title: Genomic and epigenomic analyses of monozygotic twins discordant for congenital renal agenesis.
abstract: Monozygotic twins have been widely studied to distinguish genetic and environmental factors in the pathogenesis of human diseases. For renal agenesis, the one-sided absence of renal tissue, the relative contributions of genetic and environmental factors to its pathogenesis are still unclear. In this study of a pair of monozygotic twins discordant for congenital renal agenesis, the genomic profile was analyzed from a set of blood samples using high-throughput exome-capture sequencing to detect single-nucleotide polymorphisms (SNPs), copy number variations (CNVs), and insertions and deletions (indels). Also, an epigenomic analysis used reduced-representation bisulfite sequencing to detect differentially methylated regions (DMRs). No discordant SNPs, CNVs, or indels were confirmed, but 514 DMRs were detected. KEGG analysis indicated the DMRs localized to 10 signaling pathways and 25 genes, including the mitogen-activated protein kinase pathway and 6 genes (FGF18, FGF12, PDGFRA, MAPK11, AMH, CTBP1) involved in organ development. Although methylation results from our adult patient and her sister may not represent the pattern that was present during kidney development, we could at least confirm a lack of obvious differences at the genome level, which suggests that nongenetic factors may be involved in the pathogenesis of renal agenesis.
authors.affiliation: State Key Laboratory of Kidney Disease, Institute of Nephrology, Chinese PLA General Hospital, Beijing, China; Medical College, Nankai University, Tianjin, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Jin
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Shida
authors.initials: S
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Kidney Disease, Institute of Nephrology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Hu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Dongbing
authors.initials: D
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Kidney Disease, Institute of Nephrology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Qinggang
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Kidney Disease, Institute of Nephrology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Zuoxiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Kidney Disease, Institute of Nephrology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Xueguang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Kidney Disease, Institute of Nephrology, Chinese PLA General Hospital, Beijing, China. Electronic address: xieyuansn@hotmail.com.
authors.forename: Yuansheng
authors.initials: Y
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Kidney Disease, Institute of Nephrology, Chinese PLA General Hospital, Beijing, China. Electronic address: xmchen301@126.com.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D000013:Congenital Abnormalities / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D057890:Epigenomics / Q000379:methods*; D005260:Female; D017353:Gene Deletion; D023281:Genomics / Q000379:methods*; D006801:Humans; D007668:Kidney / Q000002:abnormalities*; D007674:Kidney Diseases / Q000151:congenital* / Q000235:genetics; D016254:Mutagenesis, Insertional / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics*
keywords: Renal agenesis; congenital abnormalities of the kidney and urinary tract (CAKUT); epigenome; genome; methylation; monozygotic twins; nephrogenesis