The landscape of autosomal-recessive pathogenic variants in European populations reveals phenotype-specific effects
| Autor: | Han G. Brunner, Ephrat Levy-Lahad, Chris Tyler-Smith, Massimo Mezzavila, Christian Gilissen, Reedik Mägi, Andres Metspalu, Yali Xue, Reidar Andreson, Shai Carmi, Hila Fridman, Helger G. Yntema |
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| Přispěvatelé: | RS: GROW - R4 - Reproductive and Perinatal Medicine, Klinische Genetica, MUMC+: DA Klinische Genetica (5) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
at-risk couples autosomal recessive disorders carrier frequency pre-conception carrier screening selection Cohort Studies Europe Exome Female Genes Recessive Genetic Testing Genetic Variation Health Heterozygote Humans Intellectual Disability Whites Consanguinity Family Characteristics Phenotype Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] Genetics (clinical) Genetics 0303 health sciences education.field_of_study 030305 genetics & heredity Genetic disorder Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6] GENOME GENES GENETICS Population Biology Article White People 03 medical and health sciences All institutes and research themes of the Radboud University Medical Center medicine Recessive Allele education Gene 030304 developmental biology Carrier signal Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] MUTATIONS medicine.disease Genetic architecture |
| Zdroj: | American Journal of Human Genetics, 108, 608-619 American Journal of Human Genetics, 108(4), 608-619. Cell Press Am J Hum Genet American Journal of Human Genetics, 108, 4, pp. 608-619 |
| ISSN: | 0002-9297 |
| Popis: | The number and distribution of recessive alleles in the population for various diseases are not known at genome-wide-scale. Based on 6447 exome-sequences of healthy, genetically-unrelated Europeans of two distinct ancestries, we estimate that every individual is a carrier of at least 2 pathogenic variants in currently known autosomal recessive (AR) genes, and that 0.8-1% of European couples are at-risk of having a child affected with a severe AR genetic disorder. This risk is 16.5-fold higher for first cousins, but is significantly more increased for skeletal disorders and intellectual disabilities due to their distinct genetic architecture. |
| Databáze: | OpenAIRE |
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