Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome

Abstract

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a “comfort” zone for a high frequency of 677T between latitudes of 35–45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

Polyunsaturated fatty acid biosynthesis pathway and genetics. implications for interindividual variability in prothrombotic, inflammatory conditions such as COVID-19✰,✰✰,★,★★

“…A FADS2 -promoter SNP (rs968567) enhancing FADS2 expression was discovered [120] . A whole genome analysis of the Chinese population showed rs28456 to be associated with AA [121] . ELOVL2 and ELOVL5 maternal genetic variants were associated with PUFA levels in breast milk [89] .…”

Profiling variable-number tandem repeat variation across populations using repeat-pangenome graphs

“…Furthermore, genotyping tests for the presence of a known variant, and does not reveal the spectrum of copy number variation that exists in tandem repeat sequences. An alternative use of LRS assemblies is for population-specific references that improve SRS read mapping by adding sequences missing from the reference (Du et al 2019;Shi et al 2016) . Because missing sequences are enriched for VNTRs (Audano et al 2019) , haplotype-resolved LRS genomes may help improve alignment to VNTR regions, as well as facilitate the development of a model to discover VNTR variation by serving as a ground truth.…”

De novo genome assembly of a Han Chinese male and genome-wide detection of structural variants using Oxford Nanopore sequencing

“…As a result of using longer reads, the assembly result is better than the 30× dataset assembly obtained using the nanopore sequencing platform by Jain et al (2018), which comprised 2886 contigs with an N50 contig size of 3 Mb. Summary statistics for the sequencing and assembly of five reference genomes, including three existing individual Chinese reference genomes (Wang et al 2008;Shi et al 2016;Du et al 2019), were listed in Table 1. We aligned the assembled contigs to the GRCh38 reference, and then created chromosomes plot illustrating the contiguity of the nanopore assembly (the Cytogenetic band is background on the right, Fig.…”