CONSORTIUM TO CONSTRUCT CHROMOSOME 3 FRAMEWORK MAP

3号染色体占人类基因组的7%，约为210 兆级数据库。综合物理和遗传图谱的构建 这种基于一组常见DNA标记的染色体将是一种强大的 研究人类遗传学的工具。由5个实验室组成的联合体，全部 拥有优良资源的3号染色体已经形成了10号染色体 3号染色体高度多态标记的CM图谱。到目前为止，有 仅有为数不多的高度多态的标记被开发出来 染色体。其中四个实验室将分离出高度多态的 来自COSMID、YAC和FLOW排序库的标记以及 染色体上特定区域的微型文库。多态将 主要基于将在区域本地化的(CA)n重复 在实体地图上。多态将通过基于聚合酶链式反应的检测来检测。 根据(CA)n个重复序列两侧的序列信息。另外呢，那么 只有轻微或中度多态的已建立的基因座将是 单链构象多态和梯度凝胶分析 提高电泳法检测的多态水平。这些 试剂将在CEPH和委内瑞拉家庭中进行分型，数据将 被分析以产生基因图谱。到两年后，我们将产生10%的 杂合度为0.7或更大的标记的厘米图。在 第三年，我们将扩大地图，填补2-5厘米地图的空白 这是基因组计划的五年目标。开发一种新的 人类3号染色体的遗传连锁图谱将显著促进 生殖系疾病和恶性疾病中致病基因的鉴定。一套 已经被放置在物理和遗传图谱上的标记 基于序列的测绘将极大地加快测绘进度 3号染色体。

Chromosome 3 has 7% of the human genome and is approximately 210 megabases. The construction of integrated physical and genetic maps for this chromosome, based on a common set of DNA markers, will be a powerful tool for studying the genetics of man. A consortium of 5 laboratories all with excellent resources for chromosome 3 has been formed to develop a 10 cM map of highly polymorphic markers for chromosome 3. To date there have been only a limited number of highly polymorphic markers developed for this chromosome. Four of the laboratories will isolate highly polymorphic markers from cosmids, YACs, and flow sorted libraries as well as minilibraries for specific regions of the chromosome. Polymorphisms will be predominantly based on (CA)n repeats which will be regionally localized on a physical map. The polymorphisms will be detected by a PCR based assay from sequence information flanking the (CA)n repeats. In addition, well established loci that are only slightly or moderately polymorphic will be analyzed for single stranded conformational polymorphisms and gradient gel electrophoresis to increase the level of polymorphism detected. These reagents will be typed in CEPH and Venezuelan families and the data will be analyzed to produce a genetic map. By two years we will generate a 10 cM map of markers that have a heterozygosity of 0.7 or greater. In the third year we will expand the map and fill in gaps towards the 2-5 cM map that is the 5 year goal of the Genome Project. The development of a genetic linkage map of human chromosome 3 will significantly facilitate the identification of disease genes in germline and malignant disorders. A set of markers that have been placed on both physical and genetic maps and are based on sequence will greatly accelerate the progress of mapping chromosome 3.