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ESHG 2015- Day One Summary

Scott Brouilette, Ph.D.
| Jun 07, 2015

And so the 2015 European Society for Human Genetics officially opened to a very wet and windy Glasgow! I was in Milan for ESHG in 2014 and clearly recall the (now very prescient) predictions that it would rain in Glasgow… the opening address was filled with some interesting facts that were less related to genetics and more related to the wet- but we’ll get to that in a moment.

First up was the Welcoming Address from the ESHG president, Helena Kääriäinen, who asked how many of the audience knew that there are 71 countries in Europe… the collective silence suggested we all hoped this was a rhetorical question. But after giving a brief overview of the ESHG, Helena then focussed on a handful of projects from the last 12 months. These included the writing of papers and guidelines on topics such as NIPT and WGS usage in newborn screening, two particularly hot topics in genomics as we move forward with clinical applications of sequencing. Helena’s talk also mentioned education both for the clinical community but also the general public; the most interesting of the public engagement projects was a one-day event for school children called “A Journey Through Your Genome”. The final point of note was the formation of the European Board for Medical Genetics (EBMG) - a separate legal entity for setting professional standards.   

Next up was Angela Davies, President of the British Society of Genomic Medicine who did a great job of starting her presentation without her slides as the IT guys struggled to load her talk! Once that minor glitch was resolved, she informed the audience that in England the NHS deals with an astounding 1.5 million patients in every 24 hour window, but that NHS funding represents a lower percentage of GDP than many other countries around the world. She swiftly moved onto Genomics England and the formation of the Genomic Medicine Centres that will be integral to the  project, before discussing some issues around data security. With high-profile breaches of security (although not necessarily in genomics/healthcare) reported in the popular press, it is not surprising that the public may have serious concerns when it comes to 1) their health care records, and 2) their genomic information. But Angela then lightened the mood by telling us that the Mackintosh raincoat was actually developed in Glasgow- and we certainly needed them this day! 

We moved onto the science with the plenary sessions. Wendy Bickmore from the University of Edinburgh jumped straight into the study of long-distance regulation. Over the last 10-12 years we have seen many GWAS studies reveal significant hits residing in non-coding regions but only relatively recently has the biological importance of many such findings really been elucidated. Using techniques such as chromatin conformation capture, (3C, for a review see this link) many groups have now linked these hits to genes many kb away. Wendy gave beta-globin as an example; 25 kb away a common deletion results in the condition beta-thalassemia. And so disruptions to long-range enhancers can have pronounced effects that prove difficult to undercover without 3C, but Wendy’s group complement the technique with fluorescent staining and standard light microscopy to aid in the interpretation of the 3C data. Later in the session DG Lupiáñez (Max Planck) continued the theme of 3C and extended it to Hi-C to reveal the organisation of the genome into regulatory domains, termed Topically Associated Domains (TADs). These domains are highly conserved and led the group to ask if such domains are involved in human disease. As one could probably predict, structural variants disrupt TADs while the boundaries of the domain determine the pathogenicity of the variant. 

The early session also gave us a chance to see Matt Hurles from Sanger for an update on the Deciphering Developmental Disorders project. In terms of underlying methods, the project combines arrays and exome sequencing.The cohort itself is diverse in terms of both the clinical phenotype but also the ancestry; all subjects have developmental disorders and of the 30% diagnosed with DDD, 15% exhibit structural variations while 85% show much smaller variants. Matt then detailed how the DDD team are detecting structural variants from the exome-seq data and coined the term “Dark Structural Variants”, or DSVs: "variants we know are there but struggle to see". In brief, the pipeline examines split reads that are indicative of SVs, but this requires a sophisticated informatics approach, particularly for identification of novel SVs. Matt closed out his talk by discussing data sharing and matching disorders using the DECIPHER database. The DDD and DECIPHER projects are great examples of collaboration between the families of affected children, the National Health Service, and the Sanger, and really serve as a model for how future projects could be structured.

Later in the day, the much anticipated noninvasive prenatal testing (NIPT) session proved very popular, not least because coverage the method has received in the run up to the start of the conference. Professor Lyn Chitty from UCL opened the session by taking about the implementation of NIPT for aneuploidy testing in an NHS diagnostic laboratory, something that would represent a paradigm shift. For a review of the RAPID study see, but from an ethical perspective, research shows that women are very positive about the utility of NIPT, but that counselling at different stages of the process is vital.

As always the opening day of ESHG featured a strong line-up that stimulated much debate for the remainder of the day. And that must surely be better than discussing the weather in Scotland.