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A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves.

ABSTRACT: The domestic dog serves as an excellent model to investigate the genetic basis of disease. More than 400 heritable traits analogous to human diseases have been described in dogs. To further canine medical genetics research, we established the Dog Biomedical Variant Database Consortium (DBVDC) and present a comprehensive list of functionally annotated genome variants that were identified with whole genome sequencing of 582 dogs from 126 breeds and eight wolves. The genomes used in the study have a minimum coverage of 10× and an average coverage of ~24×. In total, we identified 23 133 692 single-nucleotide variants (SNVs) and 10 048 038 short indels, including 93% undescribed variants. On average, each individual dog genome carried ?4.1 million single-nucleotide and ~1.4 million short-indel variants with respect to the reference genome assembly. About 2% of the variants were located in coding regions of annotated genes and loci. Variant effect classification showed 247 141 SNVs and 99 562 short indels having moderate or high impact on 11 267 protein-coding genes. On average, each genome contained heterozygous loss-of-function variants in 30 potentially embryonic lethal genes and 97 genes associated with developmental disorders. More than 50 inherited disorders and traits have been unravelled using the DBVDC variant catalogue, enabling genetic testing for breeding and diagnostics. This resource of annotated variants and their corresponding genotype frequencies constitutes a highly useful tool for the identification of potential variants causative for rare inherited disorders in dogs.

SUBMITTER: Jagannathan V

PROVIDER: S-EPMC6842318 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves.

Jagannathan V V Drögemüller C C Leeb T T

Animal genetics 20190905 6

The domestic dog serves as an excellent model to investigate the genetic basis of disease. More than 400 heritable traits analogous to human diseases have been described in dogs. To further canine medical genetics research, we established the Dog Biomedical Variant Database Consortium (DBVDC) and present a comprehensive list of functionally annotated genome variants that were identified with whole genome sequencing of 582 dogs from 126 breeds and eight wolves. The genomes used in the study have ...[more]

PMID: 31486122

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Project description:BACKGROUND:Advances in genome technology have simplified a new comprehension of the genetic and historical processes crucial to rapid phenotypic evolution under domestication. To get new insight into the genetic basis of the dog domestication process, we conducted whole-genome sequence analysis of three wolves and three dogs from Iran which covers the eastern part of the Fertile Crescent located in Southwest Asia where the independent domestication of most of the plants and animals has been documented and also high haplotype sharing between wolves and dog breeds has been reported. RESULTS:Higher diversity was found within the wolf genome compared with the dog genome. A total number of 12.45 million SNPs were detected in all individuals (10.45 and 7.82 million SNPs were identified for all the studied wolves and dogs, respectively) and a total number of 3.49 million small Indels were detected in all individuals (3.11 and 2.24 million small Indels were identified for all the studied wolves and dogs, respectively). A total of 10,571 copy number variation regions (CNVRs) were detected across the 6 individual genomes, covering 154.65?Mb, or 6.41%, of the reference genome (canFam3.1). Further analysis showed that the distribution of deleterious variants in the dog genome is higher than the wolf genome. Also, genomic annotation results from intron and intergenic regions showed that the proportion of variations in the wolf genome is higher than that in the dog genome, while the proportion of the coding sequences and 3'-UTR in the dog genome is higher than that in the wolf genome. The genes related to the olfactory and immune systems were enriched in the set of the structural variants (SVs) identified in this work. CONCLUSIONS:Our results showed more deleterious mutations and coding sequence variants in the domestic dog genome than those in wolf genome. By providing the first Iranian dog and wolf variome map, our findings contribute to understanding the genetic architecture of the dog domestication.

Project description:Adaptation during the domestication from wolves (Canis lupus) to dogs (Canis lupus familiaris) is a debated ecological topic. Changes in food and environment are major divergences in the domestication of dogs. Gut microbes play an important role in animal adaptation to the food and environmental changes. In this study, shotgun sequencing was performed to compare the species diversity and functional diversity of gut microbes in wild wolves (group CLW, n = 3), captive wolves (group CLC, n = 4), and domestic dogs (group CLF, n = 4). The results found that Bacteroidetes, Firmicutes, Fusobacteria, Proteobacteria and Actinobacteria were the most abundant phyla and Bacteroides, Fusobacterium, Prevotella, Megamonas, Paraprevotella, Faecalibacterium, Clostridium were the most abundant genera in the gut of wolves and dogs. Groups CLW, CLC and CLF have shown significant difference in gut microbial species diversity and functional diversity. Bacteroides, Fusobacterium and Faecalibacterium were most abundant genera in groups CLW, CLC and CLF, respectively. Their abundance varied significantly among groups. Compared to the wild wolves, the intestinal microbiol genes of domestic dogs were significantly enriched in the carbohydrate metabolism pathway of KEGG database. One hundred and seventy-seven enzymes were detected with significantly higher abundance in group CLF than that in group CLW, and 49 enzymes showed extremely significant higher abundance in group CLF than that in group CLW (q < 0.01) base on the function abundance annotated in CAZy database. It is noteworthy that there were also significant differences in the abundance of 140 enzymes between groups CLC and CLW (q < 0.05). Clustering analysis based on both the species and the function abundance of intestinal microbiota all found that groups CLC and CLF clustered into one branch, while samples from group CLW clustered into the other branch. This result suggests that captive wolves are more similar to domestic dogs than wild wolves in both species composition and function composition of intestinal microbiota.

Project description:Selection of behavioral traits holds a prominent role in the domestication of animals, and domesticated species are generally assumed to express reduced fear and reactivity toward novel stimuli compared to their ancestral species. However, very few studies have explicitly tested this proposed link between domestication and reduced fear responses. Of the limited number of studies experimentally addressing the alterations of fear during domestication, the majority has been done on canids. These studies on foxes, wolves, and dogs suggest that decreased expression of fear in domesticated animals is linked to a domestication-driven delay in the first onset of fearful behavior during early ontogeny. Thus, wolves are expected to express exaggerated fearfulness earlier during ontogeny compared to dogs. However, while adult dogs are less fearful toward novelty than adult wolves and wolf-dog hybrids, consensus is lacking on when differences in fear expression arise in wolves and dogs. Here we present the first extended examination of fear development in hand-raised dogs and European gray wolves, using repeated novel object tests from 6 to 26 weeks of age. Contrary to expectations, we found no evidence in support of an increase in fearfulness in wolves with age or a delayed onset of fear response in dogs compared to wolves. Instead, we found that dogs strongly reduced their fear response in the period between 6 and 26 weeks of age, resulting in a significant species difference in fear expression toward novelty from the age of 18 weeks. Critically, as wolves did not differ in their fear response toward novelty over time, the detected species difference was caused solely by a progressive reduced fear response in dogs. Our results thereby suggest that species differences in fear of novelty between wolves and dogs are not caused by a domestication-driven shift in the first onset of fear response. Instead, we suggest that a loss of sensitivity toward novelty with age in dogs causes the difference in fear expression toward novelty in wolves and dogs.

Dataset Information

A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves.

Publications

A comprehensive biomedical variant catalogue based on whole genome sequences of 582 dogs and eight wolves.

Similar Datasets

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