KIR Haplotype Sequencing A Comprehensive Picture of the Genetics of the KIR Locus

PROVIDIED。 该核心将提供来自NMDP患者和捐赠者的基因组序列数据，这些数据将 被其他项目和核心用于设计和实施适当的实验。在基础上建设 之前的工作是对MHC区域进行测序，我们已经确定了一个类似Ig的杀伤细胞的基因组序列 受体(KIR)单倍型，代表破译KIR单倍型变异的第一步。给定的基因组 序列数据，包括编码和编码内的基因含量和二级等位基因变异 在不合作的地区，将有可能开发出符合独特的 该基因家族的特征将允许直接确定完整的KIR单倍型。 目的是将这些进展应用于研究KIR对骨髓结局的影响 在此背景下，移植特别是通过NMDP，以及与免疫相关的遗传效应 计划项目我们计划实现以下具体目标：1)识别和表征新的 杀伤细胞免疫球蛋白样受体(KIR)基因座的单倍型和等位基因多态性。这将是 利用高通量基因组序列分析来自中国的KIR全基因座 多个骨髓供体和受体来源的细胞系DNA。这一目标将定义 足够数量的KIR单倍型包括绝大多数相关人群。2)发展 并定义了一组试剂和技术，作为研究潜在的KIR连接的作图工具 疾病。为了实现这一点，我们将定义和关联KIR单倍型频率、等位基因连锁 NMDP中现有基因和新基因的不平衡、重组频率和位置 从人口和一系列族裔群体中分离出来的。这将允许我们从实体KIR数据集中进行选择 我们将构建，以便选择适当的子集，以允许对整体或 KIR单倍型的主要部分。在此授权过程中，数据将在此核心之间交换 以及其他适当的项目和核心，以指导要测序的新单倍型的选择， 并指导开发和利用更精确的高级基因分型分析方法 KIR基因分型。这些数据将同时提供给感兴趣的科学界 通过数据库核心项目提交。

PROVIDIED. This Core will provide genomic sequence data derived from NMDP patients and donors that will be used by other projects and cores in the design and implementation of appropriate experiments. Building on prior work sequencing MHC regions, we have determined the genomic sequence of a Killer cell Ig-like receptor (KIR) haplotype, representing a first step in deciphering haplotypic variation at KIR. Given genomic sequence data, which includes both gene content and second level allelic variation within coding and noncociing regions, it will be possible to develop detection methodologies amenable to the unique characteristics of this gene family that will allow for the direct determination of complete KIR haplotypes. With the aim of applying these developments to studies of the involvement of KIR in the outcome of marrow transplant specifically though the NMDP, and immune related genetic effects in general, in the context of this program project we propose to accomplish the following specific aims: 1) To identify and characterize new haplotypes and allelic polymorphisms in the killer cell Ig-like receptor (KIR) genomic locus. This will be accorriDlished by utilizing high-throughputgenomic sequenceanalysis of the complete KIR locus from multiple marrow donor and recipient derived cell line DNAs. This aim will define the complete structureof sufficient numbers of KIR haplotypes to include a large majority of the relevant population. 2) To develop and define a set of reagents and technologies useful as mapping tools for the study of potential KIR-linked diseases. To accomplish this we will define and relate KIR haplotype frequencies, allelic linkage disequilibrium, recombination frequency, and location relative to existing and new genes within the NMDP population and from a spectrum of ethnic groups. This will allow us to select from the substantialKIR dataset we will build, in order to select an appropriate subset that will allow for the optimal discriminationof whole or major portions of KIR haplotypes. During the course of this grant, data will be exchanged between this core and other appropriate projects and cores in order to guide the choice of new haplotypes to be sequenced, and to direct the development and utilization of superior genotyping assays capable of moreprecisely genotyping KIR. These data will be simultaneously be made available to the interested scientific community through submissions through the database Core project.