Clin Epigenetics :精子中的生物标记物可能与后代自闭症相关

2021-01-22 探索菌 生物探索

自闭症(ASD)是发生在婴儿时期的一种特殊性精神障碍,又称婴儿孤独症。过去曾经认为,其病因可能与社会心理因素有关。然而,最近《BMC》发布的一项研究却颠覆了人们的认知。

自闭症(ASD)是发生在婴儿时期的一种特殊性精神障碍,又称婴儿孤独症。过去曾经认为,其病因可能与社会心理因素有关。然而,最近《BMC》发布的一项研究却颠覆了人们的认知,指出可能在精子中就已经存在导致后代患有自闭症的基因。

这是一项由华盛顿州立大学研究人员带来的题为 “Sperm DNA methylation epimutation biomarker for paternal offspring autism susceptibility”的研究报告,他们使用表观全基因组(低密度CpG区)范围内的关联研究法,探索了用于后代自闭症易感性研究的潜在父系精子生物标志物,结果发现男性精子中的DNA甲基化区域(DMRS)生物标记物可能与其后代的自闭症相关。

这个发现极具医学价值,它可能会发展成一种潜在的医疗工具用于辅助生殖领域,以降低自闭症谱系障碍的发病率!

精子分子诊断应用于辅助生殖领域早有报道。2015年,International Journal of Epidemiology 发表了一篇题为Paternal sperm DNA methylation associated with early signs of autism risk in an autism-enriched cohort的研究。这项研究使用了基于阵列的靶向方法对基因组的CpG区进行了验证,发现表观遗传改变(DNA甲基化)与患有自闭症儿童的父亲有关。

为了证实之前的报道,研究人员招募了36名患有自闭症和无自闭症的孩子(男性)的父亲(白种人),分成对照组、自闭症组和盲试组。参与者的人口统计学和临床信息相似,且通过西班牙巴伦西亚不育症研究所生殖医学协会(IVIRMA)伦理委员会的批准。

首先,研究人员对对照组和自闭症组的表观遗传学进行了分析。由于DNA甲基化是最早被发现、也是研究最深入的表观遗传调控机制之一,它能引起染色质结构、DNA构象、DNA稳定性及DNA与蛋白质相互作用方式的改变,从而控制基因表达。因此,研究人员收集参与者的单个精子提取其DNA,进行甲基化DNA免疫共沉淀测序(MeDIP)和生物信息学分析,从而确定了805个不同的DNA甲基化区域,并发现这些区域的基因可能充当表观遗传生物标志物,使其后代易患自闭症。

自闭症组与对照组精子DMR分析

随后,研究人员通过对盲试组中的参与者精子使用多重分析法进行分析,并删除了效应离群的DMR,以优化分析结果。令人兴奋的是,研究人员几乎正确地识别了所有自闭症患儿父亲,准确率约为90%!尽管实验需要更大的临床测试样本进行验证,但是当前的结果证实了表观遗传生物标志物存在的可能性,为未来可用于诊断父亲是否会生育患有自闭症的孩子提供临床依据。

                                                     DMR相关的基因类别

自闭症发病率随着时间急剧增加,这个魔咒般的疾病正以每20分钟确诊一例的速度吞噬着人们的健康。为了能将这项研究成果发展成一种潜在的医疗工具,还需要做更多的工作并扩大试验范围,因此,研究人员正在着手进行一项涉及100多名男性的更广泛的研究。希望这项研究能为未来的辅助生殖领域提供新的发展思路。

原始出处:

Nicolás Garrido, Fabio Cruz, Rocio Rivera Egea,et al. Sperm DNA methylation epimutation biomarker for paternal offspring autism susceptibility.Clin Epigenetics. 2021 Jan 7;13(1):6.doi: 10.1186/s13148-020-00995-2.

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time=2021-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1527790, encodeId=66af152e7908f, content=<a href='/topic/show?id=68b5863e5d2' target=_blank style='color:#2F92EE;'>#自闭#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86375, encryptionId=68b5863e5d2, topicName=自闭)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=159511872623, createdName=xiongke014, createdTime=Sun Jan 24 01:44:34 CST 2021, time=2021-01-24, status=1, ipAttribution=)]
  4. 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  5. 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time=2021-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1527790, encodeId=66af152e7908f, content=<a href='/topic/show?id=68b5863e5d2' target=_blank style='color:#2F92EE;'>#自闭#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86375, encryptionId=68b5863e5d2, topicName=自闭)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=159511872623, createdName=xiongke014, createdTime=Sun Jan 24 01:44:34 CST 2021, time=2021-01-24, status=1, ipAttribution=)]
    2021-07-15 huperzia
  6. 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time=2021-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1527790, encodeId=66af152e7908f, content=<a href='/topic/show?id=68b5863e5d2' target=_blank style='color:#2F92EE;'>#自闭#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86375, encryptionId=68b5863e5d2, topicName=自闭)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=159511872623, createdName=xiongke014, createdTime=Sun Jan 24 01:44:34 CST 2021, time=2021-01-24, status=1, ipAttribution=)]
    2021-04-08 wjywjy
  7. 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time=2021-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1527790, encodeId=66af152e7908f, content=<a href='/topic/show?id=68b5863e5d2' target=_blank style='color:#2F92EE;'>#自闭#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86375, encryptionId=68b5863e5d2, topicName=自闭)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=159511872623, createdName=xiongke014, createdTime=Sun Jan 24 01:44:34 CST 2021, time=2021-01-24, status=1, ipAttribution=)]
  8. [GetPortalCommentsPageByObjectIdResponse(id=2049360, encodeId=705d2049360c3, content=<a href='/topic/show?id=4363e929ad' target=_blank style='color:#2F92EE;'>#Gene#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7929, encryptionId=4363e929ad, topicName=Gene)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=63a4277, createdName=cy0324, createdTime=Wed Jun 23 11:44:34 CST 2021, time=2021-06-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1734296, encodeId=0aab1e34296e7, content=<a href='/topic/show?id=d4f412668a4' target=_blank style='color:#2F92EE;'>#NET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12668, encryptionId=d4f412668a4, topicName=NET)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7ea033781210, 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  9. 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content=<a href='/topic/show?id=3a59693e129' target=_blank style='color:#2F92EE;'>#生物标记物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69371, encryptionId=3a59693e129, topicName=生物标记物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=55ce62, createdName=hbwxf, createdTime=Sun Jan 24 01:44:34 CST 2021, time=2021-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1426404, encodeId=7e7e1426404bc, content=<a href='/topic/show?id=032b948ec5' target=_blank style='color:#2F92EE;'>#IgE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9487, encryptionId=032b948ec5, topicName=IgE)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0cff4064659, createdName=zhenjiu124, createdTime=Sun Jan 24 01:44:34 CST 2021, time=2021-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1527790, encodeId=66af152e7908f, content=<a href='/topic/show?id=68b5863e5d2' target=_blank style='color:#2F92EE;'>#自闭#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=86375, encryptionId=68b5863e5d2, topicName=自闭)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=159511872623, createdName=xiongke014, createdTime=Sun Jan 24 01:44:34 CST 2021, time=2021-01-24, status=1, ipAttribution=)]
    2021-01-24 zhenjiu124
  10. 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