scholarly journals The emerging spectrum of allelic variation in schizophrenia: current evidence and strategies for the identification and functional characterization of common and rare variants

2012 ◽  
Vol 18 (1) ◽  
pp. 38-52 ◽  
Author(s):  
B J Mowry ◽  
J Gratten
Keyword(s):  
Rare Variants ◽  
Allelic Variation ◽  
Functional Characterization ◽  
Current Evidence

scholarly journals Identification and functional characterization of NODAL rare variants in heterotaxy and isolated cardiovascular malformations

2008 ◽  
Vol 18 (5) ◽  
pp. 861-871 ◽  
Author(s):  
Bhagyalaxmi Mohapatra ◽  
Brett Casey ◽  
Hua Li ◽  
Trang Ho-Dawson ◽  
Liana Smith ◽  
...  
Keyword(s):  
Rare Variants ◽  
Functional Characterization ◽  
Cardiovascular Malformations

scholarly journals Functional Characterization of TNNC1 Rare Variants Identified in Dilated Cardiomyopathy

2011 ◽  
Vol 286 (39) ◽  
pp. 34404-34412 ◽  
Author(s):  
Jose Renato Pinto ◽  
Jill D. Siegfried ◽  
Michelle S. Parvatiyar ◽  
Duanxiang Li ◽  
Nadine Norton ◽  
...  
Keyword(s):  
Dilated Cardiomyopathy ◽  
Rare Variants ◽  
Functional Characterization

scholarly journals Functional Characterization of Clinically-Relevant Rare Variants in ABCG2 Identified in a Gout and Hyperuricemia Cohort

Cells ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 363 ◽  
Author(s):  
Toyoda ◽  
Mančíková ◽  
Krylov ◽  
Morimoto ◽  
Pavelcová ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Rare Variants ◽  
Direct Sequencing ◽  
Functional Characterization ◽  
Cellular Proteins ◽  
European Descent ◽  
Primary Gout ◽  
Abcg2 Protein ◽  
Functional Analyses

ATP-binding cassette subfamily G member 2 (ABCG2) is a physiologically important urate transporter. Accumulating evidence demonstrates that congenital dysfunction of ABCG2 is an important genetic risk factor in gout and hyperuricemia; recent studies suggest the clinical significance of both common and rare variants of ABCG2. However, the effects of rare variants of ABCG2 on the risk of such diseases are not fully understood. Here, using a cohort of 250 Czech individuals of European descent (68 primary hyperuricemia patients and 182 primary gout patients), we examined exonic non-synonymous variants of ABCG2. Based on the results of direct sequencing and database information, we experimentally characterized nine rare variants of ABCG2: R147W (rs372192400), T153M (rs753759474), F373C (rs752626614), T421A (rs199854112), T434M (rs769734146), S476P (not annotated), S572R (rs200894058), D620N (rs34783571), and a three-base deletion K360del (rs750972998). Functional analyses of these rare variants revealed a deficiency in the plasma membrane localization of R147W and S572R, lower levels of cellular proteins of T153M and F373C, and null urate uptake function of T434M and S476P. Accordingly, we newly identified six rare variants of ABCG2 that showed lower or null function. Our findings contribute to deepening the understanding of ABCG2-related gout/hyperuricemia risk and the biochemical characteristics of the ABCG2 protein.

scholarly journals Functional Characterization of 21 Rare Allelic CYP1A2 Variants Identified in a Population of 4773 Japanese Individuals by Assessing Phenacetin O-Deethylation

2021 ◽  
Vol 11 (8) ◽  
pp. 690
Author(s):  
Masaki Kumondai ◽  
Evelyn Marie Gutiérrez Rico ◽  
Eiji Hishinuma ◽  
Yuya Nakanishi ◽  
Shuki Yamazaki ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Protein Function ◽  
Rare Variants ◽  
Functional Characterization ◽  
Three Dimensional ◽  
Additional Information ◽  
Metabolic Reactions ◽  
Underlying Mechanisms ◽  
Cytochrome Content

Cytochrome P450 1A2 (CYP1A2), which accounts for approximately 13% of the total hepatic cytochrome content, catalyzes the metabolic reactions of approximately 9% of frequently used drugs, including theophylline and olanzapine. Substantial inter-individual differences in enzymatic activity have been observed among patients, which could be caused by genetic polymorphisms. Therefore, we functionally characterized 21 novel CYP1A2 variants identified in 4773 Japanese individuals by determining the kinetic parameters of phenacetin O-deethylation. Our results showed that most of the evaluated variants exhibited decreased or no enzymatic activity, which may be attributed to potential structural alterations. Notably, the Leu98Gln, Gly233Arg, Ser380del Gly454Asp, and Arg457Trp variants did not exhibit quantifiable enzymatic activity. Additionally, three-dimensional (3D) docking analyses were performed to further understand the underlying mechanisms behind variant pharmacokinetics. Our data further suggest that despite mutations occurring on the protein surface, accumulating interactions could result in the impairment of protein function through the destabilization of binding regions and changes in protein folding. Therefore, our findings provide additional information regarding rare CYP1A2 genetic variants and how their underlying effects could clarify discrepancies noted in previous phenotypical studies. This would allow the improvement of personalized therapeutics and highlight the importance of identifying and characterizing rare variants.

scholarly journals Functional Characterization of Rare Variants Implicated in Susceptibility to Lone Atrial Fibrillation

2015 ◽  
Vol 8 (5) ◽  
pp. 1095-1104 ◽  
Author(s):  
Kenshi Hayashi ◽  
Tetsuo Konno ◽  
Hayato Tada ◽  
Satoyuki Tani ◽  
Li Liu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Rare Variants ◽  
Functional Characterization ◽  
Lone Atrial Fibrillation

scholarly journals Functional Characterization of Rare Variants in the SHOX2 Gene Identified in Sinus Node Dysfunction and Atrial Fibrillation

2019 ◽  
Vol 10 ◽  
Author(s):  
Sandra Hoffmann ◽  
Christoph Paone ◽  
Simon A. Sumer ◽  
Sabrina Diebold ◽  
Birgit Weiss ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Rare Variants ◽  
Sinus Node ◽  
Functional Characterization ◽  
Sinus Node Dysfunction

Cloning and functional characterization of allelic variation in the porcine prolactin receptor

2007 ◽  
Vol 33 (3) ◽  
pp. 313-334 ◽  
Author(s):  
Josephine F. Trott ◽  
Nicholas R. Farley ◽  
Douglas J. Taatjes ◽  
Russell C. Hovey
Keyword(s):  
Allelic Variation ◽  
Prolactin Receptor ◽  
Functional Characterization

Functional characterization of rare variants in human dopamine receptor D4 gene by genotype–phenotype correlations

Neuroscience ◽  
2014 ◽  
Vol 262 ◽  
pp. 176-189 ◽  
Author(s):  
K.A. Michealraj ◽  
N. Jatana ◽  
Md. Jafurulla ◽  
L. Narayanan ◽  
A. Chattopadhyay ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
Rare Variants ◽  
Functional Characterization ◽  
Dopamine Receptor D4

Functional characterization of human brown adipose tissue metabolism

2020 ◽  
Vol 477 (7) ◽  
pp. 1261-1286 ◽  
Author(s):  
Marie Anne Richard ◽  
Hannah Pallubinsky ◽  
Denis P. Blondin
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Functional Characterization ◽  
Human Infants ◽  
Positron Emission ◽  
Brown Adipose ◽  
Treatment Of Obesity ◽  
And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

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