Determination of SMN1 and SMN2 Copy Numbers in a Korean Population using Multiplex Ligation-dependent Probe Amplification
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초록
Determination of the copy number of the survival motor neuron (SMN) gene is important for detecting spinal muscular atrophy (SMA) carriers and compound heterozygous patients. Multiplex ligationdependent probe amplification (MLPA) assay is a simple and efficient technique used for detecting variations in the copy numbers of different genes. Race- and ethnicity-based variation in the SMA carrier frequency and the ‘2+0’ genotype of SMN1 are important factors that should be considered when estimating the risk of being an SMA carrier. Since SMN2 plays a disease-modifying role, accurate determination of SMN2 copy numbers in SMA patients can serve as a useful prognostic tool. Therefore, information on the SMN2 genotype distributions in normal populations will be helpful in selecting appropriate reference samples for MLPA analysis. To determine SMA carrier frequencies and SMN genotype distribution, we determined the copy numbers of SMN1 and SMN2 genes using the MLPA assay in 100 unrelated Korean individuals with no family history of SMA. The frequency of SMA carriers in the Korean population appears to be 1 in 50, which indicates that the prevalence of SMA among Koreans is the same as that among individuals in the Western countries. Two of the 100 normal individuals enrolled in this study showed 3 copies of the SMN1 gene. Therefore, 1.0% of the 198 normal alleles in this population was estimated to be 2-copy alleles (‘2+0’ genotype). SMN2 copy numbers showed a high degree of individual variation. Our results showed that 64% of the individuals had 2 copies of SMN2, but 36% individuals had between 0, 1, or 3 copies of the gene. (Korean J Lab Med 2010;30:93-6)
Abstract
Determination of the copy number of the survival motor neuron (SMN) gene is important for detecting spinal muscular atrophy (SMA) carriers and compound heterozygous patients. Multiplex ligationdependent probe amplification (MLPA) assay is a simple and efficient technique used for detecting variations in the copy numbers of different genes. Race- and ethnicity-based variation in the SMA carrier frequency and the ‘2+0’ genotype of SMN1 are important factors that should be considered when estimating the risk of being an SMA carrier. Since SMN2 plays a disease-modifying role, accurate determination of SMN2 copy numbers in SMA patients can serve as a useful prognostic tool. Therefore, information on the SMN2 genotype distributions in normal populations will be helpful in selecting appropriate reference samples for MLPA analysis. To determine SMA carrier frequencies and SMN genotype distribution, we determined the copy numbers of SMN1 and SMN2 genes using the MLPA assay in 100 unrelated Korean individuals with no family history of SMA. The frequency of SMA carriers in the Korean population appears to be 1 in 50, which indicates that the prevalence of SMA among Koreans is the same as that among individuals in the Western countries. Two of the 100 normal individuals enrolled in this study showed 3 copies of the SMN1 gene. Therefore, 1.0% of the 198 normal alleles in this population was estimated to be 2-copy alleles (‘2+0’ genotype). SMN2 copy numbers showed a high degree of individual variation. Our results showed that 64% of the individuals had 2 copies of SMN2, but 36% individuals had between 0, 1, or 3 copies of the gene. (Korean J Lab Med 2010;30:93-6)
참고문헌 (12)
- Lefebvre S, "Identification and characterization of a spinal muscular atrophy-determining gene", Cell, 80, pp.155~165 (1995)
- Ogino S, "Spinal muscular atrophy: molecular genetics and diagnostics", Expert Rev Mol Diagn, 4, pp.15~29 (2004)
- Hendrickson BC, "Differences in SMN1 allele frequencies among ethnic groups within North America", J Med Genet, 46, pp.641~644 (2009)
- Prior TW, "Carrier screening for spinal muscular atrophy", Genet Med, 10, pp.840~842 (2008)
- Lee Tae Mi, "Quantitative Analysis of SMN1 Gene and Estimation of SMN1 Deletion Carrier Frequency in Korean Population based on Real-Time PCR", Journal of Korean Medical Science, 19(6), pp.870~873 (2004), 대한의학회
- Su YN, "Quantitative analysis of SMN1 and SMN2 genes based on DHPLC: a highly efficient and reliable carrier-screening test", Hum Mutat, 25, pp.460~467 (2005)
- van der Steege G, "PCR-based DNA test to confirm clinical diagnosis of autosomal recessive spinal muscular atrophy", Lancet, 345, pp.985~986 (1995)
- Wang CC, "Universal multiplex PCR and CE for quantification of SMN1", SMN2 genes in spinal muscular atrophy, 2009, pp.30, 1102~1110
- Scarciolla O, "Spinal muscular atrophy genotyping by gene dosage using multiple ligation-dependent probe amplification", Neurogenetics, 7, pp.269~276 (2006)
- Cusin V, "Prevalence of SMN1 deletion and duplication in carrier and normal populations:implication for genetic counselling", J Med Genet, 40, pp.e39~ (2003)
- Ogino S, "New insights on the evolution of the SMN1 and SMN2 region: simulation and meta-analysis for allele and haplotype frequency calculations", Eur J Hum Genet, 12, pp.1015~1023 (2004)
- Huang CH, "Copy number analysis of survival motor neuron genes by multiplex ligation-dependent probe amplification", Genet Med, 9, pp.241~248 (2007)