29. April 2013 · Comments Off on Team retreat 2013 · Categories: Uncategorized · Tags: , , , , , , ,

Lichfield Cathedral
On the weekend of 22nd of March, we went on our annual team retreat to Waterhouses, a village in the south of the Staffordshire Peak District. We set off from Oxford following a symposium at the Wellcome Trust Center of Human Genetics. Along the way we stopped in Lichfield to visit the famous Cathedral and the house of Erasmus Darwin (grandfather of Charles Darwin, www.erasmusdarwin.org). Surprisingly, Erasmus Darwin’s work hinted at the possibility of evolution, and although they had never met, Charles’ inspiration could have potentially come from his grandfather. We also had a nice meal in the Damn Fine Café, which had a selection of food and drink perfect for a cold winter’s afternoon.

We were really fortunate not to have lingered too long in Lichfield, as a large snowstorm rapidly descended upon the region. More »

The American Society of Human Genetics (ASHG, pronounced “A-shag”), annual meeting is a scientific, networking and socializing milestone every year. This year the meeting was 8 time zones away from the UK in San Francisco, CA. It was a busy year for our group, with 4 talks and a poster being presented, a variety of collaborators’ meetings to attend, a choice of hundreds of talks to listen to, and, of course, plenty of drinking to do.

Each member of the group who was there offers their thoughts after the break. It’s interesting to see that while we covered a wide variety of topics across the group, the most consistent message is that this year didn’t yield any major discoveries that will change the field. Instead, we all saw incremental progress in applying next-gen sequencing and similar technologies to many different problems. Perhaps this is simply a reflection of the nature of modern human genetics: a gradual improvement of our understanding, rather than a sudden revelation.

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17. February 2012 · Comments Off on Are loss-of-function variants relevant to complex disease? · Categories: Papers · Tags: , , , , , , , ,

Three members of the group (James, Luke & Jeff) were involved in a substantial undertaking (led by our colleague Daniel MacArthur) to study loss-of-function (LoF) variants in otherwise “normal” human genomes. These are mutations which are predicted to obliterate the function of a gene: things like gained stop codons, coding frameshift insertions and the like. The paper has just come out in Science, and Daniel has a great write-up over at Genomes Unzipped. We made two contributions to the project (reflecting our principal interests):

  1. Because real LoF variants are (generally) selected against, but sequencing errors which look like LoF aren’t, this class of variation is hugely enriched in all sorts of sequencing and annotation errors. We therefore spent a lot of effort in hand validating LoF calls (using Evoker) to try to separate the wheat from the chaff.
  2. One might expect LoF variants to be more likely than an average SNP to affect disease risk, but it didn’t really seem to be the case. Only one very well known LoF variant (the Crohn’s disease NOD2 frameshift) from the paper showed any appreciable association to disease. Perhaps these variants are just too strongly selected against to rise to frequencies visible to GWAS?