Changing the history and future of human genetics

An international group of leading geneticists has reviewed the incredible advances made in the previous 25 years of human medical genetics, and charts the field's future in the prestigious journal, Nature.

Among the review's recommendations are a call for increased diversity in the populations represented in genetic databases, to address the overrepresentation of people of western European descent. 

The review points to some exciting possibilities for using genetic information in the future. These include the ability to generate a 'risk score' based on a person's genome for diseases like heart disease and obesity arising from the interaction of hundreds of genes, allowing early and pro-active intervention. The work will also identify disease biomarkers, potential negative side effects of any treatment and improve drug development pipeline efficiency.

Clinical use of these powerful new genetic tools will be hugely improved by the growth of biobanks and the reducing cost of sequencing individual genomes. This will improve equitable access to emerging genetic insights into health across our communities.

The global consortium of authors from leading institutions in Australia, Germany, Switzerland, the UK & USA included Professor Kathryn North, director of the Murdoch Children's Research Institute (MCRI) in Melbourne.

Professor North said, "Continued advances in human genetic medicine are now going to come from massive international collaborations.

"We in the field are so excited by the potential for global genomics initiatives to bring a preventative perspective to health, by proactively managing genomic, clinical and lifestyle factors using risk scores, biomarker and biopsy combinations and wearable technologies. The future is likely to bring spectacular advances in new treatments for many diseases."

In the review, the group outlined the genetic discoveries and technological advances that have dramatically improved scientific understanding of both rare and common diseases, and driven development of novel preventative and therapeutic strategies.

Rare inherited diseases like Huntington's disease and cystic fibrosis are caused by inheriting a single mutated gene which causes disease from birth or soon after. Over the past 25 years, technological advances in gene sequencing technology have increased the number of identified disease-causing genes from just 250 to around 4000.

In contrast, common diseases arise from a complex interplay between many causes, both genetic and environmental. Genetic predisposition to disease arises from variations in tens or hundreds of genes, each with a small, subtle effect that when added together in the 'correct' combination result in disease. 

There are now around 70 000 such variations identified, contributing to diseases such as obesity, schizophrenia, depression and asthma. Additionally, other genes or environmental and lifestyle modifications can amplify or mitigate the effect of the genes conferring disease predisposition.

Crucially, the authors caution that continued genomic medicine research needs to continue within a bioethical framework. 

Professor North said, "We absolutely need to recognize the personal relevance of human genetics and the critical importance of autonomous consent and privacy protection, minimising the adverse consequences of genetic exceptionalism. All our research is conducted against a backdrop of strong governance and the responsible exchange of clinical and research data.

"Widening personal access to large-scale genetic and molecular data promises to reshape medical care and provide benefits to individuals and societies across the world."