Open Access
ARTICLE
The impact of paralog genes: detection of copy number variation in spinal muscle atrophy patients
Sergio LAURITO1, 2, Juan A. CUETO1, 3, Jimena PEREZ1, María ROQUÉ1, 2
1
IHEM, Universidad Nacional de Cuyo, CONICET
2
Departamento de Biología, Universidad Nacional de Cuyo, Facultad de Ciencias Exactas y Naturales
3
Instituto de Fisiología, Universidad Nacional de Cuyo, Facultad de Ciencias Médicas
* Address correspondence to: María Roqué,
BIOCELL 2018, 42(3), 87-92. https://doi.org/10.32604/biocell.2018.07016
Abstract
Spinal muscular atrophy (SMA) is caused by dysfunction of the alpha motor neurons of the spinal cord.
It is an autosomal recessive disease associated to the SMN1 gene, located in the subtelomeric region of 5q13. A
paralog SMN2 gene is located at the centromeric region of the same chromosome, which apparently originated by
an ancestral inverted duplication occurring only in humans. The exon sequence differs in two nucleotides in exon 7
and exon 8, which leads to an SMN2 transcript that lacks exon 7 and results in a truncated protein. Part (10%) of the
SMN2 transcripts avoids the splicing of exon 7 but most of the copies are dysfunctional. In a disease scenario, the
more SMN2 copies the higher possibility to restore at least partly the effects of SMN1 deficiency. Some therapeutic
approaches are being developed to increase the expression of SMN2. To determine the number of SMN1 and SMN2
copies, the methodology must distinguish accurately between both genes. In this work, we present the results obtained
using multiplex ligation-dependent probe amplification (MLPA) in 60 SMA suspected patients/carriers derived from
different regions of Argentina. In 32 of these DNA samples we found alterations in SMN1. Among these, 16 presented a
heterozygous deletion (carrier status) and 14 an homozygous deletion (patient status) in exon 7 and 8 of SMN1. In one
case, exon 7 was found homozygously deleted but exon 8 presented a single copy, and in another case, exon 7 was found
heterozygously deleted while exon 8 was normal. Almost half of the patients (7/15) presented a normal diploid number
of SMN2 while the other half (8/15) presented an increased number. In this work we showed how a probe-based
methodology such as MLPA was able to distinguish between the paralog genes and determine the amount of copies in
DNA samples from suspected patients/carriers of SMA.
Keywords
Cite This Article
LAURITO, S., CUETO, J. A., PEREZ, J., ROQUÉ, M. (2018). The impact of paralog genes: detection of copy number variation in spinal muscle atrophy patients.
BIOCELL, 42(3), 87–92.
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