Allele Levels Research Articles

Association of Dopamine Transporter Gene with Heroin Dependence in an Indian Subpopulation from Manipur.

Dopamine transporter (DAT) or solute carrier family 6 member 3 (SLC6A3) is a transmembrane protein regulating dopaminergic neurotransmission. It has been implicated in playing important roles in the dopaminergic reward pathways, and thus, DAT1 is a strong candidate gene for association studies with heroin dependence. A case-control study involving 279 individuals (147 controls and 132 heroin-dependent cases) was conducted. Ten polymorphisms of the DAT1 (SLC6A3) gene were analysed for its association with heroin dependence. Following the Hardy-Weinberg equilibrium (HWE) test, genetic association analyses were performed for the study groups. The post hoc statistical power of the study was 0.655 (65.5%). Single-nucleotide polymorphism (SNP) rs246997 was found to be significantly associated with heroin dependence at allelic, genotypic, and haplotypic levels. A significant difference in the distribution of 11R allele and 10R/11R genotype of rs28363170 between heroin-dependent cases and controls was also observed. Nominal significance at degrees of freedom (df) = 5 was also observed for rs28363170. Five bimarker-based haplotype combinations were also found to be associated with heroin dependence. For the first time, 13R allele (7R/13R genotype) and 14R allele (7R/14R genotype) were identified for rs3836790 in the population. The study also reports that the 11R allele and 10R/11R genotype of rs28363170 is associated with protection against heroin dependence. 7R and 6R alleles were also found to be the common alleles of rs3836790 in the study population. The study provides evidence for the association of polymorphisms of DAT1 (SLC6A3) with heroin dependence.

Common variants in IL17F gene contributed to the risk of hip osteoarthritis susceptibility in Han Chinese population.

The prevalence of hip and knee osteoarthritis (OA) varies by ethnicity, suggesting genetic heterogeneity in populations and predilection sites. Given the unknown mechanism of IL17F gene in the etiology of OA, it is necessary to examine the potential shared susceptibility of IL17F gene between knee OA and hip OA (HOA). This study aimed to evaluate the association of the IL17F gene and susceptibility to HOA in a Han Chinese population. A total of 2650 study subjects, comprising 796 HOA patients and 1854 controls, were recruited into the present study. Seven tag single nucleotide polymorphisms (SNPs) were selected for genotyping. Single marker-based genetic association analyses were conducted at both the genotypic and allelic levels. χ2 statistics were calculated for statistical testing, and odds ratios were obtained to estimate the effects of genotypes and alleles for each SNP. The SNP rs763780 was identified to be significantly associated with the risk of HOA at both genotypic (χ2 =12.45, P = .002) and allelic levels (χ2 =11.83, P = .0006). A linkage disequilibrium (LD) block comprised of 3 SNPs (rs12201582-rs12203736-rs722323) was also significantly associated with the risk of HOA. In addition, rs2294835 was identified to be associated with HOA severity (χ2 =12.10, P = .02). Our results showed that IL17F gene contributed to the risk of HOA in a Han Chinese population, which would help to elucidate the pathogenesis of OA and facilitate the development of novel medicines and treatments for OA.

Common variants in LTBP3 gene contributed to the risk of hip osteoarthritis in Han Chinese population.

Osteoarthritis (OA) is a common chronic joint disease affected by environmental and genetic factors. The LTBP3 gene may be involved in the occurrence and development of OA by regulating TGF-β activity and the TGF-β signaling pathway. A total of 2780 study subjects, including 884 hip OA cases and 1896 controls, were recruited. Nine tag single-nucleotide polymorphisms (SNPs) located within the LTBP3 gene region were selected for genotyping. Genetic association analyses were performed at both the genotypic and allelic levels. GTEx data were extracted to investigate the functional consequence of significant SNPs. SNP rs10896015 was significantly associated with the risk of hip OA at both the genotypic (P=0.0019) and allelic levels (P=0.0009). The A allele of this SNP was significantly associated with a decreased risk of HOA (OR [95%CI] = 0.79 [0.69–0.91]). This SNP was also significantly associated with the clinical severity of hip OA. SNP rs10896015 could affect the gene expression of 11 genes, including LTBP3, in multiple human tissues based on GTEx data. We obtained evidence for a genetic association between the LTBP3 gene and hip OA susceptibility and clinical severity based on Chinese Han populations. Our findings replicated the association signals reported by a recent genome-wide association study and deepen the basic understanding of osteoarthritis pathology.

Associations of Single Nucleotide Polymorphism in miR-146a Gene with Susceptibility to Breast Cancer in the Iranian Female.

Background:MicroRNAs (miRNAs), short regulatory RNAs, function as negative regulators able to modulate gene expression. Just as other genetic variant, single nucleotide polymorphisms (SNPs) in miRNA genes, may have an impact on their expression and/or maturation and hence leading to different consequences in carcinogenesis. Accordingly, this study aimed to assess the frequency of miR-146a G/C (rs2910164) polymorphism and its association with susceptibility to breast cancer in Iranian women. Methods:We conducted a case-control study using Tetra ARMS polymerase chain reaction (Tetra ARMS PCR) method in 100 Iranian female participants (50 breast cancer patients and 50 controls). Besides, a number of sequenced samples were chosen to confirm the accuracy of genotyping by Tetra ARMA PCR. SPSS software was utilized for all statistical analyses. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were applied to analyze the association between the SNP frequency and breast cancer. Results:The frequency of genotypes for G/G, G/C, and C/C were 23 (46%), 26 (52%), and 1 (2%) among cases and 15 (30%), 33 (66%), and 2(4%) among controls, respectively. The results generated by the groups did not show any significant correlation between miR-146a G/C (rs2910164) polymorphism and breast cancer, either at genotype or allele levels (P>0.05). F-SNP-based in silico analysis indicated possible modifications in transcriptional regulations induced by miR-146a G/C (rs2910164) variations. Conclusion:Overall, our results indicated no correlation between miR-146a G/C (rs2910164) polymorphism and genetic susceptibility to breast cancer in Iranian female populations. However, these findings need to be further confirmed by analyses of a larger number of cases.

Distinct Life Histories Impact Dikaryotic Genome Evolution in the Rust Fungus Puccinia striiformis Causing Stripe Rust in Wheat.

Stripe rust of wheat, caused by the obligate biotrophic fungus Puccinia striiformis f.sp. tritici, is a major threat to wheat production worldwide with an estimated yearly loss of US $1 billion. The recent advances in long-read sequencing technologies and tailored-assembly algorithms enabled us to disentangle the two haploid genomes of Pst. This provides us with haplotype-specific information at a whole-genome level. Exploiting this novel information, we perform whole-genome comparative genomics of two P. striiformis f.sp. tritici isolates with contrasting life histories. We compare one isolate of the old European lineage (PstS0), which has been asexual for over 50 years, and a Warrior isolate (PstS7 lineage) from a novel incursion into Europe in 2011 from a sexual population in the Himalayan region. This comparison provides evidence that long-term asexual evolution leads to genome expansion, accumulation of transposable elements, and increased heterozygosity at the single nucleotide, structural, and allele levels. At the whole-genome level, candidate effectors are not compartmentalized and do not exhibit reduced levels of synteny. Yet we were able to identify two subsets of candidate effector populations. About 70% of candidate effectors are invariant between the two isolates, whereas 30% are hypervariable. The latter might be involved in host adaptation on wheat and explain the different phenotypes of the two isolates. Overall, this detailed comparative analysis of two haplotype-aware assemblies of P. striiformis f.sp. tritici is the first step in understanding the evolution of dikaryotic rust fungi at a whole-genome level.

HLA-G 14 bp In/Del and +3142 C/G genotypes are differentially expressed between patients with grade IV gliomas and controls

Aim: Human Leukocyte Antigen-G (HLA-G) is a non-classical class I molecule that is involved in maternal–fetal immunotolerance. In cancer, this molecule contributes to the tumor escape. The aim of this study was to evaluate the 14 bp In/Del and +3142 C > G polymorphisms of the HLA-G 3′ UTR and its relation with plasma and tissue HLA-G expression in patients with grade IV (high-grade) and grade I/II (low-grade) gliomas and controls.Patients and methods: Peripheral blood and tumor biopsies were collected from 85 patients with gliomas and blood samples from 94 controls. Polymorphisms were analyzed from blood DNA. Soluble HLA-G (sHLA-G) was measured by ELISA in plasma of the subjects and the tissue expression by immunohistochemistry on patient’s tissue.Results: Higher levels of sHLA-G were observed in grade IV gliomas patients than in controls (p < 0.0001). In grade IV patients, the heterozygous 14pb In/Del, +3142 C/G genotypes and Del/C*In/G haplotype were associated with higher sHLA-G levels (p < 0.0001) when compared with controls. GBM patients were stratified into high and low sHLA-G expression and an association was found between +3142 C allele and high sHLA-G plasmatic levels (p = 0.0095). Tissue HLA-G immunolabel was higher in high-grade than low-grade gliomas (p = 0.0033).Conclusion: This was the first study evaluating HLA-G 3′ UTR polymorphisms and expression in patients with gliomas. The 14 bp In/Del and +3142 C/G genotypes and haplotypes showed high influence over sHLA-G expression, suggesting a heterozygous advantage in the tumor context and may contribute to a worse prognosis in glioma patients.

Agrobiodiversity and its Conservation in Nepal

Nepal is a part of the world’s biodiversity hotspot and ranks the 49th in the world for biodiversity. Agrobiodiversity and its conservation status were studied through literature review, field survey, key informant survey and focus group discussion. Results of field implementation of some good practices and action research were also documented. Among 24,300 total species in the country, 28% are agricultural genetic resources (AGRs), termed as agrobiodiversity. Agrobiodiversity has six components (crops, forages, livestock, aquatic, insects and microorganisms) and four sub-components (domesticated, semi-domesticated, wild relatives and wild edible) in Nepal. Agrobiodiversity on each component exists at agroecosystem, species, variety/breed/biotype/race/strain, genotype and allele levels, within an altitude range from 60 to 5,000 masl. There are 12 agroecosystems supporting 1026 species under crop component, 510 under forage, 35 under livestock, 250 under the aquatic animal, 17 under aquatic plant, 3,500 under insect and 800 under microorganism. An estimated loss of agrobiodiversity is 40%, however, farmers have reported up to 100% loss of AGRs in some areas for a particular species. Conservation of agrobiodiversity has been initiated since 1986. Four strategies namely ex-situ, on-farm, in-situ and breeding have been adopted for conservation and sustainable utilization of AGRs. Eighty good practices including process, methods and actions for managing agrobiodiversity have been in practice and these practices come under five conservation components (sensitization, method and approach, accelerator, value and enabling environment). Within the country, 18,765 accessions of AGRs have been conserved in different kinds of banks. A total of 24,683 accessions of Nepalese crops, forages and microbes have been conserved in different international and foreign genebanks. Some collections are conserved as safety duplication and safety backup in different CGIARs’ banks and World Seed Vault, Korea. Two global databases (GENESYS and EURISCO) have maintained 19,200 Nepalese accessions. Geographical Information System, Climate Analog Tool and biotechnological tools have been applied for better managing AGRs. Many stakeholders need to further concentrate on the conservation and utilization of AGRs. Global marketing of some native AGRs is necessary for sustaining agriculture and attracting young generations as well as conserving them through use.

Serum Has Higher Proportion of Janus Kinase 2 V617F Mutation Compared to Paired EDTA-Whole Blood Sample: A Model for Somatic Mutation Quantification Using qPCR and the 2-∆∆Cq Method.

Detection of the Janus Kinase-2 (JAK2) V617F mutation is a diagnostic criterion for myeloproliferative neoplasms, and high levels of mutant alleles are associated with worse outcomes. This mutation is usually tested on blood DNA by allele-specific qPCR (AS-qPCR) and measured using absolute quantification. However, some automated DNA extractions co-extracts of PCR inhibitors from blood and qPCR absolute quantification need increased efforts in order to maintain standard curves. JAK2 V617F can also be detected in serum using droplet digital PCR (ddPCR), a specimen with less inhibitors and favorable to automated extractions, but ddPCR instruments are not wide available as qPCR thermocyclers. Here, we evaluate whether JAK2 V617F could be accurately quantified by AS-qPCR using the 2-∆∆Cq method on blood DNA and validate the assay using gold-standard molecular diagnostic protocols. Next, we apply the validated method to assess if the mutation could be reliably detected/quantified in serum. JAK2 V617F could be quantified by AS-qPCR using the 2-∆∆Cq method—the assay was highly accurate (bias of 1.91%) compared to a commercial kit, highly precise (total CV% of 0.40%, 1.92%, 11.12% for samples with 93%, 54%, and 2.5% of mutant allele), highly sensitive (limit of detection of 0.15%), and demonstrated a linear detection response from 1.1% to 99.9%. Serum presented a higher mutant allele burden compared to the paired whole blood (mean of 4%), which allows for an increased JAK2 mutant detection rate and favors increased JAK2 V617F high-throughput analysis.

Molecular characterization of a gastric cancer transmitted from an organ donor to four transplant recipients.

414 Background: Donor-derived malignancy may occur even when not suspected based on donor or recipient factors, including age and time to cancer diagnosis. Early recognition of donor-derived malignancy has treatment implications. We describe the molecular characterization of a gastric cancer transmitted from an organ donor to heart, liver (LR), left kidney (LKR), and right kidney-pancreas (KPR) recipients. Methods: IRB approval for chart review was obtained; LR, LKR, and KPR also provided research consent for molecular profiling. Short Tandem Repeat (STR) genotyping was performed by polymerase chain reaction and gel electrophoresis. Tumor and germline DNA from patients and the organ donor were subjected to next generation sequencing (NGS) of 479 genes. Fluorescence in situ hybridization (FISH) was used to confirm MET amplification. Results: Donor origin was established by STR analysis, with the tumors showing high levels of donor alleles. Pathology revealed a poorly differentiated adenocarcinoma with signet ring features. Immunohistochemical staining and CA-19-9 elevation were most consistent with gastric or pancreas origin. Tumor sequencing was notable for somatic mutation of CDH1, MET amplification and wild-type KRAS genes. Tumors from LR and KPR were nearly identical based on pathogenic variants, allele frequency, and copy number variation. Insufficient tumor cellularity in all LKR specimens precluded NGS profiling, but clinical testing found that the cancer was mismatch repair proficient; ERBB2 equivocal; and PDL-1 positive. A circulating tumor DNA test did not uncover any genomic alterations; however, MET amplification was confirmed in this tumor using FISH probes. Conclusions: STR analysis and reporting should be standard immediately following diagnosis of cancer in an organ transplant recipient to ascertain donor derivation. Further molecular characterization, including NGS, may aid in defining primary tumor origin. Here, diagnosis with PDL1-positive gastric cancer enabled use of pembrolizumab. One patient remains alive and without evidence of cancer following prompt organ explant after cancer was reported in other recipients.

Abstract TMP28: Serotonin Transporter Polymorphism Impact on Cortisol Level and Outcome After Stroke

Background: The short (s) allele of a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is related to reduced serotonin transporter efficiency and an increased vulnerability to stress and mental disorders. The 5-HTTLPR s allele was reported as associate with hypothalamic-pituitary-adrenal (HPA)-axis reactivity to stress, depression and negatively impact on memory. Acute stroke is associated with elevated cortisol levels as part of the body’s reaction to a stress provoking event. We investigated whether 5-HTT genotype interacts with physiological stress to impact on outcome after stroke. Methods: Data from 485 non-depressed cognitively intact first-ever mild to moderate stroke patients from the TABASCO study were available. Patients underwent 3T MRI scans, saliva cortisol measure and comprehensive neuropsychological assessments at admission, 6, and 12 and 24 months thereafter. Results: Carriers of the 5-HTT-s allele (23.2%) had significantly higher admission bedtime salivary cortisol (p=0.042) and more depressive symptoms 12 and 24 months after the index event (p=0.043, p=0.05, respectively) than non-carriers. Higher admission salivary cortisol levels negatively correlated with hippocampal and amigdalar volume at admission (r=-0.257, p=0.004; r=-0.177, p=0.048, respectively) as well as with lower cognitive and higher depression scores 24 months post-stroke (r=-0.2, p=0.032, r=0.245, p=0.007, respectively). The association between salivary cortisol levels, depressive and cognitive scores was stronger in 5-HTT-s carriers than non-carriers. Conclusions: We report that carriers of the 5-HTT-s allele may be at risk to develop depressive symptoms post-stroke. The interactive effects of the s allele and cortisol levels on hippocampal volume and post-stroke depressive symptoms, as well as cognitive performance, suggest that the negative effect of the serotonin polymorphism on the development of post-stroke depression and cognitive decline is mediated by the HPA axis. Since genetic factors may influence vulnerability to the adverse effects of stress, serotonin receptors may provide a novel target for therapeutics to prevent depression and cognitive deterioration in stroke patients.

Differential Allele-Specific Expression Uncovers Breast Cancer Genes Dysregulated by Cis Noncoding Mutations.

Identifying cancer-relevant mutations in noncoding regions is challenging due to the large numbers of such mutations, their low levels of recurrence, and difficulties in interpreting their functional impact. To uncover genes that are dysregulated due to somatic mutations in cis, we build upon the concept of differential allele-specific expression (ASE) and introduce methods to identify genes within an individual's cancer whose ASE differs from what is found in matched normal tissue. When applied to breast cancer tumor samples, our methods detect the known allele-specific effects of copy number variation and nonsense-mediated decay. Further, genes that are found to recurrently exhibit differential ASE across samples are cancer relevant. Genes with cis mutations are enriched for differential ASE, and we find 147 potentially functional noncoding mutations cis to genes that exhibit significant differential ASE. We conclude that differential ASE is a promising means for discovering gene dysregulation due to cis noncoding mutations.

Genetic diversity and population structure analysis of Ghanaian and exotic cassava accessions using simple sequence repeat (SSR) markers

Genetic diversity is fundamentally important in crop improvement and provides plants with the capacity to meet the demands of changing environments. This work was carried out to assess the diversity and the extent of genetic relatedness among a number of assembled cassava (Manihot esculenta Crantz) accessions. We conducted a microsatellite marker analysis of 89 cassava accessions collected from Ghanaian and exotic sources. These accessions were assayed using 35 simple sequence repeat (SSR) markers. A total of 167 alleles were detected from 35 polymorphic markers with an average of 4.77 alleles per locus. High allelic frequency was detected across the accessions, ranging from 0.32 to 0.99 with an average of 0.62 per marker. Observed heterozygosity ranged from 0.03 - 0.97 across the accessions. Polymorphism information content (PIC) ranged from 0.03 to 0.78 with a mean of 0.45, indicating high level of polymorphism across the accessions. Comparatively, higher number of alleles, gene diversity and observed heterozygosity were detected among the local accessions compared with the exotic accessions indicating rich genetic diversity among them. Population structure analysis based on STRUCTURE identified two subpopulations and a large number of admixtures. Cluster analysis based on the neighbour joining algorithim further separated the collection into seven sub-groupings irrespective of geographical origin. This indicates the possible sharing of common genomic regions occurring across the accessions. High allelic frequency differences and levels of heterozygosity were observed among the germplasm. These findings indicated significant genetic variability in the germplasm to warrant selection.

Is it possible ABC transporters genetic variants influence the outcomes of a weight-loss diet in obese women?

ATP-Binding Cassette (ABC) transporters are involved in cholesterol metabolism and their dysfunctions could lead to obesity-associated complications. It was investigated whether SNPs in the ABCA1 (rs1800977 and rs2230806), ABCA7 (rs2279796) and ABCG1 (rs692383 and rs3827225) genes can modulate the responsiveness of 137 obese women to a weight-loss dietary intervention. Thus, anthropometric and lipid profiles were collected at baseline and after nine weeks of a calorie-restricted diet of 600kcal per day and participants were genotyped for the ABC genes SNPs. Regarding the transversal analysis, the ABCA7 rs2279796 GG genotype was associated with higher levels of total cholesterol and LDL-c at baseline (p = 0.044 for both). Association between ABCG1 rs692383 AA genotype and lower BMI were found in the post-diet moment, however, statistical significance was lost after multi-test correction. Regarding the longitudinal analysis, after multi-test correction, the association remained between ABCG1 rs692383 G allele and HDL-c levels: G allele carriers had a lower HDL-c reduction (p = 0.043). Results suggest the standard weight-loss diet applied in this study could attenuate the ABCA7 rs2279796 GG genotype effects found at baseline and non-dyslipidemic obese women with ABCG1 rs692383 G allele are benefitting from the diet with a lower reduction in HDL-c levels.

Evaluation of relationship between SPON1 gene and genetic susceptibility of postmenopausal osteoporosis

Purpose Postmenopausal osteoporosis (PMOP) is one of systemic bone degenerative diseases characterised by decreased bone mineral density (BMD). Previous studies suggest that the SPON1 gene may be associated with BMD and play an important role in the occurrence and development of PMOP. In this study, we aimed to investigate the potential association between PMOP and the SPON1 gene. Methods A total of 8062 postmenopausal women comprising 2684 primary PMOP patients, and 5378 healthy controls were recruited. Forty tag SNPs were selected for genotyping to evaluate the association of the SPON1 gene with PMOP and BMD. Genetic association and bioinformatics analyses were performed for PMOP. Results SNP rs2697825 was identified to be significantly associated with the risk of PMOP at both allelic (T-statistics = −3.84, p = .0001) and genotypic levels (χ 2=15.86, p = .0004). The G allele of SNP rs2697825 was significantly associated with a decreased risk of PMOP with an OR [95%] of 0.84 [0.77–0.92]. The G allele of SNP rs2697825 was associated with increased BMD at both the lumbar spine and femoral neck. Conclusions Our results provide further evidence to support the important role for the SPON1 gene in the aetiology of PMOP, adding to the current understanding of the susceptibility to osteoporosis.

A novel maize dwarf mutant generated by Ty1-copia LTR-retrotransposon insertion in Brachytic2 after spaceflight.

Retrotransposon insertion in Brachytic2 generated a new incomplete recessive dwarf allele after spaceflight can moderately reduce plant height in heterozygous and potentially improve maize yield. Plant height and ear height are two important agronomic traits in maize breeding. In this study, two dwarf mutants short internode length1 (sil1) and short internode length2 (sil2) were obtained from two of 398 spaceflighted seeds of inbred line 18-599. The decrease in longitudinal cell number and cell length led to the shortened internodes of sil1 and sil2. A Ty1-copia LTR-retrotransposon, termed ZmRE-1, inserted in the fifth exon of Brachytic2 (Br2) was identified in sil1 and sil2 at exactly the same site, which indicated the transposition of ZmRE-1 probably correlated with the spaceflight. This new dwarf mutant allele was named as br2-sil in this study. The insertion of ZmRE-1 not only led to the loss of normal transcript of Br2 allele, but also reduced the transcript expression of br2-sil allele. Chop-qPCR displayed that the promoter region DNA methylation level of br2-sil allele in sil1 was higher than that of Br2 allele in WT-sil1. We speculated that the increased methylation level might downregulate the br2-sil expression. There was no difference in the seed-setting rate between sil1 and WT-sil1. Meanwhile, br2-sil could reduce plant and ear height effectively in Br2/br2-sil genotype without negative effects on grain yield. Therefore, the application of br2-sil in breeding has the potential to improve the grain yield per unit area through increasing the planting density.

Correlation between a variable number tandem repeat (VNTR) polymorphism in SMYD3 gene and breast cancer: A genotype-phenotype study

Genetic predisposition to breast cancer (BC) has become one of the most studied aspects of the disease. Advances in the field of cancer research have revealed the role of different genetic polymorphisms within genes of interest in the development of BC. This study aimed to explore the impact of a variable number tandem repeat (VNTR) genetic variant found within the SET and MYND domain containing protein 3 (SMYD3) gene on BC risk in Jordan and examine key clinical and pathological prognostic factors. Genotyping of blood samples from 180 cases with breast cancer and 180 healthy individuals from the Jordanian population was carried out via a combination of PCR and agarose gel electrophoresis. A highly significant association was found at level of genotype (P-value = 0.009) and allele (P-value = 0.0001) between BC development and the VNTR variant in the SMYD3 gene among Jordanian women. Moreover, we found that the VNTR of SMYD3 gene may interfere with BC risk among patients with different immunohistochemistry (IHC) profiles (P-value < 0.05). This study reported that there is a significant correlation between BC development and the VNTR in the SMYD3 gene. These findings can help alleviate the burden of BC in developing countries including Jordan and to fill the gaps in current literature. Since this study was carried out on Jordanian Arabs, more studies on the link between BC and the SMYD3 VNTR variant are recommended to determine this polymorphism’s impact on other ethnic groups.

Human leucocyte antigen diversity: A biological gift to escape infections, no longer a barrier for haploidentical Hemopoietic Stem Cell Transplantation.

Since the beginning of life, every multicellular organism appeared to have a complex innate immune system although the adaptive immune system, centred on lymphocytes bearing antigen receptors generated by somatic recombination, arose in jawed fish approximately 500 million years ago. The major histocompatibility complex MHC, named the Human leucocyte antigen (HLA) system in humans, represents a vital function structure in the organism by presenting pathogen-derived peptides to T cells as the main initial step of the adaptive immune response. The huge level of polymorphism observed in HLA genes definitely reflects selection, favouring heterozygosity at the individual or population level, in a pathogen-rich environment, although many are located in introns or in exons that do not code for the antigen-biding site of the HLA. Over the past three decades, the extent of allelic diversity at HLA loci has been well characterized using high-resolution HLA-DNA typing and the number of new HLA alleles, produced through next-generation sequencing methods, is even more rapidly increasing. The level of the HLA system polymorphism represents an obstacle to the search of potential compatible donors for patients affected by haematological disease proposed for a hematopoietic stem cell transplant (HSCT). Data reported in literature clearly show that antigenic and/or allelic mismatches between related or unrelated donors and patients influences the successful HSCT outcome. However, the recent development of the new transplant strategy based on the choice of haploidentical donors for HSCT is questioning the role of HLA compatibility, since the great HLA disparities present do not worsen the overall clinical outcome. Nowadays, NGS has contributed to define at allelic levels the HLA polymorphism and solve potential ambiguities. However, HLA functions and tissue typing probably need to be further investigated in the next future, to understand the reasons why in haploidentical transplants the presence of a whole mismatch haplotype between donors and recipients, both the survival rate and the incidence of acute GvHD or graft rejection are similar to those reported for unrelated HSCTs.

Association of Diamine oxidase (DAO) variants with the risk for migraine from North Indian population

BackgroundMigraine is a common neurovascular disorder affected by various levels of neurotransmitters. Low histamine metabolism is also related with pathophysiology of migraine. As diamine oxidase (DAO) gene variants are linked with higher levels of histamine in migraine patients, we investigated the possible relationship of two variants rs2052129 and rs10156191of this gene with migraine risk in North Indian population. MethodsA case-control study for 250 migraine patients and 250 matched healthy controls was conducted by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). ResultsWe found statistically significant differences in allelic frequencies of rs2052129 (p = .009, OR = 1.462; 95% CI: 1.098–1.947) and rs10156191 (p = .019, OR = 1.430; 95% CI: 1.060–1.928) variants in DAO gene. For rs1015691, we were able to show statistically significant association at all genotypic, dominant and allelic levels in both MA (for T allele, p = .020; OR = 1.662, 95% CI: 1.083–2.551) as well as in female subgroup (for T allele, p = .025, OR = 1.460; 95% CI: 1.049–2.033). But no such significant association was found in clinical sub grouping of migraine in rs2052129 as p > .05. However in gender analysis, protective effect of T allele in male migraine patients for rs2052129 (OR < 1) was found. ConclusionsOur findings clearly indicated that a female patient with rs10156191T allele and in MA subgroup showed an increased risk for migraine. Our data also indicated that rs2052129T variant showed a significant role in migraine susceptibility of this population.

DENND1A and THADA Gene Polymorphism Among Iraqi Women With Polycystic Ovary Syndrome

Objectives: To study the two gene polymorphism (DENND1A and THADA genes) among Iraqi women with polycystic ovary syndrome (PCOS). Materials and Methods: This case-control study was done at the Gynaecological Department of Al-Yarmouk Teaching Hospital of AI-Mustansiriyah College of Medicine, Baghdad during January-December 2018. Two-hundred women were enrolled in the study, including 100 women with PCOS as the case group and 100 healthy and age-matched women as the control group. Main outcome measures were to analyze DENND1a gene polymorphism rs2479106 and THADA gene polymorphism rs12478601 at genotype and allelic levels. Results: The DENND1A gene polymorphism rs2479106 had three genotypes of AA, AG, and GG. The homozygous mutant genotype (GG) was considerably related to the incidence of PCOS (OR=5.43, 95% CI=1.13-25.97, P=0.034) with 5-time more risk compared with those carrying the wild homozygous genotype (AA). The heterozygous genotype (AG) was more but not statistically different (OR=1.73, 95% CI=0.85-3.54, P=0.131). At the allelic level, G allele was two times more frequent among cases compared to control cases with a highly significant difference. THADA gene polymorphism rs12478601 had three genotypes of CC, CT, and TT. Although TT genotype was repeated more among the case group than controls, the difference was not significant (P=0.346). Likewise, no significant differences were found in the allele distribution of this polymorphism. Conclusions: In general, the DENND1A-rs 2479106 polymorphism was considerably related to the incidence of PCOS among Iraqi women while THADA-rs12478601 polymorphism was not.

Chromosomal location and molecular characterization of three grain hardness genes in Agropyron cristatum

Grain hardness is an important characteristic of wheat quality. This trait is mainly related to the variation in, and the presence of, puroindolines (Pina and Pinb genes), and, to a lesser extent, the grain softness protein (Gsp-1) gene. The current study evaluated the allelic variability levels of these three genes in 12 diploid lines from Agropyron cristatum, a species from the tertiary wheat genepool. Along with their chromosomal locations, the molecular characterizations of the main allelic variants were found and their phylogenetic relationships with wheat genomes were determined. The hardness (Ha) locus, which includes the Pina, Pinb and Gsp-1 genes, was physically mapped on the short arm of chromosome 5P of A. cristatum. This conservation of synteny in homeologous group 5 suggests that the genes isolated in the present study are orthologues of the wheat Pina, Pinb and Gsp-1 genes. The identified polymorphisms resulted in three alleles, two for the Pinb and Gsp-1 genes, but only one allele for the Pina gene. Diverse changes were detected in the deduced mature proteins of these alleles, which could influence their hardness characteristics. The Pina, Pinb and Gsp-1 genes from diploid A. cristatum might be good sources of genetic variability that could extend the range of wheat grain textures in parallel with the introgression of other useful agronomic traits.