Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approach
Abstract The field of noninvasive prenatal diagnosis (NIPD) has undergone significant progress over the last decade. Direct haplotyping has been successfully applied for NIPD of few single-gene disorders. However, technical issues remain for triplet-repeat expansions. The objective of this study was...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-15307-2 |
| _version_ | 1818158458182041600 |
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| author | C. Liautard-Haag G. Durif C. VanGoethem D. Baux A. Louis L. Cayrefourcq M. Lamairia M. Willems C. Zordan V. Dorian C. Rooryck C. Goizet A. Chaussenot L. Monteil P. Calvas C. Miry R. Favre E. Le Boette M. Fradin A. F. Roux M. Cossée M. Koenig C. Alix-Panabière C. Guissart M. C. Vincent |
| author_facet | C. Liautard-Haag G. Durif C. VanGoethem D. Baux A. Louis L. Cayrefourcq M. Lamairia M. Willems C. Zordan V. Dorian C. Rooryck C. Goizet A. Chaussenot L. Monteil P. Calvas C. Miry R. Favre E. Le Boette M. Fradin A. F. Roux M. Cossée M. Koenig C. Alix-Panabière C. Guissart M. C. Vincent |
| author_sort | C. Liautard-Haag |
| collection | DOAJ |
| description | Abstract The field of noninvasive prenatal diagnosis (NIPD) has undergone significant progress over the last decade. Direct haplotyping has been successfully applied for NIPD of few single-gene disorders. However, technical issues remain for triplet-repeat expansions. The objective of this study was to develop an NIPD approach for couples at risk of transmitting dynamic mutations. This method includes targeted enrichment for linked-read libraries and targeted maternal plasma DNA sequencing. We also developed an innovative Bayesian procedure to integrate the Hoobari fetal genotyping model for inferring the fetal haplotype and the targeted gene variant status. Our method of directly resolving parental haplotypes through targeted linked-read sequencing was smoothly performed using blood samples from families with Huntington’s disease or myotonic dystrophy type 1. The Bayesian analysis of transmission of parental haplotypes allowed defining the genotype of five fetuses. The predicted variant status of four of these fetuses was in agreement with the invasive prenatal diagnosis findings. Conversely, no conclusive result was obtained for the NIPD of fragile X syndrome. Although improvements should be made to achieve clinically acceptable accuracy, our study shows that linked-read sequencing and parental haplotype phasing can be successfully used for NIPD of triplet-repeat expansion diseases. Trial registration: NCT04698551_date of first registration: 07/01/2021. |
| first_indexed | 2024-12-11T15:30:24Z |
| format | Article |
| id | doaj.art-b11178f6c4834f728d43cfbfab77784f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-11T15:30:24Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-b11178f6c4834f728d43cfbfab77784f2022-12-22T01:00:05ZengNature PortfolioScientific Reports2045-23222022-07-011211910.1038/s41598-022-15307-2Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approachC. Liautard-Haag0G. Durif1C. VanGoethem2D. Baux3A. Louis4L. Cayrefourcq5M. Lamairia6M. Willems7C. Zordan8V. Dorian9C. Rooryck10C. Goizet11A. Chaussenot12L. Monteil13P. Calvas14C. Miry15R. Favre16E. Le Boette17M. Fradin18A. F. Roux19M. Cossée20M. Koenig21C. Alix-Panabière22C. Guissart23M. C. Vincent24Laboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU MontpellierIMAG, Université de Montpellier, CNRSLaboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU MontpellierLaboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU MontpellierLaboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU MontpellierLaboratory of Rare Human Circulating Cells (LCCRH), University Medical Center of MontpellierLaboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU MontpellierDépartement de Génétique Médicale, Maladies Rares et Médecine Personnalisée, Centre de Référence Anomalies du Développement et Syndromes Malformatifs, Université de Montpellier, CHU de MontpellierService de Génétique Médicale, Groupe Hospitalier Pellegrin, CHU de BordeauxService de Génétique Médicale, Groupe Hospitalier Pellegrin, CHU de BordeauxService de Génétique Médicale, Groupe Hospitalier Pellegrin, CHU de BordeauxService de Génétique Médicale, Groupe Hospitalier Pellegrin, CHU de BordeauxService de Génétique Médicale, Centre de Référence des Maladies Mitochondriales, Hôpital de l’Archet 2Service de Génétique Médicale, CHU de ToulouseService de Génétique Médicale, CHU de ToulouseDepartment of Maternal Fetal Medicine, Strasbourg University HospitalDepartment of Maternal Fetal Medicine, Strasbourg University HospitalService de Génétique Médicale, Centre Hospitalier de Saint BrieucService de Génétique Médicale, Centre Hospitalier de Saint BrieucLaboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU MontpellierLaboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU MontpellierLaboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU MontpellierLaboratory of Rare Human Circulating Cells (LCCRH), University Medical Center of MontpellierLaboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU MontpellierLaboratoire de Génétique Moléculaire, Institut Universitaire de Recherche Clinique, Université de Montpellier, CHU MontpellierAbstract The field of noninvasive prenatal diagnosis (NIPD) has undergone significant progress over the last decade. Direct haplotyping has been successfully applied for NIPD of few single-gene disorders. However, technical issues remain for triplet-repeat expansions. The objective of this study was to develop an NIPD approach for couples at risk of transmitting dynamic mutations. This method includes targeted enrichment for linked-read libraries and targeted maternal plasma DNA sequencing. We also developed an innovative Bayesian procedure to integrate the Hoobari fetal genotyping model for inferring the fetal haplotype and the targeted gene variant status. Our method of directly resolving parental haplotypes through targeted linked-read sequencing was smoothly performed using blood samples from families with Huntington’s disease or myotonic dystrophy type 1. The Bayesian analysis of transmission of parental haplotypes allowed defining the genotype of five fetuses. The predicted variant status of four of these fetuses was in agreement with the invasive prenatal diagnosis findings. Conversely, no conclusive result was obtained for the NIPD of fragile X syndrome. Although improvements should be made to achieve clinically acceptable accuracy, our study shows that linked-read sequencing and parental haplotype phasing can be successfully used for NIPD of triplet-repeat expansion diseases. Trial registration: NCT04698551_date of first registration: 07/01/2021.https://doi.org/10.1038/s41598-022-15307-2 |
| spellingShingle | C. Liautard-Haag G. Durif C. VanGoethem D. Baux A. Louis L. Cayrefourcq M. Lamairia M. Willems C. Zordan V. Dorian C. Rooryck C. Goizet A. Chaussenot L. Monteil P. Calvas C. Miry R. Favre E. Le Boette M. Fradin A. F. Roux M. Cossée M. Koenig C. Alix-Panabière C. Guissart M. C. Vincent Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approach Scientific Reports |
| title | Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approach |
| title_full | Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approach |
| title_fullStr | Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approach |
| title_full_unstemmed | Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approach |
| title_short | Noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and Bayesian approach |
| title_sort | noninvasive prenatal diagnosis of genetic diseases induced by triplet repeat expansion by linked read haplotyping and bayesian approach |
| url | https://doi.org/10.1038/s41598-022-15307-2 |
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