VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease
Summary: The human genome comprises approximately 3% of tandem repeats with variable length (VNTR), a few of which have been linked to human rare diseases. Autosomal dominant tubulointerstitial kidney disease—MUC1 (ADTKD-MUC1) is caused by specific frameshift variants in the coding VNTR of the MUC1...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223012488 |
| _version_ | 1797774555681390592 |
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| author | Hassan Saei Vincent Morinière Laurence Heidet Olivier Gribouval Said Lebbah Frederic Tores Manon Mautret-Godefroy Bertrand Knebelmann Stéphane Burtey Vincent Vuiblet Corinne Antignac Patrick Nitschké Guillaume Dorval |
| author_facet | Hassan Saei Vincent Morinière Laurence Heidet Olivier Gribouval Said Lebbah Frederic Tores Manon Mautret-Godefroy Bertrand Knebelmann Stéphane Burtey Vincent Vuiblet Corinne Antignac Patrick Nitschké Guillaume Dorval |
| author_sort | Hassan Saei |
| collection | DOAJ |
| description | Summary: The human genome comprises approximately 3% of tandem repeats with variable length (VNTR), a few of which have been linked to human rare diseases. Autosomal dominant tubulointerstitial kidney disease—MUC1 (ADTKD-MUC1) is caused by specific frameshift variants in the coding VNTR of the MUC1 gene. Calling variants from VNTR using short-read sequencing (SRS) is challenging due to poor read mappability. We developed a computational pipeline, VNtyper, for reliable detection of MUC1 VNTR pathogenic variants and demonstrated its clinical utility in two distinct cohorts: (1) a historical cohort including 108 families with ADTKD and (2) a replication naive cohort comprising 2,910 patients previously tested on a panel of genes involved in monogenic renal diseases. In the historical cohort all cases known to carry pathogenic MUC1 variants were re-identified, and a new 25bp-frameshift insertion in an additional mislaid family was detected. In the replication cohort, we discovered and validated 30 new patients. |
| first_indexed | 2024-03-12T22:21:52Z |
| format | Article |
| id | doaj.art-82acd8cadcc1476ab800c431abf7e136 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T22:21:52Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-82acd8cadcc1476ab800c431abf7e1362023-07-23T04:55:48ZengElsevieriScience2589-00422023-07-01267107171VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney diseaseHassan Saei0Vincent Morinière1Laurence Heidet2Olivier Gribouval3Said Lebbah4Frederic Tores5Manon Mautret-Godefroy6Bertrand Knebelmann7Stéphane Burtey8Vincent Vuiblet9Corinne Antignac10Patrick Nitschké11Guillaume Dorval12Laboratoire des Maladies Rénales Héréditaires, Inserm UMR 1163, Institut Imagine, Université Paris Cité, Paris, FranceService de Médecine Génomique des Maladies Rares, Hôpital Necker-Enfants Malades, Assistance publique, Hôpitaux de Paris (AP-HP), Paris, FranceLaboratoire des Maladies Rénales Héréditaires, Inserm UMR 1163, Institut Imagine, Université Paris Cité, Paris, France; Service de Néphrologie Pédiatrique, Centre de Référence MARHEA, Hôpital Necker-Enfants Malades, Assistance publique, Hôpitaux de Paris (AP-HP), Paris, FranceLaboratoire des Maladies Rénales Héréditaires, Inserm UMR 1163, Institut Imagine, Université Paris Cité, Paris, FranceDépartement de Santé Publique, Unité de Recherche Clinique, Hôpital Pitié-Salpêtrière, Assistance publique, Hôpitaux de Paris (AP-HP), Paris, FrancePlateforme Bio-informatique, Inserm UMR 1163, Institut Imagine, Université Paris Cité, Paris, FranceService de Médecine Génomique des Maladies Rares, Hôpital Necker-Enfants Malades, Assistance publique, Hôpitaux de Paris (AP-HP), Paris, FranceService de Néphrologie, Centre de Référence MARHEA, Hôpital Necker-Enfants Malades, Assistance publique, Hôpitaux de Paris (AP-HP), Paris, FranceInserm, C2VN, INRAE, C2VN, Aix-Marseille Université, Marseille, France; Centre de Néphrologie et Transplantation Rénale, AP-HM Hôpital de la Conception, Marseille, FranceService de Néphrologie, CHU de Reims, Reims, France; Service de Pathologie, CHU De Reims, Reims, France; Institut d'Intelligence Artificielle en Santé, Université de Reims Champagne-Ardenne et CHU de Reims, Reims, FranceLaboratoire des Maladies Rénales Héréditaires, Inserm UMR 1163, Institut Imagine, Université Paris Cité, Paris, France; Service de Médecine Génomique des Maladies Rares, Hôpital Necker-Enfants Malades, Assistance publique, Hôpitaux de Paris (AP-HP), Paris, FrancePlateforme Bio-informatique, Inserm UMR 1163, Institut Imagine, Université Paris Cité, Paris, FranceLaboratoire des Maladies Rénales Héréditaires, Inserm UMR 1163, Institut Imagine, Université Paris Cité, Paris, France; Service de Médecine Génomique des Maladies Rares, Hôpital Necker-Enfants Malades, Assistance publique, Hôpitaux de Paris (AP-HP), Paris, France; Corresponding authorSummary: The human genome comprises approximately 3% of tandem repeats with variable length (VNTR), a few of which have been linked to human rare diseases. Autosomal dominant tubulointerstitial kidney disease—MUC1 (ADTKD-MUC1) is caused by specific frameshift variants in the coding VNTR of the MUC1 gene. Calling variants from VNTR using short-read sequencing (SRS) is challenging due to poor read mappability. We developed a computational pipeline, VNtyper, for reliable detection of MUC1 VNTR pathogenic variants and demonstrated its clinical utility in two distinct cohorts: (1) a historical cohort including 108 families with ADTKD and (2) a replication naive cohort comprising 2,910 patients previously tested on a panel of genes involved in monogenic renal diseases. In the historical cohort all cases known to carry pathogenic MUC1 variants were re-identified, and a new 25bp-frameshift insertion in an additional mislaid family was detected. In the replication cohort, we discovered and validated 30 new patients.http://www.sciencedirect.com/science/article/pii/S2589004223012488GeneticsGenomicsTechniques in geneticsGenotyping |
| spellingShingle | Hassan Saei Vincent Morinière Laurence Heidet Olivier Gribouval Said Lebbah Frederic Tores Manon Mautret-Godefroy Bertrand Knebelmann Stéphane Burtey Vincent Vuiblet Corinne Antignac Patrick Nitschké Guillaume Dorval VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease iScience Genetics Genomics Techniques in genetics Genotyping |
| title | VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease |
| title_full | VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease |
| title_fullStr | VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease |
| title_full_unstemmed | VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease |
| title_short | VNtyper enables accurate alignment-free genotyping of MUC1 coding VNTR using short-read sequencing data in autosomal dominant tubulointerstitial kidney disease |
| title_sort | vntyper enables accurate alignment free genotyping of muc1 coding vntr using short read sequencing data in autosomal dominant tubulointerstitial kidney disease |
| topic | Genetics Genomics Techniques in genetics Genotyping |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223012488 |
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