A Simplified Method for Segregation Analysis (SISA) to Determine Penetrance and Expression of a Genetic Variant in a Family
A Simplified Method for Segregation Analysis (SISA) to Determine Penetrance and Expression of a Genetic Variant in a Family
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DOI：
10.1002/humu.21441
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发表时间：
2011-05-01
期刊：
影响因子：
3.9
通讯作者：
Maehle, Lovise
中科院分区：
文献类型：
--
作者：
Moller, Pal;Clark, Neal;Maehle, Lovise
提出了一种用于评估任何复杂谱系中遗传变异的外显率和表达的简化快速分离分析（SISA）方法。为此目的，变体和基因之间重组的概率为零。一个假设是意义未定的变异（VUS）仅被引入该家族一次。如果是这样，则证明携带 VUS 的两名成员之间的所有家庭成员都是义务携带者。可以计算疾病和 VUS 因偶然、外显率和表达而共分离的概率。 SISA 返回值不包括个人标识符，并且不需要明确的知情同意。向中央数据库提交 SISA 返回值不会产生道德问题。多个系列的值可以合并。家庭的价值观可以由贡献者更新。每当测序显示已知的癌症易感基因中存在 VUS 时，SISA 就会用于考虑外显率。可以使用遗传诊所现有的任何家庭结构。人们可以通过在远亲中证明相同的 VUS 来包括家庭中的扩展血统，从而识别出其间的所有必然携带者。这种扩展是通过将族扩展到用于选择族的簇之外来避免选择偏差的一种方法。 Hum Mutat 32:568-571, 2011。(C) 2011 Wiley-Liss, Inc.
A method for SImplified rapid Segregation Analysis (SISA) to assess penetrance and expression of genetic variants in pedigrees of any complexity is presented. For this purpose the probability for recombination between the variant and the gene is zero. An assumption is that the variant of undetermined significance (VUS) is introduced into the family once only. If so, all family members in between two members demonstrated to carry a VUS, are obligate carriers. Probabilities for cosegregation of disease and VUS by chance, penetrance, and expression, may be calculated. SISA return values do not include person identifiers and need no explicit informed consent. There will be no ethical complications in submitting SISA return values to central databases. Values for several families may be combined. Values for a family may be updated by the contributor. SISA is used to consider penetrance whenever sequencing demonstrates a VUS in the known cancer-predisposing genes. Any family structure at hand in a genetic clinic may be used. One may include an extended lineage in a family through demonstrating the same VUS in a distant relative, and thereby identifying all obligate carriers in between. Such extension is a way to escape the selection biases through expanding the families outside the clusters used to select the families. Hum Mutat 32:568-571, 2011. (C) 2011 Wiley-Liss, Inc.