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Biomarker for Spinal Muscular Atrophy: Expression of SMN in Peripheral Blood of SMA Patients and Healthy Controls.

Czech C, Tang W, Bugawan T, Mano C, Horn C, Iglesias VA, Fröhner S, Zaworski PG, Paushkin S, Chen K, Kremer T - PLoS ONE (2015)

Bottom Line: SMA patients have at least one copy of a similar gene, SMN2, which produces functional SMN protein, although in reduced quantities.SMN copy number, mRNA and Protein levels in whole blood of patients were measured and compared against a cohort of healthy controls.The results show differential regulation of expression of SMN2 in peripheral blood between patients and healthy subjects.

View Article: PubMed Central - PubMed

Affiliation: Roche Pharmaceutical Research & Early Development, Neuroscience, Roche Innovation Center Basel F. Hoffmann -La Roche, Basel.

ABSTRACT
Spinal muscular atrophy is caused by a functional deletion of SMN1 on Chromosome 5, which leads to a progressive loss of motor function in affected patients. SMA patients have at least one copy of a similar gene, SMN2, which produces functional SMN protein, although in reduced quantities. The severity of SMA is variable, partially due to differences in SMN2 copy numbers. Here, we report the results of a biomarker study characterizing SMA patients of varying disease severity. SMN copy number, mRNA and Protein levels in whole blood of patients were measured and compared against a cohort of healthy controls. The results show differential regulation of expression of SMN2 in peripheral blood between patients and healthy subjects.

No MeSH data available.


Related in: MedlinePlus

SMN copy number determines expression of SMN in healthy subjects.The copy number and the expression levels of SMN2 are closely linked; two copies show almost double expression of SMN2. Expression level is calculated using 2ˆ-deltaCp of the reference gene. Copy number is determined using digital PCR as described in Methods. Similar for SMN1, increases in copy number lead to increases in mRNA expression.
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pone.0139950.g002: SMN copy number determines expression of SMN in healthy subjects.The copy number and the expression levels of SMN2 are closely linked; two copies show almost double expression of SMN2. Expression level is calculated using 2ˆ-deltaCp of the reference gene. Copy number is determined using digital PCR as described in Methods. Similar for SMN1, increases in copy number lead to increases in mRNA expression.

Mentions: Interestingly, as shown in Fig 2, there is a very close match of SMN copy number and level of mRNA expression in healthy subjects. Two copies of SMN2 leads to almost doubling of the average mRNA expression levels in the subjects (1 SMN2 copy = 0.069 and 2 SMN2 copies = 0.128) (Fig 2A) and also increasing the copy number of SMN1 leads to a concomitant increase of SMN1 expression (2 copies = 0.31; 3 copies = 0.44; 4 copies = 0.48) (Fig 2B). The association between copy number and transcript level is stronger for SMN2 compared to SMN1. These data suggest that the expression of SMN mRNA in healthy subjects is proportional to the number of gene copies.


Biomarker for Spinal Muscular Atrophy: Expression of SMN in Peripheral Blood of SMA Patients and Healthy Controls.

Czech C, Tang W, Bugawan T, Mano C, Horn C, Iglesias VA, Fröhner S, Zaworski PG, Paushkin S, Chen K, Kremer T - PLoS ONE (2015)

SMN copy number determines expression of SMN in healthy subjects.The copy number and the expression levels of SMN2 are closely linked; two copies show almost double expression of SMN2. Expression level is calculated using 2ˆ-deltaCp of the reference gene. Copy number is determined using digital PCR as described in Methods. Similar for SMN1, increases in copy number lead to increases in mRNA expression.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4607439&req=5

pone.0139950.g002: SMN copy number determines expression of SMN in healthy subjects.The copy number and the expression levels of SMN2 are closely linked; two copies show almost double expression of SMN2. Expression level is calculated using 2ˆ-deltaCp of the reference gene. Copy number is determined using digital PCR as described in Methods. Similar for SMN1, increases in copy number lead to increases in mRNA expression.
Mentions: Interestingly, as shown in Fig 2, there is a very close match of SMN copy number and level of mRNA expression in healthy subjects. Two copies of SMN2 leads to almost doubling of the average mRNA expression levels in the subjects (1 SMN2 copy = 0.069 and 2 SMN2 copies = 0.128) (Fig 2A) and also increasing the copy number of SMN1 leads to a concomitant increase of SMN1 expression (2 copies = 0.31; 3 copies = 0.44; 4 copies = 0.48) (Fig 2B). The association between copy number and transcript level is stronger for SMN2 compared to SMN1. These data suggest that the expression of SMN mRNA in healthy subjects is proportional to the number of gene copies.

Bottom Line: SMA patients have at least one copy of a similar gene, SMN2, which produces functional SMN protein, although in reduced quantities.SMN copy number, mRNA and Protein levels in whole blood of patients were measured and compared against a cohort of healthy controls.The results show differential regulation of expression of SMN2 in peripheral blood between patients and healthy subjects.

View Article: PubMed Central - PubMed

Affiliation: Roche Pharmaceutical Research & Early Development, Neuroscience, Roche Innovation Center Basel F. Hoffmann -La Roche, Basel.

ABSTRACT
Spinal muscular atrophy is caused by a functional deletion of SMN1 on Chromosome 5, which leads to a progressive loss of motor function in affected patients. SMA patients have at least one copy of a similar gene, SMN2, which produces functional SMN protein, although in reduced quantities. The severity of SMA is variable, partially due to differences in SMN2 copy numbers. Here, we report the results of a biomarker study characterizing SMA patients of varying disease severity. SMN copy number, mRNA and Protein levels in whole blood of patients were measured and compared against a cohort of healthy controls. The results show differential regulation of expression of SMN2 in peripheral blood between patients and healthy subjects.

No MeSH data available.


Related in: MedlinePlus