Wednesday, 11 April 2012

The Genetic Link – Discovering Causes of Parkinson’s Disease


Chances are that many of us know someone with Parkinson’s disease. It’s a disorder whereby the neurons contained within the substantia nigra either die or become impaired. We see the effect of this as tremor, rigidity in the muscles, and slow movement. This has a tremendous effect on lifestyle, especially given that Parkinson’s is a progressive disorder [1]. As such, Parkinson’s research is important to the lives of the 0.4% of Australians with the condition [2]. It has until now been considered a sporadic disease – that is, random and without genetic cause [3]. But what has recently caught the attention of researchers is the fact that between 10%-30% of those with the disease have an immediate relation who also suffers from the disease [4], prompting an international team of researchers to investigate potential genetic causes.

A family in Northern France with a prevalence of the disease had their genomic DNA mapped and compared[4]. This is a process known as genotyping [5]. In this French family, there was only one similarity that was found in all ten blood-relatives suffering from Parkinson’s disorder which was not found in either groups of unrelated control subjects [4].This was a mutation in the eukaryotic translation initiation factor 4-gamma gene, EIF4G1 [4]. Researchers therefore had an inkling that this somehow caused Parkinson’s. To support their findings, international researchers genotyped the DNA of families with a history of Parkinson’s that descended from USA, Canada, Ireland, Italy and Tunisia. They found very little in common between the genotypes. However, the EIF4G1 mutation was found, and was the only common factor which these later-tested subjects all shared both with each other, and with the French family which was initially tested[4]. This gives strong evidence that the EIF4G1 gene is a cause of Parkinson’s for some sufferers.

Figure 1: Our DNA may hold the key not only to finding the cause of degenerative disorders such as Parkinson’s, but also potentially to finding cures and treatment options.

But just what is EIF4G1 used for? Co-lead investigator Justus C. Daehsel Ph.D of Mayo Clinic, which lead the research, explains that it “controls the levels of proteins that help a cell to cope with different forms of stress, such as those routinely found in ageing cells” [6]. Basically, EIF4G1 affects the initiation of mRNA translation [4], particularly in the forming of those proteins responsible for the management of stress in cells [6]. Stress to cells is a normal occurrence as the body ages, but a lack of response to such stress results in brain cell death [6]. So, it would make sense that a mutation to EIF4G1 would result in cell death, causing Parkinson’s disease.

Just a single nucleotide in the EIF4G1 gene was changed to cause this mutation, yet it had such large implications for the subjects. There are also many other possible genetic mutations which are believed to cause Parkinson’s development. But with each discovery of a cause, we are, according to Mayo Clinic neuroscientist Owen Ross Ph.D, one step closer to new frontiers in the treatment of Parkinson’s [4].       


Image:  Top News 2012, Importance of Exercising Increases; It Alters DNA, viewed 20 March 2012, <>.

1.       Parkinson’s Australia 2008, What is Parkinson’s, viewed 18 March 2012, <>.
2.       ABC Health and Wellbeing 2002, Parkinson’s disease, ABC, viewed 19 March 2012, <>.
3.       MedicineNet 2012, Sporadic definition, viewed 17 March 2012, <>.
4.        Chartier-Harlin, M, Dachsel, JC, Vilariño-Güell, C, Lincoln, SJ, Leprêtre, F, Hulihan, M, Kachergus,J, Milnerwood, AJ,Tapia, L, Song, M, Rhun, EL, Mutez, E, Larvor,L, Duflot, A, Vanbesien-Mailliot, C, Kreisler, A, Ross, OA,  Nishioka, K, Soto-Ortolaza, AI, Cobb, SA, Melrose, HL, Behrouz, B, Keeling, BH, Bacon, JA, Hentati, E, Williams, L, Yanagiya, A, Sonenberg, N, Lockhart, PJ,  Zubair, AC, Uitti, RJ, Aasly, JO, Krygowska-Wajs, A, Opala, G, Wszolek, ZK, Frigerio, R, Maraganore, DM, Gosal, D, Lynch, T, Hutchinson, M,  Bentivoglio, AR, Valente, EM, Nichols, WC, Pankratz, N, Foroud, T, Gibson, RA, Hentati, F, Dickson, DW,3  Destée, A,and Farrer, MJ, 2011, ‘Translation Initiator EIF4G1 Mutations in Familial Parkinson Disease’,  The American Society of Human Genetics, vol. 89, no. 3, viewed 13 March 2012, <>.
5.       Qiagen 2012, Qiagen – Genotyping, Australia, viewed 18 March 2012, <>.
6.       Mayo Clinic 2011, Scientists Discover Genetic Mutation that Causes Parkinson’s Disease, Mayo Foundation for Medical Education and Research, viewed 13 March 2012, <>.

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