Samples from dead individuals help us understand the genetic code behind the disease

than 99.9 per cent of the genetic sequences of individuals are the same, with less than 0.1 per cent difference, but why are we so different?Human genome sequences (3 billion pairs of bases) are often likened to a 6 billion-word book of heaven, and the sequencing of the human genome project simply turns the book into "clear text", which humans still do not understand.A large research project called Genotype-Tissue Expression (GTEx) is trying to find the answer - to find the relationship between sequences and actual symptoms (diseases) and to determine how different genes affect expression. The GTEx program is the largest human organ transcription group research program available. The study, funded by the National Institutes of Health (NIH) and involving researchers from several leading U.S. research institutions, including the Massachusetts Institute of Technology, Harvard University and the University of Chicago, attempted to "directly translate" the results of genome sequencing by analyzing the genomes, transcriptions, and proteomics of deceased people of different genders.After 10 years of research, GTEx plans to publish its latest analysis in early September, in the form of a series of papers published in journals such as Science cells. It is worth mentioning that GTEx data is widely used as a reference data set for designing new methods and tools, resulting in a large number of statistical methods that facilitate more in-depth study.Find the genes associated with the "little troubles" in your lifeHere are everyone's little worries, welcome to the "seat on the number" -If you're not old enough to be a middle-age greasy man, you may be worrying: why my hairline is rising;If you're a stressed working woman, you may be worried: breast nods at last year's check-up don't know what's going on, breast cancer rates are said to be highIf you're a new mom, you're probably worried: My family is overweight! Why are you so fat that you can't even see your neck except breast milk; you...In the results of the GTEx study, these questions were answered in the analysis of genomes, transcriptions, and proteomics.These answers come from the sequencing, aggregation, analysis of a large amount of data... Relying on a large number of innovative analytical methods. The researchers aggregated all the research data into a GTEx dataset, which has now been updated to the eighth edition, and includes data from 17,382 samples from 838 bodies, 52 tissues, and two cell line.The researchers sequenced the samples with genome-wide sequences, transcription group expressions, and correlations to identify which genes were closely related to which characters.For the first time, the study found that a gene named C9orf66, which is associated with hair loss, is much more expressive in men than in women; the CCDC88C gene, which has a higher level of expression in women, is a gene associated with breast cancer; and that the baby weight that nobids are most concerned about may not be related to the baby itself, but is closely related to the HKDC1 gene in Baoma' body, which has the function of regulating blood sugar during pregnancy, and its expression affects the reproductive weight of women.Of course, there are many discoveries closely related to real life, such as the high expression of some genes that promote the expression of cancer genes, women live longer than men, and other associated genes, in the latest research, people can be early signs of life activity in the human genome in the vast map of the "by the map", give functional "footnotes."The identification of rare disease-related genetic mutationsto pay attention to and study the 0.1% gene difference between humans, in fact, has a long history. The academic community often refers to it as the Genome-wide Association Study (GWAS), which, as the name suggests, is designed to find a link between genes and functions. 0.1% of different gene sequences mean that there are at least 300,000 common SNPs (single nucleotide polymorphisms, i.e. changes in single bases) out of 3 billion base pairs throughout the genome. "GWAS has only looked at common SNP bits, which means there are still many rare variants that have not yet been identified." Some analysts believe that the study of rare mutations requires more accurate measurements than common mutations, in other words, only large-scale genome-wide analysis (at least all-exon sequencing) can meet the needs of the study. In previously released phase i and II results, GTEx plans to also focus on the regulation of transcription groups by common mutations. And the third phase of the announced GTEx program has finally expanded to a rare mutation. GTEx's greatest advantage over other databases is gene expression from a variety of organs. However, GTEx does not have very detailed personality information except for basic information such as sex and age, as samples are obtained from individuals who have died unexpectedly. This time, in collaboration with the UK Biobank, which has previously studied rare mutations, many rare mutations that have a significant impact on gene expression have been identified and corresponding associated symptoms (diseases) have been identified. This greatly enhances the significance of GTEx's own research. The results of the GTEx series of research papers, "Identifying functional rare mutations through trans-organ transcription group signals", show that rare mutations contained in the human genome increase the risk of certain diseases, and the study detected rare mutations associated with extreme gene expression by analyzing 838 genome-wide data and transcription group data from multiple organs. The researchers integrated three extreme expression signals from 49 organs and eventually identified for the first time a rare mutation with high impact and a link to the disease. The study also gives a method to identify rare mutations, which can be used to explain the genome of individuals and the discovery of rare mutations, and provides a powerful means for studying the genetic function of rare mutations and improving the detection ability of diseases. Trying to reveal the pattern of telomeres in different organs are the ends of chromosomes. Because the length of the telomeres reflects the history and replication potential of cells, it is called the "silky dividing clock" of cell life. Changes in telomere length are thought to be the "pendulum sound" of the body's approach to death as it ages. So far, the difference in telomere length has never been accurately measured, especially in different organs in humans, the pattern of telomere length is what is not clear. GTEx plans to make systematic measurements for the first time. What's more, the researchers found a "scale" -- because blood cells have the shortest telomeres, their telomere length can be used as a reference for telomere lengths in other organs. The researchers measured the relative telomere length in more than 25 tissues in 952 donors, according to the authors of one of a series of papers, Determining Telomere Length in Human Tissues. The telomere length of 639 unique tissue samples was measured using multifactor quantitative analysis techniques, also known as Luminex analysis, resulting in the largest shareable data set. After the measurements, the team combined the data with data from GTEx supply characteristics, genetic variation, and tissue-specific expressions, using model analysis to find out exactly what factors were relevant to the change in telomere length. It was eventually found that tissue type and supply age had the greatest impact, and smoking or not could even fine-tune telomere length. Of the different tissues tested, telomere length was the shortest in the blood and the longest in testicular tissue. In most tissues, telomere length is negatively associated with age, and the older the telomeres are, the shorter the telomeres. Studies have also shown that differences in telomere length based on ancestors are present in reproductive cells and passed on to fertilized eggs. As a "continuing" of the Human Genome Project, the GTEx program has been expected to reveal many important mysteries, accumulate more data, and develop more effective methods. The indirect impact of major life science programs is enormous, for example, the Human Genome Project has greatly contributed to sequencing efficiency, making genome-wide sequencing faster and faster, and costs falling again and again. GTEx's breakthrough is more like cutting a mouth for the "hard bone" of the mystery of life, and larger, deeper and important explorations will attract more attention and research, and accumulate more popularity and experience for human beings to "unmasking themselves". No wonder some researchers predict that as the GTEx project continues to advance, evaluating gene regulation effects in disease changes and differences in different environments will be supported and will help advance the goals of precision medicine research programs.
(Science and Technology Daily)