Paternal age effects on sperm epigenome and the resultant offspring.

父亲年龄对精子表观基因组及其后代的影响。

• 批准号: 240711082
• 负责人: Dr. Nady El Hajj, Ph.D.
• 金额: --
• 依托单位: Institut für Humangenetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/240711082?language=en
• 关键词: Paternal; age; effects; sperm; epigenome

Epidemiological studies provide evidence for an influence of paternal age on the prevalence of certain diseases in the offspring, including autism and cancer. Genome-wide sequencing techniques revealed that the offspring of older men carry more genetic mutations. It is well known that the number of germ cell divisions in males increase with age; therefore, the higher de novo mutation rate in the offspring of older fathers may have originated in sperm. We speculate that in addition to an increased number of genetic mutations, the sperm of older males contain more epigenetic perturbations when compared to their younger counterparts. The inheritance of spermspecific epimutations may contribute to the etiology of disorders showing a “paternal age effect”. To explore this possibility we will perform genome-wide methylation (Illumina 450K arrays) analysis with sperm samples of old versus young males. The methylation of well selected candidate genes will be additionally measured via deep bisulfite sequencing to detect rare epimutations. As a followup, we will analyze the fetal cord blood methylome of the resultant offspring to assess whether paternal age has an epigenetic influence on the next generation. The aim of this project is to provide insight on the epigenetic effect of paternal aging on sperm and on the onset of certain disorders in the offspring of older fathers.

流行病学研究提供了证据，证明父亲的年龄对子女中某些疾病的患病率有影响，包括自闭症和癌症。全基因组测序技术显示，老年男性的后代携带更多的基因突变。众所周知，男性生殖细胞分裂的数量随着年龄的增长而增加；因此，年长父亲的后代中较高的从头突变率可能源于精子。我们推测，除了基因突变的数量增加外，与年轻男性相比，老年男性的精子包含更多的表观遗传学扰动。精子特异性表观突变的遗传可能有助于表现出“父系年龄效应”的疾病的病因学。为了探索这种可能性，我们将对老年男性和年轻男性的精子样本进行全基因组甲基化(Illumina 450K阵列)分析。精心挑选的候选基因的甲基化将通过深度亚硫酸氢盐测序进行额外测量，以检测罕见的表位突变。作为后续，我们将分析由此产生的后代的胎儿脐带血甲基组，以评估父亲的年龄是否对下一代有表观遗传影响。这个项目的目的是深入了解父系老化对精子的表观遗传学影响，以及大龄父亲的后代出现某些疾病的原因。