Genomic and Epigenomic Analyses of Monozygotic Twins Discordant for Congenital Renal Agenesis

Jin, Meiling; Zhu, Shida; Hu, Panpan; Liu, Dongbing; Li, Qinggang; Li, Zuoxiang; Zhang, Xueguang; Xie, Yuansheng; Chen, Xiangmei

doi:10.1053/j.ajkd.2014.01.423

Cited by 31 publications

(29 citation statements)

References 23 publications

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“…A pair of 30-year-old monozygotic twins who were discordant for congenital renal agenesis, were analyzed by whole exome sequencing, CNV analysis based on exome data, and reduced-representation bisulfite sequencing, in order to identify differential patterns in DNA methylation. 110 The analyses revealed 514 differentially methylated regions between the twins, but no differential single nucleotide variants or CNVs. Although regulatory regions of the genome were not checked for differences at the sequence level, this study suggests that environmental factors can contribute to the pathogenesis of CAKUT via epigenetic modifications.…”

Section: Gene-based or Genome-wide Association Studiesmentioning

confidence: 98%

“…Although regulatory regions of the genome were not checked for differences at the sequence level, this study suggests that environmental factors can contribute to the pathogenesis of CAKUT via epigenetic modifications. 110 Based on these data, epigenetic studies in CAKUT present novel opportunities to understand disease mecha nisms as they might explain the interaction between genetic and environmental risk factors and how variable genetic penetrance might arise. An investigation into the association between epigenetic changes and CAKUT in a large case-control study should now be performed.…”

Section: Gene-based or Genome-wide Association Studiesmentioning

confidence: 99%

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Genetic, environmental, and epigenetic factors involved in CAKUT

et al. 2015

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Congenital anomalies of the kidney and urinary tract (CAKUT) refer to a spectrum of structural renal malformations and are the leading cause of end-stage renal disease in children. The genetic diagnosis of CAKUT has proven to be challenging due to genetic and phenotypic heterogeneity and incomplete genetic penetrance. Monogenic causes of CAKUT have been identified using different approaches, including single gene screening, and gene panel and whole exome sequencing. The majority of the identified mutations, however, lack substantial evidence to support a pathogenic role in CAKUT. Copy number variants or single nucleotide variants that are associated with CAKUT have also been identified. Numerous studies support the influence of epigenetic and environmental factors on kidney development and the natural history of CAKUT, suggesting that the pathogenesis of this syndrome is multifactorial. In this Review we describe the current knowledge regarding the genetic susceptibility underlying CAKUT and the approaches used to investigate the genetic basis of CAKUT. We outline the associated environmental risk factors and epigenetic influences on CAKUT and discuss the challenges and strategies used to fully address the involvement and interplay of these factors in the pathogenesis of the disease.

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Section: Gene-based or Genome-wide Association Studiesmentioning

confidence: 98%

Section: Gene-based or Genome-wide Association Studiesmentioning

confidence: 99%

Genetic, environmental, and epigenetic factors involved in CAKUT

et al. 2015

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“…Other studies involving patients with CAKUT have also failed in isolating genetic monogenetic determinants [7, 13, 47 -49]. Recently, Jin et al [47] published a study investigating monozygotic twins discordant for congenital renal agenesis from a set of blood samples using high-throughput exome-capture sequencing to detect single-nucleotide polymorphisms [SNPs], copy number variations [CNVs], insertions and deletions [indels] and differentially methylated regions [DMRs]. In this study, no discordant SNPs, CNVs, or indels were confirmed.…”

Section: Discussionmentioning

confidence: 99%

Single Nucleotide Variants in A Family of Monozygotic Twins Discordant for the Phenotype Congenital Megaureter: A Genomic Analysis

Santos¹,

Rodrigues²,

Cardenas³

et al. 2017

TOUNJ

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Introduction:Congenital megaureter constitutes the second most frequent cause of hydronephrosis in children. There is still much debate on what extent environmental or genetic factors are involved in the pathogenesis of congenital megaureter. Objectives:This study aimed at investigating a pair of monozygotic twins discordant for the expression of bilateral congenital megaureter using the whole exome sequencing technique. Methods:Peripheral blood DNA was extracted and then sequenced using the whole exome technique from a pair of twins discordant for the presence of bilateral congenital refluxing unobstructed megaureter, his parents and a set of 11 non-related individuals with confirmed diagnosis of congenital megaureter. The DNA of the set of 11 non-related individuals was pooled in three groups. The monozygotic twins and their parents had DNA samples sequenced separately. Sanger validation was performed after data was filtered. Results:In the proband were identified 256 candidate genes, including TBX3, GATA6, DHH, LDB3, and HNF1, which are expressed in the urinary tract during the embryonic period. After Sanger validation, the SNVs found in the genes TBX3, GATA6, DHH and LDB3 were not confirmed in the proband. The SNV chr17:36104650 in the HNF1b gene was confirmed in the proband, his twin brother and the mother, however was not found in the pool of 11 non-related individuals with congenital megaureter. Conclusion:Due to the possible complex causative network of genetic variations and the challenges regarding the use of the whole exome sequencing technique we could not unequivocally associate the genetic variations identified in this study with the development of the congenital megaureter.

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“…A pain sensitive meta-analysis (MA) highlighted Table 3 Epigenome-wide epigenetic studies in twins. The list is obtained from a Pubmed search with search terms 'Epigenetic,' 'twin,' 'DNA methylation,' 'histone, ' Baranzini et al, 2010;Baranzini, 2011;Bell et al, 2014;Bocklandt et al, 2011;Boks et al, 2009;Bonsch et al, 2012;Bonilla et al, 2013;Byrne et al, 2013;Davies et al, 2014;Dempster et al, 2011;Disanto et al, 2013;Fraga et al, 2005;Furukawa et al, 2013;Gervin et al, 2012;Gordon et al, 2012;Grundberg et al, 2013;Heyn et al, 2013;Javierre et al, 2010;Jin et al, 2014;Kaminsky et al, 2008;Kaminsky et al, 2009;Kinoshita et al, 2013;Letourneau et al, 2014;Martino et al, 2013;Marsit et al, 2013;Miyake et al, 2013;Nguyen et al, 2010;Nitert et al, 2012;Rakyan et al, 2010;Rakyan et al, 2011a;Ribel-Madsen et al, 2012;Sarachana et al, 2010;Selmi et al, 2012;Stefan et al, 2014;Te et al, 2010;Umeton et al, 2011;Wong et al, 2013;Yu et al, 2012. Twin Studies and Epigenetics nine MAP-DMRs of which one was in the promoter of TRPA1, an established pain-sensitivity gene. T...…”

Section: Epigenome-wide Association Scans For Complex Traits and Disementioning

confidence: 99%