Chen, Z;
Lin, K;
Macklis, JD;
Al-Chalabi, A;
(2016)
Proposed association between the hexanucleotide repeat of C9orf72 and opposability index of the thumb.
Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
, 18
(3-4)
pp. 175-181.
10.1080/21678421.2016.1257024.
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Abstract
OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal disease caused by motor neuron and sub-cerebral projection neuron degeneration. We sought to explore the particular susceptibility of humans to neurodegeneration and whether any characteristic human features might predispose to selective vulnerability of the critical motor circuitry in ALS. The pathophysiology of the C9orf72 repeat is not yet understood, despite its role as a common cause of ALS and frontotemporal dementia. METHODS: We examined the development of the monosynaptic cortico-motoneuronal system, key to skilled hand movements, measured by the thumb opposability index, and its relationship to the C9orf72 hexanucleotide repeat expansion, a strong predisposing factor for neurodegeneration, using the genomic tool BLAST. RESULTS: We found a statistically significant linear relationship between the C9orf72 hexanucleotide bit score, a measure of genomic conservation of the aligned region across different species, and the thumb opposability index (Pearson's correlation coefficient of 0.78, p value 0.023). The C9orf72 hexanucleotide repeat was only found in humans, chimpanzees and gorillas, species with higher opposability indices. CONCLUSIONS: This may support a role of the hexanucleotide repeat in the same developmental pathways in species with higher prehensility, which may be associated with the selective vulnerability of cortico-motoneuronal cells in humans, manifested most obviously as the 'split hand' syndrome in ALS.
| Type: | Article |
|---|---|
| Title: | Proposed association between the hexanucleotide repeat of C9orf72 and opposability index of the thumb |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1080/21678421.2016.1257024 |
| Publisher version: | https://doi.org/10.1080/21678421.2016.1257024 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | C9orf72, cortico-motoneuronal vulnerability, thumb opposability, Amyotrophic Lateral Sclerosis, Animals, C9orf72 Protein, Efferent Pathways, Gorilla gorilla, Hand, Haplorhini, Motor Skills, Pan troglodytes, Repetitive Sequences, Nucleic Acid, Species Specificity, Thumb |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10058759 |
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