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Local Heroes

Luc Smink
| Jun 24, 2012

germanyThe first session of ESHG 2012 in Nuremberg was referred to as the Local Heroes session, a great lineup of three speakers from the host country. The first speaker was Prof. Dr. Stefan Mundlos from the Charite in Berlin. Professor Mundlos’ talk was about the regulome as the next frontier in Human Genetics. So far, the big focus has been on coding sequences, but it is only 1.5% of the total genome, so what is in the rest? These “gene deserts” contain highly conserved regions. He described the usage of histone marks to identify regulatory elements by ChIP-Seq. Regulatory elements control the expression pattern spatially and temporally and he gave a number of different examples such as the HOX cluster, as well as SOX9.

The next speaker was Prof. Dr. Peter Lichter from the DKFZ in Heidelberg, talking about three different cancers: pediatric low grade astrocytoma, medullablastoma and glioblastoma. Brain tumours are one of the major childhood cancers. Astrocytoma is a benign tumour, but it is very difficult to treat with chemo- and radio therapy. So far, 80 tumour-normal pairs have been sequenced for astrocytoma; this yielded a single new BRAF mutation, but the surprising observation was that there were relatively few mutations in astrocytoma. Prof. Lichter also described the sequencing of 60 medulloblastoma tumour-normal pairs, 39 by Whole Genome Sequencing (WGS) and 21 by Whole Exome Sequencing (WES), the findings of which were replicated in a targeted approach sequencing 2,734 genes in a further 65 tumour-normal pairs. They found a correlation of age with the number of tumours, what is the reason for this? One hypothesis was whether these tumours arise early, but that late onset disease requires more driver mutations. Finally, WES of glioblastoma identified 2 recurrent histone H3.3 mutations. Are tumours essentially an epigenetic disease?

The final talk in this session was from Prof Dr Heribert Schunkert from Lubeck on myocardial infarction (MI), common disease, common variants, common mechanisms. Whole-Genome Association studies provided a gold rush for MI and coronary artery disease (CAD) research, identifying 13 loci. To maximize the results, a consortium was formed, the Coronary ARtery DIsease Genome-wide Replication And Meta-analysis (CARDIoGRAM) consortium was formed, allowing a study of 60,000 cases with 120,000 controls. This study identified large number of hits, but where do we go from here in the post GWAS era?

There was a lovely example of the use of WES to find new mechanisms of MI in a family, where 4 genes were found that didn’t show up in any of previous studies. A digenic mutation in GUYCYIA3 and CCT7 was found to have a strong effect in causing MI. However, there is a lot to still to find, and Prof Schunkert commented that NGS will play a key role in this.