Using Zebrafish to Provide Genetic Answers

Susan Brooks, a medical geneticist of the Rutgers Robert Wood Johnson Medical School used zebrafish as a model organism to help identify the cause of a rare genetic disorder affecting a boy and his two uncles.  The boy suffered from seizures, fevers, slow growth, and poor head growth resulting in microcephaly.  Susan Brooks discovered that the peculiar disorder was most likely caused by a recessive mutation on the X-chromosome, as the boy's uncles shared similar symptoms.   These X-linked mutations can be carried by both males and females, but cause symptoms only in males with very few exceptions.

Scientists found a mutation carried by the affected males and their mothers, within a gene known as RPL 10.  It is located on the X-chromosome and encodes part of the ribosome, which is a vital piece of molecular equipment that is responsible for translating genetic code into proteins.  Scientists used zebrafish to test the effect of the mutation.  Duke University researchers led by Erica Davis from the Center for Human Disease Modeling displayed that the diminishing expression of the RPL 10 gene caused organisms to develop notably smaller heads, or the fish version of microcephaly.

The image above displays the effect of the expression of the RPL 10 gene (top), 

versus the suppressed expression of the RPL 10 gene (bottom) in the heads of zebrafish.

Unfortunately, identifying the likely cause of the disorder does not ensure a cure for the boy and his two uncles, but it is the first step for future research in developing treatments.  Erica Davis stated, "This was a one-of-a-kind family affected by a disorder that no one had ever seen before, but they are not alone.  The best way of finding answers for these families is for clinicians and model organism researchers to join forces."  Zebrafish and humans share approximately 70% of protein-coding genes, and 84% when the genes known to be associated with disease are considered.  Zebrafish are a very important model organism in genetics.  They are cheaper to maintain and grow faster than mice.

This article caught my eye immediately, as I conducted research with Dr. Brian Rogerson last semester using zebrafish.  We analyzed AICD (Activation-induced cytidine deaminase) levels in young and old zebrafish, which is an enzyme known to be responsible for the mutation of antibody genes.  Due to being familiar with the use of zebrafish as a model organism, I am very interested in learning about how they are being used in other studies.  I find it fascinating that the diminished expression of the RPL 10 gene had a very similar impact on zebrafish, as it did on humans.  It opens up an unlimited number of possibilities in the future regarding the use of zebrafish in studying human disease.

Article [1]: http://medicalxpress.com/news/2014-10-family-zebrafish-genetic.html 
Related Article: http://www.genetics-gsa.org/news/templates/?a=210&z=1