Biology subjects

Gocho, C.

Publications and source records attributed to Gocho, C..

3 recordsLinked to original sources

bioRxiv2020

Japonica Array NEO with increased genome-wide coverage and abundant disease risk SNPs

BackgroundIncreasing the power of genome-wide association studies in diverse populations is important for understanding the genetic determinants of disease risks, and large-scale genotype data are collected by genome cohort and biobank projects all over the world. In particular, ethnic-specific SNP arrays are becoming more important because the use of universal SNP arrays has some limitations in terms of cost-effectiveness and throughput. As part of the Tohoku Medical Megabank Project, which integrates prospective genome cohorts into a biobank, we have been developing a series of Japonica Arrays for genotyping participants based on reference panels constructed from whole-genome sequence data of the Japanese population. ResultsWe designed a novel version of the SNP Array for the Japanese population, called Japonica Array NEO, comprising a total of 666,883 SNPs, including tag SNPs of autosomes and X chromosome with pseudoautosomal regions, SNPs of Y chromosome and mitochondria, and known disease risk SNPs. Among them, 654,246 tag SNPs were selected from an expanded reference panel of 3,552 Japanese using pairwise r2 of linkage disequilibrium measures. Moreover, 28,298 SNPs were included for the evaluation of previously identified disease risk SNPs from the literature and databases, and those present in the Japanese population were extracted using the reference panel. The imputation performance of Japonica Array NEO was assessed by genotyping 286 Japanese samples. We found that the imputation quality r2 and INFO score in the minor allele frequency bin >2.5%-5% were >0.9 and >0.8, respectively, and >12 million markers were imputed with an INFO score >0.8. After verification, Japonica Arrays were used to efficiently genotype cohort participants from the sample selection to perform a quality assessment of the raw data; approximately 130,000 genotyping data of >150,000 participants has already been obtained. ConclusionsJaponica Array NEO is a promising tool for genotyping the Japanese population with genome-wide coverage, contributing to the development of genetic risk scores for this population and further identifying disease risk alleles among individuals of East Asian ancestry.

genomics↗

bioRxiv2019

Construction and Integration of Three De Novo Japanese Human Genome Assemblies toward a Population-Specific Reference

The complete sequence of the human genome is used as a reference for next-generation sequencing analyses. However, some ethnic ancestries are under-represented in the international human reference genome (e.g., GRCh37), especially Asian populations, due to a strong bias toward European and African ancestries in a single mosaic haploid genome consisting chiefly of a single donor. Here, we performed de novo assembly of the genomes from three Japanese male individuals using >100x PacBio long reads and Bionano optical maps per sample. We integrated the genomes using the major allele for consensus, and anchored the scaffolds using sequence-tagged site markers from conventional genetic and radiation hybrid maps to reconstruct each chromosome sequence. The resulting genome sequence, designated JG1, is highly contiguous, accurate, and carries the major allele in the majority of single nucleotide variant sites for a Japanese population. We adopted JG1 as the reference for confirmatory exome re-analyses of seven Japanese families with rare diseases and found that re-analysis using JG1 reduced false-positive variant calls versus GRCh37 while retaining disease-causing variants. These results suggest that integrating multiple genome assemblies from a single ethnic population can aid next-generation sequencing analyses of individuals originated from the population.

genomics↗

bioRxiv2019

3.5KJPNv2, An allele frequency panel of 3,552 Japanese Individuals

The first step towards realizing personalized healthcare is to catalog the genetic variations in a population. Since the dissemination of individual-level genomic information is strictly controlled, it will be useful to construct population-level allele frequency panels and to provide them through easy-to-use interfaces. In the Tohoku Medical Megabank Project, we have sequenced nearly 4,000 individuals from a Japanese population, and constructed an allele frequency panel of 3,552 individuals after removing related samples. The panel is called the 3.5KJPNv2. It was constructed by using a standard pipeline including the 1KGP and gnomAD algorithms to reduce technical biases and to allow comparisons to other populations. Our database is the first largescale panel providing the frequencies of variants present on the X chromosome and on the mitochondria in the Japanese population. All the data are available on our original database at https://jmorp.megabank.tohoku.ac.jp.

genomics↗