Novel genes and mutations in patients affected by recurrent pregnancy loss
| Autor: | Carlos F. Suárez, Eric Mercier, Manuel A. Patarroyo, Michiko Fukuda, Daniel Vaiman, Jean-Christophe Gris, Paula Quintero-Ronderos, Ronald Gonzalez, Paul Laissue |
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| Přispěvatelé: | Caractéristiques féminines des dysfonctions des interfaces cardio-vasculaires (EA 2992), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), National Institute of Advanced Industrial Science and Technology (AIST), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Université Montpellier 1 (UM1), Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Caucásico
Gene Mutation Secondary Gene mutation Pathology and Laboratory Medicine Gene Biochemistry Models Pregnancy Fgfr2 Gene Proteína Mmp1 Thbd Gene Modificación de ADN Genetic Stability Exome sequencing Clinical Article Gen Col6A3 Thrombin High-Throughput Nucleotide Sequencing Gen F5 Genomics Col6A3 Gene Mmp1 Gene Secuenciación de alto rendimiento Fibrinogen Alphac Factor V Deficiency Ncoa1 Gene Protein Structure Genotype Tro Gene Adamts1 Gene Variación genética Amn gen Creer gen Gen Flt1 03 medical and health sciences Protein Domains Gen Mmp9 Enfermedades del aparato genital Gen Ncoa1 Genetics Teoría cuántica Molecular Biology Assays and Analysis Techniques lcsh:R Abortion Biology and Life Sciences Computational Biology Proteins Gen Mmp1 Enfermedades Fga Gene Peptide Fragments Secuenciación de próxima generación Epas1 Gene 030104 developmental biology Quantum Theory lcsh:Q Gen Bmp7 Genotipo Estructura de la proteína Models Molecular Etiology La expresión génica Gene Expression lcsh:Medicine Bmp7 Gene Whole Exome Sequencing Database and Informatics Methods Gen Fgfr2 Gen Thbd Medicine and Health Sciences Gen Cdh11 Multidisciplinary Gen Lifr Gene Deficiencia de Factor V Deletion Mutation Phenotype Cr1 Gene Función del gen Factor Xa Amino Acid Analysis Thermodynamics Gen Adams1 Matrix Metalloproteinase 1 Transcriptome Analysis Adult Amn Gene Mmp1 Protein Gen Ido2 Protein Domain Secundario Aborto Recurrente Pathophysiology Variabilidad genética medicine Fragmento de péptido Gen Traf3Ip1 Mutación genética Molecular Model Genome Analysis Metabolism Aborto [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology Biología Disease Aborto Habitual El embarazo 0302 clinical medicine Fisiopatología DNA sequencing Infertilidad lcsh:Science Exome Mutation 030219 obstetrics & reproductive medicine Química Tlr3 Gene Estromelisina 2 Dominio de proteínas 3. Good health Genetic Variability Fenotipo Modelo molecular Human Next-Generation Sequencing Abortion Habitual Bioinformatics Secuenciación de nucleótidos de alto rendimiento Gen Tlr3 Código genético Gen Tnc Humans Protein Interaction Domains and Motifs Humano Biology Secuenciación del exoma completo Termodinámica High Throughput Sequencing Factor V Molecular Genetic Variation Cdh11 Gene medicine.disease Habitual Human genetics Molecular biology techniques Sanger Sequencing Ido2 Gene Cdh1 Gene Estabilidad Genética 0301 basic medicine Molecular biology Next Generation Sequencing Mmp9 Gene Dna Modification Estructura secundaria de proteínas medicine.disease_cause Protein Structure Secondary Fibrinógeno Alphac Sequencing techniques Peptide Fragment Flt1 Gene Exoma Fibrinógeno Protein Secondary Structure Artículo Clínico Metabolismo Dominios y motivos de interacción de proteínas Traf3Ip1 Gene Gen lifr Matriz metaloproteinasa 1 Bioinformática Protein Interaction Domains And Motifs Chemistry Genetic Code Biología Computacional Female Research Article Fragmentos de péptidos Gene Sequence F5 Gene Gen Cr1 Caucasian Research and Analysis Methods Gen Cdh1 Matrix Metalloproteinase 10 Secuencia de genes Secuenciación de Sangre Mutación Gen Fga Modelos Fibrinogen Human Genetics Reproducción Genética Gen Epas1 Recurrent Abortion Gene Function Stromelysin 2 |
| Zdroj: | PLoS ONE, Vol 12, Iss 10, p e0186149 (2017) PLoS ONE PLoS ONE, Public Library of Science, 2017, 12 (10), pp.e0186149. ⟨10.1371/journal.pone.0186149⟩ Larsen, E.C., Christiansen, O.B., Kolte, A.M., Macklon, N., New insights into mechanisms behind miscarriage (2013) BMC Med, 11, p. 154., https://doi.org/10.1186/1741-7015-11-154, https://doi.org/10.1186/1741-7015-11-154 PMID: 23803387 Repositorio EdocUR-U. Rosario Universidad del Rosario instacron:Universidad del Rosario Repositorio Institucional UDCA Universidad de Ciencias Aplicadas y Ambientales U.D.C.A instacron:Universidad de Ciencias Aplicadas y Ambientales U.D.C.A |
| ISSN: | 1932-6203 |
| Popis: | Recurrent pregnancy loss is a frequently occurring human infertility-related disease affecting ~1% of women. It has been estimated that the cause remains unexplained in >50% cases which strongly suggests that genetic factors may contribute towards the phenotype. Concerning its molecular aetiology numerous studies have had limited success in identifying the disease’s genetic causes. This might have been due to the fact that hundreds of genes are involved in each physiological step necessary for guaranteeing reproductive success in mammals. In such scenario, next generation sequencing provides a potentially interesting tool for research into recurrent pregnancy loss causative mutations. The present study involved whole-exome sequencing and an innovative bioinformatics analysis, for the first time, in 49 unrelated women affected by recurrent pregnancy loss. We identified 27 coding variants (22 genes) potentially related to the phenotype (41% of patients). The affected genes, which were enriched by potentially deleterious sequence variants, belonged to distinct molecular cascades playing key roles in implantation/pregnancy biology. Using a quantum chemical approach method we established that mutations in MMP-10 and FGA proteins led to substantial energetic modifications suggesting an impact on their functions and/or stability. The next generation sequencing and bioinformatics approaches presented here represent an efficient way to find mutations, having potentially moderate/strong functional effects, associated with recurrent pregnancy loss aetiology. We consider that some of these variants (and genes) represent probable future biomarkers for recurrent pregnancy loss. © 2017 Quintero-Ronderos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Databáze: | OpenAIRE |
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