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标题：Investigation of DNA variants specific to ROBO2 Isoform ‘a’ in Irish vesicoureteric reflux patients reveals marked CpG island variation
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作者：John M. Darlow ; Mark G. Dobson ; Andrew J. Green 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2020
卷号：10
期号：1
页码：1-9
DOI：10.1038/s41598-020-58818-6
出版社：Springer Nature
摘要：ROBO2 gene disruption causes vesicoureteric reflux (VUR) amongst other congenital anomalies. Several VUR patient cohorts have been screened for variants in the ubiquitously expressed transcript, ROBO2b, but, apart from low levels in a few adult tissues, ROBO2a expression is confined to the embryo, and might be more relevant to VUR, a developmental disorder. ROBO2a has an alternative promoter and two alternative exons which replace the first exon of ROBO2b. We screened probands from 251 Irish VUR families for DNA variants in these. The CpG island of ROBO2a, which includes the non-coding first exon, was found to contain a run of six variants abolishing/creating CpG dinucleotides, including a novel variant, present in the VUR cases in one family, that was not present in 592 healthy Irish controls. In three of these positions, the CpG was created by the non-reference allele, and the reference allele was not the nucleotide that would result from spontaneous deamination of methylcytosine to thymine, suggesting that there might have been selection for variability in number of CpGs in this island. This is in marked contrast to the CpG island at the start of ROBO2b, which only contained a single variant that abolishes a CpG.