About this blog

The goal of this blog is to catalog the process of finding the genetic cause of an inherited disease. Stacy was diagnosed with CMT4 (Charcot-Marie-Tooth Type 4) in the 1980s following a nerve biopsy which showed the characteristic onion-bulb myelin sheath around peripheral nerves and after measuring nerve conduction velocities along the length of her leg. There are many different causes of CMT, many known and many unknown. Stacy recently had her exome sequenced. My goal is to find the genetic basis of this disease. My name is Erik Corona and I am PhD student in the Stanford Medical school studying the genetics of complex disease. I will be making all results public and I will also post all code and/or scripts I use to generate these results. I will be posting screenshots of candidate structural variants and making every step along the way transparent and clear. This blog will represent a detailed case study of how we now have the technology and ability to use sequence data to find the genetic cause of a rare inherited disease. I welcome all comments, advice, and suggestions.

Data

Stacy has decided to make all the genes relevant to CMT4 public. I will be posting bam files for the regions overlapping the genes causing CMT4 as we examine every one of these genes throughout the blog. This is done to allow others to join in and analyze Stacy's exome.

Motivation

Stacy and I have been together for almost the entire time I've been working towards my PhD here at Stanford. Ever since Stacy came into my life, I have been happier, more fulfilled, and have managed to trick people into thinking I have a sense of fashion. To say the least, I consider myself extremely fortunate to have Stacy in my life. Some of you already know how painful it can be to have someone you love affected by a serious disease. As a PhD student who studies the genetics of disease, I find myself in the most fortunate position to be able to do something about it. I intend to use all of my knowledge to first isolate the mutation causing this disease and then plan to focus on furthering research into this condition. I don't know what the end result of this work will be, but at the very least I hope that it will further our understanding of this disease and be informative for the curious or others wishing to do the same.

                                                            Stacy and Erik

Rough Roadmap

Phase I Finding the Genetic Cause of the Disease:

1. Find all variants known to cause CMT4 and check Stacy's exome for their presence.
2. Find all variants known to cause any type of CMT (CMT1, CMT2, etc.).
3. Find unique mutations in genes known to cause CMT (CMT1, CMT2, CMT3, etc.). Check if they are unique by comparing against the 1000 genomes project.
4. Find all unique mutations in any gen. Once again, we will check if they're unique using 1000 genomes. Check any of these genes assists in myelin sheath formation to isolate candidates.

Phase II: Depends on results of Phase I

About Stacy

Stacy is a 28 year old female who can only walk for short periods of time with a walker due to improper myelin sheath formation around peripheral nerves. Lack of dexterity, ataxia, and inability to walk are the main symptoms. If you or anyone you know is from North Carolina or surrounding states and has been diagnosed with a demyelinating type of CMT, please contact me.