The landscape of autosomal-recessive pathogenic variants in European populations reveals phenotype-specific effects

Hila Fridman, Helger G. Yntema, Reedik Mägi, Reidar Andreson, Andres Metspalu, Massimo Mezzavila, Chris Tyler-Smith, Yali Xue, Shai Carmi, Ephrat Levy-Lahad, Christian Gilissen*, Han G. Brunner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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.

Original languageAmerican English
Pages (from-to)608-619
Number of pages12
JournalAmerican Journal of Human Genetics
Volume108
Issue number4
DOIs
StatePublished - 1 Apr 2021

Bibliographical note

Publisher Copyright:
© 2021 American Society of Human Genetics

Keywords

  • at-risk couples
  • autosomal recessive disorders
  • carrier frequency
  • pre-conception carrier screening
  • selection

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