toggle visibility Search & Display Options

Select All    Deselect All
 |   | 
Details
   print
  Records Links
Author ACMG, B. of D. url  openurl
  Title ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing Type Journal Article
  Year 2015 Publication (up) Abbreviated Journal Genet Med  
  Volume 17 Issue 1 Pages 68-69  
  Keywords  
  Abstract DISCLAIMER: These recommendations are designed primarily as an educational resource for medical geneticists and other health-care providers to help them provide quality medical genetics services. Adherence to these recommendations does not necessarily ensure a successful medical outcome. These recommendations should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, geneticists and other clinicians should apply their own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. It may be prudent, however, to document in the patient’s record the rationale for any significant deviation from these recommendations.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1098-3600 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45436  
Permanent link to this record
 

 
Author Abraham, G.; Inouye, M. url  openurl
  Title Genomic risk prediction of complex human disease and its clinical application Type Journal Article
  Year 2015 Publication (up) Abbreviated Journal Curr Opin Genet Dev  
  Volume 33 Issue Pages 10-16  
  Keywords  
  Abstract Recent advances in genome-wide association studies have stimulated interest in the genomic prediction of disease risk, potentially enabling individual-level risk estimates for early intervention and improved diagnostic procedures. Here, we review recent findings and approaches to genomic prediction model construction and performance, then contrast the potential benefits of such models in two complex human diseases, aiding diagnosis in celiac disease and prospective risk prediction for cardiovascular disease. Early indications are that optimal application of genomic risk scores will differ substantially for each disease depending on underlying genetic architecture as well as current clinical and public health practice. As costs decline, genomic profiles become common, and popular understanding of risk and its communication improves, genomic risk will become increasingly useful for the individual and the clinician.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0959-437x ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45437  
Permanent link to this record
 

 
Author Alkuraya, F.S. url  openurl
  Title Human knockout research: new horizons and opportunities Type Journal Article
  Year 2015 Publication (up) Abbreviated Journal Trends Genet  
  Volume 31 Issue 2 Pages 108-115  
  Keywords  
  Abstract Although numerous approaches have been pursued to understand the function of human genes, Mendelian genetics has by far provided the most compelling and medically actionable dataset. Biallelic loss-of-function (LOF) mutations are observed in the majority of autosomal recessive Mendelian disorders, representing natural human knockouts and offering a unique opportunity to study the physiological and developmental context of these genes. The restriction of such context to ‘disease’ states is artificial, however, and the recent ability to survey entire human genomes for biallelic LOF mutations has revealed a surprising landscape of knockout events in ‘healthy’ individuals, sparking interest in their role in phenotypic diversity beyond disease causation. As I discuss in this review, the potentially wide implications of human knockout research warrant increased investment and multidisciplinary collaborations to overcome existing challenges and reap its benefits.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0168-9525 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45506  
Permanent link to this record
 

 
Author Adebayo, D.; Morabito, V.; Davenport, A.; Jalan, R. url  openurl
  Title Renal dysfunction in cirrhosis is not just a vasomotor nephropathy Type Journal Article
  Year 2015 Publication (up) Abbreviated Journal Kidney Int  
  Volume 87 Issue 3 Pages 509-515  
  Keywords  
  Abstract The short-term mortality of cirrhotic patients who develop renal dysfunction remains unacceptably high, and as such the treatment of this condition is an unmet need. Although features of kidney injury are well recognized in these patients, the pathophysiology is complex and not completely understood. Improved understanding of the pathophysiological mechanisms involved in renal dysfunction occurring on a background of cirrhosis is key to developing effective treatment strategies to improve survival. Renal dysfunction due to hepatorenal syndrome (HRS) is characteristic of cirrhosis. Our current understanding is that HRS is functional in nature and occurs as a consequence of hemodynamic changes associated with portal hypertension. However, there is evidence in the literature suggesting that, histologically, the kidneys are not always normal in the vast majority of patients who present with renal dysfunction on the background of cirrhosis. Furthermore, there is emerging data implicating nonvasomotor mechanisms in the pathophysiology of renal dysfunction in cirrhosis. This mini-review aims to present the evidence suggesting that factors other than hemodynamic dysregulation have an important role in the development of this major complication for patients with progressive cirrhosis.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0085-2538 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45609  
Permanent link to this record
 

 
Author Astudillo, L.; Sabourdy, F.; Therville, N.; Bode, H.; Ségui, B.; Andrieu-Abadie, N.; Hornemann, T.; Levade, T. url  openurl
  Title Human genetic disorders of sphingolipid biosynthesis Type Journal Article
  Year 2015 Publication (up) Abbreviated Journal J Inherit Metab Dis  
  Volume 38 Issue 1 Pages 65-76  
  Keywords research support, non-u.s. gov’t; lipid human disease  
  Abstract Monogenic defects of sphingolipid biosynthesis have been recently identified in human patients. These enzyme deficiencies affect the synthesis of sphingolipid precursors, ceramides or complex glycosphingolipids. They are transmitted as autosomal recessive or dominant traits, and their resulting phenotypes often replicate the abnormalities seen in murine models deficient for the corresponding enzymes. In quite good agreement with the known critical roles of sphingolipids in cells from the nervous system and the epidermis, these genetic defects clinically manifest as neurological disorders, including paraplegia, epilepsy or peripheral neuropathies, or present with ichthyosis. The present review summarizes the genetic alterations, biochemical changes and clinical symptoms of this new group of inherited metabolic disorders. Hypotheses regarding the molecular pathophysiology and potential treatments of these diseases are also discussed.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0141-8955 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45621  
Permanent link to this record
 

 
Author Gros, A.; Syvannarath, V.; Lamrani, L.; Ollivier, V.; Loyau, S.; Goerge, T.; Nieswandt, B.; Jandrot-Perrus, M.; Ho-Tin-Noé, B. openurl 
  Title Single platelets seal neutrophil-induced vascular breaches via GPVI during immune complex-mediated inflammation in mice Type Journal Article
  Year 2015 Publication (up) Abbreviated Journal Blood  
  Volume Issue Pages  
  Keywords Confocal; IVM; Microscopy; Model: Mouse; Mouse; Multiphoton; Thrombosis  
  Abstract Platelets protect vascular integrity during inflammation. Recent evidence suggests that this action is independent of thrombus formation and requires the engagement of glycoprotein VI (GPVI), but it remains unclear how platelets prevent inflammatory bleeding. We investigated whether platelets and GPVI act primarily by preventing detrimental effects of neutrophils using models of immune complex(IC)-mediated inflammation in mice immuno-depleted in platelets and/or neutrophils or deficient in GPVI. Depletion of neutrophils prevented bleeding in thrombocytopenic and GPVI-/- mice during IC-mediated dermatitis. GPVI deficiency did not modify neutrophil recruitment, which was however reduced by thrombocytopenia. Neutrophil cytotoxic activities were reduced in thrombocytopenic and GPVI-/- mice during IC-mediated inflammation. Intravital microscopy revealed that in this setting, intravascular binding sites for platelets were exposed by neutrophils, and GPVI supported the recruitment of individual platelets to these spots. Furthermore, the platelet secretory response accompanying IC-mediated inflammation was partly mediated by GPVI and blocking of GPVI signalling impaired the vasculoprotective action of platelets. Together, our results show that GPVI plays a dual role in inflammation by enhancing neutrophil damaging activities while supporting the activation and hemostatic adhesion of single platelets to neutrophil-induced vascular breaches.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45622  
Permanent link to this record
 

 
Author Alsady, M.; Baumgarten, R.; Deen, P.M.; de Groot, T. url  openurl
  Title Lithium in the Kidney: Friend and Foe Type Journal Article
  Year 2015 Publication (up) Abbreviated Journal J Am Soc Nephrol  
  Volume Issue Pages  
  Keywords Nephrology  
  Abstract Trace amounts of lithium are essential for our physical and mental health, and administration of lithium has improved the quality of life of millions of patients with bipolar disorder for >60 years. However, in a substantial number of patients with bipolar disorder, long-term lithium therapy comes at the cost of severe renal side effects, including nephrogenic diabetes insipidus and rarely, ESRD. Although the mechanisms underlying the lithium-induced renal pathologies are becoming clearer, several recent animal studies revealed that short-term administration of lower amounts of lithium prevents different forms of experimental AKI. In this review, we discuss the knowledge of the pathologic and therapeutic effects of lithium in the kidney. Furthermore, we discuss the underlying mechanisms of these seemingly paradoxical effects of lithium, in which fine-tuned regulation of glycogen synthase kinase type 3, a prime target for lithium, seems to be key. The new discoveries regarding the protective effect of lithium against AKI in rodents call for follow-up studies in humans and suggest that long-term therapy with low lithium concentrations could be beneficial in CKD.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1046-6673 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45624  
Permanent link to this record
 

 
Author Andersson, R.; Sandelin, A.; Danko, C.G. url  openurl
  Title A unified architecture of transcriptional regulatory elements Type Journal Article
  Year 2015 Publication (up) Abbreviated Journal Trends Genet  
  Volume 31 Issue 8 Pages 426-433  
  Keywords  
  Abstract Gene expression is precisely controlled in time and space through the integration of signals that act at gene promoters and gene-distal enhancers. Classically, promoters and enhancers are considered separate classes of regulatory elements, often distinguished by histone modifications. However, recent studies have revealed broad similarities between enhancers and promoters, blurring the distinction: active enhancers often initiate transcription, and some gene promoters have the potential to enhance transcriptional output of other promoters. Here, we propose a model in which promoters and enhancers are considered a single class of functional element, with a unified architecture for transcription initiation. The context of interacting regulatory elements and the surrounding sequences determine local transcriptional output as well as the enhancer and promoter activities of individual elements.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0168-9525 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45626  
Permanent link to this record
 

 
Author Allum, F.; Shao, X.; Guénard, F.; Simon, M.M.; Busche, S.; Caron, M.; Lambourne, J.; Lessard, J.; Tandre, K.; Hedman, Å.K.; Kwan, T.; Ge, B.; Multiple, T.H.E.R.C.; Rönnblom, L.; McCarthy, M.I.; Deloukas, P.; Richmond, T.; Burgess, D.; Spector, T.D.; Tchernof, A.; Marceau, S.; Lathrop, M.; Vohl, M.C.; Pastinen, T.; Grundberg, E. url  openurl
  Title Characterization of functional methylomes by next-generation capture sequencing identifies novel disease-associated variants Type Journal Article
  Year 2015 Publication (up) Abbreviated Journal Nat Commun  
  Volume 6 Issue Pages 7211  
  Keywords  
  Abstract Most genome-wide methylation studies (EWAS) of multifactorial disease traits use targeted arrays or enrichment methodologies preferentially covering CpG-dense regions, to characterize sufficiently large samples. To overcome this limitation, we present here a new customizable, cost-effective approach, methylC-capture sequencing (MCC-Seq), for sequencing functional methylomes, while simultaneously providing genetic variation information. To illustrate MCC-Seq, we use whole-genome bisulfite sequencing on adipose tissue (AT) samples and public databases to design AT-specific panels. We establish its efficiency for high-density interrogation of methylome variability by systematic comparisons with other approaches and demonstrate its applicability by identifying novel methylation variation within enhancers strongly correlated to plasma triglyceride and HDL-cholesterol, including at CD36. Our more comprehensive AT panel assesses tissue methylation and genotypes in parallel at ∼4 and ∼3 M sites, respectively. Our study demonstrates that MCC-Seq provides comparable accuracy to alternative approaches but enables more efficient cataloguing of functional and disease-relevant epigenetic and genetic variants for large-scale EWAS.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 2041-1723 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45631  
Permanent link to this record
 

 
Author Ali, M.I.; Chen, X.; Didion, S.P. url  openurl
  Title Heterozygous eNOS deficiency is associated with oxidative stress and endothelial dysfunction in diet-induced obesity Type Journal Article
  Year 2015 Publication (up) Abbreviated Journal Physiol Rep  
  Volume 3 Issue 12 Pages  
  Keywords  
  Abstract Heterozygous endothelial nitric oxide synthase (eNOS) deficiency is associated with normal endothelium-dependent responses, however, little is known regarding the mechanisms that maintain or impair endothelial function with heterozygous eNOS deficiency. The goals of this study were to (1) determine mechanism(s) which serve to maintain normal endothelial function in the absence of a single eNOS gene; and (2) to determine whether heterozygous eNOS deficiency predisposes blood vessels to endothelial dysfunction in response to a high-fat diet (HFD). Responses of carotid arteries were examined in wild-type (eNOS(+/+)) and heterozygous eNOS-deficient (eNOS(+/-)) treated with either vehicle (saline), N(G)-nitro-L-arginine (L-NNA, 100 μmol/L), an inhibitor of nitric oxide synthase, or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 μmol/L), an inhibitor of soluble guanylyl cyclase (sGC), and in eNOS(+/+) and eNOS(+/-) mice fed a control (10%) or a 45% HFD (kcal from fat). Responses to acetylcholine (ACh) were similar in vehicle-treated arteries from eNOS(+/+) and eNOS(+/-) mice, and were equally inhibited by L-NNA and ODQ. Phosphorylation of eNOS Ser1176, a site associated with increased eNOS activity, was significantly greater in eNOS(+/-) mice most likely as a compensatory response for the loss of a single eNOS gene. In contrast, responses to ACh were markedly impaired in carotid arteries from eNOS(+/-), but not eNOS(+/+), mice fed a HFD. Vascular superoxide levels as well as plasma levels of the pro-inflammatory cytokine interleukin-6 (IL-6) were selectively increased in HFD-fed eNOS(+/-) mice. In reconstitution experiments, IL-6 produced concentration-dependent impairment of endothelial responses as well as greater increases in NADPH-stimulated superoxide levels in arteries from eNOS(+/-) mice fed a control diet compared to eNOS(+/+) mice. Our findings of increased Ser1176-phosphorylation reveal a mechanism by which NOS- and sGC-dependent endothelial function can be maintained with heterozygous eNOS deficiency. In addition, heterozygous eNOS deficiency predisposes blood vessels to developing endothelial dysfunction in response to a HFD. The impairment produced by a HFD in eNOS(+/-) mice appears to be mediated by IL-6-induced increases in vascular superoxide. These findings serve as an important example of eNOS haploinsufficiency, one that may contribute to the development of carotid artery disease in obese humans.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 2051-817x ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number UofT @ mathieu.lemaire @ Serial 45799  
Permanent link to this record
Select All    Deselect All
 |   | 
Details
   print

Save Citations:
Export Records: