Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease
<p<Abstract</p< <p<Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in thi...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Fernández Raquel Ma [verfasserIn] Bleda Marta [verfasserIn] Núñez-Torres Rocío [verfasserIn] Medina Ignacio [verfasserIn] Luzón-Toro Berta [verfasserIn] García-Alonso Luz [verfasserIn] Torroglosa Ana [verfasserIn] Marbà Martina [verfasserIn] Enguix-Riego Ma Valle [verfasserIn] Montaner David [verfasserIn] Antiñolo Guillermo [verfasserIn] Dopazo Joaquín [verfasserIn] Borrego Salud [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2012 |
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| Übergeordnetes Werk: |
In: Orphanet Journal of Rare Diseases - BMC, 2006, 7(2012), 1, p 103 |
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| Übergeordnetes Werk: |
volume:7 ; year:2012 ; number:1, p 103 |
| Links: |
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| DOI / URN: |
10.1186/1750-1172-7-103 |
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| Katalog-ID: |
DOAJ020975104 |
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| 520 | |a <p<Abstract</p< <p<Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in this scenario. To overcome this problem we have used here a combined strategy in which a pathway-based analysis (PBA) has been initially conducted to prioritize candidate genes in a Spanish cohort of 53 trios of short-segment Hirschsprung’s disease. Candidate genes have been further validated in an independent population of 106 trios. The study revealed a strong association of 11 gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other HSCR-related processes. Among the preselected candidates, a total of 4 loci, <it<RASGEF1A</it<, <it<IQGAP2</it<, <it<DLC1</it< and <it<CHRNA7</it<, related to signal transduction and migration processes, were found to be significantly associated to HSCR. Network analysis also confirms their involvement in the network of already known disease genes. This approach, based on the study of functionally-related gene sets, requires of lower sample sizes and opens new opportunities for the study of rare diseases.</p< | ||
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10.1186/1750-1172-7-103 doi (DE-627)DOAJ020975104 (DE-599)DOAJd840fcdeae1f4bfab9b968bd22187a6c DE-627 ger DE-627 rakwb eng Fernández Raquel Ma verfasserin aut Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in this scenario. To overcome this problem we have used here a combined strategy in which a pathway-based analysis (PBA) has been initially conducted to prioritize candidate genes in a Spanish cohort of 53 trios of short-segment Hirschsprung’s disease. Candidate genes have been further validated in an independent population of 106 trios. The study revealed a strong association of 11 gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other HSCR-related processes. Among the preselected candidates, a total of 4 loci, <it<RASGEF1A</it<, <it<IQGAP2</it<, <it<DLC1</it< and <it<CHRNA7</it<, related to signal transduction and migration processes, were found to be significantly associated to HSCR. Network analysis also confirms their involvement in the network of already known disease genes. This approach, based on the study of functionally-related gene sets, requires of lower sample sizes and opens new opportunities for the study of rare diseases.</p< HSCR Pathway-based analysis Network analysis GWAS Medicine R Bleda Marta verfasserin aut Núñez-Torres Rocío verfasserin aut Medina Ignacio verfasserin aut Luzón-Toro Berta verfasserin aut García-Alonso Luz verfasserin aut Torroglosa Ana verfasserin aut Marbà Martina verfasserin aut Enguix-Riego Ma Valle verfasserin aut Montaner David verfasserin aut Antiñolo Guillermo verfasserin aut Dopazo Joaquín verfasserin aut Borrego Salud verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 7(2012), 1, p 103 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:7 year:2012 number:1, p 103 https://doi.org/10.1186/1750-1172-7-103 kostenfrei https://doaj.org/article/d840fcdeae1f4bfab9b968bd22187a6c kostenfrei http://www.ojrd.com/content/7/1/103 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2012 1, p 103 |
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10.1186/1750-1172-7-103 doi (DE-627)DOAJ020975104 (DE-599)DOAJd840fcdeae1f4bfab9b968bd22187a6c DE-627 ger DE-627 rakwb eng Fernández Raquel Ma verfasserin aut Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in this scenario. To overcome this problem we have used here a combined strategy in which a pathway-based analysis (PBA) has been initially conducted to prioritize candidate genes in a Spanish cohort of 53 trios of short-segment Hirschsprung’s disease. Candidate genes have been further validated in an independent population of 106 trios. The study revealed a strong association of 11 gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other HSCR-related processes. Among the preselected candidates, a total of 4 loci, <it<RASGEF1A</it<, <it<IQGAP2</it<, <it<DLC1</it< and <it<CHRNA7</it<, related to signal transduction and migration processes, were found to be significantly associated to HSCR. Network analysis also confirms their involvement in the network of already known disease genes. This approach, based on the study of functionally-related gene sets, requires of lower sample sizes and opens new opportunities for the study of rare diseases.</p< HSCR Pathway-based analysis Network analysis GWAS Medicine R Bleda Marta verfasserin aut Núñez-Torres Rocío verfasserin aut Medina Ignacio verfasserin aut Luzón-Toro Berta verfasserin aut García-Alonso Luz verfasserin aut Torroglosa Ana verfasserin aut Marbà Martina verfasserin aut Enguix-Riego Ma Valle verfasserin aut Montaner David verfasserin aut Antiñolo Guillermo verfasserin aut Dopazo Joaquín verfasserin aut Borrego Salud verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 7(2012), 1, p 103 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:7 year:2012 number:1, p 103 https://doi.org/10.1186/1750-1172-7-103 kostenfrei https://doaj.org/article/d840fcdeae1f4bfab9b968bd22187a6c kostenfrei http://www.ojrd.com/content/7/1/103 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2012 1, p 103 |
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10.1186/1750-1172-7-103 doi (DE-627)DOAJ020975104 (DE-599)DOAJd840fcdeae1f4bfab9b968bd22187a6c DE-627 ger DE-627 rakwb eng Fernández Raquel Ma verfasserin aut Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in this scenario. To overcome this problem we have used here a combined strategy in which a pathway-based analysis (PBA) has been initially conducted to prioritize candidate genes in a Spanish cohort of 53 trios of short-segment Hirschsprung’s disease. Candidate genes have been further validated in an independent population of 106 trios. The study revealed a strong association of 11 gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other HSCR-related processes. Among the preselected candidates, a total of 4 loci, <it<RASGEF1A</it<, <it<IQGAP2</it<, <it<DLC1</it< and <it<CHRNA7</it<, related to signal transduction and migration processes, were found to be significantly associated to HSCR. Network analysis also confirms their involvement in the network of already known disease genes. This approach, based on the study of functionally-related gene sets, requires of lower sample sizes and opens new opportunities for the study of rare diseases.</p< HSCR Pathway-based analysis Network analysis GWAS Medicine R Bleda Marta verfasserin aut Núñez-Torres Rocío verfasserin aut Medina Ignacio verfasserin aut Luzón-Toro Berta verfasserin aut García-Alonso Luz verfasserin aut Torroglosa Ana verfasserin aut Marbà Martina verfasserin aut Enguix-Riego Ma Valle verfasserin aut Montaner David verfasserin aut Antiñolo Guillermo verfasserin aut Dopazo Joaquín verfasserin aut Borrego Salud verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 7(2012), 1, p 103 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:7 year:2012 number:1, p 103 https://doi.org/10.1186/1750-1172-7-103 kostenfrei https://doaj.org/article/d840fcdeae1f4bfab9b968bd22187a6c kostenfrei http://www.ojrd.com/content/7/1/103 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2012 1, p 103 |
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10.1186/1750-1172-7-103 doi (DE-627)DOAJ020975104 (DE-599)DOAJd840fcdeae1f4bfab9b968bd22187a6c DE-627 ger DE-627 rakwb eng Fernández Raquel Ma verfasserin aut Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease 2012 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <p<Abstract</p< <p<Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in this scenario. To overcome this problem we have used here a combined strategy in which a pathway-based analysis (PBA) has been initially conducted to prioritize candidate genes in a Spanish cohort of 53 trios of short-segment Hirschsprung’s disease. Candidate genes have been further validated in an independent population of 106 trios. The study revealed a strong association of 11 gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other HSCR-related processes. Among the preselected candidates, a total of 4 loci, <it<RASGEF1A</it<, <it<IQGAP2</it<, <it<DLC1</it< and <it<CHRNA7</it<, related to signal transduction and migration processes, were found to be significantly associated to HSCR. Network analysis also confirms their involvement in the network of already known disease genes. This approach, based on the study of functionally-related gene sets, requires of lower sample sizes and opens new opportunities for the study of rare diseases.</p< HSCR Pathway-based analysis Network analysis GWAS Medicine R Bleda Marta verfasserin aut Núñez-Torres Rocío verfasserin aut Medina Ignacio verfasserin aut Luzón-Toro Berta verfasserin aut García-Alonso Luz verfasserin aut Torroglosa Ana verfasserin aut Marbà Martina verfasserin aut Enguix-Riego Ma Valle verfasserin aut Montaner David verfasserin aut Antiñolo Guillermo verfasserin aut Dopazo Joaquín verfasserin aut Borrego Salud verfasserin aut In Orphanet Journal of Rare Diseases BMC, 2006 7(2012), 1, p 103 (DE-627)50900637X (DE-600)2225857-7 17501172 nnns volume:7 year:2012 number:1, p 103 https://doi.org/10.1186/1750-1172-7-103 kostenfrei https://doaj.org/article/d840fcdeae1f4bfab9b968bd22187a6c kostenfrei http://www.ojrd.com/content/7/1/103 kostenfrei https://doaj.org/toc/1750-1172 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2012 1, p 103 |
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Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease |
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<p<Abstract</p< <p<Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in this scenario. To overcome this problem we have used here a combined strategy in which a pathway-based analysis (PBA) has been initially conducted to prioritize candidate genes in a Spanish cohort of 53 trios of short-segment Hirschsprung’s disease. Candidate genes have been further validated in an independent population of 106 trios. The study revealed a strong association of 11 gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other HSCR-related processes. Among the preselected candidates, a total of 4 loci, <it<RASGEF1A</it<, <it<IQGAP2</it<, <it<DLC1</it< and <it<CHRNA7</it<, related to signal transduction and migration processes, were found to be significantly associated to HSCR. Network analysis also confirms their involvement in the network of already known disease genes. This approach, based on the study of functionally-related gene sets, requires of lower sample sizes and opens new opportunities for the study of rare diseases.</p< |
| abstractGer |
<p<Abstract</p< <p<Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in this scenario. To overcome this problem we have used here a combined strategy in which a pathway-based analysis (PBA) has been initially conducted to prioritize candidate genes in a Spanish cohort of 53 trios of short-segment Hirschsprung’s disease. Candidate genes have been further validated in an independent population of 106 trios. The study revealed a strong association of 11 gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other HSCR-related processes. Among the preselected candidates, a total of 4 loci, <it<RASGEF1A</it<, <it<IQGAP2</it<, <it<DLC1</it< and <it<CHRNA7</it<, related to signal transduction and migration processes, were found to be significantly associated to HSCR. Network analysis also confirms their involvement in the network of already known disease genes. This approach, based on the study of functionally-related gene sets, requires of lower sample sizes and opens new opportunities for the study of rare diseases.</p< |
| abstract_unstemmed |
<p<Abstract</p< <p<Finding gene associations in rare diseases is frequently hampered by the reduced numbers of patients accessible. Conventional gene-based association tests rely on the availability of large cohorts, which constitutes a serious limitation for its application in this scenario. To overcome this problem we have used here a combined strategy in which a pathway-based analysis (PBA) has been initially conducted to prioritize candidate genes in a Spanish cohort of 53 trios of short-segment Hirschsprung’s disease. Candidate genes have been further validated in an independent population of 106 trios. The study revealed a strong association of 11 gene ontology (GO) modules related to signal transduction and its regulation, enteric nervous system (ENS) formation and other HSCR-related processes. Among the preselected candidates, a total of 4 loci, <it<RASGEF1A</it<, <it<IQGAP2</it<, <it<DLC1</it< and <it<CHRNA7</it<, related to signal transduction and migration processes, were found to be significantly associated to HSCR. Network analysis also confirms their involvement in the network of already known disease genes. This approach, based on the study of functionally-related gene sets, requires of lower sample sizes and opens new opportunities for the study of rare diseases.</p< |
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1, p 103 |
| title_short |
Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease |
| url |
https://doi.org/10.1186/1750-1172-7-103 https://doaj.org/article/d840fcdeae1f4bfab9b968bd22187a6c http://www.ojrd.com/content/7/1/103 https://doaj.org/toc/1750-1172 |
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Bleda Marta Núñez-Torres Rocío Medina Ignacio Luzón-Toro Berta García-Alonso Luz Torroglosa Ana Marbà Martina Enguix-Riego Ma Valle Montaner David Antiñolo Guillermo Dopazo Joaquín Borrego Salud |
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Bleda Marta Núñez-Torres Rocío Medina Ignacio Luzón-Toro Berta García-Alonso Luz Torroglosa Ana Marbà Martina Enguix-Riego Ma Valle Montaner David Antiñolo Guillermo Dopazo Joaquín Borrego Salud |
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| up_date |
2024-07-03T18:07:47.263Z |
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