A common spinal muscular atrophy deletion mutation is present on a single founder haplotype in the US Hutterites
| العنوان: | A common spinal muscular atrophy deletion mutation is present on a single founder haplotype in the US Hutterites |
|---|---|
| المؤلفون: | Thomas W. Prior, Zunyan Dai, Jessica X. Chong, Kathryn J. Swoboda, Carole Ober, A Afşin Oktay |
| المصدر: | European Journal of Human Genetics. 19:1045-1051 |
| بيانات النشر: | Springer Science and Business Media LLC, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Adult, Male, Heterozygote, Adolescent, Genotype, Population, Genetic Carrier Screening, Single-nucleotide polymorphism, SMN1, Biology, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Sensitivity and Specificity, White People, Article, Muscular Atrophy, Spinal, Young Adult, Genetics, medicine, Humans, Child, education, Genetics (clinical), Aged, Sequence Deletion, Aged, 80 and over, education.field_of_study, Montana, Haplotype, Spinal muscular atrophy, Middle Aged, medicine.disease, Survival of Motor Neuron 1 Protein, Founder Effect, Haplotypes, South Dakota, Female, Founder effect |
| الوصف: | Spinal muscular atrophy (SMA) is an autosomal recessive (AR) neuromuscular disease that is one of the most common lethal genetic disorders in children, with carrier frequencies as high as ∼1 in 35 in US Whites. As part of our genetic studies in the Hutterites from South Dakota, we identified a large 22 Mb run of homozygosity, spanning the SMA locus in an affected child, of which 10 Mb was also homozygous in three affected Hutterites from Montana, supporting a single founder origin for the mutation. We developed a haplotype-based method for identifying carriers of the SMN1 deletion that leveraged existing genome-wide SNP genotype data for ∼1400 Hutterites. In combination with two direct PCR-based assays, we identified 176 carriers of the SMN1 deletion, one asymptomatic homozygous adult and three carriers of a de novo deletion. This corresponds to a carrier frequency of one in eight (12.5%) in the South Dakota Hutterites, representing the highest carrier frequency reported to date for SMA and for an AR disease in the Hutterite population. Lastly, we show that 26 SNPs can be used to predict SMA carrier status in the Hutterites, with 99.86% specificity and 99.71% sensitivity. |
| تدمد: | 1476-5438 1018-4813 |
| DOI: | 10.1038/ejhg.2011.85 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::26a9d0c240680cf16e3f3a3887b28d06 https://doi.org/10.1038/ejhg.2011.85 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....26a9d0c240680cf16e3f3a3887b28d06 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765438 10184813 |
|---|---|
| DOI: | 10.1038/ejhg.2011.85 |