Oral Presentations - Pathology and Laboratory Medicine - University ...

Graduate StudentAbstract # 63Chansonette Harvard*Harvard C. 1-3 , *Strong E. 1-3 , Martell S. 1-3 , Tyson C. 6 , McGillivray B. 4 , Hamilton S. 4 ,Marles S. 7 , Mhanni A. 7 , Chow E. 10 , Pavlidis P. 5 , Qiao Y. 1-4 , Holden J.J.A. 8,9 ,Lewis M.E. S. 1,4 , and Rajcan-Separovic, E. 1-4 *first and second author contributed equally to this work1Child and Family Research Institute, 2 Molecular Cytogenetics and Array Lab, Vancouver, BC; 3 Depts. ofPathology, 4 Medical Genetics, and 5 Psychiatry, UBC, Vancouver, BC; 6 Cytogenetics Lab, RCH, New Westminster,BC; 7 Dept. of Biochemistry and Medical Genetics, U of M, Winnipeg, MN; 8 Dept of Physiology and 9 Psychiatry,Queen’s, Kingston, ON; 10 Centre for Addiction and Mental Health, Toronto, ONphenotypic and genomic variability of the 1q21.1 copynumber variant (cnv) region in multigenerationalfamiliesBackround/ObjectivesPathologic chromosomal microdeletions and microduplication (DNA copy number variants or CNVs) detectedusing whole genome arrays, occur in 10-15% of subject with idiopathic intellectual disability (ID). In addition topathogenic CNVs array analysis detects CNV with uncertain clinical significance as they occur in both normal and IDsubjects and show variable phenotype in subjects with ID. The underlying cause of this phenotypic variability is notknown, but several explanations have recently been suggested, including a second genomic hit theory which postulatesthat a second CNV might be responsible for the variation in the phenotype.Chromosome 1q21.1 has been identified as a region showing copy number changes resulting in variable phenotypein affected ID subjects, and can also occur in unaffected relatives of the affected subjects. Our current study exploresthe possible reasons for this variability by a) comparing the 1q21.1 genomic regions deleted or duplicated in affectedsubjects and their unaffected relatives b) looking for second hit CNV by high resolution whole genome analysis whichcould contribute to phenotypic variability and c) comparing the whole genome expression profiles for the affected andunaffected subjects. We have noted that in 4 families with 4 subjects with significant ID, 2 mildly affected relativesand 2 phenotypically normal relatives the genomic regions affected did not generally differ significantly betweendifferent phenotypic groups. In one family a severely affected female showed an isolated deletion of the 1q21.1 regionwhile her mildly affected brother showed a deletion and a duplication within the same 1q21.1 region. The presence ofa second hit CNV was excluded, except in one affected subject with significant ID (this CNV is currently undergoingconfirmation). For whole genome expression studies, we have first confirmed expression of genes within the 1q21.1CNV in the blood from control individuals and then performed whole genome expression studies in affected andunaffected family members using the Illumina array. The expression data analysis is in progress. The results of ourwork are expected to contribute to the understanding of phenotypic variability of subjects with ID who have the same1q21.1 CNV and further delineate their genomic and functional correlates.74 2 0 1 0 * P o s t e r P r e s e n t a t i o n s