1. The landscape of autosomal-recessive pathogenic variants in European populations reveals phenotype-specific effects.
- Author
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Fridman, Hila, Yntema, Helger G., Mägi, Reedik, Andreson, Reidar, Metspalu, Andres, Mezzavila, Massimo, Tyler-Smith, Chris, Xue, Yali, Carmi, Shai, Levy-Lahad, Ephrat, Gilissen, Christian, and Brunner, Han G.
- Subjects
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CHILDREN with intellectual disabilities , *GENES , *INTELLECTUAL disabilities , *GENETIC disorders , *EXOMES , *RECESSIVE genes , *ALLELES - Abstract
The number and distribution of recessive alleles in the population for various diseases are not known at genome-wide-scale. Based on 6,447 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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