BCCGN Research Projects
Dr. Michelle Demos – Epilepsy Study
Dr. Michelle Demos is a neurologist who works with children with epilepsy. In many cases the underlying cause of the condition is unknown and the seizures may be poorly controlled with the available medications. Dr. Demos wanted to search for deletions and duplications in the DNA of her patients, called copy number variants (CNV’s) that could give clues about the genes and biological processes that were causing seizures and other symptoms in her patients. The Network helped her design and conduct a pilot study for eight patients using array comparative genomic hybridization (ACGH) to detect copy number variants. This study resulted in the identification of three chromosomal rearrangements that may contain regions that map to possible genes of interest. Dr. Demos intends to publish her data and is also applying for a grant so that she can conclude a much larger study of seventy patients. By using this approach Dr. Demos hopes to identify new epilepsy genes. This will improve the information that genetic counselors can give to families and may reduce the number of investigations performed on patients and lead to new approaches to treatment and improved patient care.
Christele Du Souich and Dr Neal Boerkoel – Psychiatric Disease
Fifteen percent of BC’s children and youth are affected with psychiatric diseases that impair their ability to function in daily life. BCCGN helped genetics researcher, Christele Du Souich and clinical investigator Neal Boerkoel conduct a pilot study on a multigenerational family where carrier females have psychiatric disease and affected males have severe mental retardation. One young boy had severe mental retardation, seizures and dysmorphic features with no clinical diagnosis, but a pedigree that demonstrated a classic X-linked recessive pattern of inheritance. Knowing that the gene responsible must be carried on the X-chromosome, the researchers designed a linkage experiment using SNP genotyping technology to find the exact location of the responsible gene. They first located the gene at the tip of the X chromosome and then were able to identify the exact gene using DNA sequencing technology. Once the mutation underlying the patient’s disease symptoms was identified they could council the family regarding the cause of their son’s condition and are now able to offer a genetic test to other family members who are thinking of having children to see whether they too might carry this gene.
BCCGN Researcher Publications
What can genomics do for health care? – Marion Thomas, PhD, Shelin Adam, MSc, Christele du Souich, MSc, Margot Van Allen, MD, Cornelius F. Boerkoel, MD, PhD. What can genomics do for health care?. BCMJ, Vol. 51, No. 7, September, 2009, page(s) 298-301.
Pharmacogenomics and its implications for autoimmune disease – Colin J.D. Ross, Hagit Katzov, Bruce Carleton, Michael R. Hayden, Pharmacogenomics and its implications for autoimmune disease, Journal of Autoimmunity, Volume 28, Issues 2–3, March–May 2007, Pages 122-128, ISSN 0896-8411, 10.1016/j.jaut.2007.02.008.
The Sensitivity of Massively Parallel Sequencing for Detecting Candidate Infectious Agents Associated with Human Tissue – Moore RA,Warren RL,Freeman JD,Gustavsen JA,Chénard C,et al.2011The Sensitivity of Massively Parallel Sequencing for Detecting Candidate Infectious Agents Associated with Human Tissue.PLoS ONE6(5):
19p13.2 microduplication causes a Sotos syndrome-like phenotype and alters gene expression – Lehman AM, du Souich C, Chai D, Eydoux P, Huang JL, Fok AK, Avila L, Swingland J, Delaney AD, McGillivray B, Goldowitz D, Argiropoulos B, Kobor MS, Boerkoel CF. 19p13.2 microduplication causes a Sotos syndrome-like phenotype and alters gene expression, Clinical Genetics, Volume 81, Issue 1, January 2012, pages 56–63
Genetics of bronchopulmonary dysplasia in the age of genomics – Lavoie, PM, Dube, M, Genetics of bronchopulmonary dysplasia in the age of genomics, Current Opinion in Pediatrics, Volume 22, Issue 2, April 2010, pages 134-138
Characterization of a new X-linked mental retardation syndrome with microcephaly, cortical malformation, and thin habitus – du Souich C, Chou A, Yin J, Oh T, Nelson TN, Hurlburt J, Arbour L, Friedlander R, McGillivray BC, Tyshchenko N, Rump A, Poskitt KJ, Demos MK, Van Allen MI, Boerkoel CF. 2009. Characterization of a new X-linked mental retardation syndrome with microcephaly, cortical malformation, and thin habitus. Am J Med Genet Part A 149A:2469–2478.
Extensive epigenetic reprogramming in human somatic tissues between fetus and adult – Yuen, RK,Neumann, SM, Fok, AK, Peñaherrera, MS,McFadden DE,Robinson ,WP,Kobor, MS, Extensive epigenetic reprogramming in human somatic tissues between fetus and adult, Epigenetics Chromatin.May 2011, Volume 4, Issue 7.
Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma – Castellarin, M,Warren, R, Freeman, J, Dreolini, L, Krywinski, M, Strauss, J, Barnes, R, Watson, P, Allen-Vercoe, E, Moore, R, Holt, R, Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma, Genome Res, October 2011,
Novel mRNA isoforms and mutations of uridine monophosphate synthetase and 5-fluorouracil resistance in colorectal cancer – Griffith, M, Mwenifumbo, J, Cheung, P, Paul, J et al, Novel mRNA isoforms and mutations of uridine monophosphate synthetase and 5-fluorouracil resistance in colorectal cancer, The Pharmacogenomics Journal, January 2012
Barriers for integrating personalized medicine into clinical practice: a best worst scaling choice experiment –Mehdi Najafzadeh, MSc1, Larry D. Lynd, PhD1,4, Jennifer C. Davis, PhD3, Stirling Bryan, PhD2,3, Aslam Anis, PhD2,4, Marco Marra, PhD5, Carlo A. Marra, PharmD, PhD 1,4. Barriers for integrating personalized medicine into clinical practice: a best worst scaling choice experiment – manuscript has been accepted for publication in Genetics in Medicine.