Wednesday, 28 March 2012

Genetics in Neurological Medicine

Figure 1: Focal Point of  Upper Motor Neurons
Neurological disorders are those caused by abnormalities within the body’s nervous system. This includes the nerves and their components, the brain and the spinal cord. These disease’s can be caused by defective genes (as in muscular dystrophy), incorrect development or through injury among others. Another category of neurological disorders are the degenerative diseases. Degenerative diseases either cause damage or the loss of neurons. One such disorder is Amyotrophic Lateral Sclerosis (National Library of Medicine – National Institutes of Health, 2011).

Figure 2: Typical Mobility Problems due to ALS

Amyotrophic Lateral Sclerosis (ALS) affects approximately three people in a hundred thousand. It is a progressive neurological  disorder that attacks both upper and lower motor neurons. Upper motor neurons are those located within the brain and have no direct contact with muscle fibers whilst lower motor neurons attach directly to muscle fibers and act due to upper motor neuron impulses. ALS is characterised by a gradual decline in muscle strength with sufferers often experiencing respiratory, vocal and swallowing difficulting. Lower limb spactisity is also common. The health of those afflicated degenerates steadily with paralysis common in the later stages, before death, usually from respiratory failure(Armon C, 2011). ALS generally affects the middle-aged, with patients averaging from 40-70 years. Death normally occurs within five years of diagnosis.

Figure 3: Stephen Hawking
Amyotrophic Lateral Sclerosis is classified as juvenile when it affects subjects younger than 25. Juvenile ALS can be found in subjects as young as 2 years of age.  It is most famously seen in renowned physicist Steven Hawking (pictured left). A recent investigation into juvenile ALS has suggested that ALS is caused by a missense mutation of the Sigma1 receptor (Science Daily 2011) . A missense mutation is when a single nucleotide is substituted for another causing a different amino acid to be produced, and thus an altered protein. This protein can either be the same protein, but a different shape, which would affect its functionality or a different protein altogether. In this case the mutation appears to prevent the Sigma1 receptor from functioning. This is thought to cause an accumulation of miss folded proteins upon motor neurons, causing their degeneration.  This breakthrough was made possible by the use of homozygosity mapping and gene sequencing.
Figure 4: Missense Mutations
Figure 5: Sigma 1 Receptor
Homozygosity mapping is a computational genetic   technique used to identify and accurately detect homozygous genes. This would appear to be a severe limitation however researchers from Michigan and Germany have suggested that mutations that cause disease are homozygous in 93% of cases. In the case of the ALS study homozygosity mapping revealed a shared zone between those with ALS which was lacking in those without (Biotech About 2009). This zone contained nine genes, each of which was sequenced. The Sigma1 receptor showed the mutation which is believed to cause ALS.  This is just another case where a noteworthy discovery was made in another field thanks to a new application of genetic technology. In this case, the discovery of this mutation should allow an accurate and complete diagnosis, especially with the recent advances in the human genome project. It could also possibly lead to a cure, with the correction of this mutation.

By Roger Goodyear - 42884255   

·         National Library of Medicine – National Institutes of Health 2011, Neurologic Diseases, viewed 19th March 2012, <>
·         Armon C, 2011, Amyotrophic Lateral Sclerosis, MD, MSc, MHs, viewed 19th March 2012, <>
·         Science Daily 2011, Mutation in SIGMAR1 Gene Linked to Juvenile Amyotrophic Lateral Sclerosis: Sigma-1 Receptor Offers Potential Therapeutic Target, viewed 16th March 2012, <>
·         Biotech, 2009, Homozygosity Mapping for Outbred Individuals, viewed 18th March 2012, <>

Images (in order of appearance)

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