Using Massively Parallel Reporter Assays (MPRAs) to elucidate the function of genetic variation

This is a preview of the full post which can be found on Twist’s blog.

Molecular biology has seen a windfall of data over the past 15 years thanks to the proliferation of Next Generation Sequencing (NGS) technology. Genetic data of unprecedented detail can now be gathered on a population scale and leveraged for pharmacogenomics, personalized medicine, preventative healthcare, and to advance our understanding of basic genetics. 

To realize the potential of this data researchers must first be able to elucidate the impact of genetic changes. When changes are found in protein-coding regions, the effect can be predicted based on known codon sequences. If the changes occur in non-protein-coding regions, however, the analysis becomes much more difficult.

98% of the human genome consists of non-protein-coding DNA, much of which has unknown functions. Nonetheless, noncoding DNA houses important genetic elements that can alter gene expression levels through genetic and epigenetic means, such as enhancers, silencers, promoters, and other so-called regulatory elements. The average protein-coding gene is governed by multiple non-coding regulatory elements whose activity can vary in a context-dependent manner, making it exceedingly difficult to both identify these elements and link them to the transcriptional activity of specific genes.  

Without a detailed understanding of these regulatory elements, potentially clinically relevant information coded within the growing influx of genetic data will remain undiscovered.  

To help convert data into knowledge, researchers are turning to Massively Parallel Reporter Assays (MPRAs).

Read the full article on Twist’s blog.