My laboratory studies chromosomes and their changes in a variety of human diseases such as intellectual disability, autism and cancer. We are especially interested in tiny chromosomal changes that are invisible under the microscope. We use a recently developed technology of genomic microarrays, which allows detection of microscopically invisible (or sub-microscopic) changes. Genomic microarrays are very short segments of DNA sampled from all human chromosomes and arrayed on glass slides. They provide a resolution higher than routine chromosome analysis and allow detection of very small chromosomal changes. The identification and accurate description of these small chromosomal changes will help the identification of new genetic causes of common human diseases.

The major focus of my research laboratory is the chromosomal etiology of human diseases. We use the most up-to-date molecular cytogenetic techniques such as FISH, chromosomal comparative genomic hybridization (CGH), and array CGH to identify and elucidate the nature of chromosomal abnormalities in individuals with neuro-developmental delay, congenital malformations and cancer.

Two years ago my laboratory started using CGH microarrays for identifying novel microdeletions and microduplications associated with intellectual disability. Our hypothesis is that due to a low resolution of the routine cytogenetic analysis, deletions or duplications of chromosomal regions less than 10 Mb remain undetected and that the recently developed genomic microarray technology can be used for identification of novel sub-microscopic chromosomal abnormalities at a whole genome level. In the past two years we have validated the use of the commercial genomic arrays (this array provides a 10-20 times better resolution than routine cytogenetic analysis), refined the cytogenetic rearrangements in patients with intellectual disability and identified novel cytogenetic abnormalities too small to be detected using routine cytogenetics. I see the application of genomic arrays for identification of novel microduplications/ microdeletions in individuals with intellectual disability and autism as the primary focus of my research in the future.

In addition to studying the prevalence and types of sub-microscopic rearrangements in children with intellectual disability and/or autism using genomic array, we will analyze the detected sub-microscopic chromosomal abnormalities at the molecular level in order to identify potential culprit genes. We will also look for their presence in a larger group of individuals affected with autism and intellectual disability. This goal will be achieved in collaboration with several centers across the country ( University of Alberta , Edmonton ; Queens University , Kingston ).

My laboratory is also applying the array technology to look for subtle chromosomal rearrangements in pediatric cancer, funded by the BC Children's Hospital Research Foundation. I expect that my research program will help the identification of novel and subtle chromosomal abnormalities as the cause of common human diseases such as intellectual disability, autism and cancer.

Harvard C, Malefant P, Koochek M, Lewis S, Holden JJ, Rajcan-Separovic E (2005) A variant Cri du Chat phenotype and autism spectrum disorder in a patient with de novo cryptic microdeletions involving 5p15.1 and 3p24.3-25 detected using the whole genomic array CGH, Clinical Genetics, 67(4):341-51.

Tyson C, McGilivray, Chijiwa C, Rajcan-Separovic E (2004) Elucidation of a cryptic interstitial 7q31.1 deletion in a patient with a language disorder and mental retardation by array CGH. American Journal of Medical Genetics, 129A:254-60.

Li J, Jiang t, Bejjani B, Rajcan-Separovic E, and Cai WW (2004): High resolution genome scanning using whole genome BAC arrays. In: The Genome of Homo sapiens, Volume 68, Cold Spring Harbor Symposia on Quantitative Biology, Volume 68, 323-328.

Rajcan-Separovic E, Maguire J, Loukianova T, Nisha M, Kalousek D. (2003) Loss of 1p and 7p in radiation induced meningiomas identified by comparative genomic hybridization. Cancer Genetics and Cytogenetics, 144(1) 6-11, 2003.

Bruyere H, Rajcan-Separovic E, Kalousek D (2002). Methods in Molecular Medicine: Molecular Cytogenetics: Protocols and Applications, Humana Press, September 2002 issue, 299-307.

Rajcan-Separovic E, Hendson G, Tang S, Seto E, Thomson T, Phillips D, Kalousek D. (2002) Interphase FISH in combination with DNA analysis by flow cytometry improves the results of cytogenetic analysis of pediatric medulloblastoma. Cancer Genetics and Cytogenetics 133 (1):94-7.

Lagace M, Xuan JY, Young SS, McRoberts C, Maier J, Rajcan-Separovic E, Korneluk RG (2001). Genomic organization of the X-linked inhibitor of apoptosis and identification of a novel testis-specific transcript. Genomic 77(3):181-8.

Rajcan-Separovic E, Robinson W, Stephenson M, Pantzar T, Arbour L, McFadden D, Guscot J. (2001). Recurrent trisomy 15 a female carrier of t (Y; 15). American Journal of Medical Genetics 99:320-325.

Fong W, Liston P, Rajcan-Separovic E, St. Jean M, Craig C, Korneluk RG (2000). Expression and Genetic Analysis of Xiap-Associated Factor 1 (XAF) in Cancer Cell Lines. Genomics, 70, 113-122.

CIHR short exchange visit award to visit Baylor College ( Houston , USA )

CIHR Clinical Investigatorship salary award - 2005-07

Dr Ying Qiao - Postdoctoral fellow

Chansonette Harvard - Research assistant

Maryam Koochek - MSc student

Celina Fawcett - Research assistant

Noriko Vickerson - Research assistant