Report of the comparative subcommittee for human and mouse homologies.
Report of the comparative subcommittee for human and mouse homologies.
复制标题
人类和小鼠同源性比较小组委员会的报告。
DOI：
10.1159/000133026
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
A. Searle
中科院分区：
文献类型：
--
作者：
M. Davisson;P. Lalley;J. Peters;D. Doolittle;A. Hillyard;A. Searle
自 HGM10 以来，小鼠中定位的同源基因座数量增加了四分之一。 HGM10 末端共鉴定出 400 个同源位点（357 个常染色体基因和 43 个 X 或 Y 连锁基因）；截至本次会议，已绘制了 519 个基因座（473 个常染色体基因座和 46 个 X 或 Y 连锁基因座）（表 1）。大多数添加的新基因都扩展或填充了先前识别的常染色体片段；然而，在人类染色体 8、10、16、17、19 和 22 上又发现了 6 个保守片段，使片段总数至少达到 59 个。为了进行历史比较，HGM3 (1974) 的第一份比较报告包括 5 个保守的常染色体片段和 4 个 X 连锁基因座。由于人类和小鼠基因组之间已识别的同源片段数量的增加，比较基因图谱的预测价值已大大增加。因此，比较作图是一种日益强大的工具，可以有效地绘制两个物种的新基因图谱并识别候选疾病基因。一个显着的进步是可见表型的比较作图方面的进展。随着小鼠和人类基因组高分辨率图谱的进步，识别小鼠中人类疾病基因候选基因座的能力正在迅速增强。表2列出了可以识别人类疾病基因候选基因座的小鼠突变的例子。这些突变中的每一个都产生与映射到同源区域的人类突变所产生的可见表型相似的表型。 Searle 等人 (1989) 提供了更完整的候选疾病同源物列表。直到最近，人类和小鼠基因组之间的比较作图研究还依赖于两个物种中同线组的比较或人类细胞学图谱和小鼠遗传图谱的比较。然而，在过去两年中，小鼠的物理图谱加速了，因此可以对人类和小鼠基因组同源区域的物理图谱进行比较。这些研究将使得直接解决基因顺序和基因间距离是否保守、高度保守的片段内是否存在内部重排以及物理图谱和遗传图谱如何相互关联成为可能。这些数据也将有助于识别人类疾病的小鼠模型。迄今为止，一些最详细的研究涉及 HSAlq 和 MMU1 (Kingsmoreet al., 1989)、HSAlq 和 MMU3 (Kingsmorc ct al., 1990)、小鼠 X 连锁基因的脉冲场图 (Brockdorff et al., 1989)、MMU11 的物理图 (Munkc 和 Francke, 1987) 以及 MMU11 的物理图。小鼠 Hox 基因簇（Do 和 Lonai，1988；Ferguson-Smith 和 Ruddle，1988）。在不久的将来，物理作图程序将像在人类基因组作图中一样在小鼠中常规使用。表 1 中的同源性标准列于 HGM10 比较委员会报告中。委员会强烈鼓励作者在已发表的报告中明确说明同源性标准。我们没有列出假基因，除非有具体证据表明它们之间的同源性。该表显示了基于细胞学作图的人类基因座的图谱位置和基于重组分析（以着丝粒的 cM 为单位）的小鼠基因的图谱位置，因为这些是当前可用的每个物种的信息最丰富的作图类型。尽管这两种类型的图谱是使用不同的程序构建的，但它们很好地近似了两个物种中同源基因的比较位置。它 …
The number of homologous loci mapped in mouse has increased by one quarter since HGM10. A total of 400 homologous loci (357 autosomal and 43 X-or Y-linked genes) were identified at the end of HGM10; 519 loci (473 autosomal and 46 X-or Y-linked) have been mapped as of this meeting (Table 1). Most new genes added have extended or filled out previously identified autosomal segments; however, six additional conserved segments have been identified on human chromosomes 8, 10, 16, 17, 19, and 22 bringing the total number of segments to at least 59. For historical comparison, the first comparative report at HGM3 (1974) included 5 conserved autosomal segments and 4 X-linked loci. The predictive value of comparative gene mapping has increased enormously due to these increased numbers of identified homologous segments between the human and mouse genomes. Thus, comparative mapping is an increasingly powerful tool for efficiently mapping new genes in both species and for identifying candidate disease genes. A notable advancement is the progress in comparative mapping of visible phenotypes. With the advances toward high resolution maps in mouse and human genomes, the ability to identify candidate loci in the mouse for human disease genes is increasing rapidly. Examples of mutations in mice that may identify candidate loci for human disease genes are listed in Table 2. Each of these mutations produces a visible phenotype resembling that produced by a human mutation that maps to the homologous region. A more complete list of candidate disease homologs appears in Searle et al.(1989). Until recently comparative mapping studies between the human and mouse genomes have relied upon comparisons of syntenic groups in both species or comparisons of cytological maps of human and genetic maps of the mouse. Physical mapping in the mouse, however, has accelerated during the past two years so that comparisons between the physical maps of regions of homology of human and mouse genomes can be made. These studies will make it possible to address directly whether gene order and intergcnic distances have been conserved, whether there have been internal rearrangements within highly conserved segments, and how the physical and genetic maps relate to each other. These data will also be instrumental in identifying mouse models of human diseases. Some of the most detailed studies thus far involve comparisons between HSAlqand MMU1 (Kingsmoreet al., 1989), HSAlq and MMU3 (Kingsmorc ct al., 1990), a pulse field map of X-linked genes in the mouse (Brockdorff et al., 1989), a physical map of MMU11 (Munkc and Francke, 1987) and physical maps of the mouse Hox gene clusters (Do and Lonai, 1988; Ferguson-Smith and Ruddle, 1988). In the near future, physical mapping procedures will be used as routinely in the mouse as they are in human genome mapping. Criteria for the homologies in Table 1 were listed in the HGM10 Comparative Committee Report. The Committee strongly encourages authors to be explicit about criteria for homology in published reports. We have not listed pseudogenes unless there is specific evidence for homology between them. The table displays map positions for human loci based on cytological mapping and for mouse genes based on recombination analysis (in cM from the centromere), because these are the most informative kinds of mapping for each species currently available. Although the two types of maps are constructed using different procedures, they give a good approximation of the comparative positions of homologous genes in the two species. It …