New gene sequencing technique opens door to improved organ donor matching

A team of Australian biomedical scientists from Monash University has discovered a novel technique to reveal hitherto difficult to access layers of information about individuals’ genetic make-up. Initially, the new technique could be applied to enable more successful matching of organ donors with recipients, but ultimately it could have applications for treating a wide array of diseases.

In a study published on 27 July in Scientific Reports, Associate Professor Helen Irving and Professor Colin Pouton of Monash Institute of Pharmaceutical Sciences, and Dr Nick Murphy, a Monash PhD graduate now at Melbourne IVF,  describe a new way of determining the sequence of individual chromosomes.

This new level of detail is likely to change the way genome sequencing is carried out in the future, and could revolutionise basic research and clinical practice.

“Craig Venter, the pioneer of the human genome, said in 2010 that ‘…establishing the complete set of genetic information that we received from each parent is crucial to understanding the links between heritability, gene function, regulatory sequences and our predisposition to disease,’” said Associate Professor Irving.

“Until now, although that has been technically possible, it has been prohibitively expensive and complex. Because our new technique is significantly lower cost, it opens up a range of therapeutic applications.”

Knowledge of the sequences of all parental genes holds huge potential for treating almost any disease, from Alzheimer’s and Parkinson’s to heart disease – anything with a genetic component,” said Professor Pouton.

“One of the major stumbling blocks we face in designing effective treatments is the level of knowledge we have about a patient’s genome.”

One piece of information that has been difficult to come by concerns the precise location of single nucleotide polymorphisms, or ‘SNPs’. Our chromosomes come in pairs (one from each parent). They are largely copies of each other, but in places they are slightly different. Those places are called SNPs. One of the things we need to know to design effective therapies is which SNP is on which copy of each chromosome, a process known as ‘haplotyping’.”

Previously, in order to obtain this information, a researcher would have needed to sequence the mixed chromosomes on a massive scale, which is time consuming and extremely costly. The new technique developed at MIPS allows researchers to instead zero in on single chromosomes and determine their haplotypes.

“Our study focused on a chromosome called chromosome 6. We chose it because it has a key influence in the successful matching of organ donors with recipients,” said Dr Murphy.

“Currently, doctors attempt to estimate the haplotype of the important region of this chromosome by tracing characteristics derived from population studies, which is cumbersome and often imprecise. Our new method will allow them to do the same thing more accurately.”

However, the application of the research is much broader than organ transplants.

“Because it is a rapid and efficient method of haplotyping that can be applied to any chromosome pair, it will eventually enable medical professionals to zoom in on just the information they require for a particular therapy. Ultimately, it should enable routine, complete haplotyping of the human genome.”