ONE CENTIMORGAN GENETIC MAPS OF CHROMOSOMES X AND 17

此应用程序是对RFA的响应，其目标是创建 一张高密度限制性片段长度多态图谱 人类基因组的(RFLP)。我们最近已经定位了这些基因 Alport综合征至XP和神经纤维瘤病至中心周围 作为这些研究的一部分，我们分离出了 并对来自这些染色体的探针进行了表征。在这 应用程序，我们建议继续隔离X和17上的探针 直到X染色体有200个标记，17号染色体有100个标记 生成具有标记之间平均距离的初始地图 大约1厘米摩根。地图将基于链接 CEPH参考家系中确定的关系。我们有 与四个不同的实验室建立了合作关系 是分离和/或表征了各种各样的物理 17号染色体上的断点。我们将使用之前的一组 特征的X染色体重排和新的X染色体- 包含我们从Hunt Willard到Hunt Willard的杂交的片段 物理定位X连锁的多态探针。我们将应用一个 我们开发的一系列模型，集成了 细胞学，物理和遗传数据，这将估计 交叉分布和交叉干扰，改善 多个基因座的排序，并解释了性别差异 重组。使用这些方法发现的地图上的差距 将通过为已知的 在适当的区域。

This application is in response to an RFA with the goal of creating a high density map of restriction fragment length polymorphisms (RFLPs) of .the human genome. We have recently localized the genes for Alport syndrome to Xp and Neurofibromatosis to the pericentric region of chromosome 17. As part of these studies, we have isolated and characterized probes from these chromosomes. In this application, we propose to continue isolating probes on X and 17 until there are 200 markers for the X and 100 for chromosome 17 yielding an initial map with an average distance between markers of approximately 1 centiMorgan. The maps will be based on linkage relationships determined in the CEPH reference families. We have established collaborations with four different laboratories which are isolating and/or characterizing a wide variety of physical breakpoints on chromosome 17. We will use a set of previously characterized X-chromosome rearrangements and novel X-chromosome- fragment containing hybrids available to us from Hunt Willard to physically localize X-linked polymorphic probes. We will apply a series of models which we have developed which integrate cytological, physical, and genetic data, which will estimate chiasma distributions and chiasma interference, improve the ordering of multiple loci, and account for sex differences in recombination. Gaps in the map which are found with these methods will be filled by finding new polymorphism for probes known to be in the appropriate region.