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      Genome-wide associations with longevity and reproductive traits in U.S. rangeland ewes

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          Abstract

          Introduction: Improving ewe longevity is an important breeding and management goal, as death loss and early culling of mature ewes are economic burdens in the sheep industry. Ewe longevity can be improved by selecting for positive reproductive outcomes. However, the breeding approaches for accomplishing this come with the challenge of recording a lifetime trait. Characterizing genetic factors underpinning ewe longevity and related traits could result in the development of genomic selection strategies to improve the stayability of sheep through early, informed selection of replacement ewes.

          Methods: Towards this aim, a genome-wide association study (GWAS) was performed to identify genetic markers associated with ewe longevity, reproductive, and production traits. Traits evaluated included longevity (i.e., length of time in the flock), parity and the lifetime number of lambs born, lambs born alive, lambs weaned, and weight of lambs weaned. Ewe records from previous studies were used. Specifically, Rambouillet (n = 480), Polypay (n = 404), Suffolk (n = 182), and Columbia (n = 64) breed ewes (N = 1,130) were analyzed against 503,617 SNPs in across-breed and within-breed GWAS conducted with the Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) model in R.

          Results: The across-breed GWAS identified 25 significant SNPs and the within-breed GWAS for Rambouillet, Polypay, and Suffolk ewes identified an additional 19 significant SNPs. The most significant markers were rs411309094 (13:22,467,143) associated with longevity in across-breed GWAS ( p-value = 8.3E-13) and rs429525276 (2:148,398,336) associated with both longevity ( p-value = 6.4E-15) and parity ( p-value = 4.8E-15) in Rambouillet GWAS. Significant SNPs were identified within or in proximity (±50 kb) of genes with known or proposed roles in reproduction, dentition, and the immune system. These genes include ALPL, ANOS1, ARHGEF26, ASIC2, ASTN2, ATP8A2, CAMK2D, CEP89, DISC1, ITGB6, KCNH8, MBNL3, MINDY4, MTSS1, PLEKHA7, PRIM2, RNF43, ROBO2, SLCO1A2, TMEM266, TNFRSF21, and ZNF804B.

          Discussion: This study proposes multiple SNPs as candidates for use in selection indices and suggests genes for further research towards improving understanding of the genetic factors contributing to longevity, reproductive, and production traits of ewes.

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          Most cited references63

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          TASSEL: software for association mapping of complex traits in diverse samples.

          Association analyses that exploit the natural diversity of a genome to map at very high resolutions are becoming increasingly important. In most studies, however, researchers must contend with the confounding effects of both population and family structure. TASSEL (Trait Analysis by aSSociation, Evolution and Linkage) implements general linear model and mixed linear model approaches for controlling population and family structure. For result interpretation, the program allows for linkage disequilibrium statistics to be calculated and visualized graphically. Database browsing and data importation is facilitated by integrated middleware. Other features include analyzing insertions/deletions, calculating diversity statistics, integration of phenotypic and genotypic data, imputing missing data and calculating principal components.
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            User's guide to correlation coefficients

            When writing a manuscript, we often use words such as perfect, strong, good or weak to name the strength of the relationship between variables. However, it is unclear where a good relationship turns into a strong one. The same strength of r is named differently by several researchers. Therefore, there is an absolute necessity to explicitly report the strength and direction of r while reporting correlation coefficients in manuscripts. This article aims to familiarize medical readers with several different correlation coefficients reported in medical manuscripts, clarify confounding aspects and summarize the naming practices for the strength of correlation coefficients.
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              The diverse functions of the PD1 inhibitory pathway

              T cell activation is a highly regulated process involving peptide-MHC engagement of the T cell receptor and positive costimulatory signals. Upon activation, coinhibitory 'checkpoints', including programmed cell death protein 1 (PD1), become induced to regulate T cells. PD1 has an essential role in balancing protective immunity and immunopathology, homeostasis and tolerance. However, during responses to chronic pathogens and tumours, PD1 expression can limit protective immunity. Recently developed PD1 pathway inhibitors have revolutionized cancer treatment for some patients, but the majority of patients do not show complete responses, and adverse events have been noted. This Review discusses the diverse roles of the PD1 pathway in regulating immune responses and how this knowledge can improve cancer immunotherapy as well as restore and/or maintain tolerance during autoimmunity and transplantation.

                Author and article information

                Contributors
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                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                27 May 2024
                2024
                : 15
                : 1398123
                Affiliations
                [1] 1 Department of Animal, Veterinary and Food Sciences , University of Idaho , Moscow, ID, United States
                [2] 2 USDA , Agriculture Research Service , Range Sheep Production Efficiency Research Unit , U.S. Sheep Experiment Station , Dubois, ID, United States
                [3] 3 Animal Diseases Research Unit , Agricultural Research Service , US Department of Agriculture , Pullman, WA, United States
                [4] 4 Texas A&M AgriLife Research and Extension , San Angelo, TX, United States
                Author notes

                Edited by: Fernando Baldi, São Paulo State University, Brazil

                Reviewed by: Lucio Flavio Macedo Mota, São Paulo State University, Brazil

                Luis Gabriel González Herrera, National University of Colombia, Colombia

                *Correspondence: Brenda M. Murdoch, bmurdoch@ 123456uidaho.edu ; Gabrielle M. Becker, gbecker@ 123456uidaho.edu
                Article
                1398123
                10.3389/fgene.2024.1398123
                11163081
                38859938
                5b85927e-5824-4573-8d54-7ca5fd485967
                Copyright © 2024 Smitchger, Taylor, Mousel, Schaub, Thorne, Becker and Murdoch.

                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
                : 08 March 2024
                : 18 April 2024
                Funding
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. JT and MM received research funds USDA-ARS CWA No. 2056-31610-007-000-D and 2090-32000-036-00D ( http://www.ars.usda.gov/main/main.htm). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Genetics
                Original Research
                Custom metadata
                Livestock Genomics

                Genetics
                gwas,sheep,productive life,premature culling,lifetime lambs born,lifetime lambs weaned,litter size,weaning weight

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