Identity by descent analysis identifies founder events and links SOD1 familial and sporadic ALS cases.

Autor:	Henden L; Macquarie University Centre for Motor Neuron Disease Research, Department of Biological Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW Australia., Twine NA; Transformational Bioinformatics, Commonwealth Scientific and Industrial Research Organisation, Sydney, NSW Australia., Szul P; Data61, Commonwealth Scientific and Industrial Research Organisation, Dutton Park, QLD Australia., McCann EP; Macquarie University Centre for Motor Neuron Disease Research, Department of Biological Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW Australia., Nicholson GA; Macquarie University Centre for Motor Neuron Disease Research, Department of Biological Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW Australia.; Concord Clinical School, ANZAC Research Institute, Concord Repatriation Hospital, Sydney, NSW Australia.; Sydney Medical School, University of Sydney, Sydney, NSW Australia., Rowe DB; Macquarie University Centre for Motor Neuron Disease Research, Department of Biological Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW Australia.; Department of Clinical Medicine, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW Australia., Kiernan MC; Brain and Mind Centre, The University of Sydney, Sydney, NSW Australia.; Department of Neurology, Royal Prince Alfred Hospital, Sydney, NSW Australia., Bauer DC; Transformational Bioinformatics, Commonwealth Scientific and Industrial Research Organisation, Sydney, NSW Australia., Blair IP; Macquarie University Centre for Motor Neuron Disease Research, Department of Biological Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW Australia., Williams KL; Macquarie University Centre for Motor Neuron Disease Research, Department of Biological Sciences, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW Australia.
Jazyk:	angličtina
Zdroj:	NPJ genomic medicine [NPJ Genom Med] 2020 Aug 07; Vol. 5, pp. 32. Date of Electronic Publication: 2020 Aug 07 (Print Publication: 2020).
DOI:	10.1038/s41525-020-00139-8
Abstrakt:	Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterised by the loss of upper and lower motor neurons resulting in paralysis and eventual death. Approximately 10% of ALS cases have a family history of disease, while the remainder present as apparently sporadic cases. Heritability studies suggest a significant genetic component to sporadic ALS, and although most sporadic cases have an unknown genetic aetiology, some familial ALS mutations have also been found in sporadic cases. This suggests that some sporadic cases may be unrecognised familial cases with reduced disease penetrance in their ancestors. A powerful strategy to uncover a familial link is identity-by-descent (IBD) analysis, which detects genomic regions that have been inherited from a common ancestor. IBD analysis was performed on 83 Australian familial ALS cases from 25 families and three sporadic ALS cases, each of whom carried one of three SOD1 mutations (p.I114T, p.V149G and p.E101G). We defined five unique 350-SNP haplotypes that carry these mutations in our cohort, indicative of five founder events. This included two founder haplotypes that carry SOD1 p.I114T; linking familial and sporadic cases. We found that SOD1 p.E101G arose independently in each family that carries this mutation and linked two families that carry SOD1 p.V149G. The age of disease onset varied between cases that carried each SOD1 p.I114T haplotype. Linking families with identical ALS mutations allows for larger sample sizes and increased statistical power to identify putative phenotypic modifiers. Competing Interests: Competing interestsThe authors declare no competing interests. (© The Author(s) 2020.)
Databáze:	MEDLINE
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