Language
Country/Area
No result found
Gene-first exploration: How to use genes to decode the mystery of complex diseases?
In today's medical research, the relationship between genes and diseases is receiving more and more attention. In particular, the genotype-first approach has begun to transform our understanding of complex diseases. This approach differs from the traditional phenotype-first strategy, which first determines the individual's genotype through molecular testing and then classifies the relevant clinical phenotype. This emerging approach is revolutionizing medical diagnosis and research.
The gene-first approach can avoid initial phenotypic bias and further facilitate the identification of genes that are the cause of the disease.
Background
The concept of gene-first dates back to 1960, when cytogenetic studies first demonstrated the potential of using genotype to predict phenotype. With the advancement of genomics technology, this method has become widely used. Especially in the study of complex diseases, many diseases exhibit diverse phenotypes and variability, making the prior identification of genotypes particularly important.
Methods
The gene-first approach mainly includes the following steps:
- Establish study population and genotyping
- Analyze genetic variation in this population
- Different research groups are formed based on genotype
- Associate genotypes with phenotypes in their respective populations
These steps typically rely on next-generation sequencing technologies and microarray analysis. The raw data undergo statistical analysis to determine the relationship between the genotype of a particular variant and the observed phenotype.
This approach enables clinicians and researchers to identify the cause of disease through common genotypes rather than relying on diverse clinical presentations.
Clinical Applications and Examples
Gene-first approaches excel in the diagnosis of rare diseases and the identification of novel gene-phenotype associations. For example, in 2014, researchers using an isolated population in Finland found an association between higher frequencies of deleterious variants and specific phenotypes using a gene-first approach.
In addition, the method has been used to parse autism spectrum disorder (ASD), further advancing the understanding of using genes to identify different subtypes. This has profound implications for future diagnosis and treatment.
Advantages and limitations
AdvantagesMoving to genotype-first identification has many benefits, including:
- Enables better identification of new disease syndromes and genetic subtypes
- This approach allows consideration of the role of the variant in phenotypic outcomes regardless of whether the healthy parent carries the variant
Restrictions
However, gene-first approaches also have some limitations, including the potential need to follow cases over a long period of time to assess changes in gene-phenotype associations over time. This approach may also lack necessary practicality due to the lack of clinically identifiable phenotypes.
ConclusionGene-first approaches are becoming an important tool for studying complex diseases, providing a new way of understanding and treating them. With the advancement of technology, this method will undoubtedly play an increasingly important role in future clinical practice and research. In the future, can we completely decode the genetic secrets of more complex diseases?
