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

基因变异是进化创新的主要来源，也是一个重要因素 用于表型变异。因此，了解这种变异在 包括基础生物学和进化论，以及最终的孟德尔式和复杂疾病。 我们将通过自发的突变过程来研究遗传变异的起源。 对测序数据集的计算分析将揭示机械力 人类潜在的生殖系和体细胞癌突变。我们将设计新的统计方法 将在群体遗传学、癌症基因组学中应用的从头突变模型 和神经精神疾病的遗传学。 接下来，我们将改进解释和预测地震影响的计算方法 分子功能突变，包括编码变异和非编码变异。我们的方法 整合来自进化遗传学和生物物理学的数据，并依赖于比较、功能 和结构数据。新开发的方法将在医疗和医疗领域都有应用 种群遗传学。 我们将研究等位基因的种群动态，以估计形成遗传的力量 种群内的变异。我们将依靠种群遗传学模型来分析 人类表型的进化维持和遗传结构。着迷于 基因和表型的关系，我们将结合理论模型和 对大规模测序数据集进行统计分析以推断等位基因的性质 具有复杂特征的建筑。我们将设计新的方法来描述和预测 常见疾病风险的遗传成分。好了！

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. !