Haplotype analysis of population and pedigree data in association studies

描述(申请人提供)：关联研究基于全基因组分析和通过连锁不平衡(LD)定位的精细定位，已经变得越来越受欢迎，因为它们代表了一种潜在的比连锁分析更具成本效益和更强大的基因定位方法。单倍型是指位于同一染色体上的标记等位基因的组合，这些标记等位基因往往是一起遗传的。单倍型在关联研究中扮演着重要的角色，因为基于单倍型的方法可以提供额外的力量来定位疾病基因，并提供对影响遗传标记之间相关性的因素的洞察(即，LD)。这样的洞察力可能会为理解人类进化以及识别两个或更多因果变异之间的顺式相互作用提供必要的信息。由于这些原因，基于单倍型的方法引起了人们的极大关注，并一直是遗传学会的极大兴趣。然而，尽管这一研究领域取得了快速的进展，但利用大量紧密连锁的单核苷酸多态(SNPs)进行单倍型分析才刚刚起步，这给科学家带来了巨大的挑战，因为每个个体的单倍型是在大规模研究中产生的。此外，目前还不清楚如何最好地进行单倍型分析，以及单倍型分析可以在什么程度和什么背景下增加关联研究的能力。因此，集中讨论单倍型分析的相关方法和应用问题可以激发新的想法，交流不同的观点/方法，从而导致更强大和有效的单倍型分析。为了解决这一需求，我们请求资金支持在关联研究中对人群和系谱数据进行单倍型分析的会议，在该会议上，单倍型分析的主要研究人员聚集在一起，讨论如何最好地利用单倍型来识别常见人类疾病的基因。这次会议的具体目的是回顾单倍型分析的最新方法学发展，探索为单倍型分析设计的新的统计和计算方法，讨论最佳利用单倍型的策略，并向一般科学界传播从这次会议中学到的知识和教训。会议将于2007年12月举行，来自学术界、政府和工业界的科学家将出席会议。

DESCRIPTION (provided by applicant): Association studies either based on genome wide analysis and localized fine mapping through linkage disequilibrium (LD) have become increasingly popular as they represent a potentially more cost effective and powerful approach for gene mapping than linkage analysis. Haplotypes refer to combinations of marker alleles which are located closely together on the same chromosome and which tend to be inherited together. Haplotypes play an important role in association studies because haplotype based approaches may provide additional power for mapping disease genes and also provide insight on the factors influencing the dependencies among genetic markers (i.e., LD). Such insights may provide information essential for understanding human evolution and also for identifying cis-interactions between two or more causal variants. For these reasons, haplotype based methods have drawn much attention and have long been of great interest of genetic societies. However, despite the rapid progress on this research area, haplotype analysis using a large number of tightly linked single nucleotide polymorphisms (SNPs) is just being developed and poses great challenges to scientists because the genotype other than the haplotypes of each individual is generated in large scale studies. In addition, it is still unclear how best to perform the haplotype analysis and to what extent and in what context the haplotype analysis can increase power for association studies. Therefore, a focused meeting on relevant methodological and applied issues on haplotype analysis can stimulate novel ideas and exchange different views/approaches that can lead to more powerful and efficient analyses of haplotypes. To address this need, we request funds to support a conference on haplotype analysis of population and pedigree data in association studies in which leading researchers on haplotype analysis convene to discuss the best use of haplotypes to identify genes underlying common human diseases. The specific aims of this conference are to review the up-to-date methodological development of haplotype analysis, to explore novel statistical and computational methods designed for haplotype analysis, to discuss strategies for the best use of haplotypes, and to disseminate the knowledge and lessons learned from this conference to the general scientific community. The meeting will take place in December of 2007 and be attended by scientists from academia, government, and industry.