Search results for "Polymorphism"
showing 10 items of 1968 documents
The Demographic Costs of Sexually Antagonistic Selection in Partially Selfing Populations
2022
When selection differs between the sexes, genes expressed by both males and females can experience sexually antagonistic (SA) selection, where beneficial alleles for one sex are deleterious for the other. Classic population genetics theory has been fundamental to understanding how and when SA genetic variation can be maintained by balancing selection, but these models have rarely considered the demographic consequences of coexisting alleles with deleterious fitness effects in each sex. In this article, we develop a stage-structured Mendelian matrix model and jointly analyze the evolutionary and demographic consequences of SA selection in obligately outcrossing (i.e., dioecious/gonochorous) …
Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma
2014
Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 x 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 x 10(-11) for rs2472493 near ABCA1 and P = 6.39 x 10(-11) for rs8176693…
Gitelman-Like Syndrome Caused by Pathogenic Variants in mtDNA
2022
Contains fulltext : 248375.pdf (Publisher’s version ) (Closed access) BACKGROUND: Gitelman syndrome is the most frequent hereditary salt-losing tubulopathy characterized by hypokalemic alkalosis and hypomagnesemia. Gitelman syndrome is caused by biallelic pathogenic variants in SLC12A3, encoding the Na(+)-Cl(-) cotransporter (NCC) expressed in the distal convoluted tubule. Pathogenic variants of CLCNKB, HNF1B, FXYD2, or KCNJ10 may result in the same renal phenotype of Gitelman syndrome, as they can lead to reduced NCC activity. For approximately 10 percent of patients with a Gitelman syndrome phenotype, the genotype is unknown. METHODS: We identified mitochondrial DNA (mtDNA) variants in th…
Killer cell immunoglobulin-like receptor genes in Latvian patients with type 1 diabetes mellitus and healthy controls.
2004
T1DM is very common in Sweden and is positively associated with HLA class II genes. Approximately 89% of the newly diagnosed patients carry the high-risk HLA DR4-DQ8 and DR3-DQ2. The remaining 11% develop T1DM without them. This can be due to involvement of other genes and environmental factors. Natural killer (NK) cells of the innate immune system are important in antiviral and antitumor immunity. They are implicated in the etiology of autoimmune T1DM. Human NK cells express killer cell immunoglobulin-like receptors (KIR) that belong to the polymorphic multigene family in chromosome 19q3.4. They modulate NK cell response by interacting with HLA class I. In addition, polymorphic MICA in HLA…
Variable phenotype in 17q12 microdeletions: Clinical and molecular characterization of a new case
2014
Microdeletions of 17q12 including the hepatocyte nuclear factor 1 beta (HNF1B) gene, as well as point mutations of this gene, are associated with the Renal Cysts and Diabetes syndrome (RCAD, OMIM 137920) and genitourinary alterations. Also, microdeletions encompassing HNF1B were identified as a cause of Mayer-Rokitansky-Kuster-Hauser Syndrome (MRKH, OMIM 277000) in females and, recently, were associated with intellectual disability, autistic features, cerebral anomaly and facial dysmorphisms. In this report, we describe a boy with a deletion in 17q12 region detected by SNP array, encompassing the HNF1B gene, that showed dysmorphic features, intellectual disability (ID), serious speech delay…
Forward genetics inWolbachia: Regulation ofWolbachiaproliferation by the amplification and deletion of an addictive genomic island
2021
Copyright: © 2021 Duarte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis.
2013
Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, r…
Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association…
2007
Contains fulltext : 52515.pdf (Publisher’s version ) (Closed access) BACKGROUND: Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. …
Discovery and Fine Mapping of Serum Protein Loci through Transethnic Meta-analysis
2012
Many disorders are associated with altered serum protein concentrations, including malnutrition, cancer, and cardiovascular, kidney, and inflammatory diseases. Although these protein concentrations are highly heritable, relatively little is known about their underlying genetic determinants. Through transethnic meta-analysis of European-ancestry and Japanese genome-wide association studies, we identified six loci at genome-wide significance (p −8 ) for serum albumin ( HPN-SCN1B , GCKR-FNDC4 , SERPINF2-WDR81 , TNFRSF11A-ZCCHC2 , FRMD5-WDR76 , and RPS11-FCGRT , in up to 53,190 European-ancestry and 9,380 Japanese individuals) and three loci for total protein ( TNFRS13B , 6q21.3, and ELL2 , in …
Genotyping NAT2 with only two SNPs (rs1041983 and rs1801280) outperforms the tagging SNP rs1495741 and is equivalent to the conventional 7-SNP NAT2 g…
2011
Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP wit…