SKELETAL DYSPLASIAS OF PAKISTAN

本申请旨在为巴基斯坦骨骼发育不良家族的确定、临床和影像学定义以及遗传模式的确定提供支持。 在选定的具有新表型的家庭中，还将进行血液收集用于分子遗传学研究。 该提案旨在扩大和深化雪松西奈研究所和巴基斯坦阿扎姆大学研究小组之间正在进行的合作努力。在这样做的过程中，拟议的工作将扩大和加强母基金的研究工作。本文的研究工作将围绕以下具体目标展开：1.描述巴基斯坦骨骼发育不良的临床和影像学表型和遗传模式，并在一个家庭的子集，以确定染色体定位和分离疾病基因。我们将检验这一假设，即这些疾病代表了新的表型，一旦确定，将在其他人群中识别。 分子研究有望揭示新的基因位点和重要的骨骼发生基因。在巴基斯坦，对遗传性疾病的重要性和了解尚处于起步阶段，这种合作将使信息和资源能够流动，可用于照顾患有遗传性疾病的巴基斯坦家庭。连锁和突变分析数据将是有用的，在确定携带者的隐性和X连锁疾病的个人家庭成员和亚群的人口。研究结果也将使其他人群中具有相同或相关表型的家庭受益。

This application seeks to provide support for the ascertainment, clinical and radiographic definition, and determination of the inheritance pattern in skeletal dysplasia families in Pakistan. In selected families with novel phenotypes, blood collection for molecular genetic studies will also be undertaken. The proposal seeks to broaden and deepen an ongoing collaborative effort between research groups at Cedars-Sinai Research Institute and Quaid-i-Azam University in Pakistan. In doing so, the proposed work will both expand and enhance the research efforts of the parent grant. The work will be accomplished under the following Specific Aim: 1. To describe the clinical and radiographic phenotypes and the inheritance patterns in skeletal dysplasias of Pakistan and, in a subset of families, to identify the chromosomal location of and isolate the disease genes. We will test the hypothesis that these disorders represent novel phenotypes that, once identified, will be recognized in other populations. Molecular investigations are expected to reveal novel loci and genes important for skeletogenesis. In Pakistan, the importance and understanding of genetic disorders is in its infancy, and this collaboration will allow the flow of information and resources that can be applied in caring for Pakistani families with inherited disorders. Linkage and mutation analysis data will be useful in identifying carriers of recessive and X-linked disorders in individual family members and within subsets of the population. The results will also benefit families with identical or related phenotypes in other populations.