The Tohoku Medical Megabank Organization reports the whole-genome sequences of 1,070 healthy Japanese individuals and construction of a Japanese population reference panel (1KJPN). Here we identify through this high-coverage sequencing (32.4 × on average), 21.2 million, including 12 million novel, single-nucleotide variants (SNVs) at an estimated false discovery rate of <1.0%. This detailed analysis detected signatures for purifying selection on regulatory elements as well as coding regions. We also catalogue structural variants, including 3.4 million insertions and deletions, and 25,923 genic copy-number variants. The 1KJPN was effective for imputing genotypes of the Japanese population genome wide. These data demonstrate the value of high-coverage sequencing for constructing population-specific variant panels, which covers 99.0% SNVs of minor allele frequency ≥0.1%, and its value for identifying causal rare variants of complex human disease phenotypes in genetic association studies.

To test the hypothesis that the domestic dogs are derived from several different ancestral gray wolf populations, we compared the sequence of the displacement (D)-loop region of the mitochondrial DNA (mtDNA) from 24 breeds of domestic dog (34 individual dogs) and 3 subspecies of gray wolf (Canis lupus lupus, C. l. pallipes and C. l. chanco; 19 individuals). The intraspecific sequence variations within domestic dogs (0.00~3.19%) and within wolves (0.00~2.88%) were comparable to the interspecific variations between domestic dogs and wolves (0.30~3.35%). A repetitive sequence with repeat units (TACACGTA/GCG) that causes the size variation in the Dloop region was also found in both dogs and wolves. However, no nucleotide substitutions or repetitive arrays were specific for domestic dogs or for wolves. These results showed that there is a close genetic relationship between dogs and wolves. Two major clades appeared in the phylogenetic trees constructed by neighbor-joining and by the maximum parsimony method; one clade containing Chinese wolf (C. l. chanco) showed extensive variations while the other showed only slight variation. This showed that there were two major genetic components both in domestic dogs and in wolves. However, neither clades nor haplotypes specific for any dog breed were observed, whereas subspecies-specific clades were found in Asiatic wolves. These results suggested that the extant breeds of domestic dogs have maintained a large degree of mtDNA polymorphisms introduced from their ancestral wolf populations, and that extensive interbreedings had occurred among multiple matriarchal origins.

BackgroundBecause the Japanese native cattle Kuchinoshima-Ushi have been isolated in a small island and their lineage has been intensely protected, it has been assumed to date that numerous and valuable genomic variations are conserved in this cattle breed.ResultsIn this study, we evaluated genetic features of this breed, including single nucleotide polymorphism (SNP) information, by whole-genome sequencing using a Genome Analyzer II. A total of 64.2 Gb of sequence was generated, of which 86% of the obtained reads were successfully mapped to the reference sequence (Btau 4.0) with BWA. On an average, 93% of the genome was covered by the reads and the number of mapped reads corresponded to 15.8-fold coverage across the covered region. From these data, we identified 6.3 million SNPs, of which more than 5.5 million (87%) were found to be new. Out of the SNPs annotated in the bovine sequence assembly, 20,432 were found in protein-coding regions containing 11,713 nonsynonymous SNPs in 4,643 genes. Furthermore, phylogenetic analysis using sequence data from 10 genes (more than 10 kbp) showed that Kuchinoshima-Ushi is clearly distinct from European domestic breeds of cattle.ConclusionsThese results provide a framework for further genetic studies in the Kuchinoshima-Ushi population and research on functions of SNP-containing genes, which would aid in understanding the molecular basis underlying phenotypic variation of economically important traits in cattle and in improving intrinsic defects in domestic cattle breeds.