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

Zhenglin DU; Liang MA; Hongzhu QU; Wei Chen; Bing Zhang; Xi LU; Weibo Zhai; Xin Sheng; Yongqiao Sun; Wenjie LI; Meng Lei; Qiuhui QI; Na Yuan; Shuo Shi; Jingyao Zeng; Jinyue Wang; Yadong Yang; Qi Liu; Yaqiang Hong; Lili Dong; Zhewen Zhang; Dong Zou; Yanqing Wang; Shuhui Song; Fan Liu; Xiangdong Fang; Hua Chen; Xin Liu; Jingfa Xiao; Changqing Zeng

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

Author: Zhenglin DU ^{1
,

2} ; Liang MA ^{1
,

3} ; Hongzhu QU ^{1
,

4} ; Wei CHEN ^{1
,

3} ; Bing ZHANG ⁵ ; Xi LU ⁵ ; Weibo ZHAI ⁵ ; Xin SHENG ^{1
,

2} ; Yongqiao SUN ⁵ ; Wenjie LI ⁵ ; Meng LEI ⁵ ; Qiuhui QI ⁵ ; Na YUAN ^{1
,

2} ; Shuo SHI ^{1
,

2} ; Jingyao ZENG ^{1
,

2} ; Jinyue WANG ^{1
,

2} ; Yadong YANG ^{1
,

4} ; Qi LIU ^{1
,

3} ; Yaqiang HONG ^{1
,

3} ; Lili DONG ^{1
,

2} ; Zhewen ZHANG ^{1
,

2} ; Dong ZOU ^{1
,

2} ; Yanqing WANG ^{1
,

2} ; Shuhui SONG ^{1
,

2} ; Fan LIU ^{1
,

6
,

7} ; Xiangdong FANG ^{1
,

7
,

8} ; Hua CHEN ^{1
,

6
,

7} ; Xin LIU ^{1
,

6
,

7} ; Jingfa XIAO ^{1
,

9
,

10} ; Changqing ZENG ^{1
,

6
,

11}
Author Information

1. Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
2. BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
3. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
4. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
5. Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.
6. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
7. University of Chinese Academy of Sciences, Beijing 100049, China.
8. CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
9. BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
10. University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: xiaojingfa@big.ac.cn.
11. University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: czeng@big.ac.cn.
Publication Type:Journal Article
Keywords: De novo assembly; Large population; Phenotype association; Reference genome; Variation map
From: Genomics, Proteomics & Bioinformatics 2019;17(3):229-247
CountryChina
Language:English
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.