This web page was produced as an assignment for an undergraduate course at Davidson College.

Ingrid Wagnon's Genomics Home Page

Assignment 1 : Developmental Disorders and de novo Mutations

The research project reported in the article "Prevalence and architecture of de novo mutations in developmental disorders" (McRae et al. 2017) was to find de novo mutations (DNMs) of crucial developmental genes in patients affected by severe, unknown developmental disorder. “De novo mutations” means that the mutations aren’t present in parent’s genome. These mutations can be present in the parent’s gametes or can occur during the development of the zygote. Besides identifying the genes touched by DNMs, they also tried to identify main factors that can influence the DNMs frequency.

In this study, the main point is not to test a hypothesis but to discover new mutations that could have a role in undiagnosed developmental disorders. It required the combination of several data base to integrate all the information concerning the phenotypes of the individuals, the already-known mutations, the genomes of the patients…

Two principal genomic technologies were used during this study: Exome sequencing and the examination of Single Nucleotide variants, insertions and deletions. For the exome sequencing, they selected the targeted sections of DNA (which are exons) and sequenced them using the Illumina HiSeq instruments. They analyzed data concerning Single Nucleotide by comparing the different sequence of DNA with each other.

They identified 94 genes containing DNM linked to developmental disorders, among which 14 weren’t suspected before. It has been estimated than 2 to 5 percent of new born infants are concerned by developmental disorders. The findings of this study can be very useful by helping psychiatrists to establish their diagnosis and their therapy choices. The rare disorders could be categorized and identified as long as we know which genes are being mutated.

I found this project quiet interesting taking into account all the data that were used and analyzed. I also chose this article because I found Developmental Disorders (and all psychiatric disorders in general) very intriguing. I think the more we explore the causes of psychiatric disorders, their mechanisms and all their possible mutations in details, the more we have a chance to develop appropriate and efficient therapies, and the more we have a chance to find relevant elements that could help in the understanding of other disorders (not only developmental and maybe not only psychiatric) like autism for example. I also think that trying to find some risk factors is interesting in order to work upstream the disorders and raise awareness among parents (make some prevention).


Sources:
McRae JF et al., 2017. Prevalence and architecture of de novo mutations in developmental disorders. Nature [Internet]. [cited 29 Jan 2017]. Available from: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature21062.html

Exome Sequencing Reveals Novel Genes Linked to Developmental Disorders [Internet]. 2017. [cited 2017 Jan 29]. Available from https://www.genomeweb.com/sequencing/exome-sequencing-reveals-novel-genes-linked-developmental-disorders

Links:
http://www.nature.com/nature/journal/vaop/ncurrent/full/nature21062.html
https://www.genomeweb.com/sequencing/exome-sequencing-reveals-novel-genes-linked-developmental-disorders

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