Week 10

Hello everyone! I hope everyone had a wonderful week!

So, today marked my last day on site! I can’t believe SRP are basically over :(

This week, I spent a good chunk of my time on site working on my presentation and finalizing all the details of the variant study! While working on my presentation, I found myself wanted to talk about all the rare diseases I had seen, the neurological tests, and the course of treatment. But, since my research was only specific to one person, I had to limit that and talk about the one patient in lots of detail.

Aside from getting the chance to see so many rare neurological disorders, I think my favorite part of this internship was how interactive I got to be with some of the patients. Whether it was playing with a child while Dr. Narayanan talked to the parent about their problem, or holding a puppet elephant to help test for eye movement, I was able to engage the patient while helping in the evaluation process.

My main goal with this internship was to experience what it was like to work in a doctor's office and learn about how genetics and genetic testing can be used to make personalized treatment plans for each patient. I have truly enjoyed every part of this SRP process!

I’m planning on continuing working with Dr. Narayanan during the summer and will continue learning about the process of exome sequencing! But, a huge thank you to you guys for reading my blog every week (and complimenting my gifs)!

Here's another cute gif! See you guys next week for my final post!

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!

Week 8

Hello everyone!! I hope everyone had a splendid week!

This week was another interesting and exciting week on site with lots of new cases! But, for this blog post I’m gonna focus more on explaining what exome sequencing is, its benefits, and shortcomings.

Before I go into exome sequencing, I’m gonna define a few terms. There’s a real chance you guys will already know what this stuff means but just bear with me (is it bear or bare in this case? Whatever you know what I mean). I guess the best way to start going through this is at the base level, so an exon. Exons are segments of DNA which contain the necessary information for coding a protein. Exons create exomes which are the protein coding region of a genome, and a genome is the entire collection of genetic material.

Whole exome sequencing is the method by which protein coding regions (exons) of over 20,000 genes in the genome are sequenced. But, the exome only represents less than 2% of the genome. So at this point, I was curious about the other 98% of the genome - what if the variant lies there and that’s what is causing the disease? However, 85% of disease causing genetic variants are found in the exome section of the DNA. Since DNA is made up of introns and exons, and since the exons are responsible for protein coding and introns do not protein code, the mutations found in exons are often more harmful. By only sequencing and looking at the protein coding regions of the genome, researchers and clinicians are given a more manageable data set. A more focused and refined data set makes going through the data easier for the researchers and clinicians. Also, with this more focused approach, the researchers are more efficient while sifting through all the genetic variants, and determining which one might be causing the disease.

There are limitations to exome sequencing because it is still relatively new technology. The sequencing only proves to be successful around 25-40% of the time. The main reason for the percentage being so low is that even though 20,000 genes have been sequenced, many more genes still have to be discovered and there is always the possibility of the mutation being in the undiscovered genes. There are also issues with the technology used to sequence. Even though the technology is constantly changing and advancing, sometimes certain regions are too difficult to sequence, and also large deletions and duplications are not always picked up during testing.

However, the biggest success of genetic sequencing is that it can allow for a diagnosis to be made which will in turn lead to a more personalized, and effective treatment plan for the child. It can also be applied to family planning. After determining the disease the child has, parents are made aware of their risk of having another child with the same disorder. As a whole, sequencing helps the scientific community and allows for a greater understanding of rare disorders. Also, a lot of these diseases can be very emotionally taxing and many families have outreach programs that connect them to each other as a support system.

Ok, so that was a lot, but it’s all I’ve got for you guys this week. Surprisingly (or not so much I guess) it was pretty hard to find gifs that fit in with the context of this post, so hopefully this cute bunny makes up for it! See you guys next week!

Week 7

Hi guys! It's so hard to believe that it's already week 7 of senior projects! How did that happen?

So, this week, on Monday a patient and their family actually drove from Mexico to the office to see Dr. Narayanan. I’ll start with a little backstory on this patient - the patient was developing completely normally until around the age of 5 and after that they began deteriorating rapidly. They lost the ability to communicate, had severe decrease in mental cognition, lost the ability to walk among other things. At first, doctors in Mexico believed it was some sort of spinal infection and they ran a spinal tap but all the results came out as normal. After the normal results, the doctors in Mexico thought it might be a mitochondrial disorder or something genetic, but because they lack the resources to do genetic testing, the doctors referred the patient to Dr. Narayanan. After an hour long initial examination and review of the patient history and notes, Dr. Narayanan suspected that this patient has some sort of a neurodegenerative disease which is caused by an issue with neurotransmitters responsible for dopamine in the brain. But, in order to confirm this diagnosis Dr. Narayanan ordered another spinal tap (this time requesting different tests) and enrolled the patient into the genetic sequencing study. After this, Keri (the clinical director) invited me to sit in on the consenting process and getting the patient enrolled into the study.

This week there was also the Annual Clinical Genetics Meeting (ACGM) which Dr. Narayanan attends each year and Keri presented at this year. Because of this, Dr. Narayanan was swamped this week so we did not have a chance to chat about the sequencing results of my specific patient yet. However, I thought I would take you guys through the process of consenting the patient into the genetic studies. It's actually pretty simple - Keri and the family sit down together and go through a packet which outlines what the testing is, how it is done, and how they use a big database to see if any other people have the same mutations as the patient enrolled in the study. After this, Keri draws blood or takes a cheek swab from the child, and takes blood from both parents and a sibling if they are willing. Then, those are sent off to the lab to be sequenced which can take anywhere from 6 months to a year depending on the severity of a case.

Ok, well that’s all I’ve got for you guys this week! Here’s a funny gif of Loca, the pug that just can't run!

Week 6

Hi everyone! I hope that everyone had a wonderful, and well-deserved spring break!

So this week, I was back on site and the week went a little slower at the office. A lot of the cases I saw were routine check ups on kids who had been suffering through epilepsy and needed either prescription refills or were just back for their 6-month check up.

But, don’t worry, I do have an interesting case to share with you guys. On Monday, I saw a patient who is two and a half years old and has been diagnosed with Congenital Arthrogryposis. Congenital Arthrogryposis is a neuromuscular disease which is characterized by contractures which happen at birth. A contracture is when muscles tighten and harder which causes issues with your joints. This is normally caused by a lack of movement in utero and a greater amount of connective tissue around the joints, which also limits movement. The affected limbs are typically underdeveloped and feel soft. At birth, this baby was born with her feet at her head and her joints were essentially frozen in place. The baby is in physical therapy to help ease and allow for some movement, but most movement is very painful and the range of motion is incredibly limited.

As far as the patient I am focusing on - the boy with myoclonus and ataxia - Dr. Narayanan and I have not yet discussed the data that they received from the exome sequencing. He had to go to California for a meeting today, so I was not able to go on site.

However, he will be back on Monday and we will hopefully discuss the results this coming week! But, so far on my research with this patient, I have seen how Dr. Narayanan has isolated his main concerns about the patient and why he thought exome sequencing would be a good idea. There are a few factors that make children poor candidates for sequencing which are being born very early and having a condition like bacterial meningitis or cerebral palsy. Because this patient did not present with those issues and his test for spinocerebellar ataxia came out negative, exome sequencing seemed like the next step in finding a diagnosis.

Well, I guess that’s all I’ve got for you guys this week! But, here’s an adorable gif that everyone should see. See you next week!

Week 5

Lol, maybe not fo'ever. Just this week. See you guys next week! 

Week 4

Hi everyone!! I hope your week went well! Before I get into what I did this week here’s a gif of a puppy that I thought I would share.

This week I went about my weekly shadowing of Dr. Narayanan on Mondays and Fridays. I saw a whole bunch of cases this week that were all so different and interesting. One of the more interesting ones was a 2 year old girl who suffered from Russell Silver Syndrome. Russell Silver syndrome is a growth disorder where children present with low muscle tone (which causes hypoglycemia), low birth weight, development at a much slower rate, but their head growth remains normal so it looks like they have a really big head. Along with having Russell Silvers syndrome, this little girl also has Temple Syndrome. Temple syndrome is caused by abnormalities on chromosome 14. Typically, each normal child inherits one chromosome from their mom, and one from their dad, but this patient inherited both from her mom on chromosome 14, which is called uniparental disomy. Patients with Temple syndrome often hit puberty much earlier on, and are also more inclined to obesity.

So, last week I got some of the patient notes for the patient I will be following. Dr. Narayanan and I were talking about the case and he explained to me how patient history is super important in deciding whether or not a patient is a viable candidate for sequencing. So, I thought I would share a little bit of that with you.

This patient had a normal birth and regular neonatal examination but when he was around 5 years old his kindergarten teachers had some concerns. After further testing, he presented with cerebellar ataxia, hyperreflexia, dysarthria, some cognitive delays, and convulsive epilepsy.c The main concern was with determining what was causing his ataxia. Cerebellar ataxia occurs when the cerebellum is damaged which causes issues with controlling muscle coordination. At first they believed the cause of the cerebellar ataxia was because of spinocerebellar degeneration. They ran tests for that which all came out negative. Because of the negative test results, Dr. Narayanan thought they should be enrolled into genomic studies for further testing.

Well, I guess that’s all I’ve got for you guys this week! And, since I started this blog post off with a cute dog gif, I guess I should finish the post that way too!