| 1. |
- Meadows, Jennifer, et al.
(författare)
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Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture
- 2023
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Ingår i: Genome Biology. - : BioMed Central (BMC). - 1465-6906 .- 1474-760X. ; 24
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Tidskriftsartikel (refereegranskat)abstract
- Background: The international Dog10K project aims to sequence and analyze several thousand canine genomes. Incorporating 20 x data from 1987 individuals, including 1611 dogs (321 breeds), 309 village dogs, 63 wolves, and four coyotes, we identify genomic variation across the canid family, setting the stage for detailed studies of domestication, behavior, morphology, disease susceptibility, and genome architecture and function.Results: We report the analysis of > 48 M single-nucleotide, indel, and structural variants spanning the autosomes, X chromosome, and mitochondria. We discover more than 75% of variation for 239 sampled breeds. Allele sharing analysis indicates that 94.9% of breeds form monophyletic clusters and 25 major clades. German Shepherd Dogs and related breeds show the highest allele sharing with independent breeds from multiple clades. On average, each breed dog differs from the UU_Cfam_GSD_1.0 reference at 26,960 deletions and 14,034 insertions greater than 50 bp, with wolves having 14% more variants. Discovered variants include retrogene insertions from 926 parent genes. To aid functional prioritization, single-nucleotide variants were annotated with SnpEff and Zoonomia phyloP constraint scores. Constrained positions were negatively correlated with allele frequency. Finally, the utility of the Dog10K data as an imputation reference panel is assessed, generating high-confidence calls across varied genotyping platform densities including for breeds not included in the Dog10K collection.Conclusions: We have developed a dense dataset of 1987 sequenced canids that reveals patterns of allele sharing, identifies likely functional variants, informs breed structure, and enables accurate imputation. Dog10K data are publicly available.
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| 2. |
- Lingaas, Frode, et al.
(författare)
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Bayesian mixed model analysis uncovered 21 risk loci for chronic kidney disease in boxer dogs
- 2023
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 19:1
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Tidskriftsartikel (refereegranskat)abstract
- Author summaryChronic kidney disease (CKD) is described as a set of heterogeneous disorders affecting kidney structure and function. CKD is common in dogs and has been diagnosed in nearly all breeds. In this study, we identified 21 genetic regions associated with CKD in a boxer population and investigated the relevant genes and putative regulatory variants in these regions. Studies of canine CKD may help to better understand the pathology of kidney disease in both dogs and humans, and shows an important potential for early identification of high-risk individuals. Chronic kidney disease (CKD) affects 10% of the human population, with only a small fraction genetically defined. CKD is also common in dogs and has been diagnosed in nearly all breeds, but its genetic basis remains unclear. Here, we performed a Bayesian mixed model genome-wide association analysis for canine CKD in a boxer population of 117 canine cases and 137 controls, and identified 21 genetic regions associated with the disease. At the top markers from each CKD region, the cases carried an average of 20.2 risk alleles, significantly higher than controls (15.6 risk alleles). An ANOVA test showed that the 21 CKD regions together explained 57% of CKD phenotypic variation in the population. Based on whole genome sequencing data of 20 boxers, we identified 5,206 variants in LD with the top 50 BayesR markers. Following comparative analysis with human regulatory data, 17 putative regulatory variants were identified and tested with electrophoretic mobility shift assays. In total four variants, three intronic variants from the MAGI2 and GALNT18 genes, and one variant in an intergenic region on chr28, showed alternative binding ability for the risk and protective alleles in kidney cell lines. Many genes from the 21 CKD regions, RELN, MAGI2, FGFR2 and others, have been implicated in human kidney development or disease. The results from this study provide new information that may enlighten the etiology of CKD in both dogs and humans.
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| 3. |
- Wang, Guo-Dong, et al.
(författare)
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Out of southern East Asia : the natural history of domestic dogs across the world
- 2016
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Ingår i: Cell Research. - : Nature Publishing Group. - 1001-0602 .- 1748-7838. ; 26:1, s. 21-33
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Tidskriftsartikel (refereegranskat)abstract
- The origin and evolution of the domestic dog remains a controversial question for the scientific community, with basic aspects such as the place and date of origin, and the number of times dogs were domesticated, open to dispute. Using whole genome sequences from a total of 58 canids (12 gray wolves, 27 primitive dogs from Asia and Africa, and a collection of 19 diverse breeds from across the world), we find that dogs from southern East Asia have significantly higher genetic diversity compared to other populations, and are the most basal group relating to gray wolves, indicating an ancient origin of domestic dogs in southern East Asia 33 000 years ago. Around 15 000 years ago, a subset of ancestral dogs started migrating to the Middle East, Africa and Europe, arriving in Europe at about 10 000 years ago. One of the out of Asia lineages also migrated back to the east, creating a series of admixed populations with the endemic Asian lineages in northern China before migrating to the New World. For the first time, our study unravels an extraordinary journey that the domestic dog has traveled on earth.
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