Systematic analysis and prediction of genes associated with monogenic disorders on human chromosome X

Elsa Leitão; Christopher Schröder; Ilaria Parenti; Carine Dalle; Agnès Rastetter; Theresa Kühnel; Alma Kuechler; Sabine Kaya; Bénédicte Gérard; Elise Schaefer; Caroline Nava; Nathalie Drouot; Camille Engel; Juliette Piard; Bénédicte Duban-Bedu; Laurent Villard; Alexander P A Stegmann; Els K Vanhoutte; Job A J Verdonschot; Frank J Kaiser; Frédéric Tran Mau-Them; Marcello Scala; Pasquale Striano; Suzanna G M Frints; Emanuela Argilli; Elliott H Sherr; Fikret Elder; Julien Buratti; Boris Keren; Cyril Mignot; Delphine Héron; Jean-Louis Mandel; Jozef Gecz; Vera M Kalscheuer; Bernhard Horsthemke; Amélie Piton; Christel Depienne

doi:10.1038/s41467-022-34264-y

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Systematic analysis and prediction of genes associated with monogenic disorders on human chromosome X

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Systematic analysis and prediction of genes associated with monogenic disorders on human chromosome X

Elsa Leitão, Christopher Schröder, Ilaria Parenti, Carine Dalle, Agnès Rastetter, Theresa Kühnel, Alma Kuechler, Sabine Kaya, Bénédicte Gérard, Elise Schaefer, …

Nature communications, Vol.13(1), pp.6570-17

02/11/2022

DOI: https://doi.org/10.1038/s41467-022-34264-y

PMID: 36323681

Résumé

Autism Spectrum Disorder - genetics

Chromosomes, Human, X - genetics

Databases, Genetic

Genes, X-Linked

Humans

Intellectual Disability - genetics

Disease gene discovery on chromosome (chr) X is challenging owing to its unique modes of inheritance. We undertook a systematic analysis of human chrX genes. We observe a higher proportion of disorder-associated genes and an enrichment of genes involved in cognition, language, and seizures on chrX compared to autosomes. We analyze gene constraints, exon and promoter conservation, expression, and paralogues, and report 127 genes sharing one or more attributes with known chrX disorder genes. Using machine learning classifiers trained to distinguish disease-associated from dispensable genes, we classify 247 genes, including 115 of the 127, as having high probability of being disease-associated. We provide evidence of an excess of variants in predicted genes in existing databases. Finally, we report damaging variants in CDK16 and TRPC5 in patients with intellectual disability or autism spectrum disorders. This study predicts large-scale gene-disease associations that could be used for prioritization of X-linked pathogenic variants.

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Titre: Systematic analysis and prediction of genes associated with monogenic disorders on human chromosome X
Créateurs - sans rôle: Elsa Leitão - Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany
Christopher Schröder - Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany
Ilaria Parenti - Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany
Carine Dalle - Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France
Agnès Rastetter - Institut du Cerveau
Theresa Kühnel - Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany
Alma Kuechler - University of Duisburg-Essen
Sabine Kaya - Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany
Bénédicte Gérard - Unité de Génétique Moléculaire, IGMA, Hôpitaux Universitaire de Strasbourg, Strasbourg, France
Elise Schaefer - Service de Génétique Médicale, IGMA, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
Caroline Nava - Institut du Cerveau et de la Moelle épinière (ICM), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, F-75013, Paris, France
Nathalie Drouot - Université de Strasbourg
Camille Engel - Université de Strasbourg, Illkirch, 67400, France
Juliette Piard - Université de Bourgogne
Bénédicte Duban-Bedu - Centre de génétique chromosomique, Hôpital Saint-Vincent de Paul, Lille, France
Laurent Villard - Département de Génétique Médicale, APHM, Hôpital d'Enfants de La Timone, Marseille, France
Alexander P A Stegmann - Department of Clinical Genetics, Maastricht University Medical Center+, Maastricht, The Netherlands
Els K Vanhoutte - Maastricht University
Job A J Verdonschot - Cardiovascular Research Institute (CARIM), Departments of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands
Frank J Kaiser - University of Duisburg-Essen
Frédéric Tran Mau-Them - Unité Fonctionnelle Innovation en Diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France
Marcello Scala - Istituto Giannina Gaslini
Pasquale Striano - Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, 16147, Genoa, Italy
Suzanna G M Frints - Department of Genetics and Cell Biology, Faculty of Health Medicine Life Sciences, Maastricht University Medical Center+, Maastricht University, Maastricht, The Netherlands
Emanuela Argilli - Institute of Human Genetics and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA
Elliott H Sherr - University of California, San Francisco
Fikret Elder - UF de Génomique du Développement, Département de Génétique, Groupe Hospitalier Pitié-Salpêtrière, APHP-Sorbonne Université, Paris, France
Julien Buratti - UF de Génomique du Développement, Département de Génétique, Groupe Hospitalier Pitié-Salpêtrière, APHP-Sorbonne Université, Paris, France
Boris Keren - Sorbonne Université
Cyril Mignot - Sorbonne Université
Delphine Héron - Sorbonne Université
Jean-Louis Mandel - Université de Strasbourg, Illkirch, 67400, France
Jozef Gecz - The University of Adelaide
Vera M Kalscheuer - Research Group Development and Disease, Max Planck Institute for Molecular Genetics, Berlin, Germany
Bernhard Horsthemke - Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany
Amélie Piton - Université de Strasbourg, Illkirch, 67400, France
Christel Depienne - Institute of Human Genetics, University Hospital Essen, University Duisburg-Essen, Essen, Germany. christel.depienne@uni-due.de
Détails de publication: Nature communications, Vol.13(1), pp.6570-17
Note de subvention: R01 NS058721 / NINDS NIH HHS Wellcome Trust
Identifiants: 99149283409311
Unité académique: BioCampus Montpellier - BCM
Langue: English
Type de ressource: Journal article