32 results on '"Vaags, Andrea K."'
Search Results
2. CHD2 haploinsufficiency is associated with developmental delay, intellectual disability, epilepsy and neurobehavioural problems
- Author
-
Chénier, Sébastien, Yoon, Grace, Argiropoulos, Bob, Lauzon, Julie, Laframboise, Rachel, Ahn, Joo Wook, Ogilvie, Caroline Mackie, Lionel, Anath C, Marshall, Christian R, Vaags, Andrea K, Hashemi, Bita, Boisvert, Karine, Mathonnet, Géraldine, Tihy, Frédérique, So, Joyce, Scherer, Stephen W, Lemyre, Emmanuelle, and Stavropoulos, Dimitri J
- Subjects
Biomedical and Clinical Sciences ,Neurosciences ,Genetics ,Intellectual and Developmental Disabilities (IDD) ,Mental Health ,Brain Disorders ,Human Fetal Tissue ,Pediatric ,Biotechnology ,Autism ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,Mental health ,Autism spectrum disorder ,CHD2 ,Developmental delay ,Epilepsy ,Learning disability ,Psychology - Abstract
BackgroundThe chromodomain helicase DNA binding domain (CHD) proteins modulate gene expression via their ability to remodel chromatin structure and influence histone acetylation. Recent studies have shown that CHD2 protein plays a critical role in embryonic development, tumor suppression and survival. Like other genes encoding members of the CHD family, pathogenic mutations in the CHD2 gene are expected to be implicated in human disease. In fact, there is emerging evidence suggesting that CHD2 might contribute to a broad spectrum of neurodevelopmental disorders. Despite growing evidence, a description of the full phenotypic spectrum of this condition is lacking.MethodsWe conducted a multicentre study to identify and characterise the clinical features associated with haploinsufficiency of CHD2. Patients with deletions of this gene were identified from among broadly ascertained clinical cohorts undergoing genomic microarray analysis for developmental delay, congenital anomalies and/or autism spectrum disorder.ResultsDetailed clinical assessments by clinical geneticists showed recurrent clinical symptoms, including developmental delay, intellectual disability, epilepsy, behavioural problems and autism-like features without characteristic facial gestalt or brain malformations observed on magnetic resonance imaging scans. Parental analysis showed that the deletions affecting CHD2 were de novo in all four patients, and analysis of high-resolution microarray data derived from 26,826 unaffected controls showed no deletions of this gene.ConclusionsThe results of this study, in addition to our review of the literature, support a causative role of CHD2 haploinsufficiency in developmental delay, intellectual disability, epilepsy and behavioural problems, with phenotypic variability between individuals.
- Published
- 2014
3. Disruption of the ASTN2/TRIM32 locus at 9q33.1 is a risk factor in males for autism spectrum disorders, ADHD and other neurodevelopmental phenotypes
- Author
-
Lionel, Anath C, Tammimies, Kristiina, Vaags, Andrea K, Rosenfeld, Jill A, Ahn, Joo Wook, Merico, Daniele, Noor, Abdul, Runke, Cassandra K, Pillalamarri, Vamsee K, Carter, Melissa T, Gazzellone, Matthew J, Thiruvahindrapuram, Bhooma, Fagerberg, Christina, Laulund, Lone W, Pellecchia, Giovanna, Lamoureux, Sylvia, Deshpande, Charu, Clayton-Smith, Jill, White, Ann C, Leather, Susan, Trounce, John, Bedford, H Melanie, Hatchwell, Eli, Eis, Peggy S, Yuen, Ryan KC, Walker, Susan, Uddin, Mohammed, Geraghty, Michael T, Nikkel, Sarah M, Tomiak, Eva M, Fernandez, Bridget A, Soreni, Noam, Crosbie, Jennifer, Arnold, Paul D, Schachar, Russell J, Roberts, Wendy, Paterson, Andrew D, So, Joyce, Szatmari, Peter, Chrysler, Christina, Woodbury-Smith, Marc, Lowry, R Brian, Zwaigenbaum, Lonnie, Mandyam, Divya, Wei, John, MacDonald, Jeffrey R, Howe, Jennifer L, Nalpathamkalam, Thomas, Wang, Zhuozhi, Tolson, Daniel, Cobb, David S, Wilks, Timothy M, Sorensen, Mark J, Bader, Patricia I, An, Yu, Wu, Bai-Lin, Musumeci, Sebastiano Antonino, Romano, Corrado, Postorivo, Diana, Nardone, Anna M, Della Monica, Matteo, Scarano, Gioacchino, Zoccante, Leonardo, Novara, Francesca, Zuffardi, Orsetta, Ciccone, Roberto, Antona, Vincenzo, Carella, Massimo, Zelante, Leopoldo, Cavalli, Pietro, Poggiani, Carlo, Cavallari, Ugo, Argiropoulos, Bob, Chernos, Judy, Brasch-Andersen, Charlotte, Speevak, Marsha, Fichera, Marco, Ogilvie, Caroline Mackie, Shen, Yiping, Hodge, Jennelle C, Talkowski, Michael E, Stavropoulos, Dimitri J, Marshall, Christian R, and Scherer, Stephen W
- Subjects
Pediatric Research Initiative ,Pediatric ,Intellectual and Developmental Disabilities (IDD) ,Mental Health ,Brain Disorders ,Human Genome ,Neurosciences ,Autism ,Clinical Research ,Behavioral and Social Science ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Adolescent ,Adult ,Attention Deficit Disorder with Hyperactivity ,Case-Control Studies ,Child ,Child Development Disorders ,Pervasive ,Child ,Preschool ,Chromosomes ,Human ,Pair 9 ,DNA Copy Number Variations ,Exons ,Female ,Gene Expression ,Genetic Association Studies ,Genetic Predisposition to Disease ,Glycoproteins ,Humans ,Infant ,Infant ,Newborn ,Male ,Nerve Tissue Proteins ,Organ Specificity ,Phenotype ,Polymorphism ,Single Nucleotide ,Protein Isoforms ,Receptors ,Cell Surface ,Risk Factors ,Sequence Deletion ,Transcription Factors ,Transcription Initiation Site ,Tripartite Motif Proteins ,Ubiquitin-Protein Ligases ,Young Adult ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Rare copy number variants (CNVs) disrupting ASTN2 or both ASTN2 and TRIM32 have been reported at 9q33.1 by genome-wide studies in a few individuals with neurodevelopmental disorders (NDDs). The vertebrate-specific astrotactins, ASTN2 and its paralog ASTN1, have key roles in glial-guided neuronal migration during brain development. To determine the prevalence of astrotactin mutations and delineate their associated phenotypic spectrum, we screened ASTN2/TRIM32 and ASTN1 (1q25.2) for exonic CNVs in clinical microarray data from 89 985 individuals across 10 sites, including 64 114 NDD subjects. In this clinical dataset, we identified 46 deletions and 12 duplications affecting ASTN2. Deletions of ASTN1 were much rarer. Deletions near the 3' terminus of ASTN2, which would disrupt all transcript isoforms (a subset of these deletions also included TRIM32), were significantly enriched in the NDD subjects (P = 0.002) compared with 44 085 population-based controls. Frequent phenotypes observed in individuals with such deletions include autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), speech delay, anxiety and obsessive compulsive disorder (OCD). The 3'-terminal ASTN2 deletions were significantly enriched compared with controls in males with NDDs, but not in females. Upon quantifying ASTN2 human brain RNA, we observed shorter isoforms expressed from an alternative transcription start site of recent evolutionary origin near the 3' end. Spatiotemporal expression profiling in the human brain revealed consistently high ASTN1 expression while ASTN2 expression peaked in the early embryonic neocortex and postnatal cerebellar cortex. Our findings shed new light on the role of the astrotactins in psychopathology and their interplay in human neurodevelopment.
- Published
- 2014
4. Development of a comprehensive approach to adult hereditary cancer testing in Ontario.
- Author
-
Bell, Kathleen Anne, Kim, Raymond, Aronson, Melyssa, Gillies, Brittany, Awan, Arif Ali, Chun, Kathy, Hart, Jennifer, Healey, Rachel, Kim, Linda, Klaric, Goran, Panabaker, Karen, Sabatini, Peter J. B., Sadikovic, Bekim, Selvarajah, Shamini, Smith, Amanda C., Stockley, Tracy L., Vaags, Andrea K., Eisen, Andrea, Pollett, Aaron, and Feilotter, Harriet
- Abstract
Background Genetic testing for hereditary cancer susceptibility has advanced over time due to the discovery of new risk genes, improved technology and decreased cost. In the province of Ontario, testing eligibility criteria were initially developed to include hereditary breast, ovarian and colorectal cancer syndromes. The rapid evolution of genetic technologies has facilitated the ability to interrogate a large number of genes concurrently. This, coupled with new knowledge about risk genes, necessitated a coordinated approach to expanding the scope of genes and indications tested and synchronisation of access and test utilisation across the province as required in a publicly funded universal healthcare system. Methods Ontario Health--Cancer Care Ontario convened expert working groups to develop a standardised and comprehensive cancer gene list for adults and accompanying hereditary cancer testing (HCT) criteria using an evidence-based framework and broad laboratory and clinical genetics engagement. Results A standardised 76-cancer-gene panel, organised into 13 larger disease site panels and 25 single/small gene panels, was developed and endorsed by the working groups. Provincial genetic testing eligibility criteria were updated to align with the new panels and to guide clinical decision-making. In the first year following the implementation of these changes, 10 564 HCT panels were performed with an overall mutation detection rate of 12.2%. Conclusion Using an evidence framework and broad clinical engagement to develop and endorse an updated guidance document, cancer genetic testing for adults in Ontario is now standardised and coordinated across the province. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
5. Development of a comprehensive approach to adult hereditary cancer testing in Ontario
- Author
-
Bell, Kathleen Anne, primary, Kim, Raymond, additional, Aronson, Melyssa, additional, Gillies, Brittany, additional, Ali Awan, Arif, additional, Chun, Kathy, additional, Hart, Jennifer, additional, Healey, Rachel, additional, Kim, Linda, additional, Klaric, Goran, additional, Panabaker, Karen, additional, Sabatini, Peter J B, additional, Sadikovic, Bekim, additional, Selvarajah, Shamini, additional, Smith, Amanda C, additional, Stockley, Tracy L, additional, Vaags, Andrea K, additional, Eisen, Andrea, additional, Pollett, Aaron, additional, and Feilotter, Harriet, additional
- Published
- 2022
- Full Text
- View/download PDF
6. Practice guidelines for BRCA1/2 tumour testing in ovarian cancer
- Author
-
Grafodatskaya, Daria, primary, O’Rielly, Darren D, additional, Bedard, Karine, additional, Butcher, Darci T, additional, Howlett, Christopher J, additional, Lytwyn, Alice, additional, McCready, Elizabeth, additional, Parboosingh, Jillian, additional, Spriggs, Elizabeth L, additional, Vaags, Andrea K, additional, and Stockley, Tracy L, additional
- Published
- 2022
- Full Text
- View/download PDF
7. Microdeletions of ELP4 Are Associated with Language Impairment, Autism Spectrum Disorder, and Mental Retardation
- Author
-
Addis, Laura, Ahn, Joo Wook, Dobson, Richard, Dixit, Abhishek, Ogilvie, Caroline M, Pinto, Dalila, Vaags, Andrea K, Coon, Hilary, Chaste, Pauline, Wilson, Scott, Parr, Jeremy R, Andrieux, Joris, Lenne, Bruno, Tumer, Zeynep, Leuzzi, Vincenzo, Aubell, Kristina, Koillinen, Hannele, Curran, Sarah, Marshall, Christian R, Scherer, Stephen W, Strug, Lisa J, Collier, David A, and Pal, Deb K
- Published
- 2015
- Full Text
- View/download PDF
8. Absent CNKSR2 causes seizures and intellectual, attention, and language deficits
- Author
-
Vaags, Andrea K., Bowdin, Sarah, Smith, Mary-Lou, Gilbert-Dussardier, Brigitte, Brocke-Holmefjord, Katja S., Sinopoli, Katia, Gilles, Cindy, Haaland, Tove B., Vincent-Delorme, Catherine, Lagrue, Emmanuelle, Harbuz, Radu, Walker, Susan, Marshall, Christian R., Houge, Gunnar, Kalscheuer, Vera M., Scherer, Stephen W., and Minassian, Berge A.
- Published
- 2014
- Full Text
- View/download PDF
9. Long-term tracking of bone marrow progenitor cells following intracoronary injection post-myocardial infarction in swine using MRI
- Author
-
Graham, John J., Foltz, Warren D., Vaags, Andrea K., Ward, Michael R., Yang, Yuesong, Connelly, Kim A., Vijayaraghavan, Ram, Detsky, Jay S., Hough, Margaret R., Stewart, Duncan J., Wright, Graham A., and Dick, Alexander J.
- Subjects
Heart attack -- Research ,Magnetic resonance imaging -- Usage ,Bone marrow cells -- Health aspects ,Biological sciences - Abstract
Magnetic resonance imaging (MRI) can track progenitor cells following direct intramyocardial injection. However, in the vast majority of post-myocardial infarction (MI) clinical trials, cells are delivered by the intracoronary (IC) route, which results in far greater dispersion within the myocardium. Therefore, we assessed whether the more diffuse distribution of cells following IC delivery could be imaged longitudinally with MRI. In 11 pigs (7 active, 4 controls), MI was induced by 90-min balloon occlusion of the left anterior descending coronary artery. Seven (0) days [median (interquartile range)] following Ml, bone marrow progenitor cells (BMCs) were colabeled with an iron-fluorophore and a cell viability marker and delivered to the left anterior descending coronary artery distal to an inflated over-the-wire percutaneous transluminal coronary angioplasty balloon. [T2.sup.*]-weighted images were used to assess the location of the magnetically labeled cells over a 6-wk period post-MI. Immediately following cell delivery, hypointensity characteristic of the magnetic label was observed in the infarct border rather than within the infarct itself. At 6 wk, the cell signal hypointensity persisted, albeit with significantly decreased intensity. BMC delivery resulted in significant improvement in infarct volume and ejection fraction (EF): infarct volume in cell-treated animals decreased from 7.1 [+ or -] 1.5 to 4.9 [+ or -] 1.0 ml (P < 0.01); infarct volume in controls was virtually unchanged at 4.64 [+ or -] 2.1 to 4.39 [+ or -] 2.1 ml (P = 0.7). EF in cell-treated animals went from 30.4 [+ or -] 5.2% preinjection to 34.5 [+ or -] 2.5% 6 wk postinjection (P = 0.013); EF in control animals went from 34.3 [+ or -] 4.7 to 31.9 [+ or -] 6.8% (P = 0.5). Immunohistochemical analysis revealed intracellular colocalization of the iron fluorophore and cell viability dye with the labeled cells continuing to express the same surface markers as at baseline. MRI can track the persistence and distribution of magnetically labeled BMCs over a 6-wk period following IC delivery. Signal hypointensity declines with time, particularly in the first week following delivery. These cells maintain their original phenotype during this time course. Delivery of these cells appears safe and results in improvement in infarct size and left ventricular ejection fraction. magnetic resonance imaging; myocardial infarction doi: 10.1152/ajpheart.01260.2008.
- Published
- 2010
10. Data sharing to improve concordance in variant interpretation across laboratories: results from the Canadian Open Genetics Repository
- Author
-
Mighton, Chloe, primary, Smith, Amanda C, additional, Mayers, Justin, additional, Tomaszewski, Robert, additional, Taylor, Sherryl, additional, Hume, Stacey, additional, Agatep, Ron, additional, Spriggs, Elizabeth, additional, Feilotter, Harriet E, additional, Semenuk, Laura, additional, Wong, Henry, additional, Lazo de la Vega, Lorena, additional, Marshall, Christian R, additional, Axford, Michelle M, additional, Silver, Talia, additional, Charames, George S, additional, Di Gioacchino, Vanessa, additional, Watkins, Nicholas, additional, Foulkes, William D, additional, Clavier, Marcos, additional, Hamel, Nancy, additional, Chong, George, additional, Lamont, Ryan E, additional, Parboosingh, Jillian, additional, Karsan, Aly, additional, Bosdet, Ian, additional, Young, Sean S, additional, Tucker, Tracy, additional, Akbari, Mohammad Reza, additional, Speevak, Marsha D, additional, Vaags, Andrea K, additional, Lebo, Matthew S, additional, and Lerner-Ellis, Jordan, additional
- Published
- 2021
- Full Text
- View/download PDF
11. eNOS Overexpressing Bone Marrow Cells are Safe and Effective in a Porcine Model of Myocardial Regeneration Following Acute Myocardial Infarction
- Author
-
Ward, Michael R., Connelly, Kim A., Vijayaraghavan, Ram, Vaags, Andrea K., Graham, John J., Foltz, Warren, Hough, Margaret R., Stewart, Duncan J., and Dick, Alexander
- Published
- 2013
- Full Text
- View/download PDF
12. Rare exonic deletions implicate the synaptic organizer Gephyrin (GPHN) in risk for autism, schizophrenia and seizures
- Author
-
Lionel, Anath C., Vaags, Andrea K., Sato, Daisuke, Gazzellone, Matthew J., Mitchell, Elyse B., Chen, Hong Yang, Costain, Gregory, Walker, Susan, Egger, Gerald, Thiruvahindrapuram, Bhooma, Merico, Daniele, Prasad, Aparna, Anagnostou, Evdokia, Fombonne, Eric, Zwaigenbaum, Lonnie, Roberts, Wendy, Szatmari, Peter, Fernandez, Bridget A., Georgieva, Lyudmila, Brzustowicz, Linda M., Roetzer, Katharina, Kaschnitz, Wolfgang, Vincent, John B., Windpassinger, Christian, Marshall, Christian R., Trifiletti, Rosario R., Kirmani, Salman, Kirov, George, Petek, Erwin, Hodge, Jennelle C., Bassett, Anne S., and Scherer, Stephen W.
- Published
- 2013
- Full Text
- View/download PDF
13. Deletions in 16q24.2 are associated with autism spectrum disorder, intellectual disability and congenital renal malformation
- Author
-
Handrigan, Gregory Ryan, Chitayat, David, Lionel, Anath C, Pinsk, Maury, Vaags, Andrea K, Marshall, Christian R, Dyack, Sarah, Escobar, Luis F, Fernandez, Bridget A, Stegman, Joseph C, Rosenfeld, Jill A, Shaffer, Lisa G, Goodenberger, McKinsey, Hodge, Jennelle C, Cain, Jason E, Babul-Hirji, Riyana, Stavropoulos, Dimitri J, Yiu, Verna, Scherer, Stephen W, and Rosenblum, Norman D
- Published
- 2013
- Full Text
- View/download PDF
14. Data sharing to improve concordance in variant interpretation across laboratories: results from the Canadian Open Genetics Repository
- Author
-
Mighton, Chloe, Smith, Amanda C, Mayers, Justin, Tomaszewski, Robert, Taylor, Sherryl, Hume, Stacey, Agatep, Ron, Spriggs, Elizabeth, Feilotter, Harriet E, Semenuk, Laura, Wong, Henry, Lazo de la Vega, Lorena, Marshall, Christian R, Axford, Michelle M, Silver, Talia, Charames, George S, Di Gioacchino, Vanessa, Watkins, Nicholas, Foulkes, William D, Clavier, Marcos, Hamel, Nancy, Chong, George, Lamont, Ryan E, Parboosingh, Jillian, Karsan, Aly, Bosdet, Ian, Young, Sean S, Tucker, Tracy, Akbari, Mohammad Reza, Speevak, Marsha D, Vaags, Andrea K, Lebo, Matthew S, and Lerner-Ellis, Jordan
- Abstract
BackgroundThis study aimed to identify and resolve discordant variant interpretations across clinical molecular genetic laboratories through the Canadian Open Genetics Repository (COGR), an online collaborative effort for variant sharing and interpretation.MethodsLaboratories uploaded variant data to the Franklin Genoox platform. Reports were issued to each laboratory, summarising variants where conflicting classifications with another laboratory were noted. Laboratories could then reassess variants to resolve discordances. Discordance was calculated using a five-tier model (pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign (LB), benign (B)), a three-tier model (LP/P are positive, VUS are inconclusive, LB/B are negative) and a two-tier model (LP/P are clinically actionable, VUS/LB/B are not). We compared the COGR classifications to automated classifications generated by Franklin.ResultsTwelve laboratories submitted classifications for 44 510 unique variants. 2419 variants (5.4%) were classified by two or more laboratories. From baseline to after reassessment, the number of discordant variants decreased from 833 (34.4% of variants reported by two or more laboratories) to 723 (29.9%) based on the five-tier model, 403 (16.7%) to 279 (11.5%) based on the three-tier model and 77 (3.2%) to 37 (1.5%) based on the two-tier model. Compared with the COGR classification, the automated Franklin classifications had 94.5% sensitivity and 96.6% specificity for identifying actionable (P or LP) variants.ConclusionsThe COGR provides a standardised mechanism for laboratories to identify discordant variant interpretations and reduce discordance in genetic test result delivery. Such quality assurance programmes are important as genetic testing is implemented more widely in clinical care.
- Published
- 2022
- Full Text
- View/download PDF
15. Practice guidelines for BRCA1/2tumour testing in ovarian cancer
- Author
-
Grafodatskaya, Daria, O’Rielly, Darren D, Bedard, Karine, Butcher, Darci T, Howlett, Christopher J, Lytwyn, Alice, McCready, Elizabeth, Parboosingh, Jillian, Spriggs, Elizabeth L, Vaags, Andrea K, and Stockley, Tracy L
- Abstract
The purpose of this document is to provide pre-analytical, analytical and post-analytical considerations and recommendations to Canadian clinical laboratories developing, validating and offering next-generation sequencing (NGS)-based BRCA1and BRCA2(BRCA1/2) tumour testing in ovarian cancers. This document was drafted by the members of the Canadian College of Medical Geneticists (CCMG) somatic BRCA Ad Hoc Working Group, and representatives from the Canadian Association of Pathologists. The document was circulated to the CCMG members for comment. Following incorporation of feedback, this document has been approved by the CCMG board of directors. The CCMG is a Canadian organisation responsible for certifying medical geneticists and clinical laboratory geneticists, and for establishing professional and ethical standards for clinical genetics services in Canada. The current CCMG Practice Guidelines were developed as a resource for clinical laboratories in Canada; however, they are not inclusive of all information laboratories should consider in the validation and use of NGS for BRCA1/2tumour testing in ovarian cancers.
- Published
- 2022
- Full Text
- View/download PDF
16. Microdeletions of ELP4 are associated with language impairment, autism spectrum disorder and epilepsy
- Author
-
Pal, Deb, Addis, Laura, Ahn, Joo Wook, Dobson, Richard, Dixit, Abhishek, Ogilvie, Caroline, Pinto, Dalila, Vaags, Andrea K., Coon, Hilary, Chaste, Pauline, Wilson, Scott, Parr, Jeremy R., Andrieux, Joris, lenne, bruno, turner, zeynep, leuzzi, vincenzo, aubell, kristina, koillinen, hannele, Curran, Sarah, Marshall, Christian R., Scherer, Stephen W., and Strug, Lisa J.
- Subjects
mental disorders - Abstract
Copy number variations (CNV) are important in the aetiology of neurodevelopmental disorders and show broad phenotypic manifestations. We compared the presence of small CNVs disrupting the ELP4-PAX6 locus in 4,092 U.K. individuals with a range of neurodevelopmental conditions, clinically referred for array comparative genomic hybridisation (aCGH), with WTCCC controls (n=4,783). The phenotypic analysis was then extended using the DECIPHER database. We followed up association using an autism patient cohort (n=3,143) compared with six additional control groups (n=6,469). In the clinical discovery series we identified eight cases with ELP4 deletions, and one with a partial duplication of ELP4 and PAX6. These cases were referred for neurological phenotypes including language impairment, developmental delay, autism and epilepsy. Six further cases with a primary diagnosis of ASD and similar secondary phenotypes were identified with ELP4 deletions, as well as another six (out of 9) with neurodevelopmental phenotypes from DECIPHER. CNVs at ELP4 were only present in 1/11,252 controls. We found a significant excess of CNVs in discovery cases compared with controls, p=7.5x10-3; as well as for autism, p=2.7x10-3. Our results suggest ELP4 deletions are highly likely to be pathogenic, predisposing to a range of neurodevelopmental phenotypes from ASD to language impairment and epilepsy.
- Published
- 2015
17. Microdeletions ofELP4Are Associated with Language Impairment, Autism Spectrum Disorder, and Mental Retardation
- Author
-
Addis, Laura, primary, Ahn, Joo Wook, additional, Dobson, Richard, additional, Dixit, Abhishek, additional, Ogilvie, Caroline M, additional, Pinto, Dalila, additional, Vaags, Andrea K, additional, Coon, Hilary, additional, Chaste, Pauline, additional, Wilson, Scott, additional, Parr, Jeremy R, additional, Andrieux, Joris, additional, Lenne, Bruno, additional, Tumer, Zeynep, additional, Leuzzi, Vincenzo, additional, Aubell, Kristina, additional, Koillinen, Hannele, additional, Curran, Sarah, additional, Marshall, Christian R, additional, Scherer, Stephen W, additional, Strug, Lisa J, additional, Collier, David A, additional, and Pal, Deb K, additional
- Published
- 2015
- Full Text
- View/download PDF
18. Ectopic TLX1 Expression Accelerates Malignancies in Mice Deficient in DNA-PK
- Author
-
Krutikov, Konstantin, primary, Zheng, Yanzhen, additional, Chesney, Alden, additional, Huang, Xiaoyong, additional, Vaags, Andrea K., additional, Evdokimova, Valentina, additional, Hough, Margaret R., additional, and Chen, Edwin, additional
- Published
- 2014
- Full Text
- View/download PDF
19. Rare Deletions at the Neurexin 3 Locus in Autism Spectrum Disorder
- Author
-
Vaags, Andrea K., primary, Lionel, Anath C., additional, Sato, Daisuke, additional, Goodenberger, McKinsey, additional, Stein, Quinn P., additional, Curran, Sarah, additional, Ogilvie, Caroline, additional, Ahn, Joo Wook, additional, Drmic, Irene, additional, Senman, Lili, additional, Chrysler, Christina, additional, Thompson, Ann, additional, Russell, Carolyn, additional, Prasad, Aparna, additional, Walker, Susan, additional, Pinto, Dalila, additional, Marshall, Christian R., additional, Stavropoulos, Dimitri J., additional, Zwaigenbaum, Lonnie, additional, Fernandez, Bridget A., additional, Fombonne, Eric, additional, Bolton, Patrick F., additional, Collier, David A., additional, Hodge, Jennelle C., additional, Roberts, Wendy, additional, Szatmari, Peter, additional, and Scherer, Stephen W., additional
- Published
- 2012
- Full Text
- View/download PDF
20. Migration of Cells From the Yolk Sac to Hematopoietic Tissues After Transplantation of Early and Mid Gestation Canine Fetuses
- Author
-
Vaags, Andrea K., primary, Gartley, Cathy J., additional, Halling, Krista B., additional, Dobson, Howard, additional, Zheng, Yanzhen, additional, Foltz, Warren D., additional, Dick, Alexander J., additional, Kruth, Stephen A., additional, and Hough, Margaret R., additional
- Published
- 2011
- Full Text
- View/download PDF
21. Migration of Cells From the Yolk Sac to Hematopoietic Tissues After In Utero Transplantation of Early and Mid Gestation Canine Fetuses
- Author
-
Vaags, Andrea K., primary, Gartley, Cathy J., additional, Halling, Krista B., additional, Dobson, Howard, additional, Zheng, Yanzhen, additional, Foltz, Warren D., additional, Dick, Alexander J., additional, Kruth, Stephen A., additional, and Hough, Margaret R., additional
- Published
- 2011
- Full Text
- View/download PDF
22. Derivation and Characterization of Canine Embryonic Stem Cell Lines with In Vitro and In Vivo Differentiation Potential.
- Author
-
Hough, Margaret R., primary, Vaags, Andrea K., additional, Goncalves, Anderson, additional, Gartley, Cathy J., additional, Zheng, Yanzhen, additional, Chesney, Alden, additional, and Kruth, Stephen A., additional
- Published
- 2010
- Full Text
- View/download PDF
23. Derivation and Characterization of Canine Embryonic Stem Cell Lines with In Vitro and In Vivo Differentiation Potential
- Author
-
Vaags, Andrea K., primary, Rosic-Kablar, Suzana, additional, Gartley, Cathy J., additional, Zheng, Yan Zhen, additional, Chesney, Alden, additional, Villagómez, Daniel A.F., additional, Kruth, Stephen A., additional, and Hough, Margaret R., additional
- Published
- 2009
- Full Text
- View/download PDF
24. Migration of Donor Cells from the Yolk Sac to Fetal Tissues after In Utero Transplantation of Early to Mid-Gestation Canine Fetuses.
- Author
-
Vaags, Andrea K., primary, Gartley, Cathy, additional, Zheng, Yanzhen, additional, Dobson, Howard, additional, Halling, Krista B., additional, Foltz, Warren D., additional, Dick, Alexander J., additional, Kruth, Stephen A., additional, and Hough, Margaret R., additional
- Published
- 2007
- Full Text
- View/download PDF
25. In Utero Transplantation of Stem Cells to the Yolk Sac of Early to Mid Gestation Canine Fetuses.
- Author
-
Vaags, Andrea K., primary, Gartley, Cathy, additional, Foltz, Warren D., additional, Halling, Krista B., additional, Dobson, Howard, additional, Dick, Alexander J., additional, Kruth, Stephen A., additional, and Hough, Margaret R., additional
- Published
- 2006
- Full Text
- View/download PDF
26. Ectopic TLX1 Expression Accelerates Malignancies in Mice Deficient in DNA-PK.
- Author
-
Krutikov, Konstantin, Zheng, Yanzhen, Chesney, Alden, Huang, Xiaoyong, Vaags, Andrea K., Evdokimova, Valentina, Hough, Margaret R., and Chen, Edwin
- Subjects
ECTOPIC hormones ,LABORATORY mice ,HOMEOBOX genes ,CHROMOSOMES ,CYTOMETRY ,LEUKEMIA etiology - Abstract
The noncluster homeobox gene HOX11/TLX1 (TLX1) is detected at the breakpoint of the t(10;14)(q24;q11) chromosome translocation in patients with T cell acute lymphoblastic leukemia (T-ALL). This translocation results in the inappropriate expression of TLX1 in T cells. The oncogenic potential of TLX1 was demonstrated in IgHμ-TLX1
Tg mice which develop mature B cell lymphoma after a long latency period, suggesting the requirement of additional mutations to initiate malignancy. To determine whether dysregulation of genes involved in the DNA damage response contributed to tumor progression, we crossed IgHμ-TLX1Tg mice with mice deficient in the DNA repair enzyme DNA-PK (PrkdcScid/Scid mice). IgHµ-TLX1Tg PrkdcScid/Scid mice developed T-ALL and acute myeloid leukemia (AML) with reduced latency relative to control PrkdcScid/Scid mice. Further analysis of thymi from premalignant mice revealed greater thymic cellularity concomitant with increased thymocyte proliferation and decreased apoptotic index. Moreover, premalignant and malignant thymocytes exhibited impaired spindle checkpoint function, in association with aneuploid karyotypes. Gene expression profiling of premalignant IgHµ-TLX1Tg PrkdcScid/Scid thymocytes revealed dysregulated expression of cell cycle, apoptotic and mitotic spindle checkpoint genes in double negative 2 (DN2) and DN3 stage thymocytes. Collectively, these findings reveal a novel synergy between TLX1 and impaired DNA repair pathway in leukemogenesis. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
27. eNOSOverexpressing Bone Marrow Cells are Safe and Effective in a Porcine Model of Myocardial Regeneration Following Acute Myocardial Infarction
- Author
-
Ward, Michael R., Connelly, Kim A., Vijayaraghavan, Ram, Vaags, Andrea K., Graham, John J., Foltz, Warren, Hough, Margaret R., Stewart, Duncan J., and Dick, Alexander
- Published
- 2013
- Full Text
- View/download PDF
28. 1036. Engraftment of side population Stem Cells in Canine Recipients
- Author
-
Vaags, Andrea K., Caton, David, Halling, Krista, Gartley, Cathy, Rosic-Kablar, Suzana, Kruth, Stephen A., and Hough, Margaret R.
- Subjects
- *
MICROBIOLOGY , *HEMATOLOGY - Abstract
An abstract of the article "Engraftment of side population Stem Cells in Canine Recipients," by Andrea K. Vaags and colleagues is presented.
- Published
- 2005
- Full Text
- View/download PDF
29. Migration of Donor Cells from the Yolk Sac to Fetal Tissues after In UteroTransplantation of Early to Mid-Gestation Canine Fetuses.
- Author
-
Vaags, Andrea K., Gartley, Cathy, Zheng, Yanzhen, Dobson, Howard, Halling, Krista B., Foltz, Warren D., Dick, Alexander J., Kruth, Stephen A., and Hough, Margaret R.
- Abstract
Transplantation of stem and progenitor cells, under permissive conditions, can result in the long-term engraftment of allogeneic donor cells. In uterotransplantation is of particular interest in that mixed chimerism may allow for the amelioration of disorders before birth and the development of immune tolerance towards donor cells prior to the maturation of the immune system. In order to more fully establish the feasibility of in uterocell transplantation, we are developing a canine model through the injection of allogeneic cells to the yolk sacs of day 25 or day 35 fetuses. Cell tracking was facilitated by labeling transplanted male canine cells with micron-sized superparamagnetic, fluorescent, polystyrene beads. Total bone marrow (BMMC) and mesenchymal stromal cells (MSC) were labeled for 16 hours with fluorescent superparamagnetic beads, prior to transplantation. Five pregnancies were studied, wherein 1–2 × 106MSC or 0.1–1 × 107BMMC were delivered to individual yolk sacs of day 25 (n=13) or day 35 (n=14) fetuses under ultrasound guidance. Each pregnancy included 1–2 fetuses that received an equal volume saline injection (n=7). Fetuses developed in uterofor an additional seven to fourteen days at which time ovariohysterectomy and fetal retrieval were performed. Ex vivowhole body fluorescence imaging of fetuses verified cell migration from the yolk sac injection site to the fetus proper based on increased levels of green fluorescence in injected versus non-injected controls. The signal was predominantly localized to the thoracic and abdominal regions, with no fluorescence visible in the yolk sac. Fluorescence microscopy for detection of the fluorophore and light microscopy of Prussian Blue stained sections for detection of superparamagnetic iron particles was performed to assess donor cell localization. The co-localization of iron particles and fluorescence label was detected on images taken from sequential sections. These analyses indicated that labeled BMMC and MSC migrated from the yolk sac to the fetal liver and to a lesser extent to the developing bone marrow cavity. In some cases, the use of superparamagnetic particles has been confounded by free particles being scavenged by macrophage. To determine if cell labeling was restricted to macrophage, sections were stained with an anti-macrophage antibody and analyzed by fluorescence microscopy. Co-localization of the anti-macrophage stain and the fluorescence of the particle was not detected. Furthermore, molecular confirmation of male donor cell engraftment in the livers of female fetuses was obtained via canine Y chromosome specific Q-PCR. Y chromosome positive cells were detected in female fetuses receiving either male MSC or BMMC, but not in saline injected controls. Our studies demonstrate that injection of cells into the yolk sac during early to mid gestation is an effective strategy to deliver cells to the developing fetus, and in particular to sites of fetal hematopoiesis. We are currently following in uterotransplant recipients to determine whether long-term engraftment and immune tolerance of donor cells during the neonatal period can be achieved.
- Published
- 2007
- Full Text
- View/download PDF
30. In UteroTransplantation of Stem Cells to the Yolk Sac of Early to Mid Gestation Canine Fetuses.
- Author
-
Vaags, Andrea K., Gartley, Cathy, Foltz, Warren D., Halling, Krista B., Dobson, Howard, Dick, Alexander J., Kruth, Stephen A., and Hough, Margaret R.
- Abstract
In uterostem cell therapy holds promise for the amelioration of disorders before birth. Futhermore, due to the preimmune state of the developing fetus, recipients do not reject allogeneic cell transplants and postnatal transplantation from the same donor may be possible without the need for anti-rejection drugs. In order to more fully establish the feasibility of in uterocell transplantation, we are developing a canine model through the injection of allogeneic cells to the yolk sac of day 25 or day 35 fetuses. Cell tracking was facilitated by labeling male canine cells with micron-sized superparamagnetic and fluorescent polystyrene beads. Both magnetic resonance imaging (MRI) and fluorescence imaging were employed to assess the fetal distribution of transplanted cells.
- Published
- 2006
- Full Text
- View/download PDF
31. Ectopic TLX1 Expression Accelerates Malignancies in Mice Deficient in DNA-PK.
- Author
-
Krutikov, Konstantin, Zheng, Yanzhen, Chesney, Alden, Huang, Xiaoyong, Vaags, Andrea K., Evdokimova, Valentina, Hough, Margaret R., and Chen, Edwin
- Subjects
- *
ECTOPIC hormones , *LABORATORY mice , *HOMEOBOX genes , *CHROMOSOMES , *CYTOMETRY , *LEUKEMIA etiology - Abstract
The noncluster homeobox gene HOX11/TLX1 (TLX1) is detected at the breakpoint of the t(10;14)(q24;q11) chromosome translocation in patients with T cell acute lymphoblastic leukemia (T-ALL). This translocation results in the inappropriate expression of TLX1 in T cells. The oncogenic potential of TLX1 was demonstrated in IgHμ-TLX1Tg mice which develop mature B cell lymphoma after a long latency period, suggesting the requirement of additional mutations to initiate malignancy. To determine whether dysregulation of genes involved in the DNA damage response contributed to tumor progression, we crossed IgHμ-TLX1Tg mice with mice deficient in the DNA repair enzyme DNA-PK (PrkdcScid/Scid mice). IgHµ-TLX1TgPrkdcScid/Scid mice developed T-ALL and acute myeloid leukemia (AML) with reduced latency relative to control PrkdcScid/Scid mice. Further analysis of thymi from premalignant mice revealed greater thymic cellularity concomitant with increased thymocyte proliferation and decreased apoptotic index. Moreover, premalignant and malignant thymocytes exhibited impaired spindle checkpoint function, in association with aneuploid karyotypes. Gene expression profiling of premalignant IgHµ-TLX1TgPrkdcScid/Scid thymocytes revealed dysregulated expression of cell cycle, apoptotic and mitotic spindle checkpoint genes in double negative 2 (DN2) and DN3 stage thymocytes. Collectively, these findings reveal a novel synergy between TLX1 and impaired DNA repair pathway in leukemogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
32. HIV TAT variants differentially influence the production of glucocerebrosidase in Sf9 cells.
- Author
-
Vaags AK, Campbell TN, and Choy FY
- Subjects
- Cell Line, Cell Membrane metabolism, Cells, Cultured, Gaucher Disease metabolism, Gaucher Disease therapy, Gene Products, tat genetics, Glucosylceramidase genetics, Humans, Protein Transport genetics, Transcription, Genetic, Transduction, Genetic, Gene Products, tat metabolism, Glucosylceramidase biosynthesis
- Abstract
Gaucher disease, the most common lysosomal storage disorder, is currently treated with enzyme replacement therapy. This approach, however, is ineffective in altering the progression of neurodegeneration in type 2 and type 3 patients due to the difficulty of transferring the recombinant enzyme across the blood-brain barrier. Human immunodeficiency virus type 1 trans-activating transcriptional activator protein (HIV TAT) contains a protein transduction domain that can be added to a fusion protein partner to allow for transport of the partner across membranes. Consequently, we examined the creation, production, and secretion of fusion constructs containing glucocerebrosidase and either wild-type TAT or modified TAT in Sf9 cells. All three constructs exhibited successful expression, with wild-type TAT chimeras showing lower levels of expression than modified TAT chimeras.
- Published
- 2005
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.