Thousands of genomes sequenced to map Han Chinese genetic variation

The first genetic historical map of the Han Chinese has been published in the American Journal of Human Genetics by scientists from the Genome Institute of Singapore (GIS). Based on genome-wide variation in 8,200 individuals, the new map has provided many insights into the evolutionary history and population structure of the Han Chinese which is the largest ethnic population in the world. The map is of great importance as it has helped uncover subtle differences in the genetic diversity of Asian populations, and identifying and understanding such differences is crucial in exploring and explaining how the environment interacts with genes to cause diseases. The GIS scientists hope that their findings will aid in the design of future studies to identify which genes cause ethnic Chinese individuals to be more susceptible to common diseases such as diabetes.

'Genome association studies have provided significant insights into the genes involved in common disorders such as diabetes, high cholesterol, allergies, and neurological disorders, but most of this work has been done on Caucasian populations,' said Dr Edison Liu, executive director of GIS, adding: 'More recently, Dr Liu Jianjun from our institute has been working with his Chinese colleagues to define the genetic causes of some of these diseases in Asian populations. This work refined those tools so that the results will not be obscured by subtle differences in the genetic diversity of Asian populations.'

Over 90 per cent of people in China belong to the Han Chinese population, however, most international genetic studies have only sampled Han Chinese individuals from a small number of locations, therefore revealing only a tiny fraction of the genetic diversity thought to exist in the population. Dr. Jianjun's large-scale study included 6,580 individuals from 10 Chinese provinces, 1,050 samples from the large Chinese cities of Beijing and Shanghai, and a further 570 samples from Singaporeans of Han Chinese descent. It is this great number of samples, from a wide variety of locations, which gave the GIS scientists the resolution needed to construct their genetic map and uncover the subtle genetic differences present in the Asian population.

Interestingly, the study found that genetic divergence among the Han Chinese was closely linked with the geographical map of China. When comparisons were made an individual's genome tended to cluster with others from the same province, and in one particular province, Guangdong, it was even found that genetic variation was correlated with language dialect group. Both of these findings suggest the persistence of local co-ancestry in the country. When looking at the bigger picture the GIS scientists noticed there was no significant genetic variation when looking across China from east to west, but identified a 'gradient' of genetic patterns that varied from south to north, which is consistent with the Han Chinese's historical migration pattern. The findings from the study also suggested that Han Chinese individuals in Singapore are generally more closely related to people from Southern China, whilst people from Japan were more closely related with those from Northern China. Unsurprisingly, individuals from Beijing and Shanghai had a wide range of 'north-south' genetic patterns, reflecting the modern phenomenon of migration away from rural provinces to cities in order to find employment.

'By investigating the genome-wide DNA variation, we can determine whether an anonymous person is a Chinese, what the ancestral origin of this person in China may be, and sometimes which dialect group of the Han Chinese this person may belong to,' said Dr Liu Jianjun, lead author of the paper, adding: 'More importantly, our study provides information for a better design of genetic studies in the search for genes that confer susceptibility to various diseases.'