中国医学界专家欢迎基因测序技术走入临床——记“北京同仁医院基因测序技术临床应用学术研讨会”

由中华医学会北京分会检验分会主办,首都医科大学附属北京同仁医院承办,Life Technologies公司协办的"北京同仁医院基因测序技术临床应用学术研讨会"近日在京召开。300多位医学领域的专家、学者、临床医生、     

GWAS 2011: Opportunities and challenges

The wide adoption of genome-wide association study (GWAS) has dramatically changed the landscape of the genetic studies of human diseases.Banking on the study design that employs large and multiple-independent samples,linkage disequilibrium (LD) -based systematic genome-wide interrogation,and vigorous statistical standard for declaring genetic association,GWAS has greatly advanced the genetic studies of human disease by successfully identifying over 4 thousands of genetic susceptibility SNPs or loci for 210 diseases/traits in human.Besides its unrivaled scientific achievements,GWAS has also transformed the communities of human genetics by stimulating unprecedented broad and large-scale collaboration and data sharing across different groups and countries,which has enabled some mega genetic studies where dozens or hundreds of thousands of samples were investigated through mete-analysis,providing enormous statistical power for discovering genetic variants,even the ones with very moderate effect on disease phenotype or physiological trait.While the success of GWAS has been widely recognized,there are many concerns on GWAS that are being passionately debated.In particular,there ate heated discussions on why only a limited proportion,quiet often a small proportion,of genetic heritability can be explained by the GWAS findings,and whether and how the GWAS findings have really advanced the biological investigation and understanding of disease mechanisms.Concerning these shortcomings of GWAS,many have genuinely questioned the perspective of translating the GWAS findings into clinical practice.To provide a platform to discuss the progresses and shortcomings of GWAS,a nature conference,titled “GWAS 2011:Opportunities and Challenges”,was organized through the collaboration between the Nature Genetics and Anhui Medical University,which was held in Hefei,China on May 19-21,2011.     

中药网络药理学研究中的生物信息学方法

为了更有效地治疗癌症、心血管疾病、免疫系统疾病等复杂疾病,基于分子网络的多靶点药物发现理念逐渐成为一种新的趋势,而中药整体、辨证、协同的用药观再一次引起了药物发现领域的极大兴趣。中药在治疗复杂慢性疾病方面有确切的疗效和较小的毒副作用。中药网络药理学从分子网络调控的水平上阐明中药的作用机制,为多靶点药物发现提供有益的启示和借鉴,并有可能从临床有效的中药反向开发现代多组分、多靶点新药。针对基于生物分子网络的中药药理学研究路线中的4 个步骤,介绍近年来中药网络药理学研究中相关的生物信息学方法。     

一种有效的复杂疾病基因定位的检测法

连锁不平衡（LD）应用于某些复杂疾病基因的定位,近年来发展了许多LD定位方法,除TDT外,大多数LD定位方法须先假定无人群混和,人群混合可增大在疾病基因定位时犯Ⅰ类错误的机率,产生无效结果。此方法利用LD来检测标记位点和疾病敏感位点（DSL）的连锁（有连锁不平衡）相关（有连锁）。分析时采用不相关样本,已知其父母基因型和至少父母之一为杂合子,再将随机样本依基因型不同分类,然后对来自不同类的数据应用有力的统计方法进行单独和联合分析。此LD定位法不仅适用于患病和正常个体,而且有效消除据父母基因分类的样本定位时人群混合的影响,分析结果和模拟结果也表明此方法解决了在检测标记位点和疾病敏感位点之间的连锁和相关时人群混和的问题,但与TDT比,此法在检测的位点为DSL时丙能有效和充分地利用矫正数据,检测位点不是DSL时,此法和TDT法可相互补充更有效地检测连锁的DSL。     

Identification of two novel missense WFS1 mutations, H696Y and R703H,in patients with non-syndromic low-frequency sensorineural hearing loss

Non-syndromic low-frequency sensorineural hearing loss (LFSNHL) is an unusual type of hearing loss in which frequencies ≤2000 Hz predominantly are affected. To date, different mutations in two genes, DIAPH1 and WFSI, have been found to be associated with LFSNHL.Here, we report a five-generation Chinese family with postlingual and progressive LFSNHL. We mapped the disease locus to a 2.5 Mb region on chromosome 4p16 between markers SNP_A-2167174 and D4S431, overlapping with the DFNA6/14/38 locus. Sequencing of candidate gene revealed a heterozygous c.2086C＞T substitution in exon 8 of WFS1, leading to p. H696Y substitution at the C-terminus of Wolframin (WFS1).In addition, we performed mutational screening of WFS1 in 37 sporadic patients, 7-50 years of age, with LFSNHL. We detected a heterozygous c.2108G＞A substitution in exon 8 of WFS1, leading to p. R703H substitution in a patient. The H696 and R703 in WFS1 are highly conserved across species, including human, orangutan, rat, mouse, and frog (Xenopus). Sequence analysis demonstrated the absence of c.2086C＞T or c.2108G＞A substitutions in the WFS1 genes among 200 unrelated control subjects of Chinese background, supporting the hypothesis that they represent causative mutations, and not rare polymorphisms. Our data provide additional molecular and clinical information for establishing a better genotype-phenotype correlation for LFSNHL.     

单核苷酸多态性

单核苷酸多态性指基因组内特定核苷酸位置上存在两种不同的碱基,且最少一种在群体的频率不小于1％。由于其丰富、稳定、易实现分析的自动化,大规模的SNP鉴定和公共SNP数据库的建立已经开始。它作为一种全新的研究工具,希望利用它对复杂疾病基因进行大规模的连锁不平衡与相关分析,从而促进多基因疾病发病机理的研究和药物基因组学的发展。     

比较基因组学和人类基因组研究

在人类基因组计划突飞猛进地开展的同时,模式生物基因组计划也在轰轰烈烈地进行,并取得许多实质性的进展,是人类对于模式生物基因组有了更广泛更深刻的认识。这些知识的积累,从根本上推动了人类基因组计划的进行。     

比较基因组学和人类基因组研究

在人类基因组计划突飞猛时地开展的同时,模式生物基因组计划也在轰轰烈烈地进行,并取得许多实质性的进展,是人类对于模式生物基因组有了更广泛更深刻的认识。这些知识的积累,从根本上推动了人类基因组计划的进行。     

遗传病基因的进化

在人类进化过程中,遗传疾病的基因也在发展演化中。由于携带者优势、奠基者效应、遗传漂变、减数分裂驱动和高突变率等因素,使一些疾病的基因不被淘汰,这是在人类基因组研究结果基础上得出的结论。随着更多的疾病基因被克隆和研究,人类将对这一问题有更多的认识。     

人类基因组计划研究进展

本文简要介绍了人类基因组计划的研究目标、内容、策略和人类基因组计划研究的新进展,如遗传图谱、转录图谱的构建、序列分析、疾病基因的鉴定等。同时还介绍了可能力。快基因组全序列分析的新策略和基因组后研究的几种方法。