One million Chinese genomes
Prenatal testing and Chinese genetics
Maxim Rousseau, Polit.roo
Recently, the first results of a genetic study of Chinese residents, covering more than 140 thousand people, were published.
This is the largest genetic study at the moment, but its authors are ready to surpass their own record in the foreseeable future. For their work, the scientists used DNA samples collected during diagnostic tests of pregnant women.
Although the so-called non-invasive prenatal testing (NIPT) has appeared quite recently, it has already become widespread in many countries. It is especially popular in China, where about 70% of all such studies are done. According to Chinese doctors, six to seven million women have already undergone this procedure in the country, and more than ten million worldwide. The predecessors of this method were methods of genetic diagnosis, in which the material was taken directly from the membranes of the fetus, amniotic fluid or umbilical cord blood. Penetration into the uterus in such studies is associated with some risk to the fetus.
Noninvasive testing consists in analyzing blood from the mother's vein and extracting fetal DNA from it. Such testing is used for early detection of various chromosomal abnormalities. It can be carried out starting from the tenth week of pregnancy and, unlike previous methods, it does not pose a danger to the fetus.
In a study conducted by scientists from the Chinese biotechnology Center BGI, the South China University of Technology, the University of California at Berkeley and the University of Copenhagen, DNA samples obtained during such testing were used to determine the genetic diversity of the Chinese population, susceptibility to various diseases, migrations and other information. The growing spread of NIPT made it possible to make the study massive. Although the cost of DNA sequencing has decreased in recent years and there are already works in which the genomes of tens of thousands of people are analyzed, obtaining data on hundreds of thousands or millions of people until recently seemed impossible.
The authors of the current study, published in the journal Cell (Liu et al., Genomic Analyses from Non-invasive Prenatal Testing Reveal Genetic Associations, Patterns of Viral Infections, and Chinese Population History), processed DNA samples obtained from 141,431 pregnant women, which is about one ten thousandth of the Chinese population and is quite a representative sample. The study covered 31 of China's 34 provinces. In addition to the Han Chinese, the most numerous nationality of the PRC, among the women whose DNA was analyzed were representatives of 36 of the 55 major ethnic minorities of China, including Uighurs, Kazakhs and Mongols of Inner Mongolia. Each of more than 140 thousand women signed an informed consent to participate anonymously in the study. The data obtained in the course of the work are posted in the National Genetic Bank of China. The site published information about the frequency of alleles of 9.05 million single-nucleotide polymorphisms.
It should be remembered, however, that noninvasive prenatal diagnostics is low-frequency genome sequencing, that is, with such a study, sufficient information can be obtained only about 6-10 percent of the maternal genome, whereas now such studies are usually based on 80 percent of the genome or more. The authors of the study managed to partially compensate for the low proportion of the sequenced genome with NIPT using specially created software. The authors believe that low-frequency genome sequencing in a large number of people may be more informative than a more detailed reading of the genome in small groups. It is necessary to take into account the difference in cost. Noninvasive prenatal diagnostics in China costs about one hundred US dollars, while genome-wide sequencing costs about a thousand dollars per person.
Analysis of the collected data allowed scientists to reveal details of the history of various ethnic groups in China, to identify new genetic loci associated with the phenotype features, for example, they identified 48 variations of genes associated with height and 13 variants associated with body mass index. The information received will still be processed and new conclusions will surely be drawn based on it. In the meantime, for example, it has been possible to establish a connection between one of the variants of the NRG1 gene with an increased probability of twins and hyperthyroidism (enhanced thyroid function). Variants of the SCMH1 and HCN1 genes were associated with an older age of the mother during the first pregnancy. The results obtained coincide with those obtained for these genes in studies conducted on mice.
The results were also important for viral epidemiology and disease monitoring. After all, the genetic material of viruses can also be determined in the isolated DNA. Modification of one of the genes, as the study showed, was associated with a higher concentration of herpesvirus type six in maternal blood. Interestingly, the statistics of viral infection in Chinese and European pregnant women turned out to be different (data on them were obtained in previous studies). In Europe, the most frequent viruses were herpesviruses of the seventh and fourth types, and in Chinese women, hepatitis B virus is in the first place in frequency, followed by endogenous retrotransposon virus HERV-K113 and herpesvirus of the sixth type.
The Han population turned out to be relatively genetically homogeneous, which the authors explain by mass labor migrations in China after 1949, when large masses of the population moved to the other end of the country. However, certain genetic differences have also been found between the northern and southern Han Chinese. Geographical heterogeneity is most pronounced in six genes.
These genes are associated with the immune response, fatty acid metabolism, bipolar disorder, and even the composition of earwax (as it was established several years ago, its composition determines genetically and may indicate the origin of a person). Some of the identified genes correlate with climatic conditions. In general, the results show how environmental factors influence the genetic evolution of the Chinese population. For example, alleles of the FADS2 gene, common in northern China, are associated with the predominantly meat diet of local residents in ancient times, while its other variants in the south are associated with a significant proportion of plant foods.
Other peoples show a significantly higher level of genetic diversity compared to the Han. Researchers have also found genetic variants in many Chinese that are common among Indians, Southeast Asians and even Europeans. These are traces of interethnic contacts that took place in the course of history, in particular as a result of trade on the Great Silk Road.
As noninvasive prenatal diagnostics is gaining popularity, new opportunities for population-based genetic research are opening up. "We have demonstrated that it is possible to solve many classic genetic and medical problems of the population by analyzing NIPT data. Since millions of people around the world will be tested, it is becoming increasingly important to establish cooperation in order to obtain more informed consent from patients and properly process medical information," says the first author of the current work Siyang Liu, senior researcher at BGI. Her colleague Xun Xu adds: "For me, this is a very interesting new model for biological research. It provides a powerful tool and platform for future work. Now we are proving that this data, as well as the structure and methods can be used to study many things. This is just the beginning."
The current work has become the first stage of the Million Chinese Genome Project. At the same time, scientists are already working on a new study based on three and a half million DNA samples.
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