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Artículos de revistas sobre el tema "Linkage disequilibrium"

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Publicado: 4 de junio de 2021

Última modificación: 6 de julio de 2024

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1

Tachida, Hidenori. "Decay of linkage disequilibrium in a finite island model". Genetical Research 64, n.º 2 (octubre de 1994): 137–44. http://dx.doi.org/10.1017/s0016672300032742.

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SummaryTime-dependent behaviour of linkage disequilibrium when there was initial linkage disequilibrium is studied in a finite island model assuming neutrality. Explicit expressions for linkage disequilibrium parameters are obtained. From these expressions, the initial and the ultimate decay rates of linkage disequilibrium parameters are found to be increased and decreased, respectively, by finiteness of the population when recombination rate, migration rate and inverse of subpopulation size are of comparable order. Thus, linkage disequilibrium created in the past may persist longerin smaller subdivided populations. Also, differentiation of the gametic parameter of linkage disequilibrium among subpopulations is found to diminish quickly compared tothe linkage disequilibrium in the whole population. Implications of these results for the interpretation of linkage disequilibria in natural populations are discussed.

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2

Weitzman, Jonathan B. "Linkage disequilibrium". Genome Biology 2 (2001): spotlight—20010514–01. http://dx.doi.org/10.1186/gb-spotlight-20010514-01.

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3

Miyashita, Naohiko T., Montserrat Aguadé y Charles H. Langley. "Linkage disequilibrium in the white locus region of Drosophila melanogaster". Genetical Research 62, n.º 2 (octubre de 1993): 101–9. http://dx.doi.org/10.1017/s0016672300031694.

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SummaryLinkage disequilibrium between molecular polymorphisms in a 10 kb region in the white locus of Drosophila melanogaster, revealed with a battery of four-cutter restriction enzymes, was investigated in 266 lines sampled from seven natural populations around the world. A total of 73 (35 restriction site, 37 insertion/deletion and 1 inversion) polymorphisms were detected, of which 55 non-unique polymorphisms were analysed for linkage disequilibrium. Clustering of significant linkage disequilibrium was observed in the transcriptional unit of the white locus as in Miyashita & Langley (1988). It was shown that about two thirds of the 2-locus combinations showing significant linkage disequilibrium have similar degree and direction of association over different populations. Despite lower divergence in allelic frequencies of molecular polymorphisms among populations, an increase in the proportion of 2-locus pairs showing significant linkage disequilibrium is observed in the transcriptional unit. Large values of Ohta's D measure ratio (1982 a, b) cluster in the transcriptional unit, and correspond to significant linkage disequilibria. Although the exact molecular mechanism is not clear, these results suggest that epistatic selection is responsible for significant linkage disequilibrium in the transcriptional unit of this locus

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4

Wu, Rongling y Zhao-Bang Zeng. "Joint Linkage and Linkage Disequilibrium Mapping in Natural Populations". Genetics 157, n.º 2 (1 de febrero de 2001): 899–909. http://dx.doi.org/10.1093/genetics/157.2.899.

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Abstract A new strategy for studying the genome structure and organization of natural populations is proposed on the basis of a combined analysis of linkage and linkage disequilibrium using known polymorphic markers. This strategy exploits a random sample drawn from a panmictic natural population and the open-pollinated progeny of the sample. It is established on the principle of gene transmission from the parental to progeny generation during which the linkage between different markers is broken down due to meiotic recombination. The strategy has power to simultaneously capture the information about the linkage of the markers (as measured by recombination fraction) and the degree of their linkage disequilibrium created at a historic time. Simulation studies indicate that the statistical method implemented by the Fisher-scoring algorithm can provide accurate and precise estimates for the allele frequencies, recombination fractions, and linkage disequilibria between different markers. The strategy has great implications for constructing a dense linkage disequilibrium map that can facilitate the identification and positional cloning of the genes underlying both simple and complex traits.

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5

Kuno, Shin-ichi. "Division of linkage disequilibrium between absolute linkage disequilibrium and linkage equilibrium". Journal of Human Genetics 50, n.º 6 (junio de 2005): 315–16. http://dx.doi.org/10.1007/s10038-005-0256-6.

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6

Baird, Stuart J. E. "Exploring linkage disequilibrium". Molecular Ecology Resources 15, n.º 5 (11 de agosto de 2015): 1017–19. http://dx.doi.org/10.1111/1755-0998.12424.

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7

Schaeffer, S. W. y E. L. Miller. "Estimates of linkage disequilibrium and the recombination parameter determined from segregating nucleotide sites in the alcohol dehydrogenase region of Drosophila pseudoobscura." Genetics 135, n.º 2 (1 de octubre de 1993): 541–52. http://dx.doi.org/10.1093/genetics/135.2.541.

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Abstract The alcohol dehydrogenase (Adh) region of Drosophila pseudoobscura, which includes the two genes Adh and Adh-Dup, was used to examine the pattern and organization of linkage disequilibrium among pairs of segregating nucleotide sites. A collection of 99 strains from the geographic range of D. pseudoobscura were nucleotide-sequenced with polymerase chain reaction-mediated techniques. All pairs of the 359 polymorphic sites in the 3.5-kb Adh region were tested for significant linkage disequilibrium with Fisher's exact test. Of the 74,278 pairwise comparisons of segregating sites, 127 were in significant linkage disequilibrium at the 5% level. The distribution of five linkage disequilibrium estimators D(ij), D2, r(ij), r2 and D(ij) were compared to theoretical distributions. The observed distributions of D(ij), D2, r(ij) and r2 were consistent with the theoretical distribution given an infinite sites model. The observed distribution of D(ij) differed from the theoretical distribution because of an excess of values at -1 and 1. No spatial pattern was observed in the linkage disequilibrium pattern in the Adh region except for two clusters of sites nonrandomly associated in the adult intron and intron 2 of Adh. The magnitude of linkage disequilibrium decreases significantly as nucleotide distance increases, or a distance effect. Adh-Dup had a larger estimate of the recombination parameter, 4Nc, than Adh, where N is the effective population size and c is the recombination rate. A comparison of the mutation and recombination parameters shows that 7-17 recombination events occur for each mutation event. The heterogeneous estimates of the recombination parameter and the inverse relationship between linkage disequilibrium and nucleotide distance are no longer significant when the two clusters of Adh intron sites are excluded from analyses. The most likely explanation for the two clusters of linkage disequilibria is epistatic selection between sites in the cluster to maintain pre-mRNA secondary structure.

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8

Lou, Xiang-Yang, George Casella, Ramon C. Littell, Mark C. K. Yang, Julie A. Johnson y Rongling Wu. "A Haplotype-Based Algorithm for Multilocus Linkage Disequilibrium Mapping of Quantitative Trait Loci With Epistasis". Genetics 163, n.º 4 (1 de abril de 2003): 1533–48. http://dx.doi.org/10.1093/genetics/163.4.1533.

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

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9

Hsu, Fang-Chi, Kung-Yee Liang y Terri H. Beaty. "Multipoint linkage disequilibrium mapping approach: Incorporating evidence of linkage and linkage disequilibrium from unlinked region". Genetic Epidemiology 25, n.º 1 (11 de junio de 2003): 1–13. http://dx.doi.org/10.1002/gepi.10241.

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10

Sabatti, Chiara y Neil Risch. "Homozygosity and Linkage Disequilibrium". Genetics 160, n.º 4 (1 de abril de 2002): 1707–19. http://dx.doi.org/10.1093/genetics/160.4.1707.

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Abstract We illustrate how homozygosity of haplotypes can be used to measure the level of disequilibrium between two or more markers. An excess of either homozygosity or heterozygosity signals a departure from the gametic phase equilibrium: We describe the specific form of dependence that is associated with high (low) homozygosity and derive various linkage disequilibrium measures. They feature a clear biological interpretation, can be used to construct tests, and are standardized to allow comparison across loci and populations. They are particularly advantageous to measure linkage disequilibrium between highly polymorphic markers.

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11

Gorelick, Root y Manfred D. Laubichler. "Decomposing Multilocus Linkage Disequilibrium". Genetics 166, n.º 3 (marzo de 2004): 1581–83. http://dx.doi.org/10.1534/genetics.166.3.1581.

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12

Goldstein, David B. "Islands of linkage disequilibrium". Nature Genetics 29, n.º 2 (octubre de 2001): 109–11. http://dx.doi.org/10.1038/ng1001-109.

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13

Aissani, Brahim. "Confounding by linkage disequilibrium". Journal of Human Genetics 59, n.º 2 (19 de diciembre de 2013): 110–15. http://dx.doi.org/10.1038/jhg.2013.130.

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14

SECALL, MIRIAM y FRITZ H. BACH. "Linkage Disequilibrium or Epistasis?" Tissue Antigens 6, n.º 2 (11 de diciembre de 2008): 161–62. http://dx.doi.org/10.1111/j.1399-0039.1975.tb00629.x.

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15

Gibson, Jane, William Tapper, Weihua Zhang, Newton Morton y Andrew Collins. "Cosmopolitan linkage disequilibrium maps". Human Genomics 2, n.º 1 (2005): 20. http://dx.doi.org/10.1186/1479-7364-2-1-20.

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16

Smit-McBride, Z., A. Moya y F. J. Ayala. "Linkage disequilibrium in natural and experimental populations of Drosophila melanogaster." Genetics 120, n.º 4 (1 de diciembre de 1988): 1043–51. http://dx.doi.org/10.1093/genetics/120.4.1043.

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Abstract We have studied linkage disequilibrium in Drosophila melanogaster in two samples from a wild population and in four large laboratory populations derived from the wild samples. We have assayed four polymorphic enzyme loci, fairly closely linked in the third chromosome: Sod Est-6, Pgm, and Odh. The assay method used allows us to identify the allele associations separately in each of the two homologous chromosomes from each male sampled. We have detected significant linkage disequilibrium between two loci in 16.7% of the cases in the wild samples and in 27.8% of the cases in the experimental populations, considerably more than would be expected by chance alone. We have also found three-locus disequilibria in more instances than would be expected by chance. Some disequilibria present in the wild samples disappear in the experimental populations derived from them, but new ones appear over the generations. The effective population sizes required to generate the observed disequilibria by randomness range from 40 to more than 60,000 individuals in the natural population, depending on which locus pair is considered, and from 100 to more than 60,000 in the experimental populations. These population sizes are unrealistic; the fact that different locus-pairs yield disparate estimates within the same population argues against the likelihood that the disequilibria may have arisen as a consequence of population bottlenecks. Migration, or population mixing, cannot be excluded as the process generating the disequilibria in the wild samples, but can in the experimental populations. We conclude that linkage disequilibrium in these populations is most likely due to natural selection acting on the allozymes, or on loci very tightly linked to them.

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17

Goddard, M. E. y T. H. E. Meuwissen. "The use of linkage disequilibrium to map quantitative trait loci". Australian Journal of Experimental Agriculture 45, n.º 8 (2005): 837. http://dx.doi.org/10.1071/ea05066.

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This paper reviews the causes of linkage disequilibrium and its use in mapping quantitative trait loci. The many causes of linkage disequilibrium can be understood as due to similarity in the coalescence tree of different loci. Consideration of the way this comes about allows us to divide linkage disequilibrium into 2 types: linkage disequilibrium between any 2 loci, even if they are unlinked, caused by variation in the relatedness of pairs of animals; and linkage disequilibrium due to the inheritance of chromosome segments that are identical by descent from a common ancestor. The extent of linkage disequilibrium due to the latter cause can be logically measured by the chromosome segment homozygosity which is the probability that chromosome segments taken at random from the population are identical by descent. This latter cause of linkage disequilibrium allows us to map quantitative trait loci to chromosome regions. The former cause of linkage disequilibrium can cause artefactual quantitative trait loci at any position in the genome. These artefacts can be avoided by fitting the relatedness of animals in the statistical model used to map quantitative trait loci. In the future it may be convenient to estimate this degree of relatedness between individuals from markers covering the whole genome. The statistical model for mapping quantitative trait loci also requires us to estimate the probability that 2 animals share quantitative trait loci alleles at a particular position because they have inherited a chromosome segment containing the quantitative trait loci identical by descent. Current methods to do this all involve approximations. Methods based on concepts of coalescence and chromosome segment homozygosity are useful, but improvements are needed for practical analysis of large datasets. Once these probabilities are estimated they can be used in flexible linear models that conveniently combine linkage and linkage disequilibrium information.

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18

Thomson, Glenys y William Klitz. "Disequilibrium Pattern Analysis. I. Theory". Genetics 116, n.º 4 (1 de agosto de 1987): 623–32. http://dx.doi.org/10.1093/genetics/116.4.623.

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ABSTRACT We have developed a method, disequilibrium pattern analysis, for examining the disequilibrium distribution of the entire array of two locus multiallelic haplotypes in a population. It is shown that a selected haplotype will produce a distinct pattern of linkage disequilibrium values for all generations while the selection is acting. This pattern will also presumably be maintained for many generations after the selection event, until the disequilibrium pattern is eventually broken down by genetic drift and recombination. Related haplotypes, sharing an allele with a selected haplotype, assume a value of linkage disequilibrium proportional to the frequency of the unshared allele and have a single negative value of the normalized linkage disequilibrium. The analysis assumes zero linkage disequilibrium for all allelic combinations initially. The same basic results continue to apply if the selection involves a new mutant, the occurrence of which creates linkage disequilibrium for some haplotypes. The disequilibrium pattern predicted under selection is robust with respect to the influence of migration and random genetic drift. This method is applicable to population data having linked polymorphic loci including that determined from protein or DNA sequencing.

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19

�idlov�, Veronika, Radovan Kasarda, Nina Moravc�kov�, Anna Trakovick�, Ino Curik y Maja Ferencakovic. "Extent of genome-wide linkage disequilibrium in Pinzgau cattle". Journal of Central European Agriculture 17, n.º 2 (2016): 294–302. http://dx.doi.org/10.5513/jcea01/17.2.1704.

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20

HANSEN, MATS, THOMAS KRAFT, SARA GANESTAM, TORBJÖRN SÄLL y NILS-OTTO NILSSON. "Linkage disequilibrium mapping of the bolting gene in sea beet using AFLP markers". Genetical Research 77, n.º 1 (febrero de 2001): 61–66. http://dx.doi.org/10.1017/s0016672300004857.

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The possibility of using linkage disequilibrium mapping in natural plant populations was assessed. In studying linkage disequilibrium among 137 mapped AFLP markers in four populations of sea beet (Beta vulgaris ssp. maritima (L.) Arcang.) it was shown that tightly linked loci could be detected by screening for associations. It was hypothesized that the short distances spanned by linkage disequilibrium enable markers that are very tightly linked to a target gene to be identified. The hypothesis was tested by whole-genome screening of AFLP markers for association with the gene for the annual growth habit, the B gene, in a sample of 106 sea beets. Despite the dominant nature of AFLP, two markers showing significant linkage disequilibrium with the B gene were detected. The results indicate the potential use of linkage disequilibrium for gene mapping in natural plant populations.

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21

Schaid, Daniel J. "Linkage Disequilibrium Testing When Linkage Phase Is Unknown". Genetics 166, n.º 1 (enero de 2004): 505–12. http://dx.doi.org/10.1534/genetics.166.1.505.

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22

Aragaki, Corinne, Filemon Quiaoit, Li Hsu y Lue Ping Zhao. "Mapping alcoholism genes using linkage/linkage disequilibrium analysis". Genetic Epidemiology 17, S1 (1999): S43—S48. http://dx.doi.org/10.1002/gepi.1370170708.

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23

Hedrick, Philip W. "Assortative Mating and Linkage Disequilibrium". G3: Genes|Genomes|Genetics 7, n.º 1 (26 de octubre de 2016): 55–62. http://dx.doi.org/10.1534/g3.116.034967.

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24

McRae, A. F., J. C. McEwan, K. G. Dodds, T. Wilson, A. M. Crawford y J. Slate. "Linkage Disequilibrium in Domestic Sheep". Genetics 160, n.º 3 (1 de marzo de 2002): 1113–22. http://dx.doi.org/10.1093/genetics/160.3.1113.

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Abstract The last decade has seen a dramatic increase in the number of livestock QTL mapping studies. The next challenge awaiting livestock geneticists is to determine the actual genes responsible for variation of economically important traits. With the advent of high density single nucleotide polymorphism (SNP) maps, it may be possible to fine map genes by exploiting linkage disequilibrium between genes of interest and adjacent markers. However, the extent of linkage disequilibrium (LD) is generally unknown for livestock populations. In this article microsatellite genotype data are used to assess the extent of LD in two populations of domestic sheep. High levels of LD were found to extend for tens of centimorgans and declined as a function of marker distance. However, LD was also frequently observed between unlinked markers. The prospects for LD mapping in livestock appear encouraging provided that type I error can be minimized. Properties of the multiallelic LD coefficient D′ were also explored. D′ was found to be significantly related to marker heterozygosity, although the relationship did not appear to unduly influence the overall conclusions. Of potentially greater concern was the observation that D′ may be skewed when rare alleles are present. It is recommended that the statistical significance of LD is used in conjunction with coefficients such as D′ to determine the true extent of LD.

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25

Schaper, E., A. Eriksson, M. Rafajlovic, S. Sagitov y B. Mehlig. "Linkage Disequilibrium Under Recurrent Bottlenecks". Genetics 190, n.º 1 (2 de noviembre de 2011): 217–29. http://dx.doi.org/10.1534/genetics.111.134437.

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26

Huang, Kang, Derek W. Dunn, Wenkai Li, Dan Wang y Baoguo Li. "Linkage disequilibrium under polysomic inheritance". Heredity 128, n.º 1 (enero de 2022): 11–20. http://dx.doi.org/10.1038/s41437-021-00482-1.

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27

Agapow, Paul-Michael y Austin Burt. "Indices of multilocus linkage disequilibrium". Molecular Ecology Notes 1, n.º 1-2 (marzo de 2001): 101–2. http://dx.doi.org/10.1046/j.1471-8278.2000.00014.x.

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28

Laurie, Cathy C., Deborah A. Nickerson, Amy D. Anderson, Bruce S. Weir, Robert J. Livingston, Matthew D. Dean, Kimberly L. Smith, Eric E. Schadt y Michael W. Nachman. "Linkage Disequilibrium in Wild Mice". PLoS Genetics 3, n.º 8 (24 de agosto de 2007): e144. http://dx.doi.org/10.1371/journal.pgen.0030144.

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29

Laurie, Cathy C., Deborah A. Nickerson, Amy D. Anderson, Bruce Weir, Robert J. Livingston, Matthew D. Dean, Kimberly L. Smith, Eric E. Schadt y Michael W. Nachman. "Linkage disequilibrium in wild mice". PLoS Genetics preprint, n.º 2007 (2005): e144. http://dx.doi.org/10.1371/journal.pgen.0030144.eor.

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30

Alfred, Jane. "Linkage disequilibrium — a global view". Nature Reviews Genetics 2, n.º 6 (junio de 2001): 406. http://dx.doi.org/10.1038/35076552.

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31

Lonjou, C., W. Zhang, A. Collins, W. J. Tapper, E. Elahi, N. Maniatis y N. E. Morton. "Linkage disequilibrium in human populations". Proceedings of the National Academy of Sciences 100, n.º 10 (29 de abril de 2003): 6069–74. http://dx.doi.org/10.1073/pnas.1031521100.

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32

Maniatis, Nikolas, Andrew Collins, Jane Gibson, Weihua Zhang, William Tapper y Newton E. Morton. "Positional Cloning by Linkage Disequilibrium". American Journal of Human Genetics 74, n.º 5 (mayo de 2004): 846–55. http://dx.doi.org/10.1086/383589.

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33

Gaut, Brandon S. y Anthony D. Long. "The Lowdown on Linkage Disequilibrium". Plant Cell 15, n.º 7 (julio de 2003): 1502–6. http://dx.doi.org/10.1105/tpc.150730.

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34

Green, Jack y J. C. Woodrow. "Linkage disequilibrium involving three loci". Tissue Antigens 29, n.º 1 (11 de diciembre de 2008): 18–20. http://dx.doi.org/10.1111/j.1399-0039.1987.tb01544.x.

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35

Siegmund, Kimberly D., Bryan Langholz, Peter Kraft y Duncan C. Thomas. "Testing Linkage Disequilibrium in Sibships". American Journal of Human Genetics 67, n.º 1 (julio de 2000): 244–48. http://dx.doi.org/10.1086/302973.

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36

Weir, B. S. "Linkage Disequilibrium and Association Mapping". Annual Review of Genomics and Human Genetics 9, n.º 1 (septiembre de 2008): 129–42. http://dx.doi.org/10.1146/annurev.genom.9.081307.164347.

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37

Xiong, Momiao. "Haplotype bolck linkage disequilibrium mapping". Frontiers in Bioscience 8, n.º 1 (2003): a85–93. http://dx.doi.org/10.2741/919.

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38

WANG, Rong-Huan. "Linkage disequilibrium in plant genomes". HEREDITAS 29, n.º 11 (2007): 1317. http://dx.doi.org/10.1360/yc-007-1317.

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39

Cheung, Vivian G., Jeffrey P. Gregg, Kathryn J. Gogolin-Ewens, Jonathan Bandong, Charles A. Stanley, Lester Baker, Michael J. Higgins et al. "Linkage-disequilibrium mapping without genotyping". Nature Genetics 18, n.º 3 (marzo de 1998): 225–30. http://dx.doi.org/10.1038/ng0398-225.

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40

Boehnke, Michael. "A look at linkage disequilibrium". Nature Genetics 25, n.º 3 (julio de 2000): 246–47. http://dx.doi.org/10.1038/76980.

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41

Romanov, Dmitriy y Nikolai Skoblikow. "Linkage Disequilibrium in Targeted Sequencing". Mathematical Biology and Bioinformatics 17, n.º 2 (22 de noviembre de 2022): 325–37. http://dx.doi.org/10.17537/2022.17.325.

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We propose an approach for optimizing the development of gene diagnostic panels, which is based on the construction of non-equilibrium linkage maps. In the process of gene selection we essentially use genome-wide association analysis (GWAS). Whole-genome analysis of associations makes it possible to reveal the relationship of genomic variants with the studied phenotype. However, the nucleotide variants that showed the highest degree of association can only be statistically associated with the phenotype, not being the true cause of the phenotype. In this case, they may be in the block of linked inheritance with nucleotide variants that really affect the manifestation of the phenotype. The construction of maps of non-equilibrium linkage of nucleotides makes it possible to optimally determine the boundaries of linkage blocks, in which the desired variants fall. The aim of this study was to optimize the demarcation of genomic loci to create targeted panels aimed at predicting susceptibility to SARS-CoV-2 and the severity of COVID-19. The proposed method for selecting loci for a target panel, taking into account nonequilibrium linkage, makes it possible to use the phenomenon of nonequilibrium linkage in order to maximally cover the regions involved in the development of the phenotype, while simultaneously minimizing the length of these regions, and, at the same time, the cost of sequencing.

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42

Rinaldo, Alessandro, Silviu-Alin Bacanu, B. Devlin, Vibhor Sonpar, Larry Wasserman y Kathryn Roeder. "Characterization of multilocus linkage disequilibrium". Genetic Epidemiology 28, n.º 3 (2005): 193–206. http://dx.doi.org/10.1002/gepi.20056.

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43

Garris, Amanda J., Susan R. McCouch y Stephen Kresovich. "Population Structure and Its Effect on Haplotype Diversity and Linkage Disequilibrium Surrounding the xa5 Locus of Rice (Oryza sativa L.)". Genetics 165, n.º 2 (1 de octubre de 2003): 759–69. http://dx.doi.org/10.1093/genetics/165.2.759.

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

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44

Lewontin, R. C. "The detection of linkage disequilibrium in molecular sequence data." Genetics 140, n.º 1 (1 de mayo de 1995): 377–88. http://dx.doi.org/10.1093/genetics/140.1.377.

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Abstract Studies of genetic variation in natural populations at the sequence level usually show that most polymorphic sites are very asymmetrical in allele frequencies, with the rarer allele at a site near fixation. When the rarer allele at a site is present only a few times in the sample, say below five representatives, it becomes very difficult to detect linkage disequilibrium between sites from tests of association. This is a consequence of the numerical properties of even the most powerful test of association, Fisher's exact test. Sites with fewer than five representatives in the sample should be excluded from association tests, but this generally leaves few site pairs eligible for testing. A test for overall linkage disequilibrium, based on the sign of the observed linkage disequilibria, is derived which can use all the data. It is shown that more power can be achieved by increasing the length of sequence determined than by increasing the number of genomes sampled for the same total work.

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45

Jelić, Mihailo, José A. Castro, Zorana Kurbalija Novičić, Bojan Kenig, Danica Dimitrijević, Marija Savić Veselinović, Miloš Jovanović, Dragomir Milovanović, Marina Stamenković-Radak y Marko Andjelković. "Absence of linkage disequilibria between chromosomal arrangements and mtDNA haplotypes in natural populations of Drosophila subobscura from the Balkan Peninsula". Genome 55, n.º 3 (marzo de 2012): 214–21. http://dx.doi.org/10.1139/g2012-004.

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The genetic structure of Drosophila subobscura from the Balkan Peninsula was studied with respect to restriction site polymorphism of mitochondrial DNA in populations from the Derventa River Gorge and Sicevo Gorge (Serbia). To investigate the role of cytonuclear interactions in shaping mitochondrial DNA variability in natural populations of this species, the study was complemented with the analysis of linkage disequilibria between mitochondrial haplotypes and chromosomal inversion arrangements. Similar to other populations of D. subobscura, two main haplotypes (I and II) were found, as well as a series of less common ones. The frequencies of haplotypes I and II accounted for 25.8% and 71.0%, respectively, in the population from the Derventa River Gorge, and for 32.4% and 58.1%, respectively, in the population from Sicevo Gorge. One of the haplotypes harbored a large insertion (2.7 kb) in the A+T rich region. The frequency distribution of both haplotypes did not depart from neutrality. Contrary to prior studies, we did not detect any significant linkage disequilibrium between the two most frequent mtDNA haplotypes and any of the chromosomal arrangements in either of the populations. We conclude that linkage disequilibrium is not a general occurrence in natural populations of D. subobscura, and we discuss how transient coadaptations, ecologically specific selective pressures, and demographics could contribute to population-specific patterns of linkage disequilibrium.

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46

Hudson, Richard R. "THE SAMPLING DISTRIBUTION OF LINKAGE DISEQUILIBRIUM UNDER AN INFINITE ALLELE MODEL WITHOUT SELECTION". Genetics 109, n.º 3 (1 de marzo de 1985): 611–31. http://dx.doi.org/10.1093/genetics/109.3.611.

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ABSTRACT The sampling distributions of several statistics that measure the association of alleles on gametes (linkage disequilibrium) are estimated under a two-locus neutral infinite allele model using an efficient Monte Carlo method. An often used approximation for the mean squared linkage disequilibrium is shown to be inaccurate unless the proper statistical conditioning is used. The joint distribution of linkage disequilibrium and the allele frequencies in the sample is studied. This estimated joint distribution is sufficient for obtaining an approximate maximum likelihood estimate of C = 4Nc, where N is the population size and c is the recombination rate. It has been suggested that observations of high linkage disequilibrium might be a good basis for rejecting a neutral model in favor of a model in which natural selection maintains genetic variation. It is found that a single sample of chromosomes, examined at two loci cannot provide sufficient information for such a test if C < 10, because with C this small, very high levels of linkage disequilibrium are not unexpected under the neutral model. In samples of size 50, it is found that, even when C is as large as 50, the distribution of linkage disequilibrium conditional on the allele frequencies is substantially different from the distribution when there is no linkage between the loci. When conditioned on the number of alleles at each locus in the sample, all of the sample statistics examined are nearly independent of λ = 4Nμ, where μ is the neutral mutation rate.

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47

Salem, M. M. I., G. Thompson, S. Chen, A. Beja-Pereira y J. Carvalheira. "Linkage disequilibrium and haplotype block structure in Portuguese Holstein cattle". Czech Journal of Animal Science 63, No. 2 (19 de enero de 2018): 61–69. http://dx.doi.org/10.17221/56/2017-cjas.

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The objectives of this study were to estimate linkage disequilibrium (LD), describe and scan a haplotype block for the presence of genes that may affect milk production traits in Portuguese Holstein cattle. Totally 526 animals were genotyped using the Illumina BovineSNP50 BeadChip, which contained a total of 52 890 single nucleotide polymorphisms (SNPs). The final set of markers remaining after considering quality control standards consisted of 37 031 SNPs located on 29 autosomes. The LD parameters historical recombinations through allelic association (D') and squared correlation coefficient between locus alleles frequencies ( r<sup>2</sup>) were estimated and haplotype block analyses were performed using the Haploview software. The averages of D' and r<sup>2</sup> values were 0.628 and 0.122, respectively. The LD value decreased with increasing physical distance. The D' and r<sup>2</sup> values decreased respectively from 0.815 and 0.283 at the distance of 0–30 kb to 0.578 and 0.090 at the distance of 401–500 kb. The identified total number of blocks was 969 and consisted of 4259 SNPs that covered 159.06 Mb (6.24% of the total genome) on 29 autosomes. Several genes inside the haplotype blocks were detected; CSN1S2 gene in haplotype block 51 on BTA 6, IL6 and B4GALT1 genes in haplotype blocks 6 and 33 on BTA 8, IL1B and ID2 genes in haplotype blocks 19 and 29 on BTA 11, and DGAT1 gene in haplotype block 1 on BTA 14. The extension of LD using BovineSNP50 BeadChip did not exceed 500 kb and its parameters r<sup>2</sup> and D’ were less than 0.2 and 0.70, respectively, after 70–100 kb. Consequently, the 50K BeadChip would have a poor power in genome wide association studies at distances between adjacent markers lower than 70 kb.

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48

Hernández-Sánchez, Jules, Peter Visscher, Graham Plastow y Chris Haley. "Candidate Gene Analysis for Quantitative Traits Using the Transmission Disequilibrium Test: The Example of the Melanocortin 4-Receptor in Pigs". Genetics 164, n.º 2 (1 de junio de 2003): 637–44. http://dx.doi.org/10.1093/genetics/164.2.637.

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Abstract Population-wide associations between loci due to linkage disequilibrium can be used to map quantitative trait loci (QTL) with high resolution. However, spurious associations between markers and QTL can also arise as a consequence of population stratification. Statistical methods that cannot differentiate between loci associations due to linkage disequilibria from those caused in other ways can render false-positive results. The transmission-disequilibrium test (TDT) is a robust test for detecting QTL. The TDT exploits within-family associations that are not affected by population stratification. However, some TDTs are formulated in a rigid form, with reduced potential applications. In this study we generalize TDT using mixed linear models to allow greater statistical flexibility. Allelic effects are estimated with two independent parameters: one exploiting the robust within-family information and the other the potentially biased between-family information. A significant difference between these two parameters can be used as evidence for spurious association. This methodology was then used to test the effects of the fourth melanocortin receptor (MC4R) on production traits in the pig. The new analyses supported the previously reported results; i.e., the studied polymorphism is either causal or in very strong linkage disequilibrium with the causal mutation, and provided no evidence for spurious association.

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49

Wu, Rongling, Chang-Xing Ma y George Casella. "Joint Linkage and Linkage Disequilibrium Mapping of Quantitative Trait Loci in Natural Populations". Genetics 160, n.º 2 (1 de febrero de 2002): 779–92. http://dx.doi.org/10.1093/genetics/160.2.779.

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AbstractLinkage analysis and allelic association (also referred to as linkage disequilibrium) studies are two major approaches for mapping genes that control simple or complex traits in plants, animals, and humans. But these two approaches have limited utility when used alone, because they use only part of the information that is available for a mapping population. More recently, a new mapping strategy has been designed to integrate the advantages of linkage analysis and linkage disequilibrium analysis for genome mapping in outcrossing populations. The new strategy makes use of a random sample from a panmictic population and the open-pollinated progeny of the sample. In this article, we extend the new strategy to map quantitative trait loci (QTL), using molecular markers within the EM-implemented maximum-likelihood framework. The most significant advantage of this extension is that both linkage and linkage disequilibrium between a marker and QTL can be estimated simultaneously, thus increasing the efficiency and effectiveness of genome mapping for recalcitrant outcrossing species. Simulation studies are performed to test the statistical properties of the MLEs of genetic and genomic parameters including QTL allele frequency, QTL effects, QTL position, and the linkage disequilibrium of the QTL and a marker. The potential utility of our mapping strategy is discussed.

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50

Kumar, Arun y J. P. Gupta. "Linkage disequilibrium, natural selection, and epistatic gene interaction in Drosophila nasuta". Genome 30, n.º 4 (1 de agosto de 1988): 495–98. http://dx.doi.org/10.1139/g88-082.

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The data of linkage disequilibrium between III-2 and 111-35 gene arrangements in natural populations of Drosophila nasuta is presented. The results demonstrated that there was significant linkage disequilibrium between the above gene arrangements in natural populations. Among all nine possible karyotypic combinations, only four combinations were seen. The absence of some combinations might be because of sublethal combinations of genes that reduced the viabilities of their carriers. The frequency of double inversion heterozygotes was always in excess and only 1.29% single hetrozygotes were observed. Based on these findings, we suggest that natural selection acting through the suppression of recombination and epistatic gene interaction providing fitness are the main factor for the maintenance of linkage disequilibrium between the above linked gene arrangements in natural populations of D. nasuta.Key words: linkage disequilibrium, selection, epistasis, Drosophila nasuta.

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