Emily and Janine to present at Student Seminar Thursday (25.June) at noon

Emily and Janine will be presenting Student Seminar this week in CBRB 2289 at noon. In keeping with Erik’s tradition, I have asked the speakers to provide a brief overview for their talks. Hope to see you there!

Background for Emily’s talk

Clinical data used to establish the pathogenicity of alleles

Clinical data used to establish the pathogenicity of alleles

The Stone Lab studies the molecular genetics of inherited eye disease, specifically focusing on diseases of the retina.  My project involves characterizing variation in the ABCA4 (OMIM) gene and correlating the molecular data with extensive clinical data in order to understand how variations in one gene can cause three very distinct clinical phenotypes.

Shortly after Allikmets and coworkers identified ABCA4 as the gene responsible for Stargardt disease (1997), Cremers et al. (1998) and Maugeri, et al. (2000) reported that variations in ABCA4 could also cause cone rod dystrophy. Cremers et al. (1998) and Martínez-Mir, et al. (1998) also identified cases of retinitis pigmentosa caused by variations in ABCA4 and suggested that varying amounts of residual gene function were responsible for the differences in phenotype seen in patients with ABCA4-related disease.  Over 400 different ABCA4 variations have been identified in patients with retinal disease and the fact that these variations usually behave in a recessive fashion makes it difficult to deduce the contribution that each allele makes to an individual patient’s disease.  That is, in outbred populations of North America, almost all patients with ABCA4-associated disease are compound heterozygotes.

We hypothesize that one could deduce the relative pathogenicity of some of the more common ABCA4 alleles by studying groups of compound heterozygotes who share one disease allele.  Within such a group, any differences in phenotype that are not due to the environment or the genetic background should be attributable to the difference in the second alleles.

Background for Janine’s talk

Janine in Back Island Left Cropped 3x4

DYT1 (OMIM) is the most common form of inherited dystonia (OMIM), a disabling neurologically based movement disorder.  This incurable disease is caused by the deletion of a glutamic acid residue in the protein torsinA (torA(ΔE)).  Because this mutation is found in nearly all DYT1 patients and that torA(ΔE) is believed to act in a dominant negative manner over torA(WT), allele-specific silencing of torA(ΔE) may be a potential therapeutic strategy for DYT1.  To test this our lab has developed shRNAs that specifically and effectively silence torA(ΔE) in cell cultures.  Viral delivery of these therapeutic constructs to DYT1 mouse models have shown unexpected RNAi toxicity, including behavioral defects and lethality.  Sensitivity to this shRNA induced toxicity appeared to vary between different backgrounds, something that should be factored into the design of future therapeutic RNAi trials.  Alterations to our therapeutic approach and plan for further experiments will be presented.

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Posted on June 22, 2009, in Student Seminar and tagged , , , , , , , , , , . Bookmark the permalink. 1 Comment.

  1. Hi
    I am a 66 yr old engineer with cone dystrophy that manifested itself about 10 yrs ago and has left me legally blind. I still maintain an active professional career but have not been able to drive for 9 yrs., which required major lifestyle changes. It is always gratifying to see ongoing work by students into such genetic abnormalities and I congradulate Emily and Janine on their findings and wish them the best of success in their careers.
    Bill Fellner P. Eng.

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