Using Whole Genome Sequencing in Patients with Neuromyelitis Optica
In the April 2014 Edition of Neurology, Benjamin Greenberg, Douglas Kerr, Tim Harris, Aaron Day-Williams and John Carulliwrote about a study that was conducted to deduce the inheritance pattern of those who suffered from Neuromyelitis Optica.
Neuromyelitis Optica is an uncommon autoimmune disorder that can affect the nervous system, optic nerves, and the spinal cord. Those who have this disease commonly experience pain in the eyes and vision loss. Along with this typically weakness, numbness and sometimes paralysis of the legs are experienced.
A study was done in order to see if there is any evidence that there is an inheritance pattern with this particular disease through the use of human whole genome sequencing. Consequently, this was also the largest study of its kind- involving 150 patients with this particular disease. While there have been other studies that covered this topic, they were limited to single-nucleotide polymorphisms (SNP).
DNA samples were taken from 150 patients along with 10 samples from 5 of the patient’s parents and were sequenced. The samples were sequenced at 30X coverage with Illumina’s Short Read Technology. For gene definition, ENSEMBL was used. Variants were labeled for frequency and novelty and missense mutations were also analyzed.
The results from this particular experiment and the whole genome sequencing confirmed past studies that explored the associations with HLA types. More than a third of the seropositive Neuromyelitis Optica patients had the alleles for the HLA-DBQ1 gene. 32 of those patients had alleles for the HLA-DRB1 gene. There were no mutations that were specifically identified within the AQP4 genes.
It was concluded that patients with Neuromyelitis Optica have a different set of HLA restrictions based on their serostatus. To date, this is the largest NMO study that has ever been conducted.
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