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July Shining a Light On Genomic Dark Matter
Shining a Light On Genomic Dark Matter
Pioneering first-in-world technique development in human genome research at NUI Galway takes another step towards completing the human genome
The McStay laboratory in the Centre for Chromosome Biology at NUI Galway has made a significant contribution to the ongoing *human genome project. Contrary to popular belief the human genome sequence is incomplete. Professor Brian McStay has led the development of a pioneering new technique that provides new human genome sequences, essential to support advances in a field important for improving human health.
Professor McStay’s laboratory at NUI Galway study uncharacterised regions of the genome, aiming to understand their normal function and how genetic alterations within them influence human health. This latest genome discovery will boost Ireland’s biomedical research credentials internationally and underlines the quality of world class research taking place in Ireland.
It is now over 18 years since the first draft of the human genome was released, yet, key regions of our genome remain uncharacterised. Due to difficulties in determining the DNA sequence of these missing regions and their critical role in our biology, they are sometimes referred to as genomic dark matter (analogous to the missing mass in the universe). Prominent among these missing regions are five chromosomes with unusual short arms, the so-called acrocentric chromosomes, numbered 13, 14, 15, 21 and 22 (see Figure 1 attached).
Chromosomes are cellular structures for packaging DNA molecules, which in turn contain genes that define a person’s physical traits and uniqueness. Each of a person’s cells contains DNA measuring nearly two meters in length, yet the cells containing them only measure millionths of meters in length. Therefore, within chromosomes, long DNA molecules are wound into ever tighter coils ultimately producing short squat structures, with long arms either side of a central constriction.
When at their most condensed, chromosomes are often described as resembling butterflies with each wing corresponding to a chromosome arm, and are now small enough to be successfully partitioned into new cells during cell division. The acrocentric chromosomes are unusual in that one of the arms is very small and highly specialised. Through an ill-understood process DNA contained within their small arms is required to form factories, termed nucleoli, to produce complex machines, termed ribosomes. Ribosomes are machines within our cells that convert the genetic information that is coded in the DNA of a person’s genes into the functional proteins that build people’s bodies.
Professor Brian McStay, Professor of Biochemistry, Centre for Chromosome Biology, NUI Galway, said: “Given their fundamental role in our biology it is critical these missing regions of our genome be included in updated human genome references as this will make them accessible to researchers worldwide and accelerate the discovery of how they function.”
Professor Noel Lowndes, Established Professor of Biochemistry and Director of the Centre for Chromosome Biology, NUI Galway, said: “The McStay laboratory have developed novel genomic methodologies that can now be applied to other regions of the human genome still missing from the latest human genome releases. Support for pioneering biomedical research like this is critical to better understand our fundamental human make up, which in turn is central to providing new avenues for scientists to explore in the search for more effective treatment of disease.”
The McStay laboratory has a long-standing interest in understanding how nucleoli form and function. In work that is funded by a partnership between the Wellcome Trust in the UK, Science Foundation Ireland and the Health Research Board in Ireland, they have developed and implemented novel approaches at determining the DNA sequence required to form nucleoli. These DNA sequences, previously part of the genome dark matter have now been incorporated into the most recent human genome draft by the Genome Reference Consortium (GRC). See links below to recent GRC blogs associated with the latest release (GRCh38.p13) of the human genome which references this work.
Genome Reference Consortium on the latest releases of the human genome and references to the work of the McStay laboratory:
For more information about the Centre for Chromosome Biology, visit: www.chromosome.ie