发布人：张基建 信息来源：基础医学院 发布日期：2010.11.26 阅读次数：1772 [内部信息]
报告题目：The Quest in Rare Genetic Variants
报告人：于福利博士（Fuli YU）
报告人单位：Baylor College of Medicine（美国）
报告时间：2010年11月 29日（星期一）下午2:30
报告地点：郑州大学基础医学院学术报告厅（新校区二楼）
报告人简介：
于福利博士，现为美国贝勒医学院助理教授。他原毕业于南开大学分子生物学和生物化学专业，于2005年在美国贝勒医学院获分子和人类遗传学专业博士学位，2005~2008在哈佛大学遗传系进行博士后研究，2008年8月——至今在美国贝勒医学院人类基因组测序中心任助教授。他在读博士期间参与了人类基因组计划的第12号染色体测序工作，在发展人类基因组重要技术——分子倒置探针技术（Molecular Inversion Probe, MIP）的过程中发挥了关键作用。他参与了国际单倍型项目（International HapMap Project，简称HapMap）并发挥了重要作用；目前他参与了“1000个基因组计划”（1000 Genomes Project）研究并领导贝勒医学院在该项目中的生物信息和SNP数据处理工作。其研究方向：大规模基因组技术；医学遗传学中有关复杂疾病的研究；群体遗传学中有关人类进化的研究。他并为Journal of Biomedicine and Biotechnology（SCI收录杂志，影响因子1.750）等杂志编辑。已经在Science和Nature上发表论文多篇。
讲座摘要：
The Quest in Rare Genetic Variants
The 1000 Genomes Exon Pilot Project generated high coverage sequence data primarily in the coding regions of approximately 1,000 genes from 697 individuals sampled from seven different populations. The data was collected using multiple DNA capture technologies combined with two different next generation sequencing platforms (Illumina and 454). Boston College (BC), Baylor College of Medicine-Human Genome Sequencing Center (BCM-HGSC) and the Broad Institute (BI) independently implemented informatics pipelines for data analysis that made SNP and indel discoveries with high confidence. The results have been released at the DCC website (www.1000genomes.org) for public download.
The median per-individual sequence coverage within the seven populations ranged from 30X to 67X. Analysis of all 697 samples by both BC and BI yielded ~13,000 total overlapping variant sites (SNPs). The Exon Pilot working group has carried out extensive experimental validations (>1200 sites) in five tiers using either Sequenom or PCR-Sanger pipelines, to understand the quality of the SNP call release. The validation experiment targeted various categories, including singleton-low frequency SNPs called by different groups, and functional SNPs, for example nonsynonymous SNPs, splice sites. Analysis based on comparison to the validation results indicates that the accuracy of the SNP calls is very high overall with validation rate at 95-98% for rare SNPs including singletons.
The considerable sequence depth makes it possible to detect low-frequency variants with very high sensitivity, and therefore, ascertain the low-frequency end of the site frequency spectrum with much better accuracy than achievable in low-coverage sequence data. The ability to detect rare alleles in genomic regions of interest, and the modest cost compared to high-depth whole-genome sequencing, make capture-sequencing approaches attractive for medical re-sequencing studies. The 1000 Genomes Project aims to expand the exome sequencing program to the whole exome coverage in ~2500 individuals. This genetic variation resource enables detailed understanding of the variant frequency spectrum, particularly the percentage of the rare variants in the coding regions. These less common SNPs and their population-specific metrics (such as MAF, frequency spectrum and LD patterns) have not been well cataloged or characterized, which potentially alter gene functions and likely contribute to human disease risks.郑州大学版权所有，禁止非法转载！2020-09-30 16:00:19