Identification of somatic mutations in monozygotic twins discordant for psychiatric disorders.
Identification of somatic mutations in monozygotic twins discordant for psychiatric disorders.
复制标题
DOI：
10.1038/s41537-018-0049-5
复制
发表时间：
2018-04-13
影响因子：
5.4
通讯作者：
Iwamoto K
中科院分区：
文献类型：
--
作者：
Nishioka M;Bundo M;Ueda J;Yoshikawa A;Nishimura F;Sasaki T;Kakiuchi C;Kasai K;Kato T;Iwamoto K
单卵双胞胎被认为具有相同的基因组。基于这一假设，单卵双胞胎的表型不一致以前被归因于环境因素。然而，最近的基因组研究已经确定了特征性的体细胞突变在单卵双胞胎不一致的Darier病，货车德沃德综合征，Dravet综合征。在这里，我们探讨了四对精神分裂症或妄想症不一致的单卵双胞胎的体细胞突变。我们分析了从血液样本中获得的全外显子组序列数据，并在一对不一致的妄想症双胞胎中鉴定了7个体细胞突变。所有这七个突变都通过独立的扩增子测序验证，其中五个通过焦磷酸测序进一步验证。妄想症患者的一个体细胞突变显示ABCC9的错义变体，等位基因分数为7.32%。虽然体细胞突变和表型不一致之间的关联不能最终建立在这项研究中，我们的研究结果表明，体细胞突变在单卵双胞胎可能有助于精神疾病的发展，并可以作为高优先级的候选人遗传研究。当涉及到精神疾病时，同卵双胞胎并不总是完全相同的，出生后出现的DNA突变可以解释为什么。日本理研脑科学研究所的加藤忠文和熊本大学的岩本和也领导的研究人员通过对研究对象血液中基因组的整个蛋白质编码部分进行测序，寻找四对精神分裂症或妄想症不一致的同卵双胞胎之间的DNA差异。
在一对兄弟姐妹中，他们发现了七个遗传差异，其中一个在患有妄想症的姐妹中，改变了与睡眠和其他大脑功能有关的蛋白质序列。研究结果表明，除了表观遗传和环境差异外，后天突变可以解释基因相同的双胞胎之间精神疾病的不一致性。
Monozygotic twins are assumed to have identical genomes. Based on this assumption, phenotypic discordance in monozygotic twins has been previously attributed to environmental factors. However, recent genomic studies have identified characteristic somatic mutations in monozygotic twins discordant for Darier disease, Van der Woude syndrome, and Dravet syndrome. Here, we explored somatic mutations in four pairs of monozygotic twins discordant for schizophrenia or delusional disorder. We analyzed whole exome sequence data obtained from blood samples and identified seven somatic mutations in one twin pair discordant for delusional disorder. All seven of these mutations were validated by independent amplicon sequencing, and five of them were further validated by pyrosequencing. One somatic mutation in the patient with delusional disorder showed a missense variant in ABCC9 with an allele fraction of 7.32%. Although an association between the somatic mutations and phenotypic discordance could not be established conclusively in this study, our results suggest that somatic mutations in monozygotic twins may contribute to the development of psychiatric disorders, and can serve as high-priority candidates for genetic studies. Identical twins are not always identical when it comes to psychiatric disorders—and DNA mutations that arise after birth could explain why. Researchers in Japan led by Tadafumi Kato from the RIKEN Brain Science Institute and
Kazuya Iwamoto from Kumamoto University searched for DNA differences between four pairs of identical twins discordant for schizophrenia or delusional disorder by sequencing the entire protein-coding portion of the genome from the study subjects’ blood. In one sibling pair, they found seven genetic differences, including one in the sister with the delusional disorder that altered the sequence of a protein implicated in sleep and other brain functions. The findings suggest that, alongside epigenetic and environmental differences, acquired mutations can account for discordances in psychiatric illnesses among otherwise genetically identical twins.
登录
查看更多内容
影响因子：
64.8
作者：
Iossifov, Ivan;O'Roak, Brian J.;Sanders, Stephan J.;Ronemus, Michael;Krumm, Niklas;Levy, Dan;Stessman, Holly A.;Witherspoon, Kali T.;Vives, Laura;Patterson, Karynne E.;Smith, Joshua D.;Paeper, Bryan;Nickerson, Deborah A.;Dea, Jeanselle;Dong, Shan;Gonzalez, Luis E.;Mandell, Jeffrey D.;Mane, Shrikant M.;Murtha, Michael T.;Sullivan, Catherine A.;Walker, Michael F.;Waqar, Zainulabedin;Wei, Liping;Willsey, A. Jeremy;Yamrom, Boris;Lee, Yoon-ha;Grabowska, Ewa;Dalkic, Ertugrul;Wang, Zihua;Marks, Steven;Andrews, Peter;Leotta, Anthony;Kendall, Jude;Hakker, Inessa;Rosenbaum, Julie;Ma, Beicong;Rodgers, Linda;Troge, Jennifer;Narzisi, Giuseppe;Yoon, Seungtai;Schatz, Michael C.;Ye, Kenny;McCombie, W. Richard;Shendure, Jay;Eichler, Evan E.;State, Matthew W.;Wigler, Michael
通讯作者：
Wigler, Michael
DOI：
10.1056/nejmoa1409405
发表时间：
2014-12-25
期刊：
The New England journal of medicine
影响因子：
--
作者：
Genovese G;Kähler AK;Handsaker RE;Lindberg J;Rose SA;Bakhoum SF;Chambert K;Mick E;Neale BM;Fromer M;Purcell SM;Svantesson O;Landén M;Höglund M;Lehmann S;Gabriel SB;Moran JL;Lander ES;Sullivan PF;Sklar P;Grönberg H;Hultman CM;McCarroll SA
通讯作者：
McCarroll SA
DOI：
10.1073/pnas.1100273108
发表时间：
2011-12-20
影响因子：
11.1
作者：
Coufal, Nicole G.;Luis Garcia-Perez, Jose;Gage, Fred H.
通讯作者：
Gage, Fred H.
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
11
作者：
Allebrandt, K. V.;Amin, N.;Roenneberg, T.
通讯作者：
Roenneberg, T.