Detecting highly conserved regions of the human genome by multispecies sequence comparisons.
Detecting highly conserved regions of the human genome by multispecies sequence comparisons.
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通过多物种序列比较检测人类基因组的高度保守区域。
DOI：
10.1101/sqb.2003.68.255
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发表时间：
2003
期刊：
影响因子：
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通讯作者：
Green,ED
中科院分区：
文献类型：
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作者：
Margulies,EH;NISCComparativeSequencingProgram;Green,ED
从随后的数据比较中获得的见解已经催化了许多其他的基因组测序项目，其中最大的努力集中在一个物种的整个基因组序列的生成上。为此，现在有小鼠（Waterston等，2002）、大鼠（http：//genome. ucsc。edu/cgi-bin/hgGateway？org=大鼠）和河豚（Aparicio et al. 2002）基因组，斑马鱼、鸡和黑猩猩基因组的快速成熟序列，以及对狗、牛和爪蟾基因组测序的承诺（图1）。这种全基因组测序项目提供了有关相应物种遗传结构的完整见解，并允许与其他可用的全基因组序列进行详细比较（Ureta-Vidal等人，2003年）。然而，目前基因组测序的成本（用于产生哺乳动物基因组的高质量草图序列高达5000万至1亿美元）限制了至少在可预见的未来可以以全基因组方式测序的脊椎动物基因组的数量。作为全基因组测序工作的补充，可以对许多其他物种进行小的、确定的基因组区域的靶向测序，从而可以对更大的、进化上更多样化的序列集进行比较分析（图1）。具体而言，这涉及首先从一系列物种中鉴定和分离感兴趣的基因组区域（通常使用细菌人工染色体[BAC]克隆; Shizuya等人，1992; Birren等人，1997）。这一过程已经通过建立不断增长的可用脊椎动物BAC文库库（参见http：//www.基因组gov/10001852和http：//bacpac。chori。org）和开发用于从多个物种平行有效分离靶特异性BAC的方法（托马斯等人，2002）。然后可以使用标准的鸟枪测序方法容易地完成分离的BAC的测序（Wilson和Mardis 1997;绿色2001）。尽管这种靶向测序方法仅产生小基因组区域的数据，但它固有地提供了用于比较来自比通过全基因组方法可以容易地实现的多得多的物种的序列的多功能性。此外，通过仅生成限定的基因组区域的数据，靶向测序策略的成本显著低于其全基因组对应物。简而言之，全基因组测序产生的数据在个体物种水平上是全面的，但在进化多样性方面则更为有限。相比之下，靶向测序产生的数据在个体物种水平上更有限，但提供了用更进化多样性的序列进行比较分析的机会。
The insights gained from subsequent comparisons of the resulting data have catalyzed numerous additional genome-sequencing projects, with the largest efforts focusing on the generation of sequence for the entire genome of a species. Toward that end, there are now mature draft sequences of the mouse (Waterston et al. 2002), rat (http://genome. ucsc. edu/cgi-bin/hgGateway? org= rat), and fugu (Aparicio et al. 2002) genomes, rapidly maturing sequences of the zebrafish, chicken, and chimpanzee genomes, and commitments to sequence the dog, cow, and Xenopus genomes (Fig. 1). Such genome-wide sequencing projects provide complete insight about the genetic architecture of the corresponding species and allow detailed comparisons to be performed with other available whole-genome sequences (Ureta-Vidal et al. 2003). However, the current costs of genome sequencing (upward of $50–100 million for generating a high-quality draft sequence of a mammalian genome) limit the number of vertebrate genomes that can be sequenced in a genome-wide fashion, at least for the foreseeable future. As a complement to genome-wide sequencing efforts, targeted sequencing of small, defined genomic regions can be performed for many additional species, allowing comparative analyses of larger, more evolutionarily diverse sets of sequences (Fig. 1). Specifically, this involves first identifying and isolating a genomic region (s) of interest from a series of species (typically using bacterial artificial chromosome [BAC] clones; Shizuya et al. 1992; Birren et al. 1997). This process has been aided by the establishment of an ever-growing repertoire of available vertebrate BAC libraries (see http://www. genome. gov/10001852 and http://bacpac. chori. org) and the development of methods for efficiently isolating target-specific BACs from multiple species in parallel (Thomas et al. 2002). Sequencing of the isolated BACs can then be readily accomplished using standard shotgunsequencing methods (Wilson and Mardis 1997; Green 2001). Although such a targeted sequencing approach only yields data for small genomic regions, it inherently provides the versatility for comparing sequences from many more species than can be readily accomplished by genome-wide approaches. Furthermore, by only generating data for delimited genomic regions, targeted sequencing strategies are significantly less costly than their whole-genome counterparts. In short, genome-wide sequencing produces data that are comprehensive at the individual species level, but are more limited in terms of evolutionary diversity. In contrast, targeted sequencing produces data that are more limited at the individual species level, but provide the opportunity to perform comparative analyses with more evolutionarily diverse sequences.