31. marts 2014

The FANTOM project charts an atlas of gene activity over the human body

Gene research

In 2003, the human DNA sequence was determined in the human genome project. Now, scientists in the FANTOM project determined exactly where in the body each gene encoded in DNA is active. This is important, because it is the activity of the genes that make the cells so different – brain cells use a specific set of genes that are involved in brain functions, but not genes that are involved in liver function, etc.

Click the pictures to see them in a higher format

- In the FANTOM consortium, we have for the first time systematically investigated exactly what genes that are used in virtually all cell types across the human body – so, we have painted an activity layer on the human DNA, much like annotating a map with mountains, rivers and cities, said Professor Albin Sandelin at University of Copenhagen, who led the Danish team in FANTOM.

The technology also made it possible to find the regulatory switches that are responsible for activating the genes in the right cells, called "enhancers".

- We have mapped the activities of these 44.000 enhancers across the human body and how their usage are linked to the FANTOM5 gene usage atlas. Until now, the locations and activity of these regions were limited to a handful of easily accessible cell types, said Dr. Robin Andersson at University of Copenhagen, responsible for much of the analysis of regulatory switches.

The team also found that many of the mutations linked to disease are located within these regulatory switches, thus linking the mutation to an effect. Because the experimental method can be used on small samples, this finding opens up the door for analyzing tissue samples from people suffering from disease and find out what is wrong on a molecular level.

These studies were published in two landmark papers in the prestigious Nature journal, together with many follow-up papers published in Nature Biotechnology, Genome Research, Blood, Molecular Biology and Evolution, Proceedings of the National Academy of Sciences, Nucleic Acids Research, Molecular genetics and metabolism, BMC Genomics and PLoS ONE.

The work was supported by the Lundbeck Foundation and the Novo Nordisk Foundation.

Read the two articles in Nature

A promoter level mammalian expresssion atlas
An atlas of active enhancers across human cell types and tissues


Professor Albin Sandelin, Lundbeck fellow 
The Bioinformatics Center, Department of Biology and BRIC, University of Copenhagen, Denmark
Tlf: +45 22 45 66 68
Mail: albin@binf.ku.dk
Dr. Robin Andersson
The Bioinformatics Center, Department of Biology and BRIC, University of Copenhagen, Denmark
Tlf: +46 737 359 789
Mail: robin@binf.ku.dk
Professor Michael Rehli
Klinik und Poliklinik für Innere Medizin III Universitätsklinikum Regensburg, Tyskland
Tlf: +49 941 944 5587
Mail: michael.rehli@klinik.uni-regensburg.de

Dr. Alistair Forrest, FANTOM5 analyse leder hos 
RIKEN Center for Life Science Technologies 
Mail: forrest@gsc.riken.jp

Dr. Yoshihide Hayashizaki, Director

RIKEN Preventive Medicine and Diagnosis Innovation Program
Tlf: +81 45 503 9218
Mail: yosihide@gsc.riken.jp