أعرض في EDS

Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis

التفاصيل البيبلوغرافية
العنوان: Recessive mutations in a distal PTF1A enhancer cause isolated pancreatic agenesis
المؤلفون: Weedon, M. N., Cebola, I., Patch, A. M., Flanagan, S., De Franco, E., Caswell, R., Rodríguez Seguí, Santiago Andrés, Shaw Smith, C., Cho, C., Allen, H. L., Houghton, J., Roth, C. L., Chen, R., Hussain, K., Marsh, P., Vallier, L., Murray, A., International Pancreatic Agenesis Consortium, Ellard, S., Ferrer, J., Hattersley, A. T.
المصدر: Nature genetics
بيانات النشر: Nature Research, 2013.
سنة النشر: 2013
مصطلحات موضوعية: Epigenomics, Male, International Pancreatic Agenesis Consortium, medicine.disease_cause, DISEASE, AGENESIS, 0302 clinical medicine, ELEMENTS, HUMAN GENOME, 11 Medical and Health Sciences, Genetics & Heredity, 0303 health sciences, Mutation, 3. Good health, Pedigree, Medicina Básica, medicine.anatomical_structure, DIFFERENTIATION, Enhancer Elements, Genetic, LEADS, Agenesis, Female, Pancreas, Life Sciences & Biomedicine, CIENCIAS MÉDICAS Y DE LA SALUD, GENES, Genética Humana, Genes, Recessive, Biology, Article, ENHANCER, 03 medical and health sciences, Genetics, medicine, Humans, Progenitor cell, Enhancer, Gene, Transcription factor, Embryonic Stem Cells, 030304 developmental biology, PANCREAS, Science & Technology, Chromosomes, Human, Pair 10, DELETION, Pancreatic Diseases, DNA, 06 Biological Sciences, medicine.disease, Molecular biology, PTF1A, CELLS, Human genome, VERTEBRATE, 030217 neurology & neurosurgery, Transcription Factors, Developmental Biology
الوصف: The contribution of cis-regulatory mutations to human disease remains poorly understood. Whole-genome sequencing can identify all noncoding variants, yet the discrimination of causal regulatory mutations represents a formidable challenge. We used epigenomic annotation in human embryonic stem cell (hESC)-derived pancreatic progenitor cells to guide the interpretation of whole-genome sequences from individuals with isolated pancreatic agenesis. This analysis uncovered six different recessive mutations in a previously uncharacterized ∼400-bp sequence located 25 kb downstream of PTF1A (encoding pancreas-specific transcription factor 1a) in ten families with pancreatic agenesis. We show that this region acts as a developmental enhancer of PTF1A and that the mutations abolish enhancer activity. These mutations are the most common cause of isolated pancreatic agenesis. Integrating genome sequencing and epigenomic annotation in a disease-relevant cell type can thus uncover new noncoding elements underlying human development and disease. Fil: Weedon, M. N.. University of Exeter; Reino Unido Fil: Cebola, I.. Institut d’Investigacions Biomèdiques August Pi i Sunyer; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas; España. Imperial College London; Reino Unido Fil: Patch, A. M.. University of Exeter; Reino Unido Fil: Flanagan, S.. University of Exeter; Reino Unido Fil: De Franco, E.. University of Exeter; Reino Unido Fil: Caswell, R.. University of Exeter; Reino Unido Fil: Rodríguez Seguí, Santiago Andrés. Institut d’Investigacions Biomèdiques August Pi i Sunyer; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas; España. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Shaw Smith, C.. University of Exeter; Reino Unido Fil: Cho, C.. Anne McLaren Laboratory for Regenerative Medicine; Reino Unido Fil: Allen, H. L.. University of Exeter; Reino Unido Fil: Houghton, J.. University of Exeter; Reino Unido Fil: Roth, C. L.. Seattle Children’s Hospital Research Institute; Estados Unidos Fil: Chen, R.. King’s College London; Reino Unido Fil: Hussain, K.. University College London; Reino Unido Fil: Marsh, P.. King’s College London; Reino Unido Fil: Vallier, L.. Anne McLaren Laboratory for Regenerative Medicine; Reino Unido Fil: Murray, A.. University of Exeter; Reino Unido Fil: International Pancreatic Agenesis Consortium. No especifica; Fil: Ellard, S.. University of Exeter; Reino Unido Fil: Ferrer, J.. Institut d’Investigacions Biomèdiques August Pi i Sunyer; España. Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas; España. Imperial College London; Reino Unido Fil: Hattersley, A. T.. University of Exeter; Reino Unido
وصف الملف: application/pdf
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6732dc3634efaea601cc641efbd6d195Test
http://hdl.handle.net/10044/1/71050Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....6732dc3634efaea601cc641efbd6d195
قاعدة البيانات: OpenAIRE
الوصف
الوصف غير متاح.