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      The effect of inbreeding, body size and morphology on health in dog breeds

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          Abstract

          Background

          Dog breeds are known for their distinctive body shape, size, coat color, head type and behaviors, features that are relatively similar across members of a breed. Unfortunately, dog breeds are also characterized by distinct predispositions to disease. We explored the relationships between inbreeding, morphology and health using genotype based inbreeding estimates, body weight and insurance data for morbidity.

          Results

          The average inbreeding based on genotype across 227 breeds was F adj = 0.249 (95% CI 0.235–0.263). There were significant differences in morbidity between breeds with low and high inbreeding (H = 16.49, P = 0.0004). There was also a significant difference in morbidity between brachycephalic breeds and non-brachycephalic breeds ( P = 0.0048) and between functionally distinct groups of breeds (H = 14.95 P < 0.0001). Morbidity was modeled using robust regression analysis and both body weight ( P < 0.0001) and inbreeding ( P = 0.013) were significant ( r 2  = 0.77). Smaller less inbred breeds were healthier than larger more inbred breeds.

          Conclusions

          In this study, body size and inbreeding along with deleterious morphologies contributed to increases in necessary health care in dogs.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s40575-021-00111-4.

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          Most cited references59

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          PLINK: a tool set for whole-genome association and population-based linkage analyses.

          Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.
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            A single IGF1 allele is a major determinant of small size in dogs.

            The domestic dog exhibits greater diversity in body size than any other terrestrial vertebrate. We used a strategy that exploits the breed structure of dogs to investigate the genetic basis of size. First, through a genome-wide scan, we identified a major quantitative trait locus (QTL) on chromosome 15 influencing size variation within a single breed. Second, we examined genetic variation in the 15-megabase interval surrounding the QTL in small and giant breeds and found marked evidence for a selective sweep spanning a single gene (IGF1), encoding insulin-like growth factor 1. A single IGF1 single-nucleotide polymorphism haplotype is common to all small breeds and nearly absent from giant breeds, suggesting that the same causal sequence variant is a major contributor to body size in all small dogs.
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              Bottlenecks and selective sweeps during domestication have increased deleterious genetic variation in dogs.

              Population bottlenecks, inbreeding, and artificial selection can all, in principle, influence levels of deleterious genetic variation. However, the relative importance of each of these effects on genome-wide patterns of deleterious variation remains controversial. Domestic and wild canids offer a powerful system to address the role of these factors in influencing deleterious variation because their history is dominated by known bottlenecks and intense artificial selection. Here, we assess genome-wide patterns of deleterious variation in 90 whole-genome sequences from breed dogs, village dogs, and gray wolves. We find that the ratio of amino acid changing heterozygosity to silent heterozygosity is higher in dogs than in wolves and, on average, dogs have 2-3% higher genetic load than gray wolves. Multiple lines of evidence indicate this pattern is driven by less efficient natural selection due to bottlenecks associated with domestication and breed formation, rather than recent inbreeding. Further, we find regions of the genome implicated in selective sweeps are enriched for amino acid changing variants and Mendelian disease genes. To our knowledge, these results provide the first quantitative estimates of the increased burden of deleterious variants directly associated with domestication and have important implications for selective breeding programs and the conservation of rare and endangered species. Specifically, they highlight the costs associated with selective breeding and question the practice favoring the breeding of individuals that best fit breed standards. Our results also suggest that maintaining a large population size, rather than just avoiding inbreeding, is a critical factor for preventing the accumulation of deleterious variants.
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                Author and article information

                Contributors
                dlbannasch@ucdavis.edu
                Journal
                Canine Med Genet
                Canine Med Genet
                Canine Medicine and Genetics
                BioMed Central (London )
                2662-9380
                2 December 2021
                2 December 2021
                2021
                : 8
                : 12
                Affiliations
                [1 ]GRID grid.27860.3b, ISNI 0000 0004 1936 9684, Department of Population Health and Reproduction, , School of Veterinary Medicine, University of California-Davis, ; Davis, CA 95616 USA
                [2 ]GRID grid.27860.3b, ISNI 0000 0004 1936 9684, Department of Animal Science, , University of California-Davis, ; Davis, CA 95616 USA
                [3 ]Wisdom Health Genetics, Kinship, FI-00290 Helsinki, Finland
                [4 ]GRID grid.463103.3, ISNI 0000 0004 1790 2553, Zoetis, ; Parsippany, NJ USA
                [5 ]GRID grid.27860.3b, ISNI 0000 0004 1936 9684, Department of Surgical and Radiological Sciences, , School of Veterinary Medicine, University of California-Davis, ; Davis, CA 95616 USA
                [6 ]GRID grid.27860.3b, ISNI 0000 0004 1936 9684, Department of Ophthalmology & Vision Science, , School of Medicine, University of California-Davis, ; Davis, CA 95616 USA
                Author information
                http://orcid.org/0000-0002-7614-7207
                Article
                111
                10.1186/s40575-021-00111-4
                8638537
                34852838
                d87d06a2-9778-474a-9ef6-823c3b42c59e
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 24 August 2021
                : 2 November 2021
                Funding
                Funded by: Maxine Adler Endowed Chair Funds
                Funded by: International Canine Health Award
                Categories
                Research
                Custom metadata
                © The Author(s) 2021

                canine,genetic,inherited,morbidity,mortality
                canine, genetic, inherited, morbidity, mortality

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