Current Techniques Used In Medical Genomics

Genomic variations that influence disease predisposition or response to pharmaceutical therapies (see pharmacogenetics) are not simple to characterize. Clinically useful techniques must be able to detect a few mutations, such as associated with hereditary hemochromatosis (two single nucleotide polymorphism sites), or many mutations, such as associated with cystic fibrosis (>1000 mutations). Differences in drug response can be monogenic, but more typically they are caused by a combination of several genes.[1] Recognition of onset of disease such as cancer, and monitoring treatments, depends on identification of neoplastic markers. Research continues with the goal to identify genetic mutations and gene expression changes associated with disease, disease progression, and response to treatment.

An assortment of methods is currently used in genomic research and for molecular diagnostics. DNA microarrays are the first widely used research tool to couple signal generation directly to DNA hybridization to measure genomic variations. For example, recent research using microarrays has identified gene expression changes associated with breast cancer stages.[2] However, micro-array use as clinical tool is limited by the number of manual steps involved, the time required, cost, and often by the variability between samples and between labora-tories.[3] Current clinical techniques frequently use ''home-brew'' assays and commercial instruments that require analyte-specific reagents (ASRs). In-house validation is essential and all laboratories are required to be CLIA (Clinical Laboratory Improvement Amendments) certified (http://www.cms.hhs.gov/clia).[4] Clinical laboratories currently identify single nucleotide polymorphisms (SNPs) and other diagnostic mutations using platforms that include allele-specific amplification, chemiluminescent forward dot blot assay, dot blot hybridization, gel-based restriction fragment length polymorphism (RFLP) analysis, oligonucleotide ligation, primer extension, multiplex PCR. Also in use are commercial kits such as mDx platform for hereditary hemochromatosis and Factor VLeiden from Bio-Rad Laboratories (Hercules, CA) and the Amplichip CYP450 Array that identifies common mutations associated with poor or rapid drug metabolisms from Roche Diagnostics (Indianapolis, IN). Solution-based biosensors have debuted in the clinical laboratory in the form of fluorescence resonance energy transfer (FRET) probes used in real-time PCR. Systems using TaqMan™, molecular beacon, or Scorpion™ primers fluoresce as DNA target replication proceeds, and results can be generated within 20 min to 2 hr.[5] However, typical laboratory turnaround times using these tools are on the order of weeks; as with DNA microarray analysis, multiple manual steps are involved that take time and can introduce human error. Depending on the particular test, concerns also include sample size, cost, scalability, and limited adaptability.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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