Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome
Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome
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DOI：
10.1016/j.gpb.2019.07.002
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发表时间：
2019-06-01
影响因子：
9.5
通讯作者：
Zeng, Changqing
中科院分区：
文献类型：
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作者：
Du, Zhenglin;Ma, Liang;Zeng, Changqing
为了揭示疾病和生理性状的遗传机制，需要在中国人群中进行大样本的全面测序分析。本文报道了中国科学院精准医学计划（CASPMI）的初步成果，包括北方汉族参考基因组（NH 1. 0）的从头组装和来自中国大部分地区的597名健康人的全基因组分析。鉴于现有的两个中国汉族参考基因组（YH和HX 1）均来自南方，我们结合PacBio、10 x Genomics和Bionano作图的测序策略，构建了一个来自北方个体的新参考基因组NH 1. 0。使用这种整合方法，我们获得了NH1.0基因组的N50支架大小为46.63 Mb，并对NH1.0与YH和HX 1进行了比较基因组分析。为了生成中国人群的基因组变异图谱，我们对597名参与者进行了全基因组测序，并确定了2485万（M）个单核苷酸变异（SNV），385万个小插入缺失和106,382个结构变异。在与收集的表型的关联分析中，我们发现KAT 8的rs 1549293的T等位基因与北方汉族男性的腰围显著相关。此外，与循环叶酸、维生素B12或脂质代谢相关的MTHFR、TCN 2、FADS 1和FADS 2在北方人和南方人之间观察到显著的遗传多样性。特别是，对于同型半胱氨酸增加等位基因rs 1801133（MTHFR 677 T），我们假设，存在一个“舒适”的区域之间的纬度35-45度北纬677 T的高频率。综上所述，我们的研究结果为个性化和精准医学提供了高质量的北方汉族参考基因组和新的人群特异性遗传变异数据集。
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, 10x 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.