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      Associations between polymorphisms in the myostatin gene with calving difficulty and carcass merit in cattle

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          Abstract

          A fully functional myostatin gene inhibits muscle fiber growth. The objective of the present study was to quantify the association between 21 known myostatin mutations with both calving and carcass traits in 12 cattle breeds. The myostatin genotypes of 32,770 dam-progeny combinations were used in the association analysis of calving dystocia, with the genotypes of 129,803 animals used in the mixed model association analyses of carcass weight, conformation, and fat score. The mixed model included additive genetic, maternal, and permanent environmental effects where appropriate. The mutant genotypes of nt821, Q204X, and F94L were all associated ( P < 0.01) with more calving difficulty when present in either the dam or the progeny. The nt821 deletion had the greatest association with calving difficulty when the homozygous deletion was present in either the calf (0.37 points greater calving difficulty score relative to calves carrying no copies of the deletion based on a one to four scale) or the dam (1.30 points greater calving difficulty score relative to dams carrying no copies of the deletion), although the association between the calf’s nt821 genotype and calving difficulty differed depending on the nt821 genotype of the dam. With the exception of nt748_78, nt414, and nt374_51, all other seven segregating myostatin variants were associated (range of allele substitution effect size relative to animals with no copies of the mutant allele) with carcass weight (2.36 kg lighter to 15.56 kg heavier), all 10 segregating variants with conformation (0.15 units less conformed to 2.24 units more conformed assessed on a scale of 1 to 15), and all segregating variants other than E226X with carcass fat (0.23 units less carcass fat cover to 3.85 units more carcass fat cover assessed on a scale of 1 to 15). Of these, the F94L, Q204X, and nt821 mutations generally had the greatest association with all three carcass traits, giving rise to heavier and more conformed carcasses. Despite the antagonistic genetic relationship between calving difficulty and carcass traits, the nt374_51, F94L, and E226X mutations were all associated with improved carcass merit while having minimal expected consequences on calving difficulty. Thus, animals carrying these mutation(s) may have favorable genetic merit for calving difficulty and carcass merit. Furthermore, depending on the dam genotype, a bull with two copies of the nt821 mutation can produce progeny with improved carcass merit while minimizing calving problems.

          Abstract

          This study characterized the association between the 21 known myostatin mutations with calving difficulty, carcass fat, carcass conformation, and carcass weight. Pleiotropic variants that were associated with both improved carcass merit and greater calving difficulty were identified, as were variants that were associated with improved carcass merit while having minimal consequences on calving difficulty. The latter enables breeders to select animals with these non-pleiotropic mutations to potentially produce progeny with improved carcass merit while minimizing the risk of calving difficulty.

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          Fast model-based estimation of ancestry in unrelated individuals.

          Population stratification has long been recognized as a confounding factor in genetic association studies. Estimated ancestries, derived from multi-locus genotype data, can be used to perform a statistical correction for population stratification. One popular technique for estimation of ancestry is the model-based approach embodied by the widely applied program structure. Another approach, implemented in the program EIGENSTRAT, relies on Principal Component Analysis rather than model-based estimation and does not directly deliver admixture fractions. EIGENSTRAT has gained in popularity in part owing to its remarkable speed in comparison to structure. We present a new algorithm and a program, ADMIXTURE, for model-based estimation of ancestry in unrelated individuals. ADMIXTURE adopts the likelihood model embedded in structure. However, ADMIXTURE runs considerably faster, solving problems in minutes that take structure hours. In many of our experiments, we have found that ADMIXTURE is almost as fast as EIGENSTRAT. The runtime improvements of ADMIXTURE rely on a fast block relaxation scheme using sequential quadratic programming for block updates, coupled with a novel quasi-Newton acceleration of convergence. Our algorithm also runs faster and with greater accuracy than the implementation of an Expectation-Maximization (EM) algorithm incorporated in the program FRAPPE. Our simulations show that ADMIXTURE's maximum likelihood estimates of the underlying admixture coefficients and ancestral allele frequencies are as accurate as structure's Bayesian estimates. On real-world data sets, ADMIXTURE's estimates are directly comparable to those from structure and EIGENSTRAT. Taken together, our results show that ADMIXTURE's computational speed opens up the possibility of using a much larger set of markers in model-based ancestry estimation and that its estimates are suitable for use in correcting for population stratification in association studies.
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            Haploview: analysis and visualization of LD and haplotype maps.

            Research over the last few years has revealed significant haplotype structure in the human genome. The characterization of these patterns, particularly in the context of medical genetic association studies, is becoming a routine research activity. Haploview is a software package that provides computation of linkage disequilibrium statistics and population haplotype patterns from primary genotype data in a visually appealing and interactive interface. http://www.broad.mit.edu/mpg/haploview/ jcbarret@broad.mit.edu
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              Reference-based phasing using the Haplotype Reference Consortium panel

              Haplotype phasing is a fundamental problem in medical and population genetics. Phasing is generally performed via statistical phasing within a genotyped cohort, an approach that can attain high accuracy in very large cohorts but attains lower accuracy in smaller cohorts. Here, we instead explore the paradigm of reference-based phasing. We introduce a new phasing algorithm, Eagle2, that attains high accuracy across a broad range of cohort sizes by efficiently leveraging information from large external reference panels (such as the Haplotype Reference Consortium, HRC) using a new data structure based on the positional Burrows-Wheeler transform. We demonstrate that Eagle2 attains a ≈20x speedup and ≈10% increase in accuracy compared to reference-based phasing using SHAPEIT2. On European-ancestry samples, Eagle2 with the HRC panel achieves >2x the accuracy of 1000 Genomes-based phasing. Eagle2 is open source and freely available for HRC-based phasing via the Sanger Imputation Service and the Michigan Imputation Server.
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                Author and article information

                Contributors
                Journal
                J Anim Sci
                J Anim Sci
                jansci
                Journal of Animal Science
                Oxford University Press (US )
                0021-8812
                1525-3163
                2023
                03 November 2023
                03 November 2023
                : 101
                : skad371
                Affiliations
                Department of Animal Bioscience, Animal and Grassland Research and Innovation Centre, Teagasc, Moorepark , Fermoy, Co. Cork, Ireland
                Department of Biological Sciences, Munster Technological University , Bishopstown, Co. Cork, Ireland
                Department of Biological Sciences, Munster Technological University , Bishopstown, Co. Cork, Ireland
                Irish Cattle Breeding Federation , Bandon, Co. Cork, Ireland
                Department of Animal Bioscience, Animal and Grassland Research and Innovation Centre, Teagasc, Moorepark , Fermoy, Co. Cork, Ireland
                Author notes
                Corresponding author: donagh.berry@ 123456teagasc.ie
                Author information
                https://orcid.org/0000-0001-6708-9669
                Article
                skad371
                10.1093/jas/skad371
                10684047
                37935361
                937323a9-bb8b-4c07-8b03-890a90b402e7
                © The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 January 2023
                : 02 November 2023
                : 28 November 2023
                Page count
                Pages: 16
                Funding
                Funded by: Department of Agriculture, Food and the Marine, Ireland, DOI 10.13039/501100001584;
                Award ID: 2019R553
                Categories
                Animal Genetics and Genomics
                AcademicSubjects/SCI00960

                beef cattle,carcass traits,dystocia,gdf8,haplotype,myostatin
                beef cattle, carcass traits, dystocia, gdf8, haplotype, myostatin

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