Language
Country/Area
No result found
From genes to disease: How can a gene-first approach disrupt traditional medicine?
In contemporary medical research, the traditional "phenotype-first" strategy can no longer meet our needs for a deeper understanding of complex diseases. The "gene-first" method is gradually emerging. It provides researchers with a new perspective by first determining the individual's genotype and then judging the relevant clinical manifestations accordingly.
The gene-first approach takes clinical assessment back to its roots, starting with genes and then moving on to phenotypes, an approach that avoids initial phenotypic bias.
This approach has obvious advantages, especially when facing overlapping complex diseases such as autism spectrum disorder and intellectual disability, which can effectively distinguish different disease subtypes and then determine the treatment path for the corresponding genes. .
Background
The roots of the gene-first approach can be traced back to early cytogenetic studies. In the 1960s, the discovery of trisomy 21, first mentioned in Austin’s book, made us aware of the potential of genetics in predicting phenotypes. With the rapid development of genomics, from the 1960s to the 1990s, many technologies such as chromosome banding and fluorescence in situ hybridization (FISH) were applied to the association study of genotype and phenotype.
Many complex diseases exhibit diverse phenotypes and varying degrees of expressivity, making it a challenge to clearly link disease-causing genes to phenotypes.
Clinical medicine is now increasingly aware that it is more effective to classify genomic diseases based on common genotypes rather than phenotypes. This approach overcomes the multiple misunderstandings that have arisen in the past due to phenotypes and makes communication between researchers and clinicians more effective.
Methods
Gene-first methods usually include the following basic steps: first, establish a research population and perform genotyping; second, analyze the genetic variation in the research population; third, divide the population according to the genotype; and finally, compare the genotype with the The phenotypes in the respective populations were correlated. In this process, next-generation sequencing technologies (such as whole genome sequencing and exome sequencing) are widely used to improve the accuracy of typing.
Statistical analysis of these data allows researchers to identify genetic variants that are significantly associated with disease and to conduct further follow-up disease research.
The application of these technologies not only enhances the ability to diagnose rare diseases, but also opens up a series of new genotype-phenotype relationships, allowing doctors to accurately identify diseases.
Clinical Applications and Examples
For example, a 2014 study of the Finnish population using a genes-first approach revealed a high frequency of recessive variants in that population that have direct links to rare diseases. By comparing variations in different gene groups, doctors have found that these variations often play an important role in the diagnosis and prognosis of diseases.
The gene-first approach can not only improve clinical diagnosis, but also help large pharmaceutical companies develop targeted drugs to achieve higher therapeutic effects.
In addition, for complex diseases such as autism spectrum disorder, using a gene-first approach to subtype patients can deepen our understanding of their genetic causes and may eventually allow the definition of specific subtypes. diagnostic criteria.
Advantages and limitations
With the development of gene sequencing technology, the application of gene-priority methods is becoming more and more widespread. Its main advantage is the ability to classify diseases based on shared genotypes, which will not only facilitate the identification of new syndromes but also improve our understanding of disease subtypes. However, this method also has some limitations. For example, for variants with subtle or mild symptoms, it may not provide effective guidance for prognosis in the short term.
The success of gene-phenotype association studies depends not only on the identification of genotypes but is also limited by the emergence of clinically recognizable phenotypes.
In the future, with the deepening of research and further classification of disease subtypes, many mild phenotypes may gradually show more diagnostic and prognostic value.
The gene-first approach is becoming the new standard in genomics research. Do you think this will become the mainstream direction of medical research in the future?
