Quantitative genetics back from the grave

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Edinburgh has sometimes had an uncomfortable relationship with science, as the infamous case of 19th century murderers Burke and Hare attests. Despite this, scientists from disparate disciplines converged on the city last week to perform a 30 year post-mortem on the field of quantitative genetics – and declare it alive and well.

The 4th International Conference on Quantitative Genetics was opened by renowned Edinburgh geneticist Bill Hill, who gave a lucid dissection of the field throughout its 100 year history, outlining how recent advances into the territories of evolutionary and breeding genetics suggest that declarations of the death of the discipline have been greatly exaggerated.

Edinburgh can rightly claim to have pedigree in this field. In the conference’s opening address, Bruce Walsh of the University of Arizona paid tribute to a city which produced perhaps the first quantitative genetics paper in 1867, by one Henry Charles Fleeming Jenkin, who chose to take Charles Darwin to task about the assumptions underlying his famous treatise on natural selection.

Seminal works by RA Fisher published by the Royal Society of Edinburgh, and local resident CH Waddington’s work on the concept of canalization, underscore just how appropriate it was for the long-awaited reconvening of this conference to take place in Scotland’s capital after a 5 year hiatus.

Data sharing scales up

Walsh argues that recent developments in the tools of molecular genetics have served to enhance—rather than supplant—those of quantitative genetics, opening up new possibilities for the discipline that were previously inconceivable. This, together with increased collaboration among disparate fields, means that these are exciting times for established researchers and the next generation alike.

A capacity for collaboration was also at the heart of an engaging account of the history and success of the human genome project by the recipient of this year’s Genetics Society Mendel Medal, Eric Lander, from the Broad Institute at MIT. In his prize lecture, Lander outlined how the greatest legacy of the project remains that of what can be achieved when data sharing, openness, and the free-flow of ideas occurs on a massive scale: a feat previously unprecedented in science.

Such a sentiment was echoed by other speakers such as Matt Hurles from the Sanger Institute. Discussing variation in the genome and how emerging techniques are being used to investigate the clinical basis of human developmental disorders, Hurles stated strongly “It is critically important that we share data and collaborate internationally”.

New challenges

As little as 30 years ago, the scale of data now being accumulated in genetics and genomics was inconceivable. However, unlike some disciplines grappling with the current data deluge, the bottleneck in quantitative genetics is focused firmly on phenotyping.

This brings the field full circle from the days when genotyping was the great limiting factor, and was highlighted by Ed Buckler of the USDA as one of the biggest challenges facing quantitative geneticists over the next decade.

Through a global sequencing effort to unite the world’s germplasm diversity in maize, Buckler outlined that although next-generation approaches can be utilised to understand genomic diversity in an unprecedented level of detail, selective breeding programmes in this crop are still currently falling well short of their theoretical maximum. However, current efforts to biofortify maize crops for Vitamin A do look set to benefit developing countries greatly through targeted programmes for nutrient-deficient nations.

Work such as this highlights beautifully how advances in our understanding of quantitative traits may be translated directly into societal benefits, and will continue to do so for the foreseeable future.

Healthy heights

The breadth of sessions spanning the conference week was a clear demonstration of the health of the field, with sessions covering topics from evolutionary quantitative genetics and genetic architecture, to the latest advances in statistical methods and bridging the genotype-phenotype gap.

It also became clear how novel advances can shed new light on classical problems. Francis Galton’s 19th century studies on the heritability of human height is perhaps the archetypal student’s introduction to the quantitative genetics of complex traits. Peter Visscher from the University of Queensland revisits this work in the age of genomics, using sample sizes that would have been unthinkable in Galton’s time. Large-scale studies like this and the huge diversity of leading-edge research on show in Edinburgh certainly appears to be proof enough that the current field of quantitative genetics is not just not dead, it’s positively walking tall.