Alternative splicing in normal and pathological human placentas is correlated to genetic variants.
Alternative splicing in normal and pathological human placentas is correlated to genetic variants.
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DOI：
10.1007/s00439-020-02248-x
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发表时间：
2021-05
期刊：
影响因子：
5.3
通讯作者：
Vaiman D
中科院分区：
文献类型：
--
作者：
Ruano CSM;Apicella C;Jacques S;Gascoin G;Gaspar C;Miralles F;Méhats C;Vaiman D
两种主要的产科疾病，先兆子痫（PE），妊娠引起的内皮功能障碍导致高血压和蛋白尿，以及子宫内生长受限（IUGR），胎儿无法获得正常生长，通常由胎盘功能障碍引发。许多研究已经评估了这些疾病中的基因表达失调，但没有一个研究系统地解决了选择性剪接的作用。在本研究中，我们发现选择性剪接是胎盘疾病的一个基本特征，分别影响PE与对照组和IUGR与对照组的1060和1409个基因，其中许多与胎盘功能有关。在IUGR胎盘中，选择性剪接影响与妊娠相关的基因，而在子痫前期胎盘中，它影响与妊娠和脑部疾病相关的基因组合。此外，可选择的剪接变化可以在个体水平上检测到不同胎盘之间的剪接差异。我们将这些变异与遗传变异联系起来，以确定在胎盘疾病中剪接最强烈的48个基因子集中的剪接数量性状位点（sQTL）。我们发现，选择性剪接至少部分是由位于顺式（已鉴定的52个QTL）或反式（已鉴定的52个QTL）的遗传变异主导的。特别是，我们发现了四个影响胎盘中基因剪接的染色体区域。本研究为胎盘基因表达调控提供了新的视角，值得进一步研究。在线版本包含补充材料，可在10.1007/s00439-020-02248-x获得。
Two major obstetric diseases, preeclampsia (PE), a pregnancy-induced endothelial dysfunction leading to hypertension and proteinuria, and intra-uterine growth-restriction (IUGR), a failure of the fetus to acquire its normal growth, are generally triggered by placental dysfunction. Many studies have evaluated gene expression deregulations in these diseases, but none has tackled systematically the role of alternative splicing. In the present study, we show that alternative splicing is an essential feature of placental diseases, affecting 1060 and 1409 genes in PE vs controls and IUGR vs controls, respectively, many of those involved in placental function. While in IUGR placentas, alternative splicing affects genes specifically related to pregnancy, in preeclamptic placentas, it impacts a mix of genes related to pregnancy and brain diseases. Also, alternative splicing variations can be detected at the individual level as sharp splicing differences between different placentas. We correlate these variations with genetic variants to define splicing Quantitative Trait Loci (sQTL) in the subset of the 48 genes the most strongly alternatively spliced in placental diseases. We show that alternative splicing is at least partly piloted by genetic variants located either in cis (52 QTL identified) or in trans (52 QTL identified). In particular, we found four chromosomal regions that impact the splicing of genes in the placenta. The present work provides a new vision of placental gene expression regulation that warrants further studies. The online version contains supplementary material available at 10.1007/s00439-020-02248-x.
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DOI：
10.1097/iae.0b013e3181744122
发表时间：
2008-09-01
影响因子：
3.3
作者：
Gupta, Arvind;Kaliaperumal, Subashini;Rao, Vasudev Anand
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DOI：
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影响因子：
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影响因子：
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