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• Specific VDR gene polymorphisms (FokI, ApaI, TaqI) are significantly associated with SLE susceptibility in a Chinese population. • VDR polymorphisms influence clinical outcomes like mucosal ulcers, hematologic disorders, rash, and photosensitivity in SLE patients. • The FokI polymorphism may predict increased relapse risk in SLE, with potential prognostic value. The etiology of systemic lupus erythematosus (SLE) is complex, involving both environmental and genetic factors. Previous research has indicated a potential link between autoimmune diseases, such as SLE, and variations in the vitamin D receptor gene (VDR). This study intended to explore the relationship between VDR SNPs, susceptibility to SLE, clinical parameters, and prognosis in the Chinese Han SLE population. Totally, 461 healthy individuals and 503 patients were recuited SLE diagnoses were chosen. Data on clinical symptoms, scores from the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and results from clinical examinations were collected. The study analyzed four variations in the VDR gene (FokI, BsmI, ApaI, TaqI) using MassARRAY® Iplex GOLD SNP genotyping. The dominant model showed significant correlations between susceptibility to SLE and the FokI (P < 0.001) and ApaI (P < 0.001) SNPs. Additionally, mucosal ulcer was linked to FokI, while hematologic disorder, rash, photosensitivity, and anti-dsDNA positivity were associated with ApaI. Subsequent studies indicated that the FokI SNP was connected to a poorer prognosis in SLE patients. This research indicates that VDR SNPs could potentially contribute to the susceptibility of SLE, as well as impacting the clinical presentation and outlook for Chinese individuals with SLE. (Protocol No. 2016-027, registered retrospectively). [ABSTRACT FROM AUTHOR]

• Associations of common genetic risk variants with GDM risk in the north Indian population were investigated. • Relative risk, population penetrance and attributable risk for risk allele variants was higher in GDM mother. • Four variants FTO, PPARG2, SLC30A8, and TCF7L2 were significantly associated with BMI, HbA1c and insulin. • Four variants FTO, PPARG2, SLC30A8, and TCF7L2 were significantly associated with GDM in North Indian population. The current study sought to investigate the associations of common genetic risk variants with gestational diabetes mellitus (GDM) risk in the north Indian population and to evaluate their utility in identifying GDM cases. A case-control study, including 300 pregnant women, was included, and clinical and pathological information was collected. The amplification-refractory mutation system (ARMS) was used for genotyping four single nucleotide polymorphisms (SNPs), namely FTO (rs9939609), PPARG2 (rs1801282), SLC30A8 (rs13266634), and TCF7L2 (rs12255372). The odds ratio and confidence interval were determined for each SNP in different genetic models. Further, attributable risk, population penetrance, and relative risk were also calculated. The risk allele A of FTO (rs9939609) poses a two times higher risk of GDM (p = 0.02, OR = 2.5). The CG and GG genotypes of PPARG2 (rs1801282) have half a lower risk of GDM. In SLC30A8 (rs13266634), the recessive model analysis showed a two times higher risk of having GDM, while the recessive model (TT vs. GG + GT) analysis in TCF7L2 (rs12255372) indicates a lower risk of GDM. Finally, the relative risk, population penetrance, and attributable risk for risk allele in all four variants was higher in GDM mothers. All four polymorphisms were found to be significantly associated with BMI, HbA1c, and insulin. Our study first time confirmed a significant association with GDM for four variants, FTO, PPARG2, SLC30A8, and TCF7L2, in the North Indian population. [ABSTRACT FROM AUTHOR]

[Display omitted] • DE exposure leads to significant reduction in body weight of C57BL/6 mice. • C57BL/6 and BALB/c mice showed increased lung resistance after DE exposure. • DE associated bronchiolar damage highlights strain specific susceptibility. • Activation of NLRP3/pyroptosis is involved in susceptibility of C57BL/6 mice. • Presence of SNPs in IL-1β may influence gene activation and lung inflammation. Genetic diversity among species influences the disease severity outcomes linked to air pollution. However, the mechanism responsible for this variability remain elusive and needs further investigation. To investigate the genetic factors and pathways linked with differential susceptibility in mouse strains associated with diesel exhaust exposure. C57BL/6 and Balb/c mice were exposed to diesel exhaust (DE) for 5 days/week for 30 min/day for 8 weeks. Body weight of mice was recorded every week and airway hyperresponsiveness towards DE exposure was recorded after 24 h of last exposure. Mice were euthanised to collect BALF, blood, lung tissues for immunobiochemical assays, structural integrity and genetic studies. C57BL/6 mice showed significantly decreased body weight in comparison to Balb/c mice (p < 0.05). Both mouse strains showed lung resistance and damage to elastance upon DE exposure compared to respective controls (p < 0.05) with more pronounced effects in C57BL/6 mice. Lung histology showed increase in bronchiolar infiltration and damage to the wall in C57BL/6 mice (p < 0.05). DE exposure upregulated pro-inflammatory and Th2 cytokine levels in C57BL/6 in comparison to Balb/c mice. C57BL/6 mice showed increase in Caspase-1 and ASC expression confirming activation of downstream pathway. This showed significant activation of inflammasome pathway in C57BL/6 mice with ∼2-fold increase in NLRP3 and elevated IL-1β expression. Gasdermin-D levels were increased in C57BL/6 mice demonstrating induction of pyroptosis that corroborated with IL-1β secretion (p < 0.05). Genetic variability among both species was confirmed with sanger's sequencing suggesting presence of SNPs in 3'UTRs of IL-1β gene influencing expression between mouse strains. C57BL/6 mice exhibited increased susceptibility to diesel exhaust in contrast to Balb/c mice via activation of NLRP3-related pyroptosis. Differential susceptibility between strains may be attributed via SNPs in the 3'UTRs of the IL-1β gene. [ABSTRACT FROM AUTHOR]

• 73 Eligible studies were reviewed, 300 polymorphisms, and 46 genes. • Three major clusters indicate a robust interaction network among 46 genes. • Variant alleles in CYP1A1 and CYP1B1 increase BC risk. • Slow genotypes in the NAT1 and NAT2 increased BC risk. • Latin America is underrepresented in studies of BC susceptibility and prognosis. Epidemiological studies have shown the association of genetic variants with risks of occupational and environmentally induced cancers, including bladder (BC). The current review summarizes the effects of variants in genes encoding phase I and II enzymes in well-designed studies to highlight their contribution to BC susceptibility and prognosis. Polymorphisms in genes codifying drug-metabolizing proteins are of particular interest because of their involvement in the metabolism of exogenous genotoxic compounds, such as tobacco and agrochemicals. The prognosis between muscle-invasive and non-muscle-invasive diseases is very different, and it is difficult to predict which will progress worse. Web of Science, PubMed, and Medline were searched to identify studies published between January 1, 2010, and February 2023. We included 73 eligible studies, more than 300 polymorphisms, and 46 genes/loci. The most studied candidate genes/loci of phase I metabolism were CYP1B1, CYP1A1, CYP1A2, CYP3A4, CYP2D6, CYP2A6, CYP3E1 , and ALDH2 , and those in phase II were GSTM1, GSTT1, NAT2, GSTP1, GSTA1, GSTO1 , and UGT1A1. We used the 46 genes to construct a network of proteins and to evaluate their biological functions based on the Reactome and KEGG databases. Lastly, we assessed their expression in different tissues, including normal bladder and BC samples. The drug-metabolizing pathway plays a relevant role in BC, and our review discusses a list of genes that could provide clues for further exploration of susceptibility and prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Abstract Genetic polymorphism has great influences on the improvement of cattle traits. The polymorphism of the same gene family will greatly change the growth traits of cattle, such as the pleomorphic adenoma gene (PLAG) family. Many studies have shown that the PLAG family proteins are the transcription regulators of nuclear protein, which mainly regulates the expression of many important genes in the body. In cattle, single nucleotide polymorphisms (SNPs) within or near the PLAG1 gene is associated with economic traits of height in cattle. Here we investigate a SNPs of bovine PLAG1 in 646 cattle from five breeds. We found three different genotypes by using cleaved amplification polymorphism sequence-tagged sites (CAPs), includes some significant differences in body height, chest circumference and other shapes (P < 0.05), also we found that the TT genotype had no advantage in body shape. These results indicate that the selection of PLAG1 gene could be used to ensure the breeding direction for growth traits of the beef cattle. Highlights • The SNPs region(rs210941459) which affects growth traits was identified in Chinese cattle of PLAG1 gene. • The PLAG1 gene has an important influence on the growth and development of China cattle. • The polymorphism of g.48308 in a PLAG1 gene had significant effects on body length and chest height. • There were significant differences in individual growth traits of different gene polymorphism [ABSTRACT FROM AUTHOR]

Abstract cis -Prenyltransferases (cis -PTs) constitute a large family of enzymes conserved during evolution and present in all domains of life. cis -PTs catalyze the cis -1,4-polymerization of isoprene units to generate isoprenoids with carbon skeletons varying from C10 (neryl pyrophosphate) to C > 10,000 (natural rubber). Though the previously reported CPTs in Hevea are designated based on sequence variations, their classification was done mostly by phylogenetic analysis using a mixture of partial as well as full length sequences often excluding the UTRs. In this context an attempt was made to reclassify the CPTs strictly based on their sequence similarity and distinguish the members putatively associated with rubber biosynthesis from the others. Extensive computational analysis was carried out on CPT sequences obtained from public resources and whole genome assemblies of Hevea. Based on the results from BLAST analysis, multiple sequence alignments of protein, nucleotide and untranslated regions, open reading frame analysis, gene prediction analysis and sequence length variations, we conclude that there exists mainly three CPTs namely RubCPT1, RubCPT2 and RubCPT3 putatively associated with rubber biosynthesis in Hevea brasiliensis. The rest were categorised as variants of dehydrodolichyl diphosphate synthase (DHDDS) involved in the synthesis of dolichols having short chain isoprenoids. Analysis of the sequence structure of the most highly expressed RubCPT1 in latex revealed the allele richness and diversity of this important variant prevailing in the popular rubber clones. Haplotypes consisting of SNPs with high degree of heterozygosity were also identified. Segregation and linkage disequilibrium analysis confirmed that recombination is the major contributor towards the generation of allelic diversity rather than point mutations. Alternatively, gene expression analysis indicated the possibility of association between specific haplotypes and RubCPT1 expression in Hevea clones which may have downstream impact up to the level of rubber production. The conclusions from this study may pave way for the identification and better understanding of CPTs directly involved with natural rubber biosynthesis in Hevea and the SNP data generated may aid in the development of molecular markers putatively associated with yield in rubber. Highlights • Distinguished rubber biosynthesis associated CPTs from other CPTs in Hevea and grouped them as RubCPT1, RubCPT2 & RubCPT3. • Sequence structure analysis of RubCPT1 variants from various H.brasiliensis genotypes was performed • Haplotypes consisting of SNPs with high degree of heterozygosity were identified • Indications obtained for association between specific RubCPT1 haplotypes and their expression • Identified SNPs/haplotypes which may be developed as potential markers for latex yield in rubber. [ABSTRACT FROM AUTHOR]

• Identification of a significant genetic link between APOB gene SNPs (rs1801701 and rs1042031) and MI in Pakistani Population. • Correlation between the APOB gene SNPs and elevated triglycerides levels, suggesting a potential mechanism for MI development. • Addressing a research gap by investigating APOB gene SNPs in the Pakistani population, specifically in relation to MI. • Emphasizing the importance of targeted genetic screenings and personalized interventions for better MI risk management. Myocardial infarction (MI) is when a blood clot in the coronary artery obstructs blood flow to a specific part of the heart, leading to the death of myocardium in that area. The development of MI is influenced by various environmental factors, genetic components, and their interactions, even though the exact cause has not been fully established. This is the first case-control study examining the possible association between the human Apo B gene and MI in the Punjab region of Pakistan. The study included 100 patients and 50 healthy individuals. Genomic DNA was isolated from blood samples using manual extraction methods. Subsequently, primers were optimized, and genotyping was performed using PCR, followed by DNA sequencing and RFLP analysis. The research focused on two specific APO B gene SNPs, codon 4154 G/A (rs1801701) and codon 2488 G/A (rs1042031). Both SNPs involved the substitution of guanine with adenine. It was found that individuals carrying the minor allele A of SNP rs1801701 (p < 0.001) and the minor allele A of rs1042031 (p < 0.001) had a significantly higher risk of developing MI. Additionally, haplotype analysis revealed that the AA haplotype (comprising both rs1801701 and rs1042031 SNPs) was associated with a substantially increased risk of MI (OR = 3.845). In conclusion, the study provides evidence supporting the association between specific mutations in the APOB gene and the risk of myocardial infarction in the Pakistani population. [ABSTRACT FROM AUTHOR]

• We present a systematic method for identifying genes associated with a specific complex trait. • Over 50% of the selected SNPs showed a significant association with hypertension incidence in the Mexican population. • Our findings reveal sex-dependent associations between 4 SNPs with hypertension incidence. The selection of single nucleotide polymorphisms (SNPs) to evaluate the genetic susceptibility in complex traits is often conducted in isolation, without considering the entire set of genes. Incorporating signaling pathways or gene-gene interaction search may provide a more comprehensive approach to selecting SNP candidates for further study. To propose a systematic procedure for identifying SNPs candidates with complex traits such as hypertension and blood pressure. Sequential stages to SNPs selection: 1) literature review to identify SNPs, following the PRISMA methodology, 2) identification and selection of signaling pathways and selection of gene-gene interaction networks using the STRING software, and 3) application of specific criteria for SNPs candidates, including: a) SNPs with minor allele frequency > 5% in the target population, b) SNPs located within genes involved in three or more signaling pathways, and c) SNPs that are not in linkage disequilibrium, with a D'or r2 value < 0.8. Stage 1) A total of 44 publications were selected, providing information on 230 genes evaluated with blood pressure. Stage 2) Using the STRING software, we selected 7 signaling pathways with a false discovery rate < 0.0001 and strength ≥ 0.8; and we identified 16 genes belonging to gene-gene interaction networks, six of them share ≥ 3 signaling pathways. Stage 3) Finally, 7 SNPs were selected for genotyping in the Health Workers Cohort Study. We observed a positive association between SNPs with hypertension incidence in males (rs1130214, rs3807989) and females (rs5051, rs2493123). Our methodological proposal may be a reliable way for selecting SNPs candidates to study complex traits. [ABSTRACT FROM AUTHOR]

There is tremendous increase in type 2 diabetes mellitus (T2DM) worldwide. The impact of FTO gene polymorphisms on the risk of T2DM is not yet clear because of the controversial results of studies. This meta -analysis aimed to better clarify the association between three FTO gene polymorphisms SNPs (rs9939609 , rs8050136 and rs17817449) and T2DM in a larger combined population worldwide. A comprehensive search on the PubMed, Science Direct, and Web of Science databases was conducted to identify investigations in relationship between different FTO gene polymorphisms (rs9939609 , rs8050136 and rs17817449) and T2DM globally. Published papers from January 2007 to May 2023 were collected. Inclusion criteria are limited to human case-control studies published in English and peer-reviewed, which provided data on the genotype distributions of FTO gene polymorphisms and T2DM risk. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to express the results of the meta -analysis. Potential sources of bias and heterogeneity using Egger's regression analysis were also assessed. Of 234 695 identified articles, forty-eight studies were selected including 36,051 patients with T2DM and 51,266 control subjects. Overall, we found a significant increased risk of T2DM susceptibility and rs9939609 FTO gene polymorphism in the Allele contrast (A vs. T: OR = 1,30, 95% CI = 1.14; 1.48, P < 0,05, I2 = 0,94), Recessive model (AA vs. AT + TT: OR = 1,54, 95% CI = 1.19; 2.00, P < 0,05, I2 = 0,94), Dominant model (AA + AT vs. TT: OR = 1,26, 95% CI = 1.10; 1.45, P < 0,05, I2 = 0,89), homozygote model (AA vs. TT: OR = 1,60, 95% CI = 1.26; 2.03, P < 0,05, I2 = 0,90), and heterozygote model (AA vs. AT: OR = 1,43, 95% CI = 1.09; 1.88, P = 0,008, I2 = 0,93). we also found a significantly increased risk of T2DM susceptibility and rs8050136 FTO gene polymorphism under all models. For rs17817449 we did not find any association between with T2DM. The present meta -analysis confirms that rs9939609 and rs8050136 in the FTO gene are significantly associated with T2DM, while rs17817449 does not show any association. [ABSTRACT FROM AUTHOR]

The sine oculis homeobox homolog 4 ( SIX4 ) gene belongs to the SIX gene family, which plays a critical role in muscle regeneration and early stages of ontogeny. This study aimed to detect promoter variations of bovine SIX4 genes in Qinchuan cattle, and to evaluate the effect of transcription regulations and body measurement traits. Quantitative real-time PCR (qPCR) results showed that the mRNA expression levels of SIX4 gene were found significantly highest in longissimus thoracis tissue and individual before attaining the stage of physiological maturity. Using sequencing technology on a total of 428 Qinchuan cattle, seven single nucleotide polymorphisms (SNPs) were identified in the promoter region of SIX4 , and seven haplotypes representing 18 potential transcription factor compositions of polymorphic potential cis -acting elements. Association analysis indicated that the H 3 -H 3 diplotype performed greater withers height, chest depth, chest circumference, back fat thickness and ultrasound loin muscle area ( P  < 0.05) than H 5 -H 6 , which were consistent with the promoter activity of Hap3 haplotype was higher than the Hap5 and Hap6 haplotype in vitro. These potential transcription factor information and combined genotypes H 3 -H 3 of the SIX4 gene can be used as a molecular marker for selection of economic traits in Qinchuan cattle. [ABSTRACT FROM AUTHOR]

Corins are membrane-bound protease that regulates blood pressure by activating the natriuretic peptides. These pro-atrial natriuretic peptide convertases are essential for sodium homeostasis and normal blood pressure. CORIN variants have been identified in humans and other animals, but no studies of CORIN polymorphisms have been conducted in northeastern China. This study aims to investigate the association of 2 single nucleotide polymorphisms (SNPs) in CORIN (rs2271037 and rs3749585) with hypertension, as well as their potential interactions with some risk factors of hypertension in a Han population of northeastern China. A case-control study, including 402 patients with hypertension and 406 participants with normal blood pressure, was conducted in Liaoning province. SNP genotyping was carried out by high resolution melting (HRM) after polymerase chain reaction amplifications. Since rs3749585 is located in 3′ untranslated region (UTR) of CORIN , in silico analysis was used to predict target micro RNAs on TargetScan, miRanda, and DIANA-microT. As a result, mutant T allele in rs2271037 (odds ratio [OR], 1.693; 95% confidence [CI], 1.528-1.877; p  < 0.001) and C allele in rs3749585 (OR, 1.114; 95% CI 1.011-1.227; p  = 0.029) increased the risk of hypertension, comparing with wild G allele and T allele, respectively. Patients with genotype TT (OR, 10.209; 95% CI, 6.414-16.250; p  < 0.001) and GT (OR, 1.730; 95% CI, 1.226-2.443; p  = 0.002) have higher risk of hypertension than those with genotype GG. SNP rs2271037 was significantly associated with susceptibility to hypertension in all genetic models (dominant model: OR, 2.879; 95% CI, 2.080–3.986; p  < 0.001; recessive model: OR, 7.159; 95% CI, 4.779–10.724; p  < 0.001; additive model: OR, 1.535; 95% CI, 1.163–2.027; p  = 0.002). SNP rs3749585 was significantly correlated with hypertension susceptibility only in dominant model (OR, 1.533; 95% CI, 1.073–2.189; p  = 0.019), but not in recessive model (OR, 1.220; 95% CI, 0.906–1.644; p  = 0.191) or additive model (OR, 0.915; 95% CI, 0.694–1.205; p  = 0.527). After adjusting for age, gender, body mass index (BMI), smoking, low-density lipoprotein cholesterol, and serum sodium level in logistic models, the same statistical results were obtained. Interaction study showed the association between CORIN polymorphisms and hypertension could be changed by overweight (BMI ≥ 25 kg/m 2 ). In silico analyses implicated hsa-miR-495 as a target miRNA that potentially interacts with the 3′ UTR of CORIN . In conclusion, polymorphisms of rs2271037 and rs3749585 in CORIN were significantly associated with hypertension in a Han population of northeastern China. The mutant-type T allele of rs2271037 and C allele of rs3749585 might increase the susceptibility to hypertension in this population. [ABSTRACT FROM AUTHOR]

Genome flanking regions surrounding transcription start sites (TSSs) are critical for the regulation of gene expression, containing many translational regulatory elements. To investigate whether critical single nucleotide polymorphisms (SNPs) exist around TSSs in the dairy goat genome, we performed high throughput DNA sequencing to compare two dairy goat groups with discrepant litter sizes. After genome mapping, SNP calling, and annotation, we screened the SNPs within 2 kb scales surrounding annotated TSSs in high fecundity (HF) and low fecundity (LF) groups, respectively. We attempted to identify distinct SNPs and motifs near the TSSs in both groups. The SNPs near the TSSs most were consistent; 318 new SNPs were uncovered in the HF group, of which 305 were heterozygote SNPs, 13 were homozygote SNPs, and majority of which were distributed on chromosome 2 and 29. After validation by Sanger sequencing we found that a SNP in CHI16: 27612330 C > A in the PSEN2 gene presented an A/A genotype in the HF group and an A/A or A/C genotype in the LF group. In conclusion, our study provides insightful information into the dairy goat genomic variations surrounding TSSs, which may contribute to enhanced litter size. Based on comparison studies of SNPs exist around transcription start sites between high fecundity group and low fecundity group. Our finding provides insights concerning the goat litter size phenotypic and will promote future goat breeding. [ABSTRACT FROM AUTHOR]

Preterm birth (PTB) is featured by less than 37 weeks of gestational age or fewer than 259 days since the first day from the last menstrual period. Complications of PTB are the major cause of neonatal deaths, several factors are linked to PTB increased risk including immunological and genetics. Vitamin D plays an important role in immune response modulation and its action occurs through the vitamin D receptor (VDR), which recently has been described as overexpressed in human placenta during the pregnancy. Herein we assessed two single nucleotide polymorphisms (SNPs) Fok I (rs2228570 A > G) and Cdx-2 (rs11568820 T > C), within VDR , using TaqMan fluorogenic probes, and differential susceptibility to SPTB. We assessed 104 pregnant women with SPTB and 85 women with normal birth in a Northeastern Brazilian population. Statistically significant differences for both SNPs where found when comparing allele and genotype frequencies in both groups: the T allele for rs2228570 and A allele for rs11568820 were significantly more frequent in SPTB group than in normal birth group ( p = 0.000013 and p = 0.00466, respectively). The rs11568820 A/A genotype was associated to clinical/demographic variables such as: premature birth ( p = 0.007), neonate weight ( p = 0.039), presence of infection during pregnancy ( p = 0.011) and premature birth among multiparous ( p = 0.015). The rs2228570 T/T genotype associated with gestational diabetes mellitus ( p = 0.044) and chorioamnionitis during pregnancy ( p = 0.043). In conclusion our findings indicate an association between polymorphisms Fok I and Cdx-2 within VDR gene and SPTB, suggesting their involvement in the triggering of these syndromes. [ABSTRACT FROM AUTHOR]

Identification of new polymorphic variants from RNA-seq data is difficult mainly because of the errors arising during bioinformatic analysis. Therefore, new experiments in this area are very profitable for improving new statistical methods. In our study of the porcine brain transcriptome, we have identified 10966 polymorphic variants, among which 7277 were single nucleotide polymorphisms (SNPs). Further, we have calculated allelic ratios for the SNPs identified and estimated that 52% of genes in porcine brain are subjected to allele-specific expression (ASE), a phenomenon in which one allele is preferentially expressed. Our investigation presents the first estimates of ASE in porcine brain. In addition, we have used the results of RNA-seq for the identification of SNPs in putatively imprinted genes. Finally, we have used these SNPs for the verification of the imprinted status of the INPP5f variant 2 , LRRTM1 and HM13 genes in pigs by Sanger sequencing. We observed that INPP5f variant 2 is paternally expressed, while HM13 and LRRTM1 are biallelically expressed in porcine brain. We have also confirmed maternal expression of the MEG3 gene in pigs. Our results present how RNA-seq data may be used for imprinting studies without sequencing of parental genomes. [ABSTRACT FROM AUTHOR]

microRNAs (miRNAs) are nowadays recognized as an essential component of gene regulatory networks. Furthermore, deregulation of miRNAs expression often contributes to human pathologies. Recently, a substantial number of single nucleotide polymorphism (SNPs) and rare mutations within pri-, pre- and mature miRNA sequences have been reported. These miRNA SNPs have often been associated with human disease. However, due to the complexity of miRNA biogenesis and the genome-wide functional effects of miRNAs, the determination of biological consequences of these miRNA SNPs remains challenging. Despite an increasing number of reports linking miRNA SNPs with human pathologies, few reports have analyzed the mechanism by which miRNA-SNPs contribute to disease pathogenesis. In this review, we discuss how single polynucleotide polymorphisms in miRNAs genes may influence miRNAs expression and function and thus potentially alter disease pathogenesis. [ABSTRACT FROM AUTHOR]

The SCARB1 gene encodes human scavenger receptor class B type I (SR-BI), the primary receptor for high-density lipoprotein (HDL)- cholesteryl ester uptake, and polymorphisms in this gene may influence SR-BI protein expression and serum lipid levels, modulating susceptibility to coronary heart disease (CHD) and cerebral infarction (CI). Therefore, we investigated the association between singlenucleotide polymorphisms (SNPs) in the SCARB1 gene and serum lipid levels as well as risk of CHD and CI in the Chinese Han population. Genotypes in 295 CHD patients, 302 CI patients and 312 healthy controls matched for age and gender were determined by high-resolution melting (HRM). Among the 5 SNPs investigated in this study, rs10846744 and rs2278986 were significantly associated with CHD risk. The frequency of the C allele for rs10846744 and that of the T allele for rs2278986 appeared to be significantly increased in the CHD group (OR: 1.416, 95%CI: 1.128–1.778, P = 0.0058 and OR: 1.681, 95%CI: 1.327–2.130, P < 0.0001, respectively). CHD patients with genotypes CC and CG for rs10846744 had a higher HDL-c level than those with genotype GG, and CHD patients with genotypes CC and CT for the rs2278986 SNP had a higher HDL-c level compared to those with the TT allele. The other 3 SNPs, rs5888, rs10744182 and rs838893, showed no significant association with serum lipid levels and CHD or CI risk in the Chinese population. The CCCTT and CCTTC haplotypes of rs5888, rs10846744, rs10744182, rs2278986 and rs838893 appear to significantly increase CHD risk, whereas the CGTTC, CCTCT and TGCTC haplotypes appear to significantly reduce risk. Overall, the CCTTC and TGTTC haplotypes acted as a significant risk for CI, with the CGCTC and CCCCT haplotypes conferring significantly reduced risk. These results suggest that SCARB1 gene polymorphisms may contribute to genetic susceptibility to CHD; in particular, the C allele of rs10846744 and the C allele of rs2278986 may serve as risk and protective factors for CHD, respectively. [ABSTRACT FROM AUTHOR]

• A positive association between rs2910164 C/G genotype and asthmatic risk in female. • Male asthmatic patients of rs57095329 were responsible for the clinical features. • The rs2910164 and rs57095329 influence mature miR-146a expression. • The SNPs mutations disrupted the normal structure and stability of miR-146a. Asthma, a prevalent disease characterized by innate and adaptive immune responses, has been associated with several risk factors including miR-146a. To better understand the potential impact of miR-146a SNPs on asthma susceptibility and clinical features in Southern Chinese Han population, we conducted a case-control to analyze two functional SNPs (rs2910164 and rs57095329) of the miR-146a (394 patients with asthma and 395 healthy controls). Our findings suggest that the rs2910164 C/G genotype may increase the risk for asthma in females, while the rs57095329 G/G genotype may be involved in the regulation of clinical characteristics of males with asthma. In addition, we demonstrated that the SNPs rs2910164 C/G and rs57095329 A/G variations functionally affected the miR-146a levels in patients with asthma, and may alter structure of miR-146a. Our data are the first to suggest that miR-146a SNPs may be significantly associated with onset asthma in Southern Chinese Han population. Our studies may provide new insight into the potential significance of miR-146a SNPs in asthma. [ABSTRACT FROM AUTHOR]

• Studies examining the association between the interleukin-6 (IL-6) gene rs1800795 (-174G/C) polymorphism and the risk of multiple diseases remain controversial. • Thus we aimed to accurately determine the role of −174G/C polymorphism in overall disease risk as well as acute pancreatitis, bronchial asthma, CAD, inflammatory disease, ischemic stroke, rheumatoid arthritis, T1D and T2D. • This study found that the −174G/C polymorphism is significantly associated with overall disease risk and partially with CAD, inflammatory diseases, rheumatoid arthritis and ischemic stroke. • Therefore, the IL-6 gene could be a useful prognostic biomarker for associated disease diagnosis and research. Individual genome-wide association studies (GWAS) or single case-specific meta-analyses may not be sufficient evidence to take action against a specific gene function. Thus, we tried to determine a consensus association between the IL-6 gene rs1800795 polymorphism and multiple disease risks through an updated statistical meta-analysis. After systematically searching online databases, we found 149 case-control relevant datasets with a sample size of 96,153 (cases: 38,291 and controls: 57862) and conducted the meta-analysis using updated statistical models. The analyses of this comprehensive meta-analysis revealed a significant association between IL-6 −174G/C polymorphism and overall disorder risk under all genetic models (C vs G: OR = 1.11, 95% CI = 1.08–1.13; p -value = 4.8E-17; CC vs GG: OR = 1.19, 95% CI = 1.13–1.26; p -value = 9.4E-12; CG vs GG: OR = 1.10, 95% CI = 1.06–1.14; p -value = 1.1E-07; CC + CG vs GG: OR = 1.13, 95% CI = 1.10–1.17; p -value = 1.1E-13; CC vs CG + GG: OR = 1.18, 95% CI = 1.06–1.31; p -value = 0.0019) and (OR > 1) with Asian ethnicity. The subgroup analyses based on the diseases revealed that the polymorphism was highly significantly increasing the risk of coronary artery disease (CAD) under all genetic models. Likewise, a significant association was observed with increased risk under three genetic models of inflammatory diseases (C vs G; CC vs GG; and CC vs CG + GG), and rheumatoid arthritis (C vs G; CG vs GG; and CC + CG vs GG). Conversely, the −174G/C SNP significantly decreased the risk of ischemic stroke under the two genetic models (C vs G; and CG vs GG). However, the other diseases included in this study showed no significant association with IL-6 (-174G/C) polymorphism. This meta-analysis provided strong evidence for the association between IL-6 gene rs1800795 polymorphism and multiple disease risks. The IL-6 gene could be a useful prognostic biomarker for CAD, inflammatory disease, ischemic stroke, and rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

[Display omitted] • CYP1A enzymes are critically involved in biotransformation of diverse substrates. • CYP1A-mediated metabolic activities operate multiple biological pathways. • Variability in CYP1A genes occur primarily due to the presence of SNPs. • These SNPs are associated with diverse clinical phenotypes. • Understanding impact of polymorphic CYP1A activity on metabolism is important. The human cytochrome P450 1A (CYP1A) subfamily genes, CYP1A1 and CYP1A2 , encoding monooxygenases are critically involved in biotransformation of key endogenous substrates (estradiol, arachidonic acid, cholesterol) and exogenous compounds (smoke constituents, carcinogens, caffeine, therapeutic drugs). This suggests their significant involvement in multiple biological pathways with a primary role of maintaining endogenous homeostasis and xenobiotic detoxification. Large interindividual variability exist in CYP1A gene expression and/or catalytic activity of the enzyme, which is primarily due to the existence of polymorphic alleles which encode them. These polymorphisms (mainly single nucleotide polymorphisms, SNPs) have been extensively studied as susceptibility factors in a spectrum of clinical phenotypes. An in-depth understanding of the effects of polymorphic CYP1A genes on the differential metabolic activity and the resulting biological pathways is needed to explain the clinical implications of CYP1A polymorphisms. The present review is intended to provide an integrated understanding of CYP1A metabolic activity with unique substrate specificity and their involvement in physiological and pathophysiological roles. The article further emphasizes on the impact of widely studied CYP1A1 and CYP1A2 SNPs and their complex interaction with non-genetic factors like smoking and caffeine intake on multiple clinical phenotypes. Finally, we attempted to discuss the alterations in metabolism/physiology concerning the polymorphic CYP1A genes, which may underlie the reported clinical associations. This knowledge may provide insights into the disease pathogenesis, risk stratification, response to therapy and potential drug targets for individuals with certain CYP1A genotypes. [ABSTRACT FROM AUTHOR]

Leptin ( LEP ) and leptin receptor ( LEPR ) are suggested to play a role in female reproduction and especially in pregnancy Both LEP and LEPR are synthesized by the pregnant female and embryo. The link between genetic polymorphisms of LEP and LEPR and preterm birth (PTB) is unknown. We studied maternal and neonatal LEP and LEPR genetic polymorphisms and the association with PTB. Blood for DNA analysis was collected from Israeli mothers and from venous umbilical of their respected idiopathic preterm newborns (24–36 weeks, n = 102) and control term newborns (> 37 weeks, n = 158). Genotypes of maternal and neonatal LEP (rs7799039) and LEPR (rs1137101) polymorphisms were analyzed by restriction fragment length polymorphism analysis. Genotype-phenotype association was assayed using SPSS program. We found a significant independent increased risk of PTB for women and neonates bearing the homozygous AA form of LEP genotype; where women carrying AA LEP genotype had 2.53 fold ([CI] 1.367–4.685, p = 0.03) and 2.38 fold ([CI] 1.150–4.915, p = 0.019) increased risk for PTB compared to AG and GG genotypes, respectively. Neonates carrying the LEP AA genotype had a significant 2.8 fold increased risk for PTB compared to the AG genotype (CI11.040–7.577, p = 0.042). Maternal LEPR polymorphism was significantly associated with severe PTB; where women carrying the AA and AG genotypes had a significant 4.32 and 4.76 fold increased risk for severe PTB compared to women carrying the GG genotype (CI = 1.090–17.112 and 1.332–17.027, respectively p = 0.035). In conclusion: maternal and neonatal LEP and LEPR polymorphisms are significantly associated with increased risk for PTB. [ABSTRACT FROM AUTHOR]

The present study was undertaken to characterize the genetic variation present in lymphoxin A gene ( LTA gene) encoding for the lymphotoxin A protein also known as tumor necrosis factor beta, a cytokine produced by lymphocytes, known to be cytotoxic for a wide range of tumor cells both in vitro and in vivo , and, which is essential for normal immunological development; in 40 animals of 5 diverse Bos indicus Indian zebu cattle breeds. These breeds survive under the harsh and tough tropical climatic conditions of various parts of the Indian subcontinent. The LTA gene in the present study was observed to contain 33 SNPs and 3 small insertion/deletion polymorphisms. Four SNPs occurred in the coding regions of the gene viz. g.1327A > G and g.1400C > T in exon 2 and g.1840C > T and g.1942C > T in exon 3, of which the SNP g.1327A > G in exon 2 resulted in a non-synonymous amino acid change G38D. This amino acid change was however predicted not be affecting the protein function in any manner. The gene contained putative transcription factor binding sites for the c-Re1 and for Pax-4 transcription factors. A putative promoter region was also predicted on the reverse DNA strand from position 894 to 644. Several repeat elements and microsatellite repeats were detected to be occurring across the 3.2 kb LTA gene sequence. The study showed the occurrence of 40 genotypes and 48 most probable haplotypes. The genotypes at the observed SNP positions in the LTA gene were in near Hardy–Weinberg equilibrium. A negative Tajima's D value that was not significant statistically at P > 0.10 indicated that the neutral mutation hypothesis could not be excluded. The genetic variations observed in the LTA gene in the present study have not been reported earlier and these could possibly be used as molecular markers for further studies involving association of the gene variability with disease resistance/tolerance traits. [ABSTRACT FROM AUTHOR]

• Large scale screening of single nucleotide polymorphisms in diabetes and its associated retinopathy 1. complication in Pakistani population. • The study revealed association of multiple single nucleotide polymorphisms in manifestation of diabetes and diabetes-induced retinopathy. • These study findings point to the screening of other loci and genes in Pakistani population to identify novel genetic factors. Meta-GWAS report numerous variants associated with type 2 diabetes (T2D), however, for diabetic retinopathy (DR) no loci achieved genome-wide significance. There are limited candidate gene analyses for T2D and/or DR reported from the Pakistani population. Therefore, the current study was designed to evaluate the genetic association of 10 loci with T2D, non-proliferative DR (NPDR), and proliferative DR (PDR). In total 375 T2D cases and 205 controls were collected. The T2D cases included diabetic no retinopathy (n = 196), NPDR (n = 95), and PDR (n = 84). Genomic DNA was isolated, and 19 SNPs were genotyped. To determine association of SNPs with T2D, logistic regression analyses were performed adjusting for age and sex. Moreover, for association of SNPs with NPDR and PDR logistic regression analyses adjusting for diabetes duration and age of T2D onset were performed. In multivariate analysis, the minor alleles of rs1043618 [G > C, odds ratio (OR) 95% confidence interval (CI) = 1.45 (1.13–1.87), p = 4.00E-3], rs3807987 [G > A, 1.87 (1.22–2.94), p = 0.01], rs12672038 [G > A, 1.53 (1.04–2.30), p = 0.03] and rs2055858 [G > C, 1.70 (1.20–2.43), p = 3.00E-3] were associated with higher risk while rs1801133 (C > T, 0.59 (0.42–0.83), p = 2.28E-3) was associated with a lower risk of T2D. Moreover, minor alleles of rs2055858 [G > C, 1.77 (1.17–2.68), p = 0.02], and rs3759890 [C > G, 2.17 (1.39–3.39), p = 4.00E-3] showed an association with PDR when compared with DNR. However, only the association of rs1801133 survived multiple test correction. Hence, we report that rs1801133 is associated with T2D in the Pakistani population. In addition, out of studied 10 genes 8 proteins had higher interactions among themselves that are predicted to be partially biologically connected, as a group. [ABSTRACT FROM AUTHOR]

Patatin-like phospholipase domain-containing protein 3 (PNPLA3), a member of the patatin like phospholipase domain-containing (PNPLA) family, plays an important role in energy balance, fat metabolism regulation, glucose metabolism and fatty liver disease. Tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) is a new method offering fast detection and extreme simplicity at a negligible cost for SNP genotyping. In this paper, we investigated the genetic variations at different ages of 660 Chinese indigenous cattle belonging to three breeds (QC, NY, JX) and applied T-ARMS-PCR and PCR-RFLP methods to genotype four SNPs, SNP1: g.A2980G, SNP2: g.A2996T, SNP3: g.A36718G, SNP4: g.G36850A. The statistical analyses indicated that these 4 SNPs affected growth traits markedly (P < 0.05) in QC population,whereas combined haplotypes were not (P > 0.05). The qPCR (quantitative PCR) indicated that bovine PNPLA3 gene was exclusively expressed in fat tissues. Besides, the analysis between SNP and mRNA expression revealed that, in SNP1, the expression of AG was much higher than AA and GG(P < 0.05),which was in accordance with the results of growth traits association analysis, while the results of SNP4 was not. These results supported high potential that SNPs of bovine PNPLA3 gene might be utilized as genetic markers in marker-assisted selection (MAS) for Chinese cattle breeding programs. [ABSTRACT FROM AUTHOR]

Long-chain fatty acid-CoA ligases (ACSLs) play crucial roles in fatty acid (FA) metabolism. They convert free long-chain FA into acyl-CoAs, which are key intermediates in both anabolic and catabolic pathways. A long-chain fatty acid-CoA ligase gene was cloned in the clam Meretrix meretrix ( MmeACSL1 ), with a full-length cDNA of 1865 bp encoding 475 amino acids. Its expression was only detected in hepatopancreas by semi-quantitative reverse transcription PCR. Expression level of MmeACSL1 exhibited a significant increase in a starvation experiment ( P < 0.05). This indicates that MmeACSL1 plays an important role in normal metabolism of M. meretrix and may be involved in energy supply and storage. Two exon SNPs and six intron SNPs were developed in this gene by direct sequencing. A marker-trait association analysis showed that five of these SNPs were significantly associated with growth traits ( P < 0.05). Also, haplotypes comprised of the five SNPs were revealed to be significantly growth-related ( P < 0.05), which further corroborates the relationship of this gene to growth traits of M. meretrix . [ABSTRACT FROM AUTHOR]

Gastric cancer remains one of the leading causes of death in the world, being Central and South America among the regions showing the highest incidence and mortality rates worldwide. Although several single nucleotide polymorphisms (SNPs) identified in the chromosomal region 8q24 by genome-wide association studies have been related with the risk of different kinds of cancers, their role in the susceptibility of gastric cancer in Latin American populations has not been evaluated yet. Hereby, we performed a case–control study to explore the associations between three SNPs at 8q24 and gastric cancer risk in Venezuelan patients. We analyzed rs1447295, rs4733616 and rs6983267 SNPs in 122 paraffin-embedded tumor samples from archival bank and 129 samples with chronic gastritis (obtained by upper endoscopy during the study) from the Central Hospital of Barquisimeto (Lara, Venezuela). Genotypes were determined by PCR–RFLP reactions designed in this study for efficient genotyping of formalin-fixed/paraffin-embedded tissues. No significant differences in genotype frequencies between case and control groups were found. However, carriers of the homozygous TT genotype of SNP rs4733616 had an increased risk of developing poorly differentiated gastric cancer according to the codominant (OR = 3.59, P = 0.035) and the recessive models (OR = 4.32, P = 0.014, best-fitting model of inheritance), adjusted by age and gender. Our study suggests that the SNP rs4733616 is associated with susceptibility to poorly differentiated gastric cancer in Venezuelans. Additional studies are needed to further interrogate the prognostic value of the rs4733616 marker in this high-risk population for gastric cancer. [ABSTRACT FROM AUTHOR]

Prohibitins are evolutionarily conserved proteins present in multiple cellular compartments, and are involved in diverse cellular processes, including steroid hormone transcription and gametogenesis. In the present study, we report for the first time the characterization of the prohibitin-2 ( Phb2 ) gene in the sea lice Caligus rogercresseyi . The CrPhb2 cDNA showed a total length of 1406 bp, which contained a predicted open reading frame (ORF) of 894 base pairs (bp) encoding for 298 amino acids. Multiple sequence alignments of prohibitin proteins from other arthropods revealed a high degree of amino acid sequence conservation. In silico Illumina read counts and RT-qPCR analyses showed a sex-dependent differential expression, with mRNA levels exhibiting a 1.7-fold (RT-qPCR) increase in adult females compared with adult males. A total of nine single nucleotide polymorphisms (SNPs) were identified, three were located in the 5′ UTR of the Phb2 messenger and six in the ORF, but no mutations associated with sex were found. These results contribute to expand the present knowledge of the reproduction-related genes in C. rogercresseyi , and may be useful in future experiments aimed at controlling the impacts of sea lice in fish farming. [ABSTRACT FROM AUTHOR]

Recent genome-wide association studies and replication analyses reported an association between variants of DENND1A gene and polycystic ovary syndrome (PCOS), mostly in Asians. We therefore examined whether the common DENND1A SNPs rs10818854, rs2479106, and rs10986105 are associated with PCOS in Bahraini Arab population. This case–control study involved 191 women with PCOS diagnosed according to the Rotterdam criteria, and 202 control women. SNP genotyping was performed by the allelic discrimination in real-time PCR. The outcome was that the minor allele frequencies of SNPs rs10818854, rs2479106, and rs10986105 were similar between women with PCOS and control women ( P > 0.05), even before correcting for multiple testing, and none of the tested DENND1A SNPs were associated with PCOS under co-dominant, dominant, or recessive genetic models. None of the tested DENND1A variants were associated with PCOS features (hirsutism, insulin sensitivity, menses pattern, free testosterone, and free androgen index). Taking common GTA haplotype as reference (OR = 1.00), [rs10818854/rs2479106/rs10986105] 3-locus haplotype analysis demonstrated lack of association of any of the DENND1A haplotypes with PCOS, even before correcting for multiple testing. To conclude we demonstrated lack of association of DENND1A SNPs rs10818854, rs2479106, and rs10986105, previously associated with PCOS in Asians, with PCOS in Bahraini Arab women. [ABSTRACT FROM AUTHOR]

To select the molecular markers susceptible to mastitis and reduce the loss induced by mastitis, the PCR-SSCP method was adopted to investigate the correlation between SNPs of the HSP70-2 gene and mastitis in 103 Chinese Holstein. 25 new polymorphisms were detected in this study: 9 SNPs (g.− 115 G → A, g.− 98 T → C, g.117 C → A, g.156 A → C, g.1743 G → A, g.1746 C → T, g.1761 T → G, g.1770 C → G, g.1877 G → C) were found to be associated with mastitis; 2 key SNPs led to amino-acid changes: g.1770 C → G (590 Asp → Glu), g.1877 G → C (626 Gly → Ala). 626 Gly → Ala affected the protein secondary structure. 3 potential cow HSP70-2 proteins were found in all the 103 individuals, but predicted three-dimensional structures of 3 proteins are the same with each other. It is suggested that 9 SNPs increase the susceptibility to mastitis due to their low polymorphisms and can be used as molecular markers to breed the dairy cows resistant to mastitis. [ABSTRACT FROM AUTHOR]

Xinong Saanen (SN) and Guanzhong (GZ) goat breeds were used to detect single nucleotide polymorphisms (SNPs) in the coding regions with their intron–exon boundaries and the proximal flanking regions of KITLG gene by DNA sequencing and genotyped by PCR-restriction fragment (PCR-RFLP). Four novel SNPs (g.12654 G > A , g.12772 G > A , g.12829 T > C and g.23683 C > T ) were identified (GenBank accession No. KM609289). It was shown that Xinong Saanen and Guanzhong goat breeds were in Hardy–Weinberg disequilibrium at g.12654 G > A , g.12772 G > A and g.12829 T > C loci ( P < 0.05). The g.12654 G > A , g.12772 G > A and g.12829 T > C loci were closely linked in both goat breeds ( r 2 > 0.33). Results of an association analysis indicated that SNPs g.12654 G > A , g.12772 G > A and g.12829 T > C had significant effects on litter size ( P < 0.05). The combined genotypes of four SNP loci also affected litter size with the C7( GG/GG/CC/CC ) genotype in the SN goat breed and C1( AA/GG/CC/CC ) and C7( GG/GG/CC/CC ) genotypes in the GZ goat breed having the highest litter size. The biochemical and physiological functions, together with the results obtained in our investigation, suggest that C7( GG/GG/CC/CC ) could be used in marker-assisted selection to select the individuals with higher litter size in both goat breeds. The results extend the spectrum of genetic variation of the caprine KITLG gene, which might contribute to goat genetic resources and breeding. [ABSTRACT FROM AUTHOR]

Insulin receptor substrate (IRS) proteins play key roles in signal transduction in insulin and insulin-like growth factor signaling to control postnatal growth. The fat mass and obesity-associated (FTO) protein also play an essential role in postnatal growth. The aim of this study was to investigate the association between the IRS1 and FTO genes and the regulation of growth traits in rabbits. A total of nine synonymous SNPs were detected in the IRS1 coding sequence using direct sequencing, and the c.189G>T and c.2574G>A SNPs from two linkage disequilibrium blocks were further genotyped for association analysis in 216 New Zealand rabbits. The association results revealed that the TT genotype of c.189G>T and the AA genotype of c.2574G>A were significantly associated with higher body weight at 70 (BW70) and 84 (BW84) days of age and with higher average daily gain (P < 0.05). Linear-regression analysis revealed that the two-gene combination model of FTO c.499G>A and IRS1 c.2574G>A was associated with BW70 and BW84. The combination model of the GA genotype of FTO c.499G>A with the AA genotype of IRS1 c.2574G>A was associated with preferred values for BW70 and BW84. The performance values for the FTO c.499G>A genotypes after stratification with regard to the IRS1 c.189G>T genotypes revealed that the TT genotype of IRS1 c.189G>T reduced the FTO c.499G>A significance associated with BW70 and BW84. Together, our data indicated that the IRS1 gene was associated with growth traits in rabbits. The IRS1 and FTO combination model may be exploited to assist breeders in selecting rabbits with preferred body weight. [ABSTRACT FROM AUTHOR]

ALOX5AP (5-lipoxygenase) has been recognized as a susceptibility gene for stroke. Using a case-control design, the whole coding and adjoining intronic regions of ALOX5AP were sequenced to study the role of SNPs and their interplay with other risk factors in Greek patients with stroke. Patients (n = 213) were classified by the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Their mean age of was 58.9 ± 14.64, comprising 145 males. The control group consisted of 210 subjects, ethnicity, sex and age matched, with no stroke history. Risk factors (hyperlipidemia, hypertension, atrial fibrillation, migraine, CAD, diabetes, smoking and alcohol consumption) were assessed as confounding factors and comparisons were done using logistic regression analysis. SNPs rs4769055, rs202068154 and rs3803277 located in intronic regions of the gene and according to in silico programs EX_SKIP and HSF possibly affecting splicing of exons 1 and 2 of ALOX5AP, showed significantly different frequencies between patients and controls. The genotype frequencies of rs4769055: AA, of rs202068154: AC and of rs3803277: CA were significantly higher (p < 0.001, 0.058) in controls than in patients. The results were indicative of a protective role of the three SNPs either in homozygosity or heterozygosity for MAF and more specifically rs3803277: CA/AA genotypes were protective against SVO stroke subtype. [ABSTRACT FROM AUTHOR]

TBC1D1 plays an important role in numerous fundamental physiological processes including muscle metabolism, regulation of whole body energy homeostasis and lipid metabolism. The objective of the present study was to identify single nucleotide polymorphisms (SNPs) in chicken TBC1D1 using 128 Erlang mountainous chickens and to determine if these SNPs are associated with carcass traits. The approach consisted of sequencing TBC1D1 using a panel of DNA from different individuals, revealing twenty-two SNPs. Among these SNPs, two polymorphisms (g.69307744C>T and g.69307608T>G) of block 1, four polymorphisms (g.69322320C>T, g.69322314G>A, g.69317290A>G and g.69317276T>C) of block 2 and four polymorphisms of block 3 (g.69349746G>A, g.69349736C>G, g.69349727C>T and g.69349694C>T) exhibited a high degree of linkage disequilibrium in all test populations. An association analysis was performed between the twenty-two SNPs and seven performance traits. SNPs g.69307744C>T, g.69340192G>A and g.69355665T>C were demonstrated to have a strong effect on liveweight (BW), carcass weight (CW), semi-eviscerated weight (SEW) and eviscerated weight (EW) and g.69340070C>T polymorphism was related to BW, SEW and BMW in chicken populations. However, for the other SNPs, there were no significant correlations between different genotypes and carcass traits. Meanwhile, haplotype CT-TG of block 1 and combined genotype AG-TT-AC-CT of block 3 were significantly associated with BW, CW, SEW and EW. Overall, our results provide evidence that polymorphisms in TBC1D1 are associated with carcass traits and would be a useful candidate gene in selection programs for improving carcass traits. [ABSTRACT FROM AUTHOR]

Abstract: Insulin-like growth factor 2 receptor (IGF2R) is responsible for degradation of the muscle development initiator, IGF2, and thus it can be used as a marker for selection strategies in the farm animals. The aim of this study was to search for polymorphisms in three coding loci of IGF2R, and to analyze their effect on the growth traits and on the expression levels of IGF2R and IGF2 genes in the gluteus medius muscle of Egyptian buffaloes. A novel A266C SNP was detected in the coding sequences of the third IGF2R locus (at nucleotide number 51 of exon 23) among Egyptian water buffaloes. This SNP was non-synonymous mutation and led to replacement of Y (tyrosine) amino acid (aa) by D (aspartic acid) aa. Three different single-strand conformation polymorphism patterns were observed in the third IGF2R locus: AA, AC, and CC with frequencies of 0.555, 0.195, and 0.250, respectively. Statistical analysis showed that the homozygous AA genotype significantly associated with the average daily gain than AC and CC genotypes from birth to 9mo of age. Expression analysis showed that the A266C SNP was correlated with IGF2, but not with IGF2R, mRNA levels in the gluteus medius muscle of Egyptian buffaloes. The highest IGF2 mRNA level was estimated in the muscle of animals with the AA homozygous genotype as compared to the AC heterozygotes and CC homozygotes. We conclude that A266C SNP at nucleotide number 51 of exon 23 of the IGF2R gene is associated with the ADG during the early stages of life (from birth to 9mo of age) and this effect is accompanied by, and may be caused by, increased expression levels of the IGF2 gene. [Copyright &y& Elsevier]

• Five SNPs in PTPN2 were not significantly associated with CD in Malaysian patients. • Malaysian Chinese with rs487273 G/T genotype have a lower occurrence of CD. • Rs2542152 and rs16939895 are potential biomarkers for disease phenotypes. • Further studies exploring the functional effects of these SNPs are needed. Crohn's disease (CD) is one of the sub-entities of Inflammatory Bowel Disease which causes chronic inflammation in the gastrointestinal tract. The development of CD has shown to have a strong genetic association. Therefore, the present study aimed to investigate the association between genetic polymorphisms in a susceptible locus of CD, the protein tyrosine phosphatase, non-receptor type 2 (PTPN2) gene and the development of CD in Malaysian patients. A total of 137 CD patients and 274 matched healthy controls were recruited in the present study. Genomic DNA was extracted from the venous blood of participants and five targeted single nucleotide polymorphisms (SNPs) in the PTPN2 gene were genotyped using polymerase chain reaction. Associations between the SNPs and CD were determined using Fisher's exact test and odds ratio. Findings showed that all five selected SNPs were not significantly associated with the development of CD in Malaysian patients, which was in contrast to studies among the European populations. Malaysian Chinese with rs487273 heterozygous G/T genotype was found to have a lower occurrence of CD (P -value = 0.0253; OR = 0.4396). Patients with rs2542152 homozygous T genotype were associated with stricturing behaviour (P -value = 0.0302, OR = 2.9944). The rs16939895 A/G genotype was associated with inflammation at the ileum site (P -value = 0.0387, OR = 2.2105) while homozygous G genotype was associated with colonic CD (P -value = 0.0164, OR = 2.3917). Functional studies of these SNPs are needed to evaluate their potential use as a biomarker for disease phenotypes among Asian patients. [ABSTRACT FROM AUTHOR]

• The frequency distribution of a missense mutation (NC_037347.1: c.1543A > G, p.ser515gly) in the SLC45A2 gene is consistent with the distribution of climatic conditions in China. • Association analysis showed this site is closely related environmental indicators. SLC45A2 is involved in the synthesis of melanin transporters. We investigated the association between single nucleotide polymorphisms (SNPs) of the SLC45A2 gene and humidity and hot conditions in indigenous cattle habitat. According to the Bovine Genome Variation Database and Selective Signatures (BGVD), we explored the frequency distribution of a missense mutation (NC_037347.1: c.1543A > G, p.ser515gly) in the SLC45A2 gene in Chinese indigenous cattle. This variation from serine to glycine caused a significant change in the protein modeling structure. PCR and partial DNA sequencing were used to genotype 541 individuals, including 28 Chinese indigenous cattle breeds as well as Angus and zebu. From our results, the mutant allele frequency of this SNP in Chinese native cattle increases gradually from north to south, which is consistent with the distribution of climatic conditions in China. In addition, according to association analysis of a missense mutation (NC_037347.1: c.1543A > G) (rs525805167) in Chinese cattle, it is closely related to the annual average temperature (T), relative humidity (RH), temperature and humidity index (THI) and solar radiation time (P < 0.01). Based on the statistical analysis of the data, we assumed that rs525805167 was associated with heat tolerance traits. Simple Summary: The characteristics of Chinese indigenous cattle are closely related to their climatic environment. In China, Bos taurus is mainly distributed in the northern regions; Bos indicus is mainly distributed in southern China. In addition, the average temperature is higher in the south than in the north, and there are many mixed ancestry breeds of B. taurus and B. indicus in the middle area. The SLC45A2 gene is related to melanin synthesis, which may be closely related to heat tolerance in cattle. The purpose of our study was to investigate whether the SLC45A2 gene is related to heat tolerance in Chinese indigenous cattle. [ABSTRACT FROM AUTHOR]

Abstract: Myostatin (MSTN) is a protein of the Transforming Growth Factor-β (TGF-β) superfamily and plays a crucial role in muscular development for higher vertebrates. However, its biological function in marine invertebrates remains undiscovered. This study characterizes the full-length sequence of the Mytilus chilensis myostatin gene (Mc-MSTN). Furthermore, tissue transcription patterns and putative single nucleotide polymorphisms (SNPs) were also identified. The Mc-MSTN cDNA sequence showed 3528 base pairs (bp), consisting of 161bp of 5′ UTR, 2110bp of 3′ UTR, and an open reading frame of 1257bp encoding for 418 amino acids and with an RXXR proteolytic site and nine cysteine-conserved residues. Gene transcription analysis revealed that the Mc-MSTN has ubiquitous expression among several tissues, with higher expression in the gonads and mantle than in the digestive gland, gills, and hemolymph. Furthermore, high levels of polymorphisms were detected (28 SNPs in 3′-UTR and 9 SNPs in the coding region). Two SNPs were non-synonymous and involved amino acid changes between Glu/Asp and Thr/Ile. Until now, the MSTN gene has been mainly related to muscle growth in marine bivalves. However, the present study suggests a putative biological function not entirely associated to muscle tissue and contributes molecular evidence to the current debate about the function of the MSTN gene in marine invertebrates. [Copyright &y& Elsevier]

Abstract: Dopamine D2 receptor (DRD2) gene, a member of the dopamine receptors gene family, has been studied as a candidate gene for broodiness due to its special effects on avian prolactin secretion. Here, the genomic DNA and cDNA sequences of goose (Anser cygnoides) DRD2 gene were cloned and characterized for the first time. The goose DRD2 cDNA is 1353bp in length and encodes a protein of 450 amino acids. The length of goose DRD2 genomic DNA is 8350bp, including seven exons and six introns. We identified four goose DRD2 variants, which were generated due to alternative splicing. Bioinformatics analysis indicates that all the deduced DRD2 amino acid sequences contain seven putative transmembrane domains and four potential N-glycosylation sites. A phylogenetic tree based on amino acid sequences displays that the goose DRD2 protein is closely related to those of avian species. Semi-quantitative RT-PCR analysis demonstrates that the DRD2-1, DRD2-2 and DRD2-4 transcripts are differentially expressed in the pituitary, ovary, hypothalamus, as well as in the kidney, whereas the DRD2-3 transcript is widely expressed in all the examined tissues at different levels. Meanwhile, 54 single nucleotide polymorphisms (SNPs) and 4 insert-deletion (indel) variations were identified in the coding region and partial intron region of the goose DRD2 gene. Those findings will help us gain insight into the functions of the DRD2 gene in geese. [Copyright &y& Elsevier]

Abstract: Telomeres are critical in maintaining genomic stability and integrity, and telomerase expression in spermatogonial stem cells is responsible for the maintenance of telomere length in the human male germline. Genetic variants in telomere-associated pathway genes might affect telomere length and chromosomal stability, and subsequently disease susceptibility. Thus, we hypothesize that single nucleotide polymorphisms (SNPs) in this pathway could contribute to male infertility risk. In a case–control study of 580 male infertility cases and 580 matched controls, 8 common SNPs in telomerase reverse transcriptase (TERT) and telomerase-associated protein 1 (TEP1) were genotyped. Overall, we found that TERT rs2736100 was inversely associated with male infertility risk (adjusted odds ratio (OR)=0.66, 95% confidence interval (CI): 0.47–0.92; P trend =0.011), whereas TEP1 rs1713449 was positively associated with risk of male infertility (adjusted OR=1.39, 95% CI: 1.20–1.62; P trend <0.001). In addition, subjects carrying risk genotypes of these both loci had a two-fold (95% CI: 1.34–3.15) increase in the risk of male infertility, indicating a significant gene–gene interaction between these two loci (P for multiplicative interaction=0.009). Moreover, linear regression analysis showed that individuals carrying the TEP1 rs1713419 variants have significantly higher levels of sperm DNA fragmentation (β=2.243, P =0.016). In conclusion, our results give the first evidence that genetic variations of TERT rs2736100 and TEP1 rs1713449 were associated with susceptibility to male infertility. [Copyright &y& Elsevier]

Abstract: Next generation sequencing technologies have proven to be a rapid and cost-effective means to assemble and characterize gene content and identify molecular markers in various organisms. Pepper (Capsicum annuum L., Solanaceae) is a major staple vegetable crop, which is economically important and has worldwide distribution. High-throughput transcriptome profiling of two pepper cultivars, Mandarin and Blackcluster, using 454 GS-FLX pyrosequencing yielded 279,221 and 316,357 sequenced reads with a total 120.44 and 142.54Mb of sequence data (average read length of 431 and 450 nucleotides). These reads resulted from 17,525 and 16,341 ‘isogroups’ and were assembled into 19,388 and 18,057 isotigs, and 22,217 and 13,153 singletons for both the cultivars, respectively. Assembled sequences were annotated functionally based on homology to genes in multiple public databases. Detailed sequence variant analysis identified a total of 9701 and 12,741 potential SNPs which eventually resulted in 1025 and 1059 genotype specific SNPs, for both the varieties, respectively, after examining SNP frequency distribution for each mapped unigenes. These markers for pepper will be highly valuable for marker-assisted breeding and other genetic studies. [Copyright &y& Elsevier]

Abstract: Bone morphogenetic proteins (BMPs) are members of the TGF-β (transforming growth factor-beta) superfamily, of which BMP4 is the most important due to its crucial role in follicular growth and differentiation, cumulus expansion and ovulation. Reproduction is a crucial trait in goat breeding and based on the important role of BMP4 gene in reproduction it was considered as a possible candidate gene for the prolificacy of goats. The objective of the present study was to detect polymorphism in intronic, exonic and 3′ un-translated regions of BMP4 gene in Indian goats. Nine different goat breeds (Barbari, Beetal, Black Bengal, Malabari, Jakhrana (Twinning>40%), Osmanabadi, Sangamneri (Twinning 20–30%), Sirohi and Ganjam (Twinning<10%)) differing in prolificacy and geographic distribution were employed for polymorphism scanning. Cattle sequence (AC_000167.1) was used to design primers for the amplification of a targeted region followed by direct DNA sequencing to identify the genetic variations. Single nucleotide polymorphisms (SNPs) were not detected in exon 3, the intronic region and the 3′ flanking region. A SNP (G1534A) was identified in exon 2. It was a non-synonymous mutation resulting in an arginine to lysine change in a corresponding protein sequence. G to A transition at the 1534 locus revealed two genotypes GG and GA in the nine investigated goat breeds. The GG genotype was predominant with a genotype frequency of 0.98. The GA genotype was present in the Black Bengal as well as Jakhrana breed with a genotype frequency of 0.02. A microsatellite was identified in the 3′ flanking region, only 20 nucleotides downstream from the termination site of the coding region, as a short sequence with more than nineteen continuous and repeated CA dinucleotides. Since the gene is highly evolutionarily conserved, identification of a non-synonymous SNP (G1534A) in the coding region gains further importance. To our knowledge, this is the first report of a mutation in the coding region of the caprine BMP4 gene. But whether the reproduction trait of goat is associated with the BMP4 polymorphism, needs to be further defined by association studies in more populations so as to delineate an effect on it. [Copyright &y& Elsevier]

Abstract: Medicinal plants of the Panax genus belonging to Araliaceae family are well-known, rare plants used as tonics in traditional Chinese medicine and have been described in the Chinese Pharmacopoeia. Because of the high price and the huge human demand, these commercial products often contain adulterants. In this study, 377 sequences from four species were analyzed. Single nucleotide polymorphisms (SNPs) were detected and patterns of intragenomic variation in internal transcribed spacer 2 (ITS2) from the four Panax species were studied. Intraspecific variations were analyzed based on three typical DNA barcodings (ITS2, matK and psbA-trnH). Results from this study revealed that intraspecific genetic distances in Panax ginseng and Panax quinquefolius were quite low (0–0.002) and the multi-copy ITS2 could be considered a single locus in the genomes of these two species. Five stable SNPs were detected in ITS2 region to identify the Panax medicinal species. Considering the mixed powder of P. ginseng and P. quinquefolius, double peaks could be clearly examined at SNP positions and the height of the peaks could indicate the mixed ratio roughly. Our findings indicate that SNP-based molecular barcodes could be developed as a routine method for the identification of the Panax genus with closely related species and the mixed powder P. ginseng and P. quinquefolius. [Copyright &y& Elsevier]

Abstract: Developmental Dyslexia (DD) is a heritable, complex genetic disorder characterized by specific impairment in reading and writing ability that is substantially below the expected reading ability given the person's chronological age, measured intelligence and age-appropriate education. More than ten susceptible genes have been identified for DD. A Single Nucleotide Polymorphism (SNP) of these genes was found to be associated with various phenotypes of DD. To identify the role of SNPs of four candidate genes namely, MRPL19/C2ORF3, ROBO1 and THEM2 in an Indian population, we genotyped eight SNPs of these genes in 157 children with DD and 212 normal readers using a MassARRAY technique with a MALDI-TOF MS analyzer. Power analysis of some of these SNPs showed >80% of power. Chi-square test, Odds Ratios (ORs), 95% Confidence Intervals (CIs) and Bonferroni's correction were applied to identify the significance of the genotyped SNPs and haplotypes. Our study failed to show any association of SNPs and haplotypes of these genes with DD in an Indian population. [Copyright &y& Elsevier]

Abstract: Fat mass and obesity associated (FTO) gene is an excellent candidate to affect the fatness and growth-related traits in pig and cattle. The aim of this study was to reveal the association between FTO and growth and meat quality traits in rabbits. A total of eight coding SNPs were detected, and four SNPs of them in exon 3 were further genotyped for association analysis in 442 rabbits from three breeds, including 248 New Zealand rabbits, 92 Ira rabbits, and 102 Champagne rabbits. Because there were significant differences for the allele and genotype frequencies among breeds, the association analysis was independently conducted in each breed only for these SNPs with minor allele frequency >5.0%. The results revealed that non-synonymous SNP c.499G>A (p.A167T) was significantly associated with body weight (BW) at 35, 70, and 84days of age in New Zealand rabbits (P <0.01). The CC genotype of synonymous SNP c.660T>C was significantly associated with higher BW84, average daily weight gain, and intramuscular fat content of longissimus lumborum than TT and TC genotypes in Ira rabbits (P <0.05). There were no associations between the four SNPs and growth and meat quality traits in Champagne rabbits. Meanwhile, FTO SNPs were not associated with meat pH value. Our data indicated that FTO gene could be a candidate gene associated with growth and meat quality traits in rabbits. However, the breed-specific effect should be carefully taken into consideration. [Copyright &y& Elsevier]

Abstract: Diabetic nephropathy (DN) is a major diabetic complication. However, the initiating molecular events triggering DN are unknown. MicroRNAs (miRNAs) have recently been identified as regulators that modulate the target gene expression and are involved in DN. However, the evidence of the mechanism is still insufficient in human samples. In this study, microRNA microarray assay was used to study gene differential expression profiles in DN and diabetes mellitus (DM) patients. One of the specific differentially expressed microRNAs, let-7a, was down-expressed in DN. Additionally, the expression of let-7a was also decreased in DN by real-time RT PCR in the patients' samples. Moreover, single nucleotide polymorphism (SNP) analysis was used to evaluate the relationship between three SNPs in the regulatory region of let-7a-2 gene and the risk of DN in the Chinese Han population by means of PCR-restriction fragment length polymorphism (RFLP-PCR). Also, the genotype and allele frequencies of let-7a-2 polymorphism were tested in 274 individuals, including 108 DN, 104 DM patients and 62 health control individuals (CON). It was found that a variant rs1143770 and the distributions of CT/TT genotypes were significantly different in three groups, and the CT+TT genotypes frequencies were significantly higher in DN and DM groups than that in CON group. In conclusion, let-7a-2 might participate in the regulation of the occurrence of DN, and a potential variant rs1143770 was significantly associated with the increased risk for DN. [Copyright &y& Elsevier]

Our previous studies identified a functional SNP, R952Q in the LRP8 gene, that was associated with increased platelet activation and familial and early-onset coronary artery disease (CAD) and myocardial infarction (MI) in American and Italian Caucasian populations. In this study, we analyzed four additional SNPs near R952Q (rs7546246, rs2297660, rs3737983, rs5177) to identify a specific LRP8 SNP haplotype that is associated with familial and early-onset CAD and MI. We employed a case–control association design involving 381 premature CAD and MI probands and 560 controls in GeneQuest, 441 individuals from 22 large pedigrees in GeneQuest II, and 248 MI patients with family history and 308 controls in an Italian cohort. Like R952Q, LRP8 SNPs rs7546246, rs2297660, rs3737983, and rs5177 were significantly associated with early-onset CAD/MI in both population-based and family-based association studies in GeneQuest. The results were replicated in the GeneQuest II family-based population and the Italian population. We then carried out a haplotype analysis for all five SNPs including R952Q. One common haplotype (TCCGC) was significantly associated with CAD (P =4.0×10−11) and MI (P =6.5×10−12) in GeneQuest with odds ratios of 0.53 and 0.42, respectively. The results were replicated in the Italian cohort (P =0.004, OR=0.71). The sib-TDT analysis also showed significant association between the TCCGC haplotype and CAD in GeneQuest II (P =0.001). These results suggest that a common LRP8 haplotype TCCGC confers a significant protective effect on the development of familial, early-onset CAD and/or MI. [ABSTRACT FROM AUTHOR]

Abstract: Genome-wide association studies (GWAS) have successfully identified many genetic variants associated with complex diseases and traits. However, functional consequence of genetic variants studied in GWAS is not yet fully investigated, which would hinder the application of GWAS. We therefore performed a systematic functional analysis of HapMap SNPs, which have been most commonly used as the reference panel for GWAS. Our study highlights several characteristics of HapMap SNPs and identifies subsets of genetic variants with interesting functional implication. The results show that HapMap SNPs have good coverage within RefSeq genes, especially within known disease-related genes. On the other hand, only a small percentage of SNPs are non-synonymous SNPs while many SNPs are actually located at gene deserts. Moreover, many functionally important variants are not yet still interrogated. A redesigned SNP reference panel with additional functionally important variants would be useful to identify disease-causal variants in the future genome-wide studies. [Copyright &y& Elsevier]