Specific Allele Combinations Research Articles

Harmonisation of the HLA tests for the diagnosis of coeliac disease: experiences from the Czech external proficiency testing program.

Coeliac disease (CD) is an autoimmune disorder caused by the ingestion of gluten-containing grains. One of the prerequisites for the development of the disease is the presence of specific combinations of HLA alleles at the DQA1 and DQB1 loci. The HLA test is a supportive diagnostic test. In the Czech Republic, approximately 3,500 HLA tests for CD diagnosis are performed annually in almost three dozen laboratories. The HLA Department of the Institute of Haematology and Blood Transfusion in Prague has been offering the EPT "Detection of HLA Alleles Associated with Diseases" for more than 10years. The results are evaluated in terms of the correct determination of predisposing alleles/allelic groups and clinical interpretation. Every year, we notice some problems with the detection of CD-associated alleles and the interpretation of results. Annual workshops are part of this EPT, and they also include recommendations for the interpretation of results. This interpretation is evolving based on the current knowledge in the field. The current recommendation for interpretation was adopted in 2023, dividing HLA-DQA1/DQB1 genotypes into three categories: 1) detected HLA genotype is associated with predisposition to coeliac disease; 2) coeliac disease could not be excluded based on the detected HLA genotype; 3) coeliac disease could be excluded with high probability based on the detected HLA genotype. The quality of examination is increasing but still needs improvement. Correct results and accurate interpretation can inform clinicians' decisions about the diagnosis of coeliac disease in appropriate patients.

Epistatic interaction between ERAP2 and HLA modulates HIV-1 adaptation and disease outcome in an Australian population.

A strong genetic predictor of outcome following untreated HIV-1 infection is the carriage of specific alleles of human leukocyte antigens (HLAs) that present viral epitopes to T cells. Residual variation in outcome measures may be attributed, in part, to viral adaptation to HLA-restricted T cell responses. Variants of the endoplasmic reticulum aminopeptidases (ERAPs) influence the repertoire of T cell epitopes presented by HLA alleles as they trim pathogen-derived peptide precursors to optimal lengths for antigen presentation, along with other functions unrelated to antigen presentation. We investigated whether ERAP variants influence HLA-associated HIV-1 adaptation with demonstrable effects on overall HIV-1 disease outcome. Utilizing host and viral data of 249 West Australian individuals with HIV-1 subtype B infection, we identified a novel association between two linked ERAP2 single nucleotide polymorphisms (SNPs; rs2248374 and rs2549782) with plasma HIV RNA concentration (viral load) (P adjusted = 0.0024 for both SNPs). Greater HLA-associated HIV-1 adaptation in the HIV-1 Gag gene correlated significantly with higher viral load, lower CD4+ T cell count and proportion; P = 0.0103, P = 0.0061, P = 0.0061, respectively). When considered together, there was a significant interaction between the two ERAP2 SNPs and HLA-associated HIV-1 adaptation on viral load (P = 0.0111). In a comprehensive multivariate model, addition of ERAP2 haplotypes and HLA associated adaptation as an interaction term to known HLA and CCR5 determinants and demographic factors, increased the explanatory variance of population viral load from 17.67% to 45.1% in this dataset. These effects were not replicated in publicly available datasets with comparably sized cohorts, suggesting that any true global epistasis may be dependent on specific HLA-ERAP allelic combinations. Our data raises the possibility that ERAP2 variants may shape peptide repertoires presented to HLA class I-restricted T cells to modulate the degree of viral adaptation within individuals, in turn contributing to disease variability at the population level. Analyses of other populations and experimental studies, ideally with locally derived ERAP genotyping and HLA-specific viral adaptations are needed to elucidate this further.

Impulsivity and aggression in alcohol withdrawal syndrome is modulated by the interaction of ZNF804A and mTOR polymorphism

Alcohol withdrawal syndrome (AWS) is a poorly studied phenotype of alcohol use disorder. Understanding the relationship between allelic interactions and AWS-related impulsivity and aggression could have significant implications. This study aimed to investigate the main and interacting effects of ZNF804A and mTOR on impulsivity and aggression during alcohol withdrawal. 446 Chinese Han adult males with alcohol dependence were included in the study. Impulsivity and aggression were assessed, and genomic DNA was genotyped. Single gene analysis showed that ZNF804A rs1344706 (A allele/CC homozygote) and mTOR rs1057079 (C allele/TT homozygote) were strongly associated with AWS-related impulsivity and aggression. In the allelic group, MANOVA revealed a significant gene x gene interaction, suggesting that risk varied systematically depending on both ZNF804A and mTOR alleles. Additionally, a significant interactive effect of ZNF804A rs1344706 and mTOR rs7525957 was found on motor impulsivity and physical aggression, and the ZNF804A rs1344706 gene variant had significant effects on motor impulsivity and physical aggression only in mTOR rs7525957 TT homozygous carriers. The study showed that specific allelic combinations of ZNF804A and mTOR may have protective or risk-enhancing effects on AWS-related impulsivity and aggression.

Genetic Heterogeneity and Tissue-specific Patterns of Tumors with Multiple PIK3CA Mutations.

To comprehensively characterize tissue-specific and molecular subclasses of multiple PIK3CA (multi-PIK3CA) mutations and assess their impact on potential therapeutic outcomes. We profiled a pan-cancer cohort comprised of 352,392 samples across 66 tumor types using a targeted hybrid capture-based next-generation sequencing panel covering at least 324 cancer-related genes. Molecularly defined subgroups, allelic configuration, clonality, and mutational signatures were identified and tested for association with PI3K inhibitor therapeutic response. Multi-PIK3CA mutations are found in 11% of all PIK3CA-mutant tumors, including 9% of low tumor mutational burden (TMB) PIK3CA-mutant tumors, and are enriched in breast and gynecologic cancers. Multi-PIK3CA mutations are frequently clonal and in cis on the same allele and occur at characteristic positions across tumor types. These mutations tend to be mutually exclusive of mutations in other driver genes, and of genes in the PI3K pathway. Among PIK3CA-mutant tumors with a high TMB, 18% are multi-PIK3CA mutant and often harbor an apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC) mutational signature. Despite large differences in specific allele combinations comprising multi-PIK3CA mutant tumors, especially across cancer types, patients with different classes of multi-PIK3CA mutant estrogen receptor-positive, HER2-negative breast cancers respond similarly to PI3K inhibition. Our pan-tumor study provides biological insights into the genetic heterogeneity and tissue specificities of multi-PIK3CA mutations, with potential clinical utility to guide PI3K inhibition strategies.

Olfatory HLA-associated mechanism of formation of married couples in the development of congenital heart diseases in children

Taking into account the significance of the HLA complex in the inflammatory and immune responses, we can assume that the potential for limiting or developing pathology in the next generation will be determined at the stage of selection of certain alleles in the spousal genotype.The aim. To study the role of HLA assortativity in couples with healthy children and couples with children with congenital heart diseases (CHD) through the prism of immunogenetic mechanisms of mutual olfactory choice.Materials and methods. We studied the distribution of HLA-DRB1 alleles in married couples with healthy children and with children having CHD. To identify the associations of HLA-DRB1 alleles with odor preferences, we also studied the group included young males and females. HLA-DRB1 gene typing was carried out in all participants.Results. The combination of HLA-DRB1 alleles in couples with healthy children was similar to the combination of these alleles in the mutual olfactory sympathy between unfamiliar young males and females. Allele combinations in the spouses from the experimental group differ from the group of random selection. The frequency of matches for HLA-DRB1 alleles in married couples with children having CHD without was significantly higher than in the control group.Conclusion. The first stage of selection, associated with olfactory selection, is aimed to the whole population, and it is significantly manifested in the control group (married couples with healthy children). At the same time, in the experimental group (couples with children having CHD), some deviations from the main selection were discovered. Generally, specific HLA-DRB1 allele combinations obtained on the basis of olfactory assessments, indicate the involvement of HLA molecules in pheromone reception.

Association of allelic combinations in selenoprotein and redox related genes with markers of lipid metabolism and oxidative stress – multimarkers analysis in a cross-sectional study

BackgroundSelenium (Se) and selenoproteins have been shown to be involved in lipid metabolism mainly due to their ability to modulate redox homeostasis in adipose tissue. The underlying mechanisms are yet to be evaluated. In the light of few data related to the association between polymorphic variants of selenoprotein encoding genes and metabolic syndrome or obesity in humans, the role of selenoprotein polymorphisms in lipid metabolism remains unclear. The aim of this study was to investigate the impact of allelic combination within selenoprotein and redox related genes on the markers of lipid metabolism and oxidative stress. MethodsThe study comprised 441 healthy individuals from Poland, in the 18−74 year age group. Allelic combinations were investigated within the polymorphic variants of four selenoprotein encoding genes (GPX1 rs1050450, GPX4 rs713041, SELENOP rs3877899 and SELENOF rs5859) and the redox related gene (SOD2 rs4880). The impact of the most common allelic GPX1-GPX4-SELENOP-SELENOF-SOD2 combinations was assessed on the following markers: triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), glutathione peroxidase activities (GPX1, GPX3), lipid peroxidation (as TBARS), ceruloplasmin (Cp) and superoxide dismutase 1 (SOD1). ResultsMultivariable analysis revealed significant associations between three allelic combinations and markers of lipid metabolism, including HDL-C and TC/HDL-C ratio (AAAAa), LDL-C (aaAaa), and triglycerides (aaaaA), whereas two allelic combinations (aAaAA, aaaAA) were associated with GPX3 activity. ConclusionThis study confirms the possible implication of selenoproteins in lipid metabolism and warrants further research on specific allele combinations within selenoprotein and redox related genes in order to identify functional genetic combinations linked to metabolic phenotype.

Vitamin D Receptor (VDR) Allelic Variants Correlating with Response to Vitamin D3 Supplementation in Breast Cancer Survivors

We investigated how vitamin D receptor (VDR) allelic variants affect breast cancer survivors’ responses to vitamin D3 supplementation to increase circulating 25-hydroxy vitamin D (25(OH)D) levels. Two hundred and fourteen patients who were diagnosed with breast cancer at least 6 mo, prior to the study and had completed all treatment regimens were assigned to consume 4000 IU of vitamin D3 daily for 12 weeks. Linear and multinomial logistic regression analyses were used to analyze the association of VDR single nucleotide polymorphism (SNPs) with changes in circulating 25(OH)D. The TaqI and BsmI VDR sequence variants modified the effect of vitamin D3 treatment on the plasma 25(OH)D changes (P value = 0.008 for TaqI and P value = 0.0005 for BsmI). Patients with the bb [Q4 vs. Q1 odds ratio(OR) 8.04, 95% confidence interval (CI) 1.55–41.57] and tt [Q4 vs. Q1 OR 4.64 95%CI 1.02–21.02] genotype of BsmI and TaqI had larger increases in plasma 25(OH)D levels compared to those with BB and TT genotype respectively after adjustment for potential confounders. Haplotype analyses suggested the existence of specific combination of alleles that might be associated with circulating 25(OH)D changes. VDR allelic variants modulate vitamin D3 supplementation to increase plasma 25(OH) levels in breast cancer survivors.

Characterization of the UK anthrax vaccine and human immunogenicity

ABSTRACT The manufacture of the UK Anthrax vaccine (AVP) focuses on the production of Protective Antigen (PA) from the Bacillus anthracis Sterne strain. Although used for decades, several of AVP’s fundamental properties are poorly understood, including its exact composition, the extent to which proteins other than PA may contribute to protection, and whether the degree of protection varies between individuals. This study involved three innovative investigations. Firstly, the composition of AVP was analyzed using liquid chromatography tandem mass-spectrometry (LC-MS/MS), requiring the development of a novel desorption method for releasing B. anthracis proteins from the vaccine’s aluminum-containing adjuvant. Secondly, computational MHC-binding predictions using NetMHCIIpan were made for the eight most abundant proteins of AVP, for the commonest HLA alleles in multiple ethnic groups, and for multiple B. anthracis strains. Thirdly, antibody levels and toxin neutralizing antibody (TNA) levels were measured in sera from AVP human vaccinees for both PA and Lethal Factor (LF). It was demonstrated that AVP is composed of at least 138 B. anthracis proteins, including PA (65%), LF (8%) and Edema Factor (EF) (3%), using LC-MS/MS. NetMHCIIpan predicted that peptides from all eight abundant proteins are likely to be presented to T cells, a pre-requisite for protection; however, the number of such peptides varied considerably between different HLA alleles. These analyses highlight two important properties of the AVP vaccine that have not been established previously. Firstly, the effectiveness of AVP within humans may not depend on PA alone; there is compelling evidence to suggest that LF has a protective role, with computational predictions suggesting that additional proteins may be important for individuals with specific HLA allele combinations. Secondly, in spite of differences in the sequences of key antigenic proteins from different B. anthracis strains, these are unlikely to affect the cross-strain protection afforded by AVP.

Genetics and Age-Related Eye Disease Study Formulation Interaction in Neovascular Age-Related Macular Degeneration.

This work aims to determine whether previously defined genotype risk groups interact with Age-Related Eye Disease Study formulation (AREDS-F) use in progression to neovascular age-related macular degeneration (nvAMD). We conducted a case-only study of 265 nvAMD patients. Patients were anonymously genotyped at the complement factor H and age-related maculopathy susceptibility 2 loci and segregated into genotype groups (GTGs) defined by specific combinations of risk alleles. Physicians, who were blind to patients' GTGs, obtained patients' AREDS-F use history. The facility performing genetic analysis was blind to the AREDS-F use history. We used logistic analysis to estimate the interaction coefficient between AREDS-F use and GTG 2 vs GTG 3 in a general-population model. The odds ratio of numbers of patients reporting prior AREDS-F use to nonuse for GTG 2 vs GTG 3 was 4.18 (P = .001). Logistic regression, correcting for nongenetic risk factors, gave an estimate of the β for interaction of AREDS-F with genotype of 1.57 (P = .001). This estimates a corrected odds ratio associated with the effect of interaction of 4.81 between those in GTG 2 compared with those in GTG 3. Our data indicate an interaction between GTGs and AREDS-F use that is consistent in size and direction with previously published reports, which had found that using AREDS-F supplements significantly increases the risk of nvAMD for some users and significantly protects other users.

Diversification in immunogenicity genes caused by selective pressures in invasive meningococci.

We studied population genomics of 486 Neisseria meningitidis isolates causing meningitis in the Netherlands during the period 1979–2003 and 2006–2013 using whole-genome sequencing to evaluate the impact of a hyperendemic period of serogroup B invasive disease. The majority of serogroup B isolates belonged to ST-41/44 (41 %) and ST-32 complex (16 %). Comparing the time periods, before and after the decline of serogroup B invasive disease, there was a decrease of ST-41/44 complex sequences (P=0.002). We observed the expansion of a sub-lineage within ST-41/44 complex sequences being associated with isolation from the 1979–2003 time period (P=0.014). Isolates belonging to this sub-lineage expansion within ST-41/44 complex were marked by four antigen allele variants. Presence of these allele variants was associated with isolation from the 1979–2003 time period after correction for multiple testing (Wald test, P=0.0043 for FetA 1–5; P=0.0035 for FHbp 14; P=0.012 for PorA 7–2.4 and P=0.0031 for NHBA two peptide allele). These sequences were associated with 4CMenB vaccine coverage (Fisher’s exact test, P<0.001). Outside of the sub-lineage expansion, isolates with markedly lower levels of predicted vaccine coverage clustered in phylogenetic groups showing a trend towards isolation in the 2006–2013 time period (P=0.08). In conclusion, we show the emergence and decline of a sub-lineage expansion within ST-41/44 complex isolates concurrent with a hyperendemic period in meningococcal meningitis. The expansion was marked by specific antigen peptide allele combinations. We observed preliminary evidence for decreasing 4CMenB vaccine coverage in the post-hyperendemic period.

Intronic variation of the SOHLH2 gene confers risk to male reproductive impairment

To evaluate whether SOHLH2 intronic variation contributes to the genetic predisposition to male infertility traits, including severe oligospermia (SO) and different nonobstructive azoospermia (NOA) clinical phenotypes. Genetic association study. Not applicable. Five hundred five cases (455 infertile patients diagnosed with NOA and 50 with SO) and 1,050 healthy controls from Spain and Portugal. None. Genomic DNA extraction from peripheral blood mononuclear cells, genotyping of the SOHLH2 polymorphisms rs1328626 and rs6563386 using the TaqMan allelic discrimination technology, case-control association analyses using logistic regression models, and exploration of functional annotations in publicly available databases. Evidence of association was observed for both rs6563386 with SO and rs1328626 with unsuccessful sperm retrieval after testicular sperm extraction (TESE-) in the context of NOA. A dominant effect of the minor alleles was suggested in both associations, either when the subset of patients with the manifestation were compared against the control group (rs6563386/SO: P=.021, odds ratio [OR] = 0.51; rs1328626/TESE-: P=.066, OR = 1.46) or against the group of patients without the manifestation (rs6563386/SO: P=.014, OR = 0.46; rs1328626/TESE-: P=.012, OR = 2.43). The haplotype tests suggested a combined effect of both polymorphisms. In silico analyses evidenced that this effect could be due to alteration of the isoform population. Our data suggest that intronic variation of SOHLH2 is associated with spermatogenic failure. The genetic effect is likely caused by different haplotypes of rs6563386 and rs1328626, which may predispose to SO or TESE- depending on the specific allelic combination.

Genetic risks of schizophrenia identified in a matched case-control study.

It has been suggested that dopaminergic neurotransmission plays important roles for the psychotic symptoms and probably etiology of schizophrenia. In our recent preliminary study, we demonstrated that the specific allele combinations of dopamine-related functional single nucleotide polymorphisms (SNPs), rs10770141, rs4680, and rs1800497 could indicate risks for schizophrenia. The present validation study involved a total of 2542 individuals who were age- and sex-matched in a propensity score matching analysis, and the results supported the statistical significances of the proposed genetic risks described in our previous reports. The estimated odds ratios were 1.24 (95% CI 1.06-1.45, p < 0.001) for rs4680, 1.73 (95% CI 1.47-2.02, p < 0.0001) for rs1800497, and 1.79 (95% CI 1.35-2.36, p < 0.0001) for rs10770141. A significant relationship was also revealed among these three polymorphisms and schizophrenia, with corresponding coefficients (p < 0.0001). In this study, we also present a new scoring model for the identification of individuals with the disease risks. Using the cut-off value of 2, our model exhibited sensitivity for almost two-thirds of all of the schizophrenia patients: odds ratio 1.87, 95% CI 1.59-2.19, p < 0.0001. In conclusion, we identified significant associations of dopamine-related genetic combinations with schizophrenia. These findings suggest that some types of dopaminergic neurotransmission play important roles for development of schizophrenia, and this type of approach may also be applicable for other multifactorial diseases, providing a potent new risk predictor.

3'-UTR Polymorphisms of Vitamin B-Related Genes Are Associated with Osteoporosis and Osteoporotic Vertebral Compression Fractures (OVCFs) in Postmenopausal Women.

As life expectancy increases, the prevalence of osteoporosis is increasing. In addition to vitamin D which is well established to have an association with osteoporosis, B vitamins, such as thiamine, folate (vitamin B9), and cobalamin (vitamin B12), could affect bone metabolism, bone quality, and fracture risk in humans by influencing homocysteine/folate metabolism. Despite the crucial role of B vitamins in bone metabolism, there are few studies regarding associations between B vitamin-related genes and osteoporosis. In this study, we investigated the genetic association of four single nucleotide polymorphisms (SNPs) within the 3’-untranslated regions of vitamin B-related genes, including TCN2 (encodes transcobalamin II), CD320 (encodes transcobalamin II receptor), SLC19A1 (encodes reduced folate carrier protein 1), and SLC19A2 (encodes thiamine carrier 1), with osteoporosis and osteoporotic vertebral compression fracture (OVCF). We recruited 301 postmenopausal women and performed genotyping of CD320 rs9426 C>T, TCN2 rs10418 C>T, SLC19A1 rs1051296 G>T, and SLC19A2 rs16862199 C>T using a polymerization chain reaction-restriction fragment length polymorphism assay. There was a significantly higher incidence of both osteoporosis (AOR 5.019; 95% CI, 1.533–16.430, p < 0.05) and OVCF (AOR, 5.760; 95% CI, 1.480–22.417, p < 0.05) in individuals with genotype CD320 CT+TT and high homocysteine concentrations. Allele combination analysis revealed that two combinations, namely CD320 C-TCN2 T-SLC19A1 T-SLC19A2 C (OR, 3.244; 95% CI, 1.478–7.120, p < 0.05) and CD320 T-TCN2 C-SLC19A1 G-SLC19A2 C (OR, 2.287; 95% CI, 1.094–4.782, p < 0.05), were significantly more frequent among the osteoporosis group. Our findings suggest that SNPs within the CD320 gene in 3´-UTR may contribute to osteoporosis and OVCF occurrences in some individuals. Furthermore, specific allele combinations of CD320, TCN2, SLC19A1, and SLC19A2 may contribute to increased susceptibility to osteoporosis and OVCF.

Allelic Variation for Prolamins in Spanish Durum Wheat Landraces and Its Relationship with Quality Traits

Wheat landraces are currently being explored mainly as a source of allelic variation related to crop resilience and low-input adaptation. Characterization of their high- and low-molecular weight glutenin subunits can aid breeders to select as donor local materials those ensuring good end-use properties in the derived elite cultivars. By using protein electrophoretic methods, we have determined the prolamin allelic profile of 116 Spanish durum wheat landraces. Their quality properties (as defined by grain protein content, sodium dodecyl sulfate (SDS) sedimentation volume and mixograph behavior) have also been assessed. The study has identified six novel glutenin alleles plus some other rare alleles some of which have been associated with improved durum wheat quality. Most of the novel variation detected needs to be characterized in a wider sample of varieties to establish any eventual beneficial effect on functional quality. Further analysis of the quality properties associated to specific allele combinations of Glu-A3, Glu-B3, and Glu-A1 has disclosed some clues on the influence on quality of certain non-allelic interactions between these main prolamin-encoding loci. Some of the landraces, showing outstanding values for the gluten quality parameters analyzed, might be directly used by farmers interested in the cultivation of traditional varieties for specialized food markets.

Interleukin-1 single nucleotide polymorphisms and risk of systemic lupus erythematosus among Iraqi patients

Present case-control study explored the association between five single nucleotide polymorphisms (SNPs) of interleukin-1 (IL-1) gene family (IL1A−889; rs1800587, IL1B−511; rs16944, IL1B+3962; rs1143634, IL1Rpsti 1970; rs2234650 and IL1RAmspa 11,100; rs315952) and SLE. A sample of 103 Iraqi female patients and 113 healthy matched females were investigated. Serological testing revealed that 91.1 and 88.9% of patients were seropositive for anti-nuclear and anti-double-stranded DNA antibodies, respectively, while none of the control females were seropositive. Serum level of C3 (54 vs. 108 mg/dL) and C4 (5 vs. 21 mg/dL) showed a significant decreased median in patients compared to control. Inspecting IL1 gene SNPs demonstrated a significant increased frequency of IL1A−889C allele in patients compared to control (72.8 vs.56.0%, odds ratio = 1.94, 95% confidence interval = 1.30–2.91), while T allele frequency was significantly decreased (27.2 vs.42.0%). For IL1B−511, IL1B+3962, IL1Rpsti 1970 and IL1RAmspa 11,100 SNPs, allele and genotype frequencies showed no significant variation between patients and control. A significant two-locus linkage disequilibrium (LD) was recorded between IL1B−511 and IL1RAmspa 11,100 SNPs in SLE patients only (log of likelihood odds ratio = 5.69, correlation coefficient = 0.241, LD coefficient = 0.517). Five-locus haplotype frequency estimation revealed that CCCTC and CCTCT haplotypes were positively associated with SLE risk. It is concluded that IL1A−889 SNP is associated with susceptibility to SLE, while, IL1B−511, IL1B+3962, IL1Rpsti 1970 and IL1RAmspa 11,100 SNPs may have no influence on SLE risk. Specific allelic combinations (haplotypes) between the five SNPs may also have a susceptibility role in SLE.

Molecular characterization of apple (Malus × domestica Borkh.) genotypes originating from three complementary conservation strategies

Apple (Malus × domestica Borkh.) genotypes originating from different plant collections (field collection, in vitro plant collections undergoing or not undergoing cryopreservation) were screened and characterized by SSR markers. Shoot tips excised from plants grown in vitro were successfully cryopreserved by encapsulation-dehydration. The highest regrowth frequency (69%, cultivar Goldrush) of cryopreserved apices was achieved after 24 h of osmoprotection in 0.5 M sucrose, 3 h of desiccation, and 24% water content of alginate beads. No differences in morphological characteristics including shoot length and number and length of roots were observed between controls and plants recovered after cryopreservation. SSR markers were used for calculation of genetic similarities between plants from the field collection, in vitro-micropropagated plants, or plants regenerated after liquid nitrogen storage. The set of microsatellite markers showed a low level of polymorphism among the studied genotypes, which could be distinguished by a specific combination of alleles generated by CH03g07, CH05c02, CH05d11, and CH05e03 primers. The CH03g07, CH05c02, CH05d11, CH05e03, GD96, GD147, and GD162 SSR markers exhibited low levels of polymorphism, while CH04AE07, CH04g10, GD100, and GD142 were nonpolymorphic. The Dice coefficient confirmed the effectiveness of SSRs for distinguishing between plants from ex situ collections and preserved plants. No major differences between ex situ plants, micropropagated plants, and plants recovered after cryopreservation were observed.

Risk and protective effects of serotonin and BDNF genes on stress-related adult psychiatric symptoms

We focused on individual risk by examining childhood adversity and current psychiatric symptoms in a sample of 100 college students genotyped for both the serotonin transporter (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF). Naturally occurring allelic variation in 5-HTTLPR (short/long) and BDNF (valine/methionine) have been strongly implicated in stress-related psychiatric risk, but the combined effects of these alleles on psychological functioning have yet to be fully elucidated. Univariate analysis revealed gene-environment correlations linking heightened psychiatric risk with past childhood adversity for short but not long 5-HTTLPR allelic carriers and for valine (Val) but not methionine (Met) BDNF allelic carriers. Multivariate analyses revealed a significant gene x gene interaction with results showing that risk varied systematically depending on both 5-HTTLPR and BDNF alleles, independent of childhood adversity. Hierarchical regression analyses indicated that approximately 11% of the variance in symptoms of depression could be specifically accounted for by the epistatic interaction of 5-HTTLPR and BDNF val66Met polymorphisms. Allelic group analyses indicated lowest risk, as measured by depression and anxiety, for allelic carriers of 5-HTTLPR-short and BDNF Met, followed by 5-HTTLPR-long and BDNF-Val, 5-HTTLPR-short and BDNF-Val, and 5-HTTLPR-long and BDNF-Met. Results suggest that protective or risk-enhancing effects on stress-related psychiatric functioning may depend on specific allelic combinations of 5-HTTLPR and BDNF.

Characterization of genes and alleles involved in the control of flowering time in grapevine.

Grapevine (Vitis vinifera) is one of the most important perennial crop plants in worldwide. Understanding of developmental processes like flowering, which impact quality and quantity of yield in this species is therefore of high interest. This gets even more important when considering some of the expected consequences of climate change. Earlier bud burst and flowering, for example, may result in yield loss due to spring frost. Berry ripening under higher temperatures will impact wine quality. Knowledge of interactions between a genotype or allele combination and the environment can be used for the breeding of genotypes that are better adapted to new climatic conditions. To this end, we have generated a list of more than 500 candidate genes that may play a role in the timing of flowering. The grapevine genome was exploited for flowering time control gene homologs on the basis of functional data from model organisms like A. thaliana. In a previous study, a mapping population derived from early flowering GF.GA-47-42 and late flowering ‘Villard Blanc’ was analyzed for flowering time QTLs. In a second step we have now established a workflow combining amplicon sequencing and bioinformatics to follow alleles of selected candidate genes in the F1 individuals and the parental genotypes. Allele combinations of these genes in individuals of the mapping population were correlated with early or late flowering phenotypes. Specific allele combinations of flowering time candidate genes within and outside of the QTL regions for flowering time on chromosome 1, 4, 14, 17, and 18 were found to be associated with an early flowering phenotype. In addition, expression of many of the flowering candidate genes was analyzed over consecutive stages of bud and inflorescence development indicating functional roles of these genes in the flowering control network.

Association between polymorphisms in estrogen metabolism genes and breast cancer development in Chinese women

We comprehensively identified polymorphisms in estrogen-metabolizing genes that may be associated with breast cancer initiation in Chinese women, via an ongoing prospective case-control study.An ongoing prospective case-control study of 427 female case patients diagnosed with breast cancer from August 2013 to March 2015 and 536 women (case controls) with no prior history of cancer or benign breast tumors was performed. Buccal cell specimens were obtained using the cotton swabbing method. DNA was extracted from the buccal cells using the phenol/chloroform method. Genotype was carried out for 5 single nucleotide polymorphisms (rs4646903, rs1056836, rs1695, rs4970737, and rs4680) using direct sequencing.The polymorphic genotypes of glutathione S-transferase (GSTP1) (P = .044) and catechol-O-methyltransferase (COMT) (P = .008) showed significantly different distributions, while that of cytochrome P450 (CYP1B1) (P = .051) showed a slight difference in distribution between healthy women and patients with breast cancer. Individuals with homozygous variant genotypes for GSTP1 or COMT exhibited a higher risk of developing breast cancer than those with wild-type genotypes; however, for CYP1B1, the homozygous variant genotype was associated with a lower risk, and the heterozygous genotype for these 3 genes was not associated with breast cancer development.An individual's risk of breast cancer is only influenced by the specific combination of risk-associated alleles of COMT and GSTP1, despite the protective effects of the homozygous CYP1B1 genotype revealed by univariate analysis.

Allelic Variation and Distribution of the Major Maturity Genes in Different Soybean Collections.

Soybean time of flowering and maturity are genetically controlled by E genes. Different allelic combinations of these genes determine soybean adaptation to a specific latitude. The paper describes the first attempt to assess adaptation of soybean genotypes developed and realized at Institute of Field and Vegetable Crops, Novi Sad, Serbia [Novi Sad (NS) varieties and breeding lines] based on E gene variation, as well as to comparatively assess E gene variation in North-American (NA), Chinese, and European genotypes, as most of the studies published so far deal with North-American and Chinese cultivars and breeding material. Allelic variation and distribution of the major maturity genes (E1, E2, E3, and E4) has been determined in 445 genotypes from soybean collections of NA ancestral lines, Chinese germplasm, and European varieties, as well as NS varieties and breeding lines. The study showed that allelic combinations of E1–E4 genes significantly determined the adaptation of varieties to different geographical regions, although they have different impacts on maturity. In general, each collection had one major E genotype haplogroup, comprising over 50% of the lines. The exceptions were European varieties that had two predominant haplogroups and NA ancestral lines distributed almost evenly among several haplogroups. As e1-as/e2/E3/E4 was the most common genotype in NS population, present in the best-performing genotypes in terms of yield, this specific allele combination was proposed as the optimal combination for the environments of Central-Eastern Europe.