A flexible copula‐based approach for the analysis of secondary phenotypes in ascertained samples

2019 ◽  
Vol 39 (5) ◽  
pp. 517-543
Author(s):  
Fodé Tounkara ◽  
Geneviève Lefebvre ◽  
Celia Greenwood ◽  
Karim Oualkacha
Keyword(s):  
Secondary Phenotypes

Gene Overexpression as a Tool for Identifying New trans-Acting Factors Involved in Translation Termination in Saccharomyces cerevisiae

Genetics ◽  
2002 ◽  
Vol 161 (2) ◽  
pp. 585-594
Author(s):  
Olivier Namy ◽  
Isabelle Hatin ◽  
Guillaume Stahl ◽  
Hongmei Liu ◽  
Stephanie Barnay ◽  
...  
Keyword(s):  
Protein Transport ◽  
Stop Codon ◽  
Translation Termination ◽  
Spindle Pole Body ◽  
Spindle Pole ◽  
Release Factor ◽  
Lacz Reporter Gene ◽  
Pole Body ◽  
Secondary Phenotypes ◽  
Termination Process

Abstract In eukaryotes, translation termination is dependent on the availability of both release factors, eRF1 and eRF3; however, the precise mechanisms involved remain poorly understood. In particular, the fact that the phenotype of release factor mutants is pleiotropic could imply that other factors and interactions are involved in translation termination. To identify unknown elements involved in this process, we performed a genetic screen using a reporter strain in which a leaky stop codon is inserted in the lacZ reporter gene, attempting to isolate factors modifying termination efficiency when overexpressed. Twelve suppressors and 11 antisuppressors, increasing or decreasing termination readthrough, respectively, were identified and analyzed for three secondary phenotypes often associated with translation mutations: thermosensitivity, G418 sensitivity, and sensitivity to osmotic pressure. Interestingly, among these candidates, we identified two genes, SSO1 and STU2, involved in protein transport and spindle pole body formation, respectively, suggesting puzzling connections with the translation termination process.

scholarly journals Systematic review of Kabuki Syndrome’s phenotype with KMT2D gene mutation

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Leonardo Bonini Fischetti ◽  
Julia Zaccarelli Magalhães ◽  
André Rinaldi Fukushima ◽  
Paula Waziry ◽  
Esther Lopes Ricci
Keyword(s):  
Systematic Review ◽  
Differential Diagnosis ◽  
Case Report ◽  
Animal Models ◽  
Case Reports ◽  
Accurate Diagnosis ◽  
Kabuki Syndrome ◽  
Live Births ◽  
Comparative Review ◽  
Secondary Phenotypes

Kabuki Syndrome is rare and poorly documented, initially mentioned by Niikawa and Kuroki in 1981. The prevalence of the syndrome among live births is 1:32,000. Case reports are now available, which correlates to improved techniques for accurate diagnosis. This study focused on a systematic comparative review of the phenotypes of individuals with Kabuki Syndrome, with the purpose to facilitate diagnosis. The systematic review was done with a bibliographic survey of case studies using the following databases: Pubmed, Science Direct and Google Scholar, in conjunction with the following key-words: Kabuki syndrome, phenotype, KMT2D and case report. The literature shows that patients with this syndrome present five main characteristics, besides several types of secondary phenotypes. These characteristics present variations in permeability as well as expressivity of some genes in individuals, therefore, a characterization through phenotype alone becomes limited, making it necessary to perform genetic analysis for differential diagnosis. In order to increase the knowledge and elucidate mechanisms of Kabuki syndrome, we suggest further studies that utilize animal models.

scholarly journals Analysis of secondary phenotypes in multigroup association studies

Biometrics ◽  
2019 ◽  
Vol 76 (2) ◽  
pp. 606-618
Author(s):  
Fan Zhou ◽  
Haibo Zhou ◽  
Tengfei Li ◽  
Hongtu Zhu
Keyword(s):  
Association Studies ◽  
Secondary Phenotypes

scholarly journals Attempted replication of SNPs in RANKL and OPG with musculoskeletal adverse events during aromatase inhibitor treatment for breast cancer

2018 ◽  
Vol 50 (2) ◽  
pp. 98-99 ◽  
Author(s):  
Jacqueline M. Dempsey ◽  
Jingyue Xi ◽  
N. Lynn Henry ◽  
James M. Rae ◽  
Daniel L. Hertz
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Aromatase Inhibitor ◽  
Treatment Discontinuation ◽  
Nucleotide Polymorphisms ◽  
Drug Induced ◽  
Estrogen Receptor Positive ◽  
Aromatase Inhibitor Treatment ◽  
Primary Hypothesis ◽  
Secondary Phenotypes

Aromatase inhibitor (AI) therapy is highly efficacious in the treatment of estrogen receptor-positive breast cancer; however, in a subset of patients AI use is discontinued due to drug-induced musculoskeletal adverse events (MS-AE). Several studies have investigated the role of germline single nucleotide polymorphisms (SNPs) on patients’ risk of MS-AEs; however, no associations have yet to be validated for translation into clinical practice. This study attempted to replicate SNPs in RANKL ( rs7984870 ) and OPG ( rs2073618 ) on the risk of AI-induced MS-AEs and screen for secondary associations with MS-AE-related treatment discontinuation and serum and urine markers of bone health. Previously reported associations were not replicated with our primary hypothesis, change in MS-AE from baseline to 3 mo; however, patients homozygous for the G allele of rs7984870 in RANKL had lower risk of MS-AE-associated treatment discontinuation in analyses of secondary phenotypes without statistical correction.

scholarly journals Robust analysis of secondary phenotypes in case-control genetic association studies

2016 ◽  
Vol 35 (23) ◽  
pp. 4226-4237 ◽  
Author(s):  
Chuanhua Xing ◽  
Janice M. McCarthy ◽  
Josée Dupuis ◽  
L. Adrienne Cupples ◽  
James B. Meigs ◽  
...  
Keyword(s):  
Genetic Association ◽  
Association Studies ◽  
Genetic Association Studies ◽  
Case Control ◽  
Robust Analysis ◽  
Secondary Phenotypes

scholarly journals Foreign Cry1Ab/c Delays Flowering in Insect-Resistant Transgenic Rice via Interaction With Hd3a Florigen

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianmei Fu ◽  
Guoqiang Liu ◽  
Biao Liu
Keyword(s):  
Protein Expression ◽  
Flowering Time ◽  
Transgenic Rice ◽  
Molecular Mechanisms ◽  
Alkaline Soils ◽  
Flowering Genes ◽  
Endogenous Proteins ◽  
Delayed Flowering ◽  
Secondary Phenotypes ◽  
Insect Resistant

Genetic modifications in rice, which resulted in insect resistance, have been highly efficacious. However, they have also induced undesirable secondary phenotypes, such as delayed flowering. The molecular mechanisms associated with these unwanted effects remain unclear. Here, we showed that the flowering time for insect-resistant transgenic cry1Ab/c rice Huahui-1 (HH1) was delayed, compared with that for the parental rice Minghui-63 (MH63), cultivated on farmland and saline–alkaline soils. In contrast, the insect-resistant transgenic cry1C^* rice cultivars T1C-19 and MH63 had similar flowering times under the same conditions. We quantified the following: the expression of five major flowering genes in HH1, T1C-19, and MH63; florigen Hd3a protein expression levels in HH1 and MH63; interactions between Cry1Ab/c and the five main flowering proteins; and the effects of E3s ubiquitin ligase-mediated Cry1Ab/c expression on florigen Hd3a. Hd3a transcription was significantly lower in HH1 but not in T1C-19, compared with that in MH63. The results of yeast two-hybrid, complementary bimolecular fluorescence, and co-immunoprecipitation assays revealed that florigen Hd3a interacted with the exogenous Cry1Ab/c expressed in HH1 and not the exogenous Cry1C^* expressed in T1C-19. When Cry1Ab/c, Hd3a, and E3s fusion proteins were transiently co-expressed in tobacco cells, the Hd3a expression level was significantly lower than the level of Cry1Ab/c and Hd3a co-expression. Thus, the downregulation of Hd3a expression and the interaction between Cry1Ab/c and Hd3a interfere with Hd3a protein expression and might cooperatively delay HH1 flowering time. To the best of our knowledge, this study is the first to explain the delay in flowering time in insect-resistant transgenic rice, mediated by interactions between exogenous and endogenous proteins. This information might help elucidate the molecular mechanisms associated with these unwanted phenotypes effects and improve the process of biosafety assessment of transgenic rice.

scholarly journals Genome-wide Association Analysis for Multiple Continuous Secondary Phenotypes

2013 ◽  
Vol 92 (5) ◽  
pp. 744-759 ◽  
Author(s):  
Elizabeth D. Schifano ◽  
Lin Li ◽  
David C. Christiani ◽  
Xihong Lin
Keyword(s):  
Association Analysis ◽  
Genome Wide Association ◽  
Genome Wide Association Analysis ◽  
Genome Wide ◽  
Secondary Phenotypes
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