CONSORTIUM TO CONSTRUCT CHROMOSOME 3 FRAMEWORK MAP

3号染色体占人类基因组的7%，约为210 兆。 综合物理和遗传图谱的构建 这条染色体，基于一组共同的DNA标记，将是一个强大的 研究人类遗传学的工具。一个由5个实验室组成的联盟， 3号染色体的优秀资源已经形成了开发10 3号染色体高度多态性标记的cM图谱。迄今为止， 只有有限数量的高度多态性标记开发了这个 染色体 其中四个实验室将分离出高度多态的 来自Cosmos、YAC和流式分选文库的标记，以及 染色体的特定区域的微片段。 多态性将 主要基于（CA）n重复，其将在区域上定位 在物理地图上。 多态性将通过基于PCR的试验进行检测 从（CA）n重复侧翼的序列信息。 此外， 只有轻微或中度多态性的已建立的基因座将被 分析单链构象多态性和梯度凝胶电泳 电泳以增加检测到的多态性水平。 这些 将在CEPH和委内瑞拉家庭中输入试剂，数据将 进行分析以绘制基因图谱。 到两年，我们将产生10个 具有0.7或更大杂合性的标记的cM图谱。 在 第三年，我们将扩大地图，并填补空白，向2-5厘米的地图 这是基因组计划的五年目标。 的发展 人类3号染色体的遗传连锁图将大大促进 生殖系和恶性疾病中疾病基因的鉴定。 一组 这些标记已经被放置在物理和遗传图谱上， 基于序列将大大加快制图进度 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.