Open AccessSMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR
Author(s) -
Stabley Deborah L.,
Harris Ashlee W.,
Holbrook Jennifer,
Chubbs Nicholas J.,
Lozo Kevin W.,
Crawford Thomas O.,
Swoboda Kathryn J.,
Funanage Vicky L.,
Wang Wenlan,
Mackenzie William,
Scavina Mena,
SolChurch Katia,
Butchbach Matthew E. R.
Publication year - 2015
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.141
Subject(s) - smn1 , spinal muscular atrophy , sma* , copy number variation , digital polymerase chain reaction , biology , motor neuron , gene duplication , copy number analysis , gene dosage , population , exon , microbiology and biotechnology , genetics , gene , medicine , genome , polymerase chain reaction , gene expression , neuroscience , computer science , spinal cord , environmental health , algorithm
Proximal spinal muscular atrophy ( SMA ) is an early‐onset motor neuron disease characterized by loss of α ‐motor neurons and associated muscle atrophy. SMA is caused by deletion or other disabling mutation of survival motor neuron 1 ( SMN 1 ). In the human genome, a large duplication of the SMN ‐containing region gives rise to a second copy of this gene ( SMN 2 ) that is distinguishable by a single nucleotide change in exon 7. Within the SMA population, there is substantial variation in SMN 2 copy number; in general, those individuals with SMA who have a high SMN 2 copy number have a milder disease. Because SMN 2 functions as a disease modifier, its accurate copy number determination may have clinical relevance. In this study, we describe the development of an assay to assess SMN 1 and SMN 2 copy numbers in DNA samples using an array‐based digital PCR ( dPCR ) system. This dPCR assay can accurately and reliably measure the number of SMN 1 and SMN 2 copies in DNA samples. In a cohort of SMA patient‐derived cell lines, the assay confirmed a strong inverse correlation between SMN 2 copy number and disease severity. Array dPCR is a practical technique to determine, accurately and reliably, SMN 1 and SMN 2 copy numbers from SMA samples.