基因君官网
2015年6月9日讯 /生物谷BIOON/ –一直以来，人们一直认为一个家庭成员中新出现的基因突变主要来自于亲代生殖细胞，并在精卵融合形成受精卵之后将突变遗传给后代。直到最近，来自荷兰的研究人员发现有大约6.5%的全新突变发生在胚胎发育早期，并非来自于亲代的生殖细胞。这项研究在线发表在国际学术期刊American Journal of Human Genetics。
研究人员指出，由于技术上存在很大挑战，精确判断胚胎发育早期究竟有多少新发基因突变一直非常困难，传统的基因测序仍不够灵敏，不能非常确实地发现精卵融合后发生的基因突变。
不同于生殖细胞突变，胚胎发育早期的基因变化只会在个体的一小部分细胞中出现，这一点非常重要，尤其是对于想要二胎的父母们来说。目前大部分研究认为如果第一个孩子患有新发突变导致的相关疾病，那么第二个孩子发生相同基因突变的风险 在1%到5%之间，但如果这种疾病是由于胚胎早期发育新发的基因突变导致的，那么发生相同基因突变的风险将会非常非常低。更好地了解新发突变的来源对于了解基因突变发生风险具有非常重要的意义。
同时，研究人员还指出，现阶段想要全面了解胚胎早期发育新发突变对疾病的影响，提供治疗选择仍存在很大困难，但人们已经意识到人类的基因组可能比之前想象的还要多变，并且随着测序技术的不断发展，胚胎发育早期的新发突变一定会给临床治疗带来许多启示。（基因宝jiyinbao.com）
Post-zygotic Point Mutations Are an Underrecognized Source of De Novo Genomic Variation
Rocio Acuna-Hidalgo, Tan Bo, Michael P. Kwint, Maartje van de Vorst, Michele Pinelli, Joris A. Veltman, Alexander Hoischen5correspondenceemail, Lisenka E.L.M. Vissers5, Christian Gilissen
De novo mutations are recognized both as an important source of genetic variation and as a prominent cause of sporadic disease in humans. Mutations identified as de novo are generally assumed to have occurred during gametogenesis and, consequently, to be present as germline events in an individual. Because Sanger sequencing does not provide the sensitivity to reliably distinguish somatic from germline mutations, the proportion of de novo mutations that occur somatically rather than in the germline remains largely unknown. To determine the contribution of post-zygotic events to de novo mutations, we analyzed a set of 107 de novo mutations in 50 parent-offspring trios. Using four different sequencing techniques, we found that 7 (6.5%) of these presumed germline de novo mutations were in fact present as mosaic mutations in the blood of the offspring and were therefore likely to have occurred post-zygotically. Furthermore, genome-wide analysis of “de novo” variants in the proband led to the identification of 4/4,081 variants that were also detectable in the blood of one of the parents, implying parental mosaicism as the origin of these variants. Thus, our results show that an important fraction of de novo mutations presumed to be germline in fact occurred either post-zygotically in the offspring or were inherited as a consequence of low-level mosaicism in one of the parents.