A dozen genes/regions have been confirmed as genetic risk factors for oral clefts in human association and linkage studies, and animal models argue even more genes may be involved. Genomic sequencing studies should identify specific causal variants and may reveal additional genes as influencing risk to oral clefts, which have a complex and heterogeneous etiology. We conducted a whole exome sequencing (WES) study to search for potentially causal variants using affected relatives drawn from multiplex cleft families. Two or three affected 2°, 3° and higher degree relatives from 55 multiplex families were sequenced. We examined rare single nucleotide variants (SNVs) shared by affected relatives in 348 recognized candidate genes. Exact probabilities that affected relatives would share these rare variants were calculated given pedigree structures and corrected for the number of variants tested. Five novel and potentially damaging SNVs shared by affected distant relatives were found, and confirmed by Sanger sequencing. One damaging SNV in CDH1, shared by three affected second cousins from a single family, attained statistical significance (p=0.02 after correcting for multiple tests). Family based designs such as used in this WES study offer important advantages for identifying genes likely to be causing complex and heterogeneous disorders.
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 September 2023.
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Altmetric has tracked 33,738,238 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
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