Leukaemia and L...
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New study digs deeper into the genetic basis of disease

Leukaemia and L...
Posted by
06 May 2015

Brand new genetic technology has, for the first time, enabled researchers to map the long range communication that occurs between genes and the distant regions of DNA that control their function. The technique could increase understanding of the genetic basis of cancers and other diseases, and lay the foundation for finding new ways of treating them.

Researchers from the Francis Crick Institute in London, the Babraham Institute in Cambridge and King's College in London studied DNA in human blood cell types and mice using a technique called ‘Promoter Capture Hi-C’, which was developed at the Babraham Institute. 

The development of the embryo and different cell types in the body depend on genomic regulatory elements that orchestrate the correct ‘expression’ of genes in different locations and at different times. ‘Enhancer’ regions of DNA, which enable genes to function, can be hundreds of thousands of DNA ‘letters’ away from the genes they regulate.

Dr Cameron Osborne, from King's College London, led the research while at the Babraham Institute. The researchers looked at one million regulatory elements in the mouse genome and linked these to gene ‘promoters’, which are the switches next to a gene that turn them on or off.

The findings, published in the journal Nature Genetics, represent the most extensive map of promoter–enhancer interactions in the human genome. Regions that interact with promoters were found to contain many DNA errors, or ‘mutations’, that have previously been associated with cancers. Researchers will now be able to link potentially defective regulatory elements of the genome with the genes they influence.

Dr Matt Kaiser, Head of Research at Leukaemia & Lymphoma Research, said: “There is still so much we don’t know about how genes and regulators drive cancer development and growth. These powerful tools will provide new clues to how drugs and treatments can be designed to target cancer with ever-more precision.”

The researchers, who were funded by Leukaemia & Lymphoma Research, identified millions of interactions and provided an unprecedented snapshot of the genomic regions that contact promoters. Knowing which genes a regulatory region affects has so far been extremely difficult and this has been a major roadblock to understanding of the relevance of single DNA letter variations, called “single nucleotide polymorphisms” (SNPs), in genome-wide association studies (GWAS).

Dr Cameron Osborne, from King's College London but who undertook this research while at the Babraham Institute, senior author on the Nature Genetics paper, said: “Our data physically ties the GWAS SNPs to putative gene targets, and shows that they commonly interact with more distal genes rather than the nearest neighbours. The identification of GWAS target genes has the potential to unleash a new phase of characterising polymorphisms and the genes and molecular pathways they affect.”