Timing is essential for survival and reproduction of organisms across the tree of life. The core circadian clock gene Clk is involved in the regulation of annual timing events and shows highly ...conserved sequence homology across vertebrates except for one variable region of poly-glutamine repeats. Clk genotype varies in some species with latitude, seasonal timing and migration. However, findings are inconsistent, difficult to disentangle from environmental responses, and biased towards high latitudes. Here we combine field data with a common-garden experiment to study associations of Clk polymorphism with latitude, migration and annual-cycle timing within the stonechat species complex across its trans-equatorial distribution range. Our dataset includes 950 records from 717 individuals from nine populations with diverse migratory strategies. Gene diversity was lowest in resident African and Canary Island populations and increased with latitude, independently of migration distance. Repeat length and annual-cycle timing was linked in a population-specific way. Specifically, equatorial African stonechats showed delayed timing with longer repeat length for all annual-cycle stages. Our data suggest that at low latitudes with nearly constant photoperiod, Clk genotype might orchestrate a range of consistent, individual chronotypes. In contrast, the influence of Clk on annual-cycle timing at higher latitudes might be mediated by its interactions with genes involved in (circadian) photoperiodic pathways.
Restriction-site associated DNA sequencing (RADseq) has become a powerful and useful approach for population genomics. Currently, no software exists that utilizes both paired-end reads from RADseq ...data to efficiently produce population-informative variant calls, especially for non-model organisms with large effective population sizes and high levels of genetic polymorphism. dDocent is an analysis pipeline with a user-friendly, command-line interface designed to process individually barcoded RADseq data (with double cut sites) into informative SNPs/Indels for population-level analyses. The pipeline, written in BASH, uses data reduction techniques and other stand-alone software packages to perform quality trimming and adapter removal, de novo assembly of RAD loci, read mapping, SNP and Indel calling, and baseline data filtering. Double-digest RAD data from population pairings of three different marine fishes were used to compare dDocent with Stacks, the first generally available, widely used pipeline for analysis of RADseq data. dDocent consistently identified more SNPs shared across greater numbers of individuals and with higher levels of coverage. This is due to the fact that dDocent quality trims instead of filtering, incorporates both forward and reverse reads (including reads with INDEL polymorphisms) in assembly, mapping, and SNP calling. The pipeline and a comprehensive user guide can be found at http://dDocent.wordpress.com.
ABSTRACT
Animal studies suggest that the gut‐brain peptide ghrelin plays an important role in the neurobiology of alcohol dependence (AD). Human studies show an effect of alcohol on ghrelin levels ...and a correlation between ghrelin levels and alcohol craving in alcoholics.
This investigation consisted of two studies. Study 1 was a 12‐week study with alcohol‐dependent subjects, where plasma ghrelin determinations were assessed four times (T0‐T3) and related to alcohol intake and craving Penn Alcohol Craving Score (PACS) and Obsessive Compulsive Drinking Scale (OCDS). Serum growth hormone levels and assessment of the nutritional/metabolic status were also performed. Study 2 was a pilot case‐control study to assess ghrelin gene polymorphisms (Arg51Gln and Leu72Met) in alcohol‐dependent individuals. Study 1 showed no significant differences in ghrelin levels in the whole sample, while there was a statistical difference for ghrelin between non‐abstinent and abstinent subjects. Baseline ghrelin levels were significantly and positively correlated with the PACS score at T1 and with all craving scores both at T2 and T3 (PACS, OCDS, obsessive and compulsive OCDS subscores). In Study 2, although there was a higher frequency of the Leu72Met ghrelin gene polymorphism in alcohol‐dependent individuals, the distribution between healthy controls and alcohol dependent individuals was not statistically significant.
This investigation suggests that ghrelin is potentially able to affect alcohol‐seeking behaviors, such as alcohol drinking and craving, representing a new potential neuropharmacological target for AD.
Aim: The study aimed to assess the frequency of the Gln27Glu polymorphic variant in the β2-AR gene among patients with early and late-onset asthma and assess asthma risks depending on the disease ...phenotype.
Materials and Methods: Our study included a total of 553 asthma patients who consented to participate in the study. Asthma was diagnosed according to the 2016 GINA recommendations and its later versions. The study was approved by the Bioethics Committee of the Medical Institute of Sumy State University. The analysis for determining genetic polymorphism (designated as rs1042714) was conducted through the use of polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of obtained results was performed using SPSS–17 program.
Results: It was found that there is a significant difference in the distribution of alleles and genotypes in people with early-onset asthma compared to those with late-onset asthma; the statistical analysis showed a χ2 value of 41.75 and p-value of 0.001 for early-onset asthma, and a χ2 value of 44.24 and p-value of 0.001 for late-onset asthma. We did not observe a significant increase in the early-onset asthma risk with an account of different inheritance models connected to the studied polymorphism. Research that took into account the risk of late-onset asthma discovered statistically significant results regarding the dominant (p = 0.001), super-dominant (p = 0.001), and additive (p = 0.001) models of inheritance.
Conclusions: Based on the data collected, it was found that individuals carrying the minor allele (both homozygotes and heterozygotes) were at a greater risk of developing asthma later in life. However, no such correlation was observed in patients with early-onset asthma.
Individual variations in the patient's response to the administered drugs are a frequent and important clinical problem in medicine and pharmacology. It is especially important to consider these ...issues when counting cardiovascular disease (CVD) treatment, since CVD is characterized by high incidence in the population, making cardiovascular drugs the most prescribed medication. Currently used medical therapies are adapted to best fit the needs of a wide population of patients who can benefit from them, despite the fact that a certain number of individuals will suffer from inadequate therapeutic effects or even intoxication. By examining the genetic basis that causes individual variations in the response to drugs, pharmacogenetics enables the personalization of drug therapy, with the aim to identify patients who are exposed to an increased risk of serious drug side effects and those missing the maximum drug effectiveness. Polymorphisms of genes that encode protein units of enzymes involved in the drug metabolism, mainly cytochrome P450 enzymes, receptors and drug transporters, affect both pharmacokinetics and pharmacodynamics of drugs often prescribed for CVD, such as beta-blockers, ACE inhibitors, warfarin, clopidogrel, and statins. This approach in cardiological practice would enable adjusting the therapy for patients based on gene polymorphisms, by changing the dose of the existing drugs or using another drug of choice. Although including pharmacogenetics in daily clinical practice would bring along large diagnostic costs, as well as potential legal and ethical dilemmas, a substantial number of patients, overall society, and the health system, in general, could benefit from enhanced therapeutic effects as well as decreased side effects of the applied therapy.
ObjectiveA genome-wide association study (GWAS) of gout and its subtypes was performed to identify novel gout loci, including those that are subtype-specific.MethodsPutative causal association ...signals from a GWAS of 945 clinically defined gout cases and 1213 controls from Japanese males were replicated with 1396 cases and 1268 controls using a custom chip of 1961 single nucleotide polymorphisms (SNPs). We also first conducted GWASs of gout subtypes. Replication with Caucasian and New Zealand Polynesian samples was done to further validate the loci identified in this study.ResultsIn addition to the five loci we reported previously, further susceptibility loci were identified at a genome-wide significance level (p<5.0×10−8): urate transporter genes (SLC22A12 and SLC17A1) and HIST1H2BF-HIST1H4E for all gout cases, and NIPAL1 and FAM35A for the renal underexcretion gout subtype. While NIPAL1 encodes a magnesium transporter, functional analysis did not detect urate transport via NIPAL1, suggesting an indirect association with urate handling. Localisation analysis in the human kidney revealed expression of NIPAL1 and FAM35A mainly in the distal tubules, which suggests the involvement of the distal nephron in urate handling in humans. Clinically ascertained male patients with gout and controls of Caucasian and Polynesian ancestries were also genotyped, and FAM35A was associated with gout in all cases. A meta-analysis of the three populations revealed FAM35A to be associated with gout at a genome-wide level of significance (pmeta=3.58×10−8).ConclusionsOur findings including novel gout risk loci provide further understanding of the molecular pathogenesis of gout and lead to a novel concept for the therapeutic target of gout/hyperuricaemia.
BackgroundGenetic factors may influence the pathogenic pathways leading to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We performed a meta-analysis to determine the ...genetic variants most likely associated with AAV and investigated whether diagnostic and serological subtypes within AAV have distinct genetic backgrounds.MethodsStudies investigating the association between genetic variants and AAV in humans were searched in PubMed, EMBASE and Web of Science. All variants investigated in at least two studies were selected. Subsequently, all studies assessing these variants were included in this meta-analysis. Additionally, data on these variants from the largest genome-wide association studies in AAV were included to increase the validity of this meta-analysis.ResultsThe literature search yielded 5180 articles. 62 articles investigating 140 genetic variants were included, 33 of which were associated with AAV in a meta-analysis. These genetic variants were in or near the following genes: CD226, CTLA-4, FCGR2A, HLA-B, HLA-DP, HLA-DQ, HLA-DR, HSD17B8, IRF5, PTPN22, RING1/RXRB, RXRB, STAT4, SERPINA1 and TLR9. Moreover, we identified genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis and between proteinase 3 ANCA vasculitis and myeloperoxidase ANCA vasculitis. In 76% of the genetic variants, subdivision based on ANCA serotype resulted in higher ORs than subdivision based on clinical diagnosis.ConclusionsThis meta-analysis identified 33 genetic variants associated with AAV, supporting a role for alpha-1-antitrypsin, the major histocompatibility complex system, and several distinct inflammatory processes in AAV pathogenesis. Our results indicate that subdivision of AAV based on ANCA serotype has a stronger genetic basis than subdivision based on clinical diagnosis.
Background
Psoriasis is a chronic inflammatory illness that affects 2%–3% of the world's population. Granulysin (GNLY), along with granzyme and perforin, is a cytolytic antimicrobial peptide (AMP) ...released from the granules of both natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). By immunohistochemistry, it has been shown that GNLY expression increases in psoriasis lesions.
Aims
Our work aimed to reveal the potential effect of GNLY gene polymorphism and its association with psoriasis pathogenesis.
Methods
This case–control research included 25 patients with psoriasis vulgaris and 25 healthy people who were age and gender matched. History taking and medical examination were done for all patients. Venous blood samples were withdrawn, DNA was extracted, and real‐time PCR was done.
Results
There was an insignificant difference between psoriasis cases and controls as regards gene sequence (p > 0.05). The polymorphism of GNLY gene regarding genotype distribution G/G was detected in seven patients with psoriasis (28%) and in only two controls (8%). This clarifies that GNLY rs 7908 G/G gene polymorphism may be a strong diagnostic tool for psoriasis.
Conclusions
In patients with psoriasis, the GNLY rs7908 CC genotype alongside with C allele played a preventative function and reduced disease severity (as shown by PASI score). Detection of GG genotype points out that a psoriatic case will run a progressive course, will have a severe pattern in the future, and will develop multiple site affection.
Chronic myeloid leukemia (CML) result from many reactions of heredity non-heredity factors. The null genotype for glutathione S-transferase (GSTM1 or GSTT1) is regarded a risk agent leukemia, ...especially on CML in various inhabitants. The current study focused on evaluating association of two polymorphic identified genes Glutathione S-Transferase Mu 1 and glutathione S-transferase null genotypes that respect to CML patients from Erbil province, hence this work was performed a case-control study that composed of 51 samples (62% males, 39% females) with CML included and 45 healthy controls (22% male and 78% females) have participated. Multiplex PCR was used to ascertain GSTM1 and GSTT1 null genotypes. The chi-square test was done to show any link between GSTM1 and GSTT1 null genotypes that might be occurred in CML. There are significant statistical differences between incidence of GSTM1 null genotypes among CML cases and the increased CML risk was showed in patients bearing any of the GSTM1 null genotypes (OR = 2.196, 95%CI = (0.6017-6.806), P-value = 0.2108). While there is no statistical relation of GSTT1 null genotype with the risk of CML and exhibited lower risk initiation of CML occurrence (OR: 0.391, 95% CI: 0.1741-0.9033, P-value = 0.0304). Our findings demonstrate that GSTM1 null genotype is linked with the risk of CML patient development. The statements are helpful for formulating different investigation including GSTM1, GSTT1 variation genes and comparing research outputs with geography zone diverse in Iraq.
PDF
