Gene scanning technology advances disease research

Researchers from the University of Southampton​ have devised a method, which combines thermal ramp electrophoresis with microplate array diagonal gel electrophoresis (MADGE), enabling higher levels of scanning at a fraction of the cost.

The technique, called meltMADGE, has been applied to search for rare genetic mutations in the population at large, having been used in a nationwide study in collaboration with a network of British medical researchers from the Universities of Southampton, Bristol and University College London,

In analyses of nearly 10,000 middle-aged individuals, researchers found rare mutations associated with high cholesterol, some with moderately high cholesterol and some with no effect.

This is the first time that it has been possible to find out whether there may be unknown rare genetic variations in the population, which may cause mild forms of a particular disease or feature in just one or two individuals, or may even protect them against disease.

"This development enables us to look at the whole population and find rare and "special" individuals with gene changes which may have either mild, moderate, severe or protective disease effects,"​ said Professor Ian Day, team leader at the human genetics division of the University's School of Medicine.

Professor Day's group is using combinations of meltMADGE and a second technology called endo VII MADGE to explore variations in the whole population of disease genes relevant to growth, obesity and cardiovascular disease.

The method, meltMADGE, is a reconfiguration of denaturing gradient gel electrophoresis (DGGE) (using a thermal ramp rather than a urea gradient) enabling combination with microplate array diagonal gels (MADGE). MADGE is a simple and highly effective method for high throughput screening.

It uses a 96 well gel in exactly the same format as a 96 well plate with electrophoresis occurring at an angle such that the electrophoretic path bypasses adjoining rows of wells.

By running the gel using this diagonal path, a run length of up to 26.5mm can be achieved. This allows enough separation to calculate molecular weight data and identify doublet bands. As well as the 96 well format, 192 or even 364 wells can be run out simultaneously using MADGE.

Many industry analysts believe the emergence of personalised therapy will become the biggest thing to hit the pharmaceutical industry, changing the way treatments are administered and managed.

In the future it may be possible for doctors to provide a personalised treatment for virtually any illness through the analysis of a blood sample. Similarly, doctors could also spot potential illnesses before they become a problem and take preventative measures.

The Pharmaceutical Research and Manufacturers Association of America estimates that about $100 million (€77 million) are wasted every year in the US alone because patients take drugs that are ineffective or have serious side effects.