3.5KJPNv2: an allele frequency panel of 3552 Japanese individuals including the X chromosome

Abstract

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 with easy-to-use interfaces. In the Tohoku Medical Megabank Project, we sequenced nearly 4000 individuals from a Japanese population and constructed an allele frequency panel of 3552 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 large-scale 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 .

Human ACE2 receptor polymorphisms predict SARS-CoV-2 susceptibility

“…It is very likely that there are natural variations in ACE2 in human populations, though not under selection, that may increase or decrease its affinity to SARS-CoV-2 S-protein and thereby render individuals more resistant or susceptible to the virus. To investigate this, we assessed ACE2 protein-altering variations from a number of databases including the gnomAD (Karczewski et al, 2019), RotterdamStudy (Ikram et al, 2017), ALSPAC (Fraser et al, 2013) and Asian-specific databases which included GenomeAsia100k (GenomeAsia, 2019), HGDP (Bergstrom et al, 2020), TOMMO-3.5kjpnv2 (Tadaka et al, 2019), and IndiGen (https://indigen.igib.in/), and HGDP (Bergstrom et al, 2020) ( Supplementary Table 1). We found a total of 298 unique protein altering variants across 256 codons distributed throughout the 805 amino acid long human ACE2 (Figure 1a, 1b, Supplementary Figure 1, and Supplementary Table 1).…”

“…We queried multiple genomic databases including gnomaAD (Karczewski et al, 2019) (https://gnomad.broadinstitute.org/), DicoverEHR (Dewey et al, 2016), RotterdamStudy (Ikram et al, 2017), ALSPAC (Fraser et al, 2013) and Asian specific databases which included GenomeAsia100k (GenomeAsia, 2019), HGDP (Bergstrom et al, 2020), TOMMO-3.5kjpnv2 (Tadaka et al, 2019) IndiGen (https://indigen.igib.in/) and Other aggregated data for ACE2 protein altering variations in populations groups across the world. The ACE2 genotypes in this study were from over 290,000 samples representing over 400 population groups across the world.…”

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

“…The genome-by-genome alignment and comparison by minimap2 and paftools software 36 called 2,501,575 SNVs between hs37d5 and JG1 in the autosomes and X chromosome. We then extracted the frequency of the allele employed in JG1 from the allele frequency (AF) panel of 3,552 Japanese individuals (namely, 3.5KJPNv2 AF panel 37 ) to create a site frequency spectrum, in which the horizontal axis indicates the non–hg19-type allele and the vertical axis indicates the number of such SNV sites (Figure 2c). From these data, we found 241,500 SNV sites with an AF = 1.0, indicating that all of the Japanese chromosomes in the AF panel carried the JG1-type allele at the 241,500 sites.…”

“…Paired-end reads with length of 162 bp from the three donors (jg1a, jg1b, and jg1c) were individually mapped to hs37d5.fa, and variant calling was performed according to previously described methods 37 , following GATK Best practices. The resulting VCF file was subjected to PCA using EIGENSOFT software (ver.…”

“…4.2). We chose 310 Japanese samples from the 3.5KJPNv2 cohort 37 ; 100 from Miyagi Prefecture in northern Japan; 29 from Nagahama City, in western Japan; and 181 from Nagasaki Prefecture, in southern Japan. Variants shared among the 313 samples were selected and filtered using plink software (ver.…”