Expanded genetic screening panel for the Ashkenazi Jewish population.
Expanded genetic screening panel for the Ashkenazi Jewish population.
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DOI：
10.1038/gim.2015.123
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发表时间：
2016-05
期刊：
影响因子：
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通讯作者：
Oddoux C
中科院分区：
文献类型：
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作者：
Baskovich B;Hiraki S;Upadhyay K;Meyer P;Carmi S;Barzilai N;Darvasi A;Ozelius L;Peter I;Cho JH;Atzmon G;Clark L;Yu J;Lencz T;Pe'er I;Ostrer H;Oddoux C
识别已知突变存在的携带者筛查计划已有效降低德系犹太人和其他人群中常染色体隐性遗传病的发生率。然而，这些计划尚未充分发挥其潜力。此外，许多已知的常染色体隐性和显性病症并未得到筛查，并且可能提供筛查的其他病症的分子基础尚不清楚。通过文献综述和对健康个体的全测序基因组的注释，我们扩大了突变列表。在 128 个完全测序的德系犹太人基因组样本中发现了突变，这些基因组经过临床数据库过滤，并使用美国医学遗传学学院评分 (ACMG) 系统手动管理临床有效性和实用性。通过文献综述确定了其他已知突变。一组 203 个突变被鉴定为 92 种常染色体隐性遗传、24 种常染色体显性遗传和 4 种 X 连锁疾病。对更广泛的疾病进行筛查不仅可以进一步降低常染色体隐性遗传疾病的发病率，还可以提供早期或症状前诊断的好处。
Carrier screening programs that identify the presence of known mutations have been effective for reducing the incidence of autosomal recessive conditions in the Ashkenazi Jewish population and other populations. Yet, these programs have not realized their full potential. Furthermore, many known autosomal recessive and dominant conditions are not screened for and the molecular basis of other conditions for which screening might be offered is unknown. Through literature review and annotation of full sequenced genomes from healthy individuals, we expanded the list of mutations. Mutations were identified in a sample of 128 fully sequenced Ashkenazi Jewish genomes that were filtered through clinical databases and curated manually for clinical validity and utility using the American College of Medical Genetics scoring (ACMG) system. Other known mutations were identified through literature review. A panel of 203 mutations was identified for 92 autosomal recessive, 24 autosomal dominant, and 4 X-linked disorders. Screening for a broader range of disorders could not only further reduce the incidence of autosomal recessive disorders, but could also offer the benefits of early or presymptomatic diagnosis.