Genetic interaction of GSH metabolic pathway genes in cystic fibrosis

The digestive system includes the structures and organs involved in processing of foods required for growth, development, maintenance, and body repair. Most diseases affecting this system are due to infections from bacteria, viruses, protozoa, and fungi, while others are hereditary. The ear, nose, and throat (ENT) system is a complex set of structures sharing slightly interrelated mechanisms of operation. While some disorders of the ENT are hereditary, environmental influences play a big role. Diseases that affect eyesight primarily centre on three layers of the eye (sclera, choroid, and retina) which make eyesight possible. Disorders of metabolism occur when a crucial enzyme is disabled, or if a control mechanism for a metabolic pathway is affected. The chapter focuses on 14 diseases with suspected genetic causes including cystic fibrosis, diabetes, glucose-galactose malabsorption, hemochromatosis, obesity, Wilson's Disease, Zellweger syndrome, deafness, Pendred syndrome, Best Disease, glaucoma, gyrate atrophy, male pattern baldness, and Alport syndrome.

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WS20.5 Genetic interaction of NOS-1 and CFTR gene and its association with cystic fibrosis severity

Journal of Cystic Fibrosis ◽

10.1016/s1569-1993(13)60127-7 ◽

2013 ◽

Vol 12 ◽

pp. S42

Author(s):

F.A. Marson ◽

C.S. Bertuzzo ◽

A.F. Ribeiro ◽

J.D. Ribeiro

Keyword(s):

Cystic Fibrosis ◽

Genetic Interaction ◽

Cftr Gene

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Ancient balancing selection maintains incompatible versions of a conserved metabolic pathway in yeast

10.1101/829325 ◽

2019 ◽

Cited By ~ 1

Author(s):

James Boocock ◽

Meru J Sadhu ◽

Joshua S Bloom ◽

Leonid Kruglyak

Keyword(s):

Saccharomyces Cerevisiae ◽

Metabolic Pathway ◽

Genetic Interaction ◽

Balancing Selection ◽

Sensu Stricto ◽

The Other ◽

Reference Allele ◽

Metabolic Genes ◽

Species Cluster ◽

Metabolic Strategies

AbstractDifferences in nutrient availability have led to the evolution of diverse metabolic strategies across species, but within species these strategies are expected to be similar. Here, we discovered that the galactose metabolic pathway in the yeast Saccharomyces cerevisiae exists in two functionally distinct, incompatible states maintained by ancient balancing selection. We identified a genetic interaction for growth in galactose among the metabolic genes GAL2, GAL1/10/7, and PGM1. We engineered strains with all allelic combinations at these loci and showed that the reference allele of PGM1 is incompatible with the alternative alleles of the other genes. We observed a strong signature of ancient balancing selection at all three loci and found that the alternative alleles diverged from the reference alleles before the birth of the Saccharomyces sensu stricto species cluster 10-20 million years ago. Strains with the alternative alleles are found primarily in galactose-rich dairy environments, and they grow faster in galactose, but slower in glucose, revealing a tradeoff on which balancing selection may have acted.

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Flux, toxicity and protein expression costs shape genetic interaction in a metabolic pathway

10.1101/362327 ◽

2018 ◽

Cited By ~ 1

Author(s):

Harry Kemble ◽

Catherine Eisenhauer ◽

Alejandro Couce ◽

Audrey Chapron ◽

Mélanie Magnan ◽

...

Keyword(s):

Protein Expression ◽

Molecular Interactions ◽

Metabolic Pathway ◽

Genetic Background ◽

Genetic Interaction ◽

Mechanistic Model ◽

Metabolic Genes ◽

Simultaneous Impact ◽

Molecular Phenotypes ◽

The Impact

AbstractOur ability to predict the impact of mutations on traits relevant for disease and evolution remains severely limited by the dependence of their effects on the genetic background and environment. Even when molecular interactions between genes are known, it is unclear how these translate to organism-level interactions between alleles. We therefore characterized the interplay of genetic and environmental dependencies in determining fitness by quantifying ~4,000 fitness interactions between expression variants of two metabolic genes, in different environments. We detect a remarkable variety of environment-dependent interactions, and demonstrate they can be quantitatively explained by a mechanistic model accounting for catabolic flux, metabolite toxicity and expression costs. Complex fitness interactions between mutations can therefore be predicted simply from their simultaneous impact on a few connected molecular phenotypes.

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Pregnancy in cystic fibrosis of the pancreas

JAMA ◽

10.1001/jama.195.12.993 ◽

1966 ◽

Vol 195 (12) ◽

pp. 993-1000 ◽

Cited By ~ 9

Author(s):

R. J. Grand

Keyword(s):

Cystic Fibrosis

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Freeze-Fracture Examination of Tight Junctions of Human Eccrine Sweat Glands

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002786 ◽

1980 ◽

Vol 38 ◽

pp. 634-635

Author(s):

J. V. Briggman ◽

J. Bigelow ◽

H. Bank ◽

S. S. Spicer

Keyword(s):

Cystic Fibrosis ◽

Freeze Fracture ◽

Sweat Glands ◽

Hypertonic Solution ◽

Dark Cells ◽

Clear Cells ◽

Junctional Complexes ◽

Secretory Coil ◽

Eccrine Sweat Glands ◽

Eccrine Sweat

The prevalence of strands shown by freeze-fracture in the zonula occludens of junctional complexes is thought to correspond closely with the transepi-thelial electrical resistance and with the tightness of the junction and its obstruction to paracellular flow.1 The complexity of the network of junc¬tional complex strands does not appear invariably related to the degree of tightness of the junction, however, as rabbit ileal junctions have a complex network of strands and are permeable to lanthanum. In human eccrine sweat glands the extent of paracellular relative to transcellular flow remains unknown, both for secretion of the isotonic precursor fluid by the coil and for resorption of a hypertonic solution by the duct. The studies reported here undertook, therefore, to determine with the freeze-fracture technique the complexity of the network of ridges in the junctional complexes between cells in the secretory coil and the sweat ducts. Glands from a patient with cystic fibrosis were also examined because an alteration in junctional strands could underlie the decreased Na+ resorption by sweat ducts in this disease. Freeze-fracture replicas were prepared by standard procedures on isolated coil and duct segments of human sweat glands. Junctional complexes between clear cells, between dark cells and between clear and dark cells on the main lumen, and between clear cells on intercellular canaliculi of the coil con¬tained abundant anastomosing closely spaced strands averaging 6.4 + 0.7 (mean + SE) and 9.0 +0.5 (Fig. 1) per complex, respectively. Thus, the junctions in the intercellular canaliculi of the coil appeared comparable in complexity to those of tight epithlia. Occasional junctions exhibited, in addition, 2 to 5 widely spaced anastomosing strands in a very close network basal to the compact network. The fewer junctional complexes observed thus far between the superficial duct cells consisted on the average of 6 strands arranged in a close network and 1 to 4 underlying strands that lay widely separated from one another (Fig. 2). The duct epitelium would, thus, be judged slightly more "leaky" than the coil. Infrequent junctional complexes observed to date in the secretory coil segment of a cystic fibrosis specimen disclosed rela¬tively few closely crowded strands.

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