There are an average of 54 such mutations in each person's genome. They seem to make people sick and even kill people, but they are actually harmless. Sonia Vallabh hopes that the variation of D 178N also belongs to this situation.
In 20 10, Sonia Walab sent her mother away. She died of a mysterious disease called fatal family insomnia. The misfolded prion proteins gathered together and destroyed her brain. The next year, Sonia was examined and found that she also had a copy of the prion protein gene PRNP and carried the mutation D 178N, which may lead to her mother's illness.
This is a real death sentence: the average onset age of fatal family insomnia is 50 years old, and the disease progresses rapidly. But then 26-year-old Walab didn't want to give up without a fight. Therefore, she and her husband, Eric Minikel, quit their jobs in law and transportation consulting respectively and returned to the campus to study for a doctorate in biology. They want to know everything about fatal family insomnia and how to stop it. One of their most important tasks is to determine whether the mutation of D 178N is bound to cause disease.
Few people have asked such questions before, but medical genetics is going through a stage of self-torture. Since the beginning of this century, the rapid progress of genomics research has found thousands of genetic variations related to diseases and disabilities, many of which are reliable, but many of which were once considered dangerous or even fatal are actually harmless. EXAC (Exome Aggregation Consortium), one of the biggest genetic studies in history, reveals the true characteristics of these sheep in wolf skin.
The concept of ExAC is very simple. It contains the sequences of protein coding regions (exons) in more than 60 thousand genomes in a database, so that scientists can compare them and understand the variation degree of exons. However, this resource has a far-reaching impact on biomedical research, which can not only help scientists rule out the wrong disease-gene association, but also produce new discoveries. By studying the frequency of variation in different populations, researchers can understand the functions of many genes and their encoded protein.
David Gore Zstein, a geneticist at Columbia University, said that ExAC subverted human genetic research. Researchers can start with mutations that should have interesting effects and study what happens to people who carry such mutations, rather than tracing their genetic roots from diseases or traits. "This is a brand-new way of research," he said.
ExAC also provides better information for families facing genetic diagnosis. For example, people strongly suspect that D 178N will cause prion diseases, because many patients with prion diseases carry this mutation, but it rarely appears in others. But before ExAC was founded, no one knew how rare it was. If it occurs more frequently than prion diseases, it means that the probability of Vallabh disease is much lower than previously predicted.