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

提供。 该核心将提供来自NMDP患者和供体的基因组序列数据， 其他项目和核心在设计和实施适当的实验中使用。基础上 在对MHC区域进行测序之前，我们已经确定了杀伤细胞Ig样抗原的基因组序列。 受体（KIR）单倍型，代表在破译KIR单倍型变异的第一步。给定基因组 序列数据，其包括编码内的基因内容和第二级等位基因变异， 非cociing区域，将有可能开发适合于独特的检测方法， 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参与骨髓移植的结果， 移植具体通过NMDP，和免疫相关的遗传效应一般，在这种情况下， 计划项目，我们建议实现以下具体目标：1）识别和表征新的 杀伤细胞Ig样受体（KIR）基因组基因座中的单倍型和等位基因多态性。这将是 通过利用来自于KIR基因座的高通量基因组序列分析， 多个骨髓供体和受体来源的细胞系DNA。这一目标将确定完整的结构， 足够数量的KIR单倍型以包括绝大多数相关群体。2)发展 并定义了一套试剂和技术，可作为研究潜在KIR相关的绘图工具。 疾病为了实现这一点，我们将定义和相关KIR单倍型频率，等位基因连锁 不平衡、重组频率和相对于NMDP内现有和新基因的位置 人口和种族群体的光谱。这将允许我们从大量KIR数据集中选择 我们将建立，为了选择一个适当的子集，将允许最佳的歧视，整体或 KIR单倍型的主要部分。在此期间，数据将在此核心之间交换。 以及其他适当的项目和核心，以指导待测序的新单倍型的选择， 并指导能够更精确地进行上级基因分型测定的开发和利用 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.