Intergenic variants, rs1200114 and rs1200108 are genetically associated along with a decreased ATP1B1 expression in Fuchs Endothelial Corneal Dystrophy.

Fuchs endothelial corneal dystrophy (FECD) is an age-related, bilateral corneal condition, characterized by apoptosis of the terminally differentiated endothelial cells. A genome-wide association study (GWAS) conducted in the European population in 2017, identified a new single nucleotide polymorphism (SNP), rs1200114 in the intergenic region between long intergenic non-protein coding RNA 970 (LINC00970) and ATPase Na+/K+ transporting subunit beta 1 (ATP1B1). The major focus of the current study is to understand the genetic association of this intergenic variant, rs1200114 with FECD in the Indian population. Sanger sequencing followed by statistical analysis indicated a significant difference in the allelic frequency between controls and cases (P = 0.01) with the minor allele 'G' of rs1200114 imparting a 1.64 fold increased risk for the disease. Luciferase reporter assay revealed no significant difference in the luciferase activity between allele 'A' and 'G' of rs1200114. However, quantitative RT-PCR assay revealed lower expression of ATP1B1 in FECD subjects compared with controls (P = 0.007). Therefore, to find whether another nearby SNP imparts regulatory effect, tag SNP association analysis was carried out; which revealed a significant association of another SNP, rs1200108, present in the intergenic region between LINC00970 and ATP1B1 with FECD (P = 0.009). The protective allele 'A' of rs1200108 displayed reduced reporter activity as opposed to the risk allele 'G' (P = 0.014). Furthermore, haplotype 'A-A' of rs1200108 - rs1200114 was present at a higher frequency in control subjects, suggesting it as a protective haplotype. Altogether, this study inferred the genetic association of rs1200114 and rs1200108 along with the decreased expression of ATP1B1 related to FECD pathogenesis in the Indian population.

LmTag: functional-enrichment and imputation-aware tag SNP selection for population-specific genotyping arrays.

Despite the rapid development of sequencing technology, single-nucleotide polymorphism (SNP) arrays are still the most cost-effective genotyping solutions for large-scale genomic research and applications. Recent years have witnessed the rapid development of numerous genotyping platforms of different sizes and designs, but population-specific platforms are still lacking, especially for those in developing countries. SNP arrays designed for these countries should be cost-effective (small size), yet incorporate key information needed to associate genotypes with traits. A key design principle for most current platforms is to improve genome-wide imputation so that more SNPs not included in the array (imputed SNPs) can be predicted. However, current tag SNP selection methods mostly focus on imputation accuracy and coverage, but not the functional content of the array. It is those functional SNPs that are most likely associated with traits. Here, we propose LmTag, a novel method for tag SNP selection that not only improves imputation performance but also prioritizes highly functional SNP markers. We apply LmTag on a wide range of populations using both public and in-house whole-genome sequencing databases. Our results show that LmTag improved both functional marker prioritization and genome-wide imputation accuracy compared to existing methods. This novel approach could contribute to the next generation genotyping arrays that provide excellent imputation capability as well as facilitate array-based functional genetic studies. Such arrays are particularly suitable for under-represented populations in developing countries or non-model species, where little genomics data are available while investment in genome sequencing or high-density SNP arrays is limited. $\textrm{LmTag}$ is available at: https://github.com/datngu/LmTag.

A PCR-RFLP method for genotyping of inversion 2Rc in Anopheles coluzzii.

BACKGROUND: Genotyping of polymorphic chromosomal inversions in malaria vectors such as An. coluzzii Coetzee & Wilkerson is important, both because they cause cryptic population structure that can mislead vector analysis and control and because they influence epidemiologically relevant eco-phenotypes. The conventional cytogenetic method of genotyping is an impediment because it is labor intensive, requires specialized training, and can be applied only to one gender and developmental stage. Here, we circumvent these limitations by developing a simple and rapid molecular method of genotyping inversion 2Rc in An. coluzzii that is both economical and field-friendly. This inversion is strongly implicated in temporal and spatial adaptations to climatic and ecological variation, particularly aridity. METHODS: Using a set of tag single-nucleotide polymorphisms (SNPs) strongly correlated with inversion orientation, we identified those that overlapped restriction enzyme recognition sites and developed four polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) assays that distinguish alternative allelic states at the tag SNPs. We assessed the performance of these assays using mosquito population samples from Burkina Faso that had been cytogenetically karyotyped as well as genotyped, using two complementary high-throughput molecular methods based on tag SNPs. Further validation was performed using mosquito population samples from additional West African (Benin, Mali, Senegal) and Central African (Cameroon) countries. RESULTS: Of four assays tested, two were concordant with the 2Rc cytogenetic karyotype > 90% of the time in all samples. We recommend that these two assays be employed in tandem for reliable genotyping. By accepting only those genotypic assignments where both assays agree, > 99% of assignments are expected to be accurate. CONCLUSIONS: We have developed tandem PCR-RFLP assays for the accurate genotyping of inversion 2Rc in An. coluzzii. Because this approach is simple, inexpensive, and requires only basic molecular biology equipment, it is widely accessible. These provide a crucial tool for probing the molecular basis of eco-phenotypes relevant to malaria epidemiology and vector control.

Mutation of Hashimoto's Thyroiditis and Papillary Thyroid Carcinoma Related Genes and the Screening of Candidate Genes.

Clinical studies have shown similarities in the genetic background and biological functional characteristics between Hashimoto's thyroiditis (HT) and papillary thyroid carcinoma (PTC), and that HT may increase risks of PTC. Here, we set to determine the gene expression specificity of HT and PTC by screening related genes or co-expressed genes and exploring their genetic correlation. Referencing the Oncomine database, HT-related genes were discovered to be expressed in many different types of thyroid cancer, such as TSHR that is highly expressed in thyroid cancer. An in-depth genetic analysis and verification of 35 cancer and paracancerous tissue pairs from patients with thyroid cancer, and 35 tissues and blood cells pairs from patients with Hashimoto's thyroiditis was conducted. Gene chip technology research showed that TSHR, BACH2, FOXE1, RNASET2, CTLA4, PTPN22, IL2RA and other HT-related genes were all expressed in PTC, in which TSHR was significantly over-expressed in PTC patients sensitive to radioactive iodine therapy, while BACH2 was significantly under-expressed in these patients. The biologically significant candidate Tag SNP highlighted from HT-related genes was screened by the high-throughput detection method. Somatic mutations in patients with HT and PTC were detected by target region capture technique, and 75 mutations were found in patients with HT and PTC. The upstream regulatory factors of the different genes shared by HT and PTC were analyzed based on Ingenuity Pathway Analysis (IPA), and it was found that HIF-1α and PD-L1 could be used as important upstream regulatory signal molecules. These results provide a basis for screening key diagnostic genes of PTC by highlighting the relationship between some HT-related genes and their polymorphisms in the pathogenesis of PTC.

Haplotype-based association study between PRCP gene polymorphisms and essential hypertension in Hani minority group from a remote region of China.

OBJECTIVE: Prolylcarboxypeptidase (PRCP) is both involved in the Kallikrein-Kinin system (KKS) and renin-angiotensin-aldosterone system (RAAS). This study aimed to determine the genetic impact of PRCP gene polymorphisms on essential hypertension (EH) in an isolated population from a remote region of China. METHODS: A haplotype-based study was investigated in 346 EH patients and 346 normal subjects and all samples were Hani minority residents in Southwest China. A total of 11 tag single nucleotide polymorphisms (SNPs) in PRCP gene were tested by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: Single site analysis found that PRCP gene 3'UTR SNP rs3750931 was associated with EH. The minor allele G of rs3750931 was more prevalent in the EH patients compared to control subjects after Bonferroni correction (p < 0.05). Moreover, the rs3750931 G allele carriers showed higher average blood pressure (BP) level among the subjects. The H2 (GAGCACTAACA) haplotype without rs3750931 G allele showed the protective effect for EH (OR = 0.68, 95 CI 0.54-0.85, p = 0.001). CONCLUSION: The present study indicated PRCP gene rs3750931 was associated with the risk of EH. This SNP G allele could be considered as one of risk markers for EH in Hani population.

High-Throughput Genotyping of Common Chromosomal Inversions in the Afrotropical Malaria Mosquito Anopheles Funestus.

Polymorphic chromosomal inversions have been implicated in local adaptation. In anopheline mosquitoes, inversions also contribute to epidemiologically relevant phenotypes such as resting behavior. Progress in understanding these phenotypes and their mechanistic basis has been hindered because the only available method for inversion genotyping relies on traditional cytogenetic karyotyping, a rate-limiting and technically difficult approach that is possible only for the fraction of the adult female population at the correct gonotrophic stage. Here, we focus on an understudied malaria vector of major importance in sub-Saharan Africa, Anopheles funestus. We ascertain and validate tag single nucleotide polymorphisms (SNPs) using high throughput molecular assays that allow rapid inversion genotyping of the three most common An. funestus inversions at scale, overcoming the cytogenetic karyotyping barrier. These same inversions are the only available markers for distinguishing two An. funestus ecotypes that differ in indoor resting behavior, Folonzo and Kiribina. Our new inversion genotyping tools will facilitate studies of ecotypic differentiation in An. funestus and provide a means to improve our understanding of the roles of Folonzo and Kiribina in malaria transmission.

Inversion Genotyping in the Anopheles gambiae Complex Using High-Throughput Array and Sequencing Platforms.

Chromosomal inversion polymorphisms have special importance in the Anopheles gambiae complex of malaria vector mosquitoes, due to their role in local adaptation and range expansion. The study of inversions in natural populations is reliant on polytene chromosome analysis by expert cytogeneticists, a process that is limited by the rarity of trained specialists, low throughput, and restrictive sampling requirements. To overcome this barrier, we ascertained tag single nucleotide polymorphisms (SNPs) that are highly correlated with inversion status (inverted or standard orientation). We compared the performance of the tag SNPs using two alternative high throughput molecular genotyping approaches vs. traditional cytogenetic karyotyping of the same 960 individual An. gambiae and An. coluzzii mosquitoes sampled from Burkina Faso, West Africa. We show that both molecular approaches yield comparable results, and that either one performs as well or better than cytogenetics in terms of genotyping accuracy. Given the ability of molecular genotyping approaches to be conducted at scale and at relatively low cost without restriction on mosquito sex or developmental stage, molecular genotyping via tag SNPs has the potential to revitalize research into the role of chromosomal inversions in the behavior and ongoing adaptation of An. gambiae and An. coluzzii to environmental heterogeneities.

Highly specific PCR-RFLP assays for karyotyping the widespread 2Rb inversion in malaria vectors of the Anopheles gambiae complex.

BACKGROUND: Chromosomal inversion polymorphisms play a role in adaptation to heterogeneous environments. Inversion polymorphisms are implicated in the very high ecological flexibility of the three main malaria vector species of the Afrotropical Anopheles gambiae complex, facilitating the exploitation of anthropogenic environmental modifications and promoting a strong association with humans. In addition to extending the species' spatial and temporal distribution, inversions are associated with epidemiologically relevant mosquito behavior and physiology, underscoring their medical importance. We here present novel PCR-RFLP based assays strongly predictive of genotype for the cosmopolitan 2Rb inversion in An. coluzzii and An. gambiae, a development which overcomes the numerous constraints inherent to traditional cytological karyotyping. METHODS: We designed PCR-RFLP genotyping assays based on tag SNPs previously computationally identified as strongly predictive (> 95%) of 2Rb genotype. We targeted those tags whose alternative allelic states destroyed or created the recognition site of a commercially available restriction enzyme, and designed assays with distinctive cleavage profiles for each inversion genotype. The assays were validated on 251 An. coluzzii and 451 An. gambiae cytologically karyotyped specimens from nine countries across Africa and one An. coluzzii laboratory colony. RESULTS: For three tag SNPs, PCR-RFLP assays (denoted DraIII, MspAI, and TatI) reliably produced robust amplicons and clearly distinguishable electrophoretic profiles for all three inversion genotypes. Results obtained with the DraIII assay are ≥ 95% concordant with cytogenetic assignments in both species, while MspAI and TatI assays produce patterns highly concordant with cytogenetic assignments only in An. coluzzii or An. gambiae, respectively. Joint application of species-appropriate pairs of assays increased the concordance levels to > 99% in An. coluzzii and 98% in An. gambiae. Potential sources of discordance (e.g. imperfect association between tag and inversion, allelic dropout, additional polymorphisms in the restriction target site, incomplete or failed restriction digestion) are discussed. CONCLUSIONS: The availability of highly specific, cost effective and accessible molecular assays for genotyping 2Rb in An. gambiae and An. coluzzii allows karyotyping of both sexes and all developmental stages. These novel tools will accelerate deeper investigations into the role of this ecologically and epidemiologically important chromosomal inversion in vector biology.

In Silico Karyotyping of Chromosomally Polymorphic Malaria Mosquitoes in the Anopheles gambiae Complex.

Chromosomal inversion polymorphisms play an important role in adaptation to environmental heterogeneities. For mosquito species in the Anopheles gambiae complex that are significant vectors of human malaria, paracentric inversion polymorphisms are abundant and are associated with ecologically and epidemiologically important phenotypes. Improved understanding of these traits relies on determining mosquito karyotype, which currently depends upon laborious cytogenetic methods whose application is limited both by the requirement for specialized expertise and for properly preserved adult females at specific gonotrophic stages. To overcome this limitation, we developed sets of tag single nucleotide polymorphisms (SNPs) inside inversions whose biallelic genotype is strongly correlated with inversion genotype. We leveraged 1,347 fully sequenced An. gambiae and Anopheles coluzzii genomes in the Ag1000G database of natural variation. Beginning with principal components analysis (PCA) of population samples, applied to windows of the genome containing individual chromosomal rearrangements, we classified samples into three inversion genotypes, distinguishing homozygous inverted and homozygous uninverted groups by inclusion of the small subset of specimens in Ag1000G that are associated with cytogenetic metadata. We then assessed the correlation between candidate tag SNP genotypes and PCA-based inversion genotypes in our training sets, selecting those candidates with >80% agreement. Our initial tests both in held-back validation samples from Ag1000G and in data independent of Ag1000G suggest that when used for in silico inversion genotyping of sequenced mosquitoes, these tags perform better than traditional cytogenetics, even for specimens where only a small subset of the tag SNPs can be successfully ascertained.

The Effect of HER2 Single Nucleotide Polymorphisms on Cervical Cancer Susceptibility and Survival in a Chinese Population.

Background: Cervical cancer (CCa) is a multifactorial gynecologic disease worldwide. Effects of HER2 polymorphisms, especially those in exonic region, have been investigated in many gynecologic diseases. In this study, we evaluated the influence of functional HER2 polymorphisms on susceptibility and survival of CCa in a Chinese population. Methods: We genotyped the HER2 exonic polymorphisms by TaqMan in both case-control study (413 CCa patients vs. 396 controls) and survival study (413 CCa patients). Logistic regression and Cox regression were adopted to evaluate the genetic association with the risk and outcomes of CCa, respectively. Results: In the case-control study, there was no significant difference between patients and controls in either HER2 rs1136201 or rs1058808. However, when combined, these two polymorphisms demonstrated a significant hazardous effect for CCa (P = 0.012). Besides, number of variants was also influential (P trend =0.002). In survival analysis, dominant model of rs1136201 and co-dominant modelof rs1058808 were significantly associated with the survival (P = 0.037 and P =0.028). The combination of rs1136201 and rs1058808 also negatively impacted CCa survival (P = 0.009). Cox regression further revealed the significance of the polymorphism combination (ß = 0.38, P = 0.025, HR= 1.47, 95%CI = 1.05-2.05). Functional assay of these polymorphisms demonstrated that rs1058808 G allele was associated with stronger expression of HER2 gene. Conclusions: Our results suggested that the combination of HER2 rs1136201and rs1058808 was significantly associated with the susceptibility of CCa. Besides, this combination of polymorphism s also substantially impacted the survival of CCa patients.

Analysis of the association of clinical factors and IL4 gene polymorphisms with root resorption in avulsed teeth after 1 year of replantation.

AIM: To investigate the association of clinical variables and polymorphisms (tag SNPs) in the interleukin 4 (IL4) gene, with the prognosis of avulsed and replanted teeth. METHODOLOGY: Ninety-four patients who suffered avulsion and had their teeth replanted and endodontically treated were included. Periapical radiographs were obtained soon after tooth replantation and after 1 year. For genotypic IL4 gene analysis, the DNA from oral mucosa cells was collected, and polymorphisms were investigated by real-time PCR. Univariate and multivariate analyses were performed to verify the association of clinical and genetic variables and the outcome of the replanted teeth (P < 0.05). RESULTS: After multivariate analysis, extra-alveolar time longer than 1 h was significantly associated with external root resorption. No significant association was observed between IL4 gene polymorphisms and root resorption. CONCLUSION: No association between root resorption and IL4 gene polymorphisms was observed. An extra-alveolar time of more than 1 h was associated with a susceptibility for external root resorption. Replanting the tooth in its socket immediately is the most important factor to maintain a healthy root surface.

Association study on polymorphisms of cAMP signaling pathway with recurrent major depressive disorder / 中华行为医学与脑科学杂志

Objective@#To investigate the possible role of tag single nucleotide polymorphisms in cAMP signaling pathway in patients with recurrent major depressive disorder in Chinese Han population.@*Methods@#1 030 patients with recurrent major depressive disorder according to the DSM-Ⅳ criteria were recruited as case group and 851 age- and gender- matched healthy volunteers were recruited as control group.The sequenom mass spectrometry method was adopted to explore the genotype and allele frequency distributions of tag single nucleotide polymorphisms of cAMP signaling pathway in the two groups.@*Results@#The differences of genotype and allele frequencies of the ADCY7 gene loci rs1064448 and HTR2A gene loci rs17068986 were significant between case group and control group(P<0.05). The difference of the genotype frequencies(492∶423∶112, 356∶401∶91; 538∶392∶94, 414∶371∶61; 24∶165∶838, 3∶150∶694; 219∶468∶337, 139∶418∶237; 153∶481∶393, 115∶446∶286; 53∶286∶688, 25∶296∶524)of the ADCY9 gene loci rs2531995, BDNF gene loci rs10835210, rs7124442, CREB1 gene loci 4675690, rs2551645 and the HTR2A gene loci rs3125 were significant in case-control group(P<0.05); while the rest tagSNPs had no statistical difference in genotype and allele distribution frequencies in case-control group(P>0.05). In gender-specific analyses, the differences of the genotype and allele frequencies of the ADCY7 gene loci rs106448 and CREB1 gene loci rs2551645 were significant in male case-control group(P<0.05); the differences of the genotype(195∶177∶49, 193∶423∶41; 221∶158∶42, 237∶201∶28; 83∶188∶148, 85∶237∶122; 24∶113∶284, 10∶176∶281)of the ADCY9 gene loci rs2531995, BDNF gene loci rs10835210, CREB1 gene loci rs4675690, and HTR2A gene loci rs3125 were significant in male case-control group(P<0.05); while the rest tagSNPs had no statistical difference in genotype and allele distribution frequencies in male case-control group(P>0.05). The differences of the genotype and allele frequencies of the ADCY7 gene loci rs1064448 and HTR2A gene loci rs17068986 were significant in female case-control group(P<0.05). The differences of the genotype(16∶94∶497, 1∶73∶308; 136∶280∶189, 54∶181∶115)of the BDNF gene loci rs7124442 and CREB1 gene loci rs4675690 were significant in female case-control group(P<0.05). The differences of the allele frequencies(840: 372, 493: 267) of the ADCY9 gene loci rs2531995 were significant in female case-control group(P<0.05), while the rest tagSNPs had no statistical difference in genotype and allele distribution frequencies in female case-control group(P>0.05).@*Conclusion@#The ADCY7 gene loci rs1064448 and CREB1 gene loci rs4675690 are associated with recurrent major depressive disorder in Chinese Han population.

Genome-wide survey of single-nucleotide polymorphisms reveals fine-scale population structure and signs of selection in the threatened Caribbean elkhorn coral, Acropora palmata.

The advent of next-generation sequencing tools has made it possible to conduct fine-scale surveys of population differentiation and genome-wide scans for signatures of selection in non-model organisms. Such surveys are of particular importance in sharply declining coral species, since knowledge of population boundaries and signs of local adaptation can inform restoration and conservation efforts. Here, we use genome-wide surveys of single-nucleotide polymorphisms in the threatened Caribbean elkhorn coral, Acropora palmata, to reveal fine-scale population structure and infer the major barrier to gene flow that separates the eastern and western Caribbean populations between the Bahamas and Puerto Rico. The exact location of this break had been subject to discussion because two previous studies based on microsatellite data had come to differing conclusions. We investigate this contradiction by analyzing an extended set of 11 microsatellite markers including the five previously employed and discovered that one of the original microsatellite loci is apparently under selection. Exclusion of this locus reconciles the results from the SNP and the microsatellite datasets. Scans for outlier loci in the SNP data detected 13 candidate loci under positive selection, however there was no correlation between available environmental parameters and genetic distance. Together, these results suggest that reef restoration efforts should use local sources and utilize existing functional variation among geographic regions in ex situ crossing experiments to improve stress resistance of this species.

Genetic association of polymorphisms in AXIN1 gene with clear cell renal cell carcinoma in a Chinese population.

AIM: The purpose of the present study is to investigate the association between the polymorphisms in AXIN1 with susceptibility to clear cell renal cell carcinoma (ccRCC). MATERIALS & METHODS:  A total of 284 ccRCC patients and 439 healthy volunteers were enrolled. Totally three tag single nucleotide polymorphisms in AXIN1 gene were genotyped using PCR & restriction fragment length polymorphism. RESULTS: Significantly increased ccRCC risk was observed to be associated with the CT/CC genotypes of rs1805105 and AA genotype of rs12921862. Patients carrying the rs1805105 CT genotype had a 1.92-fold increased risk to developing clinical stage III and IV cancer. CONCLUSION: Our results suggested the rs1805105 CT/CC genotypes and rs12921862 AA genotype may relate to ccRCC development.

Association Analysis of Nonsyndromic Congenital Heart Disease and Tag Single Nucleotide Polymorphisms of TBX20 and Genes in the Ras-MAPK Pathway.

AIMS: The present study was performed to determine whether there are variants in TBX20 and genes of the Ras-MAPK pathway associated with nonsyndromic congenital heart disease (ns-CHD). MATERIALS AND METHODS: A total of 223 ns-CHD patients and 273 healthy controls from China were selected as study subjects to perform an association analysis using 22 tag single-nucleotide polymorphisms (tag SNPs) located either in one of three genes in the Ras-MAPK pathway (MAP2K2, BRAF, and RAF1) or the TBX20 gene that have previously been associated with syndromic congenital heart disease. RESULTS: The results showed that none of these tag SNPs are associated with ns-CHD. CONCLUSIONS: The results suggested that these disease-causing genes, which were previously discovered in familial cases, might not be the major genetic factors causing the development of ns-CHD in Chinese.

New multilocus linkage disequilibrium measure for tag SNP selection.

Numerous approaches have been proposed for selecting an optimal tag single-nucleotide polymorphism (SNP) set. Most of these approaches are based on linkage disequilibrium (LD). Classical LD measures, such as D' and r2, are frequently used to quantify the relationship between two marker (pairwise) linkage disequilibria. Despite of their successful use in many applications, these measures cannot be used to measure the LD between multiple-marker. These LD measures need information about the frequencies of alleles collected from haplotype dataset. In this study, a cluster algorithm is proposed to cluster SNPs according to multilocus LD measure which is based on information theory. After that, tag SNPs are selected in each cluster optimized by the number of tag SNPs, prediction accuracy and so on. The experimental results show that this new LD measure can be directly applied to genotype dataset collected from the HapMap project, so that it saves the cost of haplotyping. More importantly, the proposed method significantly improves the efficiency and prediction accuracy of tag SNP selection.

Association study on interaction effects of CREB1 gene and BDNF gene polymorphisms and recurrent major depressive disorder / 中华行为医学与脑科学杂志

Objective To investigate the interactions between cAMP-response element-binding protein 1 (CREB 1) gene polymorphisms (rs889895,rs3770704,rs2551645,rs4675690) and brain derived neurotrophic factor (BDNF) gene polymorphisms (rs7124442,rs 10835210) and the association with recurrent major depressive disorder.Methods The blood samples were taken from 768 recurrent major depressive disorder patients and 511 healthy controls.The DNA was isolated from blood samples and was detected by SNP Sequenom Mass Array analysis.Chi-square test was used to compare differences in the frequency distribution of alleles and genotype between depression and controls.The generalized multifactor dimensionality reduction (GMDR) method was used to analyze the gene-gene interaction.Binary logistic regression was used to verify the optimal model.Results After adjusting the factors of sex and age,the GMDR analysis showed rs10835210 was the optimal model.In this model,the testing balanced accuracy was 0.5319 and cross-validation consistency value was 10/10.And rs10835210 had a statistically significant effect on the risk of recurrent major depressive disorder(P=0.0107).There was no significant gene-gene interaction of five tag SNPs on recurrent major depressive disorder(P＞0.05).Binary logistic regression analysis showed the AC contributed to a significantly lower risk of recurrent major depressive disorder than did the CC (OR =0.772,95％ CI=0.608-0.980,P=0.033).It was failed to find the genetic polymorphism of CREB1 rs889895.Conclusion BDNF rs10835210 may be one of the biological markers of recurrent major depressive disorder.

Genetic Architecture of Resistance to Stripe Rust in a Global Winter Wheat Germplasm Collection.

Virulence shifts in populations of Puccinia striiformis f. sp. tritici (Pst), the causal pathogen of wheat stripe rust, are a major challenge to resistance breeding. The majority of known resistance genes are already ineffective against current races of Pst, necessitating the identification and introgression of new sources of resistance. Germplasm core collections that reflect the range of genetic and phenotypic diversity of crop species are ideal platforms for examining the genetic architecture of complex traits such as resistance to stripe rust. We report the results of genetic characterization and genome-wide association analysis (GWAS) for resistance to stripe rust in a core subset of 1175 accessions in the National Small Grains Collection (NSGC) winter wheat germplasm collection, based on genotyping with the wheat 9K single nucleotide polymorphism (SNP) iSelect assay and phenotyping of seedling and adult plants under natural disease epidemics in four environments. High correlations among the field data translated into high heritability values within and across locations. Population structure was evident when accessions were grouped by stripe rust reaction. GWAS identified 127 resistance loci that were effective across at least two environments, including 20 with significant genome-wide adjusted P-values. Based on relative map positions of previously reported genes and QTL, five of the QTL with significant genome-wide adjusted P-values in this study represent potentially new loci. This study provides an overview of the diversity of Pst resistance in the NSGC winter wheat germplasm core collection, which can be exploited for diversification of stripe rust resistance in breeding programs.

Angiotensinogen gene polymorphisms and progression of chronic kidney disease in ADPKD patients.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a multisystemic and progressive disorder characterized by cyst formation and kidney enlargement and ultimately renal failure. Reduction of CKD progression in the ADPKD by pharmacological blockade of the renin-angiotensin-aldosterone system (RAAS) using ACE inhibitors indicated the involvement of RAAS pathway in the progression of CKD. The aim of the present study is to investigate the role of angiotensinogen tag-single nucleotide polymorphisms (AGT tag-SNPs) in progression of CKD. METHODS: Twelve AGT tag-SNPs were genotyped in 102 ADPKD patients and 106 non-ADPKD subjects using FRET-based KASPar method. Genotypes and haplotypes were compared between ADPKD and controls. The effect of genotypes and hypertension on CKD progression was assessed using univariate and multivariate logistic regression. Mantel-Haenszel (M-H) stratified analysis was performed to study the interaction between CKD stages and hypertension. RESULTS: Of the twelve tag-SNPs analyzed, only rs11122578 SNP deviated Hardy-Weinberg equilibrium in controls. Significant association between two AGT polymorphisms (rs11122577 and rs4762) and ADPKD was observed. Analysis of linkage disequilibrium revealed two haplotype blocks and haplotypes are not associated with ADPKD. The univariate analysis revealed that the age, hypertension, family history of diabetes and AGT rs4762 contributed to the progression of CKD in ADPKD. The modifier effect of these factors remained even after controlling other variables in multivariate analysis. CONCLUSIONS: The results of our study suggest significant association between Thr207Met polymorphism of AGT and CKD progression and acts as an effect modifier of renal disease progression in ADPKD.

Associations between CLCNKA_B tag SNPs with essential hypertension and interactions between genetic and environmental factors in an island population in China.

OBJECTIVE: Essential hypertension (EH) is known as the result from the interaction of environmental and genetic factors. We selected tag SNPs of CLCNKA_B genes as gene markers, to elucidate the relationship between CLCNKA_B and EH, and to determine the possible interaction among tag SNPs and dietary factors in island of China. METHODS: A case-control study was conducted in Changshan islands of China, blood samples of 806 participants were genotyped, and the general characteristics and dietary habits of them were collected. Unconditional logistic regression (ULR) was used to assess the effects of CLCNKA_B tag SNPs and dietary factors on EH. Generalized multifactor dimensionality reduction (GMDR) was used to test gene-environment interaction for EH risk. RESULTS: Four SNPs were identified as the tag SNPs of CLCNKA_B. Recessive model for rs5253 and rs2275166 were marginal associated with the decrease risk of EH (OR = 0.36, 95% CI = 0.12-1.07 for rs5253; OR = 0.40, 95% CI = 0.16-1.05 for rs2275166). In GMDR, the five-factor interaction model of rs1010069, salt, marine products, meat and edible oil consumption was the best model, with a maximum CVC of 10/10 and a TBA of 0.638 (p = 0.001). In ULR, compared with subjects carried wild genotypes and null dietary risk factor, those with three or more dietary risk factors and mutation genotypes had 5.90-fold EH risk (95% CI:2.24-15.53). CONCLUSION: Though the single loci of tag SNPs of CLCNKA_B are not enough to significantly increase the EH susceptibility, the combination of CLCNKA tag SNP, salt, marine products, meat and edible oil consumption is associated with elevated risk.