Allison Cox and Hung-Lin Chen Will Present their Research Thursday, 8/7/14
Whole Exome Analysis of Individuals and Families with Chronic Recurrent Multifocal Osteomyelitis (CRMO)
Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, autoinflammatory bone disease presenting in infancy and childhood. While CRMO is characterized by painful bone lesions, it is often comorbid with psoriasis or Crohn disease and many patients have close relatives with either of the more common disorders. Some syndromic cases of CRMO are caused by truncation mutations in the interleukin-1 receptor agonist (IL-1RA) gene and these children respond very well to treatment with recombinant IL-1RA. However, most cases are non-syndromic with an unknown genetic cause, although many patients respond to TNF-α blocking agents, implicating the pathway in the disease. Using whole exome sequencing paired with genetic analyses based on inheritance patterns in several affected families, I hope to determine a component of CRMO’s underlying genetics. Preliminary results implicate a shared pathway in the pathogenesis of the disease. I am currently sequencing a candidate gene in a large cohort of CRMO samples from our laboratory.
Effect of diet on genetically inherited seizure-like behavior in Drosophila
Hung-Lin Chen,1 Patrick Lansdon,1 Junko Kasuya,2 Toshihiro Kitamoto1,2
1Interdisciplinary Genetics Ph.D. Program and 2Department of Anesthesia
Nutritional therapies have the great potential to prevent or treat various neurological disorders, such as epilepsy, in an effective, natural, and economical manner. However, their exact therapeutic values have not been rigorously evaluated in most cases and the molecular mechanisms responsible for their beneficial effects remain elusive. The goal of this study is to unravel the fundamental molecular underpinnings of nutritional therapies for genetically inherited neurological dysfunctions using the fruit fly Drosophila melanogaster as a model organism. Shudderer (Shu) is a classical Drosophila mutant that is characterized by strong spontaneous jerking and twitching. Our molecular analysis revealed that Shu carries a gain-of-function mutation in the voltage-gated sodium channel gene, paralytic. Here we report that feeding Shu mutants a modified diet results in drastic improvement of their seizure-like phenotypes. Shu needs to be fed the “therapeutic” diet during the larval stage in order to receive a maximum benefit from the food, suggesting that the diet has a therapeutic effect on Shu by affecting development of the nervous system. These findings are significant because they provide an unprecedented opportunity to employ versatile experimental tools available for Drosophila and investigate the mechanisms underlying the diet-dependent improvement of inherited behavioral abnormalities under strictly controlled genetic and environmental conditions.