SMN1 (0MIM#600354) and its homologue, SMN2 (0MIM#601627), lie within the telomeric and centromeric halves, respectively, of a large inverted repeat in 5q13. SMN consists of nine exons (exons 1, 2a, 2b, 3 through 8), with the stop codon present near the end of exon 7. The coding sequence of SMN2 differs from that of SMN1 by a single nucleotide (840C>T) in exon 7. In contrast to SMN1, at least one copy of which is indispensable for the survival of motor neurons, ~ 5-10% of normal individuals lack both copies of SMN2. The failure of SMN2 to compensate fully for the loss of SMN1 is due to the sequence difference in exon 7. Although translationally silent, the 840C>T in SMN2 decreases the activity of an exonic splicing enhancer so that less full-length transcript is generated. A recent study also suggests the presence of exonic splicing silencer around the position 840 that is active in SMN2, but not in SMN1. SMN gene duplication occurred more than 5 million years ago, before the separation of human and chimpanzee lineages, but that the SMN2 gene sequence per se appeared for the first time only in Homo sapiens.
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