Can bioinformatics help trace the steps from gene mutation to disease?

In this issue of Neurology , Minassian et al. expand their earlier contributions on Lafora’s disease using new informational technology to seek homologies between regions of the EMP2A gene product laforin and other proteins of known biological activity.1 This direct application of genomics to a clinical problem may clarify a mechanism of pathogenesis and provide rationale for future therapies. Genomics uses 1) DNA sequence data and 2) computational systems to store, access and analyze the data. Together, these constitute the new field of bioinformatics. Gene sequence data were historically obtained from messenger RNA transcripts of well-known proteins (such as hemoglobin and ovalbumin). The Human Genome Project (HGP) provides DNA sequences for “new” genes without known function, based on nucleotide patterns characteristic of gene structure. The path from these newly discovered genes to the biological activities of their products requires a multifaceted approach.2 Sequence data from the HGP also allows a correlation to be made between a change in genetic structure (a mutation, deletion, or recombination) and the occurrence of disease. Bioinformatics will not explain how a gene is regulated or how changes in regulation induce disease. However, new technology to define patterns of gene transcription (a key to gene expression) is rapidly developing (table 1). View this table: Table 1. Applications for bioinformatics in research and medicine Broad access to genomic information is now possible through highly refined user-friendly software. BLAST (Basic Local Alignment Search Tool), for example, is a sensitive and time effective program for detection of biologically significant relationships between genetic molecular structure and …