? Spinal muscular atrophy (SMA) is the second most common autosomal recessive disease and is caused by the absence of a functional copy of the survival motor neuron 1 (SMN1) gene. A nearly identical gene, SMN2, is present in SMA patients although it cannot provide protection from SMA development even though SMN1 and SMN2 are greater than 99% identical at the nucleotide level and encode identical proteins. The reason for differences in SMA protection is that a single, non-polymorphic nucleotide difference results in an exon-skipping event in SMN2-derived RNA transcripts, resulting in a C-terminally truncated protein that is partially defective compared to the full-length SMN protein. The objective of this research is to address the molecular basis for this developmental neuuronal disorder and the fundamental questions of RNA processing. This objective will be accomplished by utilizing in vivo and in vitro splicing assays and proteomics to identify the characteristic determinants that regulate splicing of SMN exon 7, an important exon for the functional form of the SMN protein. ? ?
| Hu-Lince, Diane; Craig, David W; Huentelman, Matthew J et al. (2005) The Autism Genome Project: goals and strategies. Am J Pharmacogenomics 5:233-46 |
| Puffenberger, Erik G; Hu-Lince, Diane; Parod, Jennifer M et al. (2004) Mapping of sudden infant death with dysgenesis of the testes syndrome (SIDDT) by a SNP genome scan and identification of TSPYL loss of function. Proc Natl Acad Sci U S A 101:11689-94 |
