No TAP63 promoter mutation is detected in bladder exstrophy-epispadias complex patients

Tom Darling, Istiak Mahfuz, Stefan White, Wei Cheng

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Bladder exstrophy-epispadias complex (BEEC) is thought to have a genetic component in its pathogenesis. Previously we found that p63(-/-) mice show increased ventral apoptosis and develop a BEEC phenotype. Down-regulation of the anti-apoptotic DeltaNP63 and an up-regulation of pro-apoptotic TAP63 isoforms have been demonstrated in BEEC patient bladder tissues. We have previously shown that insertion/deletion polymorphisms of the DeltaNp63 promoter are associated with an increased risk of BEEC. In this study, we specifically examined the TAP63 promoter to see if any sequence changes might lead to up-regulation of TAP63 and exaggerated apoptosis in BEEC patients. METHODS: i) Bioinformatic analysis of the TAP63 promoter was performed to identify putative regulatory regions. ii) High-resolution Melt and Sanger sequencing was used to screen targeted regions in 112 BEEC patient DNA samples for potential sequence variants. iii) Sequence variation was analysed for significance against normal population frequency data. RESULTS: i) We identified multiple epigenetic markers of transcriptional regulation within highly conserved areas of the TAP63 promoter sequence. ii) Of the 112 buccal swab DNA samples, adequate and successful screening ranged between 48 and 67 for each region. iii) No novel sequence variation or mutation was uncovered. iv) Two known SNPs were identified. However, allele frequency analysis was not statistically significant. CONCLUSION: Our data do not associate genetic variation within the TAP63 promoter region with an increased risk of BEEC. Our data so far suggests that only DeltaNP63 promoter aberration is involved in BEEC pathogenesis.
Original languageEnglish
Pages (from-to)2393 - 2400
Number of pages8
JournalJournal of Pediatric Surgery
Volume48
Issue number12
DOIs
Publication statusPublished - 2013

Cite this

Darling, Tom ; Mahfuz, Istiak ; White, Stefan ; Cheng, Wei. / No TAP63 promoter mutation is detected in bladder exstrophy-epispadias complex patients. In: Journal of Pediatric Surgery. 2013 ; Vol. 48, No. 12. pp. 2393 - 2400.
@article{c468736b3e2c413b9b3f17e671c39f8a,
title = "No TAP63 promoter mutation is detected in bladder exstrophy-epispadias complex patients",
abstract = "Bladder exstrophy-epispadias complex (BEEC) is thought to have a genetic component in its pathogenesis. Previously we found that p63(-/-) mice show increased ventral apoptosis and develop a BEEC phenotype. Down-regulation of the anti-apoptotic DeltaNP63 and an up-regulation of pro-apoptotic TAP63 isoforms have been demonstrated in BEEC patient bladder tissues. We have previously shown that insertion/deletion polymorphisms of the DeltaNp63 promoter are associated with an increased risk of BEEC. In this study, we specifically examined the TAP63 promoter to see if any sequence changes might lead to up-regulation of TAP63 and exaggerated apoptosis in BEEC patients. METHODS: i) Bioinformatic analysis of the TAP63 promoter was performed to identify putative regulatory regions. ii) High-resolution Melt and Sanger sequencing was used to screen targeted regions in 112 BEEC patient DNA samples for potential sequence variants. iii) Sequence variation was analysed for significance against normal population frequency data. RESULTS: i) We identified multiple epigenetic markers of transcriptional regulation within highly conserved areas of the TAP63 promoter sequence. ii) Of the 112 buccal swab DNA samples, adequate and successful screening ranged between 48 and 67 for each region. iii) No novel sequence variation or mutation was uncovered. iv) Two known SNPs were identified. However, allele frequency analysis was not statistically significant. CONCLUSION: Our data do not associate genetic variation within the TAP63 promoter region with an increased risk of BEEC. Our data so far suggests that only DeltaNP63 promoter aberration is involved in BEEC pathogenesis.",
author = "Tom Darling and Istiak Mahfuz and Stefan White and Wei Cheng",
year = "2013",
doi = "10.1016/j.jpedsurg.2013.08.012",
language = "English",
volume = "48",
pages = "2393 -- 2400",
journal = "Journal of Pediatric Surgery",
issn = "0022-3468",
publisher = "Elsevier",
number = "12",

}

No TAP63 promoter mutation is detected in bladder exstrophy-epispadias complex patients. / Darling, Tom; Mahfuz, Istiak; White, Stefan; Cheng, Wei.

In: Journal of Pediatric Surgery, Vol. 48, No. 12, 2013, p. 2393 - 2400.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - No TAP63 promoter mutation is detected in bladder exstrophy-epispadias complex patients

AU - Darling, Tom

AU - Mahfuz, Istiak

AU - White, Stefan

AU - Cheng, Wei

PY - 2013

Y1 - 2013

N2 - Bladder exstrophy-epispadias complex (BEEC) is thought to have a genetic component in its pathogenesis. Previously we found that p63(-/-) mice show increased ventral apoptosis and develop a BEEC phenotype. Down-regulation of the anti-apoptotic DeltaNP63 and an up-regulation of pro-apoptotic TAP63 isoforms have been demonstrated in BEEC patient bladder tissues. We have previously shown that insertion/deletion polymorphisms of the DeltaNp63 promoter are associated with an increased risk of BEEC. In this study, we specifically examined the TAP63 promoter to see if any sequence changes might lead to up-regulation of TAP63 and exaggerated apoptosis in BEEC patients. METHODS: i) Bioinformatic analysis of the TAP63 promoter was performed to identify putative regulatory regions. ii) High-resolution Melt and Sanger sequencing was used to screen targeted regions in 112 BEEC patient DNA samples for potential sequence variants. iii) Sequence variation was analysed for significance against normal population frequency data. RESULTS: i) We identified multiple epigenetic markers of transcriptional regulation within highly conserved areas of the TAP63 promoter sequence. ii) Of the 112 buccal swab DNA samples, adequate and successful screening ranged between 48 and 67 for each region. iii) No novel sequence variation or mutation was uncovered. iv) Two known SNPs were identified. However, allele frequency analysis was not statistically significant. CONCLUSION: Our data do not associate genetic variation within the TAP63 promoter region with an increased risk of BEEC. Our data so far suggests that only DeltaNP63 promoter aberration is involved in BEEC pathogenesis.

AB - Bladder exstrophy-epispadias complex (BEEC) is thought to have a genetic component in its pathogenesis. Previously we found that p63(-/-) mice show increased ventral apoptosis and develop a BEEC phenotype. Down-regulation of the anti-apoptotic DeltaNP63 and an up-regulation of pro-apoptotic TAP63 isoforms have been demonstrated in BEEC patient bladder tissues. We have previously shown that insertion/deletion polymorphisms of the DeltaNp63 promoter are associated with an increased risk of BEEC. In this study, we specifically examined the TAP63 promoter to see if any sequence changes might lead to up-regulation of TAP63 and exaggerated apoptosis in BEEC patients. METHODS: i) Bioinformatic analysis of the TAP63 promoter was performed to identify putative regulatory regions. ii) High-resolution Melt and Sanger sequencing was used to screen targeted regions in 112 BEEC patient DNA samples for potential sequence variants. iii) Sequence variation was analysed for significance against normal population frequency data. RESULTS: i) We identified multiple epigenetic markers of transcriptional regulation within highly conserved areas of the TAP63 promoter sequence. ii) Of the 112 buccal swab DNA samples, adequate and successful screening ranged between 48 and 67 for each region. iii) No novel sequence variation or mutation was uncovered. iv) Two known SNPs were identified. However, allele frequency analysis was not statistically significant. CONCLUSION: Our data do not associate genetic variation within the TAP63 promoter region with an increased risk of BEEC. Our data so far suggests that only DeltaNP63 promoter aberration is involved in BEEC pathogenesis.

UR - http://goo.gl/YWrvvz

U2 - 10.1016/j.jpedsurg.2013.08.012

DO - 10.1016/j.jpedsurg.2013.08.012

M3 - Article

VL - 48

SP - 2393

EP - 2400

JO - Journal of Pediatric Surgery

JF - Journal of Pediatric Surgery

SN - 0022-3468

IS - 12

ER -