<i>SMN1</i>copy-number and sequence variant analysis from next generation sequencing data

López-López, Daniel; Loucera, Carlos; Carmona, Rosario; Aquino, Virginia; Salgado, Josefa; Pasalodos, Sara; Miranda, María; Alonso, Angel; Dopazo, Joaquı́n

doi:10.1101/2020.03.31.014589

Cited by 3 publications

(2 citation statements)

References 13 publications

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“…SMN1 copy numbers were calculated based on an approach previously described 53 . Briefly, raw proportions of SMN1 reads over the total number of SMN1 and SMN2 reads were calculated at three genomic positions that differ between the two genes, SMN1: chr5:70247724, chr5:70247773, chr5:70247921, and SMN2: chr5:69372304, chr5:69372353, chr5:69372501.…”

Section: Smn1 Copy Number Detectionmentioning

confidence: 99%

Assessing clinical utility of preconception expanded carrier screening regarding residual risk for neurodevelopmental disorders

et al. 2022

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The magnitude of clinical utility of preconception expanded carrier screening (ECS) concerning its potential to reduce the risk of affected offspring is unknown. Since neurodevelopmental disorders (NDDs) in their offspring is a major concern of parents-to-be, we addressed the question of residual risk by assessing the risk-reduction potential for NDDs in a retrospective study investigating ECS with different criteria for gene selection and definition of pathogenicity. We used exome sequencing data from 700 parents of children with NDDs and blindly screened for carrier-alleles in up to 3046 recessive/X-linked genes. Depending on variant pathogenicity thresholds and gene content, NDD-risk-reduction potential was up to 43.5% in consanguineous, and 5.1% in nonconsanguineous couples. The risk-reduction-potential was compromised by underestimation of pathogenicity of missense variants (false-negative-rate 4.6%), inherited copy-number variants and compound heterozygosity of one inherited and one de novo variant (0.9% each). Adherence to the ACMG recommendations of restricting ECS to high-frequency genes in nonconsanguineous couples would more than halve the detectable inherited NDD-risk. Thus, for optimized clinical utility of ECS, screening in recessive/X-linked genes regardless of their frequency (ACMG Tier-4) and sensible pathogenicity thresholds should be considered for all couples seeking ECS.

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Section: Smn1 Copy Number Detectionmentioning

confidence: 99%

Assessing clinical utility of preconception expanded carrier screening regarding residual risk for neurodevelopmental disorders

et al. 2022

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“…The Denaturing high performance liquid chromatography (DHPLC) could be used to detect the copies of the SMN gene by comparing the peak of amplified product with the reference, but is labor highly demanding detection environment [13,14]. Next-generation sequencing (NGS) requires relative high sequencing depth to obtain accurate carrier gene, which need deep bioinformation analysis and increases the costs [15]. High resolution melting analysis (HRMA) was applied to SMA detection which has been demonstrated in recent studies.…”

Section: Introductionmentioning

confidence: 99%

Copy number assessment of SMN1 based on real-time PCR with high-resolution melting: fast and highly reliable testing

Xu¹,

Song²,

Wang³

et al. 2022

Brain and Development

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Copy Number Assessment of SMN1 Based on Real-Time PCR With High-Resolution Melting: Fast and Highly Reliable Testing

Xu¹,

Song²,

Wang³

et al. 2021

Preprint

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Background: Spinal muscular atrophy (SMA) is a common neuromuscular disorder, caused by absence of both copies of the survival motor neuron 1 (SMN1) gene. Population-wide SMA screening to quantify copy number of SMN1 is recommended by multiple regions. SMN1 diagnostic assay with simplified procedure, high sensitivity and throughput is still needed.Methods: Real-Time PCR with High-Resolution Melting for the quantification of the SMN1 gene exon 7 copies and SMN1 gene exon 8 copies was established and confirmed by multiplex ligation-dependent probe amplification (MLPA). The diagnosis of 2563 individuals including SMA patients, suspected cases and the general population were analyzed by the real-time PCR. The results were compared with the gold standard test MPLA. Results: In this study, the homozygous deletions, heterozygous deletions were identified by Real-Time PCR with High-Resolution Melting method with an incidence of 10.18% and 2.42%, respectively. In addition, the R value distribution (P>0.05) among the 8 replicates and the coefficient of variation (CV<0.003) suggested that the qPCR screening test had high reproducibility. High concordance was obtained between Real-Time PCR with High-Resolution Melting and MPLA. Conclusions: The qPCR based on High-Resolution Melting provides a sensitive and high-throughput approach to large-scale SMA carrier screening with low cost and labor.

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SMN1copy-number and sequence variant analysis from next generation sequencing data

Cited by 3 publications

References 13 publications

Assessing clinical utility of preconception expanded carrier screening regarding residual risk for neurodevelopmental disorders

Assessing clinical utility of preconception expanded carrier screening regarding residual risk for neurodevelopmental disorders

Copy number assessment of SMN1 based on real-time PCR with high-resolution melting: fast and highly reliable testing

Copy Number Assessment of SMN1 Based on Real-Time PCR With High-Resolution Melting: Fast and Highly Reliable Testing

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