Previous studies have highlighted CFA10, on which MSRB3 is located, as associated with ear morphology7,52 (Supplementary Fig. As with body size genes, the observations associated with ear morphology highlight a recurring theme in dog genetics; i.e., that small numbers of genes/RNAs control seemingly complex phenotypes (Fig. By conducting a GWAS on 28 affected and 20 control Jack Russell Terriers, each genotyped with the CanineSNP20 BeadChip, Farias et al. Brown, E. A. et al. Coat Variation in the domestic dog is governed by variants in three genes. Nat. We undertake both selective sweep analyses and genome wide association studies (GWAS) inclusive of over 144 modern breeds, 54 wild canids and a hundred village dogs. c Expression level of ESR1 in a panel of 20 breeds, showing high expression in the Sighthounds, Irish Wolfhound and Whippet, in comparison to six different breeds with average leg length. CAS Li, B. It includes genomic sequences longer than 500 bp that have at least 97% identity to the components for at least 98 base pairs. Genetics 204, 192427192755 (2016). 5), and observed the most significant associations (pwald<51010) for HMGA2, IGF1, IGSF1, IRS4, LCORL and SMAD2. Standard breed weights (SBW), height (SBH) and life span were obtained from several sources: weights and height previously listed in Plassais et al.17, although they were updated if weights specified by the AKC5 were different. 44, 821824 (2012). A single nucleotide insertion is observed in large breeds (>41kg). determined morphological phenotypes. Rimbault, M. et al. Genome Res. We applied standard QC methods to remove duplicate samples (see Methods) and validated the breed/species of each genome using a neighbor joining phylogeny comprising variant positions and data from Parker et al.4 (Supplementary Fig. We detected a significant selection signature located on ESR1 locus (in grey). Comparing WGS from 31 dogs of 13 breeds with large, round ears to 182 dogs (85 breeds) that lack this phenotype we observe a significant association on CFA12 (pwald=4.911041). The derived allele for each of these genes was only observed in bulky breeds, including the Bernese Mountain Dog, Great Dane, English Mastiff, and Saint Bernard (Supplementary Data4 and 5). They tend to form social groups (packs) where they hunt, breed, raise and care for their pups communally. In this study, the density of WGS generated variants allows us to bypass fine mapping steps and directly identify likely functional mutations for four body size genes: LCORL, R3HDM1, ADAMTS9-AS, and HNF4G. Statistics for each genotype/marker combination are summarized in (d). Vertical bars correspond to the most associated variants identified with the 722 genomes (in red), and the 855 dogs genotyped on 170k SNP array (in brown), and horizontal bars represent the homozygous haplotype observed. Y-axis represents the relative normalized expression. CanFam3.1 Organism: Canis lupus familiaris (dog) Submitter: Dog Genome Sequencing Consortium Date: 2011/11/02 Assembly type: Assembly level: Chromosome Genome representation: full Synonyms: canFam3 GenBank assembly accession: GCA_000002285.2 (replaced) RefSeq assembly accession: GCF_000002285.3 (replaced) IDs: 317138 [UID] 313658 [GenBank] 3171. To estimate the conservation of the LCORL proteins between dog and human we obtained both protein and gene sequences from Ensembl67 and used SIM68 and LALNVIEW69 to align sequences (Fasta sequences available in Supplementary Data3). We develop a data set of 91 million variants derived from WGS of 722 individuals to identify genomic changes resulting from selective pressure occurring during breed formation and maintenance. Huang, X. The RNA map and Gene_Sequence map are built in the same way, using the same types of evidence, described above. Chromosome Number | BioNinja Shows the placement of dog genomic DNA sequences from GenBank that were not used in the assembly of contigs. Individual discordance was calculated after filtering the WGS genotypes by Genotype Quality (GQ=0, 10 and 20). FEELnc: a tool for long non-coding RNA annotation and its application to the dog transcriptome. The RefSeq genome records for Canis lupus familiaris were annotated by the NCBI Eukaryotic Genome Annotation Pipeline, an automated pipeline that annotates genes, transcripts and proteins on draft and finished genome assemblies.This report presents statistics on the annotation products, the input data used in the pipeline and intermediate . In order to annotate variants and run GWAS, we then kept only biallelic variants (SNV and indels) missing less than 10% of the individuals, for a total of 76.5 million variants using vcftools filters (min-alleles 2 andmax-alleles 2max-missing 0.9minQ 20)61. Mei, C. et al. Bioinforma. Appl. Nature 489, 5774 (2012). Genet. The mitochondrial genome presented in build 3.1, NC_002008, is not derived from the boxer used for the WGS data but was obtained from a dog of the Sapsaree breed. 7, e1002316 (2011). Comparison against 186 canid whole-genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor. Svartberg, K. & Forkman, B. Studies of the Fonnis dogs from Sardinia show commonalities between development of pure breeds and population isolates. Genet. I. This approach is thus the norm for mapping breed-associated traits. PLoS Genet. Identification of LCORL mutation in large breeds and comparison with human. Journal of Natural Environment, 68, 1, 2015, 15-21. doi: 10.22059/jne.2015.53938 It is also possible to construct more complex queries by using explicit Am. See Answer and H.G.P. The single exception was an allele frequency of 0.17 in wild canids and 0.59 in village dogs for the derived allele of IGSF1, which has been previously associated with the muscled phenotype in domestic dogs17, perhaps providing a fitness advantage in the village dog environment. J.P. built the 76 million biallelic variants bed files and performed GWAS. Partial Y-chromosome assemblies have been developed for the cat (Felis catus), dog (Canis lupus familiaris), and grey wolf (Canis lupus lupus), providing the opportunity to examine the red fox (Vulpes vulpes) Y-chromosome in the context of closely related species. 9, 14451460 (2016). Sci. A diploid somatic cell from a dog (Canis lupus familiaris) has a total of 78 chromosomes (2n = 78). Sutter, N. B. et al. Small Anim. Chromosome-length genome assembly and structural - Europe PMC J. Biol. When the GenBank_DNA map is displayed as the master map, in the default verbose mode, the descriptive text includes several columns: Total Bases, which shows the total number of bases in the GenBank record; Aligned Bases, which shows the total number of bases in the genome that were spanned by the alignment to that GenBank record; % identity for the alignment; % coverage, which shows how much of the GenBank record aligned to the genome as a percentage; Alignment-length ration, which is the ratio of the alignment length in the genome to the alignment length of the GenBank record; and Strain from which the GenBank record was derived, when available. Database 2016, baw093 (2016). 5d). 42, 937948 (2010). This study, then, provides a blueprint for expanding the utility of the canine system for identification of variants, genes, and pathways critical to mammalian health and biology. Present address: Texas A&M University, College Station, TX, 77840, USA, Present address: Laboratory of Genetic Susceptibility, National Cancer Institute, National Institutes of Health, Rockville, MD, 20850, USA, Present address: Department of Pathology, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, 02115, USA, Cancer Genetics and Comparative Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA, Jocelyn Plassais,Jaemin Kim,Brian W. Davis,Danielle M. Karyadi,Andrew N. Hogan,Alex C. Harris,Brennan Decker,Heidi G. Parker&Elaine A. Ostrander, You can also search for this author in 1b). Chromosome-length genome assembly and structural variations of the Taxonomy browser (Canis lupus familiaris) - National Center for 2b, 3c, d and 4c and Supplementary Figs. Bonferroni corrections are applied to identify significant associations (threshold=8.46) (Tables1 and 2). Behavior and tail shape values were collected from Vaysse et al. R. Soc. PLINK: a tool set for whole-genome association and population-based linkage analyses. We test which genes contribute the most to both body size and life span, defining the ancestral allele for each gene (as opposed to derived) as that present in wild canid genomes (Supplementary Data4). 2c). We excluded windows with<10 SNPs to prevent the addition of spurious signals. J. As the number of canids in the catalog increases, so will its power. wrote the manuscript, and all authors revised the manuscript. IGF1R, LCORL, STC2, GHR(1), GHR(2), SMAD2, HMGA2, ZNF608, IGF1, R3HDM1, ADAMTS9-AS, HNF4G, ACSL4, and IGSF1 account for as much as 95% of SBW variation in purebred dogs (Table4). CAS A domesticated carnivorous mammal occurring as a wide variety of breeds, many of which are traditionally used for hunting, herding, drawing sleds . Genes shown on the left of the grey line are transcribed in the - orientation (from bottom up), and those on the right in the + orientation (from top down). Efficient mapping of mendelian traits in dogs through genome-wide association. Gnomon uses protein alignments in addition to transcript alignments and, in order to capture as much coding information in the genome as possible in this assembly, Gnomon models may represent partial as well as complete coding sequences. ADW: Canis lupus familiaris: INFORMATION The genome sequence is 2,447 megabases in span. In the meantime, to ensure continued support, we are displaying the site without styles Appl. Sci. PCR products were purified by ExoSap-It reaction (Affymetrix), and then sequenced using BigDye Terminator v3.1 (Applied Biosystems) on an ABI 3730 DNA analyzer. As mentioned in the Searchable Terms section of the Entrez Map Viewer Help Document, any term & Miller, W. A time-efficient, linear-space local similarity algorithm. Derived variants at six genes explain nearly half of size reduction in dog breeds. Correspondence to Filipek-Grniok, B. et al. mRNA alignments were used to segment the genomic sequence by putative gene boundaries, and Gnomon was executed on these segments to predict genes. Natl Acad. We compare variants from 60 breeds (113 dogs) with drop and 46 (101 dogs) with prick ears (Fig. All other samples were removed (including wild canids, village and feral dogs, unknown and mixed samples), leading to a dataset of 268 dogs representing 130 breeds. The primary challenge of that approach is the multi-Mb LD observed in dog genomes10,11,12, resulting in a frequent inability to move from associated marker to genes/mutations1,16,18,21, thus limiting the utility of the dog for genetic studies. Images to the left are Great Dane (top) and Greyhound (bottom). J. Hum. We removed the two outlier breeds (the Anatolian Shepherd Dog and the Tibetan Mastiff) and thus used 734 dogs to analyze the genotype distributions in the dog population for LCORL, HMGA2, SMAD2, IGF1, IRS4 and IGSF1. We further compare each case population to the random-bred village dogs, which have not undergone structured breeding, and observe that modern breeds have experienced different levels of selective pressures to obtain the desired phenotypes. Cell 172, 393407 (2018). The evolution of the wolf occurred over a geologic time scale of at least 300 thousand years. the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in a Manhattan plots showing statistical significance (log10 scale) for the 30,000 most associated biallelic variants for each canine autosome, and all variants for the X chromosome (X-axis) for the long-leg phenotype observed in Sighthounds, Great Dane, and Great Pyrenees. While previous studies have highlighted the observation that small dog breeds live, on average, longer than larger breeds24,40, this data demonstrates clearly that only a subset of body size genes, i.e. The taxonomic classification of Canis lupus in Mammal Species of the World (3rd edition, 2005) listed 27 subspecies of North American wolf, corresponding to the 24 Canis lupus subspecies and the three Canis rufus subspecies of Hall (1981). 2). Genet. n. 1. The original range of Canis lupus consisted of the majority of the Northern hemisphere -- from the Arctic continuing south to a latitude of 20 S, which runs through southern Central Mexico, northern Africa, and southern Asia. Canis lupus familiaris (Domestic Dog) is a subspecies of mammals in the family Canidae. Sci. Our analysis also reveals three candidate genes on CFA11 (zinc finger protein 608-ZNF608)30, CFA19 (R3H domain-containing protein 1- R3HDM1)31 and CFA20 (ADAM metallopeptidase with thrombospondin type 1 motif 9 - ADAMTS9)32. Locke, A. E. et al. 4 and Supplementary Data 6 and 7). 7. ADS 4a)) versus 48 other breeds (80 small, medium and large dogs) and we find four large homozygous haplotypes that are significantly associated with long legs. Press and hold the '+' to expand and reveal all the . The sequencing strategy produced a 7.6-fold whole-genome shotgun (WGS) assembly. 7, 10460 (2016). d Combination of alleles at both loci create four phenotypes. 35, 597598 (1994). These results support and partially explain the previously reported correlation between body size and life span in domestic dog; large breeds breeds (SBW >30kg) have a shorter average life span (810 years) than miniature and toy breeds, which can live18 years24,40.
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