Nonsense Mutation in Coiled-Coil Domain Containing 151 Gene (<i>CCDC151</i>) Causes Primary Ciliary Dyskinesia

Alsaadi, Muslim M.; Erzurumluoglu, A. Mesut; Rodríguez, Santiago Cuadrado; Guthrie, Philip A. I.; Gaunt, Tom R.; Omar, Hager Z; Mubarak, Muhammed; Alharbi, Khalid Khalaf; Al-Rikabi, Ammar C.; Day, Ian N.M.

doi:10.1002/humu.22698

Cited by 37 publications

(29 citation statements)

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“…CCDC151 , which is required for the function of intraflagellar transport‐dependent motile cilia, is a novel gene with a limited number of related studies . Several studies reported that CCDC151 mutations were associated with primary ciliary dyskinesia . CHRNB2 is an acetylcholine receptor subunit whose mutations are associated with autosomal dominant nocturnal frontal lobe epilepsy .…”

Section: Discussionmentioning

confidence: 99%

Analysis of key genes and signaling pathways involved in Helicobacter pylori‐associated gastric cancer based on The Cancer Genome Atlas database and RNA sequencing data

Liu

et al. 2018

Helicobacter

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Section: Discussionmentioning

confidence: 99%

Analysis of key genes and signaling pathways involved in Helicobacter pylori‐associated gastric cancer based on The Cancer Genome Atlas database and RNA sequencing data

Liu

et al. 2018

Helicobacter

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“…As aforementioned, the participating family was previously analysed for a PCD study [ 3 , 4 ]; and this study was carried out after the family re-attended the clinic enquiring about the cause of PLS present in other siblings within the family.…”

Section: Methodsmentioning

confidence: 99%

Proxy Molecular Diagnosis from Whole-Exome Sequencing Reveals Papillon-Lefevre Syndrome Caused by a Missense Mutation in CTSC

et al. 2015

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Papillon-Lefevre syndrome (PLS) is an autosomal recessive disorder characterised by severe early onset periodontitis and palmoplantar hyperkeratosis. A previously reported missense mutation in the CTSC gene (NM_001814.4:c.899G>A:p.(G300D)) was identified in a homozygous state in two siblings diagnosed with PLS in a consanguineous family of Arabic ancestry. The variant was initially identified in a heterozygous state in a PLS unaffected sibling whose whole exome had been sequenced as part of a previous Primary ciliary dyskinesia study. Using this information, a proxy molecular diagnosis was made on the PLS affected siblings after consent was given to study this second disorder found to be segregating within the family. The prevalence of the mutation was then assayed in the local population using a representative sample of 256 unrelated individuals. The variant was absent in all subjects indicating that the variant is rare in Saudi Arabia. This family study illustrates how whole-exome sequencing can generate findings and inferences beyond its primary goal.

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“…a tenth will be variants with ‘predicted high impact’ (also known as Φ variants i.e. rare nonsense, missense, splice-site acceptor or donor variants, exonic indels [36]). There are many algorithms which predict the functional effect of these variants (Table 3).…”

Section: Stage 2 – Filtering/ranking Of Variantsmentioning

confidence: 99%

“…After all the filtering steps in the above figure are applied, the total will be reduced to a single candidate. The numbers here are for illustration purposes only (adapted from [36]). Homozygosity step is added as PCD is an autosomal recessive disorder.…”

Section: Stage 3 – Building Evidence For Causalitymentioning

confidence: 99%

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Identifying highly-penetrant disease causal mutations using next generation sequencing: Guide to whole process

Erzurumluoglu

2014

Preprint

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Recent technological advances have created challenges for geneticists and a need to adapt to a wide range of new bioinformatics tools and an expanding wealth of publicly available data (e.g. mutation databases, software). This wide range of methods and a diversity of file formats used in sequence analysis is a significant issue, with a considerable amount of time spent before anyone can even attempt to analyse the genetic basis of human disorders. Another point to consider is although many possess 'just enough' knowledge to analyse their data, they do not make full use of the tools and databases that are available and also do not know how their data was created. The primary aim of this review is to document some of the key approaches and provide an analysis schema to make the analysis process more efficient and reliable in the context of discovering highly penetrant causal mutations/genes. This review will also compare the methods used to identify highly penetrant variants when data is obtained from consanguineous individuals as opposed to non-consanguineous; and when Mendelian disorders are analysed as opposed to common-complex disorders. IN TRO D UCTIO NNext generation sequencing (NGS) and other high throughput technologies have brought new challenges concomitantly. The colossal amount of information that is produced has led researchers to look for ways of reducing the time and effort it takes to analyse the resulting data whilst also keeping up with the storage needs of the resulting files -which are in the magnitude of gigabytes each. The recently emerged variant call format (VCF) has somewhat provided a way out of this complex issue [1]. Using a reference sequence and comparing it with the query sequence, only the differences between the two are encoded into a VCF file. Not only are VCF files substantially smaller in size (>300x in relation to BAM files which store all raw read alignments), they also make the data relatively easy to analyse since there are many bioinformatics tools (e.g. annotation, mutation effect prediction) which accept the VCF format as standard input. The Genome Analysis Toolkit (GATK) made available by the Broad Institute also provides useful suggestions to bring a universal standard for the annotation and filtering of VCF files [2]. The abovementioned reasons have made VCF the established format for the sharing of genetic variation produced from large sequencing projects (e.g. 1000 Genomes Project, NHLBI Exome Project -also known as EVS). However the VCF does have some disadvantages. The files can be information dense, initially . CC-BY 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/011130 doi: bioRxiv preprint first posted online Nov. 6, 2014; 2 difficult to understand and parse. Comprehensive information about the VCF and its companion software VFCtools [1] are available online (vcftools.sourceforge.net).Because of the substantial decrease in the price o...

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Nonsense Mutation in Coiled-Coil Domain Containing 151 Gene (CCDC151) Causes Primary Ciliary Dyskinesia

Cited by 37 publications

References 12 publications

Analysis of key genes and signaling pathways involved in Helicobacter pylori‐associated gastric cancer based on The Cancer Genome Atlas database and RNA sequencing data

Analysis of key genes and signaling pathways involved in Helicobacter pylori‐associated gastric cancer based on The Cancer Genome Atlas database and RNA sequencing data

Proxy Molecular Diagnosis from Whole-Exome Sequencing Reveals Papillon-Lefevre Syndrome Caused by a Missense Mutation in CTSC

Identifying highly-penetrant disease causal mutations using next generation sequencing: Guide to whole process

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