Mentor: Evica Rajcan-Separovic

Pathology and Lab Medicine

University of British Columbia

Website: click here

Trainees

Ying Qiao, Noemie Riendeau

Research Projects: Improving the health of children with intellectual disabilities by early identification of genetic causes

Intellectual disability (ID) is a diagnosis given to persons who have life-long cognitive and adaptive impairments that commence in early life. ID affects about 1-3% of the population, thus nearly 1 million Canadians have an ID. The cause of ID is unknown in at least 40% of all cases. Recent reports have suggested that very tiny chromosome changes are the cause of many cases of ID. These tiny chromosome anomalies are usually not seen using routine microscopic analysis. However, recently developed microarray technology provides an opportunity to detect these very small changes. We propose to use this technology to look for such abnormalities in 160 children with ID. Our preliminary findings suggest that about 20% of children with ID will have a very small genetic change that we will be able to detect. Once we have identified specific genetic changes, we will examine another 1000 individuals with ID and 100 controls to see if we can find additional individuals with the same abnormality. By studying a number of individuals with the same chromosome change, we will be able to determine what physical features and medical issues are due to that genetic change. Our next step will be to develop Health Care Watches for each new condition that we identify. These will describe expected health issues, so that families and physicians can be better prepared to care for children with these new genetic syndromes. This approach will eliminate costly multiple testing and searching for answers, and should allow optimal care and health for persons with ID. Our strategy toward better understanding the genetic basis of ID advocates a gene-based template which will link diagnosis with the promotion of informed clinical observation, characterization, natural history studies and health watch guidelines critical to the anticipatory care and needs of children and families affected by ID.

Publications

1. *Li J, Jiang T, Bejjani B, Rajcan-Separovic E, Cai WW. High-resolution human genome scanning using whole-genome BAC arrays. Cold Spring Harb Symp Quant Biol. 2004;68:323-9.
   
2. Tyson C, McGillivray B, Chijiwa C, Rajcan-Separovic E. Elucidation of a cryptic interstitial 7q31.3 deletion in a patient with a language disorder and mild mental retardation by array-CGH. Am J Med Genet A. 2004 Sep 1;129(3):254-60.
   
3. Harvard C, Malenfant P, Koochek M, Creighton S, Mickelson EC, Holden JJ, Lewis ME, Rajcan-Separovic E. A variant Cri du Chat phenotype and autism spectrum disorder in a subject with de novo cryptic microdeletions involving 5p15.2 and 3p24.3-25 detected using whole genomic array CGH. Clin Genet. 2005 Apr;67(4):341-51.
   
4. Tyson C, Harvard C, Locker R, Friedman JM, Langlois S, Lewis ME, Van Allen M, Somerville M, Arbour L, Clarke L, McGilivray B, Yong SL, Siegel-Bartel J, Rajcan-Separovic E. Submicroscopic deletions and duplications in individuals with intellectual disability detected by array-CGH. Am J Med Genet A. 2005 Dec 15;139(3):173-85.
   
5. Koochek M, Harvard C, Van Allen M, Hildebrand JM, Holden JJA, Rajcan-Separovic E, MES Lewis (2006) Gain of Proximal 15q causing autism detected using whole genomic 1Mb array-CGH is a result of familial cryptic translocation t (14;15) (q11.2;q13) in a three generation family. Clin Genet; Feb; 69(2):124-34.
   
6. E. Rajcan-Separovic, C. Harvard, B. McGillivray, J.G. Hall, Y. Qiao, E. Mickelson,J.J.A. Holden and M.E.S. Lewis (2006)Clinical and molecular cytogenetic characterization of a newly recognized microdeletion syndrome involving 2p15-16.1 revealed by array CGH. Journal of Medical Genetics, in press

Presentations

1. ,0Ying Qiao, Francois Bernier, Chansonette Harvard, Jeanette J.A. Holden, M.E. Suzanne Lewis, Evica Rajcan-Separovic (2006) Two different submicroscopic chromosomal rearrangements detected in two siblings with idiopathic intellectual disability and dissimilar phenotypes, CCMG meeting, Winnipeg, oral presentation
   
2. Evica Rajcan-Separovic, Chansonette Harvard, Barbara McGillivray, Judith Hall, Ying Qiao, Jane Hurlburt, Jeanette Hildebrand, Elizabeth Mickelson, Jeanette J.A. Holden, and M.E. Suzanne Lewis. Clinical and molecular cytogenetic characterization of a newly recognized microdeletion syndrome involving 2p15-16.1. CCMG meeting, oral presentation, 2005
   
3. Chansonette Harvard, Ying Qiao, Martin Somerville, Jane Hurlburt, Maryam Koochek, Jeanette J.A. Holden, M.E. Suzanne Lewis, Evica Rajcan-Separovic. Array CGH: comparison of 0.03 and 1Mb resolution analysis.CCMG meeting, Winnipeg, 2005

Research Opportunities