Fig. 2.

The SMN locus on human Chromosome 5. Virtually all cases of SMA result from a loss of function in SMN1. However, the inverted duplication harboring SMN2 determines the severity of the disease. The SMN2 gene is present with variable copy number (between zero and eight), and all copies carry a C > T transition that reduces splicing efficiency and skips exon 7 in ~ 90% of transcripts, leading to low levels of full-length protein. The duplication creating the SMN2 gene is specific to humans, but its presence is critical to creating models that survive and have a phenotype that resembles SMA, and for testing approaches aimed at correcting its splicing and increasing the levels of full-length transcript