Determination of the allelic frequency in Smith-Lemli-Opitz syndrome by analysis of massively parallel sequencing data sets.
Determination of the allelic frequency in Smith-Lemli-Opitz syndrome by analysis of massively parallel sequencing data sets.
复制标题
DOI：
10.1111/cge.12425
复制
发表时间：
2015-06
影响因子：
3.5
通讯作者：
Wassif CA
中科院分区：
文献类型：
--
作者：
Cross JL;Iben J;Simpson CL;Thurm A;Swedo S;Tierney E;Bailey-Wilson JE;Biesecker LG;Porter FD;Wassif CA
来自人类外显子组大规模并行测序或“下一代测序”的数据在公共和私人数据库中都达到了临界量，因为这些收集现在允许研究人员以一种十年前不可行的方式对群体遗传学进行批判性评估。通过评估完整的编码序列而不仅仅是单个SNP或一系列SNP来确定致病等位基因频率的能力将导致对发病率的更准确估计。出于演示的目的，我们分析了导致Smith-Lemli-Opitz综合征(SLOS)的致病基因--7-脱氢胆固醇还原酶(DHCR7)基因，并确定了这两种基因突变的携带率，并预测了该疾病的预期发病率。据估计，SLOS的发病率从1：10,000到1：70,000不等，而据报道，载频高达1/30。利用4个外显子组数据，共17,836条染色体，我们确定了致病性DHRC7突变的携带率为1.01%，并预测SLOS病的发病率为1/39,215。这种方法突出了外显子组测序数据库的另一个有价值的方面，为与遗传咨询、产前测试和新生儿筛查相关的临床和卫生政策决策提供信息。
Data from massively parallel sequencing or “Next Generation Sequencing” of the human exome has reached a critical mass in both public and private databases, in that these collections now allow researchers to critically evaluate population genetics in a manner that was not feasible a decade ago. The ability to determine pathogenic allele frequencies by evaluation of the full coding sequences and not merely a single SNP or series of SNPs will lead to more accurate estimations of incidence. For demonstrative purposes we analyzed the causative gene for the disorder Smith-Lemli-Opitz Syndrome (SLOS), the 7-dehydrocholesterol reductase (DHCR7) gene and determined both the carrier frequency for DHCR7 mutations, and predicted an expected incidence of the disorder. Estimations of the incidence of SLOS have ranged widely from 1:10,000 to 1:70,000 while the carrier frequency has been reported as high as 1 in 30. Using four exome data sets with a total of 17,836 chromosomes, we ascertained a carrier frequency of pathogenic DHRC7 mutations of 1.01%, and predict a SLOS disease incidence of 1/39,215 conceptions. This approach highlights yet another valuable aspect of the exome sequencing databases, to inform clinical and health policy decisions related to genetic counseling, prenatal testing and newborn screening.
登录
查看更多内容
来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
3.8
作者：
Battaile, KP;Battaile, BC;Steiner, RD
通讯作者：
Steiner, RD
影响因子：
7
作者：
Biesecker, Leslie G.;Mullikin, James C.;Green, Eric D.
通讯作者：
Green, Eric D.
影响因子：
1.1
作者：
Balogh, I.;Koczok, K.;Olah, A. V.
通讯作者：
Olah, A. V.
影响因子：
3.6
作者：
Olah, Anna V.;Szabo, Gabriella P.;Balogh, Istvan
通讯作者：
Balogh, Istvan