The origin, the function and the phenotypic impact of human alleles

人类等位基因的起源、功能和表型影响

• 批准号: 10553953
• 负责人: SHAMIL SUNYAEV
• 金额: $ 58.36万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-11 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10553953
• 关键词: origin; function; phenotypic; impact; human

Genetic variation is the primary source of evolutionary innovation and a major factor responsible for phenotypic variation. Consequently, understanding such variation has great importance in both basic biology and evolution, and ultimately Mendelian and complex disease. We will study the origin of genetic variation through spontaneous mutational processes. Computational analysis of sequencing datasets will shed light on the mechanistic forces underlying germ-line and somatic cancer mutations in human. We will design new statistical models of de novo mutation that will have applications in population genetics, cancer genomics and genetics of neuropsychiatric disease. Next, we will improve computational methods for interpreting and predicting the effect of mutation on molecular function, including both coding and non-coding variation. Our methods integrate data from evolutionary genetics and biophysics and rely on comparative, functional and structural data. The newly developed methods will have applications in both medical and population genetics. We will study the population dynamics of alleles to estimate the forces that shape genetic variation within populations. We will rely on population genetics models to analyze evolutionary maintenance and genetic architecture of human phenotypes. Fascinated by the relationship between genotype and phenotype, we will combine theoretical models and statistical analysis of large-scale sequencing datasets to infer properties of the allelic architecture of complex traits. We will design new approaches to characterize and predict the genetic component of common disease risk. !

遗传变异是进化创新的主要来源和主要因素