Primary ciliary dyskinesia (PCD) is a rare disease that affects tiny, hair-like structures (called cilia) that line the airways. Respiratory cilia carry mucus (which contains inhaled dust and bacteria) toward the throat to be coughed/sneezed out of the body (or digested). In PCD patients, these cilia do not perform their job properly thus allow bacteria and dust to stay in your airways and cause chronic respiratory diseases/infections.
Cross‐sections of respiratory cilia in (A) control (non affected) and (B) CCDC151 mutated proband. Image from Alsaadi and Erzurumluoglu et al (2014, Human Mutation)
We, at the Bristol Genetic Epidemiology Lab (BGEL, University of Bristol, UK), discovered a new Primary ciliary dyskinesia (PCD) causal gene (collaborating with colleagues from the King Saud University, Saudi Arabia).
I, on the 27th of November 2013 – whilst analysing the DNA sequencing data obtained from our participants – discovered the c.925G>T:p.[E309*] mutation in a homozygous state (i.e. two copies of the mutation) within the CCDC151 gene of one of our PCD affected participants. The CCDC151 gene was a great candidate as indicated by previous animal studies, however was not observed as a ‘causal gene’ in PCD affected individuals.
Once this mutation emerged as a clear candidate, we then followed it up by further phenotyping, and bioinformatics and wet-lab studies; and this finding was eventually published more than a year later (i.e. December 2014 issue) in the very respectable clinical genetics journal ‘Human Mutation’ (manuscript sent: 2nd Jun 2014^).
Please see the paper (Alsaadi and Erzurumluoglu et al, 2014. ) and the supplementary files for further details on the methods used and full list of co-authors.
Author Contributions:
AME wrote the manuscript (with guidance from SR, TRG and INMD). AME carried out in silico and wet-lab analyses. INMD and MMA led the study; and together with SR, KKA, PAIG and TRG, provided guidance throughout study and also commented on the manuscript. MMA carried out diagnosis and obtained consent from family. ACA, MM, HZO and MMA led the collection and processing of EM images for cilia. PAIG and AME performed DNA extraction, quantification and other DNA quality control procedures. All authors approved final version of manuscript.
^Now we know that another group (Hjeij et al, 2014) had submitted a paper with similar findings (albeit with additional animal models) to the journal AJHG a week before us (23rd May 2014). Although both groups identified CCDC151 to be a PCD causal gene independently, subsequent citations have all been directed to their paper – reflecting the critical importance of publishing before anyone else.
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