Aims: To develop strategies for assessing the function and pathogenicity of variants across the whole genome, to track the origin, and eventually to identify disease-associated causal variants
Scientific rationale: Variants functional assessment plays critical roles in result interpretation and prioritization of disease-associated causal variants. Although several variant assessment strategies have been developed, there are several limitations. First, there are a vast number of rare genetic variants at the whole genome level, including coding and non-coding, with unknown genetic patterns and functional mechanisms, posing challenges for traditional methods of studying pathogenic variants. Second, the origins of variants are unclear. In addition to traditional germline variants, de novo germline variants and mosaic variants also serve as important complements to disease-associated causal variants. Tracking the origins of variants and exploring their diverse mechanisms are necessary. High-quality large-scale population cohort data, including various complex disease phenotypes (such as tumors, cardiovascular diseases, rare diseases, etc.) and various types of genomic data (such as chip, exome, and whole-genome sequencing), are urgently needed to comprehensively investigate the relationship between variants and human diseases.
Project duration: 36 months
Public health impact: Our study hope to establish a comprehensive functional and pathogenicity assessment pipeline for variants across the whole genome, which will help us understand the molecular basis of human diseases and eventually lead to the development of personalized prevention and treatment based on individual genetic characteristics.