Lily and Danielle to present at Student Seminar on Thursday (23.September at 12:30 in 2-501 BSB

Lily and Danielle will be presenting Student Seminar this week in 2-501 BSB at 12:30 (please note the room change). I have asked the speakers to provide a brief overview for their talks. Hope to see you there!

Background for Lily’s talk


Epilepsy is a complex genetic brain disorder that is characterized by seizures and afflicts 50 million people worldwide. Over 35 dominant genes in consanguineous families cause epilepsy but the role of autosomal recessive genes remains largely unexplored. Progressive Myoclonic Epilepsy (PME) is a subset of epilepsy characterized by neurodegeneration, myoclonus, and generalized seizures. A number of genes identified in consanguineous families such as CSTB, MALIN & LAFORIN are responsible for 80% of PME cases, but the remaining causes of the 20% remain unknown. Bassuk et. al identified mutations in Prickle1 and Prickle2 responsible for PME in the general population. Prickles are expressed in the developing nervous system and mature neurons, involved Planar Cell Polarity and are players in Wnt-mediated signaling; a cascade likely critical in neurodevelopment and neurodegeneration. The involvement of Malin, Laforin, and Prickles in Wnt signaling suggests that Wnt could be an anti-epileptic target. Co-Immunoprecipitation assays carried out to verify interactions between wild-type Prickle1 and members of the Wnt pathway (Disheveled, Smurf, Rest, etc) confirmed some of these Interactions. Future experiments include characterizing the effect of Prickle mutations on protein-protein interactions and neuronal differentiation. Findings from these studies would clarify molecular mechanisms by which Prickle mutations alter neuronal function and help identify novel therapeutic targets.

Background for Danielle’s talk

Identifying CNVs from SNP Arrays that Influence Schizophrenia Susceptibility

Schizophrenia (OMIM) is a serious mental disorder that strikes in early adulthood and has heritability estimates up to 80%.  It is a life-long disability without a cure and many attempts have been made to identify genetic components, but the complexity of the disease confounds these efforts.  I will identify genome-wide copy-number variants (CNVs) in a sample set and determine whether such CNVs are characterized by a common phenotypic profile.  I will run DNA on Affymetrix Genome-Wide Human SNP Array 6.0 microarrays which provide signal intensity data that can be analyzed with Affymetrix Genotyping Console 3.0 to provide copy number data.  To date we have analyzed 124 probands and 61 controls.  CNVs discussed in this abstract were confirmed by qPCR and were not found to be present in controls.  In four subjects we identified a deletion that encompasses the entire gene  (OMIM) which is located at 15q11.2.  CYFIP1 functions in synaptic plasticity, brain development, regulation of axonal and dendritic outgrowth and development and maintenance of neuronal structure.  It also interacts with fragile-X mental retardation protein (FMRP).  Of the four subjects we identified this deletion in, three are patients and one is the mother of one.  This means that we have a case where the deletion was transmitted from the mother to the offspring.  The inherited deletion is 627 kb in size and the other two are 975 kb and 581 kb, respectively.  Both genes reported here have been reported in other studies and both inherited and spontaneous mutations and both are believed to act in a gene dose dependent manner.  Preliminary results in our genome-wide analysis of copy number variation in schizophrenia have identified promising candidates for disease etiology.  Future directions include analysis and validation of CNVs in the remainder of the sample set.


Posted on September 20, 2010, in Student Seminar and tagged , , , , , , , , , . Bookmark the permalink. Leave a comment.

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