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      All sheeps and sizes: a genetic investigation of mature body size across sheep breeds reveals a polygenic nature

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          Summary

          Mature body size is genetically correlated with growth rate, an important economic trait in the sheep industry. Mature body size has been studied extensively in humans as well as cattle and other domestic animal populations but not in sheep. Six‐hundred and sixteen ewes, across 22 breeds, were measured for 28 linear measurements representing various skeletal parts. PCA from these measures generated principal components 1 and 2 which represented 66 and 7% of the phenotypic variation respectively. Two‐hundred and twenty sheep were genotyped on the Illumina Ovine HD beadchip for a GWAS investigating mature body size and linear body measurements. Forty‐six (Bonferroni P < 0.05) SNP associations across 14 chromosomes were identified utilizing principal component 1, representing overall body size, revealing mature body size to have fewer loci of large effect than other domestic species such as dogs and horses. Genome‐wide associations for individual linear measures identified major quantitative trait loci for withers height and ear length. Withers height was associated (Bonferroni P < 0.05) with 12 SNPs across six chromosomes whereas ear length was associated with a single locus on chromosome 3, containing MSRB3. This analysis identified several loci known to be associated with mature body size in other species such as NCAPG, LCORL, and HMGA2. Mature body size is more polygenic in sheep than other domesticated species, making the development of genomic selection for the trait the most efficient option for maintaining or reducing mature body size in sheep.

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          Variance component model to account for sample structure in genome-wide association studies.

          Although genome-wide association studies (GWASs) have identified numerous loci associated with complex traits, imprecise modeling of the genetic relatedness within study samples may cause substantial inflation of test statistics and possibly spurious associations. Variance component approaches, such as efficient mixed-model association (EMMA), can correct for a wide range of sample structures by explicitly accounting for pairwise relatedness between individuals, using high-density markers to model the phenotype distribution; but such approaches are computationally impractical. We report here a variance component approach implemented in publicly available software, EMMA eXpedited (EMMAX), that reduces the computational time for analyzing large GWAS data sets from years to hours. We apply this method to two human GWAS data sets, performing association analysis for ten quantitative traits from the Northern Finland Birth Cohort and seven common diseases from the Wellcome Trust Case Control Consortium. We find that EMMAX outperforms both principal component analysis and genomic control in correcting for sample structure.
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            Defining the role of common variation in the genomic and biological architecture of adult human height

            Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explain one-fifth of heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ~2,000, ~3,700 and ~9,500 SNPs explained ~21%, ~24% and ~29% of phenotypic variance. Furthermore, all common variants together captured the majority (60%) of heritability. The 697 variants clustered in 423 loci enriched for genes, pathways, and tissue-types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin, and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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              Modulating Hox gene functions during animal body patterning.

              With their power to shape animal morphology, few genes have captured the imagination of biologists as the evolutionarily conserved members of the Hox clusters have done. Recent research has provided new insight into how Hox proteins cause morphological diversity at the organismal and evolutionary levels. Furthermore, an expanding collection of sequences that are directly regulated by Hox proteins provides information on the specificity of target-gene activation, which might allow the successful prediction of novel Hox-response genes. Finally, the recent discovery of microRNA genes within the Hox gene clusters indicates yet another level of control by Hox genes in development and evolution.
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                Author and article information

                Contributors
                hjh3@cornell.edu
                Journal
                Anim Genet
                Anim Genet
                10.1111/(ISSN)1365-2052
                AGE
                Animal Genetics
                John Wiley and Sons Inc. (Hoboken )
                0268-9146
                1365-2052
                21 October 2020
                February 2021
                : 52
                : 1 ( doiID: 10.1111/age.v52.1 )
                : 99-107
                Affiliations
                [ 1 ] Department of Animal Science Cornell University Ithaca NY 14853 USA
                [ 2 ]Present address: Department of Animal & Range Sciences Montana State University 111 Animal Bioscience Building Bozeman MT 59717 USA
                Author notes
                [*] [* ] Address for correspondence

                H. J. Huson, Department of Animal Science, Cornell University, Ithaca, NY 14853, USA.

                E‐mail: hjh3@ 123456cornell.edu

                Author information
                https://orcid.org/0000-0002-1458-7688
                https://orcid.org/0000-0001-8299-0447
                Article
                AGE13016
                10.1111/age.13016
                7821113
                33089531
                ad30d44b-5b81-4a3a-9e4c-d48a60a42872
                © 2020 The Authors. Animal Genetics published by John Wiley & Sons Ltd on behalf of Stichting International Foundation for Animal Genetics

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 28 September 2020
                Page count
                Figures: 6, Tables: 1, Pages: 9, Words: 5055
                Funding
                Funded by: National Animal Genome Research Program
                Award ID: NRSP‐8
                Categories
                Full Paper
                Full Papers
                Custom metadata
                2.0
                February 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.6 mode:remove_FC converted:22.01.2021

                Genetics
                complex trait,ear length,genome‐wide association studies,principal component analysis,withers height

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