Spinal muscular atrophy diagnosis and carrier screening from genome sequencing data.
bioinformatics
carrier screening
copy-number analysis
genome sequencing (GS)
spinal muscular atrophy (SMA)
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
10
09
2019
accepted:
24
01
2020
revised:
22
01
2020
pubmed:
19
2
2020
medline:
28
4
2021
entrez:
19
2
2020
Statut:
ppublish
Résumé
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 and Genomics. 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. 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. 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.
Identifiants
pubmed: 32066871
doi: 10.1038/s41436-020-0754-0
pii: S1098-3600(21)00866-2
pmc: PMC7200598
doi:
Substances chimiques
Survival of Motor Neuron 1 Protein
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
945-953Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103446
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM114736
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG008901
Pays : United States
Organisme : Department of Health
ID : RG65966
Pays : United Kingdom
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