Dataset Information

Single-Nucleotide Polymorphism of PPAR?, a Protein at the Crossroads of Physiological and Pathological Processes.

ABSTRACT: Genome polymorphisms are responsible for phenotypic differences between humans and for individual susceptibility to genetic diseases and therapeutic responses. Non-synonymous single-nucleotide polymorphisms (nsSNPs) lead to protein variants with a change in the amino acid sequence that may affect the structure and/or function of the protein and may be utilized as efficient structural and functional markers of association to complex diseases. This study is focused on nsSNP variants of the ligand binding domain of PPAR? a nuclear receptor in the superfamily of ligand inducible transcription factors that play an important role in regulating lipid metabolism and in several processes ranging from cellular differentiation and development to carcinogenesis. Here we selected nine nsSNPs variants of the PPAR? ligand binding domain, V290M, R357A, R397C, F360L, P467L, Q286P, R288H, E324K, and E460K, expressed in cancer tissues and/or associated with partial lipodystrophy and insulin resistance. The effects of a single amino acid change on the thermodynamic stability of PPAR?, its spectral properties, and molecular dynamics have been investigated. The nsSNPs PPAR? variants show alteration of dynamics and tertiary contacts that impair the correct reciprocal positioning of helices 3 and 12, crucially important for PPAR? functioning.

SUBMITTER: Petrosino M

PROVIDER: S-EPMC5343896 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Single-Nucleotide Polymorphism of PPARγ, a Protein at the Crossroads of Physiological and Pathological Processes.

Petrosino Maria M Lori Laura L Pasquo Alessandra A Lori Clorinda C Consalvi Valerio V Minicozzi Velia V Morante Silvia S Laghezza Antonio A Giorgi Alessandra A Capelli Davide D Chiaraluce Roberta R

International journal of molecular sciences 20170210 2

Genome polymorphisms are responsible for phenotypic differences between humans and for individual susceptibility to genetic diseases and therapeutic responses. Non-synonymous single-nucleotide polymorphisms (nsSNPs) lead to protein variants with a change in the amino acid sequence that may affect the structure and/or function of the protein and may be utilized as efficient structural and functional markers of association to complex diseases. This study is focused on nsSNP variants of the ligand ...[more]

PMID: 28208577

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Project description:A linkage map of 40 linkage groups (LGs) was developed for brook charr, Salvelinus fontinalis, using an F(2) interstrain hybrid progeny (n = 171) and 256 coding gene SNP developed specifically for brook charr and validated from a large (>1000) subset of putative SNP, as well as 81 microsatellite markers. To identify quantitative trait loci (QTL) related to reproduction functions, these fish were also phenotyped at six physiological traits, including spermatozoid head diameter, sperm concentration, plasma testosterone, plasma 11-keto-testosterone, egg diameter, and plasma 17?-estradiol. Five significant QTL were detected over four LGs for egg diameter and plasma 17?-estradiol concentration in females, and sperm concentration as well as spermatozoid head diameter in males. In females, two different QTLs located on LG 11 and LG 34 were associated with the egg number, whereas one QTL was associated with plasma 17?-estradiol concentration (LG 8). Their total percent variance explained (PVE) was 26.7% and 27.6%, respectively. In males, two QTL were also detected for the sperm concentration, and their PVE were estimated at 18.58% and 14.95%, respectively. The low QTL number, associated with the high PVE, suggests that the variance in these reproductive physiological traits was either under the control of one major gene or a small number of genes. The QTL associated with sperm concentration, plasma 17?-estradiol, and egg diameter appeared to be under a dominance effect, whereas the two others were under a negative additive effect. These results show that genes underlying the phenotypic variance of these traits are under different modes of action (additive vs. dominance) and may be used to predict an increase or a decrease in their phenotypic values in subsequent generations of selective breeding. Moreover, this newly developed panel of mapped SNP located in coding gene regions will be useful for screening wild populations, especially in the context of investigating the genetic impact of massive stocking of domestic brook charr to support the angling industry throughout eastern North America.

Dataset Information

Single-Nucleotide Polymorphism of PPAR?, a Protein at the Crossroads of Physiological and Pathological Processes.

Publications

Single-Nucleotide Polymorphism of PPARγ, a Protein at the Crossroads of Physiological and Pathological Processes.

Similar Datasets

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