Polymorphism In Exon Research Articles

Association of human leukocyte antigen-G 14 bp polymorphism with recurrent pregnancy loss in European countries: a meta-analysis of literature studies

To study the controversial association between human leukocyte antigen-G (HLA-G) 14bp polymorphism and recurrent pregnancy loss (RPL). We performed a meta-analysis of studies in the literature that enrolled only women of European countries who experienced RPL spontaneously or after undergoing IVF. Systematic meta-analysis of articles published before January 2019 pertaining the association of HLA-G genotype and RPL. The search was performed in electronic databases (PubMed, Web of Science, Scopus, EMBASE), without any language or publication year restriction. Academic hospitals and private clinics. Women who experienced RPL spontaneously or after undergoing IVF. Genotyping of 14bp polymorphism (insertion/insertion, insertion/deletion, deletion/deletion) in exon 8 of the HLA-G gene. Meta-analyses of the association between HLA-G 14bp polymorphism in homozygosis (insertion/insertion) and heterozygosis (insertion/deletion) in women with RPL compared with pregnant controls with at least one live birth and no history of RPL. Ten studies were analyzed comprising 1,091 women with RPL and 808 controls without RPL. Women with RPL showed significantly higher prevalence of HLA-G 14bp insertion/insertion genotype compared with women without RPL (19.8% vs. 14.1%; odds ratio = 1.562; 95% confidence interval, 1.203-2.027), and this result was also confirmed when separately analyzing women with RPL during a spontaneous pregnancy (odds ratio, 1.562; 95% confidence interval, 1.203-2.027) and those undergoing IVF (odds ratio, 1.990; 95% confidence interval, 0.978-4.051). Women of European countries with the HLA-G 14bp insertion/insertion genotype have a significantly higher prevalence of RPL.

The molecular structure and imprinting status of the IPW (imprinted gene in the Prader-Willi syndrome region) gene in cattle.

IPW (imprinted gene in the Prader-Willi syndrome region), a long non-coding RNA, is a paternally expressed gene in the PWS/AS imprinted domain on human chromosome 15 and mouse chromosome 7. Disruption of the PWS/AS region is associated with three neurogenic disorders in humans. In this study, we identified the bovine homolog of the IPW gene; multiple transcripts obtained by RT-PCR and RACE showed a complex and tissue-specific expression pattern of IPW in the brain, heart, kidney, liver, lung, spleen and skeletal muscle. An informative single nucleotide polymorphism (rs133341090) in the long exon H was identified by sequencing the genomic DNA, and mono-allelic expression of IPW was confirmed by sequencing the cDNAs of heterozygous individuals, indicating that IPW may be imprinted in cattle. The protein-coding potential of IPW transcripts was assessed using coding potential calculator (cpc) software, which showed a negative score. In addition, sequencing analysis also indicated multiple small open reading frames in the bovine IPW transcript, but none of the ATGs was consistent with Kozak consensus. Taken together, the IPW transcripts are most likely long non-coding RNAs.

Analysis on correlation between polymorphism of MyoG gene exon I and body size traits of sheep

Myogenin (MyoG) is responsible for centering control over myocyte differentiation process and can influence the meat production of animals directly. Large tailed Han sheep, small tailed Han sheep, Yuxi fatty tailed sheep, Lanzhou large tailed sheep, Mongolia sheep and Tong Sheep were used as the experimental materials in this study. Polymorphism of MyoG gene exon I was tested by native polyacrylamide gel electrophoresis. The correlation between polymorphism of MyoG gene exon I and body size traits was analyzed. Influences of MyoG gene exon I on growth traits of sheep were discussed. Results demonstrated that 2 alleles (A, B) and 3 genotypes (AA, BB and AB) were detected in MyoG gene exon I of all 6 sheep varieties. The A allele frequencies in MyoG gene exon I of small tailed Han sheep, large tailed Han sheep, Yuxi fatty tailed sheep, Lanzhou large tailed sheep, Mongolia sheep and Tong Sheep were 0.5167, 0.2500, 0.4376, 0.6500, 0.5750 and 0.7125, while the B allele frequencies were 0.4833, 0.7500, 0.5625, 0.3500, 0.4250 and 0.2875, respectively. Chest width and neck length of the AA genotype of MyoG gene exon I were significantly higher than those of the AB genotype (P less than 0.01) and BB genotype (P less than 0.05). Body length and rump length of the AA genotype were significantly higher than those of the AB genotype (P less than 0.05). The chest depth and hip width of the AA genotype was far lower than that of the AB genotype (P less than 0.01). The hip height of the AA genotype was far lower than that of the BB genotype (P less than 0.05).

Evolution of ASPM coding variation in apes and associations with brain structure in chimpanzees.

Studying genetic mechanisms underlying primate brain morphology can provide insight into the evolution of human brain structure and cognition. In humans, loss-of-function mutations in the gene coding for ASPM (Abnormal Spindle Microtubule Assembly) have been associated with primary microcephaly, which is defined by a significantly reduced brain volume, intellectual disability and delayed development. However, less is known about the effects of common ASPM variation in humans and other primates. In this study, we characterized the degree of coding variation at ASPM in a large sample of chimpanzees (N = 241), and examined potential associations between genotype and various measures of brain morphology. We identified and genotyped five non-synonymous polymorphisms in exons 3 (V588G), 18 (Q2772K, K2796E, C2811Y) and 27 (I3427V). Using T1-weighted magnetic resonance imaging of brains, we measured total brain volume, cerebral gray and white matter volume, cerebral ventricular volume, and cortical surface area in the same chimpanzees. We found a potential association between ASPM V588G genotype and cerebral ventricular volume but not with the other measures. Additionally, we found that chimpanzee, bonobo, and human lineages each independently show a signature of accelerated ASPM protein evolution. Overall, our results suggest the potential effects of ASPM variation on cerebral cortical development, and emphasize the need for further functional studies. These results are the first evidence suggesting ASPM variation might play a role in shaping natural variation in brain structure in nonhuman primates.

PB1711 MUTATIONAL ANALYSIS WILMS TUMOR 1 GENE IN DE NOVO CASES OF ACUTE MYELOID LEUKAEMIA; PREVALENCE, CORRELATION AND REPORT OF NOVEL MUTATION IN INDIAN POPULATION

Background:Cytogenetic and molecular abnormalities associated with pathogenesis of acute myeloid leukemia (AML) are broad and heterogeneous and acts as a cardinal marker for AML classification, prognostication and risk stratification. Mutation of the Wilms tumour 1 gene (WT1) is relatively frequent in leukemia and has been found to be present in about 10% > 15% of cases of AML mainly affecting exons 7 and 9, and less frequently exons 1, 2, 3, and 8. Different studies show variable and conflicting results with few showing poor prognosis in cases of AML due to WT1 overexpression or mutation, while others suggesting that WT1 has no significant impact on the prognosis of AML.Aims:The objective of this pilot study was to evaluate the prevalence of WT1 gene mutation in de novo cases of AML and its correlation with clinical features and prognosis.Methods:Study was conducted at All India Institute of Medical Sciences, New Delhi in 100 de novo cases of AML across the all age groups. Bone marrow aspirates (BMA) or peripheral blood (PB) sample was collected from diagnosed cases of AML and were processed for genomic DNA extraction. Genomic DNA amplified by polymerase chain reaction (PCR) for targeted regions exon 7 and 9 of WT1 gene using designed primer pair (forward and reverse for both exon 7 and 9). The PCR amplified product was then subjected to direct Sanger sequencing using genetic analyzer 3100/3700 (Applied bio‐system, USA). The targeted gene sequence results were then analyzed using Chromas© 2.6 software tool. The statistical analysis of data was done using Pearson's chi‐squared test (χ2) and Fisher's exact test.Results:1. The WT1 point mutation (substitution) was identified in two cases (2%) aged 15 and 28 years respectively on exon 9 of WT1 gene. One of these two mutations was novel and has not been previously reported.2. Twelve cases (12%) were found to have synonymous single nucleotide polymorphism (SNP) in exon 7 which has been previously reported in SNP database (rs16754) as heterozygous in nature (WT1 A→G). 3. Blast percentage was >50% in both the cases harbouring WT1 mutation (mutant cases). However, there were no statistically significant differences in other clinical and haematological parameters like haemoglobin, white blood cells (WBCs) count and platelets counts between wild type and mutant cases.4. Both mutant cases were young adults, relapsed after consolidation and eventually met early death compared to wild type cases.Summary/Conclusion:Only few case studies on WT1 gene mutation in AML have been reported and there is lack of such study and precise published data from India to date. From this pilot study we conclude that WT1 mutation is not so prevalent among de novo cases of AML in Indian population. Correlation between WT1 mutation and clinical outcome of the cases suggested that mutant cases had poor clinical outcome and early death. However, this study was limited by a relatively small sample size and incorporating only the mutational hotspot region of the gene. In future we need to perform this study on larger sample size together with study of whole WT1 gene by next generation sequencing (NGS) in order to reach any statistically significant conclusion.

Polymorphisms of the Myf6 gene exon 1 and their relationship with growth and reproductive traits in Jinghai Yellow Chicken

Polymorphisms of the Myf6 gene exon 1 and their relationship with growth and reproductive traits in Jinghai Yellow Chicken

Association of COL1A2 (PvuII) gene polymorphism with risk and severity of dental fluorosis – A case control study

IntroductionDental fluorosis is a foremost public health problem in many countries, including India. Very few studies investigated gene polymorphism and risk of dental fluorosis. Genetic polymorphisms in Collagen Type I, alpha 2 (COL1A2) gene, found to be linked with bone pathogenesis, may affect the tooth formation resulting in the vulnerability to dental fluorosis. AimTo assess the association between COL1A2 (PvuII) gene polymorphism and risk as well as severity of dental fluorosis. MethodsThe present case control study was conducted among participants with (n = 60) and without (n = 60) dental fluorosis. Dental fluorosis was assessed using Modified Dean’s fluorosis index (1942). The PvuII polymorphisms (in exon 25) inside the COL1A2 gene were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) procedure. Statistical analysis were carried out with Chi-square test and Odds Ratio (OR) was determined with multivariate logistic regression analysis. ResultsThe genetic polymorphism in COL1A2 PvuII was found to be associated with the risk of dental fluorosis which was highly significant (p < 0.001). The odds ratio was 31.4 times [OR = 31.9, 95% CI: 3.9–48.7] higher for the homozygous PP genotype group and 4.0 times [OR = 4.0, 95% CI: 1.0–10.7] higher for the heterozygous Pp genotype. ConclusionGenetic polymorphism of COL1A2 was found to be associated with dental fluorosis. The present study provides an insight for identification of the population who may subsist at risk of developing dental fluorosis in their later life.

The Relation between Polymorphisms in Exon 5 and Exon 6 of GSTP1 Gene and the Risk of Lung Cancer in Iranian People

Objective:The GSTP1 gene, which is located on chromosome 11q13, consists of 7 exons and 6 introns. There are two polymorphisms in GSTP1 that have been exposed to a transposition for codon 105 (Ile/Val) and 114 (Ala/Val) in exons 5 and 6, which have been studied previously in relation to lung cancer. Since the level of GSTP1 expression in lung tissues and other human epithelial tissues is high, GSTP1Val-105 polymorphism is recognized as a sensitive factor for tobacco-related cancers, especially lung cancer.Methods:One hundred and twenty tissue block samples of patients with lung cancers and 120 peripheral blood samples of the control group were obtained from two referral cancer centers in Tehran, Iran, from 2011 to 2016. Genomic DNA was extracted from tissue blocks and buffy coat of study cases to detect SNP of GSTP1 gene using Tetra-primer ARMS-PCR.Results:There was a notable correlation between the incidence of lung cancer and variant Val105 (P-value=0.001; OR=2/6; 95% CI=1.49-4.53) and Ile105 (P-value=0.003; OR=0.41; 95% CI=0.23-0.73). The odds ratio for lung cancer in the homozygous Ile105/Ile105 genotype was 3.56 times higher than that of individual with heterozygous Ile105/Val105 (P-value<0.001; OR=3/56; 95% CI=1.826-6.934) genotype, that was statistically significant. Furthermore, the results showed that there was no significant correlation between Ala114/Val114 genotypes and lung cancer. The BC (P-value=0.007; OR=0.16; 95% CI=0.04-0.61) and AA (P=0.001) genotypes were statistically significant (P-value <0.05); and for those who had AA genotype, the odds ratio was almost six times higher than those with BC genotype.Conclusions:The study of GSTP1 polymorphisms indicated that unlike the polymorphism in exon 5, the GSTP1 exon 6 polymorphism correlated with the lung cancer risk in the select group of Iranian people. Likewise, the potential use of this genetic polymorphism as a lung cancer predictor is confirmed.

Detection of Epidermal Growth Factor Receptor (EGFR) Gene Mutation in Formalin Fixed Paraffin Embedded Tissue by Polymerase Chain Reaction-Single Strand Conformational Polymorphism (PCR-SSCP) in Non-Small Cell Lung Cancer in the Northeastern Region of Thailand

Background:The use of targeted specific genes in therapeutic and treatment decisions has been considered for lung cancer. The epidermal growth factor receptor (EGFR) gene, which is over expressed in non-small cell lung cancer (NSCLC), was considered as one of the targeted specific genes. EGFR mutations in exons 18–21, which encode a portion of the EGFR kinase domain, were found in NSCLC patients and were associated with the response of EGFR- tyrosine kinase inhibitors (EGFR-TKIs). Therefore, a molecular technique for EGFR mutation detection has important benefits for therapy in NSCLC patients. This study aims to determine the EGFR mutations in patients with NSCLC using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) in exons 18-21.Methods:DNA samples were extracted from formalin fixed paraffin embedded tissues of NSCLC patients who attended hospital. The extracted DNA was used as a template for the EGFR gene amplification.Results:Occurrence of EGFR mutations were found in 29 out of 50 cases (58%).The frequency of EGFR mutations by first PCR at exon 18, 19, 20 and 21 were 6 (12%), 19 (38%) 20 (40%) and at 21 (42%), respectively. By PCR-SSCP, the frequencies of EGFR mutations at exon 18, 19, 20 and 21 were 3(6%), 18(36%), 23(46%) and 13(26%), respectively. All of the mutations found were in agreement with DNA sequencings.Conclusion:The high frequency of EGFR mutations in NSCLC suggests that PCR-SSCP is a efficient screening method and useful for treatment plan.

Vitamin D Receptor FokI, ApaI, and TaqI Polymorphisms in Lead Exposed Subjects From Saudi Arabia.

Vitamin D receptor (VDR) gene polymorphisms were reported to influence blood lead levels (BLL) and the response of subjects to the symptoms of lead toxicity. However, no studies have been conducted in the Saudi Arabian population which has unique ethnicity and socio-demographic features. This study examined the polymorphisms in exon 2 (allele 1) and intron 8 (allele 2 and allele 3) of VDR gene and their relation to BLLs. As per the CDC guidelines, the recruited lead-exposed workers (N = 130) were categorized to two groups viz., low BLL group (<10 μg/dL) and high BLL group (>10 μg/dL). The low BLL group had a mean BLL of 4.37 μg/dL, while the high BLL group had levels of 18.12 μg/dL (p < 0.001). Overall, the genetic variants, TC and CC in the VDR FokI were significantly associated with a risk of lead toxicity and the allele “C” was a risk factor (p = 0.00026). Furthermore, the TT genotype of VDR ApaI significantly increased the risk of developing lead poisoning (p = 0.0006). The VDR TaqI SNP was not significantly associated with lead toxicity. The highest BLLs for VDR FokI-CC, VDR ApaI-GG, and VDR TaqI-TT genotypes from High BLL group were 18.42, 15.26, and 18.75 μg/dL, respectively. Older age (51–60 years) was found to be a significant confounding factor for BLLs (p = 0.012). Additional studies in larger sample sizes are needed to firmly establish the role of VDR genotypes and genetic susceptibility to lead poisoning.

Evaluation of genetic association of 40 SNPs in candidate genes with cholesterol gallstone disease in north Indian population

BackgroundIn north Indian population, Gallbladder Stone Disease (GSD) affects 7% of population, with majority of stones containing >50% cholesterol. In general, GSD susceptibility has been suggested to include the combination of predisposing alleles of multiple lithogenic (LITH) genes and environmental factors. Materials and methodsStudy included 610 GSD patients (USG positive) and 315 healthy controls. A panel of 48 SNPs was prepared for candidate genes based on pathobiology of GSD, MAF in Hapmap and 1000 genome database, and Tagger SNPs in Linkage Disequilibrium. Genotyping was carried out by Sequenom Mass ARRAY platform and statistical analyses were performed using SPSS version 16.0, Bonferroni adjustment was applied for multiple testing corrections. Potential functional consequences of the exonic polymorphisms were determined using Polyphen2, SIFT score and interaction networks of associated genes by GENEMANIA. ResultsGenotypes of 40 out of 48 SNPs followed Hardy Weinberg Equilibrium in controls and subjected to present analysis. We observed significant associations of genotypes/alleles of FGFR4, CYP7A1, APOE, TM4SF4, NR1H2, IL10, PLCE1, CYP1A1, SLC10A2, MMP2, CYP8B1, Gab1 with GSD whereas remaining SNPs revealed no association.Analysis after gender stratification and Bonferroni correction revealed that in males SNPs in TM4SF4, PLCE1 and Gab1 were significantly associated with GSD while in females APOE and CYP8B1 polymorphisms were significantly associated with GSD.All but three significantly associated SNPs were intronic. The potential functional consequences of associated exonic SNPs by Polyphen2 predicted probable damaging effects of FGFR4 and APOE variants, while PLCE1 SNP showed benign effect. Further SIFT score predicted probable tolerated effects of FGFR4 and PLCE1, while APOE variant showed deleterious effect. ConclusionsOur study suggests that FGFR4, CYP7A1, APOE, TM4SF4, NR1H2, IL10, PLCE1, CYP1A1, SLC10A2, MMP2, CYP8B1 genetic variants confer significant risk for gallstone disease in North Indian population. The association of many genes with disease risk was found to be sex-specific.

The Nopp140 gene in Drosophila melanogaster displays length polymorphisms in its large repetitive second exon

Nopp140, often called the nucleolar and Cajal body phosphoprotein (NOLC1), is an evolutionarily conserved chaperone for the transcription and processing of rRNA during ribosome subunit assembly. Metazoan Nopp140 contains an amino terminal LisH dimerization domain and a highly conserved carboxyl domain. A large central domain consists of alternating basic and acidic motifs of low sequence complexity. Orthologous versions of Nopp140 contain variable numbers of repeating basic–acidic units. While vertebrate Nopp140 genes use multiple exons to encode the central domain, the Nopp140 gene in Drosophila uses exclusively exon 2 to encode the central domain. Here, we define three overlapping repeat sequence patterns (P, P′, and P″) within the central domain of D. melanogaster Nopp140. These repeat patterns are poorly conserved in other Drosophila species. We also describe a length polymorphism in exon 2 that pertains specifically to the P′ pattern in D. melanogaster. The pattern displays either two or three 96 base pair repeats, respectively, referred to as Nopp140-Short and Nopp140-Long. Fly lines homozygous for one or the other allele, or heterozygous for both alleles, show no discernible phenotypes. PCR characterization of the long and short alleles shows a poorly defined, artifactual bias toward amplifying the long allele over the short allele. The significance of this polymorphism will be in discerning the largely unknown properties of Nopp140’s large central domain in rDNA transcription and ribosome biogenesis.

Influence of two functional polymorphisms in NOS1 on baseline cortisol and working memory in healthy subjects

IntroductionThe neuronal isoform of the nitric oxide synthase (NOS-I) encoded by NOS1 is the main source of nitric oxide (NO) in the brain. Reduced NO signaling in the prefrontal cortex has been linked to schizophrenia and cognitive processes while reduced striatal NOS1 expression has been associated with impulsive behavior. MethodsTo evaluate the effect of two functional polymorphisms in alternative first exons of NOS1, ex1f-VNTR and ex1c-SNP rs41279104, on the HPA stress axis and neurocognitive abilities, 280 healthy subjects were genotyped, had their salivary cortisol levels measured and were assessed in verbal memory, verbal fluency, working memory and verbal IQ by using the California Verbal Learning Test (CVLT), the Regensburger test of verbal fluency (RWT), a n-back task and subscales of the Wechsler Adult Intelligence Scale III (WAIS-III). ResultsSchizophrenia risk (A)-allele carriers of NOS1 ex1c-SNP rs41279104 displayed significantly lower baseline cortisol levels (p = 0.004). NOS1 ex1f-VNTR genotype carriers showed differences in working memory performance (p = 0.05) in a gene-dose effect manner, with homozygous carriers of the short impulsivity-risk allele committing most commission errors. Finally, A-allele carriers of the NOS1 ex1c-SNP rs41279104 tended to react faster during the working memory task (p = 0.065). ConclusionFor the first time, we demonstrated an influence of the NOS1 ex1c-SNP rs41279104 on salivary cortisol levels and additionally implicate the A-allele in an enhanced reaction time during a working memory task. Regarding the NOS1 ex1f-VNTR our study supports the previously reported influence on impulsivity, lending further support to the hypothesis that this genetic variant underlies impulsive behavior.

Novel report on mutation in exon 3 of myostatin (MSTN) gene in Nilagiri sheep: an endangered breed of South India.

The variability in breeding program leads to rapid loss of genetic potential for which National Bureau of Animal Genetic Resources is emphasized to conserve the indigenous breeds. The variation in myostatin (MSTN) gene and its association with growth traits will throw light on its potential use as marker in selection. Hence, the study was conducted to detect polymorphism in exon 3 of MSTN, one of the most important growth regulatory gene and its association with growth in Nilagiri sheep breed. Blood samples were collected from Nilagiri sheep (n = 103) of South India and growth data up to 1year of age was recorded. Genomic DNA was isolated and amplified for part of MSTN gene; PCR products were genotyped by restriction digestion (MspI) and confirmed by sequencing. Restriction digestion has revealed a single nucleotide polymorphism at locus G5622C in exon 3 which was confirmed by sequencing. The wild-type DNA molecule (MM) cleaved by MspI produced 301-bp and 314-bp fragments and those with mutation (mm) would remain undigested. The genotypic frequencies were MM (0.689) and Mm (0.311) with complete absence of mm genotype; and allelic frequencies were M (0.8445) and m (0.1555). The locus was in Hardy-Weinberg equilibrium. The association analysis revealed that there was no significant difference in mean birth, weaning, 6-, 9-, and 12-month weight between MM and Mm genotypes at g.5622G>C locus of exon 3 of MSTN gene. This is the first report of mutation in exon 3 of MSTN gene. The non-significant effect and absence of mm genotype at this locus needs further studies based on large population size and haplotype analysis.

Screening for ARHGAP29 gene variants in Turkish paediatric patients with non-syndromic cleft lip with or without cleft palate

ObjectiveIn this study, we aimed to screen for Rho GTPase-activating protein 29 gene (ARHGAP29) variants in Turkish paediatric patients with non-syndromic cleft lip with or without cleft palate (nsCL/P). MethodsOur study comprised 80 nsCL/P patients and 125 unrelated Turkish individuals. Molecular analysis of the ARHGAP29 variants was carried out using polymerase chain reaction amplification and direct sequencing. ResultsIn this study, rs141866812, rs143877998, rs147752270, rs141653334, rs149136237, rs374087471, rs144585524 and rs201618253 single nucleotide polymorphisms in exons 2, 21 and 23 of ARHGAP29 were screened in patients with nsCL/P and in the control group. Mutations in the ARHGAP29 gene, which were previously identified in patients with nsCL/P of different ethnicities, were not observed in the Turkish patients. ConclusionThis is the first report investigating ARHGAP29 variants in Turkish patients with nsCL/P.

Association study of G+2044A (R130Q) polymorphism in IL-13 gene with risk of developing Multiple Sclerosis in Iranian population

BackgroundMultiple Sclerosis (MS) is an autoimmune and progressive neurodegeneration disease of the central nervous system (CNS) that diagnosed by inflammation and demyelination of neurons. MS is a multifactorial disease that occurs due to interactions between environment and genetic factors. IL-13 is a cytokine and one of the candidate genes for MS that its expression reduces in MS patients. Material and methodsIn this study, 174 unrelated MS patients and 283 healthy individuals were examined. We assessed G+2044A (R130Q) polymorphism in exon 4, a single nucleotide polymorphism (SNP), in the coding region of the IL-13 gene. Genotyping of G+2044A polymorphism was performed using sequence-specific primer-polymerase chain reaction (SSP-PCR). ResultsNo significant association was found between Genotypes and allele frequency in patients and healthy individuals (P > 0.05). Comparison of the frequency of MS cases and healthy individuals based on ethnicity, a significant association was observed between Turkmen patients and MS with a protective role [P < 0.05, OR = 0.01, CI (0.004–0.04)] Moreover no significant association was seen between the inheritance models for the G+2044A SNP, but there is a significant association between gender and susceptibility to MS (P = 0.01). ConclusionAccording to our results, there is no significant difference in Genotype and allele frequency of G+2044A polymorphism among MS patients and healthy individuals. But a significant association was observed between Turkmen patients and MS with a protective role.

Next-generation HLA typing of 382 International Histocompatibility Working Group reference B-lymphoblastoid cell lines: Report from the 17th International HLA and Immunogenetics Workshop

Extended molecular characterization of HLA genes in the IHWG reference B-lymphoblastoid cell lines (B-LCLs) was one of the major goals for the 17th International HLA and Immunogenetics Workshop (IHIW). Although reference B-LCLs have been examined extensively in previous workshops complete high-resolution typing was not completed for all the classical class I and class II HLA genes. To address this, we conducted a single-blind study where select panels of B-LCL genomic DNA samples were distributed to multiple laboratories for HLA genotyping by next-generation sequencing methods. Identical cell panels comprised of 24 and 346 samples were distributed and typed by at least four laboratories in order to derive accurate consensus HLA genotypes. Overall concordance rates calculated at both 2- and 4-field allele-level resolutions ranged from 90.4% to 100%. Concordance for the class I genes ranged from 91.7 to 100%, whereas concordance for class II genes was variable; the lowest observed at HLA-DRB3 (84.2%). At the maximum allele-resolution 78 B-LCLs were defined as homozygous for all 11 loci. We identified 11 novel exon polymorphisms in the entire cell panel. A comparison of the B-LCLs NGS HLA genotypes with the HLA genotypes catalogued in the IPD-IMGT/HLA Database Cell Repository, revealed an overall allele match at 68.4%. Typing discrepancies between the two datasets were mostly due to the lower-resolution historical typing methods resulting in incomplete HLA genotypes for some samples listed in the IPD-IMGT/HLA Database Cell Repository. Our approach of multiple-laboratory NGS HLA typing of the B-LCLs has provided accurate genotyping data. The data generated by the tremendous collaborative efforts of the 17th IHIW participants is useful for updating the current cell and sequence databases and will be a valuable resource for future studies.

G994T polymorphism in exon 9 of plasma platelet-activating factor acetylhydrolase gene and lung ultrasound score as prognostic markers in evaluating the outcome of acute respiratory distress syndrome.

The present study aimed to discover potential biomarkers for predicting the prognosis of acute respiratory distress syndrome (ARDS) in conjunction with lung ultrasound (LUS). Blood samples from 112 ARDS patients were collected to compare their partial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2), positive end-expiratory pressure (PEEP), lactic acid, sequential organ failure assessment (SOFA) score, clinical pulmonary infection score (CPIS) and APACHE II score. Kaplan-Meier plots and the log-rank test were performed to analyse the association between the platelet-activating factor acetylhydrolase (PAFAH) G994T polymorphism and the outcome of ARDS regarding mortality. A negative correlation between the LUS score and PaO2/FiO2, PEEP and lactic acid, as well as with the SOFA, CPIS and APACHE II score was confirmed with correlation coefficients of -0.493, -0.548, -0.642, -0.598, -0.566 and -0.567, respectively (all P<0.05). The activity of PAFAH and high-density lipoprotein-PAFAH in the serum collected from subjects of the GG genotype was similar to that in subjects of the GT genotype, but the low-density lipoprotein-PAFAH activity in the serum collected from GG subjects was significantly higher than that in GT subjects. An evident reduction in the PEEP, level of lactic acid, as well as the SOFA, CPIS and APACHE II score was observed in GG subjects, accompanied by a significantly increased PaO2/FiO2. Kaplan-Meier analysis indicated that subjects with a high LUS score had a significantly higher survival rate than those with a low LUS score, and the mortality risk for GG subjects was significantly lower than that for GT subjects. Finally, among all groups (genotype and LUS groups), GG subjects with a high LUS score had the lowest mortality risk, whereas GT subjects with a low LUS score had the highest mortality risk. In addition, the survival rate of GT subjects with a high LUS score was higher than that of GG subjects with a low LUS score. In conclusion, the combination of the LUS score and the G994T polymorphism in exon 9 of the PAFAH gene may be used as a potential prognostic marker for ARDS.

Polymorphisms of exon 10 in the BPI gene and its association analysis with some reproductive traits and partial immune indexes in Meishan pigs

This study was conducted to detect polymorphisms of BPI gene exon 10 by PCR-RFLP in Meishan pigs and their associations with some important cytokine levels (IL-1s, IL-4, IL-6, IL-8, IL-10, TGF-1s, IFN-γ, TNF-α) and reproductive traits (total number born (TNB), number born alive (NBA), birth litter weight (BLW), and weaning litter weight (WLW)), with the aim of identifying effective genetic markers for molecular breeding. The results revealed three genotypes, including AA, AB, and BB, with the trend of AA > BB > AB in reproductive traits. Pigs with the AA genotype were significantly higher than the AB genotype in TNB and IFN-γ (P 0.05). Comprehensive analysis indicated that the polymorphisms of exon 10 in the BPI gene have significant genetic effects on some reproductive traits and cytokines in Meishan pigs, for which the AA genotype was demonstrated to be the favorable genotype, which could be used as potential genetic markers for in-depth research and examination.

HUBUNGAN MUTASI PADA GEN LEPTIN EXON 2 DENGAN BOBOT LAHIR, PERTAMBAHAN BOBOT BADAN DAN BOBOT SAPIH SAPI BALI

The one of genes that play an important role in the body metabolism that is closely related to productivity is the Leptin gene. This study aims to determine the assosiation polymorphism of exon 2 Leptin gene based on Single Nucleotide Polymorphism (SNP) with birth weight of Balinese cattle. This study used 47 DNA of Balinese cattle, their birth weight (BW), average daily gain (ADG) and yearling weight (YW) data, that were obtained from BPTU HPT Pulukan Bali. The isolation of DNA using a high salt concentrated method and DNA target was duplicated by PCR machine. Analysis genetic mutation of Leptin genes was performed by evaluating SNP in Exon 2 at R25C and R25H, from direct sequencing results, using Bioedit and MEGA 5.2 program. The association of Leptin gene polymorphism with BW, ADG and YW were analyzed using variance analysis. The result showed that there were For genotypes based on SNP R25C and R25H, ie CC, CT, CA, and AA. There were no assosiation between Leptin gene polymorphism with birth weight (BW), average daily gain (ADG) and yearling weight (YW) on Balinese cattle.