The rate of de novo CNVs in healthy controls
The rate of de novo CNVs in healthy controls
复制标题
健康对照中的从头 CNV 发生率
DOI：
10.1101/857797
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
G. Kirov
中科院分区：
文献类型：
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作者：
J. Barone;Mathew Smith;K. Kendall;M. Owen;M. O’Donovan;G. Kirov
拷贝数变异（Copy number variation， CNV）是导致人类疾病的重要原因。由于相对较高的选择压力作用于致病性CNVs，它们的比率在群体中通过从头形成保持。神经发育障碍中新生CNVs的发生率增加。然而，只有少数研究是针对相对健康的个体进行的，这使得计算这种增加率的幅度存在问题。方法：英国生物银行从英国普通人群中随机挑选了大约50万名中年成员。我们根据基因型数据重建了家庭关系，并确定了923个通过质量控制过滤器的父母-后代三人组。在这些区域，鉴定出了100 ~ 100 kb大小的潜在新生CNVs，并目测了3个成员的对数R比（LRR）和B等位基因频率（BAF）迹线。我们没有机会用实验室方法验证CNVs，但痕迹似乎是决定性的。结果和讨论我们确定了10个CNVs，大小为100kb，比率为1.1%。这些比率与之前的大型研究非常相似。利用以前的大型研究，我们提供了4844个三胞胎在相对健康人群中不同体型范围的总体发病率。这些比率可用于疾病人群研究中的比较。
Background Copy number variation (CNV) is an important cause for human disease. Due to relatively high selection pressure operating against pathogenic CNVs, their rate is maintained in the population by de novo formation. The rates of de novo CNVs are increased in neurodevelopmental disorders. However only a few studies have been performed on relatively healthy individuals, making it problematic to calculate the magnitude of this increased rate. Methods The UK Biobank recruited about half a million randomly selected middle-aged members of the general population of the UK. We re-constructed family relationships from the genotypic data and identified 923 parent-offspring trios that passed out quality control filters. Potential de novo CNVs of >100 kb in size were identified and the log R ratios (LRR) and B allele frequency (BAF) traces of the trio members were visually inspected for those regions. We had no opportunity to validate CNVs with a laboratory method, but the traces appeared conclusive. Results and Discussion We identified 10 CNVs >100kb in size, a rate of 1.1%. These rates are very similar to those in previous large studies. Using previous large studies, we provide overall rates among 4844 trios for different size ranges that are expected in relatively healthy populations. These rates can be used for comparison in studies on disease populations.
DOI：
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发表时间：
2014
期刊：
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影响因子：
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作者：
M. O’Donovan;M. Owen;A. Richards;Gerwyn Mahoney-Davies;S. Legge;J. Moran;J. Walters;L. Georgieva;A. Isles;K. Chambert
通讯作者：
M. O’Donovan;M. Owen;A. Richards;Gerwyn Mahoney-Davies;S. Legge;J. Moran;J. Walters;L. Georgieva;A. Isles;K. Chambert