Andrew Douglas
Senior Clinical Research Fellow in Motor Neuron Disease
Genetics of motor neuron disease
I am a consultant in clinical genetics at the Oxford Centre for Genomic Medicine. I have a specialist interest in neurogenetics and am studying the genetics of motor neuron disease.
Most cases of motor neuron disease (MND) are not caused by strong genetic factors and only 5-10% of cases are familial. In familial cases, a genetic mutation can be identified in up to around two thirds of cases. However, around 10% of all MND cases are found to have mutations affecting known genes linked to the condition, even where there is no wider family history of neurodegenerative disease.
Some people who carry a mutation in a gene linked to MND go on to develop the condition but others do not. The reason for this variability in disease penetrance remains unknown. I am studying the disease penetrance of MND in people known to carry MND gene mutations by looking at individual family histories and also by analysing genetic data.
Through this research, I hope to develop a more accurate model for predicting individualised risk in people with a family history of MND. This will allow at-risk relatives to make better-informed decisions about their care and may also help identify protective genetic factors which could be turned into novel therapeutic approaches.
Other research interests of mine include: the genetics of neurodegenerative disorders, the genetics of neuromuscular disorders, RNA splicing and oligonucleotide therapeutics.
Recent publications
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Personalised penetrance estimation forC9orf72-related amyotrophic lateral sclerosis and frontotemporal dementia
Journal article
Douglas AGL. et al, (2024), BMJ Neurology Open, 6, e000792 - e000792
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Reduced penetrance of gene variants causing amyotrophic lateral sclerosis.
Journal article
Douglas AGL. and Baralle D., (2023), J Med Genet
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RNA-sequencing first approach generates new diagnostic candidates in Mendelian disorders
Preprint
Jaramillo Oquendo C. et al, (2023)
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Predicting the impact of rare variants on RNA splicing in CAGI6
Preprint
Lord J. et al, (2023)
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ATP6V0C variants impair V-ATPase function causing a neurodevelopmental disorder often associated with epilepsy
Journal article
Mattison KA. et al, (2023), Brain, 146, 1357 - 1372