Population variation of common cystic fibrosis mutations
Population variation of common cystic fibrosis mutations
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常见囊性纤维化突变的群体变异
DOI：
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
J. Cheadle
中科院分区：
文献类型：
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作者：
J. Cheadle
自1989年发现囊性纤维化（CF）的基因和主要突变以来，在过去的4年中，在囊性纤维化跨膜传导调节因子（CFTR）基因中已经发现了400多个推定突变和约90个DNA序列变异。CFTR突变的列表可以在该杂志的早期报告中找到（Tsui，1992）。虽然BNF 508似乎在所有研究人群中都很常见，但其相对频率在不同地理位置之间存在差异（CF遗传分析联盟，1990）。其他CF突变的分布也被发现在不同人群中是异质的。事实上，大多数描述的突变仅在最初报告的病例中检测到。
为了更好地了解相对常见的突变在世界人群中的分布情况，于1993年10月从CF遗传分析联盟的成员中收集了30种最常见突变的CF突变筛查数据。突变列表是根据1992年5月完成的早期汇编（未发表的数据）选择的。更新的检测结果显示，只有19个突变，每个突变在50个或更多的染色体上检测到。24种常见突变的中心间分布见表1，各大洲的分布总结见表2。之前调查的两个突变，即Y122 X和3905 insT，包含在表3中。其他三个被调查但未在这里报道的突变是Q493 X，S549 R（T→G）和3849 + 4A→G（每个≤20条染色体;实际数量可从L. C. Tsui）。
由于广泛调查可能会遗漏一些研究人群中存在的相当大比例（即≥1%）的突变，因此还要求联盟成员提交表1和表2中未列出的此类独特突变的数据。结果见表3。最值得注意的是，394 delTT是一种未包括在先前调查中但在50多条染色体上检测到的突变。
值得注意的是，这里报告的频率是每个参与小组提供的最佳估计。负责每个数据集的研究者（每组最多列出3名）作为本报告的贡献者显示在相应的表格中。尽管已努力最大限度地减少冗余数据，但样本可能会略有重叠。此外，本文提供的数据基本上来自CF患者的检测;由于可能的采样偏倚，所示频率可能无法反映相应人群中这些突变的真实比例。有些数据已在以前的报告中出现。然而，由于大量的条目，仅引用原始突变描述的参考文献。
总之，本报告汇编了人群数据，以证明CFTR突变在不同人群中的分布存在显著差异;调查的24种最常见突变的总体检出率从50%到97%不等（表1，2）。这一信息在设计囊性纤维化DNA检测策略时非常重要。
Since the identification of the gene and the major mutation responsible for cystic fibrosis (CF) in 1989, more than 400 presumed mutations and about 90 DNA sequence variations have been identified in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in the past 4 years. A list of CFTR mutations can be found in an earlier report in this journal (Tsui, 1992). While ∆F508 appears to be common in all study populations its relative frequency varies among different geographic locations (CF Genetic Analysis Consortium, 1990). The distribution of other CF mutations has also been found to be heterogeneous among different populations. In fact, most of the described mutations have only been detected in the original reported cases.
To obtain a better understanding of the distribution of the relatively common mutations in the world population, CF mutation screening data were collected for the 30 most common mutations from members of the CF Genetic Analysis Consortium in October 1993. The list of mutations was chosen according to an earlier compilation completed in May 1992 (unpublished data). As the updated test results show, there were only 19 mutations, each detected on 50 or more chromosomes. The center-by-center distribution for 24 of the more commons mutations is shown in Table 1 and the distribution by continent is summarized in Table 2. Two of the previously surveyed mutations, namely, Y122X and 3905insT, are included in Table 3. The three other mutations that were surveyed but not reported here are Q493X, S549R (T→G), and 3849 + 4A→G (≤20 chromosomes each; actual numbers available from L. C. Tsui).
Since the broad survey could have missed some of the mutations that are present in substantial proportion (i.e. ≥1%) in some study populations, members of the Consortium were also asked to submit data for such unique mutations not listed in Tables 1 and 2. The results are displayed in Table 3. Most notably, 394delTT is a mutation that was not included in the previous survey but detected on more than 50 chromosomes.
It is important to note that the frequencies reported here are the best estimate provided by each participating group. The investigators (up to 3 listed per group) responsible for each data set are shown in the respective tables as contributors to this report. Although an effort has been made to minimize the redundant data, there may be a slight overlap of samples. Moreover, the data presented here are essentially derived from testing CF patients; the frequencies shown may not reflect the true proportion of these mutations in the respective populations due to possible sampling bias. Some of the data have appeared in previous reports. Because of the large number of entries, however, references are only cited for the original mutation descriptions.
In conclusion, this report has compiled population data to document that there is a striking difference in the distribution of CFTR mutations in different populations; the overall detection rate for the 24 most common mutations surveyed varies from 50% to 97% (Tables 1,2). This information is important when designing strategies for DNA testing of cystic fibrosis.
囊性纤维化跨膜电导调节器 (CFTR) 基因外显子 1 至 8 的突变鉴定。
影响因子：
4.4
作者：
Zielenski,J;Bozon,D;Kerem,B;Markiewicz,D;Durie,P;Rommens,JM;Tsui,LC
通讯作者：
Tsui,LC