Comprehensive genotyping of the C9orf72 hexanucleotide repeat region in 2095 ALS samples from the NINDS collection using a two-mode, long-read PCR assay.
C9orf72
GGGGCC hexanucleotide repeat
amyotrophic lateral sclerosis
frontotemporal dementia
microsatellite
repeat-primed PCR
Journal
Amyotrophic lateral sclerosis & frontotemporal degeneration
ISSN: 2167-9223
Titre abrégé: Amyotroph Lateral Scler Frontotemporal Degener
Pays: England
ID NLM: 101587185
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
pubmed:
16
11
2018
medline:
11
4
2020
entrez:
16
11
2018
Statut:
ppublish
Résumé
Expansion of the G A single-tube 3-primer PCR assay mode, resolved using capillary electrophoresis, was used for sizing up to 145 repeats with single-repeat accuracy, for detecting expansions irrespective of their overall size, and for flagging confounding 3' sequence variations (SVs). A modified two-primer PCR mode, resolved via agarose gel electrophoresis, provided further size information for hyper-expanded samples (>145 repeats) up to ∼5.8 kb amplicons (∼950 G Within the evaluated cohort, 177 (8.4%) samples were expanded, with 175 (99%) samples being hyper-expanded. 3'-SVs were identified in 64 (3.1%) samples, and were most common in expanded alleles. Genotypes of all 606 (29%) homozygous samples were confirmed using an orthogonal PCR assay. This study and PCR method may improve and standardize molecular characterization of the C9orf72 locus, and have the potential to inform phenotype-genotype correlations and therapeutic development in ALS/FTD.
Identifiants
pubmed: 30430876
doi: 10.1080/21678421.2018.1522353
pmc: PMC6513680
mid: NIHMS1520680
doi:
Substances chimiques
C9orf72 Protein
0
C9orf72 protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
107-114Subventions
Organisme : NINDS NIH HHS
ID : R44 NS089423
Pays : United States
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