A common spinal muscular atrophy deletion mutation is present on a single founder haplotype in the US Hutterites

作者：Chong Jessica X^*; Oktay A Afsin; Dai Zunyan; Swoboda Kathryn J; Prior Thomas W; Ober Carole

来源：European Journal of Human Genetics, 2011, 19(10): 1045-1051.

DOI：10.1038/ejhg.2011.85

• spinal muscular atrophy
• Hutterites
• founder population
• haplotype
• carrier frequency
• carrier screening

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 similar to 1 in 35 in US Whites. As part of our genetic studies in the Hutterites from South Dakota, we identified a large 22Mb 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 similar to 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. European Journal of Human Genetics (2011) 19, 1045-1051; doi:10.1038/ejhg.2011.85; published online 25 May 2011

• 出版日期2011-10