QBI Seminar: Identification and functional characterization of genetic variants in an Australian autism spectrum disorder cohort
Event Details
- Date:
- Wednesday, 08 July 2015 - Wednesday, 08 July 2015
- Time:
- 12:00 pm - 1:00 pm
- Room:
- QBI Level 7 Auditorium
- UQ Location:
- Queensland Brain Institute (St Lucia)
- URL:
- http://www.qbi.uq.edu.au/neuroscience-seminars
- Event category(s):
Event Contact
- Name:
- Ms Deirdre Wilson
- Phone:
- 66300
- Email:
- d.wilson5@uq.edu.au
- Org. Unit:
- Queensland Brain Institute
Event Description
- Full Description:
- Joon-Yong An, Queensland Brain Institute, University of Queensland
Title: Identification and functional characterization of genetic variants in an Australian autism spectrum disorder cohort
Abstract:
Recently, there is growing evidence highlighting the importance of de novo and rare loss-of-function (LoF) coding variants in autism spectrum disorder (ASD). However, it still remains unknown whether multiple rare heterozygous variants inherited from parents contribute to ASD development. Moreover, inherited variants associated with regulatory sequences have not been studied extensively. My thesis suggests how combinations of multiple rare heterozygous variants converge on functional processes and putatively contribute to the causal profile of individuals with an ASD.
The study conducted the whole exome sequencing (WES; 64Mb) and high-density SNP array (2.7M markers) for 40 ASD families (n=128; including 48 cases). Genetic variations were examined in coding regions, but also in non-coding regions by integrating multiple studies and databases for regulatory elements, such as transcription factor binding sites, promoters, enhancers, microRNA target sites and microRNA genes. Then, I defined rare variants based on minor allele frequency and functional/evolutionary conservation. To test whether rare variants are associated with ASD, I utilized the AXAS model, a gene network model recently developed for profiling the functional patterns of heterogeneous DNA variants overrepresented in ASD, X-linked intellectual disorder, attention deficit and hyperactivity disorder and schizophrenia. The AXAS model reveled the significant enrichment of rare variants with ASD in ASD cases, not in non-ASD controls (n=967). Furthermore, it also showed the genetic contribution of rare variants inherited from parents with a broader autism phenotype (BAP). Finally, I showed convergent pathways where inherited variants of different origin and de novo variations are combined in individual ASD cases, and identified multiple cases had this pattern in the L1CAM pathway involved in axon guidance. The thesis provides an important step forward in the molecular characterization of ASD with potential for developing a tool to analyze the pathogenesis of individual affected families.
Directions to UQ
- Google Map:
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- Directions:
- St Lucia Campus | Gatton campus.
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