SHEsis Software Research Articles

A preliminary report to discern the association of SNPs rs1505287 and rs4858608 of THRB gene and their haplotype analysis with hypothyroidism and hyperthyroidism among Indian population: A case-control study.

Thyroid hormone receptors are a subtype of nuclear receptors that are necessary for the actions of thyroid hormones and play a crucial role in regulating the negative feedback mechanism of the hypothalamus-pituitary-thyroid (HPT) axis. The thyroid hormone receptor beta (THRB) is present in two isoforms, both of which are expressed in several tissues across the body. The current study aims to demonstrate a correlation between two single nucleotide polymorphisms (SNPs), namely rs1505287 (G > A) and rs4858608 (T > G), of the THRB gene and the occurrence of hypothyroidism and hyperthyroidism among the Indian population. Additionally, the study investigates the relationship between these SNPs and their haplotypes. This study consists of a total of 350 samples, with 140 (73females,67males) being healthy controls, 120 (81females,39males) being hypothyroid patients, and 90 (59females,31males) being hyperthyroid patients. An automated analyzer was utilized to measure biochemical parameters, and the PCR-RFLP technique was employed to determine genotypes. For statistical analysis, SPSS software was utilized, and SHEsis software was employed to run a haplotype analysis. The frequency of the minor allele of rs1505287 is higher among hypothyroid patients, whereas the minor allele of rs4858608 is more common among control participants. No apparent genetic variance was seen for any of the SNPs when comparing control and hyperthyroid patients. The presence of H1 (A-T) and H4 (G-G) was shown to have a strong correlation with hypothyroidism, as indicated by the low p-values of 0.003482 and 0.003342, respectively. The study concludesthat allele G of rs4858608 is a protective factor against hypothyroidism, whereas allele A of rs1505287 is a risk factor for a susceptibility to hypothyroidism. None of them have been found to be linked with hyperthyroidism. This study implies the involvement of genetic variations of thyroid hormone receptors in thyroid disorders.

Gender-Dependent Associations Between Digit Ratio and Genetic Polymorphisms, BMI, and Reproductive Factors

The digit ratio (2D:4D) has been associated with prenatal hormonal influences and various traits and pathologies. This article explores the relationship between 2D:4D and a series of common polymorphisms and Torque Teno Viruses. In this study, 120 healthy participants were included. The IGF2 Apa I, ACE I/D, INS -23 Hph I, VDR Fok I, VDR Apa I, VDR Taq I, AT1R A1166C polymorphism were genotyped by PCR-RFLP technique, and the IL-6 -174 G/C polymorphism by tetra-primer ARMS-PCR. The presence of TTV was identified by a hemi-nested PCR technique. Haplotype analyses were performed using the SHEsis software. The average 2D:4D values were similar for men and women. Overweight men presented higher 2D4D ratios than normal-weight women (p 0.05). Lower 2D:4D values were recorded in women with pregnancy loss or one child or none (p 0.001). Men with lower 2D4D ratios reported a higher number of children (p 0.001). The IGF2 GG and ACE DD were associated with a higher digit ratio in all subjects and in the women’s subset. A significant association was found in men between 2D:4D and the INS-23 Hph I – IGF2 Apa I T-G haplotype (p 0.01). The data obtained in this study indicate a sexual dimorphism for the digit ratio. The associations between 2D:4D and the genetic polymorphisms studied could be influenced by gender.

Association analysis of HSP90AA1 polymorphism with thermotolerance in tropically adapted Indian crossbred cattle.

Raising cattle is a lucrative business that operates globally but is confronted by many obstacles, such as thermal stress, which results in substantial monetary losses. A vital role of heat shock proteins (HSPs) is to protect cells from cellular damage. HSP90 is a highly prevalent, extremely adaptable gene linked to physiological resilience in thermal stress. This study aimed to find genetic polymorphisms of the HSP90AA1 gene in Karan Fries cattle and explore their relationship to thermal tolerance and production traits. One SNP (g.3292A > C) was found in the Intron 8 and three SNPs loci (g.4776A > G, g.5218T > C and g.5224A > C) were found in the exon 11 of 100 multiparous Karan Fries cattle. The association study demonstrated that the SNP1-g.3292A > C was significantly (P < 0.01) linked to the variables respiratory rate (RR), heat tolerance coefficient (HTC) and total milk yield (TMY (kg)) attributes. There was no significant correlation identified between any of the other SNP sites (SNP2-g.4776A > G; SNP3-g.5218T > C; SNP4-g.5224A > C) with the heat tolerance and production attributes in Karan Fries cattle. Haploview 4.2 and SHEsis software programs were used to analyse pair linkage disequilibrium and construct haplotypes for HSP90AA1. Association studies indicated that the Hap3 (CATA) was beneficial for heat tolerance breeding in Karan Fries cattle. In conclusion, genetic polymorphisms and haplotypes in the HSP90AA1 were associated with thermal endurance attributes. This relationship can be utilized as a beneficial SNP or Hap marker for genetic heat resistance selection in cow breeding platforms.

Association between Methylenetetrahydrofolate Reductase (MTHFR) and 5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase (MTRR) Polymorphisms in Iraqi Patients with COVID-19.

The methylenetetrahydrofolate reductase (MTHFR) gene is an essential gene in the metabolism of folate-homocysteine. Recently, the level of homocysteine was found to be a significant marker in the follow-up of COVID-19 infection. Thus, this study aimed to detect the effect of genetic polymorphisms for single nucleotide polymorphisms (SNPs) (c.66A>G, c.1298A>C, and c.677CT) on COVID-19 infection. Blood samples were collected from 270 patients with COVID-19 in the medical center of Al-Shifa (Baghdad, Iraq) from November 2020 to March 2021. Tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) technique was used for the detection of genotypes of SNPs. The odds ratio (OR) was used to detect the relationship between SNPs and COVID-19 infections. Haplotype analysis was performed by SHEsis software. There was a significant difference between mild/moderate cases and severe/critical cases for ages (35-45), (46-55), and (56-65) years (P<0.0001, P=0.01, and P=0.006, respectively). The results showed significant differences in the T allele for SNP c.677>C (P<0.0001 and OR=4.58). The C allele for SNP c.1298A>C indicated significant differences (P<0.001 and OR=3.15). Besides, the G allele for SNP c.677C>T showed significant differences (P<0.001 and OR=6.64). Consequently, these SNPs showed a predisposition to the development of COVID-19 infection. With regard to the C-A-A, T-A-A and T-C-G haplotypes indicated significant differences between the control and patient groups. The C-A-A was related to a decreased risk and indicated a protective effect against COVID-19 infection development (P<0.0001 and OR=0.218). The increased risk was associated with T-A-A and T-C-G haplotypes and indicated the risk impact on COVID-19 infection development (P<0.0001, P=0.004, and OR=15.5, OR=6.772, respectively). Furthermore, the linkage disequilibrium (LD) for SNPs was studied, and the complete D' value was 99. The genetic polymorphisms of SNPs (c.66A>G, c.1298A>C, and c.677C>T) in the Iraqi population were associated with COVID-19 infection.

Correlation of TBX21 gene polymorphisms with ankylosing spondylitis in a Chinese population.

Genome-wide association studies analysis has revealed associations between ankylosing spondylitis (AS) and loci on the TBX21 gene across various populations. This study aimed to investigate if there is a connection between a higher risk of AS in a Chinese population and two polymorphism loci on the TBX21 gene. To achieve this, we performed a case-control investigation involving 363 patients with AS and 907 healthy individuals. Genotyping was carried out using the iPLEX Gold genotyping assay. The analysis of genotypes and haplotypes was performed using SPSS 23.0 and SHEsis software. The results revealed no statistically significant correlation between the two specified single-nucleotide polymorphisms of TBX21 (rs11657479 C/T and rs4794067 C/T) and susceptibility to AS. However, upon conducting stratification analysis, our findings demonstrated a significant association between rs11657479 and susceptibility to human leucocyte antigen (HLA)-B27+ AS in allelic (C vs. T: odds ratio [OR]=1.52, 95%CI=1.09-2.11, corrected p [pc]=.028), heterozygous (CT vs. TT: OR=1.63, 95%CI=1.13-2.34, pc=.016) and dominant (CT+CC vs. TT: OR=1.60, 95%CI=1.12-2.28, pc=.018) models. Furthermore, the haplotype rs4794067/C-rs11657479/C of TBX21 was found to increase the risk of HLA-B27+ AS cases. In conclusion, our findings indicate a correlation between TBX21 gene polymorphism and HLA-B27+ AS patients within the Chinese population.

The SNTB1 and ZFHX1B gene have susceptibility in northern Han Chinese populations with high myopia

The aim of this study was to explore the association between SNTB1 and ZFHX1B polymorphisms and high myopia (HM) in a Northern Han Chinese population. This case-control study included 457 HM and 860 healthy subjects from the Northern Han Chinese population. Four single nucleotide polymorphisms (SNPs) (rs7839488, rs4395927, rs4455882, and rs6469937) in SNTB1 and one SNP in ZFHX1B (rs13382811)were selected based on two previous genome-wide association study (GWAS) studies. The allele and genotype distributions of SNPs in SNTB1 and ZFHX1B were compared between the two groups using the chi-square test. The allele results were adjusted for age and sex using Plink software (Plink 1.9). Pairwise linkage disequilibrium (LD) and haplotype analyses were performed using SHEsis software. For HM subjects, the mean age was 44.80 ± 17.11 years, and for the control subjects, it was 44.41 ± 14.26 years. For rs7839488 of the SNTB1 gene, the A allele is a risk allele and the G allele is a wild allele. The A allele had no statistical significance with the HM cases and controls (OR = 0.90, 95% CI = 0.74–1.09, aP = 0.273, Pc = NS). There was a LD in SNTB1 (rs7839488, rs4395927, rs4455882, and rs6469937). The G-C-A-G haplotype frequency was higher in HM subjects than that of the controls (OR = 1.31, 95% CI = 1.07–1.60, P = 0.008). Meanwhile, the A-T-G-A haplotype frequency was slightly lower in the HM group (OR = 0.81, 95% CI = 0.66–0.99, P = 0.048). In the ZFHX1B gene, the frequency of the minor T allele of rs13382811 was significant higher in the HM group than in the control group (OR = 1.34, 95% CI = 1.11–1.61, aP = 0.001, Pc = 0.009). Furthermore, compared to the CC genotype, there were significant differences in the CT genotype (OR = 1.57, 95% CI = 1.23–2.00, aP < 0.001, Pc = 0.002). In conclusion, G-C-A-G is a risk haplotype from the SNTB1 gene in high myopia patients. The minor T-allele of ZFHX1B rs13382811 is a risk factor for high myopia. SNTB1 and ZFHX1B are both risk genes associated with increased susceptibility to high myopia in the Northern Han Chinese population.

Associations between polymorphisms in the cannabinoid receptor 1 gene, cognitive impairments and tardive dyskinesia in a Chinese population with schizophrenia

ObjectiveTardive dyskinesia (TD) is a medically induced movement disorder that occurs as a result of long-term use of antipsychotic medications, commonly seen in patients with schizophrenia (SCZ). The study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) of the CNR1 gene, TD and cognitive impairments in a Chinese population with SCZ. MethodsA total of 216 SCZ patients were recruited. The participants were divided into TD and without TD (WTD) groups using the Schooler-Kane International Diagnostic Criteria. The severity of TD was assessed using the Abnormal Involuntary Movement Scale (AIMS). Cognitive function was assessed using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) scale. Hardy-Weinberg equilibrium tests, chained disequilibrium analyses and haplotype analyses were performed using SHE-sis software. To explore the main effects of TD diagnosis, genotype and cognitive function, as well as interaction effects, analysis of covariance (ANCOVA) was employed. ResultsThe prevalence of TD was approximately 27.3%. Significant differences were observed in the rs806368 CT genotype and rs806370 TC genotype within the hypercongenic pattern between the male TD and WTD groups (OR = 2.508, 95% CI: 1.055–5.961, p = 0.037; OR = 2.552, 95% CI: 1.073–6.069, p = 0.034). Among TD patients, those carrying the rs806368 CC genotype exhibited higher limb trunk scores (p < 0.05). Moreover, there was a statistically significant difference in visuospatial/construction between the TD and WTD groups (p = 0.04), and a borderline significant difference in visuospatial/construction when considering the interaction between TD diagnosis and genotype at the rs806368 locus (p = 0.05). ConclusionCNR1 rs806368 and rs806370 polymorphisms may play a role in TD susceptibility. Additionally, CNR1 gene polymorphisms were associated with the severity of involuntary movements and cognitive impairments in TD patients.

Vitamin-d receptor (VDR) polymorphism and types of HBV related liver disease along with an SVM based disease prediction model

BackgroundPolymorphism in genes associated with Vitamin-D metabolism and its receptor molecule altogether modulates the level of active serum Vitamin-D level and as such serves as potent immune modulator. Impact of this polymorphism on outcome of HBV related liver disease is poorly understood till date. This study focus on analysing the VDR polymorphism (TaqI, ApaI, and BsmI) and its associated molecules GC-Globulin and CYP2R1 among HBV infected patients and its probable correlation with disease progression. Method and resultsThree hundred forty HBV infected patients belonging to three distinct clinical groups, Acute Viral hepatitis (AVH, n = 205), Chronic Hepatitis (CH, n = 84) and hepatocellular carcinoma (HCC, n = 51) along with 102 healthy control were included in the study. VDR, GC and CYP2R1 polymorphism were genotyped by PCR-RFLP method followed by Sanger sequencing. Haplotype distribution was analyzed using SHEsis software. Logistic regression analysis was performed to find the association between different genotype and VDR haplotype with progression of liver disease. Further, an SVM based prediction model has also been described in detection of different disease stage. ConclusionApa-I CC genotype was more frequently observed among chronic HBV patients and HCC than the acute cases among North east Indian population (OR = 2.241, C·I = 0.504–5.558. p = 0.001). The occurrence of bAt haplotype was also found to be significantly higher among Chronic (p = 0.004) and HCC (p = 0.001 < 0.05) cases in comparison to acute cases. Further, logistic regression analysis after adjusting covariates like age, gender, serum AST/ALT level, serum albumin and platelet count, showed that Apa-I CC genotype and bAt haplotype were independent predictors for advancement of acute to chronic HBV infection and further. The SVM based prediction model using similar covariates also predicts the different disease stage with 90% accuracy.

Single nucleotide polymorphism, haplotypes and genotypes of Mannose-binding lectin (MBL1) gene and their association with clinical mastitis in Murrah buffalo

The Mannose-binding lectin (MBL1) gene is an important component of immune response system. It plays vital role in activation of the complement system and act as chief defense molecule of host cell to provide protection against various diseases. In the recent study, six novel single nucleotide polymorphisms (SNPs), at 2689G&gt;C, 2751A&gt;G, 4822T&gt;C, 4853A&gt;G, 4855T&gt;C, and 4978T&gt;C resulted in 2 non synonymous type of change at 4853A&gt;G, 4855T&gt;C resulting in one amino acid substitution Ser150Gly of MBL1 protein and their association with clinical mastitis were investigated in two hundred (200) Murrah buffaloes. These SNPs in MBL1 were genotyped by using the polymerase chain reaction (PCR) and Deoxyribose nucleic acid (DNA) sequencing methods in order to reveal the association with clinical mastitis. SHEsis software tool was used for construction of haplotypes and Linkage disequilibrium analysis. Twenty one (21) haplotypes were constructed. Allelic association analysis showed that C allele of 2689 G&gt;C, A allele of 2751 A&gt;G, C allele of 4822 T&gt;C, A allele of 4853 A&gt;G, C allele of 4855 T&gt;C, and C allele of 4978 T&gt;C had significant association with increased risk of clinical mastitis in Murrah buffaloes (P&lt;0.05). Murrah buffaloes with CG genotype of 2689 G&gt;C, AG or GG genotype of 2751 A&gt;G, CC genotype of 4822T&gt;C, AG or GG genotype of 4853 A&gt;G, TC or CC genotype of 4855 T&gt;C and CC genotype of 4978 T&gt;C loci had significantly lower incidence of clinical mastitis compared to their counter genotypes. Haplotype association analysis showed that Hap21 (TATTGA) was found significantly related to higher risk of clinical mastitis (P&lt;0.05). Hap14 (TGTTGG) and Hap5 (CGCCCA) were found significantly associated with lower risk of clinical mastitis in Murrah buffalo (P&lt;0.05).

Association of TBX21 gene polymorphisms and acute anterior uveitis risk in a Chinese population: A case-control study

Copy number variations (CNVs) in TBX21 gene have been reported to be significantly and positively correlated with acute anterior uveitis (AAU). Our study was performed to further determine whether single nucleotide polymorphisms (SNPs) in TBX21 gene confer susceptibility to AAU in a Chinese population. In our case-control study, 420 AAU patients and 918 healthy controls were included. SNP genotyping was conducted via the MassARRAY™ iPLEX Gold platform. Association and haplotype analyses were performed via SPSS 23.0 and SHEsis software. No significant association was observed between two candidate SNPs of TBX21 gene (rs4794067, rs11657479) and susceptibility to AAU (Pc > 0.05). In stratification analysis, the result also showed no significant difference between the HLA-B27 positive AAU patients and non-typed healthy controls. Additionally, no association was detected between TBX21 haplotypes and AAU risk. In conclusion, the polymorphisms rs4794067 and rs11657479 in TBX21 gene did not confer disease susceptibility to AAU in a Chinese population.

Correlation Analysis between c.1365-13T>C and c.406C>T Single Nucleotide Polymorphism and the Risk of G6PD Deficiency

To investigate the possible association between c.1365-13T>C, c.406C>T polymorphism and G6PD deficiency in the population of Guangxi by the methods of case-control study. Meanwhile to investigate the mutation frequency of these two gene loci in population of Guangxi. The activity levels of G6PD and c.1365-13T>C, c.406C>T polymorphism were detected in 417 patients with G6PD deficiency and 295 healthy controls. The correlation between genotypes, alleles and G6PD activity levels was analyzed using statistical methods, and the haplotype frequencies at the two loci was analyzed using online SHEsis software. The frequencies of CC genotype (P=0.001, OR=2.684) and C allele (P=0.002, OR=1.681) of c.1365-13T>C in patients with G6PD deficiency were significant lower than those in the controls, the frequency of dominant model TT+TC vs CC（P=0.001, OR=2.694） in the G6PD deficiency group was higher than that in the control group, and the differences were statistically significant. The differences of genotype and allele frequencies in c.406C>T between G6PD deficiency patients and controls had no statistical significance (all P>0.05). Haplotype analysis showed that there were significant correlations between C-C, T-C haplotypes and G6PD expression levels. In G6PD deficiency group, patients with c.1365-13T>C TC genotype had higher levels of G6PD activity, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) compared with patients with TT genogype, but the values of red cell distribution width-coefficient of variation (RDW-CV) was lower than those in TT genotype patients, and the differences were statistically significant (P<0.05). While patients with c.1365-13T>C CC genotype had lower levels of G6PD activity compared with patients with TT genogype, but the values of MCV and MCH were higher than those in TT genotype patients (P<0.05). The average values of hematocrit(HCT), MCV, MCH and red blood cell distribution width-standard deviation (RDW-SD) in patients with c. 406C> T TT genotype were significantly higher than those in patients with c. 406C> T CC genotype.(all P<0.05). The association between G6PD c.1365-13T>C and the activity levels of G6PD is statistically significant, which is worth further study.

Association study of PCSK9 SNPs (rs505151 & rs562556) and their haplotypes with CVDs in Indian population

Background Cardiovascular disease (CVD) has emerged as the most prevalent cause of death in India. Pro-protein Convertase Subtilisin/Kexin Type 9 (PCSK9) gene has been found to be associated with lipid levels and a biomarker for susceptibility of CVD. Aim To study the association of PCSK9 SNPs rs505151 & rs562556 and their haplotypes with CVDs in the Indian population. Subjects & methods The present study comprised of 102 angiographically proven CVD patients & 100 healthy subjects. To study polymorphism, Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) method was used. Biochemical parameters were analysed by enzymatic methods or automated analysers. Haplotype analysis was done using SHEsis software. Results The dominant genetic model with an odds ratio (confidence interval) of 4.71 (2.59 − 8.5), (p value = .0001), shows the risk of CVDs. However, rs562556 (I474V) variant was not found to be associated with clinical parameters and risk of CVDs (p value >.05). Out of four haplotypes, H3 (G-A) was found to be associated with the CVDs (OR- 3.137, p value = .0001). Conclusion This study concludes that G allele of rs505151 SNP (PCSK9) and the H3 (G-A) haplotype of rs505151 & rs562556 were found to be risk factors for CVDs in the Indian population.

Association between the cashmere production performance, milk production performance, and body size traits and polymorphism of COL6A5 and LOC102181374 genes in Liaoning cashmere goats

The purpose of this study was to analyze the relationship between COL6A5 (collagen type VI alpha 5 chain) and LOC102181374 (alcohol dehydrogenase 1) genes and the production performance of Liaoning cashmere goats by single nucleotide polymorphism (SNP). We have searched for SNP loci of COL6A5 and LOC102181374 genes through sequence alignment and PCR experiments, and have used SPSS and SHEsis software to analyze production data. We obtained five SNP loci in total, including three SNP loci (G50985A, G51140T, G51175A) in COL6A5 gene and two SNP loci (A10067G, T10108C) in LOC102181374 gene. The genotypes G50985A (AG), G51140T (GT), G51175A (AA), A10067G (AA), and T10108C (CC) of these loci have certain advantages in improving the production performance of Liaoning cashmere goats. The haplotype combinations that can improve production performance in COL6A5 gene were H1H5:AGGGAG, H4H4:GGGGAA, and H4H4:GGGGAA. H3H3:GGCC and H2H4:AGTT were the dominant combinations in LOC102181374 gene. At G51175A and A10067G loci, we found that H1H2:AAAG and H1H3:AGAA have dominant effects. These results may provide some support for the molecular breeding of production traits in Liaoning cashmere goats.

Evaluation of loci to predict ear morphology using two SNaPshot assays.

Human ear morphology prediction with SNP-based genotypes is growing in forensic DNA phenotyping and is scarcely explored in Pakistan as a part of EVCs (externally visible characteristics). The ear morphology prediction assays with 21 SNPs were assessed for their potential utility in forensic identification of population.The SNaPshot™ multiplex chemistries, capillary electrophoresis methods and GeneMapper™ software were used for obtaining genotypic data. A total of 33 ear phenotypes were categorized with digital photographs of 300 volunteers. SHEsis software was applied to make LD plot. Ordinal and multinomial logistic regression was implemented for association testing. Multinomial logistic regression was executed to construct the prediction model in 90% training and 10% testing subjects.Several influential SNPs for ear phenotypic variation were found in association testing. The model based on genetic markers predicted ear phenotypes with moderate to good predictive accuracies demonstrated with the area under curve (AUC), sensitivity and specificity of predicted phenotypes.As an additional EVC, the estimated ear phenotypic profiles have the possibility of determining the human ear morphology differences in unknown biological samples found in crimes that do not result in a criminal database hit. Furthermore, this can help in facial reconstruction and act as an investigational lead.

TMPRSS6 gene mutations in six Saudi families with iron refractory iron deficiency anemia

Iron-refractory iron deficiency anemia (IRIDA) is considered an autosomal recessive iron deficiency anemia due to mutations in the transmembrane protease serine 6 (TMPRSS6) gene. Variations in iron parameters and a higher risk of iron deficiency have been linked to the TMPRSS6 mutations. Furthermore, human genome-wide association studies (GWAS) identified a common mutation (rs855791) linked to abnormal hematological parameters, highlighting the importance of the TMPRSS6 gene in the regulation of iron homeostasis. This is the first study to investigate TMPRSS6 gene mutation in six Saudi families of probands with iron deficiency anemia unresponsive to oral iron and partially responsive to parenteral iron administration. Each participant provided a vacutainer tube with three blood samples (2.5 ml each) and analyzed based on hematological, biochemical iron profiles, and followed by genotyping by PCR. The TMPRSS6 gene was amplified, sequenced, and analyzed in all probands and family members. Statistical analysis was done using SPSS and SHEsis software. Few functional mutations in these families were suggested (p.W73X, p.E523K and p.V736A). The proband of family 6 presented numerous hematological abnormalities upon initial consultation, including normocytic anemia accompanied by low Hb, normal MCV, low serum iron, low serum ferritin, and normal TIBC. While the p.W73X variant was only found in 2 families, the p.V736A variant was found in all examined Saudi families with IRIDA. Given the evidence outlined for these six cases, future genotype-phenotype correlation studies in a large number of IRIDA patients in Saudi Arabia may be very informative for patient management, in addition to increasing knowledge of TMPRSS6 function during development as well as factors in the regulation of TMPRSS6 and its effect on iron levels in the body.

Association analysis for SNPs of MSTN and IGFBP-3 genes with body size and other production traits in Liaoning Cashmere Goats

Liaoning cashmere goat (LCG) have tall bones, high cashmere production and outstanding meat production performance. In recent years, good breeding progress has not been made in terms of body size, meat yield, milk yield and other properties in terms of production. The study focused on the correlation between the SNPs of MSTN and IGFBP-3 genes with the body size performance, cashmere production and milk performance. The MSTN and IGFBP-3 gene sequence alignment and PCR-Seq polymorphism were used to detect the potential SNPs, and the correlation with production performance was analyzed by SPSS and SHEsis software. The results showed that the TT genotype at the T1662G locus of the MSTN gene is dominant and has significant advantages in body measurements such as sacrum height, chest width, and waist height. The C allele at the C4021T locus of IGFBP-3 gene shows an advantage in the body measurement performance. Among the haplotype combinations, H2H2:TGTC is preponderant combination for body size performance, H2H2:TGTC and H1H2:TGCC are preponderant combinations for cashmere production performance, H1H3:GGCC is preponderant combination for milk production performance. It may be a molecular marker for future selection and breeding.

Lack of Association Between PDCD-1 Polymorphisms and Colorectal Cancer Risk: A Case-Control Study

ABSTRACT Functional variants of immune-related genes may be implicated in the occurrence of colorectal cancer (CRC). In this study, Programmed cell death (PDCD)-1.6 (rs10204525 T/C), PDCD-1.7 (rs7421861 A/G), and PDCD-1.9 (rs2227982 A/G) loci were selected to explore gene expression and the potential susceptibility to the development of CRC. Here, 1,003 CRC patients and 1,303 controls were included and three PDCD-1 tagging loci were selected and analyzed by using SNPscan genotyping assays. SHESIS software was harnessed to obtain the haplotypes of the PDCD-1 gene. We found that the genotype and allele distribution of PDCD-1 tagging loci did not significantly affect the risk of CRC. Adjustment for body mass index, age, smoking, alcohol using and sex also found that PDCD-1 tagging loci did not influence the occurrence of CRC. In conclusion, this study suggests that the PDCD-1 tagging loci (rs10204525, rs7421861, and rs2227982) are not correlated with CRC susceptibility.

5-Amino-4-Imidazolecarboxamide Ribonucleotide Transformylase/IMP Cyclohydrolase Polymorphisms Affect the Susceptibility to Multiple Myeloma.

The upregulation of 5-amino-4-imidazolecarboxamide ribonucleotide transformylase/IMP cyclohydrolase (ATIC) may affect tumorigenesis and multiple myeloma (MM) development. A total of 97 patients with MM and 102 healthy control patients were included in the study. The SNaPshot technique was used to detect the ATIC gene polymorphisms. Linkage disequilibrium (LD) and haplotype analyses were conducted using SHEsis software. The genotype distribution or allele frequency of rs3772078 and rs16853834 was significantly different between the patients with MM and the healthy control patients (all P < .05). The rs16853834 A allele, rs3772078 CT genotype, and C allele were associated with a decreased risk of MM (all P < .05). Five single-nucleotide polymorphism combinations showed strong LD. Three haplotypes were associated with MM risk (all P < .05). We found that ATIC rs7604984 was significantly associated with serum lactate dehydrogenase levels (P = .050). We determined that the rs3772078 and rs16853834 polymorphisms are associated with a decreased risk of MM.

Granzyme B Gene Polymorphisms and Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis

Abstract Infection with the hepatitis B virus (HBV) continues to be a hazard for public health across the globe. Chronic hepatitis, cirrhosis, and hepatocellular carcinoma are all possible outcomes (HCC). It is obvious that certain patients with chronic hepatitis B (CHB) viral infection developed HCC, while other under almost similar circumstances do not. To inspect the possible there being a link between three single nucleotide gene polymorphisms (SNPs) in GzmB genes with the development of HCC. A total of 85 patients diagnosed with CHB participated in this research (40 patients with HCC and 45 patients without HCC). Three SNPs in GzmB gene (rs7144366, rs8192917 and rs2236338) were genotypes using restriction fragment length polymorphism (RFLP). The haplotype blocks derived from the three SNPs were assembled, and the linkage disequilibrium (LD) between the SNPs was determined using the SHEsis software. The homozygous mutant genotype (CC) was shown to be significantly more common in patients with HCC (27.5 %) than in those without HCC (11.11 %) (OR= 3.93, 95 percent CI=1.13-13.62, p=0.031). At allelic level, the mutant allele (C) was more frequent in patients with than those without HCC (46.25% vs. 26.67%) with a significant deviation (OR=2.36, 95%CI= 1.25- 4.49, p= 0.008). the haplotype block CCG was more common among patients with HCC (26.25%) than those without HCC (12.22%) with a significant difference (OR= 2.56, 95%= 1.14-5.71, p= 0.022). the final conclusion carrying the mutant homozygous (CC) of the SNP rs8192917 and allele C of this SNP may have a higher chance of developing HCC compared with those carrying other genotypes and T allele of the SNP. The haplotype block CCG (corresponding for TC allele of rs7144366, C allele of rs8192917 and G allele of rs2236338) might be regarded as a risk factor for the emergence of HCC in patients with CHB.

Novel functional polymorphism on PADI-4 gene and its association with arthritis onset

BackgroundCitrullinated proteins formed by peptidyl arginine deiminases (PADIs) deimination of arginine residues in proteins are of particular interest in arthritis pathogenesis. Polymorphisms on the PADI-4 gene lead to the malfunctioning of PADIs leading to the onset of arthritis. ObjectiveThepresent study was conducted to determine the polymorphisms on the PADI-4 gene and their association with rheumatoid arthritis (RA) as well as Osteoarthritis (OA). MethodologyTo achieve the above-mentioned objective a case-control study was conducted. Blood samples were collected from RA, OA, and control subjects. DNA was extracted from each blood sample by modified organic method and was quantified as well as qualified by DNA gel electrophoresis and Nanodrop. Patients were tested for rs874881, rs11203366, rs11203367, rs2240336, rs2240337, rs2240339, rs1748033 and rs2240340 polymorphic sites by amplifying targeted regions through PCR with site-specific primers. Genotyping was performed by Restriction Fragment Length Polymorphism and direct sequencing method. Mutations were identified by analyzing sequences on BioEdit software. Allelic, genetic, and multiple site analysis were performed by SHEsis and PLINK software. Change in the amino acid sequence was identified by MEGA 6.0 software. ResultsPolymorphisms were identified on all targeted polymorphic sites except rs2240337 in both RA and OA individuals. In addition, two novel mutations were also identified in exon 4 identified i-e SCV000804840: c.218T > C and SCV000807675: c.241G > T. All the SNPs except rs11203366 were found to be significantly associated with RA at an allelic level whereas all SNP’s have been significant risk factors in the onset of OA. At genotypic level rs874881, rs11203366, rs2240339, SCV000804840 and SCV000807675 were significantly associated to RA development whereas rs874881, rs11203366, rs11203367, rs2240339, SCV000804840 and SCV000807675 were genetic risk factors in OA onset. Haplotype analysis indicated that GACCACGCC and GACCACGCT were highly significant in disease development. Polymorphisms identified altered the functioning of PADIs by altering their amino acid sequence. ConclusionIn conclusion, it was found that PADI-4 gene polymorphism was not only involved in the onset of RA but was also found to be a significant risk factor in OA onset.