My laboratory studies genomic abnormalities as the cause of human diseases. We use genomic microarrays to detect tiny chromosomal microdeletions and microduplications in patients with intellectual disability, autism or reproductive disorders. Most recently, we started using next generation sequencing to identify even smaller abnormalities in the DNA from our patients. Our current interest includes finding the functional consequences of gene copy number or sequence changes in patient cells and in animal models (e.g. zebrafish or C.elegans). Our ultimate goal is to understand better the connection between the phenotypic abnormalities in our patients and the defects in their genes.


Whole exome sequencing of families with 1q21.1 microdeletion or microduplication
American Journal of Medical Genetics Part A
Ying Qiao and Chansonette Badduke and Flamingo Tang and David Cowieson and Sally Martell and Suzanne M. E. Lewis and Maria S. Peñaherrera and Wendy P. Robinson and Allen Volchuk and Evica Rajcan-Separovic
DOI: 10.1002/ajmg.a.38247

Exome sequencing identifies pathogenic variants of VPS13B in a patient with familial 16p11.2 duplication.
Dastan J and Chijiwa C and Tang F and Martell S and Qiao Y and Rajcan-Separovic E and Lewis ME
DOI: 10.1186/s12881-016-0340-0
PubMed: 27832746

Interactive Exploration, Analysis, and Visualization of Complex Phenome-Genome Datasets with ASPIREdb.
Tan PP and Rogic S and Zoubarev A and McDonald C and Lui F and Charathsandran G and Jacobson M and Belmadani M and Leong J and Van Rossum T and Portales-Casamar E and Qiao Y and Calli K and Liu X and Hudson M and Rajcan-Separovic E and Lewis MS and Pavlidis P
DOI: 10.1002/humu.23011
PubMed: 27158917

Whole exome sequencing in recurrent early pregnancy loss.
Qiao Y and Wen J and Tang F and Martell S and Shomer N and Leung PC and Stephenson MD and Rajcan-Separovic E
DOI: 10.1093/molehr/gaw008
PubMed: 26826164

Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis.
Bagheri H and Badduke C and Qiao Y and Colnaghi R and Abramowicz I and Alcantara D and Dunham C and Wen J and Wildin RS and Nowaczyk MJ and Eichmeyer J and Lehman A and Maranda B and Martell S and Shan X and Lewis SM and O'Driscoll M and Gregory-Evans CY and Rajcan-Separovic E
PubMed: 27699255

Genomic characteristics of miscarriage copy number variants.
Bagheri H and Mercier E and Qiao Y and Stephenson MD and Rajcan-Separovic E
DOI: 10.1093/molehr/gav030
PubMed: 26071097

The role of MAGT1 in genetic syndromes.
Trapani V and Shomer N and Rajcan-Separovic E
PubMed: 26422833

A Potential Contributory Role for Ciliary Dysfunction in the 16p11.2 600 kb BP4-BP5 Pathology.
Migliavacca E and Golzio C and Männik K and Blumenthal I and Oh EC and Harewood L and Kosmicki JA and Loviglio MN and Giannuzzi G and Hippolyte L and Maillard AM and Alfaiz AA and 16p11.2 European Consortium and van Haelst MM and Andrieux J and Gusella JF and Daly MJ and Beckmann JS and Jacquemont S and Talkowski ME
DOI: 10.1016/j.ajhg.2015.04.002
PubMed: 25937446

Functional consequences of copy number variants in miscarriage.
Wen J and Hanna CW and Martell S and Leung PC and Lewis SM and Robinson WP and Stephenson MD and Rajcan-Separovic E
DOI: 10.1186/s13039-015-0109-8
PubMed: 25674159

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy.
Reinthaler EM and Lal D and Lebon S and Hildebrand MS and Dahl HH and Regan BM and Feucht M and Steinböck H and Neophytou B and Ronen GM and Roche L and Gruber-Sedlmayr U and Geldner J and Haberlandt E and Hoffmann P and Herms S and Gieger C and Waldenberger M and Franke A and Wittig M
DOI: 10.1093/hmg/ddu306
PubMed: 24939913

Variant ATRX syndrome with dysfunction of ATRX and MAGT1 genes.
Qiao Y and Mondal K and Trapani V and Wen J and Carpenter G and Wildin R and Price EM and Gibbons RJ and Eichmeyer J and Jiang R and DuPont B and Martell S and Lewis SM and Robinson WP and O'Driscoll M and Wolf FI and Zwick ME and Rajcan-Separovic E
DOI: 10.1002/humu.22465
PubMed: 24130152

Copy number variants (CNVs) analysis in a deeply phenotyped cohort of individuals with intellectual disability (ID).
Qiao Y and Mercier E and Dastan J and Hurlburt J and McGillivray B and Chudley AE and Farrell S and Bernier FP and Lewis MS and Pavlidis P and Rajcan-Separovic E
DOI: 10.1186/1471-2350-15-82
PubMed: 25030379

miRNA and miRNA target genes in copy number variations occurring in individuals with intellectual disability.
Qiao Y and Badduke C and Mercier E and Lewis SM and Pavlidis P and Rajcan-Separovic E
DOI: 10.1186/1471-2164-14-544
PubMed: 23937676

Genotype-phenotype analysis of 18q12.1-q12.2 copy number variation in autism.
Wang P and Carrion P and Qiao Y and Tyson C and Hrynchak M and Calli K and Lopez-Rangel E and Andrieux J and Delobel B and Duban-Bedu B and Thuresson AC and Annerén G and Liu X and Rajcan-Separovic E and Suzanne Lewis ME
DOI: 10.1016/j.ejmg.2013.05.006
PubMed: 23727450

Phenotypic and functional consequences of haploinsufficiency of genes from exocyst and retinoic acid pathway due to a recurrent microdeletion of 2p13.2.
Wen J and Lopes F and Soares G and Farrell SA and Nelson C and Qiao Y and Martell S and Badukke C and Bessa C and Ylstra B and Lewis S and Isoherranen N and Maciel P and Rajcan-Separovic E
DOI: 10.1186/1750-1172-8-100
PubMed: 23837398

Clinical application of 2.7M Cytogenetics array for CNV detection in subjects with idiopathic autism and/or intellectual disability.
Qiao Y and Tyson C and Hrynchak M and Lopez-Rangel E and Hildebrand J and Martell S and Fawcett C and Kasmara L and Calli K and Harvard C and Liu X and Holden JJ and Lewis SM and Rajcan-Separovic E
DOI: 10.1111/j.1399-0004.2012.01860.x
PubMed: 22369279

Comparative genomic hybridization of Wilms' tumor.
Rassekh SR and Rajcan-Separovic E
DOI: 10.1007/978-1-62703-281-0_16
PubMed: 23412795

A 600 kb deletion syndrome at 16p11.2 leads to energy imbalance and neuropsychiatric disorders.
Zufferey F and Sherr EH and Beckmann ND and Hanson E and Maillard AM and Hippolyte L and Macé A and Ferrari C and Kutalik Z and Andrieux J and Aylward E and Barker M and Bernier R and Bouquillon S and Conus P and Delobel B and Faucett WA and Goin-Kochel RP and Grant E and Harewood L
DOI: 10.1136/jmedgenet-2012-101203
PubMed: 23054248

Association of GTF2i in the Williams-Beuren syndrome critical region with autism spectrum disorders.
Malenfant P and Liu X and Hudson ML and Qiao Y and Hrynchak M and Riendeau N and Hildebrand MJ and Cohen IL and Chudley AE and Forster-Gibson C and Mickelson EC and Rajcan-Separovic E and Lewis ME and Holden JJ
DOI: 10.1007/s10803-011-1389-4
PubMed: 22048961

Chromosome microarrays in human reproduction.
Rajcan-Separovic E
DOI: 10.1093/humupd/dms023
PubMed: 22661549

2p15-p16.1 microdeletion syndrome: molecular characterization and association of the OTX1 and XPO1 genes with autism spectrum disorders.
Liu X and Malenfant P and Reesor C and Lee A and Hudson ML and Harvard C and Qiao Y and Persico AM and Cohen IL and Chudley AE and Forster-Gibson C and Rajcan-Separovic E and Lewis ME and Holden JJ
DOI: 10.1038/ejhg.2011.112
PubMed: 21750575

Genomic and clinical characteristics of six patients with partially overlapping interstitial deletions at 10p12p11.
Wentzel C and Rajcan-Separovic E and Ruivenkamp CA and Chantot-Bastaraud S and Metay C and Andrieux J and Annerén G and Gijsbers AC and Druart L and Hyon C and Portnoi MF and Stattin EL and Vincent-Delorme C and Kant SG and Steinraths M and Marlin S and Giurgea I and Thuresson AC
DOI: 10.1038/ejhg.2011.71
PubMed: 21522184

Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus.
Jacquemont S and Reymond A and Zufferey F and Harewood L and Walters RG and Kutalik Z and Martinet D and Shen Y and Valsesia A and Beckmann ND and Thorleifsson G and Belfiore M and Bouquillon S and Campion D and de Leeuw N and de Vries BB and Esko T and Fernandez BA and Fernández-Aranda F and Fernández-Real JM
DOI: 10.1038/nature10406
PubMed: 21881559

Understanding the impact of 1q21.1 copy number variant.
Harvard C and Strong E and Mercier E and Colnaghi R and Alcantara D and Chow E and Martell S and Tyson C and Hrynchak M and McGillivray B and Hamilton S and Marles S and Mhanni A and Dawson AJ and Pavlidis P and Qiao Y and Holden JJ and Lewis SM and O'Driscoll M and Rajcan-Separovic E
DOI: 10.1186/1750-1172-6-54
PubMed: 21824431

Identification of copy number variants in miscarriages from couples with idiopathic recurrent pregnancy loss.
Rajcan-Separovic E and Diego-Alvarez D and Robinson WP and Tyson C and Qiao Y and Harvard C and Fawcett C and Kalousek D and Philipp T and Somerville MJ and Stephenson MD
DOI: 10.1093/humrep/deq202
PubMed: 20847186

Disruption at the PTCHD1 Locus on Xp22.11 in Autism spectrum disorder and intellectual disability.
Noor A and Whibley A and Marshall CR and Gianakopoulos PJ and Piton A and Carson AR and Orlic-Milacic M and Lionel AC and Sato D and Pinto D and Drmic I and Noakes C and Senman L and Zhang X and Mo R and Gauthier J and Crosbie J and Pagnamenta AT and Munson J and Estes AM
DOI: 10.1126/scitranslmed.3001267
PubMed: 20844286

Outcome of array CGH analysis for 255 subjects with intellectual disability and search for candidate genes using bioinformatics.
Qiao Y and Harvard C and Tyson C and Liu X and Fawcett C and Pavlidis P and Holden JJ and Lewis ME and Rajcan-Separovic E
DOI: 10.1007/s00439-010-0837-0
PubMed: 20512354

Genomic changes detected by array CGH in human embryos with developmental defects.
Rajcan-Separovic E and Qiao Y and Tyson C and Harvard C and Fawcett C and Kalousek D and Stephenson M and Philipp T
DOI: 10.1093/molehr/gap083
PubMed: 19778950

Phenomic determinants of genomic variation in autism spectrum disorders.
Qiao Y and Riendeau N and Koochek M and Liu X and Harvard C and Hildebrand MJ and Holden JJ and Rajcan-Separovic E and Lewis ME
DOI: 10.1136/jmg.2009.066795
PubMed: 19625284

Molecular cytogenetic investigation of two patients with Y chromosome rearrangements and intellectual disability.
Tyson C and Dawson AJ and Bal S and Tomiuk M and Anderson T and Tucker D and Riordan D and Chudoba I and Morash B and Mhanni A and Chudley AE and McGillivray B and Parslow M and Rappold G and Roeth R and Fawcett C and Qiao Y and Harvard C and Rajcan-Separovic E
DOI: 10.1002/ajmg.a.32535
PubMed: 19213034

Autism-associated familial microdeletion of Xp11.22.
Qiao Y and Liu X and Harvard C and Hildebrand MJ and Rajcan-Separovic E and Holden JJ and Lewis ME
DOI: 10.1111/j.1399-0004.2008.01028.x
PubMed: 18498374

Screening for submicroscopic chromosomal rearrangements in Wilms tumor using whole-genome microarrays.
Rassekh SR and Chan S and Harvard C and Dix D and Qiao Y and Rajcan-Separovic E
DOI: 10.1016/j.cancergencyto.2007.12.015
PubMed: 18406869

Phenotype-genotype characterization of alpha-thalassemia mental retardation syndrome due to isolated monosomy of 16p13.3.
Gibson WT and Harvard C and Qiao Y and Somerville MJ and Lewis ME and Rajcan-Separovic E
DOI: 10.1002/ajmg.a.32056
PubMed: 18076105

Submicroscopic deletions of 11q24-25 in individuals without Jacobsen syndrome: re-examination of the critical region by high-resolution array-CGH.
Tyson C and Qiao Y and Harvard C and Liu X and Bernier FP and McGillivray B and Farrell SA and Arbour L and Chudley AE and Clarke L and Gibson W and Dyack S and McLeod R and Costa T and Vanallen MI and Yong SL and Graham GE and Macleod P and Patel MS and Hurlburt J
DOI: 10.1186/1755-8166-1-23
PubMed: 19000322

Putatively benign copy number variants in subjects with idiopathic autism spectrum disorder and/or intellectual disability.
Qiao Y and Harvard C and Riendeau N and Fawcett C and Liu X and Holden JJ and Lewis ME and Rajcan-Separovic E
DOI: 10.1159/000184694
PubMed: 19287141

Clinical and molecular cytogenetic characterisation of a newly recognised microdeletion syndrome involving 2p15-16.1.
Rajcan-Separovic E and Harvard C and Liu X and McGillivray B and Hall JG and Qiao Y and Hurlburt J and Hildebrand J and Mickelson EC and Holden JJ and Lewis ME
DOI: 10.1136/jmg.2006.045013
PubMed: 16963482

Large-scale copy number variants (CNVs): distribution in normal subjects and FISH/real-time qPCR analysis.
Qiao Y and Liu X and Harvard C and Nolin SL and Brown WT and Koochek M and Holden JJ and Lewis ME and Rajcan-Separovic E
DOI: 10.1186/1471-2164-8-167
PubMed: 17565693

Oligonucleotide microarray analysis of genomic imbalance in children with mental retardation.
Friedman JM and Baross A and Delaney AD and Ally A and Arbour L and Armstrong L and Asano J and Bailey DK and Barber S and Birch P and Brown-John M and Cao M and Chan S and Charest DL and Farnoud N and Fernandes N and Flibotte S and Go A and Gibson WT and Holt RA
DOI: 10.1086/507471
PubMed: 16909388

15q duplication associated with autism in a multiplex family with a familial cryptic translocation t(14;15)(q11.2;q13.3) detected using array-CGH.
Koochek M and Harvard C and Hildebrand MJ and Van Allen M and Wingert H and Mickelson E and Holden JJ and Rajcan-Separovic E and Lewis ME
DOI: 10.1111/j.1399-0004.2005.00560.x
PubMed: 16433693

Submicroscopic deletions and duplications in individuals with intellectual disability detected by array-CGH.
Tyson C and Harvard C and Locker R and Friedman JM and Langlois S and Lewis ME and Van Allen M and Somerville M and Arbour L and Clarke L and McGilivray B and Yong SL and Siegel-Bartel J and Rajcan-Separovic E
DOI: 10.1002/ajmg.a.31015
PubMed: 16283669

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.
Harvard C and Malenfant P and Koochek M and Creighton S and Mickelson EC and Holden JJ and Lewis ME and Rajcan-Separovic E
DOI: 10.1111/j.1399-0004.2005.00406.x
PubMed: 15733271

Elucidation of a cryptic interstitial 7q31.3 deletion in a patient with a language disorder and mild mental retardation by array-CGH.
Tyson C and McGillivray B and Chijiwa C and Rajcan-Separovic E
DOI: 10.1002/ajmg.a.30245
PubMed: 15326624

Unexpected embryonic stem (ES) cell mutations represent a concern in gene targeting: lessons from "fierce" mice.
Kumar RA and Chan KL and Wong AH and Little KQ and Rajcan-Separovic E and Abrahams BS and Simpson EM
DOI: 10.1002/gene.20001
PubMed: 14994267

Familial cryptic translocation (2;17) ascertained through recurrent spontaneous abortions.
Bruyere H and Rajcan-Separovic E and Doyle J and Pantzar T and Langlois S
DOI: 10.1002/ajmg.a.20228
PubMed: 14608651

Non-muscle myosin heavy chain (MYH9): a new partner fused to ALK in anaplastic large cell lymphoma.
Lamant L and Gascoyne RD and Duplantier MM and Armstrong F and Raghab A and Chhanabhai M and Rajcan-Separovic E and Raghab J and Delsol G and Espinos E
DOI: 10.1002/gcc.10232
PubMed: 12800156

Metaphase FISHing of transgenic mice recommended: FISH and SKY define BAC-mediated balanced translocation.
Abrahams BS and Chong AC and Nisha M and Milette D and Brewster DA and Berry ML and Muratkhodjaev F and Mai S and Rajcan-Separovic E and Simpson EM
DOI: 10.1002/gene.10205
PubMed: 12872244

Loss of 1p and 7p in radiation-induced meningiomas identified by comparative genomic hybridization.
Rajcan-Separovic E and Maguire J and Loukianova T and Nisha M and Kalousek D
DOI: 10.1016/s0165-4608(02)00864-6
PubMed: 12810249

High-resolution human genome scanning using whole-genome BAC arrays.
Li J and Jiang T and Bejjani B and Rajcan-Separovic E and Cai WW
DOI: 10.1101/sqb.2003.68.323
PubMed: 15338633

Interphase fluorescence in situ hybridization and DNA flow cytometry analysis of medulloblastomas with a normal karyotype.
Rajcan-Separovic E and Hendson G and Tang S and Seto E and Thomson T and Phillips D and Kalousek D
DOI: 10.1016/s0165-4608(01)00558-1
PubMed: 11890998

Molecular cytogenetics in reproductive pathology.
Bruyère H and Rajcan-Separovic E and Kalousek DK
PubMed: 12397806

Genomic organization of the X-linked inhibitor of apoptosis and identification of a novel testis-specific transcript.
Lagacé M and Xuan JY and Young SS and McRoberts C and Maier J and Rajcan-Separovic E and Korneluk RG
DOI: 10.1006/geno.2001.6635
PubMed: 11597143

Defective hematopoiesis and hepatic steatosis in mice with combined deficiencies of the genes encoding Fancc and Cu/Zn superoxide dismutase.
Hadjur S and Ung K and Wadsworth L and Dimmick J and Rajcan-Separovic E and Scott RW and Buchwald M and Jirik FR
DOI: 10.1182/blood.v98.4.1003
PubMed: 11493445

Recurrent trisomy 15 in a female carrier of der(15)t(Y;15)(q12;p13).
Rajcan-Separovic E and Robinson WP and Stephenson M and Pantzar T and Arbour L and McFadden D and Guscott J
DOI: 10.1002/1096-8628(2001)9999:9999<::aid-ajmg1173>3.0.co;2-1
PubMed: 11252000

Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines.
Fong WG and Liston P and Rajcan-Separovic E and St Jean M and Craig C and Korneluk RG
DOI: 10.1006/geno.2000.6364
PubMed: 11087668

Fluorescence in situ hybridization analysis of complex translocations in two newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia patients.
Rajcan-Separovic E and Bence-Bruckler I and Wells P and Wang H
DOI: 10.1016/s0165-4608(99)00047-3
PubMed: 10526539

Fluorescence in situ hybridization analysis of the replication properties of the myotonic dystrophy protein kinase (DMPK) gene region.
Rajcan-Separovic E and Barcelo JM and Korneluk RG
PubMed: 9858828

Assignment of human inhibitor of apoptosis protein (IAP) genes xiap, hiap-1, and hiap-2 to chromosomes Xq25 and 11q22-q23 by fluorescence in situ hybridization.
Rajcan-Separovic E and Liston P and Lefebvre C and Korneluk RG
DOI: 10.1006/geno.1996.0579
PubMed: 8938457

FISH detection of chromosome polymorphism and deletions in the spinal muscular atrophy (SMA) region of 5q13.
Rajcan-Separovic E and Mahadevan MS and Lefebvre C and Besner-Johnston A and Ikeda JE and Korneluk RG and MacKenzie A
PubMed: 9067434

Identification of the origin of double minutes in normal human cells by laser-based chromosome microdissection approach.
Rajcan-Separovic E and Wang HS and Speevak MD and Janes L and Korneluk RG and Wakasa K and Ikeda JE
DOI: 10.1007/bf00214184
PubMed: 7607652

Fluorescence in situ hybridization of bovine Alu-like sequences to bovine and ovine chromosomes.
Rajcan-Separovic E and Sabour MP
PubMed: 8270208


Genomic changes in human miscarriages and their functional consequences
Pregnancy loss is a significant health concern as 15 per cent of clinically recognized pregnancies end in miscarriage, with the highest rate in the first trimester. Although finding the cause of pregnancy loss is essential for prognosis, recurrence risk counseling, and the management of all future pregnancies, the cause remains unknown in 30-50 per cent of all cases. Our studies focus on finding the genomic cause of abnormal human embryo development and miscarriage. We have shown show that 30% of sporadic and recurrent miscarriages have small and unique chromosomal gains and losses, detectable only by CMA. These genomic abnormalities are frequently inherited from one of the parents and could represent predisposing genetic factors for recurrent pregnancy loss (RPL). Functional follow-up of candidate miscarriage genes in the pregnancy loss as well as the use of next generation sequencing to identify pathogenic mutation are currently the main focus of this study (for more information see http://www.cihr-irsc.gc.ca/e/43150.html).

Genomics of intellectual disability
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 per cent of the population, and cause remains unknown in at least 40 per cent of all cases. We are using chromosome microarray technology (CMA) and next generation sequencing to detect small chromosomal and DNA changes in children with ID. We are also interested in understanding how these changes affect the gene function by assessing RNA and protein expression as well as gene-specific pathways. For more information see http://www.research-europe.com/magazine/healthcare2/hc22/index.html.

Honours & Awards

CIHR Clinical Investigatorship salary award - 2005-2009

Michael Smith Foundation for Health Research, Career Scholar Award, 2008-2014

Research Group Members

Sally Martell, Research Assistant/Technician
Ying Qiao, Research Associate