A co-segregating microduplication of chromosome 15q11.2 pinpoints two risk genes for autism spectrum disorder.
A co-segregating microduplication of chromosome 15q11.2 pinpoints two risk genes for autism spectrum disorder.
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DOI：
10.1002/ajmg.b.31055
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发表时间：
2010-06-05
影响因子：
2.8
通讯作者：
Burbach, J. Peter H.
中科院分区：
文献类型：
--
作者：
van der Zwaag, Bert;Staal, Wouter G.;Hochstenbach, Ron;Poot, Martin;Spierenburg, Henk A.;de Jonge, Maretha V.;Verbeek, Nienke E.;van't Slot, Ruben;van Es, Michael A.;Staal, Frank J.;Freitag, Christine M.;Buizer-Voskamp, Jacobine E.;Nelen, Marcel R.;van den Berg, Leonard H.;van Amstel, Hans K. Ploos;van Engeland, Herman;Burbach, J. Peter H.
高分辨率基因组拷贝数分析表明，遗传和新生拷贝数变异对自闭症病理有重要影响，识别与自闭症相关的小染色体畸变将加速发现相关的风险基因。在这里，我们报告了一个荷兰家系的染色体15q11.2的微重复，仅跨越四个基因，与自闭症共分离，通过SNP微阵列分析鉴定，并通过FISH和MLPA分析独立证实。定量RT-PCR分析显示，在患者的外周血中，存在于重复区域的这四个基因的mRNA水平增加了70%以上，对小鼠胚胎和成年脑切片的RNA原位杂交显示，这四个基因中的两个，CYFIP1和NIPA1，在发育中的小鼠脑中高度表达。这些发现指出染色体15q11.2的微重复对自闭症的贡献，并强调CYFIP1和NIPA1是自闭症风险基因，在轴突发生和突触发生中起作用。因此，这些发现进一步暗示自闭症患者神经元连接的剂量敏感分子控制缺陷。然而，患者样本中这种微重复的发生率在统计学上与对照样本没有显著差异（患者为0.94%，对照组为0.42%,p=0.247），这表明我们的研究结果应谨慎解释，并表明需要进行包括大量对照受试者的研究，以确定这些变化在人群规模上的影响。
High resolution genomic copy-number analysis has shown that inherited and de novo copy-number variations contribute significantly to autism pathology, and that identification of small chromosomal aberrations related to autism will expedite the discovery of risk genes involved. Here, we report a microduplication of chromosome 15q11.2, spanning only four genes, co-segregating with autism in a Dutch pedigree, identified by SNP microarray analysis, and independently confirmed by FISH and MLPA analysis. Quantitative RT-PCR analysis revealed over 70 % increase in peripheral blood mRNA levels for the four genes present in the duplicated region in patients, and RNA in situ hybridization on mouse embryonic and adult brain sections revealed that two of the four genes, CYFIP1 and NIPA1, were highly expressed in the developing mouse brain. These findings point towards a contribution of microduplications at chromosome 15q11.2 to autism, and highlight CYFIP1 and NIPA1 as autism risk genes functioning in axonogenesis and synaptogenesis. Thereby, these findings further implicate defects in dosage-sensitive molecular control of neuronal connectivity in autism. However, the prevalence of this microduplication in patient samples was statistically not significantly different from control samples (0.94% in patients vs 0.42% controls, p=0.247), which suggests that our findings should be interpreted with caution and indicates the need for studies that include large numbers of control subjects to ascertain the impact of these changes on a population scale.
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影响因子：
56.9
作者：
Morrow, Eric M.;Yoo, Seung-Yun;Flavell, Steven W.;Kim, Tae-Kyung;Lin, Yingxi;Hill, Robert Sean;Mukaddes, Nahit M.;Balkhy, Soher;Gascon, Generoso;Hashmi, Asif;Al-Saad, Samira;Ware, Janice;Joseph, Robert M.;Greenblatt, Rachel;Gleason, Danielle;Ertelt, Julia A.;Apse, Kira A.;Bodell, Adria;Partlow, Jennifer N.;Barry, Brenda;Yao, Hui;Markianos, Kyriacos;Ferland, Russell J.;Greenberg, Michael E.;Walsh, Christopher A.
通讯作者：
Walsh, Christopher A.
影响因子：
4
作者：
Miller DT;Shen Y;Weiss LA;Korn J;Anselm I;Bridgemohan C;Cox GF;Dickinson H;Gentile J;Harris DJ;Hegde V;Hundley R;Khwaja O;Kothare S;Luedke C;Nasir R;Poduri A;Prasad K;Raffalli P;Reinhard A;Smith SE;Sobeih MM;Soul JS;Stoler J;Takeoka M;Tan WH;Thakuria J;Wolff R;Yusupov R;Gusella JF;Daly MJ;Wu BL
通讯作者：
Wu BL
DOI：
10.1097/01.dbp.0000267563.18952.c9
发表时间：
2007-04-01
影响因子：
2.4
作者：
Nowicki, Stephen T.;Tassone, Flora;Hagerman, Randi J.
通讯作者：
Hagerman, Randi J.
影响因子：
16.2
作者：
Schenck, A;Bardoni, B;Giangrande, A
通讯作者：
Giangrande, A
影响因子：
4.4
作者：
van der Zwaag, B;Burbach, JPH;van Bokhoven, H
通讯作者：
van Bokhoven, H