Week 9

Hello hello everyone! Week 9. Wow, can't believe that happened so quickly!

So, this week on Monday I shadowed Dr. Narayanan as usual but on Wednesday Dr. Narayanan and I sat down and discussed the details of the case of the boy I am following.

But, before I get into the details of the patient I am following, I wanted to go into a little more detail about how exome sequencing is actually done. First, the DNA has to be prepared (for lack of a better way to say it). The whole gene first has to be transcribed from DNA to hnRNA. hnRNA is heterogeneous nuclear RNA which contains both the transcribed exons and introns and is considered a precursor to mRNA. hnRNA has both transcribed versions of introns and exons, but exome sequencing only looks at the exons in a gene, so the hnRNA is then translated into mRNA. During this translation, the introns are spliced by snRNPs, which are small nuclear ribonucleoprotein particles (which are made of complexes of snRNA and proteins). Since the introns are spliced out, the resulting strand is just made of exons. Then once there is this strand of exons, an exome library is created. After the library is created, computers do their fancy technology stuff and give you a variant file.

Ok, so the variant file is a super super filtered down version of each specific gene that could potentially be disease causing. For example, if in a certain race a disease has a frequency of over 3%, it is not considered to qualify as a rare so it’s thrown out and not shown on the variant file. The variant file is organized by gene name, what type of mutation it is, and whether it comes from the mother or the father of the child. This is all told by what chromosome it is found on, which happens to be another wonderful feature of this huge excel spreadsheet. The one for the patient I am following has over a 1000 rows to look through and identify a possible variant.

So, this took me a little while to wrap my head around, and I'm still trying to understand all the little details about it. Next week, I am going to talk to Dr. Narayanan more about the steps for looking through the sequenced data and how variants can be prioritized. But, that’s all I have for you guys this week! Can't believe projects are almost over :( Here's a cute dog and baby gif though!