sensitivity ranging from .895 to .992 and positive predictive values (PPV) ranging from .865 to 1 in data sets with low corruption rates. Increased corruption rates lead to decreased sensitivity for all methods. These new record linkage algorithms show promise in terms of accuracy and efficiency and may be valuable for combining large data sets at the patient level to support biomedical and clinical research. Copyright © 2014 Elsevier Inc. All rights reserved.

Age-Dependent Association between Pulmonary Tuberculosis and Common TOX Variants in the 8q12–13 Linkage Region

PubMed Central

Grant, Audrey V.; El Baghdadi, Jamila; Sabri, Ayoub; El Azbaoui, Safa; Alaoui-Tahiri, Kebir; Abderrahmani Rhorfi, Ismail; Gharbaoui, Yasser; Abid, Ahmed; Benkirane, Majid; Raharimanga, Vaomalala; Richard, Vincent; Orlova, Marianna; Boland, Anne; Migaud, Mélanie; Okada, Satoshi; Nolan, Daniel K.; Bustamante, Jacinta; Barreiro, Luis B.; Schurr, Erwin; Boisson-Dupuis, Stephanie; Rasolofo, Voahangy; Casanova, Jean-Laurent; Abel, Laurent

2013-01-01

Only a small fraction of individuals infected with Mycobacterium tuberculosis develop clinical tuberculosis (TB) in their lifetime. Genetic epidemiological evidence suggests a genetic determinism of pulmonary TB (PTB), but the molecular basis of genetic predisposition to PTB remains largely unknown. We used a positional-cloning approach to carry out ultrafine linkage-disequilibrium mapping of a previously identified susceptibility locus in chromosomal region 8q12–13 by genotyping 3,216 SNPs in a family-based Moroccan sample including 286 offspring with PTB. We observed 44 PTB-associated SNPs (p < 0.01), which were genotyped in an independent set of 317 cases and 650 controls from Morocco. A single signal, consisting of two correlated SNPs close to TOX, rs1568952 and rs2726600 (combined p = 1.1 × 10−5 and 9.2 × 10−5, respectively), was replicated. Stronger evidence of association was found in individuals who developed PTB before the age of 25 years (combined p for rs1568952 = 4.4 × 10−8; odds ratio of PTB for AA versus AG/GG = 3.09 [1.99–4.78]). The association with rs2726600 (p = 0.04) was subsequently replicated in PTB-affected subjects under 25 years in a study of 243 nuclear families from Madagascar. Stronger evidence of replication in Madagascar was obtained for additional SNPs in strong linkage disequilibrium with the two initial SNPs (p = 0.003 for rs2726597), further confirming the signal. We thus identified around rs1568952 and rs2726600 a cluster of SNPs strongly associated with early-onset PTB in Morocco and Madagascar. SNP rs2726600 is located in a transcription-factor binding site in the 3′ region of TOX, and further functional explorations will focus on CD4 T lymphocytes. PMID:23415668

Modeling haplotype block variation using Markov chains.

PubMed

Greenspan, G; Geiger, D

2006-04-01

Models of background variation in genomic regions form the basis of linkage disequilibrium mapping methods. In this work we analyze a background model that groups SNPs into haplotype blocks and represents the dependencies between blocks by a Markov chain. We develop an error measure to compare the performance of this model against the common model that assumes that blocks are independent. By examining data from the International Haplotype Mapping project, we show how the Markov model over haplotype blocks is most accurate when representing blocks in strong linkage disequilibrium. This contrasts with the independent model, which is rendered less accurate by linkage disequilibrium. We provide a theoretical explanation for this surprising property of the Markov model and relate its behavior to allele diversity.

Modeling Haplotype Block Variation Using Markov Chains

PubMed Central

Greenspan, G.; Geiger, D.

2006-01-01

Models of background variation in genomic regions form the basis of linkage disequilibrium mapping methods. In this work we analyze a background model that groups SNPs into haplotype blocks and represents the dependencies between blocks by a Markov chain. We develop an error measure to compare the performance of this model against the common model that assumes that blocks are independent. By examining data from the International Haplotype Mapping project, we show how the Markov model over haplotype blocks is most accurate when representing blocks in strong linkage disequilibrium. This contrasts with the independent model, which is rendered less accurate by linkage disequilibrium. We provide a theoretical explanation for this surprising property of the Markov model and relate its behavior to allele diversity. PMID:16361244

Evidence of linkage and association on chromosome 20 for late-onset Alzheimer disease.

PubMed

Goddard, Katrina A B; Olson, Jane M; Payami, Haydeh; van der Voet, Monique; Kuivaniemi, Helena; Tromp, Gerard

2004-06-01

Recently, we reported evidence of linkage on chromosome 20 for Alzheimer disease (AD) using a novel statistical approach to incorporate covariates (e.g., age, ApoE genotype) into the analysis. These results suggest that very elderly subjects (>85 years), and individuals who carry an epsilon2 allele at the ApoE locus are more likely to be linked to this candidate region. The region on chromosome 20 includes a strong candidate gene, cystatin C (CST3), which has previously been associated with AD in case-control studies. We investigated these findings further by genotyping additional markers to narrow the candidate region, and to identify evidence of linkage disequilibrium as additional support for a susceptibility locus on chromosome 20. We selected 43 elderly sibships (89 subjects) from the NIMH AD Genetics Initiative based on current age older than 84 years, and identified 129 unrelated control subjects who were older than 84 years from the Oregon Brain Aging Study to conduct linkage and association studies in this region. Fourteen additional markers were evaluated, including 4 markers located within or near CST3. We narrowed the candidate region on chromosome 20 to an 11.8-cM region between markers D20S174 and D20S471, which includes the CST3 candidate gene. In addition, we observed evidence of association for markers located near the CST3 candidate gene, with P values between 0.002 and 0.08 for two-locus haplotypes. These results support the presence of a susceptibility locus for AD in the vicinity of CST3 for very elderly subjects with AD.

An AFLP genetic linkage map of pacific abalone ( Haliotis discus hannai)

NASA Astrophysics Data System (ADS)

Qi, Li; Yanhong, Xu; Ruihai, Yu; Akihiro, Kijima

2007-07-01

A genetic linkage map of Pacific abalone ( Haliotis discus hannai) was constructed using AFLP markers based on a two-way pseudo-testeross strategy in a full-sib family. With 33 primer combinations, a total of 455 markers (225 from the female parent and 230 from the male parent) segregated in a 1:1 ratio, corresponding to DNA polymorphism: heterozygous in one parent and null in the other. The female framework map consisted of 174 markers distributed in 18 linkage groups, equivalent to the H. discus hannai haploid chromosome number, and spanning a total length of 2031.4 cM, with an average interval of 13.0 cM between adjacent markers. The male framework map consisted of 195 markers mapped on 19 linkage groups, spanning a total length of 2273.4 cM, with an average spacing of 12.9 cM between adjacent markers. The estimated coverage for the framework linkage maps was 81.2% for the female and 82.1% for the male, on the basis of two estimates of genome length. Fifty-two markers (11.4%) remained unlinked. The level of segregation distortion observed in this cross was 20.4%. These linkage maps will serve as a starting point for linkage studies in the Pacific abalone with potential application for marker-assisted selection in breeding programs.

Some methods for blindfolded record linkage.

PubMed

Churches, Tim; Christen, Peter

2004-06-28

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. 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. 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. Although the protocols described in this paper are not unconditionally secure, they do suggest the

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

The transmission/disequilibrium test and parental-genotype reconstruction: the reconstruction-combined transmission/ disequilibrium test.

PubMed Central

Knapp, M

1999-01-01

Spielman and Ewens recently proposed a method for testing a marker for linkage with a disease, which combines data from families with and without information on parental genotypes. For some families without parental-genotype information, it may be possible to reconstruct missing parental genotypes from the genotypes of their offspring. The treatment of such a reconstructed family as if parental genotypes have been typed, however, can introduce bias. In the present study, a new method is presented that employs parental-genotype reconstruction and corrects for the biases resulting from reconstruction. The results of an application of this method to a real data set and of a simulation study suggest that this approach may increase the power to detect linkage. PMID:10053021

The role of the GABRA2 polymorphism in multiplex alcohol dependence families with minimal comorbidity: within-family association and linkage analyses.

PubMed

Matthews, Abigail G; Hoffman, Eric K; Zezza, Nicholas; Stiffler, Scott; Hill, Shirley Y

2007-09-01

The genes encoding the gamma-aminobutyric acid(A) (GABA(A)) receptor have been the focus of several recent studies investigating the genetic etiology of alcohol dependence. Analyses of multiplex families found a particular gene, GABRA2, to be highly associated with alcohol dependence, using within-family association tests and other methods. Results were confirmed in three case-control studies. The objective of this study was to investigate the GABRA2 gene in another collection of multiplex families. Analyses were based on phenotypic and genotypic data available for 330 individuals from 65 bigenerational pedigrees with a total of 232 alcohol-dependent subjects. A proband pair of same-sex siblings meeting Diagnostic and Statistical Manual of Mental Disorders, Third Edition, criteria for alcohol dependence was required for entry of a family into the study. One member of the proband pair was identified while in treatment for alcohol dependence. Linkage and association of GABRA2 and alcohol dependence were evaluated using SIBPAL (a nonparametric linkage package) and both the Pedigree Disequilibrium Test and the Family-Based Association Test, respectively. We find no evidence of a relationship between GABRA2 and alcohol dependence. Linkage analyses exhibited no linkage using affected/affected, affected/unaffected, and unaffected/unaffected sib pairs (all p's < .13). There was no evidence of a within-family association (all p's > .39). Comorbidity may explain why our results differ from those in the literature. The presence of primary drug dependence and/or other psychiatric disorders is minimal in our pedigrees, although several of the other previously published multiplex family analyses exhibit a greater degree of comorbidity.

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

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.

SNP Discovery and Linkage Map Construction in Cultivated Tomato

PubMed Central

Shirasawa, Kenta; Isobe, Sachiko; Hirakawa, Hideki; Asamizu, Erika; Fukuoka, Hiroyuki; Just, Daniel; Rothan, Christophe; Sasamoto, Shigemi; Fujishiro, Tsunakazu; Kishida, Yoshie; Kohara, Mitsuyo; Tsuruoka, Hisano; Wada, Tsuyuko; Nakamura, Yasukazu; Sato, Shusei; Tabata, Satoshi

2010-01-01

Few intraspecific genetic linkage maps have been reported for cultivated tomato, mainly because genetic diversity within Solanum lycopersicum is much less than that between tomato species. Single nucleotide polymorphisms (SNPs), the most abundant source of genomic variation, are the most promising source of polymorphisms for the construction of linkage maps for closely related intraspecific lines. In this study, we developed SNP markers based on expressed sequence tags for the construction of intraspecific linkage maps in tomato. Out of the 5607 SNP positions detected through in silico analysis, 1536 were selected for high-throughput genotyping of two mapping populations derived from crosses between ‘Micro-Tom’ and either ‘Ailsa Craig’ or ‘M82’. A total of 1137 markers, including 793 out of the 1338 successfully genotyped SNPs, along with 344 simple sequence repeat and intronic polymorphism markers, were mapped onto two linkage maps, which covered 1467.8 and 1422.7 cM, respectively. The SNP markers developed were then screened against cultivated tomato lines in order to estimate the transferability of these SNPs to other breeding materials. The molecular markers and linkage maps represent a milestone in the genomics and genetics, and are the first step toward molecular breeding of cultivated tomato. Information on the DNA markers, linkage maps, and SNP genotypes for these tomato lines is available at http://www.kazusa.or.jp/tomato/. PMID:21044984

Tests of linkage and/or association of the LEPR gene polymorphisms with obesity phenotypes in Caucasian nuclear families.

PubMed

Liu, Yong-Jun; Rocha-Sanchez, Sonia M S; Liu, Peng-Yuan; Long, Ji-Rong; Lu, Yan; Elze, Leo; Recker, Robert R; Deng, Hong-Wen

2004-04-13

Genetic variations in the leptin receptor (LEPR) gene have been conceived to affect body weight in general populations. In this study, using the tests implemented in the statistical package QTDT, we evaluated association and/or linkage of the LEPR gene with obesity phenotypes in a large sample comprising 1,873 subjects from 405 Caucasian nuclear families. Obesity phenotypes tested include body mass index (BMI), fat mass, percentage fat mass (PFM), and lean mass, with the latter three measured by dual-energy X-ray absorptiometry (DXA). Three single nucleotide polymorphisms (SNPs), namely Lys109Arg (A/G), Lys656Asn (G/C), Pro1019Pro (G/A), in the LEPR gene were analyzed. Significant linkage disequilibrium (0.394 < or = |D'| < or = 0.688, P < 0.001) was observed between pairs of the three SNPs. No significant population stratification was found for any SNP/phenotype. In single-locus analyses, evidence of association was observed for Lys656Asn with lean mass (P = 0.002) and fat mass (P = 0.015). The contribution of this polymorphism to the phenotypic variation of lean mass and fat mass was 2.63% and 1.15%, respectively. Subjects carrying allele G at the Lys656Asn site had, on average, 3.16% higher lean mass and 2.71% higher fat mass than those without it. In the analyses for haplotypes defined by the three SNPs, significant associations were detected between haplotype GCA (P = 0.005) and lean mass. In addition, marginally significant evidence of association was observed for this haplotype with fat mass (P = 0.012). No statistically significant linkage was found, largely due to the limited power of the linkage approach to detect small genetic effects in our data sets. Our results suggest that the LEPR gene polymorphisms contribute to variation in obesity phenotypes.

Linking environmental filtering and disequilibrium to biogeography with a community climate framework.

PubMed

Blonder, Benjamin; Nogués-Bravo, David; Borregaard, Michael K; Donoghue, John C; Jørgensen, Peter M; Kraft, Nathan J B; Lessard, Jean-Philippe; Morueta-Holme, Naia; Sandel, Brody; Svenning, Jens-Christian; Violle, Cyrille; Rahbek, Carsten; Enquist, Brian J

2015-04-01

We present a framework to measure the strength of environmental filtering and disequilibrium of the species composition of a local community across time, relative to past, current, and future climates. We demonstrate the framework by measuring the impact of climate change on New World forests, integrating data for climate niches of more than 14000 species, community composition of 471 New World forest plots, and observed climate across the most recent glacial-interglacial interval. We show that a majority of communities have species compositions that are strongly filtered and are more in equilibrium with current climate than random samples from the regional pool. Variation in the level of current community disequilibrium can be predicted from Last Glacial Maximum climate and will increase with near-future climate change.

Multilocus patterns of polymorphism and selection across the X chromosome of Caenorhabditis remanei.

PubMed

Cutter, Asher D

2008-03-01

Natural selection and neutral processes such as demography, mutation, and gene conversion all contribute to patterns of polymorphism within genomes. Identifying the relative importance of these varied components in evolution provides the principal challenge for population genetics. To address this issue in the nematode Caenorhabditis remanei, I sampled nucleotide polymorphism at 40 loci across the X chromosome. The site-frequency spectrum for these loci provides no evidence for population size change, and one locus presents a candidate for linkage to a target of balancing selection. Selection for codon usage bias leads to the non-neutrality of synonymous sites, and despite its weak magnitude of effect (N(e)s approximately 0.1), is responsible for profound patterns of diversity and divergence in the C. remanei genome. Although gene conversion is evident for many loci, biased gene conversion is not identified as a significant evolutionary process in this sample. No consistent association is observed between synonymous-site diversity and linkage-disequilibrium-based estimators of the population recombination parameter, despite theoretical predictions about background selection or widespread genetic hitchhiking, but genetic map-based estimates of recombination are needed to rigorously test for a diversity-recombination relationship. Coalescent simulations also illustrate how a spurious correlation between diversity and linkage-disequilibrium-based estimators of recombination can occur, due in part to the presence of unbiased gene conversion. These results illustrate the influence that subtle natural selection can exert on polymorphism and divergence, in the form of codon usage bias, and demonstrate the potential of C. remanei for detecting natural selection from genomic scans of polymorphism.

Statistical manifestation of quantum correlations via disequilibrium

NASA Astrophysics Data System (ADS)

Pennini, F.; Plastino, A.

2017-12-01

The statistical notion of disequilibrium (D) was introduced by López-Ruiz, Mancini, and Calbet (LMC) (1995) [1] more than 20 years ago. D measures the amount of ;correlational structure; of a system. We wish to use D to analyze one of the simplest types of quantum correlations, those present in gaseous systems due to symmetry considerations. To this end we extend the LMC formalism to the grand canonical environment and show that D displays distinctive behaviors for simple gases, that allow for interesting insights into their structural properties.

Evolution of recombination in a constant environment

PubMed Central

Feldman, Marcus W.; Christiansen, Freddy B.; Brooks, Lisa D.

1980-01-01

The theory of evolution at a selectively neutral locus that controls the recombination between two major loci that are under selection is studied. If the major loci are at a stable equilibrium in linkage disequilibrium under selection and recombination, then a mutation at the modifier locus will increase in frequency when rare if and only if it decreases the recombination fraction. If the major loci are in disequilibrium at a balance between selection against deleterious alleles and mutation towards them, then two new phenomena are observed. First, a recombination increasing mutation will succeed if the disequilibrium is negative and the modifier is sufficiently tightly linked to the major loci. Second, depending on the strength of selection, even if the disequilibrium is negative, recombination reduction may occur for looser linkage between the major and modifier loci. PMID:16592864

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

Adjustment for survey non‐representativeness using record‐linkage: refined estimates of alcohol consumption by deprivation in Scotland

PubMed Central

Gorman, Emma; Leyland, Alastair H.; McCartney, Gerry; Katikireddi, Srinivasa Vittal; Rutherford, Lisa; Graham, Lesley; Robinson, Mark

2017-01-01

Abstract Background and aims Analytical approaches to addressing survey non‐participation bias typically use only demographic information to improve estimates. We applied a novel methodology which uses health information from data linkage to adjust for non‐representativeness. We illustrate the method by presenting adjusted alcohol consumption estimates for Scotland. Design Data on consenting respondents to the Scottish Health Surveys (SHeSs) 1995–2010 were linked confidentially to routinely collected hospital admission and mortality records. Synthetic observations representing non‐respondents were created using general population data. Multiple imputation was performed to compute adjusted alcohol estimates given a range of assumptions about the missing data. Adjusted estimates of mean weekly consumption were additionally calibrated to per‐capita alcohol sales data. Setting Scotland. Participants 13 936 male and 18 021 female respondents to the SHeSs 1995–2010, aged 20–64 years. Measurements Weekly alcohol consumption, non‐, binge‐ and problem‐drinking. Findings Initial adjustment for non‐response resulted in estimates of mean weekly consumption that were elevated by up to 17.8% [26.5 units (18.6–34.4)] compared with corrections based solely on socio‐demographic data [22.5 (17.7–27.3)]; other drinking behaviour estimates were little changed. Under more extreme assumptions the overall difference was up to 53%, and calibrating to sales estimates resulted in up to 88% difference. Increases were especially pronounced among males in deprived areas. Conclusions The use of routinely collected health data to reduce bias arising from survey non‐response resulted in higher alcohol consumption estimates among working‐age males in Scotland, with less impact for females. This new method of bias reduction can be generalized to other surveys to improve estimates of alternative harmful behaviours. PMID:28276110

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…

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.

Role for syn-eruptive plagioclase disequilibrium crystallisation in basaltic magma ascent dynamics

NASA Astrophysics Data System (ADS)

La Spina, Giuseppe; Burton, Mike; de'Michieli Vitturi, Mattia; Arzilli, Fabio

2017-04-01

Magma ascent dynamics in volcanic conduits play a key role in determining the eruptive style of a volcano. The lack of direct observations inside the conduit means that numerical conduit models, constrained with observational data, provide invaluable tools for quantitative insights into complex magma ascent dynamics. The highly nonlinear, interdependent processes involved in magma ascent dynamics require several simplifications when modelling their ascent. For example, timescales of magma ascent in conduit models are typically assumed to be much longer than crystallisation 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 crystallisation and exsolution processes are fundamental to our understanding of such disequilibria and ascent dynamics. Using observations from Mount Etna's 2001 eruption and a magma ascent model we are able to constrain timescales for crystallisation and exsolution processes. Our results show that plagioclase reaches equilibrium in 1-2 h, whereas ascent times were 1 h. Furthermore, we have related the amount of plagioclase in erupted products with the ascent dynamics of basaltic eruptions. We find that relatively high plagioclase content requires crystallisation in a shallow reservoir, whilst a low plagioclase content reflects a disequilibrium crystallisation occurring during a fast ascent from depth to the surface. Using these new constraints on disequilibrium plagioclase crystallisation we also reproduce observed crystal abundances for different basaltic eruptions: Etna 2002/2003, Stromboli 2007 (effusive eruption) and 1930 (paroxysm) and different Pu'u' O'o eruptions at Kilauea (episodes 49-53). Therefore, our results show that disequilibrium processes play a key role on the ascent dynamics of basaltic magmas and cannot be neglected when describing basaltic

The problem of estimating recent genetic connectivity in a changing world.

PubMed

Samarasin, Pasan; Shuter, Brian J; Wright, Stephen I; Rodd, F Helen

2017-02-01

Accurate understanding of population connectivity is important to conservation because dispersal can play an important role in population dynamics, microevolution, and assessments of extirpation risk and population rescue. Genetic methods are increasingly used to infer population connectivity because advances in technology have made them more advantageous (e.g., cost effective) relative to ecological methods. Given the reductions in wildlife population connectivity since the Industrial Revolution and more recent drastic reductions from habitat loss, it is important to know the accuracy of and biases in genetic connectivity estimators when connectivity has declined recently. Using simulated data, we investigated the accuracy and bias of 2 common estimators of migration (movement of individuals among populations) rate. We focused on the timing of the connectivity change and the magnitude of that change on the estimates of migration by using a coalescent-based method (Migrate-n) and a disequilibrium-based method (BayesAss). Contrary to expectations, when historically high connectivity had declined recently: (i) both methods over-estimated recent migration rates; (ii) the coalescent-based method (Migrate-n) provided better estimates of recent migration rate than the disequilibrium-based method (BayesAss); (iii) the coalescent-based method did not accurately reflect long-term genetic connectivity. Overall, our results highlight the problems with comparing coalescent and disequilibrium estimates to make inferences about the effects of recent landscape change on genetic connectivity among populations. We found that contrasting these 2 estimates to make inferences about genetic-connectivity changes over time could lead to inaccurate conclusions. © 2016 Society for Conservation Biology.

The benefits of data linkage for firefighter injury surveillance

PubMed Central

Widman, Shannon A; LeVasseur, Michael T; Tabb, Loni P

2018-01-01

Background While survey data are available for national estimates of fire events and firefighter fatalities, data on firefighter injury at the national and local levels remain incomplete and unreliable. Data linkage provides a vehicle to maximise case detection and deepen injury description for the US fire service. Methods By linking departmental Human Resources records, despatch data, workers' compensation and first reports of injury, researchers were able to describe reported non-fatal injuries to 3063 uniformed members of the Philadelphia Fire Department (PFD), for the period of 2005 through 2013. Results Among all four databases, the overall linkage rate was 56%. Among three of the four databases, the linkage rate was 88%. Because there was duplication of some variables among the datasets, we were able to deeply describe all the linked injuries in the master database. 45.5% of uniformed PFD members reported at least one injury during the study period. Strains, falls, burns and struck-by injuries were the most common causes. Burns resulted in the highest lost time claim payout, and strains accounted for the highest medical claim cost. More than 70% of injuries occurred in the first 15 years of experience. Discussion Data linkage provided three new benefits: (1) creation of a new variable—years of experience, (2) reduction of misclassification bias when determining cause of injury, leading to more accurate estimates of cost and (3) visualisation of injury rates when controlling for the number of fire department responses, allowing for the generation of hypotheses to investigate injury hot spots. PMID:28196830

Linkages: Effective Keys to Success.

ERIC Educational Resources Information Center

Tindall, Lloyd W.

1986-01-01

Discusses various elements of linkages: informal agreements; formal written agreements; making agreements work; the non-financial agreement; how linkages work at the elementary, secondary, and postsecondary levels in Wisconsin; mandated linkages; and the importance of linkages in the vocational education and training arena. (CT)

A Genetic Linkage Map of the Male Goat Genome

PubMed Central

Vaiman, D.; Schibler, L.; Bourgeois, F.; Oustry, A.; Amigues, Y.; Cribiu, E. P.

1996-01-01

This paper presents a first genetic linkage map of the goat genome. Primers derived from the flanking sequences of 612 bovine, ovine and goat microsatellite markers were gathered and tested for amplification with goat DNA under standardized PCR conditions. This screen made it possible to choose a set of 55 polymorphic markers that can be used in the three species and to define a panel of 223 microsatellites suitable for the goat. Twelve half-sib paternal goat families were then used to build a linkage map of the goat genome. The linkage analysis made it possible to construct a meiotic map covering 2300 cM, i.e., >80% of the total estimated length of the goat genome. Moreover, eight cosmids containing microsatellites were mapped by fluorescence in situ hybridization in goat and sheep. Together with 11 microsatellite-containing cosmids previously mapped in cattle (and supposing conservation of the banding pattern between this species and the goat) and data from the sheep map, these results made the orientation of 15 linkage groups possible. Furthermore, 12 coding sequences were mapped either genetically or physically, providing useful data for comparative mapping. PMID:8878693

Mercury flux from salt marsh sediments: Insights from a comparison between 224Ra/228Th disequilibrium and core incubation methods

NASA Astrophysics Data System (ADS)

Shi, Xiangming; Mason, Robert P.; Charette, Matthew A.; Mazrui, Nashaat M.; Cai, Pinghe

2018-02-01

In aquatic environments, sediments are the main location of mercury methylation. Thus, accurate quantification of methylmercury (MeHg) fluxes at the sediment-water interface is vital to understanding the biogeochemical cycling of mercury, especially the toxic MeHg species, and their bioaccumulation. Traditional approaches, such as core incubations, are difficult to maintain at in-situ conditions during assays, leading to over/underestimation of benthic fluxes. Alternatively, the 224Ra/228Th disequilibrium method for tracing the transfer of dissolved substances across the sediment-water interface, has proven to be a reliable approach for quantifying benthic fluxes. In this study, the 224Ra/228Th disequilibrium and core incubation methods were compared to examine the benthic fluxes of both 224Ra and MeHg in salt marsh sediments of Barn Island, Connecticut, USA from May to August, 2016. The two methods were comparable for 224Ra but contradictory for MeHg. The radiotracer approach indicated that sediments were always the dominant source of both total mercury (THg) and MeHg. The core incubation method for MeHg produced similar results in May and August, but an opposite pattern in June and July, which suggested sediments were a sink of MeHg, contrary to the evidence of significant MeHg gradients between overlying water and porewater at the sediment-water interface. The potential reasons for such differences are discussed. Overall, we conclude that the 224Ra/228Th disequilibrium approach is preferred for estimating the benthic flux of MeHg and that sediment is indeed an important MeHg source in this marshland, and likely in other shallow coastal waters.

Adaptive transmission disequilibrium test for family trio design.

PubMed

Yuan, Min; Tian, Xin; Zheng, Gang; Yang, Yaning

2009-01-01

The transmission disequilibrium test (TDT) is a standard method to detect association using family trio design. It is optimal for an additive genetic model. Other TDT-type tests optimal for recessive and dominant models have also been developed. Association tests using family data, including the TDT-type statistics, have been unified to a class of more comprehensive and flexable family-based association tests (FBAT). TDT-type tests have high efficiency when the genetic model is known or correctly specified, but may lose power if the model is mis-specified. Hence tests that are robust to genetic model mis-specification yet efficient are preferred. Constrained likelihood ratio test (CLRT) and MAX-type test have been shown to be efficiency robust. In this paper we propose a new efficiency robust procedure, referred to as adaptive TDT (aTDT). It uses the Hardy-Weinberg disequilibrium coefficient to identify the potential genetic model underlying the data and then applies the TDT-type test (or FBAT for general applications) corresponding to the selected model. Simulation demonstrates that aTDT is efficiency robust to model mis-specifications and generally outperforms the MAX test and CLRT in terms of power. We also show that aTDT has power close to, but much more robust, than the optimal TDT-type test based on a single genetic model. Applications to real and simulated data from Genetic Analysis Workshop (GAW) illustrate the use of our adaptive TDT.

Quantifying sources of bias in longitudinal data linkage studies of child abuse and neglect: measuring impact of outcome specification, linkage error, and partial cohort follow-up.

PubMed

Parrish, Jared W; Shanahan, Meghan E; Schnitzer, Patricia G; Lanier, Paul; Daniels, Julie L; Marshall, Stephen W

2017-12-01

Health informatics projects combining statewide birth populations with child welfare records have emerged as a valuable approach to conducting longitudinal research of child maltreatment. The potential bias resulting from linkage misspecification, partial cohort follow-up, and outcome misclassification in these studies has been largely unexplored. This study integrated epidemiological survey and novel administrative data sources to establish the Alaska Longitudinal Child Abuse and Neglect Linkage (ALCANLink) project. Using these data we evaluated and quantified the impact of non-linkage misspecification and single source maltreatment ascertainment use on reported maltreatment risk and effect estimates. The ALCANLink project integrates the 2009-2011 Alaska Pregnancy Risk Assessment Monitoring System (PRAMS) sample with multiple administrative databases through 2014, including one novel administrative source to track out-of-state emigration. For this project we limited our analysis to the 2009 PRAMS sample. We report on the impact of linkage quality, cohort follow-up, and multisource outcome ascertainment on the incidence proportion of reported maltreatment before age 6 and hazard ratios of selected characteristics that are often available in birth cohort linkage studies of maltreatment. Failure to account for out-of-state emigration biased the incidence proportion by 12% (from 28.3% w to 25.2% w ), and the hazard ratio (HR) by as much as 33% for some risk factors. Overly restrictive linkage parameters biased the incidence proportion downwards by 43% and the HR by as much as 27% for some factors. Multi-source linkages, on the other hand, were of little benefit for improving reported maltreatment ascertainment. Using the ALCANLink data which included a novel administrative data source, we were able to observe and quantify bias to both the incidence proportion and HR in a birth cohort linkage study of reported child maltreatment. Failure to account for out

Privacy preserving interactive record linkage (PPIRL).

PubMed

Kum, Hye-Chung; Krishnamurthy, Ashok; Machanavajjhala, Ashwin; Reiter, Michael K; Ahalt, Stanley

2014-01-01

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. 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. 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. 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.

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

A first AFLP-Based Genetic Linkage Map for Brine Shrimp Artemia franciscana and Its Application in Mapping the Sex Locus

PubMed Central

De Vos, Stephanie; Bossier, Peter; Van Stappen, Gilbert; Vercauteren, Ilse; Sorgeloos, Patrick; Vuylsteke, Marnik

2013-01-01

We report on the construction of sex-specific linkage maps, the identification of sex-linked markers and the genome size estimation for the brine shrimp Artemia franciscana. Overall, from the analysis of 433 AFLP markers segregating in a 112 full-sib family we identified 21 male and 22 female linkage groups (2n = 42), covering 1,041 and 1,313 cM respectively. Fifteen putatively homologous linkage groups, including the sex linkage groups, were identified between the female and male linkage map. Eight sex-linked AFLP marker alleles were inherited from the female parent, supporting the hypothesis of a WZ–ZZ sex-determining system. The haploid Artemia genome size was estimated to 0.93 Gb by flow cytometry. The produced Artemia linkage maps provide the basis for further fine mapping and exploring of the sex-determining region and are a possible marker resource for mapping genomic loci underlying phenotypic differences among Artemia species. PMID:23469207

Power of a Labrador Retriever-Greyhound pedigree for linkage analysis of hip dysplasia and osteoarthritis.

PubMed

Todhunter, Rory J; Casella, George; Bliss, Stuart P; Lust, George; Williams, Alma Jo; Hamilton, Samuel; Dykes, Nathan L; Yeager, Amy E; Gilbert, Robert O; Burton-Wurster, Nancy I; Mellersh, Cathryn C; Acland, Gregory M

2003-04-01

To estimate the number of dogs required to find linkage to heritable traits of hip dysplasia in dogs from an experimental pedigree. 147 Labrador Retrievers, Greyhounds, and their crossbreed offspring. Labrador Retrievers with hip dysplasia were crossed with unaffected Greyhounds. Age at detection of femoral capital ossification, distraction index (DI), hip joint dorsolateral subluxation (DLS) score, and hip joint osteoarthritis (OA) were recorded. Power to find linkage of a single marker to a quantitative trait locus (QTL) controlling 100% of the variation in a dysplastic trait in the backcross dogs was determined. For the DI at the observed effect size, recombination fraction of 0.05, and heterozygosity of 0.75, 35 dogs in the backcross of the F1 to the Greyhound generation would yield linkage at a power of 0.8. For the DLS score, 35 dogs in the backcross to the Labrador Retriever generation would be required for linkage at the same power. For OSS, 45 dogs in the backcross to the founding Labrador Retrievers would yield linkage at the same power. Fewer dogs were projected to be necessary to find linkage to hip OA. Testing for linkage to the DLS at 4 loci simultaneously, each controlling 25% of the phenotypic variation, yielded an overall power of 0.7 CONCLUSIONS AND CLINICAL SIGNIFICANCE: Based on this conservative single-marker estimate, this pedigree has the requisite power to find microsatellites linked to susceptibility loci for hip dysplasia and hip OA by breeding a reasonable number of backcross dogs.

Exploiting Genome Structure in Association Analysis

PubMed Central

Kim, Seyoung

2014-01-01

Abstract A genome-wide association study involves examining a large number of single-nucleotide polymorphisms (SNPs) to identify SNPs that are significantly associated with the given phenotype, while trying to reduce the false positive rate. Although haplotype-based association methods have been proposed to accommodate correlation information across nearby SNPs that are in linkage disequilibrium, none of these methods directly incorporated the structural information such as recombination events along chromosome. In this paper, we propose a new approach called stochastic block lasso for association mapping that exploits prior knowledge on linkage disequilibrium structure in the genome such as recombination rates and distances between adjacent SNPs in order to increase the power of detecting true associations while reducing false positives. Following a typical linear regression framework with the genotypes as inputs and the phenotype as output, our proposed method employs a sparsity-enforcing Laplacian prior for the regression coefficients, augmented by a first-order Markov process along the sequence of SNPs that incorporates the prior information on the linkage disequilibrium structure. The Markov-chain prior models the structural dependencies between a pair of adjacent SNPs, and allows us to look for association SNPs in a coupled manner, combining strength from multiple nearby SNPs. Our results on HapMap-simulated datasets and mouse datasets show that there is a significant advantage in incorporating the prior knowledge on linkage disequilibrium structure for marker identification under whole-genome association. PMID:21548809

Generalized disequilibrium test for association in qualitative traits incorporating imprinting effects based on extended pedigrees.

PubMed

Li, Jian-Long; Wang, Peng; Fung, Wing Kam; Zhou, Ji-Yuan

2017-10-16

For dichotomous traits, the generalized disequilibrium test with the moment estimate of the variance (GDT-ME) is a powerful family-based association method. Genomic imprinting is an important epigenetic phenomenon and currently, there has been increasing interest of incorporating imprinting to improve the test power of association analysis. However, GDT-ME does not take imprinting effects into account, and it has not been investigated whether it can be used for association analysis when the effects indeed exist. In this article, based on a novel decomposition of the genotype score according to the paternal or maternal source of the allele, we propose the generalized disequilibrium test with imprinting (GDTI) for complete pedigrees without any missing genotypes. Then, we extend GDTI and GDT-ME to accommodate incomplete pedigrees with some pedigrees having missing genotypes, by using a Monte Carlo (MC) sampling and estimation scheme to infer missing genotypes given available genotypes in each pedigree, denoted by MCGDTI and MCGDT-ME, respectively. The proposed GDTI and MCGDTI methods evaluate the differences of the paternal as well as maternal allele scores for all discordant relative pairs in a pedigree, including beyond first-degree relative pairs. Advantages of the proposed GDTI and MCGDTI test statistics over existing methods are demonstrated by simulation studies under various simulation settings and by application to the rheumatoid arthritis dataset. Simulation results show that the proposed tests control the size well under the null hypothesis of no association, and outperform the existing methods under various imprinting effect models. The existing GDT-ME and the proposed MCGDT-ME can be used to test for association even when imprinting effects exist. For the application to the rheumatoid arthritis data, compared to the existing methods, MCGDTI identifies more loci statistically significantly associated with the disease. Under complete and incomplete

Disequilibrium dynamics in a Keynesian model with time delays

NASA Astrophysics Data System (ADS)

Gori, Luca; Guerrini, Luca; Sodini, Mauro

2018-05-01

The aim of this research is to analyse a Keynesian goods market closed economy by considering a continuous-time setup with fixed delays. The work compares dynamic results based on linear and nonlinear adjustment mechanisms through which the aggregate supply (production) reacts to a disequilibrium in the goods market and consumption depends on income at a preceding date. Both analytical and geometrical (stability switching curves) techniques are used to characterise the stability properties of the stationary equilibrium.

Use of modern tomato breeding germplasm for deciphering the genetic control of agronomical traits by Genome Wide Association study.

PubMed

Bauchet, Guillaume; Grenier, Stéphane; Samson, Nicolas; Bonnet, Julien; Grivet, Laurent; Causse, Mathilde

2017-05-01

A panel of 300 tomato accessions including breeding materials was built and characterized with >11,000 SNP. A population structure in six subgroups was identified. Strong heterogeneity in linkage disequilibrium and recombination landscape among groups and chromosomes was shown. GWAS identified several associations for fruit weight, earliness and plant growth. Genome-wide association studies (GWAS) have become a method of choice in quantitative trait dissection. First limited to highly polymorphic and outcrossing species, it is now applied in horticultural crops, notably in tomato. Until now GWAS in tomato has been performed on panels of heirloom and wild accessions. Using modern breeding materials would be of direct interest for breeding purpose. To implement GWAS on a large panel of 300 tomato accessions including 168 breeding lines, this study assessed the genetic diversity and linkage disequilibrium decay and revealed the population structure and performed GWA experiment. Genetic diversity and population structure analyses were based on molecular markers (>11,000 SNP) covering the whole genome. Six genetic subgroups were revealed and associated to traits of agronomical interest, such as fruit weight and disease resistance. Estimates of linkage disequilibrium highlighted the heterogeneity of its decay among genetic subgroups. Haplotype definition allowed a fine characterization of the groups and their recombination landscape revealing the patterns of admixture along the genome. Selection footprints showed results in congruence with introgressions. Taken together, all these elements refined our knowledge of the genetic material included in this panel and allowed the identification of several associations for fruit weight, plant growth and earliness, deciphering the genetic architecture of these complex traits and identifying several new loci useful for tomato breeding.

Isozyme variation and linkage in six conifer species

Treesearch

M. Thompson Conkle

1981-01-01

Isozymes of female gametophyte tissue were analyzed for allelic variation in knobcone, lodgepole, loblolly, Jeffrey, and sugar pines and in Douglas-fir. Linkage was studied in the five pines. The average number of alleles and average herozygosity per enzyme locus were estimated. Knobcone pine ranked lowest among the six species in number of alleles and average...

DXS10011: studies on structure, allele distribution in three populations and genetic linkage to further q-telomeric chromosome X markers.

PubMed

Hering, Sandra; Brundirs, Nicola; Kuhlisch, Eberhard; Edelmann, Jeanett; Plate, Ines; Benecke, Mark; Van, Pham Hung; Michael, Matthias; Szibor, Reinhard

2004-12-01

The hypervariable tetranucleotide STR polymorphism DXS10011 is a powerful marker for forensic purposes. Investigation of this STR led to an allele nomenclature which is in consensus with the ISFG recommendations. DXS10011 is located at Xq28 and genetically closely linked to DXS7423 and DXS8377 but is unlinked to HPRTB and more distant X-chromosomal STRs. DXS10011 is a very complex marker exhibiting some structural variants within alleles of identical length. Two types of repeat structure (regular and inter-alleles) are known and described as types A and B. Two SNPs which are in strong linkage disequilibrium to the different sequence types were found in the repeat flanking region. The type A sequence consists of a long stretch of uninterrupted homogenous repeats which is highly susceptible to slippage mutation during male meiosis.

Phylogeography of haplotypes of five microsatellites located in a low-recombination region of the X chromosome: studies worldwide and in Brazilian populations.

PubMed

Pereira, Rinaldo Wellerson; Pena, Sérgio D J

2006-01-01

We studied five microsatellites (DXS995, DXS8076, DXS8114, DXS1002 and DXS1050) located in a region of very low recombination rate in the long arm of the human X chromosome (Xq13.3-Xq21.3). No recombination was seen in 291 meioses in CEPH families. To test whether haplotypes composed of the five microsatellites could differentiate among distinct human continental populations, we studied an international panel containing 72 males from Africa, Europe, Asia and the America. Haplotypic diversity was very high within these groups and no haplotypes were shared among them. This led to the hope that we might be able to identify continent-specific lineages. However, in a median joining network there was no clear discrimination of the different continental groups. We then tested whether we could identify X chromosomal lineages from different continental origins in Brazilians. We typed 180 white Brazilians from four different geographical regions and examined their proportions of haplotype sharing with Africans, Asians, Europeans and Amerindians. No phylogeographical patterns emerged from the data. Moreover, there were several instances of the same haplotype being shared by many (and in one instance all) groups, suggesting that recombination might be occurring. We thus studied pairwise the level of linkage disequilibrium (LD) between the microsatellites. No detectable linkage disequilibrium between the most external loci DXS995 and DXS1050 was observed. Thus, even though recombination may be absent on short time spans, as seen in the CEPH pedigrees, on a long term basis it occurs often enough to dissipate all linkage disequilibrium. On the other hand, we observed very strong linkage disequilibrium between the pairs DXS995/DXS8076 and DXS1002/DXS8114, raising the possibility of resequencing the segment between them to identify single nucleotide polymorphisms (SNPs) in their intervals. The combination of X-linked microsatellites and SNPs in strong linkage disequilibrium might

The benefits of data linkage for firefighter injury surveillance.

PubMed

Widman, Shannon A; LeVasseur, Michael T; Tabb, Loni P; Taylor, Jennifer A

2018-02-01

While survey data are available for national estimates of fire events and firefighter fatalities, data on firefighter injury at the national and local levels remain incomplete and unreliable. Data linkage provides a vehicle to maximise case detection and deepen injury description for the US fire service. By linking departmental Human Resources records, despatch data, workers' compensation and first reports of injury, researchers were able to describe reported non-fatal injuries to 3063 uniformed members of the Philadelphia Fire Department (PFD), for the period of 2005 through 2013. Among all four databases, the overall linkage rate was 56%. Among three of the four databases, the linkage rate was 88%. Because there was duplication of some variables among the datasets, we were able to deeply describe all the linked injuries in the master database. 45.5% of uniformed PFD members reported at least one injury during the study period. Strains, falls, burns and struck-by injuries were the most common causes. Burns resulted in the highest lost time claim payout, and strains accounted for the highest medical claim cost. More than 70% of injuries occurred in the first 15 years of experience. Data linkage provided three new benefits: (1) creation of a new variable-years of experience, (2) reduction of misclassification bias when determining cause of injury, leading to more accurate estimates of cost and (3) visualisation of injury rates when controlling for the number of fire department responses, allowing for the generation of hypotheses to investigate injury hot spots. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Determining the linkage of disease-resistance genes to molecular markers: the LOD-SCORE method revisited with regard to necessary sample sizes.

PubMed

Hühn, M

1995-05-01

Some approaches to molecular marker-assisted linkage detection for a dominant disease-resistance trait based on a segregating F2 population are discussed. Analysis of two-point linkage is carried out by the traditional measure of maximum lod score. It depends on (1) the maximum-likelihood estimate of the recombination fraction between the marker and the disease-resistance gene locus, (2) the observed absolute frequencies, and (3) the unknown number of tested individuals. If one replaces the absolute frequencies by expressions depending on the unknown sample size and the maximum-likelihood estimate of recombination value, the conventional rule for significant linkage (maximum lod score exceeds a given linkage threshold) can be resolved for the sample size. For each sub-population used for linkage analysis [susceptible (= recessive) individuals, resistant (= dominant) individuals, complete F2] this approach gives a lower bound for the necessary number of individuals required for the detection of significant two-point linkage by the lod-score method.

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.

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.

Effects of the Ordering of Natural Selection and Population Regulation Mechanisms on Wright-Fisher Models

PubMed Central

He, Zhangyi; Beaumont, Mark; Yu, Feng

2017-01-01

We explore the effect of different mechanisms of natural selection on the evolution of populations for one- and two-locus systems. We compare the effect of viability and fecundity selection in the context of the Wright-Fisher model with selection under the assumption of multiplicative fitness. We show that these two modes of natural selection correspond to different orderings of the processes of population regulation and natural selection in the Wright-Fisher model. We find that under the Wright-Fisher model these two different orderings can affect the distribution of trajectories of haplotype frequencies evolving with genetic recombination. However, the difference in the distribution of trajectories is only appreciable when the population is in significant linkage disequilibrium. We find that as linkage disequilibrium decays the trajectories for the two different models rapidly become indistinguishable. We discuss the significance of these findings in terms of biological examples of viability and fecundity selection, and speculate that the effect may be significant when factors such as gene migration maintain a degree of linkage disequilibrium. PMID:28500051

Mitochondrial FAD-glycerophosphate dehydrogenase and G-protein-coupled inwardly rectifying K+ channel: No evidence for linkage in maturity-onset diabetes of the young or NIDDM.

PubMed

Warren-Perry, M G; Stoffel, M; Saker, P J; Zhang, Y; Brown, L J; MacDonald, M J; Turner, R C

1996-05-01

Two genes that have potentially important regulatory roles in insulin secretion are both located on chromosome 2q24.1. G-protein-coupled muscarinic potassium channel (GIRK1) is an inwardly rectifying K+ channel that helps to maintain the resting potential and excitability of cells. Mitochondrial FAD-linked glycerophosphate dehydrogenase (m-GDH) catalyzes a rate-limiting step of the glycerol phosphate shuttle in pancreatic islets. Reduced m-GDH activity has been demonstrated in islets isolated from diabetic subjects compared with islets from nondiabetic control subjects and from the diabetic GK rat. To study the relationship between these candidate genes and NIDDM, we have examined a simple tandem-repeat polymorphism (STRP) close to both the KCN J3 (GIRK1) locus and the m-GDH locus. In a linkage study of three maturity-onset diabetes of the young (MODY) pedigrees, not linked to MODY1, MODY2, or MODY3, a cumulative score of - 9.6 at a recombination fraction of theta = 0 excluded linkage. In a population-association study, no linkage disequilibrium for the STRP was found between 190 unselected NIDDM patients and 60 geographically and age-matched white nondiabetic subjects (chi2 = 1.51 on 3 df, P = 0.68). Thus, mutations involving the genes for GIRK1 or FAD-glycerophosphate dehydrogenase are unlikely to cause MODY, and a common mutation in either gene is unlikely to contribute to NIDDM in whites. These data do not exclude mutations in some families or other ethnic groups.

A model that helps explain Sr-isotope disequilibrium between feldspar phenocrysts and melt in large-volume silicic magma systems

USGS Publications Warehouse

Duffield, W.A.; Ruiz, J.

1998-01-01

Feldspar phenocrysts of silicic volcanic rocks are commonly in Sr-isotopic disequilibrium with groundmass. In some cases the feldspar is more radiogenic, and in others it is less radiogenic. Several explanations have been published previously, but none of these is able to accommodate both senses of disequilibrium. We present a model by which either more- or less-radiogenic feldspar (or even both within a single eruptive unit) can originate. The model requires a magma body open to interaction with biotite- and feldspar-bearing wall rock. Magma is incrementally contaminated as wall rock melts incongruently. Biotite preferentially melts first, followed by feldspar. Such melting behavior, which is supported by both field and experimental studies, first contaminates magma with a relatively radiogenic addition, followed by a less-radiogenic addition. Feldspar phenocrysts lag behind melt (groundmass of volcanic rock) in incorporating the influx of contaminant, thus resulting in Sr-isotopic disequilibrium between the crystals and melt. The sense of disequilibrium recorded in a volcanic rock depends on when eruption quenches the contamination process. This model is testable by isotopic fingerprinting of individual feldspar crystals. For a given set of geologic boundary conditions, specific core-to-rim Sr-isotopic profiles are expectable. Moreover, phenocrysts that nucleate at different times during the contamination process should record different and predictable parts of the history. Initial results of Sr-isotopic fingerprinting of sanidine phenocrysts from the Taylor Creek Rhyolite are consistent with the model. More tests of the model are desirable.Feldspar phenocrysts of silicic volcanic rocks are commonly in Sr-isotopic disequilibrium with groundmass. In some cases the feldspar is more radiogenic, and in others it is less radiogenic. Several explanations have been published previously, but none of these is able to accommodate both senses of disequilibrium. We present a

Multiple loci on 8q24 associated with prostate cancer susceptibility.

PubMed

Al Olama, Ali Amin; Kote-Jarai, Zsofia; Giles, Graham G; Guy, Michelle; Morrison, Jonathan; Severi, Gianluca; Leongamornlert, Daniel A; Tymrakiewicz, Malgorzata; Jhavar, Sameer; Saunders, Ed; Hopper, John L; Southey, Melissa C; Muir, Kenneth R; English, Dallas R; Dearnaley, David P; Ardern-Jones, Audrey T; Hall, Amanda L; O'Brien, Lynne T; Wilkinson, Rosemary A; Sawyer, Emma; Lophatananon, Artitaya; Horwich, Alan; Huddart, Robert A; Khoo, Vincent S; Parker, Christopher C; Woodhouse, Christopher J; Thompson, Alan; Christmas, Tim; Ogden, Chris; Cooper, Colin; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Eeles, Rosalind A; Easton, Douglas F

2009-10-01

Previous studies have identified multiple loci on 8q24 associated with prostate cancer risk. We performed a comprehensive analysis of SNP associations across 8q24 by genotyping tag SNPs in 5,504 prostate cancer cases and 5,834 controls. We confirmed associations at three previously reported loci and identified additional loci in two other linkage disequilibrium blocks (rs1006908: per-allele OR = 0.87, P = 7.9 x 10(-8); rs620861: OR = 0.90, P = 4.8 x 10(-8)). Eight SNPs in five linkage disequilibrium blocks were independently associated with prostate cancer susceptibility.

Heritability, linkage, and genetic associations of exercise treadmill test responses.

PubMed

Ingelsson, Erik; Larson, Martin G; Vasan, Ramachandran S; O'Donnell, Christopher J; Yin, Xiaoyan; Hirschhorn, Joel N; Newton-Cheh, Christopher; Drake, Jared A; Musone, Stacey L; Heard-Costa, Nancy L; Benjamin, Emelia J; Levy, Daniel; Atwood, Larry D; Wang, Thomas J; Kathiresan, Sekar

2007-06-12

The blood pressure (BP) and heart rate responses to exercise treadmill testing predict incidence of cardiovascular disease, but the genetic determinants of hemodynamic and chronotropic responses to exercise are largely unknown. We assessed systolic BP, diastolic BP, and heart rate during the second stage of the Bruce protocol and at the third minute of recovery in 2982 Framingham Offspring participants (mean age 43 years; 53% women). With use of residuals from multivariable models adjusted for clinical correlates of exercise treadmill testing responses, we estimated the heritability (variance-components methods), genetic linkage (multipoint quantitative trait analyses), and association with 235 single-nucleotide polymorphisms in 14 candidate genes selected a priori from neurohormonal pathways for their potential role in exercise treadmill testing responses. Heritability estimates for heart rate during exercise and during recovery were 0.32 and 0.34, respectively. Heritability estimates for BP variables during exercise were 0.25 and 0.26 (systolic and diastolic BP) and during recovery, 0.16 and 0.13 (systolic and diastolic BP), respectively. Suggestive linkage was found for systolic BP during recovery from exercise (locus 1q43-44, log-of-the-odds score 2.59) and diastolic BP during recovery from exercise (locus 4p15.3, log-of-the-odds score 2.37). Among 235 single-nucleotide polymorphisms tested for association with exercise treadmill testing responses, the minimum nominal probability value was 0.003, which was nonsignificant after adjustment for multiple testing. Hemodynamic and chronotropic responses to exercise are heritable and demonstrate suggestive linkage to select loci. Genetic mapping with newer approaches such as genome-wide association may yield novel insights into the physiological responses to exercise.

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

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.

Ecological disequilibrium drives insect pest and pathogen accumulation in non-native trees

PubMed Central

Burgess, Treena I.; Le Roux, Johannes J.; Richardson, David M.; Slippers, Bernard; Wingfield, Michael J.

2017-01-01

Abstract Non-native trees have become dominant components of many landscapes, including urban ecosystems, commercial forestry plantations, fruit orchards and as invasives in natural ecosystems. Often, these trees have been separated from their natural enemies (i.e. insects and pathogens) leading to ecological disequilibrium, that is, the immediate breakdown of historically co-evolved interactions once introduced into novel environments. Long-established, non-native tree plantations provide useful experiments to explore the dimensions of such ecological disequilibria. We quantify the status quo of non-native insect pests and pathogens catching up with their tree hosts (planted Acacia, Eucalyptus and Pinus species) in South Africa, and examine which native South African enemy species utilize these trees as hosts. Interestingly, pines, with no confamilial relatives in South Africa and the longest residence time (almost two centuries), have acquired only one highly polyphagous native pathogen. This is in contrast to acacias and eucalypts, both with many native and confamilial relatives in South Africa that have acquired more native pathogens. These patterns support the known role of phylogenetic relatedness of non-native and native floras in influencing the likelihood of pathogen shifts between them. This relationship, however, does not seem to hold for native insects. Native insects appear far more likely to expand their feeding habits onto non-native tree hosts than are native pathogens, although they are generally less damaging. The ecological disequilibrium conditions of non-native trees are deeply rooted in the eco-evolutionary experience of the host plant, co-evolved natural enemies and native organisms from the introduced range. We should expect considerable spatial and temporal variation in ecological disequilibrium conditions among non-native taxa, which can be significantly influenced by biosecurity and management practices. PMID:28013250

Uranium disequilibrium in groundwater: An isotope dilution approach in hydrologic investigations

USGS Publications Warehouse

Osmond, J.K.; Rydell, H.S.; Kaufman, M.I.

1968-01-01

The distribution and environmental disequilibrium patterns of naturally occurring uranium isotopes (U234 and U238) in waters of the Floridan aquifer suggest that variations in the ratios of isotopic activity and concentrations can be used quantitatively to evaluate mixing proportions of waters from differing sources. Uranium is probably unique in its potential for this approach, which seems to have general usefulness in hydrologic investigations.

Association of polymorphic variants of PTPN22, TNF and VDR genes in children with lupus nephritis: A study in Colombian family triads.

PubMed

Garavito, Gloria; Egea, Eduardo; Fang, Luis; Malagón, Clara; Olmos, Carlos; González, Luz; Guarnizo, Pilar; Aroca, Gustavo; López, Guillermo; Iglesias, Antonio

2017-06-01

Systemic lupus erythematosus is an autoimmune disease in which the severity varies according to race, sex and age of onset. This variation is also observed in the genetic markers associated with the disease, including PTPN22, VDR and TNF genes. The genetic stratification in different populations worldwide can influence the variability. To analyze the heritability of PTPN22, VDR and TNF genetic variants and their association with pediatric lupus nephritis in Colombian families. We conducted a family-based study including 46 triads (case, father and mother). The variants rs2476601 of PTPN22; rs361525 and rs1800629 of TNF, and TaqI [rs731236], ApaI [rs7975232], BsmI [rs1544410] and FokI [rs2228570] of VDR were genotyped by qPCR. The effects of overtransmission of the risk allele from parents to children and linkage disequilibrium at the VDR and TNF loci were estimated. We found that allele A of rs2476601 in PTPN22 was distributed among 8.69 % (n=16) of the parents and 19.5 % (n=18) of the cases; this allele was overtransmitted from parents to children 17 times more often than the G allele (p=0.028). TNF and VDR polymorphisms did not exhibit transmission disequilibrium. VDR TaqI, ApaI and BsmI variants exhibited linkage disequilibrium. These findings showed an association between the PTPN22 rs2476601 polymorphism and pediatric lupus nephritis due to its overtransmission in the group of families studied.

The effect of using genealogy-based haplotypes for genomic prediction.

PubMed

Edriss, Vahid; Fernando, Rohan L; Su, Guosheng; Lund, Mogens S; Guldbrandtsen, Bernt

2013-03-06

Genomic prediction uses two sources of information: linkage disequilibrium between markers and quantitative trait loci, and additive genetic relationships between individuals. One way to increase the accuracy of genomic prediction is to capture more linkage disequilibrium by regression on haplotypes instead of regression on individual markers. The aim of this study was to investigate the accuracy of genomic prediction using haplotypes based on local genealogy information. A total of 4429 Danish Holstein bulls were genotyped with the 50K SNP chip. Haplotypes were constructed using local genealogical trees. Effects of haplotype covariates were estimated with two types of prediction models: (1) assuming that effects had the same distribution for all haplotype covariates, i.e. the GBLUP method and (2) assuming that a large proportion (π) of the haplotype covariates had zero effect, i.e. a Bayesian mixture method. About 7.5 times more covariate effects were estimated when fitting haplotypes based on local genealogical trees compared to fitting individuals markers. Genealogy-based haplotype clustering slightly increased the accuracy of genomic prediction and, in some cases, decreased the bias of prediction. With the Bayesian method, accuracy of prediction was less sensitive to parameter π when fitting haplotypes compared to fitting markers. Use of haplotypes based on genealogy can slightly increase the accuracy of genomic prediction. Improved methods to cluster the haplotypes constructed from local genealogy could lead to additional gains in accuracy.

Linkage and association of haplotypes at the APOA1/C3/A4/A5 genecluster to familial combined hyperlipidemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Eichenbaum-Voline, Sophie; Olivier, Michael; Jones, Emma L.

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 datamore » 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.« less

Polymorphism and Divergence in Two Willow Species, Salix viminalis L. and Salix schwerinii E. Wolf

PubMed Central

Berlin, Sofia; Fogelqvist, Johan; Lascoux, Martin; Lagercrantz, Ulf; Rönnberg-Wästljung, Ann Christin

2011-01-01

We investigated species divergence, present and past gene flow, levels of nucleotide polymorphism, and linkage disequilibrium in two willows from the plant genus Salix. Salix belongs together with Populus to the Salicaceae family; however, most population genetic studies of Salicaceae have been performed in Populus, the model genus in forest biology. Here we present a study on two closely related willow species Salix viminalis and S. schwerinii, in which we have resequenced 33 and 32 nuclear gene segments representing parts of 18 nuclear loci in 24 individuals for each species. We used coalescent simulations and estimated the split time to around 600,000 years ago and found that there is currently limited gene flow between the species. Mean intronic nucleotide diversity across gene segments was slightly higher in S. schwerinii (πi = 0.00849) than in S. viminalis (πi = 0.00655). Compared with other angiosperm trees, the two willows harbor intermediate levels of silent polymorphisms. The decay of linkage disequilibrium was slower in S. viminalis compared with S. schwerinii, and we speculate that this is due to different demographic histories as S. viminalis has been partly domesticated in Europe. PMID:22384349

Improving estimates of genetic maps: a meta-analysis-based approach.

PubMed

Stewart, William C L

2007-07-01

Inaccurate genetic (or linkage) maps can reduce the power to detect linkage, increase type I error, and distort haplotype and relationship inference. To improve the accuracy of existing maps, I propose a meta-analysis-based method that combines independent map estimates into a single estimate of the linkage map. The method uses the variance of each independent map estimate to combine them efficiently, whether the map estimates use the same set of markers or not. As compared with a joint analysis of the pooled genotype data, the proposed method is attractive for three reasons: (1) it has comparable efficiency to the maximum likelihood map estimate when the pooled data are homogeneous; (2) relative to existing map estimation methods, it can have increased efficiency when the pooled data are heterogeneous; and (3) it avoids the practical difficulties of pooling human subjects data. On the basis of simulated data modeled after two real data sets, the proposed method can reduce the sampling variation of linkage maps commonly used in whole-genome linkage scans. Furthermore, when the independent map estimates are also maximum likelihood estimates, the proposed method performs as well as or better than when they are estimated by the program CRIMAP. Since variance estimates of maps may not always be available, I demonstrate the feasibility of three different variance estimators. Overall, the method should prove useful to investigators who need map positions for markers not contained in publicly available maps, and to those who wish to minimize the negative effects of inaccurate maps. Copyright 2007 Wiley-Liss, Inc.

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…

Impact of reduced marker set estimation of genomic relationship matrices on genomic selection for feed efficiency in Angus cattle.

PubMed

Rolf, Megan M; Taylor, Jeremy F; Schnabel, Robert D; McKay, Stephanie D; McClure, Matthew C; Northcutt, Sally L; Kerley, Monty S; Weaber, Robert L

2010-04-19

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 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. 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.

Forks in the road: choices in procedures for designing wildland linkages.

PubMed

Beier, Paul; Majka, Daniel R; Spencer, Wayne D

2008-08-01

Models are commonly used to identify lands that will best maintain the ability of wildlife to move between wildland blocks through matrix lands after the remaining matrix has become incompatible with wildlife movement. We offer a roadmap of 16 choices and assumptions that arise in designing linkages to facilitate movement or gene flow of focal species between 2 or more predefined wildland blocks. We recommend designing linkages to serve multiple (rather than one) focal species likely to serve as a collective umbrella for all native species and ecological processes, explicitly acknowledging untested assumptions, and using uncertainty analysis to illustrate potential effects of model uncertainty. Such uncertainty is best displayed to stakeholders as maps of modeled linkages under different assumptions. We also recommend modeling corridor dwellers (species that require more than one generation to move their genes between wildland blocks) differently from passage species (for which an individual can move between wildland blocks within a few weeks). We identify a problem, which we call the subjective translation problem, that arises because the analyst must subjectively decide how to translate measurements of resource selection into resistance. This problem can be overcome by estimating resistance from observations of animal movement, genetic distances, or interpatch movements. There is room for substantial improvement in the procedures used to design linkages robust to climate change and in tools that allow stakeholders to compare an optimal linkage design to alternative designs that minimize costs or achieve other conservation goals.

Data linkage to estimate the extent and distribution of occupational disease: new onset adult asthma in Alberta, Canada.

PubMed

Cherry, Nicola; Beach, Jeremy; Burstyn, Igor; Fan, Xiangning; Guo, Na; Kapur, Nitin

2009-11-01

Although occupational asthma is a well recognized and preventable disease, the numbers of cases presenting for compensation may be far lower than the true incidence. Workers' Compensation Board (WCB) claims for any reason 1995-2004 were linked to physician billing data. New onset adult asthma (NOAA) was defined as a billing for asthma (ICD-9 code of 493) in the 12 months prior to a WCB claim without asthma in the previous 3 years. Incidence was calculated by occupation, industry and, in a case-referent analysis, exposures estimated from an asthma specific job exposure matrix. There were 782,908 WCB eligible claims, with an incidence rate for NOAA of 1.6%: 23 occupations and 21 industries had a significantly increased risk. Isocyanates (OR 1.54: 95% CI 1.01-2.36) and exposure to mixed agricultural allergens (OR = 1.59: 95% CI 1.17-2.18) were related to NOAA overall, as were exposures to cleaning chemicals in men (OR = 1.91:95% CI 1.34-2.73). Estimates of the number of cases of occupational asthma suggested a range of 4% to about half for the proportion compensated. Data linkage of administrative records can demonstrate under-reporting of occupational asthma and indicate areas for prevention. (c) 2009 Wiley-Liss, Inc.

Insights into solar nebula formation of pyrrhotite from nanoscale disequilibrium phases produced by H2S sulfidation of Fe metal

DOE PAGES

Gainsforth, Z; Lauretta, DS; Tamura, N; ...

2017-09-01

© 2017 by Walter de Gruyter Berlin/Boston. Lauretta (2005) produced sulfide in the laboratory by exposing canonical nebular metal analogs to H 2 S gas under temperatures and pressures relevant to the formation of the Solar System. The resulting reactions produced a suite of sulfides and nanophase materials not visible at the microprobe scale, but which we have now analyzed by TEM for comparison with interplanetary dust samples and comet Wild 2 samples returned by the Stardust mission. We find the unexpected result that disequilibrium formation favors pyrrhotite over troilite and also produces minority schreibersite, daubréelite, barringerite, taenite, oldhamite, andmore » perryite at the metal-sulfide interface. TEM identification of nanophases and analysis of pyrrhotite superlattice reflections illuminate the formation pathway of disequilibrium sulfide. We discuss the conditions under which such disequilibrium can occur, and implications for formation of sulfide found in extraterrestrial materials.« less

A ddRAD Based Linkage Map of the Cultivated Strawberry, Fragaria xananassa

PubMed Central

Davik, Jahn; Sargent, Daniel James; Brurberg, May Bente; Lien, Sigbjørn; Kent, Matthew; Alsheikh, Muath

2015-01-01

The cultivated strawberry (Fragaria ×ananassa Duch.) is an allo-octoploid considered difficult to disentangle genetically due to its four relatively similar sub-genomic chromosome sets. This has been alleviated by the recent release of the strawberry IStraw90 whole genome genotyping array. However, array resolution relies on the genotypes used in the array construction and may be of limited general use. SNP detection based on reduced genomic sequencing approaches has the potential of providing better coverage in cases where the studied genotypes are only distantly related from the SNP array’s construction foundation. Here we have used double digest restriction-associated DNA sequencing (ddRAD) to identify SNPs in a 145 seedling F1 hybrid population raised from the cross between the cultivars Sonata (♀) and Babette (♂). A linkage map containing 907 markers which spanned 1,581.5 cM across 31 linkage groups representing the 28 chromosomes of the species. Comparing the physical span of the SNP markers with the F. vesca genome sequence, the linkage groups resolved covered 79% of the estimated 830 Mb of the F. ×ananassa genome. Here, we have developed the first linkage map for F. ×ananassa using ddRAD and show that this technique and other related techniques are useful tools for linkage map development and downstream genetic studies in the octoploid strawberry. PMID:26398886

Linkages and Interactions Analysis of Major Effect Drought Grain Yield QTLs in Rice.

PubMed

Vikram, Prashant; Swamy, B P Mallikarjuna; Dixit, Shalabh; Trinidad, Jennylyn; Sta Cruz, Ma Teresa; Maturan, Paul C; Amante, Modesto; Kumar, Arvind

2016-01-01

Quantitative trait loci conferring high grain yield under drought in rice are important genomic resources for climate resilient breeding. Major and consistent drought grain yield QTLs usually co-locate with flowering and/or plant height QTLs, which could be due to either linkage or pleiotropy. Five mapping populations used for the identification of major and consistent drought grain yield QTLs underwent multiple-trait, multiple-interval mapping test (MT-MIM) to estimate the significance of pleiotropy effects. Results indicated towards possible linkages between the drought grain yield QTLs with co-locating flowering and/or plant height QTLs. Linkages of days to flowering and plant height were eliminated through a marker-assisted breeding approach. Drought grain yield QTLs also showed interaction effects with flowering QTLs. Drought responsiveness of the flowering locus on chromosome 3 (qDTY3.2) has been revealed through allelic analysis. Considering linkage and interaction effects associated with drought QTLs, a comprehensive marker-assisted breeding strategy was followed to develop rice genotypes with improved grain yield under drought stress.

Can Network Linkage Effects Determine Return? Evidence from Chinese Stock Market.

PubMed

Qiao, Haishu; Xia, Yue; Li, Ying

2016-01-01

This study used the dynamic conditional correlations (DCC) method to identify the linkage effects of Chinese stock market, and further detected the influence of network linkage effects on magnitude of security returns across different industries. Applying two physics-derived techniques, the minimum spanning tree and the hierarchical tree, we analyzed the stock interdependence within the network of the China Securities Index (CSI) industry index basket. We observed that that obvious linkage effects existed among stock networks. CII and CCE, CAG and ITH as well as COU, CHA and REI were confirmed as the core nodes in the three different networks respectively. We also investigated the stability of linkage effects by estimating the mean correlations and mean distances, as well as the normalized tree length of these indices. In addition, using the GMM model approach, we found inter-node influence within the stock network had a pronounced effect on stock returns. Our results generally suggested that there appeared to be greater clustering effect among the indexes belonging to related industrial sectors than those of diverse sectors, and network comovement was significantly affected by impactive financial events in the reality. Besides, stocks that were more central within the network of stock market usually had higher returns for compensation because they endured greater exposure to correlation risk.

[MapDraw: a microsoft excel macro for drawing genetic linkage maps based on given genetic linkage data].

PubMed

Liu, Ren-Hu; Meng, Jin-Ling

2003-05-01

MAPMAKER is one of the most widely used computer software package for constructing genetic linkage maps.However, the PC version, MAPMAKER 3.0 for PC, could not draw the genetic linkage maps that its Macintosh version, MAPMAKER 3.0 for Macintosh,was able to do. Especially in recent years, Macintosh computer is much less popular than PC. Most of the geneticists use PC to analyze their genetic linkage data. So a new computer software to draw the same genetic linkage maps on PC as the MAPMAKER for Macintosh to do on Macintosh has been crying for. Microsoft Excel,one component of Microsoft Office package, is one of the most popular software in laboratory data processing. Microsoft Visual Basic for Applications (VBA) is one of the most powerful functions of Microsoft Excel. Using this program language, we can take creative control of Excel, including genetic linkage map construction, automatic data processing and more. In this paper, a Microsoft Excel macro called MapDraw is constructed to draw genetic linkage maps on PC computer based on given genetic linkage data. Use this software,you can freely construct beautiful genetic linkage map in Excel and freely edit and copy it to Word or other application. This software is just an Excel format file. You can freely copy it from ftp://211.69.140.177 or ftp://brassica.hzau.edu.cn and the source code can be found in Excel's Visual Basic Editor.

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. Copyright (c) 2007 Wiley-Liss, Inc.

Equilibrium and disequilibrium chemistry of adiabatic, solar-composition planetary atmospheres

NASA Technical Reports Server (NTRS)

Lewis, J. S.

1976-01-01

The impact of atmospheric and cloud-structure models on the nonequilibrium chemical behavior of the atmospheres of the Jovian planets is discussed. Quantitative constraints on photochemical, lightning, and charged-particle production of organic matter and chromophores are emphasized whenever available. These considerations imply that inorganic chromophore production is far more important than that of organic chromophores, and that lightning is probably a negligibly significant process relative to photochemistry on Jupiter. Production of complex molecules by gas-phase disequilibrium processes on Saturn, Uranus, and Neptune is severely limited by condensation of even simple intermediates.

Estimating the risk of crime and victimisation in people with intellectual disability: a data-linkage study.

PubMed

Nixon, Margaret; Thomas, Stuart D M; Daffern, Michael; Ogloff, James R P

2017-05-01

People with intellectual disability (PWID) appear more likely to be victims and perpetrators of crime. However, extant evidence pertaining to these risks is limited by methodological weaknesses and the absence of consistent operational definitions. This research aimed to estimate the prevalence of criminal histories and victimisation using a large, well-defined sample of PWID. A case-linkage study was conducted comprising 2220 PWID registered with disability services in Victoria, Australia, whose personal details were linked with a state-wide police database. Criminal charges and reports of victimisation were compared to a non-disabled community comparison sample (n = 2085). PWID were at increased risk of having a history of criminal charges, particularly for violent and sexual offences. Although the non-disabled comparison group had a greater risk of criminal victimisation overall, PWID had a greatly increased risk of sexual and violent crime victimisation. PWID are at increased risk of victimisation and perpetration of violent and sexual crimes. Risk of sex offending and victimisation is particularly elevated, and signalling the need for specialised interventions to prevent offending and to ensure victims is assisted with access to justice, support, and treatment.

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

Microseismic Event Relocation and Focal Mechanism Estimation Based on PageRank Linkage

NASA Astrophysics Data System (ADS)

Aguiar, A. C.; Myers, S. C.

2017-12-01

Microseismicity associated with enhanced geothermal systems (EGS) is key in understanding how subsurface stimulation can modify stress, fracture rock, and increase permeability. Large numbers of microseismic events are commonly associated with hydroshearing an EGS, making data mining methods useful in their analysis. We focus on PageRank, originally developed as Google's search engine, and subsequently adapted for use in seismology to detect low-frequency earthquakes by linking events directly and indirectly through cross-correlation (Aguiar and Beroza, 2014). We expand on this application by using PageRank to define signal-correlation topology for micro-earthquakes from the Newberry Volcano EGS in Central Oregon, which has been stimulated two times using high-pressure fluid injection. We create PageRank signal families from both data sets and compare these to the spatial and temporal proximity of associated earthquakes. PageRank families are relocated using differential travel times measured by waveform cross-correlation (CC) and the Bayesloc approach (Myers et al., 2007). Prior to relocation events are loosely clustered with events at a distance from the cluster. After relocation, event families are found to be tightly clustered. Indirect linkage of signals using PageRank is a reliable way to increase the number of events confidently determined to be similar, suggesting an efficient and effective grouping of earthquakes with similar physical characteristics (ie. location, focal mechanism, stress drop). We further explore the possibility of using PageRank families to identify events with similar relative phase polarities and estimate focal mechanisms following Shelly et al. (2016) method, where CC measurements are used to determine individual polarities within event clusters. Given a positive result, PageRank might be a useful tool in adaptive approaches to enhance production at well-instrumented geothermal sites. Prepared by LLNL under Contract DE-AC52-07NA27344

The effect of using genealogy-based haplotypes for genomic prediction

PubMed Central

2013-01-01

Background Genomic prediction uses two sources of information: linkage disequilibrium between markers and quantitative trait loci, and additive genetic relationships between individuals. One way to increase the accuracy of genomic prediction is to capture more linkage disequilibrium by regression on haplotypes instead of regression on individual markers. The aim of this study was to investigate the accuracy of genomic prediction using haplotypes based on local genealogy information. Methods A total of 4429 Danish Holstein bulls were genotyped with the 50K SNP chip. Haplotypes were constructed using local genealogical trees. Effects of haplotype covariates were estimated with two types of prediction models: (1) assuming that effects had the same distribution for all haplotype covariates, i.e. the GBLUP method and (2) assuming that a large proportion (π) of the haplotype covariates had zero effect, i.e. a Bayesian mixture method. Results About 7.5 times more covariate effects were estimated when fitting haplotypes based on local genealogical trees compared to fitting individuals markers. Genealogy-based haplotype clustering slightly increased the accuracy of genomic prediction and, in some cases, decreased the bias of prediction. With the Bayesian method, accuracy of prediction was less sensitive to parameter π when fitting haplotypes compared to fitting markers. Conclusions Use of haplotypes based on genealogy can slightly increase the accuracy of genomic prediction. Improved methods to cluster the haplotypes constructed from local genealogy could lead to additional gains in accuracy. PMID:23496971

Can Network Linkage Effects Determine Return? Evidence from Chinese Stock Market

PubMed Central

Qiao, Haishu; Xia, Yue; Li, Ying

2016-01-01

This study used the dynamic conditional correlations (DCC) method to identify the linkage effects of Chinese stock market, and further detected the influence of network linkage effects on magnitude of security returns across different industries. Applying two physics-derived techniques, the minimum spanning tree and the hierarchical tree, we analyzed the stock interdependence within the network of the China Securities Index (CSI) industry index basket. We observed that that obvious linkage effects existed among stock networks. CII and CCE, CAG and ITH as well as COU, CHA and REI were confirmed as the core nodes in the three different networks respectively. We also investigated the stability of linkage effects by estimating the mean correlations and mean distances, as well as the normalized tree length of these indices. In addition, using the GMM model approach, we found inter-node influence within the stock network had a pronounced effect on stock returns. Our results generally suggested that there appeared to be greater clustering effect among the indexes belonging to related industrial sectors than those of diverse sectors, and network comovement was significantly affected by impactive financial events in the reality. Besides, stocks that were more central within the network of stock market usually had higher returns for compensation because they endured greater exposure to correlation risk. PMID:27257816

Cytonuclear disequilibrium and genetic drift in a natural population of ponderosa pine.

PubMed Central

Latta, R G; Linhart, Y B; Mitton, J B

2001-01-01

We measured the cytonuclear disequilibrium between 11 nuclear allozyme loci and both mitochondrial and chloroplast DNA haplotypes in a natural population of ponderosa pine (Pinus ponderosa, Laws). Three allozyme loci showed significant associations with mtDNA variation, while two other loci showed significant association with cpDNA. However, the absolute number of individuals involved in any of the associations was small, such that in none of the nuclear-organellar combinations was the difference between observed and expected numbers >11 individuals. Patterns of association were not consistent across loci or organellar genomes, suggesting that they are not the result of mating patterns, which would act uniformly on all loci. This pattern of disequilibria is consistent with the action of genetic drift and with existing knowledge of the structure of this population and thus does not imply the action of other evolutionary processes. The overall magnitude (normalized disequilibrium) of associations was greater for maternally inherited mtDNA than for paternally inherited cpDNA, though this difference was neither large nor significant. Such significant disequilibria involving the paternally inherited organelle indicate that not only are there a limited number of seed parents, but the effective number of pollen parents is also limited. PMID:11404345

Ultra-high density intra-specific genetic linkage maps accelerate identification of functionally relevant molecular tags governing important agronomic traits in chickpea

PubMed Central

Kujur, Alice; Upadhyaya, Hari D.; Shree, Tanima; Bajaj, Deepak; Das, Shouvik; Saxena, Maneesha S.; Badoni, Saurabh; Kumar, Vinod; Tripathi, Shailesh; Gowda, C. L. L.; Sharma, Shivali; Singh, Sube; Tyagi, Akhilesh K.; Parida, Swarup K.

2015-01-01

We discovered 26785 and 16573 high-quality SNPs differentiating two parental genotypes of a RIL mapping population using reference desi and kabuli genome-based GBS assay. Of these, 3625 and 2177 SNPs have been integrated into eight desi and kabuli chromosomes, respectively in order to construct ultra-high density (0.20–0.37 cM) intra-specific chickpea genetic linkage maps. One of these constructed high-resolution genetic map has potential to identify 33 major genomic regions harbouring 35 robust QTLs (PVE: 17.9–39.7%) associated with three agronomic traits, which were mapped within <1 cM mean marker intervals on desi chromosomes. The extended LD (linkage disequilibrium) decay (~15 cM) in chromosomes of genetic maps have encouraged us to use a rapid integrated approach (comparative QTL mapping, QTL-region specific haplotype/LD-based trait association analysis, expression profiling and gene haplotype-based association mapping) rather than a traditional QTL map-based cloning method to narrow-down one major seed weight (SW) robust QTL region. It delineated favourable natural allelic variants and superior haplotype-containing one seed-specific candidate embryo defective gene regulating SW in chickpea. The ultra-high-resolution genetic maps, QTLs/genes and alleles/haplotypes-related genomic information generated and integrated strategy for rapid QTL/gene identification developed have potential to expedite genomics-assisted breeding applications in crop plants, including chickpea for their genetic enhancement. PMID:25942004

Estimation of genealogical coancestry in plant species using a pedigree reconstruction algorithm and application to an oil palm breeding population.

PubMed

Cros, David; Sánchez, Leopoldo; Cochard, Benoit; Samper, Patrick; Denis, Marie; Bouvet, Jean-Marc; Fernández, Jesús

2014-04-01

Explicit pedigree reconstruction by simulated annealing gave reliable estimates of genealogical coancestry in plant species, especially when selfing rate was lower than 0.6, using a realistic number of markers. Genealogical coancestry information is crucial in plant breeding to estimate genetic parameters and breeding values. The approach of Fernández and Toro (Mol Ecol 15:1657-1667, 2006) to estimate genealogical coancestries from molecular data through pedigree reconstruction was limited to species with separate sexes. In this study it was extended to plants, allowing hermaphroditism and monoecy, with possible selfing. Moreover, some improvements were made to take previous knowledge on the population demographic history into account. The new method was validated using simulated and real datasets. Simulations showed that accuracy of estimates was high with 30 microsatellites, with the best results obtained for selfing rates below 0.6. In these conditions, the root mean square error (RMSE) between the true and estimated genealogical coancestry was small (<0.07), although the number of ancestors was overestimated and the selfing rate could be biased. Simulations also showed that linkage disequilibrium between markers and departure from the Hardy-Weinberg equilibrium in the founder population did not affect the efficiency of the method. Real oil palm data confirmed the simulation results, with a high correlation between the true and estimated genealogical coancestry (>0.9) and a low RMSE (<0.08) using 38 markers. The method was applied to the Deli oil palm population for which pedigree data were scarce. The estimated genealogical coancestries were highly correlated (>0.9) with the molecular coancestries using 100 markers. Reconstructed pedigrees were used to estimate effective population sizes. In conclusion, this method gave reliable genealogical coancestry estimates. The strategy was implemented in the software MOLCOANC 3.0.

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.

Association of HLA-A and Non-Classical HLA Class I Alleles

PubMed Central

Carlini, Federico; Ferreira, Virginia; Buhler, Stéphane; Tous, Audrey; Eliaou, Jean-François; René, Céline; Chiaroni, Jacques; Picard, Christophe; Di Cristofaro, Julie

2016-01-01

The HLA-A locus is surrounded by HLA class Ib genes: HLA-E, HLA-H, HLA-G and HLA-F. HLA class Ib molecules are involved in immuno-modulation with a central role for HLA-G and HLA-E, an emerging role for HLA-F and a yet unknown function for HLA-H. Thus, the principal objective of this study was to describe the main allelic associations between HLA-A and HLA-H, -G, -F and -E. Therefore, HLA-A, -E, -G, -H and -F coding polymorphisms, as well as HLA-G UnTranslated Region haplotypes (referred to as HLA-G UTRs), were explored in 191 voluntary blood donors. Allelic frequencies, Global Linkage Disequilibrium (GLD), Linkage Disequilibrium (LD) for specific pairs of alleles and two-loci haplotype frequencies were estimated. We showed that HLA-A, HLA-H, HLA-F, HLA-G and HLA-G UTRs were all in highly significant pairwise GLD, in contrast to HLA-E. Moreover, HLA-A displayed restricted associations with HLA-G UTR and HLA-H. We also confirmed several associations that were previously found to have a negative impact on transplantation outcome. In summary, our results suggest complex functional and clinical implications of the HLA-A genetic region. PMID:27701438

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…

Who Are the Okinawans? Ancestry, Genome Diversity, and Implications for the Genetic Study of Human Longevity From a Geographically Isolated Population

PubMed Central

Hsueh, Wen-Chi; He, Qimei; Willcox, D. Craig; Nievergelt, Caroline M.; Donlon, Timothy A.; Kwok, Pui-Yan; Suzuki, Makoto; Willcox, Bradley J.

2014-01-01

Isolated populations have advantages for genetic studies of longevity from decreased haplotype diversity and long-range linkage disequilibrium. This permits smaller sample sizes without loss of power, among other utilities. Little is known about the genome of the Okinawans, a potential population isolate, recognized for longevity. Therefore, we assessed genetic diversity, structure, and admixture in Okinawans, and compared this with Caucasians, Chinese, Japanese, and Africans from HapMap II, genotyped on the same Affymetrix GeneChip Human Mapping 500K array. Principal component analysis, haplotype coverage, and linkage disequilibrium decay revealed a distinct Okinawan genome—more homogeneity, less haplotype diversity, and longer range linkage disequilibrium. Population structure and admixture analyses utilizing 52 global reference populations from the Human Genome Diversity Cell Line Panel demonstrated that Okinawans clustered almost exclusively with East Asians. Sibling relative risk (λs) analysis revealed that siblings of Okinawan centenarians have 3.11 times (females) and 3.77 times (males) more likelihood of centenarianism. These findings suggest that Okinawans are genetically distinct and share several characteristics of a population isolate, which are prone to develop extreme phenotypes (eg, longevity) from genetic drift, natural selection, and population bottlenecks. These data support further exploration of genetic influence on longevity in the Okinawans. PMID:24444611

Sexual selection and sex linkage.

PubMed

Kirkpatrick, Mark; Hall, David W

2004-04-01

Some animal groups, such as birds, seem prone to extreme forms of sexual selection. One contributing factor may be sex linkage of genes affecting male displays and female preferences. Here we show that sex linkage can have substantial effects on the genetic correlation between these traits and consequently for Fisher's runaway and the good-genes mechanisms of sexual selection. Under some kinds of sex linkage (e.g. Z-linked preferences), a runaway is more likely than under autosomal inheritance, while under others (e.g., X-linked preferences and autosomal displays), the good-genes mechanism is particularly powerful. These theoretical results suggest empirical tests based on the comparative method.

Bubble fusion: Preliminary estimates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krakowski, R.A.

1995-02-01

The collapse of a gas-filled bubble in disequilibrium (i.e., internal pressure {much_lt} external pressure) can occur with a significant focusing of energy onto the entrapped gas in the form of pressure-volume work and/or acoustical shocks; the resulting heating can be sufficient to cause ionization and the emission of atomic radiations. The suggestion that extreme conditions necessary for thermonuclear fusion to occur may be possible has been examined parametrically in terms of the ratio of initial bubble pressure relative to that required for equilibrium. In this sense, the disequilibrium bubble is viewed as a three-dimensional ``sling shot`` that is ``loaded`` tomore » an extent allowed by the maximum level of disequilibrium that can stably be achieved. Values of this disequilibrium ratio in the range 10{sup {minus}5}--10{sup {minus}6} are predicted by an idealized bubble-dynamics model as necessary to achieve conditions where nuclear fusion of deuterium-tritium might be observed. Harmonic and aharmonic pressurizations/decompressions are examined as means to achieve the required levels of disequilibrium required to create fusion conditions. A number of phenomena not included in the analysis reported herein could enhance or reduce the small levels of nuclear fusions predicted.« less

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

USDA-ARS?s Scientific Manuscript database

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...

The quality of Indigenous identification in administrative health data in Australia: insights from studies using data linkage

PubMed Central

2012-01-01

Background Missing or incorrect Indigenous status in health records hinders monitoring of Indigenous health indicators. Linkage of administrative data has been used to improve the ascertainment of Indigenous status. Data linkage was pioneered in Western Australia (WA) and is now being used in other Australian states. This systematic review appraises peer-reviewed Australian studies that used data linkage to elucidate the impact of under-ascertainment of Indigenous status on health indicators. Methods A PubMed search identified eligible studies that used Australian linked data to interrogate Indigenous identification using more than one identifier and interrogated the impact of the different identifiers on estimation of Indigenous health indicators. Results Eight papers were included, five from WA and three from New South Wales (NSW). The WA papers included a self-identified Indigenous community cohort and showed improved identification in hospital separation data after 2000. In CVD hospitalised patients (2000–05), under-identification was greater in urban residents, older people and socially more advantaged Indigenous people, with varying algorithms giving different estimates of under-count. Age-standardised myocardial infarction incidence rates (2000–2004) increased by about 10%-15% with improved identification. Under-ascertainment of Indigenous identification overestimated secular improvements in life expectancy and mortality whereas correcting infectious disease notifications resulted in lower Indigenous/ non-Indigenous rate ratios. NSW has a history of poor Indigenous identification in administrative data systems, but the NSW papers confirmed the usefulness of data linkage for improving Indigenous identification and the potential for very different estimates of Indigenous disease indicators depending upon the algorithm used for identification. Conclusions Under-identification of Indigenous status must be addressed in health analyses concerning Indigenous

Linkage map of the honey bee, Apis mellifera, based on RAPD markers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hunt, G.J.; Page, R.E. Jr.

A linkage map was constructed for the honey bee based on the segregation of 365 random amplified polymorphic DNA (RAPD) markers in haploid male progeny of a single female bee. The X locus for sex determination and genes for black body color and malate dehydrogenase were mapped to separate linkage groups. RAPD markers were very efficient for mapping, with an average of about 2.8 loci mapped for each 10-nucleotide primer that was used in polymerase chain reactions. The mean interval size between markers on the map was 9.1 cM. The map covered 3110 cM of linked markers on 26 linkagemore » groups. We estimate the total genome size to be {approximately}3450 cM. The size of the map indicated a very high recombination rate for the honey bee. The relationship of physical to genetic distance was estimated at 52 kb/cM, suggesting that map-based cloning of genes will be feasible for this species. 71 refs., 6 figs., 1 tab.« less

Case-Deletion Diagnostics for Maximum Likelihood Multipoint Quantitative Trait Locus Linkage Analysis

PubMed Central

Mendoza, Maria C.B.; Burns, Trudy L.; Jones, Michael P.

2009-01-01

Objectives Case-deletion diagnostic methods are tools that allow identification of influential observations that may affect parameter estimates and model fitting conclusions. The goal of this paper was to develop two case-deletion diagnostics, the exact case deletion (ECD) and the empirical influence function (EIF), for detecting outliers that can affect results of sib-pair maximum likelihood quantitative trait locus (QTL) linkage analysis. Methods Subroutines to compute the ECD and EIF were incorporated into the maximum likelihood QTL variance estimation components of the linkage analysis program MAPMAKER/SIBS. Performance of the diagnostics was compared in simulation studies that evaluated the proportion of outliers correctly identified (sensitivity), and the proportion of non-outliers correctly identified (specificity). Results Simulations involving nuclear family data sets with one outlier showed EIF sensitivities approximated ECD sensitivities well for outlier-affected parameters. Sensitivities were high, indicating the outlier was identified a high proportion of the time. Simulations also showed the enormous computational time advantage of the EIF. Diagnostics applied to body mass index in nuclear families detected observations influential on the lod score and model parameter estimates. Conclusions The EIF is a practical diagnostic tool that has the advantages of high sensitivity and quick computation. PMID:19172086

Simulating a base population in honey bee for molecular genetic studies.

PubMed

Gupta, Pooja; Conrad, Tim; Spötter, Andreas; Reinsch, Norbert; Bienefeld, Kaspar

2012-06-27

Over the past years, reports have indicated that honey bee populations are declining and that infestation by an ecto-parasitic mite (Varroa destructor) is one of the main causes. Selective breeding of resistant bees can help to prevent losses due to the parasite, but it requires that a robust breeding program and genetic evaluation are implemented. Genomic selection has emerged as an important tool in animal breeding programs and simulation studies have shown that it yields more accurate breeding value estimates, higher genetic gain and low rates of inbreeding. Since genomic selection relies on marker data, simulations conducted on a genomic dataset are a pre-requisite before selection can be implemented. Although genomic datasets have been simulated in other species undergoing genetic evaluation, simulation of a genomic dataset specific to the honey bee is required since this species has a distinct genetic and reproductive biology. Our software program was aimed at constructing a base population by simulating a random mating honey bee population. A forward-time population simulation approach was applied since it allows modeling of genetic characteristics and reproductive behavior specific to the honey bee. Our software program yielded a genomic dataset for a base population in linkage disequilibrium. In addition, information was obtained on (1) the position of markers on each chromosome, (2) allele frequency, (3) χ(2) statistics for Hardy-Weinberg equilibrium, (4) a sorted list of markers with a minor allele frequency less than or equal to the input value, (5) average r(2) values of linkage disequilibrium between all simulated marker loci pair for all generations and (6) average r2 value of linkage disequilibrium in the last generation for selected markers with the highest minor allele frequency. We developed a software program that takes into account the genetic and reproductive biology specific to the honey bee and that can be used to constitute a genomic

Privacy-preserving record linkage using Bloom filters.

PubMed

Schnell, Rainer; Bachteler, Tobias; Reiher, Jörg

2009-08-25

Combining multiple databases with disjunctive or additional information on the same person is occurring increasingly throughout research. If unique identification numbers for these individuals are not available, probabilistic record linkage is used for the identification of matching record pairs. In many applications, identifiers have to be encrypted due to privacy concerns. A new protocol for privacy-preserving record linkage with encrypted identifiers allowing for errors in identifiers has been developed. The protocol is based on Bloom filters on q-grams of identifiers. Tests on simulated and actual databases yield linkage results comparable to non-encrypted identifiers and superior to results from phonetic encodings. We proposed a protocol for privacy-preserving record linkage with encrypted identifiers allowing for errors in identifiers. Since the protocol can be easily enhanced and has a low computational burden, the protocol might be useful for many applications requiring privacy-preserving record linkage.

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…

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

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 onlymore » 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.« less

Annotated genetic linkage maps of Pinus pinaster Ait. from a Central Spain population using microsatellite and gene based markers.

PubMed

de Miguel, Marina; de Maria, Nuria; Guevara, M Angeles; Diaz, Luis; Sáez-Laguna, Enrique; Sánchez-Gómez, David; Chancerel, Emilie; Aranda, Ismael; Collada, Carmen; Plomion, Christophe; Cabezas, José-Antonio; Cervera, María-Teresa

2012-10-04

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. 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. 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.

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

African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction.

PubMed

Levran, Orna; Randesi, Matthew; Peles, Einat; Correa da Rosa, Joel; Ott, Jurg; Rotrosen, John; Adelson, Miriam; Kreek, Mary Jeanne

2016-06-01

This study was designed to determine whether polymorphisms in acetylcholine receptors contribute to opioid dependence and/or cocaine dependence. The sample (n = 1860) was divided by drug and ancestry, and 55 polymorphisms (nine genes) were analyzed. Of the 20 SNPs that showed nominally significant associations, the association of the African-specific CHRM4 SNP rs2229163 (Asn417=) with cocaine dependence survived correction for multiple testing (Pcorrected = 0.047). CHRM4 is located in a region of strong linkage disequilibrium on chromosome 11 that includes genes associated with schizophrenia. CHRM4 SNP rs2229163 is in strong linkage disequilibrium with several African-specific SNPs in DGKZ and AMBRA1. Cholinergic receptors' variants may contribute to drug addiction and have a potential role as pharmacogenetic markers.

Privacy-preserving record linkage using Bloom filters

PubMed Central

2009-01-01

Background Combining multiple databases with disjunctive or additional information on the same person is occurring increasingly throughout research. If unique identification numbers for these individuals are not available, probabilistic record linkage is used for the identification of matching record pairs. In many applications, identifiers have to be encrypted due to privacy concerns. Methods A new protocol for privacy-preserving record linkage with encrypted identifiers allowing for errors in identifiers has been developed. The protocol is based on Bloom filters on q-grams of identifiers. Results Tests on simulated and actual databases yield linkage results comparable to non-encrypted identifiers and superior to results from phonetic encodings. Conclusion We proposed a protocol for privacy-preserving record linkage with encrypted identifiers allowing for errors in identifiers. Since the protocol can be easily enhanced and has a low computational burden, the protocol might be useful for many applications requiring privacy-preserving record linkage. PMID:19706187

A second-generation anchored genetic linkage map of the tammar wallaby (Macropus eugenii)

PubMed Central

2011-01-01

Background The tammar wallaby, Macropus eugenii, a small kangaroo used for decades for studies of reproduction and metabolism, is the model Australian marsupial for genome sequencing and genetic investigations. The production of a more comprehensive cytogenetically-anchored genetic linkage map will significantly contribute to the deciphering of the tammar wallaby genome. It has great value as a resource to identify novel genes and for comparative studies, and is vital for the ongoing genome sequence assembly and gene ordering in this species. Results A second-generation anchored tammar wallaby genetic linkage map has been constructed based on a total of 148 loci. The linkage map contains the original 64 loci included in the first-generation map, plus an additional 84 microsatellite loci that were chosen specifically to increase coverage and assist with the anchoring and orientation of linkage groups to chromosomes. These additional loci were derived from (a) sequenced BAC clones that had been previously mapped to tammar wallaby chromosomes by fluorescence in situ hybridization (FISH), (b) End sequence from BACs subsequently FISH-mapped to tammar wallaby chromosomes, and (c) tammar wallaby genes orthologous to opossum genes predicted to fill gaps in the tammar wallaby linkage map as well as three X-linked markers from a published study. Based on these 148 loci, eight linkage groups were formed. These linkage groups were assigned (via FISH-mapped markers) to all seven autosomes and the X chromosome. The sex-pooled map size is 1402.4 cM, which is estimated to provide 82.6% total coverage of the genome, with an average interval distance of 10.9 cM between adjacent markers. The overall ratio of female/male map length is 0.84, which is comparable to the ratio of 0.78 obtained for the first-generation map. Conclusions Construction of this second-generation genetic linkage map is a significant step towards complete coverage of the tammar wallaby genome and considerably

A second-generation anchored genetic linkage map of the tammar wallaby (Macropus eugenii).

PubMed

Wang, Chenwei; Webley, Lee; Wei, Ke-jun; Wakefield, Matthew J; Patel, Hardip R; Deakin, Janine E; Alsop, Amber; Marshall Graves, Jennifer A; Cooper, Desmond W; Nicholas, Frank W; Zenger, Kyall R

2011-08-19

The tammar wallaby, Macropus eugenii, a small kangaroo used for decades for studies of reproduction and metabolism, is the model Australian marsupial for genome sequencing and genetic investigations. The production of a more comprehensive cytogenetically-anchored genetic linkage map will significantly contribute to the deciphering of the tammar wallaby genome. It has great value as a resource to identify novel genes and for comparative studies, and is vital for the ongoing genome sequence assembly and gene ordering in this species. A second-generation anchored tammar wallaby genetic linkage map has been constructed based on a total of 148 loci. The linkage map contains the original 64 loci included in the first-generation map, plus an additional 84 microsatellite loci that were chosen specifically to increase coverage and assist with the anchoring and orientation of linkage groups to chromosomes. These additional loci were derived from (a) sequenced BAC clones that had been previously mapped to tammar wallaby chromosomes by fluorescence in situ hybridization (FISH), (b) End sequence from BACs subsequently FISH-mapped to tammar wallaby chromosomes, and (c) tammar wallaby genes orthologous to opossum genes predicted to fill gaps in the tammar wallaby linkage map as well as three X-linked markers from a published study. Based on these 148 loci, eight linkage groups were formed. These linkage groups were assigned (via FISH-mapped markers) to all seven autosomes and the X chromosome. The sex-pooled map size is 1402.4 cM, which is estimated to provide 82.6% total coverage of the genome, with an average interval distance of 10.9 cM between adjacent markers. The overall ratio of female/male map length is 0.84, which is comparable to the ratio of 0.78 obtained for the first-generation map. Construction of this second-generation genetic linkage map is a significant step towards complete coverage of the tammar wallaby genome and considerably extends that of the first

Restriction fragment length polymorphism and allozyme linkage map of Cuphea lanceolata.

PubMed

Webb, D M; Knapp, S J; Tagliani, L A

1992-02-01

Cuphea lanceolata Ait. has had a significant role in the domestication of Cuphea and is a useful experimental organism for investigating how medium-chain lipids are synthesized in developing seeds. To expand the genetics of this species, a linkage map of the C. lanceolata genome was constructed using five allozyme and 32 restriction-fragment-length-polymorphism (RFLP) marker loci. These loci were assigned to six linkage groups that correspond to the six chromosomes of this species. Map length is 288 cM. Levels of polymorphism were estimated for three inbred lines of C. lanceolata and an inbred line of C. viscosissima using 84 random genomic clones and two restriction enzymes, EcoRI and HindIII. Of the probes 29% detected RFLPs between C. lanceolata and C. viscosissima lines. Crosses between these species can be exploited to expand the map.

Tests for a disease-susceptibility locus allowing for an inbreeding coefficient (F).

PubMed

Song, Kijoung; Elston, Robert C

2003-11-01

We begin by discussing the false positive test results that arise because of cryptic relatedness and population substructure when testing a disease susceptibility locus. We extend and evaluate the Hardy-Weinberg disequilibrium (HWD) method, allowing for an inbreeding coefficient (F) in a similar way that Devlin and Roeder (1999) allowed for inbreeding in a case-control study. Then we compare the HWD measure and the common direct measure of linkage disequilibrium, both when there is no population substructure (F = 0) and when there is population substructure (F not = 0), for a single marker. The HWD test statistic gives rise to false positives caused by population stratification. These false positives can be controlled by adjusting the test statistic for the amount of variance inflation caused by the inbreeding coefficient (F). The power loss for the HWD test that arises when controlling for population structure is much less than that which arises for the common direct measure of linkage disequilibrium. However, in the multiplicative model, the HWD test has virtually no power even when allowing for non-zero F.

Particle swarm optimization with recombination and dynamic linkage discovery.

PubMed

Chen, Ying-Ping; Peng, Wen-Chih; Jian, Ming-Chung

2007-12-01

In this paper, we try to improve the performance of the particle swarm optimizer by incorporating the linkage concept, which is an essential mechanism in genetic algorithms, and design a new linkage identification technique called dynamic linkage discovery to address the linkage problem in real-parameter optimization problems. Dynamic linkage discovery is a costless and effective linkage recognition technique that adapts the linkage configuration by employing only the selection operator without extra judging criteria irrelevant to the objective function. Moreover, a recombination operator that utilizes the discovered linkage configuration to promote the cooperation of particle swarm optimizer and dynamic linkage discovery is accordingly developed. By integrating the particle swarm optimizer, dynamic linkage discovery, and recombination operator, we propose a new hybridization of optimization methodologies called particle swarm optimization with recombination and dynamic linkage discovery (PSO-RDL). In order to study the capability of PSO-RDL, numerical experiments were conducted on a set of benchmark functions as well as on an important real-world application. The benchmark functions used in this paper were proposed in the 2005 Institute of Electrical and Electronics Engineers Congress on Evolutionary Computation. The experimental results on the benchmark functions indicate that PSO-RDL can provide a level of performance comparable to that given by other advanced optimization techniques. In addition to the benchmark, PSO-RDL was also used to solve the economic dispatch (ED) problem for power systems, which is a real-world problem and highly constrained. The results indicate that PSO-RDL can successfully solve the ED problem for the three-unit power system and obtain the currently known best solution for the 40-unit system.

Model-Based Linkage Analysis of a Quantitative Trait.

PubMed

Song, Yeunjoo E; Song, Sunah; Schnell, Audrey H

2017-01-01

Linkage Analysis is a family-based method of analysis to examine whether any typed genetic markers cosegregate with a given trait, in this case a quantitative trait. If linkage exists, this is taken as evidence in support of a genetic basis for the trait. Historically, linkage analysis was performed using a binary disease trait, but has been extended to include quantitative disease measures. Quantitative traits are desirable as they provide more information than binary traits. Linkage analysis can be performed using single-marker methods (one marker at a time) or multipoint (using multiple markers simultaneously). In model-based linkage analysis the genetic model for the trait of interest is specified. There are many software options for performing linkage analysis. Here, we use the program package Statistical Analysis for Genetic Epidemiology (S.A.G.E.). S.A.G.E. was chosen because it also includes programs to perform data cleaning procedures and to generate and test genetic models for a quantitative trait, in addition to performing linkage analysis. We demonstrate in detail the process of running the program LODLINK to perform single-marker analysis, and MLOD to perform multipoint analysis using output from SEGREG, where SEGREG was used to determine the best fitting statistical model for the trait.

Brief report: linkage between G6PD and fragile-X syndrome.

PubMed

Filippi, G; Rinaldi, A; Archidiacono, N; Rocchi, M; Balazs, I; Siniscalco, M

1983-05-01

Eighteen Sardinian pedigrees segregating for the X-fragile site syndrome were studied with respect to the segregation of the fragile site (FS) at Xq28, mental retardation, and macro-orchidism. No exception was found in the association of this symptomatic triad (MOM-X) in 41 out of 42 patients examined. The exceptional individual had micro- rather than macro-orchidism and was found to have a 47, XXY sex chromosome complement. In six informative sibships, the MOM-X syndrome was found to segregate in close linkage association with G6PD-deficiency or protan colorblindness. The maximum likelihood estimate of recombination if 6% with 90% fiducial limits between 2.5 and 19.5% and an odds ratio in favor of measurable linkage of 428:1. However, no hint of measurable linkage was found in six pedigrees segregating for G6PD and the Renpenning syndrome or other unspecified types of X-linked mental retardation. These data give strong support to the generally held hypothesis that the FS at Zq28, characteristic of the MOM-X syndrome, is a direct expression of a genetic change in the same chromosomal region. They also clearly suggest that X-linked MR without FS may be the result of different allelic mutations at the same locus.

Estimation of genomic breeding values for milk yield in UK dairy goats.

PubMed

Mucha, S; Mrode, R; MacLaren-Lee, I; Coffey, M; Conington, J

2015-11-01

The objective of this study was to estimate genomic breeding values for milk yield in crossbred dairy goats. The research was based on data provided by 2 commercial goat farms in the UK comprising 590,409 milk yield records on 14,453 dairy goats kidding between 1987 and 2013. The population was created by crossing 3 breeds: Alpine, Saanen, and Toggenburg. In each generation the best performing animals were selected for breeding, and as a result, a synthetic breed was created. The pedigree file contained 30,139 individuals, of which 2,799 were founders. The data set contained test-day records of milk yield, lactation number, farm, age at kidding, and year and season of kidding. Data on milk composition was unavailable. In total 1,960 animals were genotyped with the Illumina 50K caprine chip. Two methods for estimation of genomic breeding value were compared-BLUP at the single nucleotide polymorphism level (BLUP-SNP) and single-step BLUP. The highest accuracy of 0.61 was obtained with single-step BLUP, and the lowest (0.36) with BLUP-SNP. Linkage disequilibrium (r(2), the squared correlation of the alleles at 2 loci) at 50 kb (distance between 2 SNP) was 0.18. This is the first attempt to implement genomic selection in UK dairy goats. Results indicate that the single-step method provides the highest accuracy for populations with a small number of genotyped individuals, where the number of genotyped males is low and females are predominant in the reference population. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Symmetric Epistasis Estimation (SEE) and its application to dissecting interaction map of Plasmodium falciparum.

PubMed

Huang, Yang; Siwo, Geoffrey; Wuchty, Stefan; Ferdig, Michael T; Przytycka, Teresa M

2012-04-01

It is being increasingly recognized that many important phenotypic traits, including various diseases, are governed by a combination of weak genetic effects and their interactions. While the detection of epistatic interactions that involve a non-additive effect of two loci on a quantitative trait is particularly challenging, this interaction type is fundamental for the understanding of genome organization and gene regulation. However, current methods that detect epistatic interactions typically rely on the existence of a strong primary effect, considerably limiting the sensitivity of the search. To fill this gap, we developed a new method, SEE (Symmetric Epistasis Estimation), allowing the genome-wide detection of epistatic interactions without the need for a strong primary effect. We applied our approach to progeny crosses of the human malaria parasite P. falciparum and S. cerevisiae. We found an abundance of epistatic interactions in the parasite and a much smaller number of such interactions in yeast. The genome of P. falciparum also harboured several epistatic interaction hotspots that putatively play a role in drug resistance mechanisms. The abundance of observed epistatic interactions might suggest a mechanism of compensation for the extremely limited repertoire of transcription factors. Interestingly, epistatic interaction hotspots were associated with elevated levels of linkage disequilibrium, an observation that suggests selection pressure acting on P. falciparum, potentially reflecting host-pathogen interactions or drug-induced selection.

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.

Molecular Characterization of the Lipid Genome-Wide Association Study Signal on Chromosome 18q11.2 Implicates HNF4A-Mediated Regulation of the TMEM241 Gene.

PubMed

Rodríguez, Alejandra; Gonzalez, Luis; Ko, Arthur; Alvarez, Marcus; Miao, Zong; Bhagat, Yash; Nikkola, Elina; Cruz-Bautista, Ivette; Arellano-Campos, Olimpia; Muñoz-Hernández, Linda L; Ordóñez-Sánchez, Maria-Luisa; Rodriguez-Guillen, Rosario; Mohlke, Karen L; Laakso, Markku; Tusie-Luna, Teresa; Aguilar-Salinas, Carlos A; Pajukanta, Päivi

2016-07-01

We recently identified a locus on chromosome 18q11.2 for high serum triglycerides in Mexicans. We hypothesize that the lead genome-wide association study single-nucleotide polymorphism rs9949617, or its linkage disequilibrium proxies, regulates 1 of the 5 genes in the triglyceride-associated region. We performed a linkage disequilibrium analysis and found 9 additional variants in linkage disequilibrium (r(2)>0.7) with the lead single-nucleotide polymorphism. To select the variants for functional analyses, we annotated the 10 variants using DNase I hypersensitive sites, transcription factor and chromatin states and identified rs17259126 as the lead candidate variant for functional in vitro validation. Using luciferase transcriptional reporter assay in liver HepG2 cells, we found that the G allele exhibits a significantly lower effect on transcription (P<0.05). The electrophoretic mobility shift and ChIPqPCR (chromatin immunoprecipitation coupled with quantitative polymerase chain reaction) assays confirmed that the minor G allele of rs17259126 disrupts an hepatocyte nuclear factor 4 α-binding site. To find the regional candidate gene, we performed a local expression quantitative trait locus analysis and found that rs17259126 and its linkage disequilibrium proxies alter expression of the regional transmembrane protein 241 (TMEM241) gene in 795 adipose RNAs from the Metabolic Syndrome In Men (METSIM) cohort (P=6.11×10(-07)-5.80×10(-04)). These results were replicated in expression profiles of TMEM241 from the Multiple Tissue Human Expression Resource (MuTHER; n=856). The Mexican genome-wide association study signal for high serum triglycerides on chromosome 18q11.2 harbors a regulatory single-nucleotide polymorphism, rs17259126, which disrupts normal hepatocyte nuclear factor 4 α binding and decreases the expression of the regional TMEM241 gene. Our data suggest that decreased transcript levels of TMEM241 contribute to increased triglyceride levels in Mexicans. �

Describing the linkages of the immigration, refugees and citizenship Canada permanent resident data and vital statistics death registry to Ontario's administrative health database.

PubMed

Chiu, Maria; Lebenbaum, Michael; Lam, Kelvin; Chong, Nelson; Azimaee, Mahmoud; Iron, Karey; Manuel, Doug; Guttmann, Astrid

2016-10-21

Ontario, the most populous province in Canada, has a universal healthcare system that routinely collects health administrative data on its 13 million legal residents that is used for health research. Record linkage has become a vital tool for this research by enriching this data with the Immigration, Refugees and Citizenship Canada Permanent Resident (IRCC-PR) database and the Office of the Registrar General's Vital Statistics-Death (ORG-VSD) registry. Our objectives were to estimate linkage rates and compare characteristics of individuals in the linked versus unlinked files. We used both deterministic and probabilistic linkage methods to link the IRCC-PR database (1985-2012) and ORG-VSD registry (1990-2012) to the Ontario's Registered Persons Database. Linkage rates were estimated and standardized differences were used to assess differences in socio-demographic and other characteristics between the linked and unlinked records. The overall linkage rates for the IRCC-PR database and ORG-VSD registry were 86.4 and 96.2 %, respectively. The majority (68.2 %) of the record linkages in IRCC-PR were achieved after three deterministic passes, 18.2 % were linked probabilistically, and 13.6 % were unlinked. Similarly the majority (79.8 %) of the record linkages in the ORG-VSD were linked using deterministic record linkage, 16.3 % were linked after probabilistic and manual review, and 3.9 % were unlinked. Unlinked and linked files were similar for most characteristics, such as age and marital status for IRCC-PR and sex and most causes of death for ORG-VSD. However, lower linkage rates were observed among people born in East Asia (78 %) in the IRCC-PR database and certain causes of death in the ORG-VSD registry, namely perinatal conditions (61.3 %) and congenital anomalies (81.3 %). The linkages of immigration and vital statistics data to existing population-based healthcare data in Ontario, Canada will enable many novel cross-sectional and longitudinal studies to

Selective DNA Pooling for Determination of Linkage between a Molecular Marker and a Quantitative Trait Locus

PubMed Central

Darvasi, A.; Soller, M.

1994-01-01

Selective genotyping is a method to reduce costs in marker-quantitative trait locus (QTL) linkage determination by genotyping only those individuals with extreme, and hence most informative, quantitative trait values. The DNA pooling strategy (termed: ``selective DNA pooling'') takes this one step further by pooling DNA from the selected individuals at each of the two phenotypic extremes, and basing the test for linkage on marker allele frequencies as estimated from the pooled samples only. This can reduce genotyping costs of marker-QTL linkage determination by up to two orders of magnitude. Theoretical analysis of selective DNA pooling shows that for experiments involving backcross, F(2) and half-sib designs, the power of selective DNA pooling for detecting genes with large effect, can be the same as that obtained by individual selective genotyping. Power for detecting genes with small effect, however, was found to decrease strongly with increase in the technical error of estimating allele frequencies in the pooled samples. The effect of technical error, however, can be markedly reduced by replication of technical procedures. It is also shown that a proportion selected of 0.1 at each tail will be appropriate for a wide range of experimental conditions. PMID:7896115

Analysis of multilocus zygotic associations.

PubMed

Yang, Rong-Cai

2002-05-01

While nonrandom associations between zygotes at different loci (zygotic associations) frequently occur in Hardy-Weinberg disequilibrium populations, statistical analysis of such associations has received little attention. In this article, we describe the joint distributions of zygotes at multiple loci, which are completely characterized by heterozygosities at individual loci and various multilocus zygotic associations. These zygotic associations are defined in the same fashion as the usual multilocus linkage (gametic) disequilibria on the basis of gametic and allelic frequencies. The estimation and test procedures are described with details being given for three loci. The sampling properties of the estimates are examined through Monte Carlo simulation. The estimates of three-locus associations are not free of bias due to the presence of two-locus associations and vice versa. The power of detecting the zygotic associations is small unless different loci are strongly associated and/or sample sizes are large (>100). The analysis of zygotic associations not only offers an effective means of packaging numerous genic disequilibria required for a complete characterization of multilocus structure, but also provides opportunities for making inference about evolutionary and demographic processes through a comparative assessment of zygotic association vs. gametic disequilibrium for the same set of loci in nonequilibrium populations.

Genome-wide population structure and evolutionary history of the Frizarta dairy sheep.

PubMed

Kominakis, A; Hager-Theodorides, A L; Saridaki, A; Antonakos, G; Tsiamis, G

2017-10-01

In the present study, we used genomic data, generated with a medium density single nucleotide polymorphisms (SNP) array, to acquire more information on the population structure and evolutionary history of the synthetic Frizarta dairy sheep. First, two typical measures of linkage disequilibrium (LD) were estimated at various physical distances that were then used to make inferences on the effective population size at key past time points. Population structure was also assessed by both multidimensional scaling analysis and k-means clustering on the distance matrix obtained from the animals' genomic relationships. The Wright's fixation F ST index was also employed to assess herds' genetic homogeneity and to indirectly estimate past migration rates. The Wright's fixation F IS index and genomic inbreeding coefficients based on the genomic relationship matrix as well as on runs of homozygosity were also estimated. The Frizarta breed displays relatively low LD levels with r 2 and |D'| equal to 0.18 and 0.50, respectively, at an average inter-marker distance of 31 kb. Linkage disequilibrium decayed rapidly by distance and persisted over just a few thousand base pairs. Rate of LD decay (β) varied widely among the 26 autosomes with larger values estimated for shorter chromosomes (e.g. β=0.057, for OAR6) and smaller values for longer ones (e.g. β=0.022, for OAR2). The inferred effective population size at the beginning of the breed's formation was as high as 549, was then reduced to 463 in 1981 (end of the breed's formation) and further declined to 187, one generation ago. Multidimensional scaling analysis and k-means clustering suggested a genetically homogenous population, F ST estimates indicated relatively low genetic differentiation between herds, whereas a heat map of the animals' genomic kinship relationships revealed a stratified population, at a herd level. Estimates of genomic inbreeding coefficients suggested that most recent parental relatedness may have been a

The narrow endemic Norwegian peat moss Sphagnum troendelagicum originated before the last glacial maximum

PubMed Central

Stenøien, H K; Shaw, A J; Stengrundet, K; Flatberg, K I

2011-01-01

It is commonly found that individual hybrid, polyploid species originate recurrently and that many polyploid species originated relatively recently. It has been previously hypothesized that the extremely rare allopolyploid peat moss Sphagnum troendelagicum has originated multiple times, possibly after the last glacial maximum in Scandinavia. This conclusion was based on low linkage disequilibrium in anonymous genetic markers within natural populations, in which sexual reproduction has never been observed. Here we employ microsatellite markers and chloroplast DNA (cpDNA)-encoded trnG sequence data to test hypotheses concerning the origin and evolution of this species. We find that S. tenellum is the maternal progenitor and S. balticum is the paternal progenitor of S. troendelagicum. Using various Bayesian approaches, we estimate that S. troendelagicum originated before the Holocene but not before c. 80 000 years ago (median expected time since speciation 40 000 years before present). The observed lack of complete linkage disequilibrium in the genome of this species suggests cryptic sexual reproduction and recombination. Several lines of evidence suggest multiple origins for S. troendelagicum, but a single origin is supported by approximate Bayesian computation analyses. We hypothesize that S. troendelagicum originated in a peat-dominated refugium before last glacial maximum, and subsequently immigrated to central Norway by means of spore flow during the last thousands of years. PMID:20717162

Posterior probability of linkage and maximal lod score.

PubMed

Génin, E; Martinez, M; Clerget-Darpoux, F

1995-01-01

To detect linkage between a trait and a marker, Morton (1955) proposed to calculate the lod score z(theta 1) at a given value theta 1 of the recombination fraction. If z(theta 1) reaches +3 then linkage is concluded. However, in practice, lod scores are calculated for different values of the recombination fraction between 0 and 0.5 and the test is based on the maximum value of the lod score Zmax. The impact of this deviation of the test on the probability that in fact linkage does not exist, when linkage was concluded, is documented here. This posterior probability of no linkage can be derived by using Bayes' theorem. It is less than 5% when the lod score at a predetermined theta 1 is used for the test. But, for a Zmax of +3, we showed that it can reach 16.4%. Thus, considering a composite alternative hypothesis instead of a single one decreases the reliability of the test. The reliability decreases rapidly when Zmax is less than +3. Given a Zmax of +2.5, there is a 33% chance that linkage does not exist. Moreover, the posterior probability depends not only on the value of Zmax but also jointly on the family structures and on the genetic model. For a given Zmax, the chance that linkage exists may then vary.

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

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

Oxygenation-linked subunit interactions in human hemoglobin: analysis of linkage functions for constituent energy terms.

PubMed

Johnson, M L; Halvorson, H R; Ackers, G K

1976-11-30

Resolution of the linkage functions between oxygenation and subunit association-dissociation equilibria in human hemoglobin into the constituent microscopic terms has been explored by numerical simulation and least-squares analysis. The correlation properties between parameters has been studied using several choices of parameter sets in order to optimize resolution. It is found that, with currently available levels of experimental precision and ranges of variables, neither linkage function can provide sufficient resolution of all the desired energy terms. The most difficult quantities to resolve always include the dimer-tetramer association constant for unliganded hemoglobin and the oxygen binding constants to alphabeta dimers. A feasible experimental strategy for overcoming these difficulties lies in independent determination of the dimer-tetramer association constants for unliganded and fully oxygenated hemoglobin. These constants, in combination with the median lignad concentration, provide an estimate of the energy for total oxygenation of tetramers which is essentially independent of the other constituent energies. It is shown that if these separately determinable parameters are fixed, the remaining terms may be estimated to good accuracy using data which represents either linkage function. In general it is desirable to combine information from both types of experimental quantities. A previous paper (Mills, F.C., Johnson, M.L., and Ackers, G.K. (1976), Biochemestry, 15, the preceding paper in this issue) describes the experimental implementation of this strategy.

Linkage and related analyses of Barrett's esophagus and its associated adenocarcinomas.

PubMed

Sun, Xiangqing; Elston, Robert; Falk, Gary W; Grady, William M; Faulx, Ashley; Mittal, Sumeet K; Canto, Marcia I; Shaheen, Nicholas J; Wang, Jean S; Iyer, Prasad G; Abrams, Julian A; Willis, Joseph E; Guda, Kishore; Markowitz, Sanford; Barnholtz-Sloan, Jill S; Chandar, Apoorva; Brock, Wendy; Chak, Amitabh

2016-07-01

Familial aggregation and segregation analysis studies have provided evidence of a genetic basis for esophageal adenocarcinoma (EAC) and its premalignant precursor, Barrett's esophagus (BE). We aim to demonstrate the utility of linkage analysis to identify the genomic regions that might contain the genetic variants that predispose individuals to this complex trait (BE and EAC). We genotyped 144 individuals in 42 multiplex pedigrees chosen from 1000 singly ascertained BE/EAC pedigrees, and performed both model-based and model-free linkage analyses, using S.A.G.E. and other software. Segregation models were fitted, from the data on both the 42 pedigrees and the 1000 pedigrees, to determine parameters for performing model-based linkage analysis. Model-based and model-free linkage analyses were conducted in two sets of pedigrees: the 42 pedigrees and a subset of 18 pedigrees with female affected members that are expected to be more genetically homogeneous. Genome-wide associations were also tested in these families. Linkage analyses on the 42 pedigrees identified several regions consistently suggestive of linkage by different linkage analysis methods on chromosomes 2q31, 12q23, and 4p14. A linkage on 15q26 is the only consistent linkage region identified in the 18 female-affected pedigrees, in which the linkage signal is higher than in the 42 pedigrees. Other tentative linkage signals are also reported. Our linkage study of BE/EAC pedigrees identified linkage regions on chromosomes 2, 4, 12, and 15, with some reported associations located within our linkage peaks. Our linkage results can help prioritize association tests to delineate the genetic determinants underlying susceptibility to BE and EAC.

Linkage and Association Mapping for Two Major Traits Used in the Maritime Pine Breeding Program: Height Growth and Stem Straightness

PubMed Central

Bink, Marco CAM; van Heerwaarden, Joost; Chancerel, Emilie; Boury, Christophe; Lesur, Isabelle; Isik, Fikret; Bouffier, Laurent; Plomion, Christophe

2016-01-01

Background Increasing our understanding of the genetic architecture of complex traits, through analyses of genotype-phenotype associations and of the genes/polymorphisms accounting for trait variation, is crucial, to improve the integration of molecular markers into forest tree breeding. In this study, two full-sib families and one breeding population of maritime pine were used to identify quantitative trait loci (QTLs) for height growth and stem straightness, through linkage analysis (LA) and linkage disequilibrium (LD) mapping approaches. Results The populations used for LA consisted of two unrelated three-generation full-sib families (n = 197 and n = 477). These populations were assessed for height growth or stem straightness and genotyped for 248 and 217 markers, respectively. The population used for LD mapping consisted of 661 founders of the first and second generations of the breeding program. This population was phenotyped for the same traits and genotyped for 2,498 single-nucleotide polymorphism (SNP) markers corresponding to 1,652 gene loci. The gene-based reference genetic map of maritime pine was used to localize and compare the QTLs detected by the two approaches, for both traits. LA identified three QTLs for stem straightness and two QTLs for height growth. The LD study yielded seven significant associations (P ≤ 0.001): four for stem straightness and three for height growth. No colocalisation was found between QTLs identified by LA and SNPs detected by LD mapping for the same trait. Conclusions This study provides the first comparison of LA and LD mapping approaches in maritime pine, highlighting the complementary nature of these two approaches for deciphering the genetic architecture of two mandatory traits of the breeding program. PMID:27806077

Linkage and Association Mapping for Two Major Traits Used in the Maritime Pine Breeding Program: Height Growth and Stem Straightness.

PubMed

Bartholomé, Jérôme; Bink, Marco Cam; van Heerwaarden, Joost; Chancerel, Emilie; Boury, Christophe; Lesur, Isabelle; Isik, Fikret; Bouffier, Laurent; Plomion, Christophe

2016-01-01

Increasing our understanding of the genetic architecture of complex traits, through analyses of genotype-phenotype associations and of the genes/polymorphisms accounting for trait variation, is crucial, to improve the integration of molecular markers into forest tree breeding. In this study, two full-sib families and one breeding population of maritime pine were used to identify quantitative trait loci (QTLs) for height growth and stem straightness, through linkage analysis (LA) and linkage disequilibrium (LD) mapping approaches. The populations used for LA consisted of two unrelated three-generation full-sib families (n = 197 and n = 477). These populations were assessed for height growth or stem straightness and genotyped for 248 and 217 markers, respectively. The population used for LD mapping consisted of 661 founders of the first and second generations of the breeding program. This population was phenotyped for the same traits and genotyped for 2,498 single-nucleotide polymorphism (SNP) markers corresponding to 1,652 gene loci. The gene-based reference genetic map of maritime pine was used to localize and compare the QTLs detected by the two approaches, for both traits. LA identified three QTLs for stem straightness and two QTLs for height growth. The LD study yielded seven significant associations (P ≤ 0.001): four for stem straightness and three for height growth. No colocalisation was found between QTLs identified by LA and SNPs detected by LD mapping for the same trait. This study provides the first comparison of LA and LD mapping approaches in maritime pine, highlighting the complementary nature of these two approaches for deciphering the genetic architecture of two mandatory traits of the breeding program.

DNA linkage studies of degenerative retinal diseases.

PubMed

Daiger, S P; Heckenlively, J R; Lewis, R A; Pelias, M Z

1987-01-01

DNA linkage studies of human genetic diseases have led to rapid characterization of a number of otherwise intractable disease loci. Detection of a linked DNA marker, the first step in "reverse genetics", has permitted cloning of the genes for Duchenne muscular dystrophy, retinoblastoma and chronic granulomatosis disease, among others. Thus, the case for applying these techniques to retinitis pigmentosa and related diseases, and the urgency in capitalizing on molecular developments, is justified and compelling. The first major success regarding RP was in demonstrating linkage of the DNA marker DXS7 (L1.28) to XRP. For autosomal forms of the disease, conventional linkage studies have provided tentative evidence for linkage of ADRP to the Rh blood group on chromosome lp and for linkage of Usher's syndrome to Gc and 4q. These provisional assignments are, at least, an important starting point for DNA analysis. The Support Program for DNA Linkage Studies of Degenerative Retinal Diseases was established to provide access for the scientific community to appropriate families, using the resources of the Human Genetic Mutant Cell Repository to prepare, store and distribute lymphoblast lines. To date, two extensive, well-characterized families are included in the program: the autosomal dominant RP family UCLA-RP01, and the Usher's syndrome families LSU-US01. It is highly likely that rapid progress will be made in mapping and characterizing the inherited retinal dystrophies. We believe the support program will facilitate this progress.

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

USDA-ARS?s Scientific Manuscript database

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

Dynamics of a durable commodity market involving trade at disequilibrium

NASA Astrophysics Data System (ADS)

Panchuk, A.; Puu, T.

2018-05-01

The present work considers a simple model of a durable commodity market involving two agents who trade stocks of two different types. Stock commodities, in contrast to flow commodities, remain on the market from period to period and, consequently, there is neither unique demand function nor unique supply function exists. We also set up exact conditions for trade at disequilibrium, the issue being usually neglected, though a fact of reality. The induced iterative system has infinite number of fixed points and path dependent dynamics. We show that a typical orbit is either attracted to one of the fixed points or eventually sticks at a no-trade point. For the latter the stock distribution always remains the same while the price displays periodic or chaotic oscillations.

Disequilibrium δ18O values in microbial carbonates as a tracer of metabolic production of dissolved inorganic carbon

NASA Astrophysics Data System (ADS)

Thaler, Caroline; Millo, Christian; Ader, Magali; Chaduteau, Carine; Guyot, François; Ménez, Bénédicte

2017-02-01

Carbon and oxygen stable isotope compositions of carbonates are widely used to retrieve paleoenvironmental information. However, bias may exist in such reconstructions as carbonate precipitation is often associated with biological activity. Several skeleton-forming eukaryotes have been shown to precipitate carbonates with significant offsets from isotopic equilibrium with water. Although poorly understood, the origin of these biologically-induced isotopic shifts in biogenic carbonates, commonly referred to as "vital effects", could be related to metabolic effects that may not be restricted to mineralizing eukaryotes. The aim of our study was to determine whether microbially-mediated carbonate precipitation can also produce offsets from equilibrium for oxygen isotopes. We present here δ18O values of calcium carbonates formed by the activity of Sporosarcina pasteurii, a carbonatogenic bacterium whose ureolytic activity produces ammonia (thus increasing pH) and dissolved inorganic carbon (DIC) that precipitates as solid carbonates in the presence of Ca2+. We show that the 1000 lnαCaCO3-H2O values for these bacterially-precipitated carbonates are up to 24.7‰ smaller than those expected for precipitation at isotopic equilibrium. A similar experiment run in the presence of carbonic anhydrase (an enzyme able to accelerate oxygen isotope equilibration between DIC and water) resulted in δ18O values of microbial carbonates in line with values expected at isotopic equilibrium with water. These results demonstrate for the first time that bacteria can induce calcium carbonate precipitation in strong oxygen isotope disequilibrium with water, similarly to what is observed for eukaryotes. This disequilibrium effect can be unambiguously ascribed to oxygen isotope disequilibrium between DIC and water inherited from the oxygen isotope composition of the ureolytically produced CO2, probably combined with a kinetic isotope effect during CO2 hydration/hydroxylation. The fact that

Privacy-preserving record linkage on large real world datasets.

PubMed

Randall, Sean M; Ferrante, Anna M; Boyd, James H; Bauer, Jacqueline K; Semmens, James B

2014-08-01

Record linkage typically involves the use of dedicated linkage units who are supplied with personally identifying information to determine individuals from within and across datasets. The personally identifying information supplied to linkage units is separated from clinical information prior to release by data custodians. While this substantially reduces the risk of disclosure of sensitive information, some residual risks still exist and remain a concern for some custodians. In this paper we trial a method of record linkage which reduces privacy risk still further on large real world administrative data. The method uses encrypted personal identifying information (bloom filters) in a probability-based linkage framework. The privacy preserving linkage method was tested on ten years of New South Wales (NSW) and Western Australian (WA) hospital admissions data, comprising in total over 26 million records. No difference in linkage quality was found when the results were compared to traditional probabilistic methods using full unencrypted personal identifiers. This presents as a possible means of reducing privacy risks related to record linkage in population level research studies. It is hoped that through adaptations of this method or similar privacy preserving methods, risks related to information disclosure can be reduced so that the benefits of linked research taking place can be fully realised. Copyright © 2013 Elsevier Inc. All rights reserved.

A Test of Outreach and Drop-in Linkage Versus Shelter Linkage for Connecting Homeless Youth to Services.

PubMed

Slesnick, Natasha; Feng, Xin; Guo, Xiamei; Brakenhoff, Brittany; Carmona, Jasmin; Murnan, Aaron; Cash, Scottye; McRee, Annie-Laurie

2016-05-01

Outreach and service linkage are key for engaging marginalized populations, such as homeless youth, in services. Research to date has focused primarily on engaging individuals already receiving some services through emergency shelters, clinics, or other programs. Less is known about those who are not connected to services and, thus, likely the most vulnerable and in need of assistance. The current study sought to engage non-service-connected homeless youth (N = 79) into a strengths-based outreach and advocacy intervention. Youth were randomly assigned to receive 6 months of advocacy that focused on linking youth to a drop-in center (n = 40) or to a crisis shelter (n = 39). All youth were assessed at baseline and 3, 6, and 9 months post-baseline. Findings indicated that youth prefer drop-in center services to the shelter. Also, the drop-in center linkage condition was associated with more service linkage overall (B = 0.34, SE = 0.04, p < 0.01) and better alcohol-l [B = -0.39, SE = 0.09, t(75) = -4.48, p < 0.001] and HIV-related outcomes [B = 0.62, SE = 0.10, t(78) = 6.34, p < 0.001] compared to the shelter linkage condition. Findings highlight the importance of outreach and service linkage for reconnecting service-marginalized youth, and drop-in centers as a primary service option for homeless youth.

Linkage studies in primary open angle glaucoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

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.more » 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.« less

Linkage Analysis of a Model Quantitative Trait in Humans: Finger Ridge Count Shows Significant Multivariate Linkage to 5q14.1

PubMed Central

Medland, Sarah E; Loesch, Danuta Z; Mdzewski, Bogdan; Zhu, Gu; Montgomery, Grant W; Martin, Nicholas G

2007-01-01

The finger ridge count (a measure of pattern size) is one of the most heritable complex traits studied in humans and has been considered a model human polygenic trait in quantitative genetic analysis. Here, we report the results of the first genome-wide linkage scan for finger ridge count in a sample of 2,114 offspring from 922 nuclear families. Both univariate linkage to the absolute ridge count (a sum of all the ridge counts on all ten fingers), and multivariate linkage analyses of the counts on individual fingers, were conducted. The multivariate analyses yielded significant linkage to 5q14.1 (Logarithm of odds [LOD] = 3.34, pointwise-empirical p-value = 0.00025) that was predominantly driven by linkage to the ring, index, and middle fingers. The strongest univariate linkage was to 1q42.2 (LOD = 2.04, point-wise p-value = 0.002, genome-wide p-value = 0.29). In summary, the combination of univariate and multivariate results was more informative than simple univariate analyses alone. Patterns of quantitative trait loci factor loadings consistent with developmental fields were observed, and the simple pleiotropic model underlying the absolute ridge count was not sufficient to characterize the interrelationships between the ridge counts of individual fingers. PMID:17907812

Multi-temporal Linkages of Net Ecosystem Exchanges (NEE) with the Climatic and Ecohydrologic Drivers in a Florida Everglades Short-hydroperiod Freshwater Marsh

NASA Astrophysics Data System (ADS)

Zaki, M. T.; Abdul-Aziz, O. I.; Ishtiaq, K. S.

2017-12-01

Wetlands are considered one of the most productive and ecologically valuable ecosystems on earth. We investigated the multi-temporal linkages of net ecosystem exchange (NEE) with the relevant climatic and ecohydrological drivers for a Florida Everglades short-hydroperiod freshwater wetland. Hourly NEE observations and the associated driving variables during 2008-12 were collected from the AmeriFlux and EDEN databases, and then averaged for the four temporal scales (1-day, 8-day, 15-day, and 30-day). Pearson correlation and factor analysis were employed to identify the interrelations and grouping patterns among the participatory variables for each time scale. The climatic and ecohydrological linkages of NEE were then reliably estimated using bootstrapped (1000 iterations) partial least squares regressions by resolving multicollinearity. The analytics identified four bio-physical components exhibiting relatively robust interrelations and grouping patterns with NEE across the temporal scales. In general, NEE was most strongly linked with the `radiation-energy (RE)' component, while having a moderate linkage with the `temperature-hydrology (TH)' and `aerodynamic (AD)' components. However, the `ambient atmospheric CO2 (AC)' component was very weakly linked to NEE. Further, RE and TH had a decreasing trend with the increasing time scales (1-30 days). In contrast, the linkages of AD and AC components increased from 1-day to 8-day scales, and then remained relatively invariable at the longer scales of aggregation. The estimated linkages provide insights into the dominant biophysical process components and drivers of ecosystem carbon in the Everglades. The invariant linking pattern and linkages would help to develop low-dimensional models to reliably predict CO2 fluxes from the tidal freshwater wetlands.

Robustness of linkage strategy that leads to large-scale cooperation.

PubMed

Inaba, Misato; Takahashi, Nobuyuki; Ohtsuki, Hisashi

2016-11-21

One of the most well-known models to characterize cooperation among unrelated individuals is Social dilemma (SD). However there is no consensus about how to solve the SD by itself. Since SDs are often embedded in other social interactions, including indirect reciprocity games (IR), human can coordinate their behaviors across multiple games. Such coordination is called 'linkage'. Recently linkage has been considered as a promising solution to resolve SDs, since excluding SD defectors (i.e. those who defected in SD) from indirectly reciprocal relationships functions as a costless sanction. A previous study performed mathematical modeling and revealed that a linkage strategy, which cooperates in SD and engages in the Standing strategy in IR based on the recipients' behaviors in both SD and IR, was an ESS against a non-linkage strategy which defects in SD and engages in the Standing strategy in IR based on recipients' behaviors only in IR (Panchanathan and Boyd, 2004). In order to investigate the robustness of the linkage strategy, we devised a non-linkage strategy, which cooperates in SD but does not link two games. First, we conducted a mathematical analysis and demonstrated that the linkage strategy was not an ESS against cooperating non-linkage strategy. Second, we conducted a series of agent-based computer simulations to examine how the strategies perform in situations in which various types of errors can occur. Our results showed that the linkage strategy was an ESS only when there are implementation errors in SD. However, the equilibrium of the linkage strategy was unstable when there are perception errors. Since we know that humans are not free from perception errors in their social life, future studies will need to show how perception errors can be overcome in order to provide support for the conclusion that linkage is a plausible solution to SDs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Automated assembly of oligosaccharides containing multiple cis-glycosidic linkages

NASA Astrophysics Data System (ADS)

Hahm, Heung Sik; Hurevich, Mattan; Seeberger, Peter H.

2016-09-01

Automated glycan assembly (AGA) has advanced from a concept to a commercial technology that rapidly provides access to diverse oligosaccharide chains as long as 30-mers. To date, AGA was mainly employed to incorporate trans-glycosidic linkages, where C2 participating protecting groups ensure stereoselective couplings. Stereocontrol during the installation of cis-glycosidic linkages cannot rely on C2-participation and anomeric mixtures are typically formed. Here, we demonstrate that oligosaccharides containing multiple cis-glycosidic linkages can be prepared efficiently by AGA using monosaccharide building blocks equipped with remote participating protecting groups. The concept is illustrated by the automated syntheses of biologically relevant oligosaccharides bearing various cis-galactosidic and cis-glucosidic linkages. This work provides further proof that AGA facilitates the synthesis of complex oligosaccharides with multiple cis-linkages and other biologically important oligosaccharides.

Sex versus asex: An analysis of the role of variance conversion.

PubMed

Lewis-Pye, Andrew E M; Montalbán, Antonio

2017-04-01

The question as to why most complex organisms reproduce sexually remains a very active research area in evolutionary biology. Theories dating back to Weismann have suggested that the key may lie in the creation of increased variability in offspring, causing enhanced response to selection. Under appropriate conditions, selection is known to result in the generation of negative linkage disequilibrium, with the effect of recombination then being to increase genetic variance by reducing these negative associations between alleles. It has therefore been a matter of significant interest to understand precisely those conditions resulting in negative linkage disequilibrium, and to recognise also the conditions in which the corresponding increase in genetic variation will be advantageous. Here, we prove rigorous results for the multi-locus case, detailing the build up of negative linkage disequilibrium, and describing the long term effect on population fitness for models with and without bounds on fitness contributions from individual alleles. Under the assumption of large but finite bounds on fitness contributions from alleles, the non-linear nature of the effect of recombination on a population presents serious obstacles in finding the genetic composition of populations at equilibrium, and in establishing convergence to those equilibria. We describe techniques for analysing the long term behaviour of sexual and asexual populations for such models, and use these techniques to establish conditions resulting in higher fitnesses for sexually reproducing populations. Copyright © 2017 Elsevier Inc. All rights reserved.

Common variants of the EPDR1 gene and the risk of Dupuytren’s disease.

PubMed

Dębniak, T; Żyluk, A; Puchalski, P; Serrano-Fernandez, P

2013-10-01

The object of this study was the investigation of 3 common variants of single nucleotide polymorphisms of the ependymin-related gene 1 and its association with the occurrence of Dupuytren's disease. DNA samples were obtained from the peripheral blood of 508 consecutive patients. The control group comprised 515 healthy adults who were age-matched with the Dupuytren's patients. 3 common variants were analysed using TaqMan® genotyping assays and sequencing. The differences in the frequencies of variants of single nucleotide polymorphisms in patients and the control group were statistically tested. Additionally, haplotype frequency and linkage disequilibrium were analysed for these variants. A statistically significant association was noted between rs16879765_CT, rs16879765_TT and rs13240429_AA variants and Dupuytren's disease. 2 haplotypes: rs2722280_C+rs13240429_A+rs16879765_C and rs2722280_C+rs13240429_G+rs16879765_T were found to be statistically significantly associated with Dupuytren's disease. Moreover, we found that rs13240429 and rs16879765 variants were in strong linkage disequilibrium, while rs2722280 was only in moderate linkage disequilibrium. No significant differences were found in the frequencies of the variants of the gene between the groups with a positive and negative familial history of Dupuytren's disease. In conclusion, results of this study suggest that EPDR1 gene can be added to a growing list of genes associated with Dupuytren's disease development. © Georg Thieme Verlag KG Stuttgart · New York.

Convective Dynamics and Disequilibrium Chemistry in the Atmospheres of Giant Planets and Brown Dwarfs

NASA Astrophysics Data System (ADS)

Bordwell, Baylee; Brown, Benjamin P.; Oishi, Jeffrey S.

2018-02-01

Disequilibrium chemical processes significantly affect the spectra of substellar objects. To study these effects, dynamical disequilibrium has been parameterized using the quench and eddy diffusion approximations, but little work has been done to explore how these approximations perform under realistic planetary conditions in different dynamical regimes. As a first step toward addressing this problem, we study the localized, small-scale convective dynamics of planetary atmospheres by direct numerical simulation of fully compressible hydrodynamics with reactive tracers using the Dedalus code. Using polytropically stratified, plane-parallel atmospheres in 2D and 3D, we explore the quenching behavior of different abstract chemical species as a function of the dynamical conditions of the atmosphere as parameterized by the Rayleigh number. We find that in both 2D and 3D, chemical species quench deeper than would be predicted based on simple mixing-length arguments. Instead, it is necessary to employ length scales based on the chemical equilibrium profile of the reacting species in order to predict quench points and perform chemical kinetics modeling in 1D. Based on the results of our simulations, we provide a new length scale, derived from the chemical scale height, that can be used to perform these calculations. This length scale is simple to calculate from known chemical data and makes reasonable predictions for our dynamical simulations.

Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism.

PubMed

Kim, S-J; Young, L J; Gonen, D; Veenstra-VanderWeele, J; Courchesne, R; Courchesne, E; Lord, C; Leventhal, B L; Cook, E H; Insel, T R

2002-01-01

Impairment in social reciprocity is a central component of autism. In preclinical studies, arginine vasopressin (AVP) has been shown to increase a range of social behaviors, including affiliation and attachment, via the V(1a) receptor (AVPR1A) in the brain. Both the behavioral effects of AVP and the neural distribution of the V1a receptor vary greatly across mammalian species. This difference in regional receptor expression as well as differences in social behavior may result from a highly variable repetitive sequence in the 5' flanking region of the V1a gene (AVPR1A). Given this comparative evidence for a role in inter-species variation in social behavior, we explored whether within our own species, variation in the human AVPR1A may contribute to individual variations in social behavior, with autism representing an extreme form of social impairment. We genotyped two microsatellite polymorphisms from the 5' flanking region of AVPR1A for 115 autism trios and found nominally significant transmission disequilibrium between autism and one of the microsatellite markers by Multiallelic Transmission/Disequilibrium test (MTDT) that was not significant after Bonferroni correction. We also screened approximately 2 kb of the 5' flanking region and the coding region and identified 10 single nucleotide polymorphisms.

Technical note: Equivalent genomic models with a residual polygenic effect.

PubMed

Liu, Z; Goddard, M E; Hayes, B J; Reinhardt, F; Reents, R

2016-03-01

Routine genomic evaluations in animal breeding are usually based on either a BLUP with genomic relationship matrix (GBLUP) or single nucleotide polymorphism (SNP) BLUP model. For a multi-step genomic evaluation, these 2 alternative genomic models were proven to give equivalent predictions for genomic reference animals. The model equivalence was verified also for young genotyped animals without phenotypes. Due to incomplete linkage disequilibrium of SNP markers to genes or causal mutations responsible for genetic inheritance of quantitative traits, SNP markers cannot explain all the genetic variance. A residual polygenic effect is normally fitted in the genomic model to account for the incomplete linkage disequilibrium. In this study, we start by showing the proof that the multi-step GBLUP and SNP BLUP models are equivalent for the reference animals, when they have a residual polygenic effect included. Second, the equivalence of both multi-step genomic models with a residual polygenic effect was also verified for young genotyped animals without phenotypes. Additionally, we derived formulas to convert genomic estimated breeding values of the GBLUP model to its components, direct genomic values and residual polygenic effect. Third, we made a proof that the equivalence of these 2 genomic models with a residual polygenic effect holds also for single-step genomic evaluation. Both the single-step GBLUP and SNP BLUP models lead to equal prediction for genotyped animals with phenotypes (e.g., reference animals), as well as for (young) genotyped animals without phenotypes. Finally, these 2 single-step genomic models with a residual polygenic effect were proven to be equivalent for estimation of SNP effects, too. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Molecular population genetics of X-linked genes in Drosophila pseudoobscura.

PubMed Central

Kovacevic, M; Schaeffer, S W

2000-01-01

This article presents a nucleotide sequence analysis of 500 bp determined in each of five X-linked genes, runt, sisterlessA, period, esterase 5, and Heat-shock protein 83, in 40 Drosophila pseudoobscura strains collected from two populations. Estimates of the neutral migration parameter for the five loci show that gene flow among D. pseudoobscura populations is sufficient to homogenize inversion frequencies across the range of the species. Nucleotide diversity at each locus fails to reject a neutral model of molecular evolution. The sample of 40 chromosomes included six Sex-ratio inversions, a series of three nonoverlapping inversions that are associated with a strong meiotic drive phenotype. The selection driven by the Sex-ratio meiotic drive element has not fixed variation across the X chromosome of D. pseudoobscura because, while significant linkage disequilibrium was observed within the sisterlessA, period, and esterase 5 genes, we did not find evidence for nonrandom association among loci. The Sex-ratio chromosome was estimated to be 25,000 years old based on the decomposition of linkage disequilibrium between esterase 5 and Heat-shock protein 83 or 1 million years old based on the net divergence of esterase 5 between Standard and Sex-ratio chromosomes. Genetic diversity was depressed within esterase 5 within Sex-ratio chromosomes, while the four other genes failed to show a reduction in heterozygosity in the Sex-ratio background. The reduced heterogeneity in esterase 5 is due either to its location near one of the Sex-ratio inversion breakpoints or that it is closely linked to a gene or genes responsible for the Sex-ratio meiotic drive system. PMID:10978282

Genetic diversity of the HLA system in human populations from the Sierra (Andean), Oriente (Amazonian) and Costa (Coastal) regions of Ecuador.

PubMed

Galarza, Juan M; Barquera, Rodrigo; Álvarez, Ana M Tito; Hernández Zaragoza, Diana I; Sevilla, Gabriela Peralta; Tamayo, Andrea; Pérez, Mariel; Dávila, David; Birnberg, Lotty; Alonzo, Víctor Acuña; Krause, Johannes; Grijalva, Marcelo

2018-06-13

We studied HLA class I (HLA-A, -B) and class II (HLA-DRB1, -DQB1) alleles by PCR-SSP based typing in a total of 1101 Ecuadorian individuals from three regions of the country, the Coastal region, the Andean region, and the Amazonian region, to obtain information regarding allelic and haplotypic frequencies and their linkage disequilibrium. We find that the most frequent HLA haplotypes with significant linkage disequilibrium in those populations are HLA-A∗24∼B∗35∼DRB1∗04∼DQB1∗03:02, A∗02∼B∗35∼DRB1∗04∼DQB1∗03:02, A∗24∼B∗35∼DRB1∗14∼DQB1∗03:01, A∗02∼B∗35∼DRB1∗14∼DQB1∗03:01 and A∗02∼B∗40:02∼DRB1∗04∼DQB1∗03:02. The only non-Native American haplotype with frequency > 1% shared by all groups was A∗29∼B∗44∼DRB1∗07∼DQB1∗02. Admixture estimates obtained by a maximum likelihood method using HLA-B as genetic estimator revealed that the main genetic components for this sample of mixed-ancestry Ecuadorians are Native American (ranging from 52.86% to 63.83%) and European (from 28.95% to 46.54%), while an African genetic component was only apparent in the Coastal region (18.19%). Our findings provide a starting point for the study of population immunogenetics of Ecuadorian populations. Copyright © 2018. Published by Elsevier Inc.

Discrimination of relationships with the same degree of kinship using chromosomal sharing patterns estimated from high-density SNPs.

PubMed

Morimoto, Chie; Manabe, Sho; Fujimoto, Shuntaro; Hamano, Yuya; Tamaki, Keiji

2018-03-01

Distinguishing relationships with the same degree of kinship (e.g., uncle-nephew and grandfather-grandson) is generally difficult in forensic genetics by using the commonly employed short tandem repeat loci. In this study, we developed a new method for discerning such relationships between two individuals by examining the number of chromosomal shared segments estimated from high-density single nucleotide polymorphisms (SNPs). We computationally generated second-degree kinships (i.e., uncle-nephew and grandfather-grandson) and third-degree kinships (i.e., first cousins and great-grandfather-great-grandson) for 174,254 autosomal SNPs considering the effect of linkage disequilibrium and recombination for each SNP. We investigated shared chromosomal segments between two individuals that were estimated based on identity by state regions. We then counted the number of segments in each pair. Based on our results, the number of shared chromosomal segments in collateral relationships was larger than that in lineal relationships with both the second-degree and third-degree kinships. This was probably caused by differences involving chromosomal transitions and recombination between relationships. As we probabilistically evaluated the relationships between simulated pairs based on the number of shared segments using logistic regression, we could determine accurate relationships in >90% of second-degree relatives and >70% of third-degree relatives, using a probability criterion for the relationship ≥0.9. Furthermore, we could judge the true relationships of actual sample pairs from volunteers, as well as simulated data. Therefore, this method can be useful for discerning relationships between two individuals with the same degree of kinship. Copyright © 2017 Elsevier B.V. All rights reserved.

The Problems of Multiple Feedback Estimation.

ERIC Educational Resources Information Center

Bulcock, Jeffrey W.

The use of two-stage least squares (2SLS) for the estimation of feedback linkages is inappropriate for nonorthogonal data sets because 2SLS is extremely sensitive to multicollinearity. It is argued that what is needed is use of a different estimating criterion than the least squares criterion. Theoretically the variance normalization criterion has…

Data Linkage: A powerful research tool with potential problems

PubMed Central

2010-01-01

Background Policy makers, clinicians and researchers are demonstrating increasing interest in using data linked from multiple sources to support measurement of clinical performance and patient health outcomes. However, the utility of data linkage may be compromised by sub-optimal or incomplete linkage, leading to systematic bias. In this study, we synthesize the evidence identifying participant or population characteristics that can influence the validity and completeness of data linkage and may be associated with systematic bias in reported outcomes. Methods A narrative review, using structured search methods was undertaken. Key words "data linkage" and Mesh term "medical record linkage" were applied to Medline, EMBASE and CINAHL databases between 1991 and 2007. Abstract inclusion criteria were; the article attempted an empirical evaluation of methodological issues relating to data linkage and reported on patient characteristics, the study design included analysis of matched versus unmatched records, and the report was in English. Included articles were grouped thematically according to patient characteristics that were compared between matched and unmatched records. Results The search identified 1810 articles of which 33 (1.8%) met inclusion criteria. There was marked heterogeneity in study methods and factors investigated. Characteristics that were unevenly distributed among matched and unmatched records were; age (72% of studies), sex (50% of studies), race (64% of studies), geographical/hospital site (93% of studies), socio-economic status (82% of studies) and health status (72% of studies). Conclusion A number of relevant patient or population factors may be associated with incomplete data linkage resulting in systematic bias in reported clinical outcomes. Readers should consider these factors in interpreting the reported results of data linkage studies. PMID:21176171

Identifying Candidate Chemical-Disease Linkages ...

EPA Pesticide Factsheets

Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This hazard information is combined with exposure models to inform risk assessment. Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This hazard information is combined with exposure models to inform risk assessment.

Sex-specific Linkage Scans in Opioid Dependence

PubMed Central

Yang, Bao-Zhu; Han, Shizhong; Kranzler, Henry R.; Palmer, Abraham A.; Gelernter, Joel

2017-01-01

Sex influences risk for opioid dependence (OD). We hypothesized that sex might interact with genetic loci that influence the risk for OD. Therefore we performed an analysis to identify sex-specific genomic susceptibility regions for OD using linkage. Over 6000 single nucleotide polymorphism (SNP) markers were genotyped for 1758 African- and European-American (AA and EA) individuals from 739 families, ascertained via affected sib-pairs with OD and/or cocaine dependence. Autosomewide non-parametric linkage scans, stratified by sex and population, were performed. We identified one significant linkage region, segregating with OD in EA men, at 71.1 cM on chromosome 4 (LOD=3.29; point-wise p=0.00005; empirical autosome-wide p=0.042), which significantly differed from the linkage signal at the same location in EA women (empirical p=0.002). Three suggestive linkage signals were identified at 181.3 cM on chromosome 7 (LOD=2.18), 104 cM on chromosome 11 (LOD=1.85), and 60.9 cM on chromosome 16 (LOD=1.93) in EA women. In AA men, four suggestive linkage signals were detected at 201.1 cM on chromosome 3 (LOD=2.32), 152.9 cM on chromosome 6 (LOD=1.86), 16.8 cM on chromosome 7 (LOD=1.95), and 36.1 cM on chromosome 17 (LOD=1.99). The significant region, mapping to 4q12-4q13.1, harbors several OD candidate genes with interconnected functionality, including VEGFR, CLOCK, PDCL2, NMU, NRSF, and IGFBP7. In conclusion, these results provide an evidence for the existence of sex-specific and population-specific differences in OD. Furthermore, these results provide positional information that will facilitate the use of targeted next-generation sequencing to search for genes that contribute to sex-specific differences in OD. PMID:27762075

A microsatellite genetic linkage map of black rockfish ( Sebastes schlegeli)

NASA Astrophysics Data System (ADS)

Chu, Guannan; Jiang, Liming; He, Yan; Yu, Haiyang; Wang, Zhigang; Jiang, Haibin; Zhang, Quanqi

2014-12-01

Ovoviviparous black rockfish ( Sebastes schlegeli) is an important marine fish species for aquaculture and fisheries in China. Genetic information of this species is scarce because of the lack of microsatellite markers. In this study, a large number of microsatellite markers of black rockfish were isolated by constructing microsatellite-enriched libraries. Female- and male-specific genetic linkage maps were constructed using 435 microsatellite markers genotyped in a full-sib family of the fish species. The female linkage map contained 140 microsatellite markers, in which 23 linkage groups had a total genetic length of 1334.1 cM and average inter-marker space of 13.3 cM. The male linkage map contained 156 microsatellite markers, in which 25 linkage groups had a total genetic length of 1359.6 cM and average inter-marker distance of 12.4 cM. The genome coverage of the female and male linkage maps was 68.6% and 69.3%, respectively. The female-to-male ratio of the recombination rate was approximately 1.07:1 in adjacent microsatellite markers. This paper presents the first genetic linkage map of microsatellites in black rockfish. The collection of polymorphic markers and sex-specific linkage maps of black rockfish could be useful for further investigations on parental assignment, population genetics, quantitative trait loci mapping, and marker-assisted selection in related breeding programs.

Simulating a base population in honey bee for molecular genetic studies

PubMed Central

2012-01-01

Background Over the past years, reports have indicated that honey bee populations are declining and that infestation by an ecto-parasitic mite (Varroa destructor) is one of the main causes. Selective breeding of resistant bees can help to prevent losses due to the parasite, but it requires that a robust breeding program and genetic evaluation are implemented. Genomic selection has emerged as an important tool in animal breeding programs and simulation studies have shown that it yields more accurate breeding value estimates, higher genetic gain and low rates of inbreeding. Since genomic selection relies on marker data, simulations conducted on a genomic dataset are a pre-requisite before selection can be implemented. Although genomic datasets have been simulated in other species undergoing genetic evaluation, simulation of a genomic dataset specific to the honey bee is required since this species has a distinct genetic and reproductive biology. Our software program was aimed at constructing a base population by simulating a random mating honey bee population. A forward-time population simulation approach was applied since it allows modeling of genetic characteristics and reproductive behavior specific to the honey bee. Results Our software program yielded a genomic dataset for a base population in linkage disequilibrium. In addition, information was obtained on (1) the position of markers on each chromosome, (2) allele frequency, (3) χ2 statistics for Hardy-Weinberg equilibrium, (4) a sorted list of markers with a minor allele frequency less than or equal to the input value, (5) average r2 values of linkage disequilibrium between all simulated marker loci pair for all generations and (6) average r2 value of linkage disequilibrium in the last generation for selected markers with the highest minor allele frequency. Conclusion We developed a software program that takes into account the genetic and reproductive biology specific to the honey bee and that can be used to

Development of 11 polymorphic microsatellite markers for the blackberry rust fungus Phragmidium violaceum

USDA-ARS?s Scientific Manuscript database

Eleven polymorphic microsatellite markers were developed for the Uredinales fungus Phragmidium violaceum, which causes leaf rust on European blackberry (Rubus fruticosus L. aggregate). Allele frequency ranged between two and seventeen alleles per locus with no evidence of linkage disequilibrium amon...

Forensic parameters for 15 autosomal STRs in Mestizo population from the state of Guerrero (South, Mexico).

PubMed

Locia-Aguilar, G J; López-Saucedo, B; Deheza-Bautista, S; Salado-Beltrán, O V; Martínez-Sevilla, V M; Rangel-Villalobos, H

2018-03-31

Allele distribution and forensic parameters were estimated for 15 STR loci (AmpFlSTR Identifiler kit) in 251 Mexican-Mestizos from the state of Guerrero (South, Mexico). Genotype distribution was in agreement with Hardy-Weinberg expectations for all 15 STRs. Similarly, linkage disequilibrium test demonstrated no association between pair of loci. The power of exclusion and power of discrimination values were 99.999634444% and >99.99999999%, respectively. Genetic relationship analysis regarding Mestizo populations from the main geographic regions of Mexico suggests that the Center and the present South regions conform one population cluster, separated from the Southeast and Northwest regions. Copyright © 2018 Elsevier B.V. All rights reserved.

Isolation and characterization of microsatellite loci in Alasmidonta heterodon (Bivalvia: Unionidae)

USGS Publications Warehouse

Shaw, K.M.; King, T.L.; Lellis, W.A.; Eackles, M.S.

2006-01-01

We developed 13 species-specific microsatellite markers for the federally endangered Atlantic slope unionid Alasmidonta heterodon. Four to 18 alleles per locus were observed among 30 individuals. Observed heterozygosity throughout the loci ranged from 26.9 to 86.2% and averaged 63.6%. Estimates of individual pairwise genetic distances indicated that levels of genetic diversity among loci were sufficient to produce unique multilocus genotypes for all animals surveyed. Randomization tests showed that genotypes for this collection were consistent with Hardy-Weinberg expectations, and no significant linkage disequilibrium was observed between loci. These loci therefore appear suitable for population surveys, kinship assessment and other such applications. ?? 2006 Blackwell Publishing Ltd.

Bayesian linkage and segregation analysis: factoring the problem.

PubMed

Matthysse, S

2000-01-01

Complex segregation analysis and linkage methods are mathematical techniques for the genetic dissection of complex diseases. They are used to delineate complex modes of familial transmission and to localize putative disease susceptibility loci to specific chromosomal locations. The computational problem of Bayesian linkage and segregation analysis is one of integration in high-dimensional spaces. In this paper, three available techniques for Bayesian linkage and segregation analysis are discussed: Markov Chain Monte Carlo (MCMC), importance sampling, and exact calculation. The contribution of each to the overall integration will be explicitly discussed.

Measuring demand for flat water recreation using a two-stage/disequilibrium travel cost model with adjustment for overdispersion and self-selection

NASA Astrophysics Data System (ADS)

McKean, John R.; Johnson, Donn; Taylor, R. Garth

2003-04-01

An alternate travel cost model is applied to an on-site sample to estimate the value of flat water recreation on the impounded lower Snake River. Four contiguous reservoirs would be eliminated if the dams are breached to protect endangered Pacific salmon and steelhead trout. The empirical method applies truncated negative binomial regression with adjustment for endogenous stratification. The two-stage decision model assumes that recreationists allocate their time among work and leisure prior to deciding among consumer goods. The allocation of time and money among goods in the second stage is conditional on the predetermined work time and income. The second stage is a disequilibrium labor market which also applies if employers set work hours or if recreationists are not in the labor force. When work time is either predetermined, fixed by contract, or nonexistent, recreationists must consider separate prices and budgets for time and money.

Mobile assemblies of Bennett linkages from four-crease origami patterns

NASA Astrophysics Data System (ADS)

Zhang, Xiao; Chen, Yan

2018-02-01

This paper deals with constructing mobile assemblies of Bennett linkages inspired by four-crease origami patterns. A transition technique has been proposed by taking the thick-panel form of an origami pattern as an intermediate bridge. A zero-thickness rigid origami pattern and its thick-panel form share the same sector angles and folding behaviours, while the thick-panel origami and the mobile assembly of linkages are kinematically equivalent with differences only in link profiles. Applying this transition technique to typical four-crease origami patterns, we have found that the Miura-ori and graded Miura-ori patterns lead to assemblies of Bennett linkages with identical link lengths. The supplementary-type origami patterns with different mountain-valley crease assignments correspond to different types of Bennett linkage assemblies with negative link lengths. And the identical linkage-type origami pattern generates a new mobile assembly. Hence, the transition technique offers a novel approach to constructing mobile assemblies of spatial linkages from origami patterns.

Mobile assemblies of Bennett linkages from four-crease origami patterns.

PubMed

Zhang, Xiao; Chen, Yan

2018-02-01

This paper deals with constructing mobile assemblies of Bennett linkages inspired by four-crease origami patterns. A transition technique has been proposed by taking the thick-panel form of an origami pattern as an intermediate bridge. A zero-thickness rigid origami pattern and its thick-panel form share the same sector angles and folding behaviours, while the thick-panel origami and the mobile assembly of linkages are kinematically equivalent with differences only in link profiles. Applying this transition technique to typical four-crease origami patterns, we have found that the Miura-ori and graded Miura-ori patterns lead to assemblies of Bennett linkages with identical link lengths. The supplementary-type origami patterns with different mountain-valley crease assignments correspond to different types of Bennett linkage assemblies with negative link lengths. And the identical linkage-type origami pattern generates a new mobile assembly. Hence, the transition technique offers a novel approach to constructing mobile assemblies of spatial linkages from origami patterns.

Magnesium isotopic evidence for chemical disequilibrium among cumulus minerals in layered mafic intrusion

NASA Astrophysics Data System (ADS)

Chen, Lie-Meng; Teng, Fang-Zhen; Song, Xie-Yan; Hu, Rui-Zhong; Yu, Song-Yue; Zhu, Dan; Kang, Jian

2018-04-01

Magnesium isotopic compositions of olivine, clinopyroxene, and ilmenite from the Baima intrusion, SW China, for the first time, are investigated to constrain the magnitude and mechanisms of Mg isotope fractionation among cumulus minerals in layered mafic intrusions and to evaluate their geological implications. Olivine and clinopyroxene have limited Mg isotope variations, with δ26Mg ranging from -0.33 to +0.05‰ and from -0.29 to -0.13‰, respectively, similar to those of mantle xenolithic peridotites. By contrast, ilmenites display extremely large Mg isotopic variation, with δ26Mg ranging from -0.50 to +1.90‰. The large inter-mineral fractionations of Mg isotopes between ilmenite and silicates may reflect both equilibrium and kinetic processes. A few ilmenites have lighter Mg isotopic compositions than coexisting silicates and contain high MgO contents without compositional zoning, indicating equilibrium fractionation. The implication is that the light Mg isotopic compositions of lunar high-Ti basalts may result from an isotopically light source enriched in cumulate ilmenites. On the other hand, most ilmenites have heavy Mg isotopic compositions, coupled with high MgO concentration and chemical zoning, which can be quantitatively modeled by kinetic Mg isotope fractionations induced by subsolidus Mg-Fe exchange between ilmenite and ferromagnesian silicates during the cooling of the Baima intrusion. The extensive occurrence of kinetic Mg isotope fractionation in ilmenites implies the possibility of widespread compositional disequilibrium among igneous minerals in magma chambers. Consequently, disequilibrium effects need to be considered in studies of basaltic magma evolution, magma chamber processes, and magmatic Fe-Ti oxide ore genesis.

Dimensional threshold for fracture linkage and hooking

NASA Astrophysics Data System (ADS)

Lamarche, Juliette; Chabani, Arezki; Gauthier, Bertrand D. M.

2018-03-01

Fracture connectivity in rocks depends on spatial properties of the pattern including length, abundance and orientation. When fractures form a single-strike set, they hardly cross-cut each other and the connectivity is limited. Linkage probability increases with increasing fracture abundance and length as small fractures connect to each other to form longer ones. A process for parallel fracture linkage is the "hooking", where two converging fracture tips mutually deviate and then converge to connect due to the interaction of their crack-tip stresses. Quantifying the processes and conditions for fracture linkage in single-strike fracture sets is crucial to better predicting fluid flow in Naturally Fractured Reservoirs. For 1734 fractures in Permian shales of the Lodève Basin, SE France, we measured geometrical parameters in 2D, characterizing three stages of the hooking process: underlapping, overlapping and linkage. We deciphered the threshold values, shape ratios and limiting conditions to switch from one stage to another one. The hook set up depends on the spacing (S) and fracture length (Lh) with the relation S ≈ 0.15 Lh. Once the hooking is initiated, with the fracture deviation length (L) L ≈ 0.4 Lh, the fractures reaches the linkage stage only when the spacing is reduced to S ≈ 0.02 Lh and the convergence (C) is < 0.1 L. These conditions apply to multi-scale fractures with a shape ratio L/S = 10 and for fracture curvature of 10°-20°.

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…

Internal Variability and Disequilibrium Confound Estimates of Climate Sensitivity from Observations

NASA Technical Reports Server (NTRS)

Marvel, Kate; Pincus, Robert; Schmidt, Gavin A.; Miller, Ron L.

2018-01-01

An emerging literature suggests that estimates of equilibrium climate sensitivity (ECS) derived from recent observations and energy balance models are biased low because models project more positive climate feedback in the far future. Here we use simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5) to show that across models, ECS inferred from the recent historical period (1979-2005) is indeed almost uniformly lower than that inferred from simulations subject to abrupt increases in CO2-radiative forcing. However, ECS inferred from simulations in which sea surface temperatures are prescribed according to observations is lower still. ECS inferred from simulations with prescribed sea surface temperatures is strongly linked to changes to tropical marine low clouds. However, feedbacks from these clouds are a weak constraint on long-term model ECS. One interpretation is that observations of recent climate changes constitute a poor direct proxy for long-term sensitivity.

Internal Variability and Disequilibrium Confound Estimates of Climate Sensitivity From Observations

NASA Astrophysics Data System (ADS)

Marvel, Kate; Pincus, Robert; Schmidt, Gavin A.; Miller, Ron L.

2018-02-01

An emerging literature suggests that estimates of equilibrium climate sensitivity (ECS) derived from recent observations and energy balance models are biased low because models project more positive climate feedback in the far future. Here we use simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5) to show that across models, ECS inferred from the recent historical period (1979-2005) is indeed almost uniformly lower than that inferred from simulations subject to abrupt increases in CO2 radiative forcing. However, ECS inferred from simulations in which sea surface temperatures are prescribed according to observations is lower still. ECS inferred from simulations with prescribed sea surface temperatures is strongly linked to changes to tropical marine low clouds. However, feedbacks from these clouds are a weak constraint on long-term model ECS. One interpretation is that observations of recent climate changes constitute a poor direct proxy for long-term sensitivity.

Record linkage for pharmacoepidemiological studies in cancer patients.

PubMed

Herk-Sukel, Myrthe P P van; Lemmens, Valery E P P; Poll-Franse, Lonneke V van de; Herings, Ron M C; Coebergh, Jan Willem W

2012-01-01

An increasing need has developed for the post-approval surveillance of (new) anti-cancer drugs by means of pharmacoepidemiology and outcomes research in the area of oncology. To create an overview that makes researchers aware of the available database linkages in Northern America and Europe which facilitate pharmacoepidemiology and outcomes research in cancer patients. In addition to our own database, i.e. the Eindhoven Cancer Registry (ECR) linked to the PHARMO Record Linkage System, we considered database linkages between a population-based cancer registry and an administrative healthcare database that at least contains information on drug use and offers a longitudinal perspective on healthcare utilization. Eligible database linkages were limited to those that had been used in multiple published articles in English language included in Pubmed. The HMO Cancer Research Network (CRN) in the US was excluded from this review, as an overview of the linked databases participating in the CRN is already provided elsewhere. Researchers who had worked with the data resources included in our review were contacted for additional information and verification of the data presented in the overview. The following database linkages were included: the Surveillance, Epidemiology, and End-Results-Medicare; cancer registry data linked to Medicaid; Canadian cancer registries linked to population-based drug databases; the Scottish cancer registry linked to the Tayside drug dispensing data; linked databases in the Nordic Countries of Europe: Norway, Sweden, Finland and Denmark; and the ECR-PHARMO linkage in the Netherlands. Descriptives of the included database linkages comprise population size, generalizability of the population, year of first data availability, contents of the cancer registry, contents of the administrative healthcare database, the possibility to select a cancer-free control cohort, and linkage to other healthcare databases. The linked databases offer a longitudinal

A guide to evaluating linkage quality for the analysis of linked data.

PubMed

Harron, Katie L; Doidge, James C; Knight, Hannah E; Gilbert, Ruth E; Goldstein, Harvey; Cromwell, David A; van der Meulen, Jan H

2017-10-01

Linked datasets are an important resource for epidemiological and clinical studies, but linkage error can lead to biased results. For data security reasons, linkage of personal identifiers is often performed by a third party, making it difficult for researchers to assess the quality of the linked dataset in the context of specific research questions. This is compounded by a lack of guidance on how to determine the potential impact of linkage error. We describe how linkage quality can be evaluated and provide widely applicable guidance for both data providers and researchers. Using an illustrative example of a linked dataset of maternal and baby hospital records, we demonstrate three approaches for evaluating linkage quality: applying the linkage algorithm to a subset of gold standard data to quantify linkage error; comparing characteristics of linked and unlinked data to identify potential sources of bias; and evaluating the sensitivity of results to changes in the linkage procedure. These approaches can inform our understanding of the potential impact of linkage error and provide an opportunity to select the most appropriate linkage procedure for a specific analysis. Evaluating linkage quality in this way will improve the quality and transparency of epidemiological and clinical research using linked data. © The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association.

Evaluation of Bovine High-Density SNP Genotyping Array in Indigenous Dairy Cattle Breeds.

PubMed

Dash, S; Singh, A; Bhatia, A K; Jayakumar, S; Sharma, A; Singh, S; Ganguly, I; Dixit, S P

2018-04-03

In total 52 samples of Sahiwal ( 19 ), Tharparkar ( 17 ), and Gir ( 16 ) were genotyped by using BovineHD SNP chip to analyze minor allele frequency (MAF), genetic diversity, and linkage disequilibrium among these cattle. The common SNPs of BovineHD and 54K SNP Chips were also extracted and evaluated for their performance. Only 40%-50% SNPs of these arrays was found informative for genetic analysis in these cattle breeds. The overall mean of MAF for SNPs of BovineHD SNPChip was 0.248 ± 0.006, 0.241 ± 0.007, and 0.242 ± 0.009 in Sahiwal, Tharparkar and Gir, respectively, while that for 54K SNPs was on lower side. The average Reynold's genetic distance between breeds ranged from 0.042 to 0.055 based on BovineHD Beadchip, and from 0.052 to 0.084 based on 54K SNP Chip. The estimates of genetic diversity based on HD and 54K chips were almost same and, hence, low density chip seems to be good enough to decipher genetic diversity of these cattle breeds. The linkage disequilibrium started decaying (r 2  < 0.2) at 140 kb inter-marker distance and, hence, a 20K low density customized SNP array from HD chip could be designed for genomic selection in these cattle else the 54K Bead Chip as such will be useful.

Genetic heritage of the Old Order Mennonites of southeastern Pennsylvania.

PubMed

Puffenberger, E G

2003-08-15

The Old Order Mennonites of southeastern Pennsylvania are a religious isolate with origins in 16th-century Switzerland. The Swiss Mennonites immigrated to Pennsylvania over a 50-year period in the early 18th century. The history of this population in the United States provides insight into the increased incidence of several genetic diseases, most notably maple syrup urine disease (MSUD), Hirschsprung disease (HSCR), and congenital nephrotic syndrome. A comparison between the Old Order Mennonites and the Old Order Amish demonstrates the unique genetic heritage of each group despite a common religious and geographic history. Unexpectedly, several diseases in both groups demonstrate allelic and/or locus heterogeneity. The population genetics of the 1312T --> A BCKDHA gene mutation, which causes classical MSUD, are presented in detail. The incidence of MSUD in the Old Order Mennonites is estimated to be 1/358 births, yielding a corrected carrier frequency of 7.96% and a mutation allele frequency of 4.15%. Analysis of the population demonstrates that repeated cycles of sampling effects, population bottlenecks, and subsequent genetic drift were important in shaping the current allele frequencies. A linkage disequilibrium analysis of 1312T --> A mutation haplotypes is provided and discussed in the context of the known genealogical history of the population. Finally, data from microsatellite marker genotyping within the Old Order Mennonite population are provided that show a significant but modest decrease in genetic diversity and elevated levels of background linkage disequilibrium. Copyright 2003 Wiley-Liss, Inc.

Polymorphisms of VEGF and VEGF receptors are associated with the occurrence of ovarian hyperstimulation syndrome (OHSS)—a retrospective case–control study

PubMed Central

2014-01-01

Background Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of IVF/ICSI therapy. The pathophysiology and etiology of the disease is still not fully clarified. Methods To assess whether polymorphisms of the VEGF/VEGF-receptor system contribute to the occurrence of ovarian hyperstimulation syndrome (OHSS), we performed a retrospective analysis of 116 OHSS patients, and 124 female controls. The following SNPs were genotyped: Rs2071559 (VEGFR2-604); rs2305948 (VEGFR2-1192); rs1870377 (VEGFR2-1719); rs2010963 (VEGF-405); and rs111458691 (VEGFR1-519). Odds ratios (ORs) were estimated with a 95% confidence interval (CI). Linkage disequilibrium (LD) analysis was performed in the three loci of the VEGFR2 gene. Result We found an overrepresentation of the T allele of the VEGFR1-519 polymorphism in OHSS patients (P = 0.02, OR: 3.62, CI: 1.16 – 11.27). By genotype modeling, we found that polymorphism of VEGFR1-519 and VEGF-405 showed significant differences in patients and controls (p = 0.02, OR: 3.79 CI: 1.98 – 11.97 and p = 0.000005, OR: 0.29, CI: 0.17 – 0.50). LD analysis revealed significant linkage disequilibrium in VEGFR2. Conclusion Polymorphisms in the VEGFR2 gene and in the VEGF gene are associated with the occurrence of OHSS. This strengthens the evidence for an important role of the VEGF/VEGF- receptor system in the occurrence of OHSS. PMID:24851136

Polymorphisms of VEGF and VEGF receptors are associated with the occurrence of ovarian hyperstimulation syndrome (OHSS)-a retrospective case-control study.

PubMed

Nouri, Kazem; Haslinger, Peter; Szabo, Ladislaus; Sator, Michael; Schreiber, Martin; Schneeberger, Christian; Pietrowski, Detlef

2014-01-01

Ovarian hyperstimulation syndrome (OHSS) is the most serious complication of IVF/ICSI therapy. The pathophysiology and etiology of the disease is still not fully clarified. To assess whether polymorphisms of the VEGF/VEGF-receptor system contribute to the occurrence of ovarian hyperstimulation syndrome (OHSS), we performed a retrospective analysis of 116 OHSS patients, and 124 female controls. The following SNPs were genotyped: Rs2071559 (VEGFR2-604); rs2305948 (VEGFR2-1192); rs1870377 (VEGFR2-1719); rs2010963 (VEGF-405); and rs111458691 (VEGFR1-519). Odds ratios (ORs) were estimated with a 95% confidence interval (CI). Linkage disequilibrium (LD) analysis was performed in the three loci of the VEGFR2 gene. We found an overrepresentation of the T allele of the VEGFR1-519 polymorphism in OHSS patients (P = 0.02, OR: 3.62, CI: 1.16 - 11.27). By genotype modeling, we found that polymorphism of VEGFR1-519 and VEGF-405 showed significant differences in patients and controls (p = 0.02, OR: 3.79 CI: 1.98 - 11.97 and p = 0.000005, OR: 0.29, CI: 0.17 - 0.50). LD analysis revealed significant linkage disequilibrium in VEGFR2. Polymorphisms in the VEGFR2 gene and in the VEGF gene are associated with the occurrence of OHSS. This strengthens the evidence for an important role of the VEGF/VEGF- receptor system in the occurrence of OHSS.

Correcting anthropogenic ocean heat uptake estimates for the Little Ice Age

NASA Astrophysics Data System (ADS)

Gebbie, Geoffrey

2017-04-01

Estimates of anthropogenic ocean heat uptake typically assume that the ocean was in equilibrium during the pre-industrial era. Recent reconstructions of the Common Era, however, show a multi-century surface cooling trend before the Industrial Revolution. Using a time-evolving state estimation method, we find that the 1750 C.E. ocean must have been out of equilibrium in order to fit the H.M.S. Challenger, WOCE, and Argo hydrographic data. When the disequilibrated ocean conditions are taken into account, the inferred ocean heat uptake from 1750-2014 C.E. is revised due to the deep ocean memory of Little Ice Age surface forcing. These effects of ocean disequilibrium should also be considered when interpreting climate sensitivity estimates.

Progress in a genome scan for linkage in schizophrenia in a large Swedish kindred

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barr, C.L.; Kennedy, J.L.; Pakstis, A.J.

1994-03-15

Genetic linkage studies of a kindred from Sweden segregating for schizophrenia have been performed using a genetic model (autosomal dominant, f - 0.72, q - 0.02, phenocopies=0.001) as described in Kennedy et al., 1988. Analyses of the restriction fragment length polymorphism (RFLP), allele-specific oligonucleotides (ASO), and short tandem repeat (STR also called microsatellite) data for 180 polymorphisms (individual probe-enzyme, ASO, or STR systems) at 155 loci have been completed using the MLINK and LIPED programs. Linkage to schizophrenia was excluded, under the given model, at 47 loci; indeterminate lod scores occurred at 108 loci. The total exclusion region across 20more » chromosomes is estimated at 330 cM; 211 cM excluded by pairwise analyses and 119 cM previously excluded by multipoint analyses. 37 refs., 2 tabs.« less

Genome-wide differentiation of various melon horticultural groups for use in genome wide association study for fruit firmness and construction of a high resolution genetic map

USDA-ARS?s Scientific Manuscript database

We generated 13,789 single nucleotide plymorphism (SNP) markers from 97 melon accessions using genotyping by sequencing and anchored them to chromosomes to understand genome-wide fixation index between various melon morphotypes and linkage disequilibrium (LD) decay for inodorus and cantalupensis, th...

A gene-based SNP resource and linkage map for the copepod Tigriopus californicus

PubMed Central

2011-01-01

Background As yet, few genomic resources have been developed in crustaceans. This lack is particularly evident in Copepoda, given the extraordinary numerical abundance, and taxonomic and ecological diversity of this group. Tigriopus californicus is ideally suited to serve as a genetic model copepod and has been the subject of extensive work in environmental stress and reproductive isolation. Accordingly, we set out to develop a broadly-useful panel of genetic markers and to construct a linkage map dense enough for quantitative trait locus detection in an interval mapping framework for T. californicus--a first for copepods. Results One hundred and ninety Single Nucleotide Polymorphisms (SNPs) were used to genotype our mapping population of 250 F2 larvae. We were able to construct a linkage map with an average intermarker distance of 1.8 cM, and a maximum intermarker distance of 10.3 cM. All markers were assembled into linkage groups, and the 12 linkage groups corresponded to the 12 known chromosomes of T. californicus. We estimate a total genome size of 401.0 cM, and a total coverage of 73.7%. Seventy five percent of the mapped markers were detected in 9 additional populations of T. californicus. Of available model arthropod genomes, we were able to show more colocalized pairs of homologues between T. californicus and the honeybee Apis mellifera, than expected by chance, suggesting preserved macrosynteny between Hymenoptera and Copepoda. Conclusions Our study provides an abundance of linked markers spanning all chromosomes. Many of these markers are also found in multiple populations of T. californicus, and in two other species in the genus. The genomic resource we have developed will enable mapping throughout the geographical range of this species and in closely related species. This linkage map will facilitate genome sequencing, mapping and assembly in an ecologically and taxonomically interesting group for which genomic resources are currently under development

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.

HIV and cancer registry linkage identifies a substantial burden of cancers in persons with HIV in India

PubMed Central

Godbole, Sheela V.; Nandy, Karabi; Gauniyal, Mansi; Nalawade, Pallavi; Sane, Suvarna; Koyande, Shravani; Toyama, Joy; Hegde, Asha; Virgo, Phil; Bhatia, Kishor; Paranjape, Ramesh S.; Risbud, Arun R.; Mbulaiteye, Sam M.; Mitsuyasu, Ronald T.

2016-01-01

Abstract We utilized computerized record-linkage methods to link HIV and cancer databases with limited unique identifiers in Pune, India, to determine feasibility of linkage and obtain preliminary estimates of cancer risk in persons living with HIV (PLHIV) as compared with the general population. Records of 32,575 PLHIV were linked to 31,754 Pune Cancer Registry records (1996–2008) using a probabilistic-matching algorithm. Cancer risk was estimated by calculating standardized incidence ratios (SIRs) in the early (4–27 months after HIV registration), late (28–60 months), and overall (4–60 months) incidence periods. Cancers diagnosed prior to or within 3 months of HIV registration were considered prevalent. Of 613 linked cancers to PLHIV, 188 were prevalent, 106 early incident, and 319 late incident. Incident cancers comprised 11.5% AIDS-defining cancers (ADCs), including cervical cancer and non-Hodgkin lymphoma (NHL), but not Kaposi sarcoma (KS), and 88.5% non-AIDS-defining cancers (NADCs). Risk for any incident cancer diagnosis in early, late, and combined periods was significantly elevated among PLHIV (SIRs: 5.6 [95% CI 4.6–6.8], 17.7 [95% CI 15.8–19.8], and 11.5 [95% CI 10–12.6], respectively). Cervical cancer risk was elevated in both incidence periods (SIRs: 9.6 [95% CI 4.8–17.2] and 22.6 [95% CI 14.3–33.9], respectively), while NHL risk was elevated only in the late incidence period (SIR: 18.0 [95% CI 9.8–30.20]). Risks for NADCs were dramatically elevated (SIR > 100) for eye-orbit, substantially (SIR > 20) for all-mouth, esophagus, breast, unspecified-leukemia, colon-rectum-anus, and other/unspecified cancers; moderately elevated (SIR > 10) for salivary gland, penis, nasopharynx, and brain-nervous system, and mildly elevated (SIR > 5) for stomach. Risks for 6 NADCs (small intestine, testis, lymphocytic leukemia, prostate, ovary, and melanoma) were not elevated and 5 cancers, including multiple myeloma not seen. Our study

HIV and cancer registry linkage identifies a substantial burden of cancers in persons with HIV in India.

PubMed

Godbole, Sheela V; Nandy, Karabi; Gauniyal, Mansi; Nalawade, Pallavi; Sane, Suvarna; Koyande, Shravani; Toyama, Joy; Hegde, Asha; Virgo, Phil; Bhatia, Kishor; Paranjape, Ramesh S; Risbud, Arun R; Mbulaiteye, Sam M; Mitsuyasu, Ronald T

2016-09-01

We utilized computerized record-linkage methods to link HIV and cancer databases with limited unique identifiers in Pune, India, to determine feasibility of linkage and obtain preliminary estimates of cancer risk in persons living with HIV (PLHIV) as compared with the general population.Records of 32,575 PLHIV were linked to 31,754 Pune Cancer Registry records (1996-2008) using a probabilistic-matching algorithm. Cancer risk was estimated by calculating standardized incidence ratios (SIRs) in the early (4-27 months after HIV registration), late (28-60 months), and overall (4-60 months) incidence periods. Cancers diagnosed prior to or within 3 months of HIV registration were considered prevalent.Of 613 linked cancers to PLHIV, 188 were prevalent, 106 early incident, and 319 late incident. Incident cancers comprised 11.5% AIDS-defining cancers (ADCs), including cervical cancer and non-Hodgkin lymphoma (NHL), but not Kaposi sarcoma (KS), and 88.5% non-AIDS-defining cancers (NADCs). Risk for any incident cancer diagnosis in early, late, and combined periods was significantly elevated among PLHIV (SIRs: 5.6 [95% CI 4.6-6.8], 17.7 [95% CI 15.8-19.8], and 11.5 [95% CI 10-12.6], respectively). Cervical cancer risk was elevated in both incidence periods (SIRs: 9.6 [95% CI 4.8-17.2] and 22.6 [95% CI 14.3-33.9], respectively), while NHL risk was elevated only in the late incidence period (SIR: 18.0 [95% CI 9.8-30.20]). Risks for NADCs were dramatically elevated (SIR > 100) for eye-orbit, substantially (SIR > 20) for all-mouth, esophagus, breast, unspecified-leukemia, colon-rectum-anus, and other/unspecified cancers; moderately elevated (SIR > 10) for salivary gland, penis, nasopharynx, and brain-nervous system, and mildly elevated (SIR > 5) for stomach. Risks for 6 NADCs (small intestine, testis, lymphocytic leukemia, prostate, ovary, and melanoma) were not elevated and 5 cancers, including multiple myeloma not seen.Our study demonstrates the feasibility of

210Pb in the western Indian Ocean: distribution, disequilibrium, and partitioning between dissolved and particulate phases

NASA Astrophysics Data System (ADS)

Chung, Y.

1987-09-01

Dissolved 210Pb profiles are presented for 13 GEOSECS stations in the western Indian Ocean. In surface water away from high southern latitudes, 210Pb is in excess over 226Ra due to the atmospheric fallout from decay of 222Rn. Except in the Circumpolar region, the dissolved 210Pb profiles display a gentle mid-depth maximum similar to the corresponding 226Ra profiles. The 210Pb/ 226Ra activity ratio ranges from 1.6 in the surface water east of Madagascar to 0.4 or less in the bottom water of all the basins. The lowest ratio observed was 0.1 in the Gulf of Aden very close to the continental land mass. A ratio of 0.6 divides the western Indian Ocean horizontally into two portions, with the contour at shallower depth in the north than in the south. The deep water disequilibrium is thus more extensive north of Madagascar than south of it. It appears that locality and bottom topography play a strong role in controlling the distributions of 210Pb and 226Ra as well as their extent of disequilibrium in the water column. The mean residence time for Pb with respect to particulate and boundary scavenging in the deep water ranges from about 15 to 75 years.

Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations-significant evidence for linkage on chromosome 4q in African Americans: the Family Investigation of Nephropathy and Diabetes Research Group.

PubMed

Malhotra, Alka; Igo, Robert P; Thameem, Farook; Kao, W H Linda; Abboud, Hanna E; Adler, Sharon G; Arar, Nedal H; Bowden, Donald W; Duggirala, Ravindranath; Freedman, Barry I; Goddard, Katrina A B; Ipp, Eli; Iyengar, Sudha K; Kimmel, Paul L; Knowler, William C; Kohn, Orly; Leehey, David; Meoni, Lucy A; Nelson, Robert G; Nicholas, Susanne B; Parekh, Rulan S; Rich, Stephen S; Chen, Yii-Der I; Saad, Mohammed F; Scavini, Marina; Schelling, Jeffrey R; Sedor, John R; Shah, Vallabh O; Taylor, Kent D; Thornley-Brown, Denyse; Zager, Philip G; Horvath, Amanda; Hanson, Robert L

2009-11-01

Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations. Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM. Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD = . 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD > 1.71 have been identified in previously published studies. The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.

Phase-Division-Based Dynamic Optimization of Linkages for Drawing Servo Presses

NASA Astrophysics Data System (ADS)

Zhang, Zhi-Gang; Wang, Li-Ping; Cao, Yan-Ke

2017-11-01

Existing linkage-optimization methods are designed for mechanical presses; few can be directly used for servo presses, so development of the servo press is limited. Based on the complementarity of linkage optimization and motion planning, a phase-division-based linkage-optimization model for a drawing servo press is established. Considering the motion-planning principles of a drawing servo press, and taking account of work rating and efficiency, the constraints of the optimization model are constructed. Linkage is optimized in two modes: use of either constant eccentric speed or constant slide speed in the work segments. The performances of optimized linkages are compared with those of a mature linkage SL4-2000A, which is optimized by a traditional method. The results show that the work rating of a drawing servo press equipped with linkages optimized by this new method improved and the root-mean-square torque of the servo motors is reduced by more than 10%. This research provides a promising method for designing energy-saving drawing servo presses with high work ratings.

Sex-specific linkage scans in opioid dependence.

PubMed

Yang, Bao-Zhu; Han, Shizhong; Kranzler, Henry R; Palmer, Abraham A; Gelernter, Joel

2017-04-01

Sex influences risk for opioid dependence (OD). We hypothesized that sex might interact with genetic loci that influence the risk for OD. Therefore we performed an analysis to identify sex-specific genomic susceptibility regions for OD using linkage. Over 6,000 single nucleotide polymorphism (SNP) markers were genotyped for 1,758 African- and European-American (AA and EA) individuals from 739 families, ascertained via affected sib-pairs with OD and/or cocaine dependence. Autosomewide non-parametric linkage scans, stratified by sex and population, were performed. We identified one significant linkage region, segregating with OD in EA men, at 71.1 cM on chromosome 4 (LOD = 3.29; point-wise P = 0.00005; empirical autosome-wide P = 0.042), which significantly differed from the linkage signal at the same location in EA women (empirical P = 0.002). Three suggestive linkage signals were identified at 181.3 cM on chromosome 7 (LOD = 2.18), 104 cM on chromosome 11 (LOD = 1.85), and 60.9 cM on chromosome 16 (LOD = 1.93) in EA women. In AA men, four suggestive linkage signals were detected at 201.1 cM on chromosome 3 (LOD = 2.32), 152.9 cM on chromosome 6 (LOD = 1.86), 16.8 cM on chromosome 7 (LOD = 1.95), and 36.1 cM on chromosome 17 (LOD = 1.99). The significant region, mapping to 4q12-4q13.1, harbors several OD candidate genes with interconnected functionality, including VEGFR, CLOCK, PDCL2, NMU, NRSF, and IGFBP7. In conclusion, these results provide an evidence for the existence of sex-specific and population-specific differences in OD. Furthermore, these results provide positional information that will facilitate the use of targeted next-generation sequencing to search for genes that contribute to sex-specific differences in OD. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Genome-wide association study identified three major QTL for carcass weight including the PLAG1-CHCHD7 QTN for stature in Japanese Black cattle

PubMed Central

2012-01-01

Background Significant quantitative trait loci (QTL) for carcass weight were previously mapped on several chromosomes in Japanese Black half-sib families. Two QTL, CW-1 and CW-2, were narrowed down to 1.1-Mb and 591-kb regions, respectively. Recent advances in genomic tools allowed us to perform a genome-wide association study (GWAS) in cattle to detect associations in a general population and estimate their effect size. Here, we performed a GWAS for carcass weight using 1156 Japanese Black steers. Results Bonferroni-corrected genome-wide significant associations were detected in three chromosomal regions on bovine chromosomes (BTA) 6, 8, and 14. The associated single nucleotide polymorphisms (SNP) on BTA 6 were in linkage disequilibrium with the SNP encoding NCAPG Ile442Met, which was previously identified as a candidate quantitative trait nucleotide for CW-2. In contrast, the most highly associated SNP on BTA 14 was located 2.3-Mb centromeric from the previously identified CW-1 region. Linkage disequilibrium mapping led to a revision of the CW-1 region within a 0.9-Mb interval around the associated SNP, and targeted resequencing followed by association analysis highlighted the quantitative trait nucleotides for bovine stature in the PLAG1-CHCHD7 intergenic region. The association on BTA 8 was accounted for by two SNP on the BovineSNP50 BeadChip and corresponded to CW-3, which was simultaneously detected by linkage analyses using half-sib families. The allele substitution effects of CW-1, CW-2, and CW-3 were 28.4, 35.3, and 35.0 kg per allele, respectively. Conclusion The GWAS revealed the genetic architecture underlying carcass weight variation in Japanese Black cattle in which three major QTL accounted for approximately one-third of the genetic variance. PMID:22607022

Position Estimation for Switched Reluctance Motor Based on the Single Threshold Angle

NASA Astrophysics Data System (ADS)

Zhang, Lei; Li, Pang; Yu, Yue

2017-05-01

This paper presents a position estimate model of switched reluctance motor based on the single threshold angle. In view of the relationship of between the inductance and rotor position, the position is estimated by comparing the real-time dynamic flux linkage with the threshold angle position flux linkage (7.5° threshold angle, 12/8SRM). The sensorless model is built by Maltab/Simulink, the simulation are implemented under the steady state and transient state different condition, and verified its validity and feasibility of the method..

Student-Teacher Linkage Verification: Model Process and Recommendations

ERIC Educational Resources Information Center

Watson, Jeffery; Graham, Matthew; Thorn, Christopher A.

2012-01-01

As momentum grows for tracking the role of individual educators in student performance, school districts across the country are implementing projects that involve linking teachers to their students. Programs that link teachers to student outcomes require a verification process for student-teacher linkages. Linkage verification improves accuracy by…

Prospective Industrial Linkage at Aqaba University College, Jordan

ERIC Educational Resources Information Center

Abu-Hamatteh, Zeid; Al-Amyan, Mozfi; Al-Azzam, Farouq

2008-01-01

The present study intends to examine the overall situation and the environment of Aqaba University College (AUC) in relation to industrial-educational interaction, and to discuss existing and possible future industrial linkage strategies. This article presents observations from AUC, as well as suggestions for action on industrial linkage. The…

Privacy-preserving genome-wide association studies on cloud environment using fully homomorphic encryption

PubMed Central

2015-01-01

Objective Developed sequencing techniques are yielding large-scale genomic data at low cost. A genome-wide association study (GWAS) targeting genetic variations that are significantly associated with a particular disease offers great potential for medical improvement. However, subjects who volunteer their genomic data expose themselves to the risk of privacy invasion; these privacy concerns prevent efficient genomic data sharing. Our goal is to presents a cryptographic solution to this problem. Methods To maintain the privacy of subjects, we propose encryption of all genotype and phenotype data. To allow the cloud to perform meaningful computation in relation to the encrypted data, we use a fully homomorphic encryption scheme. Noting that we can evaluate typical statistics for GWAS from a frequency table, our solution evaluates frequency tables with encrypted genomic and clinical data as input. We propose to use a packing technique for efficient evaluation of these frequency tables. Results Our solution supports evaluation of the D′ measure of linkage disequilibrium, the Hardy-Weinberg Equilibrium, the χ2 test, etc. In this paper, we take χ2 test and linkage disequilibrium as examples and demonstrate how we can conduct these algorithms securely and efficiently in an outsourcing setting. We demonstrate with experimentation that secure outsourcing computation of one χ2 test with 10, 000 subjects requires about 35 ms and evaluation of one linkage disequilibrium with 10, 000 subjects requires about 80 ms. Conclusions With appropriate encoding and packing technique, cryptographic solutions based on fully homomorphic encryption for secure computations of GWAS can be practical. PMID:26732892

Privacy-preserving genome-wide association studies on cloud environment using fully homomorphic encryption.

PubMed

Lu, Wen-Jie; Yamada, Yoshiji; Sakuma, Jun

2015-01-01

Developed sequencing techniques are yielding large-scale genomic data at low cost. A genome-wide association study (GWAS) targeting genetic variations that are significantly associated with a particular disease offers great potential for medical improvement. However, subjects who volunteer their genomic data expose themselves to the risk of privacy invasion; these privacy concerns prevent efficient genomic data sharing. Our goal is to presents a cryptographic solution to this problem. To maintain the privacy of subjects, we propose encryption of all genotype and phenotype data. To allow the cloud to perform meaningful computation in relation to the encrypted data, we use a fully homomorphic encryption scheme. Noting that we can evaluate typical statistics for GWAS from a frequency table, our solution evaluates frequency tables with encrypted genomic and clinical data as input. We propose to use a packing technique for efficient evaluation of these frequency tables. Our solution supports evaluation of the D' measure of linkage disequilibrium, the Hardy-Weinberg Equilibrium, the χ2 test, etc. In this paper, we take χ2 test and linkage disequilibrium as examples and demonstrate how we can conduct these algorithms securely and efficiently in an outsourcing setting. We demonstrate with experimentation that secure outsourcing computation of one χ2 test with 10, 000 subjects requires about 35 ms and evaluation of one linkage disequilibrium with 10, 000 subjects requires about 80 ms. With appropriate encoding and packing technique, cryptographic solutions based on fully homomorphic encryption for secure computations of GWAS can be practical.

A second generation genetic linkage map of Japanese flounder (Paralichthys olivaceus)

PubMed Central

2010-01-01

Background Japanese flounder (Paralichthys olivaceus) is one of the most economically important marine species in Northeast Asia. Information on genetic markers associated with quantitative trait loci (QTL) can be used in breeding programs to identify and select individuals carrying desired traits. Commercial production of Japanese flounder could be increased by developing disease-resistant fish and improving commercially important traits. Previous maps have been constructed with AFLP markers and a limited number of microsatellite markers. In this study, improved genetic linkage maps are presented. In contrast with previous studies, these maps were built mainly with a large number of codominant markers so they can potentially be used to analyze different families and populations. Results Sex-specific genetic linkage maps were constructed for the Japanese flounder including a total of 1,375 markers [1,268 microsatellites, 105 single nucleotide polymorphisms (SNPs) and two genes]; 1,167 markers are linked to the male map and 1,067 markers are linked to the female map. The lengths of the male and female maps are 1,147.7 cM and 833.8 cM, respectively. Based on estimations of map lengths, the female and male maps covered 79 and 82% of the genome, respectively. Recombination ratio in the new maps revealed F:M of 1:0.7. All linkage groups in the maps presented large differences in the location of sex-specific recombination hot-spots. Conclusions The improved genetic linkage maps are very useful for QTL analyses and marker-assisted selection (MAS) breeding programs for economically important traits in Japanese flounder. In addition, SNP flanking sequences were blasted against Tetraodon nigroviridis (puffer fish) and Danio rerio (zebrafish), and synteny analysis has been carried out. The ability to detect synteny among species or genera based on homology analysis of SNP flanking sequences may provide opportunities to complement initial QTL experiments with candidate gene

Detecting local haplotype sharing and haplotype association

USDA-ARS?s Scientific Manuscript database

A novel haplotype association method is presented, and its power is demonstrated. Relying on a statistical model for linkage disequilibrium (LD), the method first infers ancestral haplotypes and their loadings at each marker for each individual. The loadings are then used to quantify local haplotype...

Quantitative trait locus linkage analysis in a large Amish pedigree identifies novel candidate loci for erythrocyte traits

PubMed Central

Hinckley, Jesse D; Abbott, Diana; Burns, Trudy L; Heiman, Meadow; Shapiro, Amy D; Wang, Kai; Di Paola, Jorge

2013-01-01

We characterized a large Amish pedigree and, in 384 pedigree members, analyzed the genetic variance components with covariate screen as well as genome-wide quantitative trait locus (QTL) linkage analysis of red blood cell count (RBC), hemoglobin (HB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), platelet count (PLT), and white blood cell count (WBC) using SOLAR. Age and gender were found to be significant covariates in many CBC traits. We obtained significant heritability estimates for RBC, MCV, MCH, MCHC, RDW, PLT, and WBC. We report four candidate loci with Logarithm of the odds (LOD) scores above 2.0: 6q25 (MCH), 9q33 (WBC), 10p12 (RDW), and 20q13 (MCV). We also report eleven candidate loci with LOD scores between 1.5 and <2.0. Bivariate linkage analysis of MCV and MCH on chromosome 20 resulted in a higher maximum LOD score of 3.14. Linkage signals on chromosomes 4q28, 6p22, 6q25, and 20q13 are concomitant with previously reported QTL. All other linkage signals reported herein represent novel evidence of candidate QTL. Interestingly rs1800562, the most common causal variant of hereditary hemochromatosis in HFE (6p22) was associated with MCH and MCHC in this family. Linkage studies like the one presented here will allow investigators to focus the search for rare variants amidst the noise encountered in the large amounts of data generated by whole-genome sequencing. PMID:24058921

A Population Genetics Model of Marker-Assisted Selection

PubMed Central

Luo, Z. W.; Thompson, R.; Woolliams, J. A.

1997-01-01

A deterministic two-loci model was developed to predict genetic response to marker-assisted selection (MAS) in one generation and in multiple generations. Formulas were derived to relate linkage disequilibrium in a population to the proportion of additive genetic variance used by MAS, and in turn to an extra improvement in genetic response over phenotypic selection. Predictions of the response were compared to those predicted by using an infinite-loci model and the factors affecting efficiency of MAS were examined. Theoretical analyses of the present study revealed the nonlinearity between the selection intensity and genetic response in MAS. In addition to the heritability of the trait and the proportion of the marker-associated genetic variance, the frequencies of the selectively favorable alleles at the two loci, one marker and one quantitative trait locus, were found to play an important role in determining both the short- and long-term efficiencies of MAS. The evolution of linkage disequilibrium and thus the genetic response over several generations were predicted theoretically and examined by simulation. MAS dissipated the disequilibrium more quickly than drift alone. In some cases studied, the rate of dissipation was as large as that to be expected in the circumstance where the true recombination fraction was increased by three times and selection was absent. PMID:9215918

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.

Composite Bloom Filters for Secure Record Linkage

PubMed Central

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

2014-01-01

The process of record linkage seeks to integrate instances that correspond to the same entity. Record linkage has traditionally been performed through the comparison of identifying field values (e.g., Surname), however, when databases are maintained by disparate organizations, the disclosure of such information can breach the privacy of the corresponding individuals. Various private record linkage (PRL) methods have been developed to obscure such identifiers, but they vary widely in their ability to balance competing goals of accuracy, efficiency and security. The tokenization and hashing of field values into Bloom filters (BF) enables greater linkage accuracy and efficiency than other PRL methods, but the encodings may be compromised through frequency-based cryptanalysis. Our objective is to adapt a BF encoding technique to mitigate such attacks with minimal sacrifices in accuracy and efficiency. To accomplish these goals, we introduce a statistically-informed method to generate BF encodings that integrate bits from multiple fields, the frequencies of which are provably associated with a minimum number of fields. Our method enables a user-specified tradeoff between security and accuracy. We compare our encoding method with other techniques using a public dataset of voter registration records and demonstrate that the increases in security come with only minor losses to accuracy. PMID:25530689

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.

A high-density SNP linkage scan with 142 combined subtype ADHD sib pairs identifies linkage regions on chromosomes 9 and 16.

PubMed

Asherson, P; Zhou, K; Anney, R J L; Franke, B; Buitelaar, J; Ebstein, R; Gill, M; Altink, M; Arnold, R; Boer, F; Brookes, K; Buschgens, C; Butler, L; Cambell, D; Chen, W; Christiansen, H; Feldman, L; Fleischman, K; Fliers, E; Howe-Forbes, R; Goldfarb, A; Heise, A; Gabriëls, I; Johansson, L; Lubetzki, I; Marco, R; Medad, S; Minderaa, R; Mulas, F; Müller, U; Mulligan, A; Neale, B; Rijsdijk, F; Rabin, K; Rommelse, N; Sethna, V; Sorohan, J; Uebel, H; Psychogiou, L; Weeks, A; Barrett, R; Xu, X; Banaschewski, T; Sonuga-Barke, E; Eisenberg, J; Manor, I; Miranda, A; Oades, R D; Roeyers, H; Rothenberger, A; Sergeant, J; Steinhausen, H-C; Taylor, E; Thompson, M; Faraone, S V

2008-05-01

As part of the International Multi-centre ADHD Genetics project we completed an affected sibling pair study of 142 narrowly defined Diagnostic and Statistical Manual of Mental Disorders, fourth edition combined type attention deficit hyperactivity disorder (ADHD) proband-sibling pairs. No linkage was observed on the most established ADHD-linked genomic regions of 5p and 17p. We found suggestive linkage signals on chromosomes 9 and 16, respectively, with the highest multipoint nonparametric linkage signal on chromosome 16q23 at 99 cM (log of the odds, LOD=3.1) overlapping data published from the previous UCLA (University of California, Los Angeles) (LOD>1, approximately 95 cM) and Dutch (LOD>1, approximately 100 cM) studies. The second highest peak in this study was on chromosome 9q22 at 90 cM (LOD=2.13); both the previous UCLA and German studies also found some evidence of linkage at almost the same location (UCLA LOD=1.45 at 93 cM; German LOD=0.68 at 100 cM). The overlap of these two main peaks with previous findings suggests that loci linked to ADHD may lie within these regions. Meta-analysis or reanalysis of the raw data of all the available ADHD linkage scan data may help to clarify whether these represent true linked loci.

An Autosomal Genetic Linkage Map of the Sheep Genome

PubMed Central

Crawford, A. M.; Dodds, K. G.; Ede, A. J.; Pierson, C. A.; Montgomery, G. W.; Garmonsway, H. G.; Beattie, A. E.; Davies, K.; Maddox, J. F.; Kappes, S. W.; Stone, R. T.; Nguyen, T. C.; Penty, J. M.; Lord, E. A.; Broom, J. E.; Buitkamp, J.; Schwaiger, W.; Epplen, J. T.; Matthew, P.; Matthews, M. E.; Hulme, D. J.; Beh, K. J.; McGraw, R. A.; Beattie, C. W.

1995-01-01

We report the first extensive ovine genetic linkage map covering 2070 cM of the sheep genome. The map was generated from the linkage analysis of 246 polymorphic markers, in nine three-generation fullsib pedigrees, which make up the AgResearch International Mapping Flock. We have exploited many markers from cattle so that valuable comparisons between these two ruminant linkage maps can be made. The markers, used in the segregation analyses, comprised 86 anonymous microsatellite markers derived from the sheep genome, 126 anonymous microsatellites from cattle, one from deer, and 33 polymorphic markers of various types associated with known genes. The maximum number of informative meioses within the mapping flock was 222. The average number of informative meioses per marker was 140 (range 18-209). Linkage groups have been assigned to all 26 sheep autosomes. PMID:7498748

Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Villard, E.; Soubrier, F.; Tiret, L.

1996-06-01

Plasma angiotensin I-converting enzyme (ACE) levels are highly genetically determined. A previous segregation-linkage analysis suggested the existence of a functional mutation located within or close to the ACE locus, in almost complete linkage disequilibrium (LD) with the ACE insertion/deletion (I/D) polymorphism and accounting for half the ACE variance. In order to identify the functional variant at the molecular level, we compared ACE gene sequences between four subjects selected for having contrasted ACE levels and I/D genotypes. We identified 10 new polymorphisms, among which 8 were genotyped in 95 healthy nuclear families, in addition to the I/D polymorphism. These polymorphisms couldmore » be divided into two groups: five polymorphisms in the 5{prime} region and three in the coding sequence and the 3{prime} UTR. Within each group, polymorphisms were in nearly complete association, whereas polymorphisms from the two groups were in strong negative LD. After adjustment for the I/D polymorphism, all polymorphisms of the 5{prime} group remained significantly associated with ACE levels, which suggests the existence of two quantitative trait loci (QTL) acting additively on ACE levels. Segregation-linkage analyses including one or two ACE-linked QTLs in LD with two ACE markers were performed to test this hypothesis. The two QTLs and the two markers were assumed to be in complete LD. Results supported the existence of two ACE-linked QTLs, which would explain 38% and 49% of the ACE variance in parents and offspring, respectively. One of these QTLs might be the I/D polymorphism itself or the newly characterized 4656(CT){sub 2/3} polymorphism. The second QTL would have a frequency of {approximately}.20, which is incompatible with any of the yet-identified polymorphisms. More extensive sequencing and extended analyses in larger samples and in other populations will be necessary to characterize definitely the functional variants. 30 refs., 1 fig., 6 tabs.« less

Dynamic genetic linkage of intermediate blood pressure phenotypes during postural adaptations in a founder population

PubMed Central

Arenas, I. A.; Tremblay, J.; Deslauriers, B.; Sandoval, J.; Šeda, O.; Gaudet, D.; Merlo, E.; Kotchen, T.; Cowley, A. W.

2013-01-01

Blood pressure (BP) is a dynamic phenotype that varies rapidly to adjust to changing environmental conditions. Standing upright is a recent evolutionary trait, and genetic factors that influence postural adaptations may contribute to BP variability. We studied the effect of posture on the genetics of BP and intermediate BP phenotypes. We included 384 sib-pairs in 64 sib-ships from families ascertained by early-onset hypertension and dyslipidemia. Blood pressure, three hemodynamic and seven neuroendocrine intermediate BP phenotypes were measured with subjects lying supine and standing upright. The effect of posture on estimates of heritability and genetic covariance was investigated in full pedigrees. Linkage was conducted on 196 candidate genes by sib-pair analyses, and empirical estimates of significance were obtained. A permutation algorithm was implemented to study the postural effect on linkage. ADRA1A, APO, CAST, CORIN, CRHR1, EDNRB, FGF2, GC, GJA1, KCNB2, MMP3, NPY, NR3C2, PLN, TGFBR2, TNFRSF6, and TRHR showed evidence of linkage with any phenotype in the supine position and not upon standing, whereas AKR1B1, CD36, EDNRA, F5, MMP9, PKD2, PON1, PPARG, PPARGC1A, PRKCA, and RET were specifically linked to standing phenotypes. Genetic profiling was undertaken to show genetic interactions among intermediate BP phenotypes and genes specific to each posture. When investigators perform genetic studies exclusively on a single posture, important genetic components of BP are missed. Supine and standing BPs have distinct genetic signatures. Standardized maneuvers influence the results of genetic investigations into BP, thus reflecting its dynamic regulation. PMID:23269701

Equilibrium and Disequilibrium of River Basins: Effects on Stream Captures in Serra do Mar and Serra da Mantiqueira, Brazil

NASA Astrophysics Data System (ADS)

DA Silva, L. M.

2015-12-01

Landscapes are mainly driven by river processes that control the dynamic reorganization of networks. Discovering and identifying whether river basins are in geometric equilibrium or disequilibrium requires an analysis of water divides, channels that shift laterally or expand upstream and river captures. Issues specifically discussed include the variation of drainage area change and erosion rates of the basins. In southeastern Brazil there are two main escarpments with extensive geomorphic surfaces: Serra do Mar and Serra da Mantiqueira Mountains. These landscapes are constituted of Neoproterozoic and early Paleozoic rocks, presenting steep escarpments with low-elevation coastal plains and higher elevation interior plateaus. To identify whether river basins and river profiles are in equilibrium or disequilibrium in Serra do Mar and Serra da Mantiqueira Mountains, we used the proxy (χ), evaluating the effect of drainage area change and erosion rates. We selected basins that drain both sides of these two main escarpments (oceanic and continental sides) and have denudation rates derived from pre-existing cosmogenic isotopes data (Rio de Janeiro, Paraná and Minas Gerais). Despite being an ancient and tectonically stable landscape, part of the coastal plain of Serra do Mar Mountain in Rio de Janeiro and Paraná is in geometric disequilibrium, with water divides moving in the direction of higher χ values. To achieve equilibrium, some basins located in the continental side are retracting and disappearing, losing area to the coastal basins. On the contrary, there are some adjacent sub-basins that are close to equilibrium, without strong contrasts in χ values. The same pattern was observed in Serra da Mantiqueira (Minas Gerais state), with stream captures and river network reorganization in its main rivers. The initial results suggest a strong contrast between erosion rates in the continental and the oceanic portions of the escarpments.

Factors associated with linkage to HIV care and TB treatment at community-based HIV testing services in Cape Town, South Africa.

PubMed

Meehan, Sue-Ann; Sloot, Rosa; Draper, Heather R; Naidoo, Pren; Burger, Ronelle; Beyers, Nulda

2018-01-01

Diagnosing HIV and/or TB is not sufficient; linkage to care and treatment is conditional to reduce the burden of disease. This study aimed to determine factors associated with linkage to HIV care and TB treatment at community-based services in Cape Town, South Africa. This retrospective cohort study utilized routinely collected data from clients who utilized stand-alone (fixed site not attached to a health facility) and mobile HIV testing services in eight communities in the City of Cape Town Metropolitan district, between January 2008 and June 2012. Clients were included in the analysis if they were ≥12 years and had a known HIV status. Generalized estimating equations (GEE) logistic regression models were used to assess the association between determinants (sex, age, HIV testing service and co-infection status) and self-reported linkage to HIV care and/or TB treatment. Linkage to HIV care was 3 738/5 929 (63.1%). Linkage to HIV care was associated with the type of HIV testing service. Clients diagnosed with HIV at mobile services had a significantly reduced odds of linking to HIV care (aOR 0.7 (CI 95%: 0.6-0.8), p<0.001. Linkage to TB treatment was 210/275 (76.4%). Linkage to TB treatment was not associated with sex and service type, but was associated with age. Clients in older age groups were less likely to link to TB treatment compared to clients in the age group 12-24 years (all, p-value<0.05). A large proportion of clients diagnosed with HIV at mobile services did not link to care. Almost a quarter of clients diagnosed with TB did not link to treatment. Integrated community-based HIV and TB testing services are efficient in diagnosing HIV and TB, but strategies to improve linkage to care are required to control these epidemics.

Linkages between ACE Vocational Provision and Mainstream VET.

ERIC Educational Resources Information Center

Saunders, John

A study investigated linkages between adult community education (ACE) and mainstream vocational education and training (VET) in Australia, which enable people to move between the two sectors in their pursuit of vocational learning, and the ways in which linkages might be improved or new ones developed. The data from the study were derived from 69…

Validation of an instrument to measure inter-organisational linkages in general practice.

PubMed

Amoroso, Cheryl; Proudfoot, Judith; Bubner, Tanya; Jayasinghe, Upali W; Holton, Christine; Winstanley, Julie; Beilby, Justin; Harris, Mark F

2007-12-03

Linkages between general medical practices and external services are important for high quality chronic disease care. The purpose of this research is to describe the development, evaluation and use of a brief tool that measures the comprehensiveness and quality of a general practice's linkages with external providers for the management of patients with chronic disease. In this study, clinical linkages are defined as the communication, support, and referral arrangements between services for the care and assistance of patients with chronic disease. An interview to measure surgery-level (rather than individual clinician-level) clinical linkages was developed, piloted, reviewed, and evaluated with 97 Australian general practices. Two validated survey instruments were posted to patients, and a survey of locally available services was developed and posted to participating Divisions of General Practice (support organisations). Hypotheses regarding internal validity, association with local services, and patient satisfaction were tested using factor analysis, logistic regression and multilevel regression models. The resulting General Practice Clinical Linkages Interview (GP-CLI) is a nine-item tool with three underlying factors: referral and advice linkages, shared care and care planning linkages, and community access and awareness linkages. Local availability of chronic disease services has no affect on the comprehensiveness of services with which practices link, however, comprehensiveness of clinical linkages has an association with patient assessment of access, receptionist services, and of continuity of care in their general practice. The GP-CLI may be useful to researchers examining comparable health care systems for measuring the comprehensiveness and quality of linkages at a general practice-level with related services, possessing both internal and external validity. The tool can be used with large samples exploring the impact, outcomes, and facilitators of high

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

Population genetics of autopolyploids under a mixed mating model and the estimation of selfing rate.

PubMed

Hardy, Olivier J

2016-01-01

Nowadays, the population genetics analysis of autopolyploid species faces many difficulties due to (i) limited development of population genetics tools under polysomic inheritance, (ii) difficulties to assess allelic dosage when genotyping individuals and (iii) a form of inbreeding resulting from the mechanism of 'double reduction'. Consequently, few data analysis computer programs are applicable to autopolyploids. To contribute bridging this gap, this article first derives theoretical expectations for the inbreeding and identity disequilibrium coefficients under polysomic inheritance in a mixed mating model. Moment estimators of these coefficients are proposed when exact genotypes or just markers phenotypes (i.e. allelic dosage unknown) are available. This led to the development of estimators of the selfing rate based on adult genotypes or phenotypes and applicable to any even-ploidy level. Their statistical performances and robustness were assessed by numerical simulations. Contrary to inbreeding-based estimators, the identity disequilibrium-based estimator using phenotypes is robust (absolute bias generally < 0.05), even in the presence of double reduction, null alleles or biparental inbreeding due to isolation by distance. A fairly good precision of the selfing rate estimates (root mean squared error < 0.1) is already achievable using a sample of 30-50 individuals phenotyped at 10 loci bearing 5-10 alleles each, conditions reachable using microsatellite markers. Diallelic markers (e.g. SNP) can also perform satisfactorily in diploids and tetraploids but more polymorphic markers are necessary for higher ploidy levels. The method is implemented in the software SPAGeDi and should contribute to reduce the lack of population genetics tools applicable to autopolyploids. © 2015 John Wiley & Sons Ltd.

Evaluation of record linkage of two large administrative databases in a middle income country: stillbirths and notifications of dengue during pregnancy in Brazil.

PubMed

Paixão, Enny S; Harron, Katie; Andrade, Kleydson; Teixeira, Maria Glória; Fiaccone, Rosemeire L; Costa, Maria da Conceição N; Rodrigues, Laura C

2017-07-17

Due to the increasing availability of individual-level information across different electronic datasets, record linkage has become an efficient and important research tool. High quality linkage is essential for producing robust results. The objective of this study was to describe the process of preparing and linking national Brazilian datasets, and to compare the accuracy of different linkage methods for assessing the risk of stillbirth due to dengue in pregnancy. We linked mothers and stillbirths in two routinely collected datasets from Brazil for 2009-2010: for dengue in pregnancy, notifications of infectious diseases (SINAN); for stillbirths, mortality (SIM). Since there was no unique identifier, we used probabilistic linkage based on maternal name, age and municipality. We compared two probabilistic approaches, each with two thresholds: 1) a bespoke linkage algorithm; 2) a standard linkage software widely used in Brazil (ReclinkIII), and used manual review to identify further links. Sensitivity and positive predictive value (PPV) were estimated using a subset of gold-standard data created through manual review. We examined the characteristics of false-matches and missed-matches to identify any sources of bias. From records of 678,999 dengue cases and 62,373 stillbirths, the gold-standard linkage identified 191 cases. The bespoke linkage algorithm with a conservative threshold produced 131 links, with sensitivity = 64.4% (68 missed-matches) and PPV = 92.5% (8 false-matches). Manual review of uncertain links identified an additional 37 links, increasing sensitivity to 83.7%. The bespoke algorithm with a relaxed threshold identified 132 true matches (sensitivity = 69.1%), but introduced 61 false-matches (PPV = 68.4%). ReclinkIII produced lower sensitivity and PPV than the bespoke linkage algorithm. Linkage error was not associated with any recorded study variables. Despite a lack of unique identifiers for linking mothers and stillbirths, we demonstrate a

Linkage mapping in sheep and deer identifies a conserved pecora ruminant linkage group orthologous to two regions of HSA16 and a portion of HSA7Q

DOE Office of Scientific and Technical Information (OSTI.GOV)

Broom, J.E.; Tate, M.L.; Dodds, K.G.

1996-05-01

Two orthologous linkage groups have been mapped in sheep and deer. Seven loci have been mapped in deer, and 12 in sheep. The sheep linkage group is assigned of ovine chromosome 24. The linkage groups consist of loci from the short arm of human chromosome 16, spanning the region containing the human Batten disease locus, and from human chromosome 7. One locus from the long arm of human chromosome 16 is also present, demonstrating a previously unknown rearrangement between human and ruminant chromosomes. There is no significant difference in marker order and distances between the two linkage groups, implying thatmore » this linkage pattern was present in the genome of the common ancestor of the pecora ruminants. 35 refs., 1 fig., 2 tabs.« less

Recombination patterns reveal information about centromere location on linkage maps.

PubMed

Limborg, Morten T; McKinney, Garrett J; Seeb, Lisa W; Seeb, James E

2016-05-01

Linkage mapping is often used to identify genes associated with phenotypic traits and for aiding genome assemblies. Still, many emerging maps do not locate centromeres - an essential component of the genomic landscape. Here, we demonstrate that for genomes with strong chiasma interference, approximate centromere placement is possible by phasing the same data used to generate linkage maps. Assuming one obligate crossover per chromosome arm, information about centromere location can be revealed by tracking the accumulated recombination frequency along linkage groups, similar to half-tetrad analyses. We validate the method on a linkage map for sockeye salmon (Oncorhynchus nerka) with known centromeric regions. Further tests suggest that the method will work well in other salmonids and other eukaryotes. However, the method performed weakly when applied to a male linkage map (rainbow trout; O. mykiss) characterized by low and unevenly distributed recombination - a general feature of male meiosis in many species. Further, a high frequency of double crossovers along chromosome arms in barley reduced resolution for locating centromeric regions on most linkage groups. Despite these limitations, our method should work well for high-density maps in species with strong recombination interference and will enrich many existing and future mapping resources. © 2015 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd.

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

Population genetics related to adaptation in elite oat germplasm

USDA-ARS?s Scientific Manuscript database

Six hundred thirty five oat lines and 2,635 SNP loci were used to evaluate population structure, linkage disequilibrium (LD) and genotype-phenotype association with heading date. The first five principal components (PC) accounted for 25.3% of genetic variation. Neither the eigenvalues of the first 2...

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

Solid-Phase Synthesis of RNA Analogs Containing Phosphorodithioate Linkages.

PubMed

Yang, Xianbin

2017-09-18

The oligoribonucleotide phosphorodithioate (PS2-RNA) modification uses two sulfur atoms to replace two non-bridging oxygen atoms at an internucleotide phosphorodiester backbone linkage. Like a natural phosphodiester RNA backbone linkage, a PS2-modified backbone linkage is achiral at phosphorus. PS2-RNAs are highly stable to nucleases and several in vitro assays have demonstrated their biological activity. For example, PS2-RNAs silenced mRNA in vitro and bound to protein targets in the form of PS2-aptamers (thioaptamers). Thus, the interest in and promise of PS2-RNAs has drawn attention to synthesizing, isolating, and characterizing these compounds. RNA-thiophosphoramidite monomers are commercially available from AM Biotechnologies and this unit describes an effective methodology for solid-phase synthesis, deprotection, and purification of RNAs having PS2 internucleotide linkages. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

An autosomal genetic linkage map of the sheep genome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Crawford, A.M.; Ede, A.J.; Pierson, C.A.

1995-06-01

We report the first extensive ovine genetic linkage map covering 2070 cM of the sheep genome. The map was generated from the linkage analysis of 246 polymorphic markers, in nine three-generation full-sib pedigrees, which make up the AgResearch International Mapping Flock. We have exploited many markers from cattle so that valuable comparisons between these two ruminant linkage maps can be made. The markers, used in the segregation analyses, comprised 86 anonymous microsatellite markers derived from the sheep genome, 126 anonymous microsatellites from cattle, one from deer, and 33 polymorphic markers of various types associated with known genes. The maximum numbermore » of informative meioses within the mapping flock was 22. The average number of informative meioses per marker was 140 (range 18-209). Linkage groups have been assigned to all 26 sheep autosomes. 102 refs., 8 figs., 5 tabs.« less

Cognitive Disequilibrium and Service-Learning in Physical Education Teacher Education: Perceptions of Pre-Service Teachers in a Study Abroad Experience

ERIC Educational Resources Information Center

Ward, Stephen; Pellet, Heidi Henschel; Perez, Mark I.

2017-01-01

Purpose: The purpose of this study was to explore preservice teachers' experiences of cognitive disequilibrium (CD) theory during a service-learning project in a study abroad experience. Method: A case study with 8 participants was used. Data sources consisted of: Formal interviews, videos of planning, videos of teaching, videos of reflection…

A reliability design method for a lithium-ion battery pack considering the thermal disequilibrium in electric vehicles

NASA Astrophysics Data System (ADS)

Xia, Quan; Wang, Zili; Ren, Yi; Sun, Bo; Yang, Dezhen; Feng, Qiang

2018-05-01

With the rapid development of lithium-ion battery technology in the electric vehicle (EV) industry, the lifetime of the battery cell increases substantially; however, the reliability of the battery pack is still inadequate. Because of the complexity of the battery pack, a reliability design method for a lithium-ion battery pack considering the thermal disequilibrium is proposed in this paper based on cell redundancy. Based on this method, a three-dimensional electric-thermal-flow-coupled model, a stochastic degradation model of cells under field dynamic conditions and a multi-state system reliability model of a battery pack are established. The relationships between the multi-physics coupling model, the degradation model and the system reliability model are first constructed to analyze the reliability of the battery pack and followed by analysis examples with different redundancy strategies. By comparing the reliability of battery packs of different redundant cell numbers and configurations, several conclusions for the redundancy strategy are obtained. More notably, the reliability does not monotonically increase with the number of redundant cells for the thermal disequilibrium effects. In this work, the reliability of a 6 × 5 parallel-series configuration is the optimal system structure. In addition, the effect of the cell arrangement and cooling conditions are investigated.

Data Linkage in VET Research: Opportunities, Challenges and Principles. Discussion Paper

ERIC Educational Resources Information Center

Osborne, Kristen; Fowler, Craig; Circelli, Michelle

2018-01-01

This discussion paper explores the possibilities and risks that data linkage presents for the vocational education and training (VET) sector. Along with a broad overview of the nature of data linkage, it highlights possible applications for data linkage in the VET sector and examines the key challenges associated with its use. A number of case…

LD Score Regression Distinguishes Confounding from Polygenicity in Genome-Wide Association Studies

PubMed Central

Bulik-Sullivan, Brendan K.; Loh, Po-Ru; Finucane, Hilary; Ripke, Stephan; Yang, Jian; Patterson, Nick; Daly, Mark J.; Price, Alkes L.; Neale, Benjamin M.

2015-01-01

Both polygenicity (i.e., many small genetic effects) and confounding biases, such as cryptic relatedness and population stratification, can yield an inflated distribution of test statistics in genome-wide association studies (GWAS). However, current methods cannot distinguish between inflation from true polygenic signal and bias. We have developed an approach, LD Score regression, that quantifies the contribution of each by examining the relationship between test statistics and linkage disequilibrium (LD). The LD Score regression intercept can be used to estimate a more powerful and accurate correction factor than genomic control. We find strong evidence that polygenicity accounts for the majority of test statistic inflation in many GWAS of large sample size. PMID:25642630

Appliation of rad-sequencing to linkage mapping in citrus

USDA-ARS?s Scientific Manuscript database

High density linkage maps can be developed for modest cost using high-throughput DNA sequencing to genotype a defined fraction (representation) of the genome. We developed linkage maps in two citrus populations using the RAD (Restriction site Associated DNA) genotyping method which involves restrict...

Linkage results on 11q21-22 in Eastern Quebec pedigrees densely affected by schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maziade, M.; Raymond, V.; Cliche, D.

The 11q21-22 region is of interest for schizophrenia because several candidate genes are located in this section of the genome. The 11q21-22 region, including DRD2, was surveyed by linkage analysis in a sample (N = 242) made of four large multigenerational pedigrees densely affected by schizophrenia (SZ) and eight others by bipolar disorder (BP). These pedigrees were ascertained in a large area of Eastern Quebec and Northern New Brunswick and are still being extended. Family members were administered a {open_quotes}consensus best-estimate diagnosis procedure{close_quotes} (DSM-III-R criteria) blind to probands and relatives` diagnosis and to pedigree assignment (SZ or BP). For linkagemore » analysis, 11 microsatellite polymorphism (CA repeat) markers, located at 11q21-22, and comprising DRD2, were genotyped. Results show no evidence of a major gene for schizophrenia. However, a maximum lod score of 3.41 at the D11S35 locus was observed in an affected-only analysis of one large SZ family, pedigree 255. Whether or not the positive linkage trend in pedigree 255 reflects a true linkage for a small proportion of SZ needs to be confirmed through the extension of this kindred and through replication. 36 refs., 2 tabs.« less

Metabolic Linkage and Correlations to Storage Capacity in Erythrocytes from Glucose 6-Phosphate Dehydrogenase-Deficient Donors.

PubMed

Reisz, Julie A; Tzounakas, Vassilis L; Nemkov, Travis; Voulgaridou, Artemis I; Papassideri, Issidora S; Kriebardis, Anastasios G; D'Alessandro, Angelo; Antonelou, Marianna H

2017-01-01

In glucose 6-phosphate dehydrogenase (G6PD) deficiency, decreased NADPH regeneration in the pentose phosphate pathway and subnormal levels of reduced glutathione result in insufficient antioxidant defense, increased susceptibility of red blood cells (RBCs) to oxidative stress, and acute hemolysis following exposure to pro-oxidant drugs and infections. Despite the fact that redox disequilibrium is a prominent feature of RBC storage lesion, it has been reported that the G6PD-deficient RBCs store well, at least in respect to energy metabolism, but their overall metabolic phenotypes and molecular linkages to the storability profile are scarcely investigated. We performed UHPLC-MS metabolomics analyses of weekly sampled RBC concentrates from G6PD sufficient and deficient donors, stored in citrate phosphate dextrose/saline adenine glucose mannitol from day 0 to storage day 42, followed by statistical and bioinformatics integration of the data. Other than previously reported alterations in glycolysis, metabolomics analyses revealed bioactive lipids, free fatty acids, bile acids, amino acids, and purines as top variables discriminating RBC concentrates for G6PD-deficient donors. Two-way ANOVA showed significant changes in the storage-dependent variation in fumarate, one-carbon, and sulfur metabolism, glutathione homeostasis, and antioxidant defense (including urate) components in G6PD-deficient vs. sufficient donors. The levels of free fatty acids and their oxidized derivatives, as well as those of membrane-associated plasticizers were significantly lower in G6PD-deficient units in comparison to controls. By using the strongest correlations between in vivo and ex vivo metabolic and physiological parameters, consecutively present throughout the storage period, several interactomes were produced that revealed an interesting interplay between redox, energy, and hemolysis variables, which may be further associated with donor-specific differences in the post

Disequilibrium growth of olivine in mafic magmas revealed by phosphorus zoning patterns of olivine from mafic-ultramafic intrusions

NASA Astrophysics Data System (ADS)

Xing, Chang-Ming; Wang, Christina Yan; Tan, Wei

2017-12-01

Olivine from mafic-ultramafic intrusions rarely displays growth zoning in major and some minor elements, such as Fe, Mg and Ni, due to fast diffusion of these elements at high temperatures. These elements in olivine are thus not useful in deciphering magma chamber processes, such as magma convection, multiple injection and mixing. High-resolution X-ray elemental intensity mapping reveals distinct P zoning patterns of olivine from two mafic-ultramafic intrusions in SW China. Polyhedral olivine grains from lherzolite and dunite of the Abulangdang intrusion show P-rich dendrites similar to those observed in volcanic rocks. Rounded olivine grains from net-textured Fe-Ti oxide ores of the Baima layered intrusion have irregular P-rich patches/bands crosscut and interlocked by P-poor olivine domains. P-rich patches/bands contain 250 to 612 ppm P, much higher than P-poor olivine domains with 123 to 230 ppm P. In electron backscattered diffraction (EBSD) maps, P-rich patches/bands within a single olivine grain have the same crystallographic orientation, indicating that they were remnants of the same crystal. Thus, both P-rich patches/bands and P-poor olivine domains in the same grain show a disequilibrium texture and clearly record two-stage growth. The P-rich patches/bands are likely the remnants of a polyhedral olivine crystal that formed in the first stage, whereas the P-poor olivine domains containing rounded Ti-rich magnetite and Fe-rich melt inclusions may have formed from an Fe-rich ambient melt in the second stage. The complex P zoning of olivine can be attributed to the dissolution of early polyhedral olivine and re-precipitation from the Fe-rich ambient melt. The early polyhedral olivine was in chemical disequilibrium with the ambient melt that may have been developed by silicate liquid immiscibility in a crystal mush. Our study implies that olivine crystals in igneous cumulates with an equilibrium appearance may have experienced disequilibrium growth processes

Arctic-midlatitude weather linkages in North America

NASA Astrophysics Data System (ADS)

Overland, James E.; Wang, Muyin

2018-06-01

There is intense public interest in whether major Arctic changes can and will impact midlatitude weather such as cold air outbreaks on the central and east side of continents. Although there is progress in linkage research for eastern Asia, a clear gap is conformation for North America. We show two stationary temperature/geopotential height patterns where warmer Arctic temperatures have reinforced existing tropospheric jet stream wave amplitudes over North America: a Greenland/Baffin Block pattern during December 2010 and an Alaska Ridge pattern during December 2017. Even with continuing Arctic warming over the past decade, other recent eastern US winter months were less susceptible for an Arctic linkage: the jet stream was represented by either zonal flow, progressive weather systems, or unfavorable phasing of the long wave pattern. The present analysis lays the scientific controversy over the validity of linkages to the inherent intermittency of jet stream dynamics, which provides only an occasional bridge between Arctic thermodynamic forcing and extended midlatitude weather events.

High-frequency stock linkage and multi-dimensional stationary processes

NASA Astrophysics Data System (ADS)

Wang, Xi; Bao, Si; Chen, Jingchao

2017-02-01

In recent years, China's stock market has experienced dramatic fluctuations; in particular, in the second half of 2014 and 2015, the market rose sharply and fell quickly. Many classical financial phenomena, such as stock plate linkage, appeared repeatedly during this period. In general, these phenomena have usually been studied using daily-level data or minute-level data. Our paper focuses on the linkage phenomenon in Chinese stock 5-second-level data during this extremely volatile period. The method used to select the linkage points and the arbitrage strategy are both based on multi-dimensional stationary processes. A new program method for testing the multi-dimensional stationary process is proposed in our paper, and the detailed program is presented in the paper's appendix. Because of the existence of the stationary process, the strategy's logarithmic cumulative average return will converge under the condition of the strong ergodic theorem, and this ensures the effectiveness of the stocks' linkage points and the more stable statistical arbitrage strategy.

Detecting structure of haplotypes and local ancestry

USDA-ARS?s Scientific Manuscript database

We present a two-layer hidden Markov model to detect the structure of haplotypes for unrelated individuals. This allows us to model two scales of linkage disequilibrium (one within a group of haplotypes and one between groups), thereby taking advantage of rich haplotype information to infer local an...

Structured mating: Patterns and implications

PubMed Central

Sebro, Ronnie; Peloso, Gina M.; Risch, Neil J.

2017-01-01

Genetic similarity of spouses can reflect factors influencing mate choice, such as physical/behavioral characteristics, and patterns of social endogamy. Spouse correlations for both genetic ancestry and measured traits may impact genotype distributions (Hardy Weinberg and linkage equilibrium), and therefore genetic association studies. Here we evaluate white spouse-pairs from the Framingham Heart Study (FHS) original and offspring cohorts (N = 124 and 755, respectively) to explore spousal genetic similarity and its consequences. Two principal components (PCs) of the genome-wide association (GWA) data were identified, with the first (PC1) delineating clines of Northern/Western to Southern European ancestry and the second (PC2) delineating clines of Ashkenazi Jewish ancestry. In the original (older) cohort, there was a striking positive correlation between the spouses in PC1 (r = 0.73, P = 3x10-22) and also for PC2 (r = 0.80, P = 7x10-29). In the offspring cohort, the spouse correlations were lower but still highly significant for PC1 (r = 0.38, P = 7x10-28) and for PC2 (r = 0.45, P = 2x10-39). We observed significant Hardy-Weinberg disequilibrium for single nucleotide polymorphisms (SNPs) loading heavily on PC1 and PC2 across 3 generations, and also significant linkage disequilibrium between unlinked SNPs; both decreased with time, consistent with reduced ancestral endogamy over generations and congruent with theoretical calculations. Ignoring ancestry, estimates of spouse kinship have a mean significantly greater than 0, and more so in the earlier generations. Adjusting kinship estimates for genetic ancestry through the use of PCs led to a mean spouse kinship not different from 0, demonstrating that spouse genetic similarity could be fully attributed to ancestral assortative mating. These findings also have significance for studies of heritability that are based on distantly related individuals (kinship less than 0.05), as we also demonstrate the poor correlation

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.

The Second Economy in Disequilibrium and Shortage Models of Centrally Planned Economies

DTIC Science & Technology

1988-07-01

CPEs 70 IV. The Second Economy in Disequilibrium Models 76 A. General Equilibrium Models with a Second Economy 78 B. The Portes Macroeconomic ...44,~g3 C AC4 v- 44,A0-.’ 3-3. 3 ~ .1 a a 0, a~ 0.a c 63 9 o -o.a- *~~~t a A . 2. 0 V 0 m -6 o 0 *Z 1 0 6Q 446O l ~ 4 ~ ~ ~ 1 0 v 90 3 ~ . 0 6 C a A OA ...A - - A C A A A C - - C * - A AY 0 - - A C A - A A - - ’A - ’A 4 A C A 6- C A ’A A - - .C A - - - - oA A A A 6-C - .C ’AA - A A A CI 4 = A

Constraints on the origin of Os-isotope disequilibrium in included and interstitial sulfides in mantle peridotites: Implications for the interpretation of Os-isotope signatures in MORB and Abyssal Peridotites

NASA Astrophysics Data System (ADS)

Lassiter, J. C.

2016-12-01

The use of isotope variations in basalts to probe the composition and evolution of the mantle is predicated on the assumption of local (i.e., grain-scale) isotopic equilibrium during mantle melting (Hofmann & Hart, 1978). However, several studies report Os-isotope disequilibrium in distinct populations of sulfides in some peridotites. In principle, grain-scale isotopic heterogeneity could reflect variable radiogenic ingrowth in ancient sulfides with variable Re/Os, or partial re-equilibration of low-Re/Os sulfides with high-Re/Os silicate phases along grain boundaries during mantle melting (e.g., Alard et al., 2005). Both cases require that sulfides fail to maintain isotopic equilibrium with neighboring phases over geologically long ( Ga) time scales. The preservation of Os-isotope disequilibrium in peridotites has been ascribed to the armoring effect of low-[Os] silicates, which limit diffusive exchange between isolated Os-rich phases. This raises the prospect that peridotite-derived melts may not inherit the Os-isotope composition of their source. The timescale required for diffusive equilibration between separate sulfide grains or between Os-rich sulfides and Os-poor silicates is a function of average sulfide size and spacing, Os diffusivity in armoring silicate minerals, and Os partitioning between silicate and sulfide phases. For typical sulfide abundances and sizes in mantle peridotites, neighboring sulfides are expected to re-equilibrate in less than a few 10s of m.y. at adiabatic mantle temperatures, even for very high (>106) sulfide/silicate KD values. Maintenance of disequilibrium requires very large sulfides (>100 um) separated by several mm and diffusion rates (D < 10-20 m2/s) slower than for most other elements in olivine. Equilibration timescales between sulfides and surrounding silicates are similar, so that large-scale isotopic disequilibrium between sulfides and silicates is also unlikely within the convecting mantle. Instead, observed grain

Measuring U-series Disequilibrium in Weathering Rinds to Study the Influence of Environmental Factors to Weathering Rates in Tropical Basse-Terre Island (French Guadeloupe)

NASA Astrophysics Data System (ADS)

Guo, J.; Ma, L.; Sak, P. B.; Gaillardet, J.; Chabaux, F. J.; Brantley, S. L.

2015-12-01

Chemical weathering is a critical process to global CO2 consumption, river/ocean chemistry, and nutrient import to biosphere. Weathering rinds experience minimal physical erosion and provide a well-constrained system to study the chemical weathering process. Here, we applied U-series disequilibrium dating method to study weathering advance rates on the wet side of Basse-Terre Island, French Guadeloupe, aiming to understand the role of the precipitation in controlling weathering rates and elucidate the behavior and immobilization mechanisms of U-series isotopes during rind formation. Six weathering clasts from 5 watersheds with mean annual precipitation varying from 2000 to 3000 mm/yr were measured for U-series isotope ratios and major element compositions on linear core-to-rind transects. One sample experienced complete core-to-rind transformation, while the rest clasts contain both rinds and unweathered cores. Our results show that the unweathered cores are under U-series secular equilibrium, while all the rind materials show significant U-series disequilibrium. For most rinds, linear core-to-rind increases of (230Th/232Th) activity ratios suggest a simple continuous U addition history. However, (234U/238U) and (238U/232Th) trends in several clasts show evidences of remobilization of Uranium besides the U addition, complicating the use of U-series dating method. The similarity between U/Th ratios and major elements trends like Fe, Al, P in some transects and the ongoing leaching experiments suggest that redox and organic colloids could control the mobilization of U-series isotopes in the rinds. Rind formation ages and weathering advance rate (0.07-0.29mm/kyr) were calculated for those rinds with a simple U-addition history. Our preliminary results show that local precipitation gradient significantly influenced the weathering advance rate, revealing the potential of estimating weathering advance rates at a large spatial scale using the U-series dating method.

Identification of Major Quantitative Trait Loci for Seed Oil Content in Soybeans by Combining Linkage and Genome-Wide Association Mapping.

PubMed

Cao, Yongce; Li, Shuguang; Wang, Zili; Chang, Fangguo; Kong, Jiejie; Gai, Junyi; Zhao, Tuanjie

2017-01-01

Soybean oil is the most widely produced vegetable oil in the world and its content in soybean seed is an important quality trait in breeding programs. More than 100 quantitative trait loci (QTLs) for soybean oil content have been identified. However, most of them are genotype specific and/or environment sensitive. Here, we used both a linkage and association mapping methodology to dissect the genetic basis of seed oil content of Chinese soybean cultivars in various environments in the Jiang-Huai River Valley. One recombinant inbred line (RIL) population (NJMN-RIL), with 104 lines developed from a cross between M8108 and NN1138-2 , was planted in five environments to investigate phenotypic data, and a new genetic map with 2,062 specific-locus amplified fragment markers was constructed to map oil content QTLs. A derived F 2 population between MN-5 (a line of NJMN-RIL) and NN1138-2 was also developed to confirm one major QTL. A soybean breeding germplasm population (279 lines) was established to perform a genome-wide association study (GWAS) using 59,845 high-quality single nucleotide polymorphism markers. In the NJMN-RIL population, 8 QTLs were found that explained a range of phenotypic variance from 6.3 to 26.3% in certain planting environments. Among them, qOil-5-1, qOil-10-1 , and qOil-14-1 were detected in different environments, and qOil-5-1 was further confirmed using the secondary F 2 population. Three loci located on chromosomes 5 and 20 were detected in a 2-year long GWAS, and one locus that overlapped with qOil-5-1 was found repeatedly and treated as the same locus. qOil-5-1 was further localized to a linkage disequilibrium block region of approximately 440 kb. These results will not only increase our understanding of the genetic control of seed oil content in soybean, but will also be helpful in marker-assisted selection for breeding high seed oil content soybean and gene cloning to elucidate the mechanisms of seed oil content.

Tracking linkage to HIV care for former prisoners

PubMed Central

Montague, Brian T.; Rosen, David L.; Solomon, Liza; Nunn, Amy; Green, Traci; Costa, Michael; Baillargeon, Jacques; Wohl, David A.; Paar, David P.; Rich, Josiah D.; Study Group, on behalf of the LINCS

2012-01-01

Improving testing and uptake to care among highly impacted populations is a critical element of Seek, Test, Treat and Retain strategies for reducing HIV incidence in the community. HIV disproportionately impacts prisoners. Though, incarceration provides an opportunity to diagnose and initiate therapy, treatment is frequently disrupted after release. Though model programs exist to support linkage to care on release, there is a lack of scalable metrics with which to assess adequacy of linkage to care after release. The linking data from Ryan White program Client Level Data (CLD) files reported to HRSA with corrections release data offers an attractive means of generating these metrics. Identified only by use of a confidential encrypted Unique Client Identifier (eUCI) these CLD files allow collection of key clinical indicators across the system of Ryan White funded providers. Using eUCIs generated from corrections release data sets as a linkage tool, the time to the first service at community providers along with key clinical indicators of patient status at entry into care can be determined as measures of linkage adequacy. Using this strategy, high and low performing sites can be identified and best practices can be identified to reproduce these successes in other settings. PMID:22561157

Linkage analysis of alternative anxiety phenotypes in multiply affected panic disorder families

PubMed Central

Fyer, Abby J.; Costa, Ramiro; Haghighi, Fatemeh; Logue, Mark W.; Knowles, James A.; Weissman, Myrna M.; Hodge, Susan E.; Hamilton, Steven P.

2013-01-01

Background The choice of phenotype definitions for genetic studies of panic and phobic disorders is complicated by family, twin and neurobiological data indicating both distinct and shared risk factors as well as heterogeneity within categories. We previously reported a genome scan in 120 multiplex panic disorder (PD) families using a phenotype that closely adhered to the DSM IV PD definition. Here we extend this work by conducting exploratory linkage analyses in this same pedigree set using ten additional literature- based panic and phobia-related phenotypes that take into account aspects of these hypothesized complexities. Methods Multiply affected families (> 2 individuals with PD) were recruited from clinical and non-clinical sources, evaluated by clinician administered semi-structured interview and subsequent blind consensus best estimate procedure. Each phenotype was analyzed under dominant and recessive models using parametric 2-point (homogeneity and heterogeneity), multipoint, and non-parametric methods. Empirically based permutations were used to estimate model specific and global (across all phenotypes) p-values. Results The highest score was a 2-point lod (4.27, global p < 0.08) on chromosome 13 (D13S793, 76cM) for the phenotype “specific or social phobia” under a recessive model and conditions of homogeneity. There was minimal support for linkage to any of the remaining nine phenotypes. Conclusions Though interpretation of findings is limited by sample size and the large number of phenotypes and models analyzed these data suggest a region on chromosome 13 as a potential site for further exploration in relation to risk for specific and social phobias. PMID:22525237

Construction of a reference genetic linkage map for carnation (Dianthus caryophyllus L.)

PubMed Central

2013-01-01

Background Genetic linkage maps are important tools for many genetic applications including mapping of quantitative trait loci (QTLs), identifying DNA markers for fingerprinting, and map-based gene cloning. Carnation (Dianthus caryophyllus L.) is an important ornamental flower worldwide. We previously reported a random amplified polymorphic DNA (RAPD)-based genetic linkage map derived from Dianthus capitatus ssp. andrezejowskianus and a simple sequence repeat (SSR)-based genetic linkage map constructed using data from intraspecific F2 populations; however, the number of markers was insufficient, and so the number of linkage groups (LGs) did not coincide with the number of chromosomes (x = 15). Therefore, we aimed to produce a high-density genetic map to improve its usefulness for breeding purposes and genetic research. Results We improved the SSR-based genetic linkage map using SSR markers derived from a genomic library, expression sequence tags, and RNA-seq data. Linkage analysis revealed that 412 SSR loci (including 234 newly developed SSR loci) could be mapped to 17 linkage groups (LGs) covering 969.6 cM. Comparison of five minor LGs covering less than 50 cM with LGs in our previous RAPD-based genetic map suggested that four LGs could be integrated into two LGs by anchoring common SSR loci. Consequently, the number of LGs corresponded to the number of chromosomes (x = 15). We added 192 new SSRs, eight RAPD, and two sequence-tagged site loci to refine the RAPD-based genetic linkage map, which comprised 15 LGs consisting of 348 loci covering 978.3 cM. The two maps had 125 SSR loci in common, and most of the positions of markers were conserved between them. We identified 635 loci in carnation using the two linkage maps. We also mapped QTLs for two traits (bacterial wilt resistance and anthocyanin pigmentation in the flower) and a phenotypic locus for flower-type by analyzing previously reported genotype and phenotype data. Conclusions The improved genetic

Construction of a reference genetic linkage map for carnation (Dianthus caryophyllus L.).

PubMed

Yagi, Masafumi; Yamamoto, Toshiya; Isobe, Sachiko; Hirakawa, Hideki; Tabata, Satoshi; Tanase, Koji; Yamaguchi, Hiroyasu; Onozaki, Takashi

2013-10-26

Genetic linkage maps are important tools for many genetic applications including mapping of quantitative trait loci (QTLs), identifying DNA markers for fingerprinting, and map-based gene cloning. Carnation (Dianthus caryophyllus L.) is an important ornamental flower worldwide. We previously reported a random amplified polymorphic DNA (RAPD)-based genetic linkage map derived from Dianthus capitatus ssp. andrezejowskianus and a simple sequence repeat (SSR)-based genetic linkage map constructed using data from intraspecific F2 populations; however, the number of markers was insufficient, and so the number of linkage groups (LGs) did not coincide with the number of chromosomes (x = 15). Therefore, we aimed to produce a high-density genetic map to improve its usefulness for breeding purposes and genetic research. We improved the SSR-based genetic linkage map using SSR markers derived from a genomic library, expression sequence tags, and RNA-seq data. Linkage analysis revealed that 412 SSR loci (including 234 newly developed SSR loci) could be mapped to 17 linkage groups (LGs) covering 969.6 cM. Comparison of five minor LGs covering less than 50 cM with LGs in our previous RAPD-based genetic map suggested that four LGs could be integrated into two LGs by anchoring common SSR loci. Consequently, the number of LGs corresponded to the number of chromosomes (x = 15). We added 192 new SSRs, eight RAPD, and two sequence-tagged site loci to refine the RAPD-based genetic linkage map, which comprised 15 LGs consisting of 348 loci covering 978.3 cM. The two maps had 125 SSR loci in common, and most of the positions of markers were conserved between them. We identified 635 loci in carnation using the two linkage maps. We also mapped QTLs for two traits (bacterial wilt resistance and anthocyanin pigmentation in the flower) and a phenotypic locus for flower-type by analyzing previously reported genotype and phenotype data. The improved genetic linkage maps and SSR markers developed

No clustering for linkage map based on low-copy and undermethylated microsatellites.

PubMed

Zhou, Yi; Gwaze, David P; Reyes-Valdés, M Humberto; Bui, Thomas; Williams, Claire G

2003-10-01

Clustering has been reported for conifer genetic maps based on hypomethylated or low-copy molecular markers, resulting in uneven marker distribution. To test this, a framework genetic map was constructed from three types of microsatellites: low-copy, undermethylated, and genomic. These Pinus taeda L. microsatellites were mapped using a three-generation pedigree with 118 progeny. The microsatellites were highly informative; of the 32 markers in intercross configuration, 29 were segregating for three or four alleles in the progeny. The sex-averaged map placed 51 of the 95 markers in 15 linkage groups at LOD > 4.0. No clustering or uneven distribution across the genome was observed. The three types of P. taeda microsatellites were randomly dispersed within each linkage group. The 51 microsatellites covered a map distance of 795 cM, an average distance of 21.8 cM between markers, roughly half of the estimated total map length. The minimum and maximum distances between any two bins was 4.4 and 45.3 cM, respectively. These microsatellites provided anchor points for framework mapping for polymorphism in P. taeda and other closely related hard pines.

Linkage localization of X-linked Charcot-Marie-Tooth disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bergoffen, J.; Trofatter, J.; Haines, J.L.

1993-02-01

Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy, is a heterogeneous group of slowly progressive, degenerative disorders of peripheral nerve. X-linked CMT (CMTX) (McKusick 302800), a subdivision of type I, or demyelinating, CMT is an X-linked dominant condition with variable penetrance. Previous linkage analysis using RFLPs demonstrated linkage to markers on the proximal long and short arms of the X chromosome, with the more likely localization on the proximal long arm of the X chromosome. Available variable simple-sequence repeats (VSSRs) broaden the possibilities for linkage analysis. This paper presents new linkage data and recombination analysis derived frommore » work with four VSSR markers - AR, PGKP1, DXS453, and DXYS1X - in addition to analysis using RFLP markers described elsewhere. These studies localize the CMTX gene to the proximal Xq segment between PGKP1 (Xq11.2-12) and DXS72 (Xq21.1), with a combined maximum multipoint lod score of 15.3 at DXS453 ([theta] = 0). 32 refs., 3 figs., 2 tabs.« less

When Does Frequency-Independent Selection Maintain Genetic Variation?

PubMed

Novak, Sebastian; Barton, Nicholas H

2017-10-01

Frequency-independent selection is generally considered as a force that acts to reduce the genetic variation in evolving populations, yet rigorous arguments for this idea are scarce. When selection fluctuates in time, it is unclear whether frequency-independent selection may maintain genetic polymorphism without invoking additional mechanisms. We show that constant frequency-independent selection with arbitrary epistasis on a well-mixed haploid population eliminates genetic variation if we assume linkage equilibrium between alleles. To this end, we introduce the notion of frequency-independent selection at the level of alleles, which is sufficient to prove our claim and contains the notion of frequency-independent selection on haploids. When selection and recombination are weak but of the same order, there may be strong linkage disequilibrium; numerical calculations show that stable equilibria are highly unlikely. Using the example of a diallelic two-locus model, we then demonstrate that frequency-independent selection that fluctuates in time can maintain stable polymorphism if linkage disequilibrium changes its sign periodically. We put our findings in the context of results from the existing literature and point out those scenarios in which the possible role of frequency-independent selection in maintaining genetic variation remains unclear. Copyright © 2017 by the Genetics Society of America.