Estimating yields of prenatal carrier screening and implications for design of expanded carrier screening panels
Estimating yields of prenatal carrier screening and implications for design of expanded carrier screening panels
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DOI：
10.1038/s41436-019-0472-7
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发表时间：
2019-09-01
影响因子：
8.8
通讯作者：
Gregg, Anthony R.
中科院分区：
文献类型：
--
作者：
Guo, Michael H.;Gregg, Anthony R.
目的：产前遗传携带者筛查可以识别有可能生出患有隐性遗传疾病的孩子的父母。然而，最适合筛选的条件/基因仍然存在争议。需要对基因的携带率进行估计，以指导构建携带者筛查小组。方法：我们利用外显子组测序数据库（n = 123,136）来估计与严重隐性病症相关的 415 个基因的六个主要祖先的携带率。结果：我们发现 32.6%（东亚）至 62.9%（德系犹太人）的个体在 415 个基因中至少有一个是变异携带者。对于夫妇来说，筛查所有 415 个基因将发现 0.17-2.52% 的夫妇有可能生出受其中一种疾病影响的孩子。仅筛查携带率 >1.0% 的 40 个基因即可识别出超过 76% 的高危夫妇。旨在捕获携带率 >1.0% 的基因的血统特异性 panel 将包括 5 至 28 个基因，而类似的 panethnic panel 将包括 40 个基因。结论：我们的工作指导了携带者筛查 panel 的设计，并提供数据来帮助咨询未来的父母。我们的结果强调了跨基因的高累积携带率，强调了仔细选择基因进行筛选的必要性。
Purpose: Prenatal genetic carrier screening can identify parents at risk of having a child affected by a recessive condition. However, the conditions/genes most appropriate for screening remain a matter of debate. Estimates of carrier rates across genes are needed to guide construction of carrier screening panels.Method: We leveraged an exome sequencing database (n=123,136) to estimate carrier rates across six major ancestries for 415 genes associated with severe recessive conditions.Results: We found that 32.6% (East Asian) to 62.9% (Ashkenazi Jewish) of individuals are variant carriers in at least one of the 415 genes. For couples, screening all 415 genes would identify 0.17-2.52% of couples as being at risk for having a child affected by one of these conditions. Screening just the 40 genes with carrier rate >1.0% would identify more than 76% of these at-risk couples. An ancestry-specific panel designed to capture genes with carrier rates >1.0% would include 5 to 28 genes, while a comparable panethnic panel would include 40 genes.Conclusion: Our work guides the design of carrier screening panels and provides data to assist in counseling prospective parents. Our results highlight a high cumulative carrier rate across genes, underscoring the need for careful selection of genes for screening.