Comprehensive analysis of geographic and breed-purpose influences on genetic diversity and inherited disease risk in the Doberman dog breed

(2023) 10:7 Wade et al. Canine Medicine and Genetics https://doi.org/10.1186/s40575-023-00130-3 Canine Medicine and Genetics Open Access RESEARCH Comprehensive analysis of geographic and breed‑purpose influences on genetic diversity and inherited disease risk in the Doberman dog breed Claire M. Wade1* , Robin Nuttall2 and Sophie Liu3 Abstract Background Publicly available phenotype data and genotyping array data from two citizen science projects: “Doberman Health Surveys” and “The Doberman Diversity Project” were analyzed to explore relative homozygosity, diversity, and disorder risk according to geographical locale and breeding purpose in the Doberman. Results From the phenotypic data cohort, life expectancy of a Doberman at birth is 9.1 years. The leading causes of death were heart disease (accounting for 28% of deaths) and cancers (collectively accounting for 14% of deaths). By genotyping, the world Doberman population exists as four major cohorts (European exhibition-bred, Americas exhibition-bred, European work, Americas pet/informal). Considering the entire Doberman population, four genomic regions longer than 500 Kb are fixed in 90% or more of 3,226 dogs included in this study. The four fixed regions reside on two autosomal chromosomes: CFA3:0.8–2.3 Mb (1.55 Mb); CFA3: 57.9–59.8 Mb (1.8 Mb); CFA31:0–1.2 Mb (1.2 Mb); and CFA31:4.80–6.47 Mb (1.67 Mb). Using public variant call files including variants for eight Doberman pinschers, we observed 30 potentially functional alternate variants that were evolutionarily diverged relative to the wider sequenced dog population within the four strongly homozygous chromosomal regions. Effective population size (Ne) is a statistical measure of breed diversity at the time of sampling that approximates the number of unique individuals. The major identified sub-populations of Dobermans demonstrated Ne in the range 70–236. The mean level of inbreeding in the Doberman breed is 40% as calculated by the number of array variants in runs of homozygosity divided by the assayed genome size (excluding the X chromosome). The lowest observed level of inbreeding in the Dobermans assayed was 15% in animals that were first generation mixes of European and USA bred Dobermans. Array variant analysis shows that inter-crossing between European and USA-bred Dobermans has capacity to re-introduce variation at many loci that are strongly homozygous. Conclusions We conclude that efforts to improve breed diversity first should focus on regions with the highest fixation levels, but managers must ensure that mutation loads are not worsened by increasing the frequencies of rarer haplotypes in the identified regions. The analysis of global data identified regions of strong fixation that might impact known disorder risks in the breed. Plausible gene candidates for future analysis of the genetic basis of cardiac disease and cancer were identified in the analysis. *Correspondence: Claire M. Wade Full list of author information is available at the end of the article © The Author(s) 2023. Open Access This 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://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Wade et al. Canine Medicine and Genetics (2023) 10:7 Page 2 of 17 Keywords Doberman, Diversity, Disorder, Population genetics Background The Doberman dog breed was founded in the late nineteenth century by German individual Karl Friedrich Louis Dobermann and was initially developed as a dog for personal protection in Mr Dobermann’s work as a tax collector. The breed foundation is said to include Pinscher, Weimaraner, Rottweiler and German Shepherd dog breeds and was recognised by the German Kennel Club in 1899 (The Kennel Club https://www.thekennelc lub.org.uk/search/breeds-a-to-z/breeds/working/dober mann/ accessed September 7 2021). Since its founding, the intelligence and trainability of the breed has been valued by military and police forces. The breed was first exported from Germany in the 1920s and since then, the breed has had a purpose divided between the original breed working function and as a family companion. As is common in working dog breeds, division of purpose has resulted in differences in breeding objectives between breeders producing animals fit for each purpose. To enhance the protective demeanour of the animal, conformation showing rewards an upright head and neck carriage (specifically referred to as having a general appearance of “proud carriage”), and breeders in some countries have employed tail and or ear docking. Docking is used on the breed until the current time in the USA and Canada but has been eschewed by Federation Cynologique Internationale (FCI) and The Kennel Club (KC) standards since 2015. Differences in breed standards between countries have the potential to affect genes underlying traits in the standards, including conformation of the head carriage, ears and tail in dogs bred for exhibition and temperament for working dogs. Over time the name of the breed has been simplified from Dobermann pinscher to Doberman. The breed standards and breeding practices of many pedigreed dog breeds have been closely scrutinized in recent times. This scrutiny has revealed potential negative impacts of cosmetic procedures on dog health and welfare (for example, through tail-docking or ear-cropping, or alternatively breeding for tail-less) and negative impacts of breeding practices relating to desirable phenotypes on dog health and longevity [1]. Breeding for novel phenotypes excluded from the breed standard (for example rare coat color or variation in size e.g., giant or miniature) is more common in animals bred for purposes other than exhibition. Genome-wide homozygosity has been negatively associated with breed mean lifespan (after correction for body-size) and positively associated with disease risk [2–6]. In a study of Kennel Club registered dog breeds in the UK, of 25 breeds with age at death registered for more than 50 individuals, the Doberman had the shortest observed lifespan [7]. Breed mean (...truncated)