Genome map to play role in analysis of diseases

A pan-genome reference of 36 Chinese ethnic groups, a joint research result of 26 domestic institutions that will play a valuable role in the reconstruction of the timeline of human evolution and the mechanism analysis of major genetic diseases among Chinese populations, was recently released.

A paper about the study led by Fudan University, Xi'an Jiaotong University and the Chinese Academy of Medical Sciences, was published on the website of the journal Nature on Wednesday.

In the research, scientists discovered the reference sequence of approximately 190 million base pairs missing from the human universal reference genome, including 5.9 million small variants and 34,000 structural variations being newly identified. The variants and variations involve a large number of potential functional elements, including at least 1,367 protein-coding genes.

"We found that the reference sequence missing from the universal reference genome included a colossal amount of information about adaptive evolution and genetic variation originating from ancient humans, and was related to phenotypes or functions, such as keratinization, UV response, DNA repair, immunological responses and life span," said Xu Shuhua, a correspondent author of the paper.

Scientists conducted deep sequencing on 58 individual samples representing 36 Chinese ethnic groups, using the latest third-generation high-fidelity genome sequencing technology.

"This research also showed that it is necessary to establish a pan-genome map of our own population," said Xu, who is also a professor at the School of Life Sciences, Fudan University.

He explained that the commonly used human reference genomes so far are constructed based on predominantly white European samples, which makes it difficult to represent the genomic diversity of non-European populations, especially in China.

In a study recently published by the Human Pan-genome Reference Consortium, only three Chinese were included in the total of 46 samples worldwide, and all of them are from the Han ethnic group.

Experts said that the long population history and rich geographical and climatic environment have shaped the unique genetic diversity of the Chinese nation.

It is significant to build a pan-genome map of the Chinese population that can represent the genetic diversity of the Chinese nation, which will greatly improve the sensitivity and accuracy of capturing rare or low-frequency genetic variations, and thus support the research of Chinese genetic diversity and the molecular mechanism of complex diseases as well as the research and application of precision medicine, said Xu.

"For example, among the variants we identified in this research, some participate in the metabolism and removal of drugs and are related to mental diseases, pains, tumors and heart diseases. Some may provide new explanations to the genetic mechanism and pathogenesis of anemia among Chinese people," he said.

Zhao Xingming, a professor at the Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, said that brain disease research based on this pan-genome reference is already underway.

"It may bring new insights into prevention and treatment of diseases, including schizophrenia and autism," said Zhao, who is also a correspondent author of the paper.

For the next phase, Xu said the research is expected to include samples of all 56 Chinese ethnic groups and the sample size will rise to 500.