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      On the Extent of Linkage Disequilibrium in the Genome of Farm Animals

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          Abstract

          Given the importance of linkage disequilibrium (LD) in gene mapping and evolutionary inferences, I characterize in this review the pattern of LD and discuss the influence of human intervention during domestication, breed establishment, and subsequent genetic improvement on shaping the genome of livestock species. To this end, I summarize data on the profile of LD based on array genotypes vs. sequencing data in cattle and chicken, two major livestock species, and compare to the human case. This comparison provides insights into the real dimension of the pairwise allelic correlation and haplo-block structuring. The dependency of LD on allelic frequency is pictured and a recently introduced metric for moderating it is outlined. In the context of the contact farm animals had with human, the impact of genetic forces including admixture, mutation, recombination rate, selection, and effective population size on LD is discussed. The review further highlights the interplay of LD with runs of homozygosity and concludes with the operational implications of the widely used association and selection mapping studies in relation to LD.

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          Most cited references67

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          The hitch-hiking effect of a favourable gene

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            Linkage disequilibrium--understanding the evolutionary past and mapping the medical future.

            Linkage disequilibrium--the nonrandom association of alleles at different loci--is a sensitive indicator of the population genetic forces that structure a genome. Because of the explosive growth of methods for assessing genetic variation at a fine scale, evolutionary biologists and human geneticists are increasingly exploiting linkage disequilibrium in order to understand past evolutionary and demographic events, to map genes that are associated with quantitative characters and inherited diseases, and to understand the joint evolution of linked sets of genes. This article introduces linkage disequilibrium, reviews the population genetic processes that affect it and describes some of its uses. At present, linkage disequilibrium is used much more extensively in the study of humans than in non-humans, but that is changing as technological advances make extensive genomic studies feasible in other species.
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              Rare-variant association analysis: study designs and statistical tests.

              Despite the extensive discovery of trait- and disease-associated common variants, much of the genetic contribution to complex traits remains unexplained. Rare variants can explain additional disease risk or trait variability. An increasing number of studies are underway to identify trait- and disease-associated rare variants. In this review, we provide an overview of statistical issues in rare-variant association studies with a focus on study designs and statistical tests. We present the design and analysis pipeline of rare-variant studies and review cost-effective sequencing designs and genotyping platforms. We compare various gene- or region-based association tests, including burden tests, variance-component tests, and combined omnibus tests, in terms of their assumptions and performance. Also discussed are the related topics of meta-analysis, population-stratification adjustment, genotype imputation, follow-up studies, and heritability due to rare variants. We provide guidelines for analysis and discuss some of the challenges inherent in these studies and future research directions. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                17 January 2020
                2019
                : 10
                : 1304
                Affiliations
                [1] 1 Leibniz Institute for Farm Animal Biology (FBN), Institute of Genetics and Biometry , Dummerstorf, Germany
                [2] 2 Animal Breeding and Genetics Group, Department of Animal Sciences, Center for Integrated Breeding Research, University of Göttingen , Göttingen, Germany
                Author notes

                Edited by: Gábor Mészáros, University of Natural Resources and Life Sciences Vienna, Austria

                Reviewed by: Farai Catherine Muchadeyi, Agricultural Research Council of South Africa (ARC-SA), South Africa; Maja Ferenčaković, University of Zagreb, Croatia

                *Correspondence: Saber Qanbari, qanbari@ 123456fbn-dummerstorf.de

                This article was submitted to Livestock Genomics, a section of the journal Frontiers in Genetics

                Article
                10.3389/fgene.2019.01304
                6978288
                32010183
                5b505964-b3da-478f-bf7b-f26bb79e0af2
                Copyright © 2020 Qanbari

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 July 2019
                : 26 November 2019
                Page count
                Figures: 6, Tables: 0, Equations: 1, References: 96, Pages: 11, Words: 5287
                Categories
                Genetics
                Review

                Genetics
                association mapping,selection mapping,runs of homozygosity,allele frequency spectrum (afs),haplotype block

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