scholarly journals Joint Linkage and Linkage Disequilibrium Mapping in Natural Populations

Genetics ◽  
2001 ◽  
Vol 157 (2) ◽  
pp. 899-909
Author(s):  
Rongling Wu ◽  
Zhao-Bang Zeng
Keyword(s):  
Linkage Disequilibrium ◽  
Complex Traits ◽  
Positional Cloning ◽  
Genome Structure ◽  
Natural Populations ◽  
Linkage Disequilibrium Mapping ◽  
Linkage Disequilibria ◽  
Time Simulation ◽  
New Strategy ◽  
Fisher Scoring Algorithm

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.

A Haplotype-Based Algorithm for Multilocus Linkage Disequilibrium Mapping of Quantitative Trait Loci With Epistasis

Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1533-1548 ◽  
Author(s):  
Xiang-Yang Lou ◽  
George Casella ◽  
Ramon C Littell ◽  
Mark C K Yang ◽  
Julie A Johnson ◽  
...  
Keyword(s):  
Parameter Estimation ◽  
Linkage Disequilibrium ◽  
Quantitative Trait Loci ◽  
Quantitative Trait ◽  
Complex Traits ◽  
Association Studies ◽  
Natural Populations ◽  
Evolutionary Relationship ◽  
Linkage Disequilibrium Mapping ◽  
Trait Loci

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.

Joint Linkage and Linkage Disequilibrium Mapping of Quantitative Trait Loci in Natural Populations

Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 779-792 ◽  
Author(s):  
Rongling Wu ◽  
Chang-Xing Ma ◽  
George Casella
Keyword(s):  
Linkage Disequilibrium ◽  
Quantitative Trait Loci ◽  
Linkage Analysis ◽  
Quantitative Trait ◽  
Genome Mapping ◽  
Linkage Disequilibrium Mapping ◽  
Allelic Association ◽  
Mapping Strategy ◽  
Trait Loci ◽  
New Strategy

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.

scholarly journals Cost-Effective Designs for Linkage Disequilibrium Mapping of Complex Traits

2003 ◽  
Vol 72 (5) ◽  
pp. 1213-1220 ◽  
Author(s):  
Susan K. Service ◽  
Lodewijk A. Sandkuijl ◽  
Nelson B. Freimer
Keyword(s):  
Linkage Disequilibrium ◽  
Complex Traits ◽  
Cost Effective ◽  
Linkage Disequilibrium Mapping

scholarly journals THE EFFECT OF COMBINING ALLELES INTO ELECTROPHORETIC CLASSES ON DETECTING LINKAGE DISEQUILIBRIUM

Genetics ◽  
1977 ◽  
Vol 85 (3) ◽  
pp. 543-556
Author(s):  
E Zouros ◽  
G B Golding ◽  
Trudy F C MacKay
Keyword(s):  
Linkage Disequilibrium ◽  
Sample Size ◽  
Natural Populations ◽  
Epistatic Interactions ◽  
Detection Power ◽  
Linkage Disequilibria ◽  
Allelic Distribution ◽  
Order Of Magnitude ◽  
Actual Degree

ABSTRACT When alleles are combined into few detectable classes, linkage correlations are underestimated most of the time. The probability that the linkage correlation will be underestimated is a function of the actual degree of correlation and the evenness of the allelic distribution, but is mainly determined by the distribution of alleles into distinguishable classes. With only two alleles per class this probability will usually be higher than 0.7. Also, the consistency in the sign of the linkage disequilibrium over many populations may escape detection. An increase of sample size by one order of magnitude or more may be required to compensate for the loss in detection power. It follows that the available electrophoretic studies of linkage correlations, although negative in their majority, do not suggest that epistatic interactions and linkage disequilibria are rare in natural populations.

scholarly journals Analysis of linkage disequilibria between allozyme loci in natural populations of Drosophila melanogaster

1978 ◽  
Vol 32 (3) ◽  
pp. 215-229 ◽  
Author(s):  
Charles H. Langley ◽  
Diana B. Smith ◽  
F. M. Johnson
Keyword(s):  
Drosophila Melanogaster ◽  
Linkage Disequilibrium ◽  
Natural Population ◽  
Analysis Of Variance ◽  
Natural Populations ◽  
Correlation Coefficients ◽  
Absolute Value ◽  
Linkage Disequilibria ◽  
Enzyme Loci ◽  
Allozyme Loci

SUMMARYLinkage disequilibria between pairs of 8 polymorphic enzyme loci (αGpdh, Mdh, Adh, Est-6, Pgm, Odh, Est-C and Acph) in some 100 natural population samples of Drosophila melanogaster were examined. The estimates of linkage disequilibrium were made from zygotic frequencies. The magnitude of linkage disequilibria are small and similar to those in previous reports. Variation in linkage disequilibrium among related subpopulations was analysed by analysis of variance of the correlation coefficients. Despite the small absolute value of linkage disequilibrium there is a suggestion of a correlation among related subpopulations. The magnitude of linkage disequilibrium was observed to be positively correlated with linkage. Two cage populations were observed to demonstrate large amounts of linkage disequilibrium between closely linked loci in contrast to the situation in natural populations. This is attributable to the finite sizes of these cage populations.

scholarly journals Decay of linkage disequilibrium in a finite island model

1994 ◽  
Vol 64 (2) ◽  
pp. 137-144 ◽  
Author(s):  
Hidenori Tachida
Keyword(s):  
Linkage Disequilibrium ◽  
Migration Rate ◽  
Natural Populations ◽  
Decay Rates ◽  
Island Model ◽  
The Past ◽  
Linkage Disequilibria ◽  
Subdivided Populations ◽  
Time Dependent Behaviour ◽  
Dependent Behaviour

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.

The diastrophic dysplasia gene encodes a novel sulfate transporter: Positional cloning by fine-structure linkage disequilibrium mapping

Cell ◽  
1994 ◽  
Vol 78 (6) ◽  
pp. 1073-1087 ◽  
Author(s):  
Johanna Hästbacka ◽  
Albert de la Chapelle ◽  
Melanie M. Mahtani ◽  
Greg Clines ◽  
Mary Pat Reeve-Daly ◽  
...  
Keyword(s):  
Fine Structure ◽  
Linkage Disequilibrium ◽  
Positional Cloning ◽  
Linkage Disequilibrium Mapping ◽  
Sulfate Transporter ◽  
Diastrophic Dysplasia

scholarly journals THE GENETICS OF DROSOPHILA SUBOBSCURA POPULATIONS. IX. STUDIES ON LINKAGE DISEQUILIBRIUM IN FOUR NATURAL POPULATIONS

Genetics ◽  
1979 ◽  
Vol 93 (2) ◽  
pp. 497-523
Author(s):  
M Loukas ◽  
C B Krimbas ◽  
Y Vergini
Keyword(s):  
Linkage Disequilibrium ◽  
Geographical Variation ◽  
Natural Populations ◽  
Strong Linkage Disequilibrium ◽  
Linkage Equilibrium ◽  
Strong Linkage ◽  
Linkage Disequilibria ◽  
Break Points ◽  
Complex Locus ◽  
Two Populations

ABSTRACT Gametic frequencies were obtained in four natural populations of D. subobscura by extracting wild chromosomes and subsequently analyzing them for inversions and allozymes. The genes Lap and Pept-1, both located within the same inversions of chromosome 0, were found in striking nonrandom associations with them of the same kind and degree in all populations studied. On the contrary, the gene Acph, also located within the previously mentioned inversions, was found in linkage disequilibrium with them only in two populations and of opposite directions. This is also the case for the genes Est-9 and Hk, both located within chromosome E inversions. While the gene Est-9 was in strong linkage disequilibrium with the inversions, of the same kind and degree in all populations studied, Hk was found to be in linkage equilibrium. Allele frequencies for the 29 genes studied do not show geographical variation except for the genes Lap, Pept-1 and Est-9, the ones found in linkage disequilibria with the geographically varying gene arrangements. Although mechanical or historical explanations for these equilibria cannot be ruled out, these data cannot be explained satisfactorily by the "middle gene explanation," which states that loci displaying such linkage disequilibria are the ones located near the break points of inversions, while the ones displaying linkage equilibria with them are located in the middle of them. There is no evidence for consistent linkage disequilibria between pairs of loci, except for the closely linked genes of the complex locus, Est-9. This would imply, if it is not a peculiarity of the Est-9 complex, that the linkage disequilibria aye found only between very closely linked loci or that, far less closely linked genes, the associations are too weak to be detected by the usual samples sizes.

scholarly journals The detection of linkage disequilibrium in molecular sequence data.

Genetics ◽  
1995 ◽  
Vol 140 (1) ◽  
pp. 377-388 ◽  
Author(s):  
R C Lewontin
Keyword(s):  
Linkage Disequilibrium ◽  
Sequence Data ◽  
Natural Populations ◽  
Total Work ◽  
Molecular Sequence Data ◽  
Exact Test ◽  
Molecular Sequence ◽  
Linkage Disequilibria ◽  
Tests Of Association ◽  
A Site

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.

Absence of linkage disequilibria between chromosomal arrangements and mtDNA haplotypes in natural populations of Drosophila subobscura from the Balkan Peninsula

Genome ◽  
2012 ◽  
Vol 55 (3) ◽  
pp. 214-221 ◽  
Author(s):  
Mihailo Jelić ◽  
José A. Castro ◽  
Zorana Kurbalija Novičić ◽  
Bojan Kenig ◽  
Danica Dimitrijević ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Linkage Disequilibrium ◽  
Natural Populations ◽  
Balkan Peninsula ◽  
Drosophila Subobscura ◽  
Mitochondrial Haplotypes ◽  
Linkage Disequilibria ◽  
Mtdna Haplotypes ◽  
Mitochondrial Dna Variability

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.

Sign in / Sign up

Export Citation Format

Share Document