Noemie Riendeau
NOÉMIE RIENDEAU- MSC DEFENSE PROGRAMME
B.Sc., McGill University, 2005
Friday, September 4, 2009, 2:00 pm Room D210, Children’s
and Women’s Health Centre of BC 4480 Oak Street, Vancouver
Noemie Reindeau- Defense Programme pdf
Chair: Dr. Marco Marra (Medical Genetics)
Supervisory Committee:
Dr. Suzanne Lewis, Research Supervisor (Medical Genetics)
Dr. Evica Rajcan-Separovic, Research Co-Supervisor
(Pathology)
Dr. Wendy Robinson (Medical Genetics)
University Examiner:
SUPERVISORY COMMITTEE
Dr. Suzanne Lewis
Dr. Evica Rajcan-Separovic
Dr. Wendy Robinson
Dr. Margot Van Allen
ABSTRACT
Background: Autism Spectrum Disorders
(ASDs) are common, heritable neurobiologic conditions of unknown etiology
confounded by significant clinical and genetic heterogeneity. In recent years, array CGH technology
has been used to screen the genome for pathogenic copy number variants (pCNVs)
associated with ASDs and data from 6 studies suggests that pCNVs contribute to
ASD pathogenesis in 6-27% of cases. However, the role of pCNVs in ASDs remains
poorly understood, due to the absence of comprehensive phenotyping of ASD
subjects.
Methods: To address this, we collected detailed clinical,
medical, physical and morphologic information on all subjects and investigated
whether these phenotypes would be good indicators of pCNV risk. We studied
somatic phenotypes, as opposed to behavioural indices that change over time and
with treatment, in an attempt to provide better evidence for the
biological/embryological origin of ASDs and help define new syndromes.
Results: Seven disease-specific and
potentially pathogenic CNVs were uncovered in 6/40 patients (15%). Two changes
were de novo and 5 were inherited from normal parents, but had never been
reported in normal populations before.
All pCNVs were discovered in individuals without family history of
autism, ranged in sizes from 175kb to 2.5Mb, and revealed 9 good candidate genes. Our results suggest that
whilst no single phenotypic feature investigated associates with pCNV risk,
there is an indication that the presence of phenotypic abnormalities involving
multiple body areas may be a better indicator of pCNVs in ASDs than the
presence or number of minor physical anomalies alone. In addition, our findings
lend support to the idea that complex autism, involving significant
dysmorphology, is etiologically distinct from essential autism, with an
increased prevalence of ID, seizures and health problems, and a higher
proportion of individuals without family history of ASDs.
Conclusion: We identified novel areas of chromosomal
imbalance associated with ASDs and provide detailed phenotypic information for
every subject for which these new pCNVs were detected. The extensive
phenotyping of affected individuals carrying clinically relevant CNVs is needed
in order to understand their role in the etiology of autism and ultimately
provide earlier and more reliable means for diagnosis and treatment.
PUBLICATIONS
Qiao Y., Harvard C., Riendeau
N., Fawcett C., Liu X., Holden JJ., Lewis ME., Rajcan-Separovic E. (2008) Putatively benign copy number
variants in subjects with idiopathic autism spectrum disorder and/or
intellectual disability. Cytogenet
Genome Res 123(1-4): 79-87
SELECTED PRESENTATIONS
October 2007 FISH confirmation of array-detected
microduplications: an assessment of discrepancies with real-time qPCR findings
November 2008 Phenomic determinants of genomic variation
in autism spectrum
disorders
June 2009 Autism Spectrum disorders: Identification of
novel microdeletions and microduplications and their associated phenotypes
AWARDS
2006-2007 UBC Graduate Entrance Scholarship
2006-2007 CIHR Canada Graduate Scholarship-Masters
2006-2009 CIHR/NAAR Inter-Institute Interdisciplinary
Strategic Training Program
in Autism Spectrum Disorders
2007-2009 Fondation pour la Recherche en Santé du
Québec-Bourse de Maîtrise (Masters Scholarship)
2007-2009 Michael Smith Foundation for Health Research,
Junior Graduate
Studentship