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Genetic Regions (genetic + regions)
Selected AbstractsHFE, SLC40A1, HAMP, HJV, TFR2, and FTL mutations detected by denaturing high-performance liquid chromatography after iron phenotyping and HFE C282Y and H63D genotyping in 785 HEIRS Study participants,,AMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2009James C. Barton We sought to identify mutations that could explain iron phenotype heterogeneity in adults with previous HFE genotyping to detect C282Y and H63D. HEIRS Study participants genotyped for C282Y and H63D were designated as high transferrin saturation (TS) and/or serum ferritin (SF) (high TS/SF), low TS/SF, or controls. We grouped 191 C282Y homozygotes as high TS/SF, low TS/SF, or controls, and 594 other participants by race/ethnicity as high TS/SF or controls. Using denaturing high-performance liquid chromatography (DHPLC), we screened 20 regions of HFE, SLC40A1, HAMP, HJV, TFR2, and FTL in each participant. DHPLC analyses were successful in 99.3% of 791 participants and detected 117 different mutations. In C282Y homozygotes, 4.0% of high TS/SF participants had SLC40A1 Q248H, HAMP -72C>T, or HAMP R59G heterozygosity (0% Controls; P = 0.1200). In whites, 4.1% with high TS/SF and 1.3% of controls had HFE S65C or E168Q (P = 0.3049). HJV c.-6C>G and FTL L55L frequencies were greater in whites with high TS/SF than controls (0.0811 vs. 0.0200, P = 0.0144; 0.5743 vs. 0.4400, P = 0.0204, respectively). One Hispanic with high TS/SF (1.3%) had HAMP G71D heterozygosity. In blacks, SLC40A1 Q248H frequencies did not differ significantly between high TS/SF and control participants. Among Asians, 2.8% with high TS/SF were HFE V295A heterozygotes. Mutations other than HFE C282Y and H63D reported to be pathogenic were infrequently detected in high TS/SF participants. Genetic regions in linkage disequilibrium with HJV c.-6C>G and FTL L55L could partly explain high TS/SF phenotypes in whites. Am. J. Hematol., 2009. Published 2009 Wiley-Liss, Inc. [source] Parent-of-origin, imprinting, mitochondrial, and X-linked effects in traits related to alcohol dependence: Presentation Group 18 of Genetic Analysis Workshop 14GENETIC EPIDEMIOLOGY, Issue S1 2005Konstantin Strauch Abstract The participants of Presentation Group 18 of Genetic Analysis Workshop 14 analyzed the Collaborative Study on the Genetics of Alcoholism data set to investigate sex-specific effects for phenotypes related to alcohol dependence. In particular, the participants looked at imprinting (which is also known as parent-of-origin effect), differences between recombination fractions for the two sexes, and mitochondrial and X-chromosomal effects. Five of the seven groups employed newly developed or existing methods that take imprinting into account when testing for linkage, or test for imprinting itself. Single-marker and multipoint analyses were performed for microsatellite as well as single-nucleotide polymorphism markers, and several groups used a sex-specific genetic map in addition to a sex-averaged map. Evidence for paternal imprinting (i.e., maternal expression) was consistently obtained by at least two groups at genetic regions on chromosomes 10, 12, and 21 that possibly harbor genes responsible for alcoholism. Evidence for maternal imprinting (which is equivalent to paternal expression) was consistently found at a locus on chromosome 11. Two groups applied extensions of variance components analysis that model a mitochondrial or X-chromosomal effect to latent class variables and electrophysiological traits employed in the diagnosis of alcoholism. The analysis, without using genetic markers, revealed mitochondrial or X-chromosomal effects for several of these traits. Accounting for sex-specific environmental variances appeared to be crucial for the identification of an X-chromosomal factor. In linkage analysis using marker data, modeling a mitochondrial variance component increased the linkage signals obtained for autosomal loci. Genet. Epidemiol. 29(Suppl. 1):S125,S132, 2005. © 2005 Wiley-Liss, Inc. [source] Heterogeneity testing in meta-analysis of genome searchesGENETIC EPIDEMIOLOGY, Issue 2 2005Elias Zintzaras Abstract Genome searches for identifying susceptibility loci for the same complex disease often give inconclusive or inconsistent results. Genome Search Meta-analysis (GSMA) is an established non-parametric method to identify genetic regions that rank high on average in terms of linkage statistics (e.g., lod scores) across studies. Meta-analysis typically aims not only to obtain average estimates, but also to quantify heterogeneity. However, heterogeneity testing between studies included in GSMA has not been developed yet. Heterogeneity may be produced by differences in study designs, study populations, and chance, and the extent of heterogeneity might influence the conclusions of a meta-analysis. Here, we propose and explore metrics that indicate the extent of heterogeneity for specific loci in GSMA based on Monte Carlo permutation tests. We have also developed software that performs both the GSMA and the heterogeneity testing. To illustrate the concept, the proposed methodology was applied to published data from meta-analyses of rheumatoid arthritis (4 scans) and schizophrenia (20 scans). In the first meta-analysis, we identified 11 bins with statistically low heterogeneity and 8 with statistically high heterogeneity. The respective numbers were 9 and 6 for the schizophrenia meta-analysis. For rheumatoid arthritis, bins 6.2 (the HLA region that is a well-documented susceptibility locus for the disease) and 16.3 (16q12.2-q23.1) had both high average ranks and low between-study heterogeneity. For schizophrenia, this was seen for bin 3.2 (3p25.3-p22.1) and heterogeneity was still significantly low after adjusting for its high average rank. Concordance was high between the proposed metrics and between weighted and unweighted analyses. Data from genome searches should be synthesized and interpreted considering both average ranks and heterogeneity between studies. Genet. Epidemiol. 28:123,137, 2005. © 2004 Wiley-Liss, Inc. [source] Genetic analysis of phenotypes derived from longitudinal data: Presentation Group 1 of Genetic Analysis Workshop 13GENETIC EPIDEMIOLOGY, Issue S1 2003Konstantin Strauch Abstract The participants of Presentation Group 1 used the GAW13 data to derive new phenotypes, which were then analyzed for linkage and, in one case, for association to the genetic markers. Since the trait measurements ranged over longer time periods, the participants looked at the time dependence of particular traits in addition to the trait itself. The phenotypes analyzed with the Framingham data can be roughly divided into 1) body weight-related traits, which also include a type 2 diabetes progression trait, and 2) traits related to systolic blood pressure. Both trait classes are associated with metabolic syndrome. For traits related to body weight, linkage was consistently identified by at least two participating groups to genetic regions on chromosomes 4, 8, 11, and 18. For systolic blood pressure, or its derivatives, at least two groups obtained linkage for regions on chromosomes 4, 6, 8, 11, 14, 16, and 19. Five of the 13 participating groups focused on the simulated data. Due to the rather sparse grid of microsatellite markers, an association analysis for several traits was not successful. Linkage analysis of hypertension and body mass index using LODs and heterogeneity LODs (HLODs) had low power. For the glucose phenotype, a combination of random coefficient regression models and variance component linkage analysis turned out to be strikingly powerful in the identification of a trait locus simulated on chromosome 5. Haseman-Elston regression methods, applied to the same phenotype, had low power, but the above-mentioned chromosome 5 locus was not included in this analysis. Genet Epidemiol 25 (Suppl. 1):S5,S17, 2003. © 2003 Wiley-Liss, Inc. [source] Genetics and genomics of ankylosing spondylitisIMMUNOLOGICAL REVIEWS, Issue 1 2010Gethin P. Thomas Summary:, Ankylosing spondylitis (AS) is a common, highly heritable arthropathy, the pathogenesis of which is poorly understood. The mechanism by which the main gene for the disease, HLA-B27, leads to AS is unknown. Genetic and genomic studies have demonstrated involvement of the interleukin-23 (IL-23) signaling pathway in AS, a finding which has stimulated much new research into the disease and has led to therapeutic trials. Several other genes and genetic regions, including further major histocompatibility complex (MHC) and non-MHC loci, have been shown to be involved in the disease, but it is not clear yet how they actually induce the condition. These findings have shown that there is a strong genetic overlap between AS and Crohn's disease in particular, although there are also major differences in the genes involved in the two conditions, presumably explaining their different presentations. Genomic and proteomic studies are in an early phase but have potential both as diagnostic/prognostic tools and as a further hypothesis-free tool to investigate AS pathogenesis. Given the slow progress in studying the mechanism of association of HLA-B27 with AS, these may prove to be more fruitful approaches to investigating the pathogenesis of the disease. [source] Adaptive evolution of lateral plates in three-spined stickleback Gasterosteus aculeatus: a case study in functional analysis of natural variationJOURNAL OF FISH BIOLOGY, Issue 2 2010R. D. H. Barrett The three-spined stickleback Gasterosteus aculeatus is a model species for studying questions in ecology and evolution. The rapid diversification of G. aculeatus in post-glacial freshwater environments, combined with recently developed molecular tools, provides a unique opportunity to study the functional basis of fitness variation in natural populations. In derived freshwater populations, a number of morphological traits have diverged in parallel from the marine ancestral state, including the number of lateral armour plates. Evolution of reduced armour in freshwater populations is due to positive selection from both abiotic and biotic mechanisms. The major effect gene (ectodysplasin-A or Eda), along with several minor effect genetic regions, has recently been shown to control lateral plate variation. Field experiments have further determined the fitness consequences of allelic variation at the major effect locus. This work helps elucidate the mechanisms connecting genetic variation with phenotypic variation and fitness in the wild, a synthesis that should be applicable to many other phenotypic traits and species of fishes. [source] Genetics of cardiovascular diseases: An overviewNURSING & HEALTH SCIENCES, Issue 2 2005Carmen T Ramirez edd, acnp(c), apn-g(c) Cardiovascular disease is the leading cause of illness and death in the USA, as well as other countries. Advances in genetics have led researchers to identified associations between a number of cardiac syndromes and diagnostic molecular findings. Therefore, a more precise understanding of the molecular pathways involved in cardiovascular diseases is clinically significant. Current literature suggests that while etiologies remain complex, a number of cardiovascular diseases can be linked to specific metabolic inheritable factors. A broad multifactorial model is gradually being replaced with disease specific models where independent genetic and/or teratogenic pathways may lead to a particular outcome. These genetic pathways include chromosome deletions, disruptions (translocations), duplications of particular genetic regions, point mutations involving single genes, or alteration in the ability for a gene to be transcribed into a functional protein. In this review the molecular mechanisms underlying cardiovascular diseases and their clinical manifestations will be explained. [source] Association mapping of straighthead disorder induced by arsenic in Oryza sativaPLANT BREEDING, Issue 6 2009H. A. Agrama Abstract Straighthead is a physiological disorder in rice (Oryza sativa L.) resulting in sterile florets, poorly developed panicles and yield loss. Because of its sporadic nature and unidentified causes for the disorder, molecular marker assisted selection is essential for resistance improvement in breeding programmes. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association mapping to identify genetic regions associated with straighthead disorder using 547 accessions of germplasm from the USDA rice core collection. Straighthead was evaluated in arsenic treated soil and genotyping was conducted with 75 molecular markers covering the entire rice genome about every 25 cM. A mixed-linear model approach combining the principal component assignments with kinship estimates proved to be particularly promising for association mapping. The extent of linkage disequilibrium was described among the markers. Six markers were found to be significantly associated with straighthead, explaining 35% of the total phenotypic variation. However, only two SSR markers, RM413 and RM277 on chromosome 5 and 12, respectively, have a significant association with low rating indicating straighthead resistance. Confirmation of the marker-straighthead association using segregating populations is necessary before marker-assisted selection can be applied. [source] Atelinae phylogenetic relationships: The trichotomy revived?AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 4 2004A.C. Collins Abstract This research examines phylogenetic relationships between members of the Atelinae subfamily (Alouatta, Ateles, Brachyteles, and Lagothrix), based on analysis of three genetic regions. Two loci, cytochrome c oxidase subunit II (COII) and the hypervariable I portion of the control region, are part of the mitochondrial genome. The other is a single-copy nuclear gene, Aldolase A Intron V. Analysis of these genetic regions provides support for tribe Alouattini containing the Alouatta species, while tribe Atelini contains the other three genera. However, these three genetic regions produce conflicting results for relationships among tribe Atelini members. Previous genetic studies supported grouping Brachyteles with Lagothrix, leaving Ateles in a separate subclade. The present data sets vary based on the genetic region analyzed and method of analysis suggesting all possible cladistic relationships. These results are more consistent with investigations of morphology and behavior among these primates. The primary cause of discrepancy between this study and previous genetic studies is postulated to reside in increased sampling in the present study of genetic variation among members of the Atelinae, specifically Ateles. The present study utilized samples of Ateles from all postulated species for this genetically variable primate, while previous studies used only one or two species of Ateles. This paper demonstrates that shifting relationships are produced when different species of Ateles are used to reconstruct phylogenies. This research concludes that a trichotomy should still be supported between members of tribe Atelini until further analyses, which include additional Atelinae haplotypes are conducted. Am J Phys Anthropol, 2003. © 2003 Wiley-Liss, Inc. [source] Association of a single-nucleotide polymorphism in CD40 with the rate of joint destruction in rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 8 2009Michael P. M. van der Linden Objective The severity of joint destruction in rheumatoid arthritis (RA) is highly variable from patient to patient and is influenced by genetic factors. Genome-wide association studies have enormously boosted the field of the genetics of RA susceptibility, but risk loci for RA severity remain poorly defined. A recent meta-analysis of genome-wide association studies identified 6 genetic regions for susceptibility to autoantibody-positive RA: CD40, KIF5A/PIP4K2C, CDK6, CCL21, PRKCQ, and MMEL1/TNFRSF14. The purpose of this study was to investigate whether these newly described genetic regions are associated with the rate of joint destruction. Methods RA patients enrolled in the Leiden Early Arthritis Clinic were studied (n = 563). Yearly radiographs were scored using the Sharp/van der Heijde method (median followup 5 years; maximum followup 9 years). The rate of joint destruction between genotype groups was compared using a linear mixed model, correcting for age, sex, and treatment strategies. A total of 393 anti,citrullinated protein antibody (ACPA),positive RA patients from the North American Rheumatoid Arthritis Consortium (NARAC) who had radiographic data available were used for the replication study. Results The TT and CC/CG genotypes of 2 single-nucleotide polymorphisms, rs4810485 (CD40) and rs42041 (CDK6), respectively, were associated with a higher rate of joint destruction in ACPA-positive RA patients (P = 0.003 and P = 0.012, respectively), with rs4810485 being significant after Bonferroni correction for multiple testing. The association of the CD40 minor allele with the rate of radiographic progression was replicated in the NARAC cohort (P = 0.021). Conclusion A polymorphism in the CD40 locus is associated with the rate of joint destruction in patients with ACPA-positive RA. Our findings provide one of the first non,HLA-related genetic severity factors that has been replicated. [source] First report on autochthonous urease-positive Trichophyton rubrum (T. raubitschekii) from South-east EuropeBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2005M. Arabatzis Summary Background,Trichophyton raubitschekii is a dermatophyte belonging to the T. rubrum complex and is differentiated principally by its positive urease activity and production of profuse macroconidia and microconidia in culture. It is classically isolated from African, South-east Asian and Australian aboriginal patients with tinea corporis or tinea cruris. Objectives, This study was undertaken to screen Greek and Bulgarian clinical isolates identified as T. rubrum for T. raubitschekii and to delineate these strains by two molecular methods used for the first time in T. rubrum epidemiological studies. Methods, Ninety-five Greek and 10 Bulgarian strains, originating from various body sites, initially identified as T. rubrum, were screened for urease activity. The biochemical properties and morphology of the urease-positive strains were determined. Strains were delineated with polymerase chain reaction (PCR)-ribotyping amplifying repeat elements of the intergenic spacer region and by PCR fingerprinting. Results, Five Greek and one Bulgarian T. raubitschekii strains were identified comprising isolates from patients with tinea manuum (one), tinea corporis (one), tinea cruris (one) and tinea unguium (three). Only one strain had the classical T. raubitschekii microscopic morphology, whereas the remaining five presented a dominant arthroconidial phenotype. Both typing methods clustered all T. raubitschekii and T. rubrum isolates together in the same group, indicating strain homogeneity in the genetic regions examined. Conclusions, The reported isolation of T. raubitschekii in the Balkan and South-eastern Mediterranean regions extends the geographical distribution of this species. As the more primitive T. raubitschekii probably represents the parental population of T. rubrum, the Greek and Bulgarian T. raubitschekii strains could represent a remnant of the T. rubrum spread that took place after the First World War, rather than being a recent epidemiological event. [source] | |||||||||||||