DNA methylation errors at imprinted loci after assisted conception originate in the parental sperm.
DNA methylation errors at imprinted loci after assisted conception originate in the parental sperm.
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DOI：
10.1038/ejhg.2009.68
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发表时间：
2009-12
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影响因子：
--
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与人类辅助生殖技术（ART）相关的印记疾病（如Beckwith-Wiedemann综合征）的患病率增加。对动物模型的研究表明，体外培养可能是这些印迹错误的来源。然而，在这项研究中，我们报告说，在某些情况下，错误是遗传自父亲。我们分析了78对DNA样本中7个常染色体印记基因座和XIST基因座的DNA甲基化。在ART样本中有异常DNA甲基化的十七个案例中有七个（41%），在父母精子中存在相同的改变。此外，我们还鉴定了编码DNMT 3L的基因中的DNA序列变异，这些变异与异常的父亲DNA甲基化有关。印迹错误和DNA序列变异在少精子症患者中更为普遍。我们的数据表明，通过ART出生的个体中印记疾病的发病率增加，在某些情况下，可能是由于使用了具有内在印记突变的精子。
There is an increased prevalence of imprinting disorders, such as Beckwith–Wiedemann syndrome, associated with human assisted reproductive technologies (ART). Work on animal models suggests that in vitro culture may be the source of these imprinting errors. However, in this study we report that, in some cases, the errors are inherited from the father. We analyzed DNA methylation at seven autosomal imprinted loci and the XIST locus in 78 paired DNA samples. In seven out of seventeen cases where there was abnormal DNA methylation in the ART sample (41%), the identical alterations were present in the parental sperm. Furthermore, we also identified DNA sequence variations in the gene encoding DNMT3L, which were associated with the abnormal paternal DNA methylation. Both the imprinting errors and the DNA sequence variants were more prevalent in patients with oligospermia. Our data suggest that the increase in the incidence of imprinting disorders in individuals born by ART may be due, in some cases, to the use of sperm with intrinsic imprinting mutations.
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