Allele Of SNP Research Articles

Spontaneous generation of diversity in Arachis neopolyploids (Arachis ipaënsis × Arachis duranensis)4x replays the early stages of peanut evolution.

Polyploidy is considered a driving force in plant evolution and domestication. Although in the genus Arachis, several diploid species were traditionally cultivated for their seeds, only the allotetraploid peanut Arachis hypogaea became the successful, widely spread legume crop. This suggests that polyploidy has given selective advantage for domestication of peanut. Here, we study induced allotetraploid (neopolyploid) lineages obtained from crosses between the peanut’s progenitor species, Arachis ipaënsis and Arachis duranensis, at earlier and later generations. We observed plant morphology, seed dimensions, and genome structure using cytogenetics (FISH and GISH) and SNP genotyping. The neopolyploid lineages show more variable fertility and seed morphology than their progenitors and cultivated peanut. They also showed sexual and somatic genome instability, evidenced by changes of number of detectable 45S rDNA sites, and extensive homoeologous recombination indicated by mosaic patterns of chromosomes and changes in dosage of SNP alleles derived from the diploid species. Genome instability was not randomly distributed across the genome: the more syntenic chromosomes, the higher homoeologous recombination. Instability levels are higher than observed on peanut lines, therefore it is likely that more unstable lines tend to perish. We conclude that early stages of the origin and domestication of the allotetraploid peanut involved two genetic bottlenecks: the first, common to most allotetraploids, is composed of the rare hybridization and polyploidization events, followed by sexual reproductive isolation from its wild diploid relatives. Here, we suggest a second bottleneck: the survival of the only very few lineages that had stronger mechanisms for limiting genomic instability.

P-117 Pre-selected for an award: Bioinformatic analysis of NRF2 in the study of association of NRF2 variant and male infertility related to smoking status

Abstract Study question Could Nrf2 polymorphism (-617C>A; rs6721961) and oxidative stress (OS)-induced changes of signature seminal plasma (SP) miRNAs related to Nrf2 provide possible biomarkers of male infertility? Summary answer -617C>A SNP is associated with infertility through sperm OS DNA damage and miR-582-5p and miR-20a-5p, differentially represented between spermatozoa of smokers-non-smokers, might regulate Nrf2/ARE axis. What is known already As an extrinsic factor causing OS, smoking decreases male infertility by causing sperm membrane damage and DNA fragmentation. Expression of proteins related to the antioxidant defense system and phase 2 detoxifying enzymes controlled mainly by Nrf2/ARE pathway components is vital in managing OS-induced DNA damage. miRNAs, which multiple of are produced abundantly in male germ cells throughout spermatogenesis, have been detected in SP and contribute to multiple biological processes related to male reproductive events. miRNA-expression alterations may be induced in response to OS and without involving DNA sequence changes, miRNAs can provide additional mechanism of regulating the Nrf2 gene expression. Study design, size, duration Wild-type (WT) and SNP (-617) alleles in the Nrf2 gene were studied in 100 infertile cases and 100 controls and their associations with seminal parameters in relation to smoking status were assessed. In infertile cases, sperm DNA damage level was determined and compared among Nrf2 genotypes. Interactions between differentially expressed miRNAs (DEMIs) in response to smoking and Nrf2/ARE pathway components were visualized on a miRNA-mRNA regulatory network using CluePedia (v1.5.7) plugin of Cytoscape software (v3.8.2). Participants/materials, setting, methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to genotype the Nrf2 SNP (-617). DNA damages were analyzed by Comet assay. DEMIs were identified by a comprehensive bioinformatics analysis using the miRNA expression dataset GSE44134 downloaded from the GEO database. Predicted targets of DEMIs in smokers were identified by mirDIP portal. Known interactions between Nrf2 and its first neighbors were visualized after selecting STRING-actions, miRTarBase and miRecords validated miRNA source files from CluePedia panel. Main results and the role of chance There was significant difference for Nrf2 polymorphism between fertile and infertile males. The A allele was detected more frequently in the patient group; (P = 0.001). The frequencies of the C and A alleles of the Nrf2 were 62% and 38% in patients, and 78% and 44% in control group. The AA genotype was higher in the infertiles; 14% vs. 3% (P = 0.001). In smokers, sperm quality decreased significantly in AA genotype. The risk of DNA damage was highest with 224.58 AU in the AA genotype group, whereas it is the lowest with 164.56 AU in those carrying the CC genotype (P < 0.005). 21 differentially expressed miRNAs (including 7 downregulated and 14 upregulated in smokers) were identified. Among the upregulated DEMIs, miR-582-5p, miR-20a-5p, miR-573, miR-186-5p, miR-499a-5p were found to target the Nrf2 mRNA, suggesting their usage as biomarkers capable of indicating the antioxidant ability of the male reproductive system. The interrelations between Nrf2/Nrf2 direct interactors and DEMIs revealed the regulatory role of hsa-miR-20a-5p in SQSTM1/p62-Keap1-Nrf2 axis linked to selective autophagy. hsa-miR-582-5p was found to regulate the JNK/Jun/caspase-3 pathway, previously shown to be activated in response to OS, in which JUN can activate or suppress the Nrf2 expression. Limitations, reasons for caution Small number of cases while evaluating the effect of smoking weakens our ability to generalize the results. Including other coexisting factors and larger patient groups carrying other functional variants of Nrf2 as well as confirming the results at the protein level would further strengthen the results of the study. Wider implications of the findings This study is the first to report -617C>A polymorphism in the Nrf2 gene in the Turkish population and such a SNP may cause impaired fertility in men, especially in smokers, through oxidative metabolism. Considering these data may be valuable in determining risk groups. Trial registration number N/A

P–117 Bioinformatic analysis of NRF2 in the study of association of NRF2 variant and male infertility related to smoking status

Abstract Study question Could Nrf2 polymorphism (–617C>A; rs6721961) and oxidative stress (OS)-induced changes of signature seminal plasma (SP) miRNAs related to Nrf2 provide possible biomarkers of male infertility? Summary answer –617C>A SNP is associated with infertility through sperm OS DNA damage and miR–582–5p and miR–20a–5p, differentially represented between spermatozoa of smokers-non-smokers, might regulate Nrf2/ARE axis. What is known already As an extrinsic factor causing OS, smoking decreases male infertility by causing sperm membrane damage and DNA fragmentation. Expression of proteins related to the antioxidant defense system and phase 2 detoxifying enzymes controlled mainly by Nrf2/ARE pathway components is vital in managing OS-induced DNA damage. miRNAs, which multiple of are produced abundantly in male germ cells throughout spermatogenesis, have been detected in SP and contribute to multiple biological processes related to male reproductive events. miRNA-expression alterations may be induced in response to OS and without involving DNA sequence changes, miRNAs can provide additional mechanism of regulating the Nrf2 gene expression. Study design, size, duration Wild-type (WT) and SNP (–617) alleles in the Nrf2 gene were studied in 100 infertile cases and 100 controls and their associations with seminal parameters in relation to smoking status were assessed. In infertile cases, sperm DNA damage level was determined and compared among Nrf2 genotypes. Interactions between differentially expressed miRNAs (DEMIs) in response to smoking and Nrf2/ARE pathway components were visualized on a miRNA-mRNA regulatory network using CluePedia (v1.5.7) plugin of Cytoscape software (v3.8.2). Participants/materials, setting, methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was utilized to genotype the Nrf2 SNP (–617). DNA damages were analyzed by Comet assay. DEMIs were identified by a comprehensive bioinformatics analysis using the miRNA expression dataset GSE44134 downloaded from the GEO database. Predicted targets of DEMIs in smokers were identified by mirDIP portal. Known interactions between Nrf2 and its first neighbors were visualized after selecting STRING-actions, miRTarBase and miRecords validated miRNA source files from CluePedia panel. Main results and the role of chance There was significant difference for Nrf2 polymorphism between fertile and infertile males. The A allele was detected more frequently in the patient group; (P = 0.001). The frequencies of the C and A alleles of the Nrf2 were 62% and 38% in patients, and 78% and 44% in control group. The AA genotype was higher in the infertiles; 14% vs. 3% (P = 0.001). In smokers, sperm quality decreased significantly in AA genotype. The risk of DNA damage was highest with 224.58 AU in the AA genotype group, whereas it is the lowest with 164.56 AU in those carrying the CC genotype (P < 0.005). 21 differentially expressed miRNAs (including 7 downregulated and 14 upregulated in smokers) were identified. Among the upregulated DEMIs, miR–582–5p, miR–20a–5p, miR–573, miR–186–5p, miR–499a–5p were found to target the Nrf2 mRNA, suggesting their usage as biomarkers capable of indicating the antioxidant ability of the male reproductive system. The interrelations between Nrf2/Nrf2 direct interactors and DEMIs revealed the regulatory role of hsa-miR–20a–5p in SQSTM1/p62-Keap1-Nrf2 axis linked to selective autophagy. hsa-miR–582–5p was found to regulate the JNK/Jun/caspase–3 pathway, previously shown to be activated in response to OS, in which JUN can activate or suppress the Nrf2 expression. Limitations, reasons for caution Small number of cases while evaluating the effect of smoking weakens our ability to generalize the results. Including other coexisting factors and larger patient groups carrying other functional variants of Nrf2 as well as confirming the results at the protein level would further strengthen the results of the study. Wider implications of the findings: This study is the first to report –617C>A polymorphism in the Nrf2 gene in the Turkish population and such a SNP may cause impaired fertility in men, especially in smokers, through oxidative metabolism. Considering these data may be valuable in determining risk groups. Trial registration number N/A

Elucidation of familial relationships using hair shaft proteomics

This study examines the potential of hair shaft proteomic analysis to delineate genetic relatedness. Proteomic profiling and amino acid sequence analysis provide information for quantitative and statistically-based analysis of individualization and sample similarity. Protein expression levels are a function of cell-specific transcriptional and translational programs. These programs are greatly influenced by an individual’s genetic background, and are therefore influenced by familial relatedness as well as ancestry and genetic disease. Proteomic profiles should therefore be more similar among related individuals than unrelated individuals. Likewise, profiles of genetically variant peptides that contain single amino acid polymorphisms, the result of non-synonymous SNP alleles, should behave similarly. The proteomically-inferred SNP alleles should also provide a basis for calculation of combined paternity and sibship indices. We test these hypotheses using matching proteomic and genetic datasets from a family of two adults and four siblings, one of which has a genetic condition that perturbs hair structure and properties. We demonstrate that related individuals, compared to those who are unrelated, have more similar proteomic profiles, profiles of genetically variant peptides and higher combined paternity indices and combined sibship indices. This study builds on previous analyses of hair shaft protein profiling and genetically variant peptide profiles in different real-world scenarios including different human hair shaft body locations and pigmentation status. It also validates the inclusion of proteomic information with other biomolecular substrates in forensic hair shaft analysis, including mitochondrial and nuclear DNA.

Abstract 807: Asian prevalent ABCB5 genetic variants rs2074000 and rs17143187 predicts overall survival and clinical outcomes in hepatocellular carcinoma patients

Abstract Background/Aims Incidence of HCC varies in diverse localities with differences on ethnicity and risk factors. The majority of HCC cases worldwide are from China, thus raising the concern on genetic susceptibility in addition to the prevalence of hepatitis virus infection. Drug transporter ABCB5 has been reported to be overexpressed in HCC and associated with poor survival. Recently a panel of SNPs and INDELs in ABCB5 gene have been reported to associate with HCC risk (Leung et al. 2020). We aim to further examine the ethnic differences on the ABCB5 genetic variations between local cohort and the data from The 1000 Genome Project. Subjects and Methods 300 HCC and 300 healthy blood samples were prospectively collected with informed consent. All patients had been diagnosed with primary HCC and underwent partial hepatectomy. Clinical information including sex, age, tumor stage and survival outcomes were collected prospectively. Genomic DNA were extracted from blood samples and SNPs were examined. SNP allele frequencies in different populations were obtained from The 1000 Genomes Browser by NCBI. Results Twelve ABCB5 genetic variants were within the coding regions, with one splicing variant, one stop codon change, while 2 were synonymous and 8 were non-synonymous changes. In particular, allele frequencies of rs2074000 observed in healthy local cohorts (C: 0.517 vs A: 0.483) were comparable to East Asian, while the genetic variation was absent in European in 1000 Genomes Project (CHB - C: 0.534 vs A: 0.466; CHS - C: 0.548 vs A: 0.452; GBR - C: 1.000 vs A: 0.000; CEU - C: 1.000 vs A: 0.000; P<0.001). Similarly, allele frequencies of rs17143187 in healthy local cohorts (G: 0.518 vs C: 0.482) were comparable to East Asian (CHB - G: 0.539 vs C: 0.461; CHS - G: 0.567 vs C: 0.433), while it was absent among European (GBR and CEU - G: 1.000 vs C: 0.000) (P<0.001). Data from our local HCC cohorts further demonstrated that rs2074000 and rs17143187 were independent protective factors in overall survival (Cox HR; rs2074000: 0.676, 95% CI: 0.49-0.93, P=0.017; rs17143187: 0.709, 95% CI: 0.51-0.98, P=0.038). These ABCB5 genetic variants were associated with early tumor stage (OR; rs2074000: 0.351, 95% CI: 0.21-0.59, P<0.001; rs17143187: 0.382, 95% CI: 0.22-0.65, P<0.001) and solitary tumor nodule (OR; rs2074000: 0.507, 95% CI: 0.30-0.86, P=0.012; rs17143187: 0.517, 95% CI: 0.30-0.88, P=0.015). Conclusions ABCB5 genetic variants rs2074000 and rs17143187 mainly prevalent in East Asian predicted better overall survival among HCC patients. ABCB5 is crucial in tumor-initiating cells in melanoma. ABCB5 rs2074000 (non-synonymous SNP, Gln to Lys, classified as damaging by SIFT score) and rs17143187 (splicing variant) both predicted to confer non-functional proteins, thus partly explain the protective effects. Further functional studies are warranted to comprehend the underlying mechanisms. Citation Format: Chun Philip Yeung, Ching Ning Charing Chong, Tan To Cheung, Kelvin Kwok Chai Ng, Paul Bo San Lai, Siu Tim Cheung. Asian prevalent ABCB5 genetic variants rs2074000 and rs17143187 predicts overall survival and clinical outcomes in hepatocellular carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 807.

Integrative analysis of GWAS and transcriptome to reveal novel loci regulation flowering time in semi-winter rapeseed

Flowering is an important turning point from vegetative growth to reproductive growth, and vernalization is an essential condition for the flowering of annual winter plants. To investigate the genetic architecture of flowering time in rapeseed, we used the 60 K Brassica Infinium SNP array to perform a genome-wide analysis of haplotype blocks associated with flowering time in 203 Chinese semi-winter rapeseed inbred lines. Twenty-one haplotype regions carrying one or more candidate genes showed a significant association with flowering time. Interestingly, we detected a SNP (Bn-scaff_22728_1-p285715) located in exon 3 of the BnVIN3-C03 gene that showed a significant association with flowering time on chromosome C03. Based on the SNP alleles A and G, two groups of accessions with early and late flowering time phenotypes were selected, respectively, and PCR amplification and gene expression analysis were combined to reveal the structural variation of the BnVIN3-C03 gene that affected flowering time. Moreover, we found that BnVIN3-C03 inhibited the expression of BnFLC-A02, BnFLC-A03.1, BnFLC-A10 and BnFLC-C03.1, thus modulating the flowering time of Brassica napus. This result provides insight into the genetic improvement of flowering time in B. napus.

Role of Inhibitory Check Point (CTLA-4) in Iraqi Women with Breast Cancer

Breast cancer is the most important and frequently diagnosed cancer among women worldwide. The CTLA4 is a member of Immunoglobulin super family and binds to the CD80 and CD86 co-stimulatory molecules.(binds to CD80/86 on APCs with a higher affinity than CD28, thereby inhibiting co-stimulatory signals.CTLA-4 (Gene ID:1493, MIM number: 123890) is a new member of the immunoglobulin super family known as insulin-dependent diabetes mellitus 12 (IDDM 12) ,and cluster of differentiation 152 (CD152).The CTLA-4 protein consists of a 37 amino acid leader peptide, an extracellular immunoglobulin (Ig) V like domain or the ligand-binding domain (116 amino acid), a hydrophobic trans membrane region (37 amino acid), and a cytoplasmic domain. The aim of the present study of the association of CTLA-4 serum level and polymorphism with breast cancer in Iraqi women suffers from breast cancer. Materials and Methods: peripheral Blood samples were collected from 45 Iraqi patients women diagnosed with breast cancer patient, and 45 healthy women were matched with patients as a control. ELISA technique has been used to determine the serum level of sCTLA-4.The polymerase chain reaction (PCR) performed on 45 patients and 45 control, to determine the genetic variation in the +49 exon 1 region of CTLA-4 gene. Results: the serum level of understudying groups recorded an non-significant difference increasing in the serum level of CTLA-4 under (p>0.05). in mean ± SE (3.17 ± 0.82 ng/ml) patients as compared to control (2.72 ± 0.29 ng/ml) under (p>0.05). Genetic polymorphism of CTLA.4 gene (rs231775) which illustrated the distribution of genotypes of CTLA.4 in patients and control. The heterozygous genotype AG recorded high frequency in patients (35.56%) than control (0.00%) with a highly significant difference under (P<0.05). Homozygote genotype AA recorded high frequency in control (95.56%) than patients (64.44) and has a highly significant difference, and the homozygous genotype GG frequency (0.00%) was non- significant in patients compared to control (4.44%). The allele frequency for allele A was (0.82%) in patients compared with control (0.96%) while for the frequency of allele G was (0.18%) in patients compared with control (0.04%) with a significant difference. Conclusion: elevation of serum concentration of sCTLA-4 could consider as a clinical biomarker for prognosis breast cancer. There are some difference noticed in CTLA-4 gene with SNP (rs231775A/G) which showed a significant differences between patients and control, A allele of SNP (rs231775A/G) may have role to prevent the risk of breast cancer in Iraqi females, while allele G has an etiological fraction.

Functional Variants Surrounding Endothelin 2 Are Associated With Mycobacterium avium Subspecies paratuberculosis Infection.

Bovine paratuberculosis, caused by Mycobacterium avium subspecies paratuberculosis (MAP), continues to impact the dairy industry through increased morbidity, mortality, and lost production. Although genome-wide association analyses (GWAAs) have identified loci associated with susceptibility to MAP, limited progress has been made in identifying mutations that cause disease susceptibility. A 235-kb region on Bos taurus chromosome 3 (BTA3), containing a 70-kb haplotype block surrounding endothelin 2 (EDN2), has previously been associated with the risk of MAP infection. EDN2 is highly expressed in the gut and is involved in intracellular calcium signaling and a wide array of biological processes. The objective of this study was to identify putative causal mutations for disease susceptibility in the region surrounding EDN2 in Holstein and Jersey cattle. Using sequence data from 10 Holstein and 10 Jersey cattle, common variants within the 70-kb region containing EDN2 were identified. A custom SNP genotyping array fine-mapped the region using 221 Holstein and 51 Jersey cattle and identified 17 putative causal variants (P < 0.01) located in the 5′ region of EDN2 and a SNP in the 3′ UTR (P = 0.00009) associated with MAP infection. MicroRNA interference assays, mRNA stability assays, and electrophoretic mobility shift assays were performed to determine if allelic changes at each SNP resulted in differences in EDN2 stability or expression. Two SNPs [rs109651404 (G/A) and rs110287192 (G/T)] located within the promoter region of EDN2 displayed differential binding affinity for transcription factors in binding sequences harboring the alternate SNP alleles. The luciferase reporter assay revealed that the transcriptional activity of the EDN2 promoter was increased (P < 0.05) with the A allele for rs109651404 and the G allele for rs110287192. These results suggest that the variants rs109651404 and rs110287192 are mutations that alter transcription and thus may alter susceptibility to MAP infection in Holstein and Jersey cattle.

Population structure and genetic diversity of the Pee Dee cotton breeding program.

Accelerated marker-assisted selection and genomic selection breeding systems require genotyping data to select the best parents for combining beneficial traits. Since 1935, the Pee Dee (PD) cotton germplasm enhancement program has developed an important genetic resource for upland cotton (Gossypium hirsutum L.), contributing alleles for improved fiber quality, agronomic performance, and genetic diversity. To date, a detailed genetic survey of the program's eight historical breeding cycles has yet to be undertaken. The objectives of this study were to evaluate genetic diversity across and within-breeding groups, examine population structure, and contextualize these findings relative to the global upland cotton gene pool. The CottonSNP63K array was used to identify 17,441 polymorphic markers in a panel of 114 diverse PD genotypes. A subset of 4597 markers was selected to decrease marker density bias. Identity-by-state pairwise distance varied substantially, ranging from 0.55 to 0.97. Pedigree-based estimates of relatedness were not very predictive of observed genetic similarities. Few rare alleles were present, with 99.1% of SNP alleles appearing within the first four breeding cycles. Population structure analysis with principal component analysis, discriminant analysis of principal components, fastSTRUCTURE, and a phylogenetic approach revealed an admixed population with moderate substructure. A small core collection (n &lt; 20) captured 99% of the program's allelic diversity. Allele frequency analysis indicated potential selection signatures associated with stress resistance and fiber cell growth. The results of this study will steer future utilization of the program's germplasm resources and aid in combining program-specific beneficial alleles and maintaining genetic diversity.

Interleukin-33 gene variants (rs928413, rs16924159 and rs7037276) and susceptibility to asthma among Iraqi adult patients

Interleukin-33 is proposed to influence asthma susceptibility. Three IL33 gene variants (rs928413, rs16924159 and rs7037276) were included in a case-control study conducted on 104 Iraqi asthmatics and 111 controls. Tetra-primer-amplification-refractory-mutation-system-polymerase-chain-reaction method was used to determine these variants. Logistic regression analysis showed that A allele and AA genotype of rs928413 were significantly associated with an increased asthma risk under allele and recessive models, respectively. Regarding rs16924159, allele, recessive, dominant and codominant models demonstrated a significant association with asthma susceptibility, but the highest risk was found for AA genotype under recessive model. For SNP rs7037276, neither alleles nor genotypes were associated with asthma risk. Tri-locus haplotype analysis (in the order rs928413, rs16924159 and rs7037276) revealed that A-G-T haplotype frequency was significantly elevated in asthmatics compared to controls, while frequency of G-G-T haplotype was significantly decreased. In conclusions, two IL33 gene SNPs (rs928413 and rs16924159) were proposed to be associated with asthma susceptibility.

The Variant Allele Frequency of the lncRNA Prostate Cancer-Associated Noncoding RNA 1 (PRNCR1) rs1456315 C/T Polymorphism in Saudi Population and Colorectal Cancer Risk

ingle-nucleotide polymorphisms (SNPs) in long noncoding RNA (lncRNA) genes are associated with the onset and progression of multiple cancers in humans. These SNPs are potential biomarkers for predicting cancer risk. The variable frequency of the lncRNA prostate cancer-associated noncoding RNA 1 (PRNCR1) rs1456315 C/T polymorphism may affect different ethnic groups differently, however, the information lacks for the Saudi population. The aim of this study was to assess the allelic distribution and frequency of the PRNCR1 rs1456315 C/T polymorphism in the Saudi Arabian population, as well as compare it to other populations around the world. PUBMED (Medline) and other related web-databases were referred to extract data from epidemiological studies performed in different ethnic groups. The frequency of PRNCR1 rs1456315 variant allele (C) was found to be 34.62% and a significantly different frequency was observed for the USA (p=0.01), Iran (p < /em><0.007) and China (p=0.01) ethnicity, when the Saudi occurrence is compared to those populations. Present results reveal a distinct pattern of lncRNA prostate cancer-associated noncoding RNA 1 (PRNCR1) rs1456315 polymorphism variant allele in the Saudi Arabian population, which may be due to ethnic differences. The findings could assist in the risk assessment of people harbouring risk allele of rs1456315 SNP and their subsequent cancer susceptibility.

Met carriers of the BDNF Val66Met polymorphism show reduced Glx/NAA in the pregenual ACC in two independent cohorts

The Met allele of the Val66Met SNP of the BDNF gene (rs6265) is associated with impaired activity-dependent release of brain-derived neurotrophic factor (BDNF), resulting in reduced synaptic plasticity, impaired glutamatergic neurotransmission, and morphological changes. While previous work has demonstrated Val66Met effects on magnetic resonance spectroscopy (MRS) markers of either glutamatergic metabolism (Glx) or neuronal integrity (NAA), no study has investigated Val66Met effects on these related processes simultaneously. As these metabolites share a metabolic pathway, the Glx/NAA ratio may be a more sensitive marker of changes associated with the Val66Met SNP. This ratio is increased in psychiatric disorders linked to decreased functioning in the anterior cingulate cortex (ACC). In this study, we investigated the correlation of the Val66Met polymorphism of the BDNF gene with Glx/NAA in the pregenual anterior cingulate cortex (pgACC) using MRS at 3 Tesla (T) (n = 30, all males) and 7 T (n = 98, 40 females). In both cohorts, Met carriers had lower Glx/NAA compared to Val homozygotes. Follow-up analyses using absolute quantification revealed that the Met carriers do not show decreased pgACC glutamate or glutamine levels, but instead show increased NAA compared to the Val homozygotes. This finding may in part explain conflicting evidence for Val66Met as a risk factor for developing psychiatric illnesses.

Opportunities and challenges in assessing climate change vulnerability through genomics

By investigating how past selection has affected allele frequencies across space, genomic tools are providing new insights into adaptive evolutionary processes. Now researchers are considering how this genomic information can be used to predict the future vulnerability of species under climate change. Genomic vulnerability assessments show promise, but challenges remain.

Maternal and child fatty acid desaturase genotype as determinants of cord blood long-chain PUFA (LCPUFA) concentrations in the Seychelles Child Development Study.

Optimal maternal long-chain PUFA (LCPUFA) status is essential for the developing fetus. The fatty acid desaturase (FADS) genes are involved in the endogenous synthesis of LCPUFA. The minor allele of various FADS SNP have been associated with increased maternal concentrations of the precursors linoleic acid (LA) and α-linolenic acid (ALA), and lower concentrations of arachidonic acid (AA) and DHA. There is limited research on the influence of FADS genotype on cord PUFA status. The current study investigated the influence of maternal and child genetic variation in FADS genotype on cord blood PUFA status in a high fish-eating cohort. Cord blood samples (n 1088) collected from the Seychelles Child Development Study (SCDS) Nutrition Cohort 2 (NC2) were analysed for total serum PUFA. Of those with cord PUFA data available, maternal (n 1062) and child (n 916), FADS1 (rs174537 and rs174561), FADS2 (rs174575), and FADS1-FADS2 (rs3834458) were determined. Regression analysis determined that maternal minor allele homozygosity was associated with lower cord blood concentrations of DHA and the sum of EPA + DHA. Lower cord blood AA concentrations were observed in children who were minor allele homozygous for rs3834458 (β = 0·075; P = 0·037). Children who were minor allele carriers for rs174537, rs174561, rs174575 and rs3834458 had a lower cord blood AA:LA ratio (P < 0·05 for all). Both maternal and child FADS genotype were associated with cord LCPUFA concentrations, and therefore, the influence of FADS genotype was observed despite the high intake of preformed dietary LCPUFA from fish in this population.

Association of KDR rs1870377 genotype with clopidogrel resistance in patients with post percutaneous coronary intervention

BackgroundClopidogrel is an antiplatelet therapy that is widely used in pre and post percutaneous (PCI) coronary intervention procedures to prevent platelet aggregation and stent restenosis. However, there is a wide inter-individual variation in clopidogrel response and some patients showed resistance against the activity of Clopidogrel. Kinase insert domain receptor (KDR) gene is responsible for the transcription of vascular endothelial growth factor receptor 2 (VEGFR2) that plays a major role in the cardiovascular diseases (CVDs) and platelet aggregation. The aim of this study was to find out the association of KDR rs1870377 genotype with clopidogrel resistance (CR) in CVD patients, of Iraqi Arabic origin, hospitalized for elective PCI. Materials and methodsThis study was a case-control study with a total of 324 PCI patients. Those patients were classified into 213 patients with non-clopidogrel resistant and 111 patients with CR, depending on the analysis of platelet activity phenotype after clopidogrel administration. KDR rs1870377 was genotyped for all patients using polymerase chain reaction-restriction fragment length polymorphism technique and confirmed by DNA Sänger sequencing through applying Biosystems Model (ABI3730x1). ResultsKDR rs1870377 SNP is strongly associated (Chi-sqaure, p vale <0.05) with CR under dominant, co-dominant and recessive models. Additionally, A allele in the rs1870377 SNP may have an impact on the serum levels of VEGFR2 and low density lipoprotein. ConclusionsKDR rs1870377 SNP is a potential genetic biomarker of CR among CVD patients of Iraqi Arabic origin. Further clinical studies, with larger sample, are required to confirm the findings of this study.

Research on the Relationship Between Schizophrenia and Excitatory Amino Acid Transporter 1 Gene Based on Nanogold Amplification Technology.

Schizophrenia is one of the most common central nervous system diseases, which is caused by abnormal discharge of neurons in the brain. Its occurrence and development are affected by both genetic and environmental factors. The variation of gene level can affect the development of schizophrenia and the treatment of prognosis by affecting the susceptibility, clinical phenotype and drug response. At present, the research results of susceptibility genes screened by candidate gene association research are not consistent. The method of gene recognition on DNA was studied by QCM and nano gold composite. By using this method, the enantioselective recognition of cysteine on cyclodextrin self-assembled membrane was studied. In this study, EAAT1 gene, which is highly expressed in astrocytes, was used as a candidate gene to analyze the relationship between polymorphism and schizophrenia. The experimental results show that the introduction of nano gold can significantly improve the sensing signal, detection sensitivity and gene differentiation. In addition, this study suggested that EAAT1 gene might be a susceptibility gene of schizophrenia in the population. The results showed that a common SNP allele rs1030239-g was the risk factor (83.8% vs. 79.2%, P = 0.00067, or = 1.35, 95% CI = 1.08-1.69). The results showed that A-T-G increased the risk of schizophrenia.

The severity of the pathogen-induced acute sickness response is affected by polymorphisms in genes of the NLRP3 inflammasome pathway

The acute sickness response (ASR) is a stereotyped set of symptoms including fatigue, pain, and disturbed mood, which are present in most acute infections. The immunological mechanisms of the ASR are conserved, with variations in severity determined partly by the pathogen, but also by polymorphisms in host genes. The ASR was characterised in three different serologically-confirmed acute infections in Caucasians (n = 484) across four symptom domains or endophenotypes (termed ‘Fatigue’, ‘Musculoskeletal pain’, ‘Mood disturbance’, and ‘Acute sickness’). Correlations were sought with functional single nucleotide polymorphisms in the NLRP3 inflammasone pathway and severity of the endophenotypes. Individuals with severe Fatigue, Musculoskeletal pain, or Mood endophenotypes were more likely to have prior episodes of significant fatigue (11.4 vs. 3.8%, p = 0.07), pain (14.3 vs. 1.2%, p = 0.001), or Mood disturbance (13 vs 1%, p=0.001), suggesting trait characteristics. The high functioning allele of the rs35829419 SNP in NLRP3 was more common in those with severe Fatigue (OR = 13.3, 95% CI: 1.7–104), particularly in a dominant inheritance pattern (OR = 13.4, 95% CI: 1.8–586.3). In a multivariable analysis assuming dominant inheritance, both rs35829419 and the rs4848306 SNP in Interleukin(IL)-1β, were independently associated with severe Fatigue (OR = 29.6, 95% CI: 2.6–330.9 and OR = 13, 95% CI: 2.7–61.8, respectively). The severity of fatigue in acute infection is influenced by genetic polymorphisms in NLRP3 and IL-1β.

Common bean SNP alleles and candidate genes affecting photosynthesis under contrasting water regimes

Water deficit is a major worldwide constraint to common bean (Phaseolus vulgaris L.) production, being photosynthesis one of the most affected physiological processes. To gain insights into the genetic basis of the photosynthetic response of common bean under water-limited conditions, a collection of 158 Portuguese accessions was grown under both well-watered and water-deficit regimes. Leaf gas-exchange parameters were measured and photosynthetic pigments quantified. The same collection was genotyped using SNP arrays, and SNP-trait associations tested considering a linear mixed model accounting for the genetic relatedness among accessions. A total of 133 SNP-trait associations were identified for net CO2 assimilation rate, transpiration rate, stomatal conductance, and chlorophylls a and b, carotenes, and xanthophyll contents. Ninety of these associations were detected under water-deficit and 43 under well-watered conditions, with only two associations common to both treatments. Identified candidate genes revealed that stomatal regulation, protein translocation across membranes, redox mechanisms, hormone, and osmotic stress signaling were the most relevant processes involved in common bean response to water-limited conditions. These candidates are now preferential targets for common bean water-deficit-tolerance breeding. Additionally, new sources of water-deficit tolerance of Andean, Mesoamerican, and admixed origin were detected as accessions valuable for breeding, and not yet explored.

Association between genetic variants of the norepinephrine transporter gene (SLC6A2) and bipolar I disorder

We aimed to investigate the associations between genetic variants of the norepinephrine transporter gene (NET, also known as SLC6A2) and diagnosis of bipolar I disorder. In addition, we examined the relationship between the genetic variants and manic and psychotic symptoms in patients with bipolar I disorder. The three SNPs rs28386840, rs2242446, and rs5569 were genotyped in 326 patients: patients with bipolar I disorder (n = 160) and a control group (n = 166). Subsequently, multivariate logistic regression analysis adjusting for age and sex was conducted to identify independent influences of the SNPs on diagnosis of bipolar I disorder. A possible association between manic and psychotic symptoms and variants of SLC6A2 was also investigated in patients with bipolar I disorder. The rs28836840 SNP in the 5’-UTR of SLC6A2 was significantly associated with bipolar I disorder and with severity of manic and psychotic symptoms in this disorder. Individuals carrying a T allele in the rs28836840 SNP were likely to have a lower risk of bipolar I disorder or lower severity of manic and psychotic symptoms in patients with bipolar I disorder (bipolar I disorder diagnosis: OR = 0.643, 95% Cl = 0.468–0.883, p = 0.006; manic symptoms: β = −2.457, 95% Cl = −4.674 ~ −0.239, p = 0.031; psychotic symptoms: β = −2.501, 95% Cl = −4.700 ~ −0.301, p = 0.027). For the rs2242446 and rs5569 SNPs, there were no significant differences between patients with bipolar I disorder and those without. Our results revealed associations of the rs28386840 SNP with bipolar I disorder diagnosis and with severity of manic and psychotic symptoms. However, the findings reported here require replication in larger samples and various ethnic groups.

GENOMICS OF SARS-COV-2: A STUDY

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a type of novel coronavirus responsible for the COVID-19 outbreak, which attained pandemic proportions in 2020. SARS-CoV-2 belongs to that group of coronaviruses which infect the lower respiratory tract. The complete genome was found to be 29.9kb in size. The viral genome encodes 16 non-structural proteins (Nsps), essential for pathogenesis and replication. Structural proteins- envelope (E), membrane (M), nucleocapsid (N), and spike (S) glycoprotein are also encoded, important for virus subtyping and response to vaccines. L and S type of SARS-CoV-2 were identified in Wuhan initially. Later on, as the pandemic spread across the globe, A and C subtypes were identified to me the common type of strains across the Americas and Europe respectively. In Asia, B subtype was found to be common. ACE2 (angiotensin-converting enzyme 2), a receptor is utilised by SARS-CoV-2 for entry into host cell. People of European descent have a higher frequency of alternate allele of rs763395248 SNP in T92I risk variant compared to African and Asian population. In Asian populations, SNPs like rs758278442 and rs759134032 in the region of protective variants (K31R and Y83H) of ACE2 gene show higher frequency of mutant alleles than American and European populations. According to a structural modelling study, certain ACE2 variants may provide potential resistance to SARS-CoV-2 infection.