Catalogue of the largest human genetic variants to date announced

Helps to deepen understanding of gene function and discover disease-related genes

  Science and Technology Daily, Beijing, May 31 (Reporter Zhang Mengran) British "Nature", "Nature · Newsletter" "Nature · Medicine" recently published a series of reports from multiple research institutions, focusing on a collection of more than 140,000 The application of the human sample database-the genome aggregation database (gnomAD), which has the largest public catalog of human genetic variants to date, and is a valuable resource for us to deeply understand the function of human genes and discover genes related to new diseases.

  The functions of most genes in the human genome are still unknown. One way to reveal the function of genes is to observe the results of mutations in genes. These variants tend to produce undesirable results, but they are usually rare. Large-scale gene sequencing studies can help investigate the effects of these loss-of-function variants, or they can bring important insights into human biological characteristics and diseases.

  In an overview report published by Nature, Conrad Kazewisky, a scientist at the Massachusetts Institute of Technology-Harvard Bod Institute and his colleagues, described a total of 125,748 exomes. And 443,769 predicted loss-of-function variants identified in 15,708 genome-wide sequencing data sets. In view of the fact that these variants are expected to affect the normal functioning of their encoded proteins, the team further evaluated the impact of these variants on physiological functions: whether they had little effect or caused serious health problems. Two other reports published by Nature at the same time used the database to create a library of structural variants, and evaluated the effects of gene deletion, replication, and even reversal.

  Other reports released at the same time explore how to use human loss-of-function variants to evaluate candidate drug targets, improve clinical interpretation of genetic variants, and how to examine specific loss-of-function variants in more detail. For example, Nicola Wiffin and colleagues at the Imperial College London analyzed a variant of a gene associated with increased risk of Parkinson ’s disease, and the results showed that targeting this gene may be a safe treatment.

  Scientists say that the sample size of the gnomAD project is more than double that of its predecessor, and the previous Exome Aggregation Consortium (ExAC) collected more than 60,000 exome data. Kazewski and colleagues also pointed out that they are still far from identifying all the predicted loss-of-function variants in humans. Nevertheless, they believe that this resource can enhance our assessment of rare and common genetic diseases.


  The development of biology and medicine has led scientists to study many diseases directly at the molecular and genetic levels. In-depth study of the human genome has become the key to unlocking the causes of many major diseases. Parkinson's disease, Alzheimer's disease, autism and other series of diseases with complex etiologies are listed here. In addition to finding the cause, deciphering the human genome can also locate important drug targets for the treatment of many diseases, thereby bringing hope for the development of more effective biological drugs and the development of more accurate diagnosis and treatment plans.