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The copy number variation landscape of congenital anomalies of the kidney and urinary tract
Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (i.e. affecting coding r...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
2018
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668343/ https://www.ncbi.nlm.nih.gov/pubmed/30578417 http://dx.doi.org/10.1038/s41588-018-0281-y |
| _version_ | 1783440198967754752 |
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| author | Verbitsky, Miguel Westland, Rik Perez, Alejandra Kiryluk, Krzysztof Liu, Qingxue Krithivasan, Priya Mitrotti, Adele Fasel, David A. Batourina, Ekaterina Sampson, Matthew G. Bodria, Monica Werth, Max Kao, Charlly Martino, Jeremiah Capone, Valentina P. Vivante, Asaf Shril, Shirlee Kil, Byum Hee Marasa, Maddalena Zhang, Jun Y. Na, Young-Ji Lim, Tze Y. Ahram, Dina Weng, Patricia L. Heinzen, Erin L. Carrea, Alba Piaggio, Giorgio Gesualdo, Loreto Manca, Valeria Masnata, Giuseppe Gigante, Maddalena Cusi, Daniele Izzi, Claudia Scolari, Francesco van Wijk, Joanna A.E. Saraga, Marijan Santoro, Domenico Conti, Giovanni Zamboli, Pasquale White, Hope Drozdz, Dorota Zachwieja, Katarzyna Miklaszewska, Monika Tkaczyk, Marcin Tomczyk, Daria Krakowska, Anna Sikora, Przemyslaw Jarmoliński, Tomasz Borszewska-Kornacka, Maria K. Pawluch, Robert Szczepanska, Maria Adamczyk, Piotr Mizerska-Wasiak, Malgorzata Krzemien, Grazyna Szmigielska, Agnieszka Zaniew, Marcin Dobson, Mark G. Darlow, John M. Puri, Prem Barton, David E. Furth, Susan L. Warady, Bradley A. Gucev, Zoran Lozanovski, Vladimir J. Tasic, Velibor Pisani, Isabella Allegri, Landino Rodas, Lida M. Campistol, Josep M. Jeanpierre, Cécile Alam, Shumyle Casale, Pasquale Wong, Craig S. Lin, Fangming Miranda, Débora M. Oliveira, Eduardo A. Simões-e-Silva, Ana Cristina Barasch, Jonathan M. Levy, Brynn Wu, Nan Hildebrandt, Friedhelm Ghiggeri, Gian Marco Latos-Bielenska, Anna Materna-Kiryluk, Anna Zhang, Feng Hakonarson, Hakon Papaioannou, Virginia E. Mendelsohn, Cathy L. Gharavi, Ali G. Sanna-Cherchi, Simone |
| author_facet | Verbitsky, Miguel Westland, Rik Perez, Alejandra Kiryluk, Krzysztof Liu, Qingxue Krithivasan, Priya Mitrotti, Adele Fasel, David A. Batourina, Ekaterina Sampson, Matthew G. Bodria, Monica Werth, Max Kao, Charlly Martino, Jeremiah Capone, Valentina P. Vivante, Asaf Shril, Shirlee Kil, Byum Hee Marasa, Maddalena Zhang, Jun Y. Na, Young-Ji Lim, Tze Y. Ahram, Dina Weng, Patricia L. Heinzen, Erin L. Carrea, Alba Piaggio, Giorgio Gesualdo, Loreto Manca, Valeria Masnata, Giuseppe Gigante, Maddalena Cusi, Daniele Izzi, Claudia Scolari, Francesco van Wijk, Joanna A.E. Saraga, Marijan Santoro, Domenico Conti, Giovanni Zamboli, Pasquale White, Hope Drozdz, Dorota Zachwieja, Katarzyna Miklaszewska, Monika Tkaczyk, Marcin Tomczyk, Daria Krakowska, Anna Sikora, Przemyslaw Jarmoliński, Tomasz Borszewska-Kornacka, Maria K. Pawluch, Robert Szczepanska, Maria Adamczyk, Piotr Mizerska-Wasiak, Malgorzata Krzemien, Grazyna Szmigielska, Agnieszka Zaniew, Marcin Dobson, Mark G. Darlow, John M. Puri, Prem Barton, David E. Furth, Susan L. Warady, Bradley A. Gucev, Zoran Lozanovski, Vladimir J. Tasic, Velibor Pisani, Isabella Allegri, Landino Rodas, Lida M. Campistol, Josep M. Jeanpierre, Cécile Alam, Shumyle Casale, Pasquale Wong, Craig S. Lin, Fangming Miranda, Débora M. Oliveira, Eduardo A. Simões-e-Silva, Ana Cristina Barasch, Jonathan M. Levy, Brynn Wu, Nan Hildebrandt, Friedhelm Ghiggeri, Gian Marco Latos-Bielenska, Anna Materna-Kiryluk, Anna Zhang, Feng Hakonarson, Hakon Papaioannou, Virginia E. Mendelsohn, Cathy L. Gharavi, Ali G. Sanna-Cherchi, Simone |
| author_sort | Verbitsky, Miguel |
| collection | PubMed |
| description | Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (i.e. affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12, and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1-p16.3, and 22q11.2 were specific for KA; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome. |
| format | Online Article Text |
| id | pubmed-6668343 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-66683432019-07-31 The copy number variation landscape of congenital anomalies of the kidney and urinary tract Verbitsky, Miguel Westland, Rik Perez, Alejandra Kiryluk, Krzysztof Liu, Qingxue Krithivasan, Priya Mitrotti, Adele Fasel, David A. Batourina, Ekaterina Sampson, Matthew G. Bodria, Monica Werth, Max Kao, Charlly Martino, Jeremiah Capone, Valentina P. Vivante, Asaf Shril, Shirlee Kil, Byum Hee Marasa, Maddalena Zhang, Jun Y. Na, Young-Ji Lim, Tze Y. Ahram, Dina Weng, Patricia L. Heinzen, Erin L. Carrea, Alba Piaggio, Giorgio Gesualdo, Loreto Manca, Valeria Masnata, Giuseppe Gigante, Maddalena Cusi, Daniele Izzi, Claudia Scolari, Francesco van Wijk, Joanna A.E. Saraga, Marijan Santoro, Domenico Conti, Giovanni Zamboli, Pasquale White, Hope Drozdz, Dorota Zachwieja, Katarzyna Miklaszewska, Monika Tkaczyk, Marcin Tomczyk, Daria Krakowska, Anna Sikora, Przemyslaw Jarmoliński, Tomasz Borszewska-Kornacka, Maria K. Pawluch, Robert Szczepanska, Maria Adamczyk, Piotr Mizerska-Wasiak, Malgorzata Krzemien, Grazyna Szmigielska, Agnieszka Zaniew, Marcin Dobson, Mark G. Darlow, John M. Puri, Prem Barton, David E. Furth, Susan L. Warady, Bradley A. Gucev, Zoran Lozanovski, Vladimir J. Tasic, Velibor Pisani, Isabella Allegri, Landino Rodas, Lida M. Campistol, Josep M. Jeanpierre, Cécile Alam, Shumyle Casale, Pasquale Wong, Craig S. Lin, Fangming Miranda, Débora M. Oliveira, Eduardo A. Simões-e-Silva, Ana Cristina Barasch, Jonathan M. Levy, Brynn Wu, Nan Hildebrandt, Friedhelm Ghiggeri, Gian Marco Latos-Bielenska, Anna Materna-Kiryluk, Anna Zhang, Feng Hakonarson, Hakon Papaioannou, Virginia E. Mendelsohn, Cathy L. Gharavi, Ali G. Sanna-Cherchi, Simone Nat Genet Article Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (i.e. affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12, and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1-p16.3, and 22q11.2 were specific for KA; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome. 2018-12-21 2019-01 /pmc/articles/PMC6668343/ /pubmed/30578417 http://dx.doi.org/10.1038/s41588-018-0281-y Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| spellingShingle | Article Verbitsky, Miguel Westland, Rik Perez, Alejandra Kiryluk, Krzysztof Liu, Qingxue Krithivasan, Priya Mitrotti, Adele Fasel, David A. Batourina, Ekaterina Sampson, Matthew G. Bodria, Monica Werth, Max Kao, Charlly Martino, Jeremiah Capone, Valentina P. Vivante, Asaf Shril, Shirlee Kil, Byum Hee Marasa, Maddalena Zhang, Jun Y. Na, Young-Ji Lim, Tze Y. Ahram, Dina Weng, Patricia L. Heinzen, Erin L. Carrea, Alba Piaggio, Giorgio Gesualdo, Loreto Manca, Valeria Masnata, Giuseppe Gigante, Maddalena Cusi, Daniele Izzi, Claudia Scolari, Francesco van Wijk, Joanna A.E. Saraga, Marijan Santoro, Domenico Conti, Giovanni Zamboli, Pasquale White, Hope Drozdz, Dorota Zachwieja, Katarzyna Miklaszewska, Monika Tkaczyk, Marcin Tomczyk, Daria Krakowska, Anna Sikora, Przemyslaw Jarmoliński, Tomasz Borszewska-Kornacka, Maria K. Pawluch, Robert Szczepanska, Maria Adamczyk, Piotr Mizerska-Wasiak, Malgorzata Krzemien, Grazyna Szmigielska, Agnieszka Zaniew, Marcin Dobson, Mark G. Darlow, John M. Puri, Prem Barton, David E. Furth, Susan L. Warady, Bradley A. Gucev, Zoran Lozanovski, Vladimir J. Tasic, Velibor Pisani, Isabella Allegri, Landino Rodas, Lida M. Campistol, Josep M. Jeanpierre, Cécile Alam, Shumyle Casale, Pasquale Wong, Craig S. Lin, Fangming Miranda, Débora M. Oliveira, Eduardo A. Simões-e-Silva, Ana Cristina Barasch, Jonathan M. Levy, Brynn Wu, Nan Hildebrandt, Friedhelm Ghiggeri, Gian Marco Latos-Bielenska, Anna Materna-Kiryluk, Anna Zhang, Feng Hakonarson, Hakon Papaioannou, Virginia E. Mendelsohn, Cathy L. Gharavi, Ali G. Sanna-Cherchi, Simone The copy number variation landscape of congenital anomalies of the kidney and urinary tract |
| title | The copy number variation landscape of congenital anomalies of the kidney and urinary tract |
| title_full | The copy number variation landscape of congenital anomalies of the kidney and urinary tract |
| title_fullStr | The copy number variation landscape of congenital anomalies of the kidney and urinary tract |
| title_full_unstemmed | The copy number variation landscape of congenital anomalies of the kidney and urinary tract |
| title_short | The copy number variation landscape of congenital anomalies of the kidney and urinary tract |
| title_sort | copy number variation landscape of congenital anomalies of the kidney and urinary tract |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668343/ https://www.ncbi.nlm.nih.gov/pubmed/30578417 http://dx.doi.org/10.1038/s41588-018-0281-y |
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