Lysosomal Storage Disorder.
Lysosome is an organelle contains an enzyme responsible for the hydrolysis of the substances into their simpler form.But what happened to lysosome to cause disease,we study here!
Enzyme present in lysosome is either reduced or absent if that condition happens substances accumulate into lysosome and produce toxic materials due to this lysosome caused the no of diseases.
Gaucher’s disease is an inherited genetic disorder that causes due to buildup of lipid accumulation.Previously Gaucher’s disease can not be prevented because it’s inherited through genes from parents.
Current advances we possibly treat it using therapeutic novel agent
Modifiers, are the secondary gene which modulate somehow for the function of primary mutation.
How do we identify them?By using the two methods
1) Linkage analysis :Family of different patients are check to identify the modifier gene it’s different but not impossible!
2) Genome Wide Association Studies.
For identifying the potential strain in Gaucher’s disease, Basically chemical inhibitor of enzymes are taken and fifteen different mice are collected treated them everyday with injection with this inhibitor and get the results of different Phenotypes response short-lived Or long life span strain.After this strain map with a modifier gene to carry out Genome Association Studies to study the well developed disease or not.In Parkinson disease we did the same experiment and measured the level of B- glucosidase enzyme.
Why do we use this different strains data to map with genes because genomes and Transcriptomes are known to us then form the biopsy network using this, we get the variants of genes which caused the disease.From this we find USP38 with modifier is the novel cause of Parkinsons disease
Do you know?In historical disease Parkinson’s disease it is considered as mitochondria disease!
How does it happen?
B-glucosidase enzyme normally goes to lysosome but in this case it also goes to mitochondria then how we treat Parkinsons disease as a mitochondrial aspect.
For modifier gene, we again go for linkage analysis and GWAS. We got the peak at chr no 15 on both analysis from further detail study we got NRT -1 as a modifier gene.In this case we use yeast as a model organism for studying phenotypic variability, Paraquat using a herbisidae.NRT prevents paraquat toxicity in yeast, also NRT act as Anti-aging agent.In human IPSC dopaminergic works as paraquat in neurons with these cells die so using NRT in human we survive them
The following points are also covered in session.
3.Niemaan-Pick type C (NPC disease)
4.Influence of the genetic background on the response to Rapamycin in NPC mice.
Hope you all enjoy it.
Special thanks to Prof Andres Klein for this insightful webinar.
