Primary ciliary dyskinesia (PCD) is a disorder characterized by chronic respiratory distress that has a history of going undiagnosed.

Combined whole-exome sequencing (WES) and copy-number variant (CNV) analysis can aid in diagnosing patients with PCD, according to research published in G3 this month.

PCD arises from mutations in cilia-associated genes—and results from the paralysis of motile cilia. Normally, cilia on respiratory epithelial cells beat to move mucus along the tract; without this motion, mucus can build up and lead to respiratory infection. These cilia defects can also cause reproductive problems, hearing loss, chronic sinusitis, and situs inversus (where the left-right organization of the internal organs is reversed).

Efficient diagnosis of PCD is a challenge; there are 32 genes associated with the disorder, and previous diagnoses have relied on electron microscopy (EM) of cilia to analyze their structure. In this recent paper, Marshall et al. present a cost-effective and efficient genetic workflow that uses WES combined with CNV analysis to identify causative mutations in PCD patients.

Sanger sequencing has been effective in the past, but as genes continue to be added to the PCD-associated pool, sequencing individual genes becomes time-consuming and costly, and not all genes can be effectively sequenced this way. Additionally, copy-number variation is seen in around 10% of autosomal-recessive disorders (like PCD) but is undetectable by Sanger sequencing.

The researchers analyzed 20 unsolved PCD families through a combination of WES and CNV analysis. They found that their approach was useful for identifying biallelic pathogenic mutations, obtaining information on all known PCD genes, and identifying possible variants of unknown significance that could be associated with PCD, leading to an overall diagnostic rate of 76%.

CITATION Marshall C.R., Scherer S.W., Zariwala M.A., Lau L., Paton T.A., Stockley T., Jobling R.K, Ray P.N., Knowles M.R., FORGE Canada Consortium, Hall D.A., Dell S.D., Kim, R.H. 2015. Whole-Exome Sequencing and Targeted Copy Number Analysis in Primary Ciliary Dyskinesia. G3, 5(8): 1775-81. doi:10.1534/g3.115.019851 http://www.g3journal.org/content/5/8/1775.full

, ,

Scientific Editor and Programs Manager. Genetics and Molecular Biology PhD. Find me on Twitter: @_sbay

View all posts by Sarah Bay »

Read more in

  • Hongyu Zhao joins GENETICS as new Senior Editor

    A new senior editor is joining GENETICS in the Statistical Genetics and Genomics section. We’re excited to welcome Hongyu Zhao to the editorial team. Hongyu ZhaoSenior Editor Hongyu Zhao is the Ira V. Hiscock Professor of Biostatistics, Professor of Genetics, and Professor of Statistics and Data Science at Yale University. He received his BS in…

  • Julio Molina Pineda at TAGC 2024

    GSA Member Julio Molina Pineda Receives DeLill Nasser Award, Shines at TAGC 2024 

    “At any career stage, the GSA membership is an amazing investment for any genetics professional!” Julio Molina Pineda is a PhD Candidate in Cell and Molecular Biology and a Research Assistant at the University of Arkansas, and a Doctoral Academy Fellow at the Lewis Lab. In 2023, Julio was awarded the DeLill Nasser Award for…

  • Ed Grell at his dissecting microscope using ether to anesthetize his flies.

    In Memoriam: Ellsworth Herman Grell (1932–2023), a pioneer of Drosophila genome engineering and annotation

    Ellsworth (Ed) Grell blessed the Drosophila community through three enduring legacies: as a pioneer of chromosome mechanics, as a primary organizer and synthesizer of genetic knowledge in Drosophila, and as a graceful mentor to those fortunate to have known him personally. Ed grew up in rural Nebraska, completed his undergraduate studies at Iowa State, and…

  • Congratulations to the #Fungal24 Poster Award winners!

    We are pleased to announce the recipients of the GSA Poster Awards for posters presented at the 32nd Fungal Genetics Conference! Undergraduate and graduate student members of GSA were eligible for the awards, and a hard-working team of judges made the determinations. Congratulations to all! Felicia Ebot Ojong, The University of Georgia My research is focused…

  • Poster presentation tips for TAGC 2024

    You’ve been selected to present a poster at The Allied Genetics Conference 2024 in March—you’ve celebrated, made plans to attend, now what? This is an exciting opportunity to showcase your research and engage with fellow members of the genetics community, so you want to make sure you’re prepared. We wanted to offer you some tips…

  • Maximize your TAGC 2024 experience 

    A guide to all that National Harbor & DC have to offer Are you joining us for The Allied Genetics Conference 2024 in March? Make the most of your #TAGC24 experience in National Harbor! We know the science will keep you busy, but you deserve to unwind and have some fun, so we’ve curated a…

  • Early Career Leadership Spotlight: Sarah Petrosky

    We’re taking time to get to know the members of the GSA’s Early Career Scientist Committees. Join us to learn more about our early career scientist advocates. Sarah PetroskyMultimedia SubcommitteeUniversity of Pittsburgh Research Interest I am interested in understanding adaptation that has been happening recently in populations by dissecting the ways that genes underlying an adaptation…

  • TAGC 2024 Early Career Award Winners

    GSA is pleased to announce the winners of the early career awards presented at The Allied Genetics Conference 2024. These awards are specific to particular TAGC communities and recognize early career scientists’ outstanding work on their respective research organisms. The awardees will present their talks in keynote sessions at TAGC 2024.  Don’t miss the opportunity…

  • Preeminent geneticists recognized with revamped GSA Awards

    In 2022, GSA’s Board of Directors launched an audit to review the five major awards conferred by the Society. Today, we are thrilled to announce the recipients of the reimagined GSA Awards, including the new Genetics Society of America Early Career Medal. The scientists honored this year are recognized by their peers for their outstanding…

  • Fly Board funds outreach programs to spread the word about Drosophila research

    In 2020, the Fly Board voted to use part of its reserve fund to support efforts to increase trainee participation as well as equity and diversity in the Drosophila community. An awards committee decides how the money will be spent each year, and from 2020–2022, the committee posted a very broad call for applications from…

  • New members of the GSA Board of Directors: 2024–2026

    We are pleased to announce the election of four new leaders to the GSA Board of Directors: 2024 Vice President/2025 President Brenda Andrews Professor, University of Toronto It’s an honor to continue my association with the Society by serving as Vice President of the Board of Directors. I have broad knowledge of the ongoing activities…