Accelerating Novel Candidate Gene Discovery in Neurogenetic Disorders via Whole-Exome Sequencing of Prescreened Multiplex Consanguineous Families

We show that the analysis of the entire set of autozygous intervals per individual in multiplex consanguineous patients, as a prescreen, can markedly increase the yield of WES to identify candidate genes not previously associated with disease

Anas M. Alazami


Scholarcy highlights

  • Neurogenetic disorders represent the largest category of Mendelian diseases in humans
  • With the aim of closing this gap, we performed whole-exome sequencing on 143 multiplex consanguineous families in whom known disease genes had been excluded by autozygosity mapping and candidate gene analysis
  • This prescreening step led to the identification of 69 recessive genes not previously associated with disease, of which 33 are here described
  • This study contributes to the global effort toward a full compendium of disease genes affecting brain function
  • When no compelling disease genes were evident in the regions of homozygosity, patient DNA was subjected to WES under the assumption that this will reveal a novel disease gene
  • ISCA2 has modest sequence identity to the α chain of the IscA
  • When disease genes within the ROH are examined for a likely candidate, it is possible that the clinical picture may sufficiently deviate from the classical phenotype ascribed to a particular gene such that the gene falls outside our consideration

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