SINEs of destruction

Abstract

Fukuyama-type congenital muscular dystrophy (FCMD) is among the most common autosomal recessive disorders in Japan. Kobayashi et al., 1998xAn ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy. Kobayashi, K. et al. Nature. 1998; 394: 388–392Crossref | PubMed | Scopus (0)See all ReferencesKobayashi et al., 1998have now shown that in 87% of cases it is associated with a 3-kb insertion into the 3′ untranslated region of the FCMD gene located on Chromosome 9 of the human genome. FCMD codes for fukutin, which is thought to be a secreted protein but whose function in the pathogenesis of muscular dystrophies is not yet understood. The inserted DNA sequence causes a decrease of transcription and/or an instability of mRNA, resulting in loss of function. It represents a complex retrotransposon-like insertion containing tandemly repeated sequences and a SINE (short interspersed nuclear element). This mutation appears to be the result of an ancient retrotransposition event, indicated by a 17-bp target-site duplication flanking the inserted sequence. SINE sequences included in this retrotranscript infest the human genome and comprise >10% of its DNA. Alu, a SINE, is already known to cause new mutations, such as an insertion in the NF1 gene, which results in neurofibromatosis. The insertion of another mobile element, the human retrotransposon LINE 1 (long interspersed nuclear element 1) into specific genes has been shown to be the cause of human diseases such as haemophilia, Duchenne muscular dystrophy and colon cancer. We should be prepared to hear more in the future about these mobile elements as a cause of genetic disorders.