It's Written in your DNA--Or is it?

Author:McKinlay, Pam
 
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Popular belief holds that we have a gene for this and a gene for that, but a single gene is seldom responsible for a single trait. Rather, traits are much more complex, with many genes and hundreds if not thousands of interactions involved, with many small cumulative changes on genes affecting health outcomes. The ultimate aim at the forefront of genetics research is to eradicate disease, lift people out of poverty and ease suffering. (1) The main areas of investigation include: understanding variation in the human genome (code), understanding the biology of the genome (structure and function of DNA) and understanding the biology of disease. (2)

The biology of the genome and epigenome are relatively new fields. In these, the significance of three-dimensional structure on chromosomal regions is considered and the effects these have on changing the expression of the protein coding genes. Chemical modification of molecules in the epigenome control the compact nature of the DNA strand, but a full reading of the genome remains as much a mystery as the Rosetta Stone was for almost a century in the 1800s. The task ahead is to unlock the syntax and discover the role genetics and epigenetics (3) play in our health and wellbeing. (4 5)

THE NEW LANDSCAPE OF DNA

Julia Horsfield's research area is the protein complex known as cohesin. (6) Her research group looks at the components of DNA strands ("noodles" in the nuclear soup) at a molecular level through the lens of biochemical experiments using proximity ligation. The lab captures molecular data to reveal information about the chromosome's contours and topological behaviour at the instant of fixation for investigation--noting of course that chromosome are fluid and dynamic, flexing and changing as they constantly transition between different states (work/ gene expression/protein manufacture and cell division). Research into the cohesin complex reveals that it controls DNA packaging within the "noodle soup" (7) of the cell nucleus. The way DNA strands fold control which bits of a chromosome are active, in communication with each other and neighbouring strands, and which bits are not. (8) Thus cohesin acts as a regulator to control which loops are working in concert, or otherwise, with the RNA gene expression machinery and other chromatin modifiers to determine the spatial and temporal organization within the cell. Cohesin is also important at the time of cell or DNA replication.

In the first part of proximity ligation, formaldehye fixes the loops in stasis. They are cut up...

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