Role of Modifier Genes in Idiopathic Cardiomyopathies

The ubiquitin proteasome system (UPS) has been the subject of intensive research over the past 20 years to define its role in normal physiology and in pathophysiology. Many of these studies have focused in on the cardiovascular system and have determined that the UPS becomes dysfunctional in several pathologies such as familial and idiopathic cardiomyopathies, atherosclerosis, and myocardial ischemia. This review presents a synopsis of the literature as it relates to the role of the UPS in myocardial ischemia. Studies have shown that the UPS is dysfunctional during myocardial ischemia, and recent studies have shed some light on possible mechanisms. Other studies have defined a role for the UPS in ischemic preconditioning which is best associated with myocardial ischemia and is thus presented here. Very recent studies have started to define roles for specific proteasome subunits and components of the ubiquitination machinery in various aspects of myocardial ischemia. Lastly, despite the evidence linking myocardial ischemia and proteasome dysfunction, there are continuing suggestions that proteasome inhibitors may be useful to mitigate ischemic injury. This review presents the rationale behind this and discusses both supportive and nonsupportive studies and presents possible future directions that may help in clarifying this controversy.

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Genotype-phenotype correlation in cystic fibrosis: The role of modifier genes

American Journal of Medical Genetics ◽

10.1002/ajmg.10461 ◽

2002 ◽

Vol 111 (1) ◽

pp. 88-95 ◽

Cited By ~ 99

Author(s):

Francesco Salvatore ◽

Olga Scudiero ◽

Giuseppe Castaldo

Keyword(s):

Cystic Fibrosis ◽

Modifier Genes ◽

Phenotype Correlation ◽

Genotype Phenotype Correlation

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Cystic Fibrosis Lung Immunity: The Role of the Macrophage

Journal of Innate Immunity ◽

10.1159/000446825 ◽

2016 ◽

Vol 8 (6) ◽

pp. 550-563 ◽

Cited By ~ 54

Author(s):

Emanuela M. Bruscia ◽

Tracey L. Bonfield

Keyword(s):

Cystic Fibrosis ◽

Modifier Genes ◽

Cystic Fibrosis Lung ◽

Environmental Cues ◽

Major Morbidity ◽

Adaptive Immune ◽

Lung Infections ◽

Lung Immunity

Cystic fibrosis (CF) pathophysiology is hallmarked by excessive inflammation and the inability to efficiently resolve lung infections, contributing to major morbidity and eventually the mortality of patients with this disease. Macrophages (MΦs) are major players in lung homeostasis through their diverse contributions to both the innate and adaptive immune networks. The setting of MΦ function and activity in CF is multifaceted, encompassing the response to the unique environmental cues in the CF lung as well as the intrinsic changes resulting from CFTR dysfunction. The complexity is further enhanced with the identification of modifier genes, which modulate the CFTR contribution to disease, resulting in epigenetic and transcriptional shifts in MΦ phenotype. This review focuses on the contribution of MΦ to lung homeostasis, providing an overview of the diverse literature and various perspectives on the role of these immune guardians in CF.

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Genetic control of meiotic recombination in Petunia hybrida: dosage effect of gene Rm1 on segments Hf1-Lg1 and An2-Rt; role of modifiers

Genome ◽

10.1139/g91-079 ◽

1991 ◽

Vol 34 (4) ◽

pp. 515-523 ◽

Cited By ~ 7

Author(s):

N. Robert ◽

E. Farcy ◽

A. Cornu

Keyword(s):

Genetic Control ◽

Meiotic Recombination ◽

Petunia Hybrida ◽

Modifier Genes ◽

Dosage Effect ◽

Chromosome Segment ◽

Marker Pair ◽

Incomplete Dominance ◽

Chromosome Segments

Populations segregating at locus Rm1 were used to measure recombination within two chromosome segments in Petunia hybrida. Gene Rm1 shows incomplete dominance and action that differs according to marker pair studied. It enhances recombination within the segment Hf1-Lg1 and restores it for the pair An2-Rt. Minor modifier genes exist, which act independent of or epistatic to Rm1 action. Like Rm1, they have effects that differ according to the chromosome segment analyzed, with the effects being more pronounced for strongly linked loci. Some of these genes are probably recessive.Key words: Petunia hybrida, gene Rm1, meiotic recombination, dosage effect.

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