Studying how genetic variants affect mechanism in biological systems

2018 ◽  
Vol 62 (4) ◽  
pp. 575-582
Author(s):  
Francesco Raimondi ◽  
Robert B. Russell
Keyword(s):  
Genetic Variation ◽  
Molecular Mechanism ◽  
Genetic Variants ◽  
Biological Function ◽  
Biological Systems ◽  
Protein Structures ◽  
Clinical Applications ◽  
Biological Pathways ◽  
The Relationship

Genetic variants are currently a major component of system-wide investigations into biological function or disease. Approaches to select variants (often out of thousands of candidates) that are responsible for a particular phenomenon have many clinical applications and can help illuminate differences between individuals. Selecting meaningful variants is greatly aided by integration with information about molecular mechanism, whether known from protein structures or interactions or biological pathways. In this review we discuss the nature of genetic variants, and recent studies highlighting what is currently known about the relationship between genetic variation, biomolecular function, and disease.

Abstract 18134: Phenome-wide Study of Electronic Medical Record Data Reveals Novel Association of Natriuretic Peptide A Genetic Variant With Rheumatoid Arthritis

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Naveen Pereira ◽  
Gregory Jenkins ◽  
Ifthikar Kullo ◽  
Suzette Bielinski ◽  
John Burnett ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Genetic Variation ◽  
Medical Record ◽  
Electronic Medical Record ◽  
Natriuretic Peptide ◽  
Genetic Variants ◽  
Association Studies ◽  
Disease Phenotypes ◽  
Novel Association ◽  
The Relationship

Introduction: Phenome-wide association studies (PheWAS) using electronic medical record (EMR)-linked biobanks have been used not only to identify and replicate known associations of genetic variants with disease phenotypes but have also resulted in the discovery of potentially novel genotype-phenotype relationships. The natriuretic peptide (NP) system plays an important role in a broad range of disease processes including cardiovascular and inflammatory diseases. We hypothesized that performing a PheWAS using previously known functional genetic variants of the NP system may result in novel disease associations that could provide mechanistic insights in an unbiased manner. Methods: We scanned for associations between 9 single-nucleotide polymorphisms (SNPs) in the NP system and 27 EMR-derived chronic disease phenotypes in 3,025 individuals participating in a case-control study of peripheral arterial disease. The EMR phenotypes were identified using two or more ICD-9-CM diagnosis codes based on the AHRQ Clinical Classifications Software (CCS). The relationship of SNPs and phenotypes were modeled using logistic regression adjusting for gender. Results: We identified rs5065, a SNP located in the stop codon of exon 3 of the NPPA gene, to be the strongest associated SNP with rheumatoid arthritis (RA) (OR=0.78, p=0.0008, q-value=0.11). The SNP leads to the extension of atrial natriuretic peptide (ANP) by 2 additional arginines at the C terminus. Cardiovascular disease is known to be the leading cause of death in patients with RA and ANP plays an important immunomodulatory role by inhibiting inducible nitric oxide synthase, reducing TNF-α production and attenuating prostaglandin E2 production in macrophages. Circulating NPs have been used to screen for occult cardiac disease and are associated with mortality in RA. This study demonstrates for the first time the importance of the relationship between genetic variation in the NP system and RA. Conclusions: PheWAS was successfully used as a tool to identify a novel association of functional genetic variation in the NPPA gene with RA. The observation is hypothesis generating and further replication studies are required to determine the role of rs5065 in cardiovascular outcomes of RA.

Induction of Metallothionein

1989 ◽  
Vol 8 (7) ◽  
pp. 1315-1321 ◽  
Author(s):  
Curtis D. Klaassen ◽  
Lois D. Lehman-Mckeeman
Keyword(s):  
Heavy Metals ◽  
Heavy Metal ◽  
Molecular Mechanism ◽  
Organic Compounds ◽  
Metal Binding ◽  
Binding Proteins ◽  
Biological Function ◽  
Metal Homeostasis ◽  
Pivotal Role ◽  
The Relationship

Metallothioneins (MTs) are cysteine-rich metal-binding proteins. These proteins play a pivotal role in heavy metal homeostasis and have been widely studied by biochemists, toxicologists, nutritional scientists, and molecular biologists. It is well established that MTs are inducible proteins. They are normally synthesized at low basal levels, but exposure to a wide variety of heavy metals and many organic compounds will dramatically increase synthesis of MTs. This paper summarizes MT induction by reviewing the chemicals that induce these proteins, the molecular mechanism involved in this induction, and the relationship between MT induction and biological function.

Migraine: Genetic Variants and Clinical Phenotypes

2019 ◽  
Vol 26 (34) ◽  
pp. 6207-6221 ◽  
Author(s):  
Innocenzo Rainero ◽  
Alessandro Vacca ◽  
Flora Govone ◽  
Annalisa Gai ◽  
Lorenzo Pinessi ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Association Studies ◽  
Mthfr Gene ◽  
Genome Wide Association Studies ◽  
Clinical Phenotypes ◽  
Network Analyses ◽  
Genome Wide ◽  
Genomic Studies ◽  
The Common ◽  
The Relationship

Migraine is a common, chronic neurovascular disorder caused by a complex interaction between genetic and environmental risk factors. In the last two decades, molecular genetics of migraine have been intensively investigated. In a few cases, migraine is transmitted as a monogenic disorder, and the disease phenotype cosegregates with mutations in different genes like CACNA1A, ATP1A2, SCN1A, KCNK18, and NOTCH3. In the common forms of migraine, candidate genes as well as genome-wide association studies have shown that a large number of genetic variants may increase the risk of developing migraine. At present, few studies investigated the genotype-phenotype correlation in patients with migraine. The purpose of this review was to discuss recent studies investigating the relationship between different genetic variants and the clinical characteristics of migraine. Analysis of genotype-phenotype correlations in migraineurs is complicated by several confounding factors and, to date, only polymorphisms of the MTHFR gene have been shown to have an effect on migraine phenotype. Additional genomic studies and network analyses are needed to clarify the complex pathways underlying migraine and its clinical phenotypes.

THE RELATIONSHIP BETWEEN OBSTRUCTIVE SLEEP APNOEA AND TASK-1 GENETIC VARIANTS

2018 ◽  
Vol 36 (Supplement 1) ◽  
pp. e205
Author(s):  
N. Li ◽  
T. Shi ◽  
X. Yao ◽  
Y. Wang ◽  
M. Heizhati ◽  
...  
Keyword(s):  
Obstructive Sleep Apnoea ◽  
Genetic Variants ◽  
Sleep Apnoea ◽  
Obstructive Sleep ◽  
The Relationship ◽  
And Task

scholarly journals Evolution and evolvability: celebrating Darwin 200

2008 ◽  
Vol 5 (1) ◽  
pp. 44-46 ◽  
Author(s):  
John F.Y Brookfield
Keyword(s):  
Genetic Variation ◽  
Natural Selection ◽  
Time Scales ◽  
Evolutionary Change ◽  
Adaptive Mutation ◽  
Genetic Covariances ◽  
The Relationship ◽  
The Way

The concept of ‘evolvability’ is increasingly coming to dominate considerations of evolutionary change. There are, however, a number of different interpretations that have been put on the idea of evolvability, differing in the time scales over which the concept is applied. For some, evolvability characterizes the potential for future adaptive mutation and evolution. Others use evolvability to capture the nature of genetic variation as it exists in populations, particularly in terms of the genetic covariances between traits. In the latter use of the term, the applicability of the idea of evolvability as a measure of population's capacity to respond to natural selection rests on one, but not the only, view of the way in which we should envisage the process of natural selection. Perhaps the most potentially confusing aspects of the concept of evolvability are seen in the relationship between evolvability and robustness.

Genetic variation and relationship of ultrasonic measures and carcass composition in Suffolk cross lambs

1996 ◽  
Vol 1996 ◽  
pp. 111-111
Author(s):  
V.C. Flamarique ◽  
R.M. Lewis ◽  
G. Simm
Keyword(s):  
Genetic Variation ◽  
Selection Criteria ◽  
Live Weight ◽  
Ultrasonic Measurement ◽  
Carcass Composition ◽  
Selection Indices ◽  
Terminal Sire ◽  
Relationship Of ◽  
The Relationship

Excess fat in lamb is regarded as an important reason for less lamb meat being purchased by consumers. This has encouraged the development and use (particularly in Terminal Sire breeds) of selection indices that can identify animals that will sire leaner progeny. These indices usually include live weight and in vivo predictors of body composition, such as an ultrasonic measurement of muscle and fat depth, as selection criteria (Simm and Dingwall, 1989). But the usefulness of such in vivo measurements as predictors of carcass composition depends on the correlation between, and the variation in, live and carcass measures. The objectives of this study were to determine the strength of the relationship between ultrasound and dissection measures of carcass composition, and the degree of genetic variation in these measures, in crossbred progeny of Suffolk rams.

Serum C reactive protein levels and genetic variation in the CRP gene are not associated with the prevalence, incidence or progression of osteoarthritis independent of body mass index

2010 ◽  
Vol 69 (11) ◽  
pp. 1976-1982 ◽  
Author(s):  
Hanneke J M Kerkhof ◽  
Sita M A Bierma-Zeinstra ◽  
Martha C Castano-Betancourt ◽  
Moniek P de Maat ◽  
Albert Hofman ◽  
...  
Keyword(s):  
Systematic Review ◽  
Body Mass Index ◽  
Genetic Variation ◽  
Body Mass ◽  
Analysis Of Covariance ◽  
C Reactive Protein ◽  
Knee Oa ◽  
Reactive Protein ◽  
Serum Crp ◽  
The Relationship

ObjectiveTo study the relationship between serum C reactive protein (CRP) levels, genetic variation in the CRP gene and the prevalence, incidence and progression of radiographic osteoarthritis (ROA) in the Rotterdam Study-I (RS-I). A systematic review of studies assessing the relationship between osteoarthritis (OA) and CRP levels was also performed.MethodsThe association between CRP levels and genetic variation in the CRP gene and ROA was examined in 861 patients with hand OA, 718 with knee OA, 349 with hip OA and 2806 controls in the RS-I using one-way analysis of covariance and logistic regression, respectively. PubMed was searched for articles published between January 1992 and August 2009 assessing the relationship between CRP levels and OA.ResultsIn RS-I the prevalence of knee OA, but not hip OA or hand OA, was associated with 14% higher serum CRP levels compared with controls (p=0.001). This association disappeared after adjustment for age and especially body mass index (BMI) (p=0.33). Genetic variation of the CRP gene was not consistently associated with the prevalence, incidence or progression of OA within RS-I. The systematic review included 18 studies (including RS-I) on serum CRP levels and the prevalence, incidence or progression of OA. Consistently higher crude CRP levels were found in cases of prevalent knee OA compared with controls. No association was observed between serum CRP levels and the prevalence of knee OA following adjustment for BMI (n=3 studies, meta-analysis p value=0.61).ConclusionThere is no evidence of association between serum CRP levels or genetic variation in the CRP gene with the prevalence, incidence or progression of OA independent of BMI.

scholarly journals THE RELATIONSHIP BETWEEN GENETIC VARIANTS OF B-LACTOGLOBULIN AND K-CASEIN AND SELECTED PARAMETERS OF THE SUITABILITY OF MILK FOR CHEESE PRODUCTION

2016 ◽  
Vol 15 (3) ◽  
pp. 53-66
Author(s):  
Anna Wolanciuk ◽  
◽  
Joanna Barłowska ◽  
Zygmunt Litwińczuk ◽  
Wioletta Sawicka-Zugaj ◽  
...  
Keyword(s):  
Genetic Variants ◽  
The Relationship ◽  
Cheese Production
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