Precision medicine in Neurodevelopmental diseases
The present lecture focuses on the genomics, its significance in treating current genetic diseases and future scope. Started with the basic introduction of human genome the lecturer presented the most advanced approach of genomics in combating the multiple incurable human diseases via developing tailored mouse models.
Human genome includes 3 billion nucleotide bases that are inherited from the parents. Human genome sequencing was one of the greatest achievements of the medical science that have grown rapidly. The total cost for the first sequencing project had been 3 billion USD that lasted for around ten years but now one can get his sequence in just 1000 USD within few hours. For sequencing, only DNA is required that can be retrieved from any body cell, such as blood and a unique Code is generated. If sequencing is conducted letter by letter, it will take more than 35 years. The difference in one letter can develop drastic genetic diseases and for this one letter, the whole genome is read to reach the final diagnosis. The lecturer described this concept through giving an example of an 18-month girl with a rare progressive neurological condition. Due to its exclusivity physicians assumed it an autoimmune condition and referred her for sequencing. Through, the case was urgent; the exome sequencing was preferred to retrieve fast results. Exomes are protein coding genes that exist in the number of 200,000 in human. The results showed two mutations in SLC52A2 genes disrupting two significant functions. Its impact results in the absence of a protein that helps in transporting the Riboflavin inside the cells. Thus, the patient was prescribed riboflavin supplements and the condition of the patients improved drastically. Giving this example lecture explained how this approach can be applied to other genetic disorders, such as epilepsies and no tears condition (NGLY1 deficiency). Another important discussion was that many drugs have the capability to induce mutations. KCNT1 mutation is altered by quinidine that develops into epilepsies via interfering with potassium channel. Therefore, treatment with the same can improve the condition. The novel concept of precise medicine is to design specific mouse model against the human patient to study the condition through inserting the impacted gene set and providing the appropriate medicine to the mouse model. The results can be examined and if successful the process can be repeated with the patients. Such as to study this case the quinidine was injected to the mouse and a genetic mouse model with phenotype was developed (Bearden 457-461.).
According to the lecturer, the age impacts the mutation rates at the highest rate. MicroRNA selection approach is also a very precise strategy to identify the mutational point accurately and deliver the appropriate treatment. MicroRNAs are endogenous RNAs that target the specific regulations linked to epilepsy. Four out of the known 43 genes inhabit genome-wide ranks [1-4], p=2.7 x 10-11 (Dhindsa).
Thus, genomics shows potential in the future era of precise medicines. It is a very bright approach that will help million of people. It would help us to understand what does and does not happen in human genomes. This technology will assist in targeting the right point of mutation along with preventing from the risk of misdiagnosis and wrong medication.
Works cited
Bearden, David, et al. "Targeted treatment of migrating partial seizures of infancy with
quinidine." Annals of neurology 76.3 (2014): 457-461.
Dhindsa, Ryan S., et al. "Epileptic encephalopathy-causing mutations in DNM1 impair synaptic
vesicle endocytosis." Neurology Genetics 1.1 (2015): e4.
