Title |
High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency
|
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Published in |
Nature Genetics, September 2010
|
DOI | 10.1038/ng.659 |
Pubmed ID | |
Authors |
Sarah E Calvo, Elena J Tucker, Alison G Compton, Denise M Kirby, Gabriel Crawford, Noel P Burtt, Manuel Rivas, Candace Guiducci, Damien L Bruno, Olga A Goldberger, Michelle C Redman, Esko Wiltshire, Callum J Wilson, David Altshuler, Stacey B Gabriel, Mark J Daly, David R Thorburn, Vamsi K Mootha |
Abstract |
Discovering the molecular basis of mitochondrial respiratory chain disease is challenging given the large number of both mitochondrial and nuclear genes that are involved. We report a strategy of focused candidate gene prediction, high-throughput sequencing and experimental validation to uncover the molecular basis of mitochondrial complex I disorders. We created seven pools of DNA from a cohort of 103 cases and 42 healthy controls and then performed deep sequencing of 103 candidate genes to identify 151 rare variants that were predicted to affect protein function. We established genetic diagnoses in 13 of 60 previously unsolved cases using confirmatory experiments, including cDNA complementation to show that mutations in NUBPL and FOXRED1 can cause complex I deficiency. Our study illustrates how large-scale sequencing, coupled with functional prediction and experimental validation, can be used to identify causal mutations in individual cases. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 8 | 3% |
United Kingdom | 5 | 2% |
Germany | 3 | <1% |
Belgium | 2 | <1% |
France | 1 | <1% |
Austria | 1 | <1% |
Switzerland | 1 | <1% |
Portugal | 1 | <1% |
India | 1 | <1% |
Other | 6 | 2% |
Unknown | 276 | 90% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 83 | 27% |
Student > Ph. D. Student | 80 | 26% |
Other | 26 | 9% |
Professor > Associate Professor | 22 | 7% |
Student > Bachelor | 18 | 6% |
Other | 54 | 18% |
Unknown | 22 | 7% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 137 | 45% |
Biochemistry, Genetics and Molecular Biology | 61 | 20% |
Medicine and Dentistry | 44 | 14% |
Neuroscience | 9 | 3% |
Computer Science | 5 | 2% |
Other | 22 | 7% |
Unknown | 27 | 9% |