TY - JOUR
AU - Eberle, Michael A
AB - <p>Purpose
Spinal muscular atrophy (SMA), caused by loss of the SMN1 gene, is a leading cause of early childhood death. Due to the near identical sequences of SMN1 and SMN2, analysis of this region is challenging. Population-wide SMA screening to quantify the SMN1 copy number (CN) is recommended by the American College of Medical Genetics. 
Methods
We developed a method that accurately identifies the CN of SMN1 and SMN2 using genome sequencing (GS) data by analyzing read depth and eight informative reference genome differences between SMN1/2.
Results
We characterized SMN1/2 in 12,747 genomes, identified 1568 samples with SMN1 gains or losses and 6615 samples with SMN2 gains or losses and calculated a pan-ethnic carrier frequency of 2%, consistent with previous studies. Additionally, 99.8% of our SMN1 and 99.7% of SMN2 CN calls agreed with orthogonal methods, with a recall of 100% for SMA and 97.8% for carriers, and a precision of 100% for both SMA and carriers.
Conclusion
This SMN copy number caller can be used to identify both carrier and affected status of SMA, enabling SMA testing to be offered as a comprehensive test in neonatal care and an accurate carrier screening tool in GS sequencing projects.</p>
TI - Spinal muscular atrophy diagnosis and carrier screening from whole-genome sequencing data
JF - medRxiv
DO - 10.1101/19006635
DA - 2019-12-18
UR - https://www.deepdyve.com/lp/medrxiv/spinal-muscular-atrophy-diagnosis-and-carrier-screening-from-whole-Z6rnNAl8fv
SP - 19006635
DP - DeepDyve
ER -