New molecular research technologies in the study of muscle disease

Abstract

To describe the current technologies and progress in DNA polymorphism association studies, mRNA expression profiling (microarrays), and proteomics with respect to muscle disease, and the increasing impact of public-access databases of genome-wide information. mRNA expression profiling is becoming the most mature of the highly parallel molecular technologies, with microarrays now able to query the large majority of all genes using 1 million oligonucleotide probes built on 1.2-cm2 glass substrates. Applications of microarrays to normal muscle physiology and muscle disease are discussed. Single nucleotide polymorphism association studies promise to determine the predisposition of individuals to acquired muscle disease, including sarcopenia and atrophy, although such studies are in their infancy. Proteomics technologies do not enjoy the sensitivity and specificity of hybridization, and must instead rely on mass spectrometers. Mass spectrometry technology is advancing rapidly, although the sensitivity and throughput is far behind that of mRNA expression profiling. As the gene mutations responsible for many types of muscular dystrophy and myopathy have been discovered, protein and gene testing has been integrated into the standard patient diagnostic workup. Future developments will include simpler and less expensive molecular diagnostics, advances in the understanding of downstream consequences of these defects, and the genetic predispositions underlying acquired muscle disease.