Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Combinations of Genetic Variants Occurring Exclusively in Patients.

ABSTRACT: In studies of polygenic disorders, scanning the genetic variants can be used to identify variant combinations. Combinations that are exclusively found in patients can be separated from those combinations occurring in control persons. Statistical analyses can be performed to determine whether the combinations that occur exclusively among patients are significantly associated with the investigated disorder. This research strategy has been applied in materials from various polygenic disorders, identifying clusters of patient-specific genetic variant combinations that are significant associated with the investigated disorders. Combinations from these clusters are found in the genomes of up to 55% of investigated patients, and are not present in the genomes of any control persons.

SUBMITTER: Mellerup E

PROVIDER: S-EPMC5367802 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Combinations of Genetic Variants Occurring Exclusively in Patients.

Mellerup Erling E Møller Gert Lykke GL

Computational and structural biotechnology journal 20170310

In studies of polygenic disorders, scanning the genetic variants can be used to identify variant combinations. Combinations that are exclusively found in patients can be separated from those combinations occurring in control persons. Statistical analyses can be performed to determine whether the combinations that occur exclusively among patients are significantly associated with the investigated disorder. This research strategy has been applied in materials from various polygenic disorders, iden ...[more]

PMID: 28377798

Similar Datasets

Combinations of genetic variants associated with bipolar disorder.

Project description:The main objective of the study was to find genetic variants that in combination are significantly associated with bipolar disorder. In previous studies of bipolar disorder, combinations of three and four single nucleotide polymorphisms (SNP) genotypes taken from 803 SNPs were analyzed, and five clusters of combinations were found to be significantly associated with bipolar disorder. In the present study, combinations of ten SNP genotypes taken from the same 803 SNPs were analyzed, and one cluster of combinations was found to be significantly associated with bipolar disorder. Combinations from the new cluster and from the five previous clusters were identified in the genomes of 266 or 44% of the 607 patients in the study whereas none of the 1355 control participants had any of these combinations in their genome.The SNP genotypes in the smaller combinations were the normal homozygote, heterozygote or variant homozygote. In the combinations containing 10 SNP genotypes almost all the genotypes were the normal homozygote. Such a finding may indicate that accumulation in the genome of combinations containing few SNP genotypes may be a risk factor for bipolar disorder when those combinations contain relatively many rare SNP genotypes, whereas combinations need to contain many SNP genotypes to be a risk factor when most of the SNP genotypes are the normal homozygote.

| S-EPMC5739413 | biostudies-literature

Naturally Occurring Genetic Variants in the Oxytocin Receptor Alter Receptor Signaling Profiles.

Project description:The hormone oxytocin is commonly administered during childbirth to initiate and strengthen uterine contractions and prevent postpartum hemorrhage. However, patients have wide variation in the oxytocin dose required for a clinical response. To begin to uncover the mechanisms underlying this variability, we screened the 11 most prevalent missense genetic variants in the oxytocin receptor (OXTR) gene. We found that five variants, V45L, P108A, L206V, V281M, and E339K, significantly altered oxytocin-induced Ca2+ signaling or β-arrestin recruitment and proceeded to assess the effects of these variants on OXTR trafficking to the cell membrane, desensitization, and internalization. The variants P108A and L206V increased OXTR localization to the cell membrane, whereas V281M and E339K caused OXTR to be retained inside the cell. We examined how the variants altered the balance between OXTR activation and desensitization, which is critical for appropriate oxytocin dosing. The E339K variant impaired OXTR activation, internalization, and desensitization to roughly equal extents. In contrast, V281M decreased OXTR activation but had no effect on internalization and desensitization. V45L and P108A did not alter OXTR activation but did impair β-arrestin recruitment, internalization, and desensitization. Molecular dynamics simulations predicted that V45L and P108A prevent extension of the first intracellular loop of OXTR, thus inhibiting β-arrestin binding. Overall, our data suggest mechanisms by which OXTR genetic variants could alter clinical response to oxytocin.

| S-EPMC8506602 | biostudies-literature

Poly(anhydride-esters) comprised exclusively of naturally occurring antimicrobials and EDTA: antioxidant and antibacterial activities.

Project description:Carvacrol, thymol, and eugenol are naturally occurring phenolic compounds known to possess antimicrobial activity against a range of bacteria, as well as antioxidant activity. Biodegradable poly(anhydride-esters) composed of an ethylenediaminetetraacetic acid (EDTA) backbone and antimicrobial pendant groups (i.e., carvacrol, thymol, or eugenol) were synthesized via solution polymerization. The resulting polymers were characterized to confirm their chemical composition and understand their thermal properties and molecular weight. In vitro release studies demonstrated that polymer hydrolytic degradation was complete after 16 days, resulting in the release of free antimicrobials and EDTA. Antioxidant and antibacterial assays determined that polymer release media exhibited bioactivity similar to that of free compound, demonstrating that polymer incorporation and subsequent release had no effect on activity. These polymers completely degrade into components that are biologically relevant and have the capability to promote preservation of consumer products in the food and personal care industries via antimicrobial and antioxidant pathways.

| S-EPMC4020595 | biostudies-literature

Genetic Copy Number Variants in Myocardial Infarction Patients with Hyperlipidemia

Project description:We identified 7 CNV regions that were associated significantly with hyperlipidemia and myocardial infarction in our patients through multistage analysis (P<0.001). The inclusion criteria for enrolling patients were drawn from the Prospective Cardiovascular Munster study [http://www.ncbi.nlm.nih.gov/pubmed/3202078] and Framingham Heart Study [http://www.ncbi.nlm.nih.gov/pubmed/9737513]. In brief, patients aged between 20 and 75 years with coronary arterial disease with more than 50% stenosis, as proven by cardiac catheterization, and a history of hyperlipidemia with serum cholesterol level greater than 240 mg/dL or low-density lipoprotein greater than 155 mg/dL were enrolled. Affymetrix SNP arrays were performed according to the manufacturer's directions on DNA extracted from whole blood samples. 40 Samples.

2014-08-09 | E-GEOD-31276 | biostudies-arrayexpress

Genetic variants of human red-cell membrane sialoglycoprotein beta. Study of the alterations occurring in the sialoglycoprotein-beta gene.

Project description:We have studied the DNA of individuals who express an altered sialoglycoprotein beta on their red cells by using Southern blotting with sialoglycoprotein-beta cDNA probes. Individuals of the Leach phenotype do not express any beta (sialoglycoprotein beta) or gamma (sialoglycoprotein gamma) on their red cells, and we show that about 7 kb of DNA, including the 3' end of the beta gene, is deleted in this DNA. Any protein product of this gene is likely to lack the membrane-associating domain of beta. We have also examined the DNA of two types of other individuals (Yus-type and Gerbich-type) who have red cells that lack beta and gamma, but contain abnormal sialoglycoproteins related to beta. These two types of DNA contain different internal deletions of about 6 kb in the beta gene. We suggest that these deletions result from the presence of two different sets of internal homology in the beta gene, and on this basis we propose structures for the abnormal Yus-type and Gerbich-type sialoglycoproteins which are consistent with the other evidence that is available. We provide evidence that beta and gamma are products of the same gene and suggest a possible mechanism for the origin of gamma based on leaky initiation of translation of beta mRNA.

| S-EPMC1148871 | biostudies-other

Genetic Copy Number Variants in Myocardial Infarction Patients with Hyperlipidemia

2014-08-09 | GSE31276 | GEO

Naturally occurring hyperactive variants of human parkin.

Project description:Parkinson's disease (PD) is the second most common neurodegenerative disease in the world. Although most cases are sporadic and occur later in life, 10-15% of cases are genetic. Loss-of-function mutations in the ring-between-ring E3 ubiquitin ligase parkin, encoded by the PRKN gene, cause autosomal recessive forms of early onset PD. Together with the kinase PINK1, parkin forms a mitochondrial quality control pathway that tags damaged mitochondria for clearance. Under basal conditions, parkin is inhibited and compounds that increase its activity have been proposed as a therapy for PD. Recently, several naturally occurring hyperactive parkin variants were identified, which increased mitophagy in cultured cells. Here, we validate the hyperactivities of these variants in vitro and compare the levels of activity of the variants to those of the wild-type and the well-characterized hyperactive variant, W403A. We also study the effects of mutating the parkin ACT (activating element) on parkin activity in vitro. This work advances our understanding of the pathogenicity of parkin variants and is an important first step in the design of molecules to increase parkin activity.

| S-EPMC11310320 | biostudies-literature

Molecular imprint of exposure to naturally occurring genetic variants of human cytomegalovirus on the T cell repertoire.

Project description:Exposure to naturally occurring variants of herpesviruses in clinical settings can have a dramatic impact on anti-viral immunity. Here we have evaluated the molecular imprint of variant peptide-MHC complexes on the T-cell repertoire during human cytomegalovirus (CMV) infection and demonstrate that primary co-infection with genetic variants of CMV was coincident with development of strain-specific T-cell immunity followed by emergence of cross-reactive virus-specific T-cells. Cross-reactive CMV-specific T cells exhibited a highly conserved public T cell repertoire, while T cells directed towards specific genetic variants displayed oligoclonal repertoires, unique to each individual. T cell recognition foot-print and pMHC-I structural analyses revealed that the cross-reactive T cells accommodate alterations in the pMHC complex with a broader foot-print focussing on the core of the peptide epitope. These findings provide novel molecular insight into how infection with naturally occurring genetic variants of persistent human herpesviruses imprints on the evolution of the anti-viral T-cell repertoire.

| S-EPMC3918921 | biostudies-literature

Combinations of Genetic Data Present in Bipolar Patients, but Absent in Control Persons.

Project description:The main objective of the study was to find combinations of genetic variants significantly associated with bipolar disorder. In a previous study of bipolar disorder, combinations of three single nucleotide polymorphism (SNP) genotypes taken from 803 SNPs were analyzed, and four clusters of combinations were found to be significantly associated with bipolar disorder. In the present study, combinations of four SNP genotypes taken from the same 803 SNPs were analyzed, and one cluster of combinations was found to be significantly associated with bipolar disorder. Combinations from the new cluster and from the four previous clusters were identified in the genomes of 209 of the 607 patients in the study whereas none of the 1355 control participants had any of these combinations in their genome.

| S-EPMC4654514 | biostudies-literature

Naturally occurring genetic variants in human chromogranin A (CHGA) associated with hypertension as well as hypertensive renal disease.

Project description:Chromogranin A (CHGA) plays a fundamental role in the biogenesis of catecholamine secretory granules. Changes in storage and release of CHGA in clinical and experimental hypertension prompted us to study whether genetic variation at the CHGA locus might contribute to alterations in autonomic function, and hence hypertension and its target organ consequences such as hypertensive renal disease (nephrosclerosis). Systematic polymorphism discovery across the human CHGA locus revealed both common and unusual variants in both the open reading frame and such regulatory regions as the proximal promoter and 30-UTR. In chromaffin cell-transfected CHGA 30-UTR and promoter/luciferase reporter plasmids, the functional consequences of the regulatory/non-coding allelic variants were documented. Variants in both the proximal promoter and the 30-UTR displayed statistical associations with hypertension. Genetic variation in the proximal CHGA promoter predicted glomerular filtration rate in healthy twins. However, for hypertensive renal damage, both end-stage renal disease and rate of progression of earlier disease were best predicted by variants in the 30-UTR. Finally, mechanistic studies were undertaken initiated by the clue that CHGA promoter variation predicted circulating endothelin-1. In cultured endothelial cells, CHGA triggered co-release of not only the vasoconstrictor and pro-fibrotic endothelin-1, but also the pro-coagulant von Willebrand Factor and the pro-angiogenic angiopoietin-2. These findings, coupled with stimulation of endothelin-1 release from glomerular capillary endothelial cells by CHGA, suggest a plausible mechanism whereby genetic variation at the CHGA locus eventuates in alterations in human renal function. These results document the consequences of genetic variation at the CHGA locus for cardiorenal disease and suggest mechanisms whereby such variation achieves functional effects.

| S-EPMC3008929 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data